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RATIONALE: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare autoimmune disease that can affect multiple organ systems. The standard treatment mainly relies on glucocorticoids and immunosuppressive agents. In our study, we present an EGPA patient who had pulmonary tuberculous mycobacteria infection, such cases are rarely reported. PATIENT CONCERNS: A 71-year-old male patient was diagnosed with EGPA (systemic type) and pulmonary tuberculosis simultaneously. DIAGNOSES: The Five-Factor score indicated that the patient required glucocorticoids combined with immunosuppressive agents for induction therapy, however, the use of immunosuppressive agents would significantly inhibit antituberculosis treatment. Nowadays, treating active autoimmune disease in patients with infections remains a clinical challenge. INTERVENTIONS: Considering the patient did not show life-threatening or severe organ involvement and reduced the effect of antituberculosis immunity, we used glucocorticoids alone. OUTCOMES: Finally, the patient had no adverse events, the eosinophil counts were markedly decreased and symptoms of EGPA were relieved. LESSONS: The patient of EGPA combined with pulmonary tuberculosis successfully treated with glucocorticoids alone may provide significant support in selecting the appropriate treatments for similar cases in the future.

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Glucocorticoides , Tuberculosis Pulmonar , Humanos , Masculino , Anciano , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/diagnóstico , Inmunosupresores/uso terapéutico

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BACKGROUND: Bone-derived protein osteocalcin, which has beneficial effects on brain function, may be a future research direction for neurological disorders. A growing body of evidence suggests a link between osteocalcin and neurological disorders, but the exact relationship is contradictory and unclear. SCOPE OF REVIEW: The aim of this review is to summarize the current research on the interaction between osteocalcin and the central nervous system and to propose some speculative future research directions. MAJOR CONCLUSIONS: In the normal central nervous system, osteocalcin is involved in neuronal structure, neuroprotection, and the regulation of cognition and anxiety. Studies on osteocalcin-related abnormalities in the central nervous system are divided into animal model studies and human studies, depending on the subject. In humans, the link between osteocalcin and brain function is inconsistent. These conflicting data may be due to methodological inconsistencies. By reviewing the related literature on osteocalcin, some comorbidities of the bone and nervous system and future research directions related to osteocalcin are proposed.

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Sistema Nervioso Central , Osteocalcina , Humanos , Osteocalcina/metabolismo , Osteocalcina/fisiología , Animales , Sistema Nervioso Central/metabolismo

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BACKGROUND: Thyroid surgery has undergone significant transformation with the introduction of minimally invasive techniques, particularly robotic and endoscopic thyroidectomy. These advancements offer improved precision and faster recovery but also present unique challenges. This study aims to compare the learning curves, operational efficiencies, and patient outcomes of robotic versus endoscopic thyroidectomy. METHODS: A retrospective cohort study was conducted, analyzing 258 robotic (da Vinci) and 214 endoscopic thyroidectomy cases. Key metrics such as operation duration, drainage volume, lymph node dissection outcomes, and hypoparathyroidism incidence were assessed to understand surgical learning curves and efficiency. RESULTS: Robotic thyroidectomy showed a longer learning curve with initially longer operation times and higher drainage volumes but superior lymph node dissection outcomes. Both techniques were safe, with no permanent hypoparathyroidism or recurrent laryngeal nerve damage reported. The study delineated four distinct stages in the robotic and endoscopic surgery learning curve, each marked by specific improvements in proficiency. Endoscopic thyroidectomy displayed a shorter learning curve, leading to quicker operational efficiency gains. CONCLUSION: Robotic and endoscopic thyroidectomies are viable minimally invasive approaches, each with its learning curves and efficiency metrics. Despite initial challenges and a longer learning period for robotic surgery, its benefits in complex dissections may justify specialized training. Structured training programs tailored to each technique are crucial for improving outcomes and efficiency. Future research should focus on optimizing training protocols and increasing accessibility to these technologies, enhancing patient care in thyroid surgery.

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PURPOSE: To develop and validate a nomogram based on 3D-PDU parameters and clinical characteristics to predict LNM and LVSI in early-stage cervical cancer preoperatively. MATERIALS AND METHODS: A total of first diagnosis 138 patients with cervical cancer who had undergone 3D-PDU examination before radical hysterectomy plus lymph dissection between 2014 and 2019 were enrolled for this study. Multivariate logistic regression analyses were performed to analyze the 3D-PDU parameters and selected clinicopathologic features and develop a nomogram to predict the probability of LNM and LVSI in the early stage. ROC curve was used to evaluate model differentiation, calibration curve and Hosmer-Lemeshow test were used to evaluate calibration, and DCA was used to evaluate clinical practicability. RESULTS: Menopause status, FIGO stage and VI were independent predictors of LNM. BMI and maximum tumor diameter were independent predictors of LVSI. The predicted AUC of the LNM and LSVI models were 0.845 (95%CI,0.765-0.926) and 0.714 (95%CI,0.615-0.813). Calibration curve and H-L test (LNM groups P = 0.478; LVSI P = 0.783) all showed that the predicted value of the model had a good fit with the actual observed value, and DCA indicated that the model had a good clinical net benefit. CONCLUSION: The proposed nomogram based on 3D-PDU parameters and clinical characteristics has been proposed to predict LNM and LVSI with high accuracy, demonstrating for the first time the potential of non-invasive prediction. The probability derived from this nomogram may have the potential to provide valuable guidance for physicians to develop clinical individualized treatment plans of FIGO patients with early cervical cancer.

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Metástasis Linfática , Nomogramas , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/diagnóstico , Metástasis Linfática/patología , Persona de Mediana Edad , Adulto , Imagenología Tridimensional/métodos , Histerectomía/métodos , Estadificación de Neoplasias , Escisión del Ganglio Linfático/métodos , Ultrasonografía/métodos , Invasividad Neoplásica , Ganglios Linfáticos/patología , Estudios Retrospectivos , Anciano , Valor Predictivo de las Pruebas

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BACKGROUND: Venoms have repeatedly evolved over 100 occasions throughout the animal tree of life, making them excellent systems for exploring convergent evolutionary novelty. Growing evidence supports that venom evolution is predominantly driven by prey or host-related selection pressures, and the expression patterns of venom glands reflect adaptive evolution. However, it remains elusive whether the evolution of expression patterns in venom glands is likewise a convergent evolution driven by their prey/host species. RESULTS: We utilized parasitoid wasps that had independently adapted to Drosophila hosts as models to investigate the convergent evolution of venom gland transcriptomes in 19 hymenopteran species spanning ~ 200 million years of evolution. Comparative transcriptome analysis reveals that the global expression patterns among the venom glands of Drosophila parasitoid wasps do not achieve higher similarity compared to non-Drosophila parasitoid wasps. Further evolutionary analyses of expression patterns at the single gene, orthogroup, and Gene Ontology (GO) term levels indicate that some orthogroups/GO terms show correlation with the Drosophila parasitoid wasps. However, these groups rarely include genes highly expressed in venom glands or putative venom genes in the Drosophila parasitoid wasps. CONCLUSIONS: Our study suggests that convergent evolution may not play a predominant force shaping gene expression levels in the venom gland of the Drosophila parasitoid wasps, offering novel insights into the co-evolution between venom and prey/host.

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Evolución Molecular , Transcriptoma , Venenos de Avispas , Avispas , Animales , Avispas/genética , Avispas/fisiología , Venenos de Avispas/genética , Drosophila/genética , Drosophila/parasitología , Interacciones Huésped-Parásitos/genética , Evolución Biológica

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Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the western blot data shown for the MMP­9 experiment in Fig. 4 on p. 1493 were strikingly similar to the western blots shown for the total­Akt experiments in Fig. 6 on p. 1494. After having re­examined their original data files, the authors realized that Fig. 6 had been inadvertently assembled incorrectly. The revised version of Fig. 6, containing the correct data for the total­Akt experiments, is shown below. Note that the corrections made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 31: 1489­1497, 2014; DOI: 10.3892/or.2013.2961].

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Background: The previous findings on the correlation between spirometry and high-density lipoprotein (HDL) cholesterol are intriguing yet conflicting. The aim of this research is to evaluate the relationship between HDL levels and spirometry as well as imaging parameters in patients with chronic obstructive pulmonary disease (COPD) in China. Methods: This study encompasses a total of 907 COPD patients. Participants with complete data from questionnaire interviews, lipid profile examinations, spirometry testing, and computed tomography (CT) scans were included in the analysis. A generalized additive model was employed to identify the non-linear relationship between HDL levels and both spirometry and imaging parameters. In the presence of non-linear correlations, segmented linear regression model was applied to ascertain threshold effects. Results: After adjusting for various factors, we found a non-linear correlation between HDL levels and spirometry/imaging parameters, with an inflection point at 4.2 (66 mg/dL). When Ln (HDL) was below 4.2, each unit increase correlated significantly with reduced post-bronchodilator FEV1 (0.32L, 95% CI: 0.09-0.55), decreased predicted FEV1% (11.0%, 95% CI: 2.7-19.3), and lowered FEV1/FVC (8.0%, 95% CI: 4.0-12.0), along with notable increases in Ln (LAA-950) by 1.20 (95% CI: 0.60-1.79) and Ln (LAA-856) by 0.77 (95% CI: 0.37-1.17). However, no significant associations were observed when Ln (HDL) was greater than or equal to 4.2. Conclusion: A non-linear correlation existed between HDL levels with lung function and CT imaging in COPD patients. Prior to reaching 66 mg/dL, an elevation in HDL was significantly associated with impaired lung function, more severe gas trapping and emphysema.

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Biomarcadores , Pulmón , Dinámicas no Lineales , Enfermedad Pulmonar Obstructiva Crónica , Espirometría , Tomografía Computarizada por Rayos X , Humanos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Masculino , Femenino , China/epidemiología , Persona de Mediana Edad , Anciano , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Volumen Espiratorio Forzado , Biomarcadores/sangre , HDL-Colesterol/sangre , Valor Predictivo de las Pruebas , Estudios Transversales , Modelos Lineales , Lipoproteínas HDL/sangre , Capacidad Vital

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PURPOSE: This study aimed to create a preoperative risk assessment form for COVID-19-positive hepatobiliary patients to guide further prevention of complications after surgery and reduce morbidity and mortality. DESIGN: Based on the literature, focus groups, and case studies, a multidisciplinary panel of 15 experts conducted three rounds of a Delphi study that resulted in the development of a preoperative risk assessment form to be used by healthcare professionals in the treatment of COVID-19-positive hepatobiliary patients. METHODS: A preoperative risk assessment form for health professionals to use among COVID-19-positive hepatobiliary patients was developed based on literature, focus groups, and case studies. A 3-round Delphi study was conducted to validate and revise the risk assessment form using a multidisciplinary panel of 15 experts involved in hepatobiliary surgery. FINDINGS: The experts demonstrated high cooperation and familiarity with the research topic, with positive coefficients ranging from 93.33% to 100% and authority coefficients ranging from 0.83 to 0.86. The coordination coefficients were 0.33, 0.26, and 0.22, respectively, indicating good coordination among expert opinions. The final risk assessment form included 9 primary (first-level) indicators, 38 secondary (second-level) indicators, and 122 tertiary (third-level) indicators. CONCLUSIONS: The preoperative risk assessment form for hepatobiliary surgery patients infected with COVID-19 is scientifically rigorous, reliable, and valid. This screening tool may be used by health providers to identify high-risk patients, prevent postoperative complications, and reduce morbidity and mortality.

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Objective: To develop a highly sensitive and rapid nucleic acid detection method for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We designed, developed, and manufactured an integrated disposable device for SARS-CoV-2 nucleic acid extraction and detection. The precision of the liquid transfer and temperature control was tested. A comparison between our device and a commercial kit for SARS-Cov-2 nucleic acid extraction was performed using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). The entire process, from SARS-CoV-2 nucleic acid extraction to amplification, was evaluated. Results: The precision of the syringe transfer volume was 19.2 ± 1.9 µL (set value was 20), 32.2 ± 1.6 (set value was 30), and 57.2 ± 3.5 (set value was 60). Temperature control in the amplification tube was measured at 60.0 ± 0.0 °C (set value was 60) and 95.1 ± 0.2 °C (set value was 95) respectively. SARS-Cov-2 nucleic acid extraction yield through the device was 7.10 × 10 6 copies/mL, while a commercial kit yielded 2.98 × 10 6 copies/mL. The mean time to complete the entire assay, from SARS-CoV-2 nucleic acid extraction to amplification detection, was 36 min and 45 s. The detection limit for SARS-CoV-2 nucleic acid was 250 copies/mL. Conclusion: The integrated disposable devices may be used for SARS-CoV-2 Point-of-Care test (POCT).

Asunto(s)

COVID-19 , Equipos Desechables , ARN Viral , SARS-CoV-2 , SARS-CoV-2/aislamiento & purificación , COVID-19/diagnóstico , COVID-19/virología , Humanos , ARN Viral/aislamiento & purificación , ARN Viral/análisis , Prueba de Ácido Nucleico para COVID-19/instrumentación , Prueba de Ácido Nucleico para COVID-19/métodos , Técnicas de Amplificación de Ácido Nucleico/instrumentación , Técnicas de Amplificación de Ácido Nucleico/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/instrumentación

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BACKGROUND: Impaired ventilatory efficiency during exercise is a predictor of mortality in chronic obstructive pulmonary disease. However, little is known about the clinical features and associated factors of impaired ventilatory efficiency in China. METHODS: We conducted a cross-sectional community-based study in China and collected demographic and clinical information, cardiopulmonary exercise testing, spirometry, and CT data. Impaired ventilatory efficiency was defined by a nadir ventilatory equivalent for CO2 production above the upper limit of normal. Multivariable linear and logistic regression models were used to explore the clinical features and associated factors of impaired ventilatory efficiency. RESULTS: The final analyses included 941 subjects, 702 (74.6%) of whom had normal ventilatory efficiency and 239 (25.4%) had impaired ventilatory efficiency. Participants with impaired ventilatory efficiency had more chronic respiratory symptoms, poorer lung function and exercise capacity, and more severe emphysema (natural logarithm transformation of the low-attenuation area of the lung with attenuation values below -950 Hounsfield units, logLAA-950: 0.19±0.65 vs -0.28±0.63, p<0.001) and air trapping (logLAA-856: 1.03±0.65 vs 0.68±0.70, p<0.001) than those with normal ventilatory efficiency. Older age (60-69 years, OR 3.10 (95% CI 1.33 to 7.21), p=0.009 and 70-80 years, OR 6.48 (95% CI 2.56 to 16.43), p<0.001 vs 40-49 years) and smoking (former, OR 3.19 (95% CI 1.29 to 7.86), p=0.012; current, OR 4.27 (95% CI 1.78 to 10.24), p=0.001 vs never) were identified as high risk factors of impaired ventilatory efficiency. CONCLUSIONS: Impaired ventilatory efficiency was associated with poorer respiratory characteristics. Longitudinal studies are warranted to explore the progression of individuals with impaired ventilatory efficiency.

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Enfermedad Pulmonar Obstructiva Crónica , Humanos , China/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Anciano , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Espirometría , Prueba de Esfuerzo , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Tolerancia al Ejercicio , Factores de Riesgo , Ventilación Pulmonar

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MicroRNAs (miRNAs) have started to play an important role in pest control, and novel miRNA-based transgenic insect-resistant plants are now emerging. However, an environmental risk assessment of these novel transgenic plants expressing insect miRNAs must be undertaken before promoting their application. Here, transgenic miR-14 rice, which has high resistance to the rice stem borer Chilo suppressalis, was used as an example for evaluation in this study. Taking the tier 1 risk assessment method in Bacillus thuringiensis (Bt) crops as a reference, the effects of the direct exposure of a non-target parasitoid, Cotesia chilonis, to a high concentration of miRNA were evaluated. The results showed that direct feeding with miR-14 at high concentration had no significant effects on the biological parameters of Co. chilonis, whereas when miR-14 was injected into Ch. suppressalis-parasitized larvae, the development duration of Co. chilonis was significantly affected. In combination with the real conditions of the rice paddy field, it could be inferred that transgenic miR-14 rice has no significant negative effects on the important non-target parasitoid, Co. chilonis. These results will provide a foundation for the establishment of a new safety evaluation system for novel RNAi-based transgenic plants.

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Polycystic ovary syndrome (PCOS) is a complex common endocrine disorder affecting women of reproductive age. Ovulatory dysfunction is recognized as a primary infertile factor, however, even when ovulation is medically induced and restored, PCOS patients continue to experience reduced cumulative pregnancy rates and a higher spontaneous miscarriage rate. Hyperandrogenism, a hallmark feature of PCOS, affects ovarian folliculogenesis, endometrial receptivity, and the establishment and maintenance of pregnancy. Decidualization denotes the transformation that the stromal compart of the endometrium must undergo to accommodate pregnancy, driven by the rising progesterone levels and local cAMP production. However, studies on the impact of hyperandrogenism on decidualization are limited. In this study, we observed that primary endometrial stromal cells from women with PCOS exhibit abnormal responses to progesterone during in vitro decidualization. A high concentration of testosterone inhibits human endometrial stromal cells (HESCs) decidualization. RNA-Seq analysis demonstrated that pyruvate dehydrogenase kinase 4 (PDK4) expression was significantly lower in the endometrium of PCOS patients with hyperandrogenism compared to those without hyperandrogenism. We also characterized that the expression of PDK4 is elevated in the endometrium stroma at the mid-secretory phase. Artificial decidualization could enhance PDK4 expression, while downregulation of PDK4 leads to abnormal decidualization both in vivo and in vitro. Mechanistically, testosterone excess inhibits IGFBP1 and PRL expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. Based on co-immunoprecipitation analysis, we observed an interaction between SIRT1 and PDK4, promoting glycolysis to facilitate decidualization. Restrain of AR activation resumes the AMPK/SIRT1/PDK4 pathway suppressed by testosterone excess, indicating that testosterone primarily acts on decidualization through AR stimulation. Androgen excess in the endometrium inhibits decidualization by disrupting the AMPK/SIRT1/PDK4 signaling pathway. These data demonstrate the critical roles of endometrial PDK4 in regulating decidualization and provide valuable information for understanding the underlying mechanism during decidualization.

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Proteínas Quinasas Activadas por AMP , Endometrio , Síndrome del Ovario Poliquístico , Sirtuina 1 , Células del Estroma , Humanos , Femenino , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/patología , Células del Estroma/metabolismo , Células del Estroma/patología , Células del Estroma/efectos de los fármacos , Sirtuina 1/metabolismo , Sirtuina 1/genética , Endometrio/metabolismo , Endometrio/patología , Endometrio/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Adulto , Hiperandrogenismo/metabolismo , Hiperandrogenismo/patología , Decidua/metabolismo , Decidua/patología , Testosterona/metabolismo , Testosterona/farmacología , Andrógenos/farmacología , Andrógenos/metabolismo , Progesterona/metabolismo , Progesterona/farmacología , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/metabolismo , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/genética , Transducción de Señal/efectos de los fármacos

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Curcumin (Cur) as a natural food additive and photosensitizer has been widely applied on photodynamic sterilization and preservation for food, but the poor aqueous solubility and light stability restrict its extensive application. In this study, we report a Cur nanocapsules (Cur-CDs) made by carbon dots (CDs). Attributing to the hydrogen bonds formed between Cur and CDs, Cur-CDs exhibits excellent Cur aqueous solubility each to 9286.98 ng/mL (enhanced by 246.27 times) and light stability (enhanced by 1.51 times). The photogenerated electron transmission from Cur to CDs in addition resulted in >1.23 and 1.60 times generation of •O2- and •OH, compared to that of bare Cur. Accordingly, 5.73 × 103 CFU L. monocytogenes, and 5.43 × 103 CFU S. aureus were killed by 0.06 mg/mL Cur-CDs within 20 mins of blue light, showing the promising potential in the development and application of safe and environmentally friendly non-thermal sterilization technology based on Cur-CDs.

Asunto(s)

Carbono , Curcumina , Listeria monocytogenes , Nanocápsulas , Fármacos Fotosensibilizantes , Puntos Cuánticos , Staphylococcus aureus , Listeria monocytogenes/efectos de los fármacos , Listeria monocytogenes/crecimiento & desarrollo , Listeria monocytogenes/efectos de la radiación , Curcumina/farmacología , Curcumina/química , Carbono/química , Carbono/farmacología , Staphylococcus aureus/efectos de los fármacos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Puntos Cuánticos/química , Nanocápsulas/química , Esterilización , Antibacterianos/farmacología , Antibacterianos/química , Luz

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Studies on the spatio-temporal variation and coordinated development level of compactness with carbon emission intensity in the Chengdu-Chongqing urban agglomeration is of great significance to achieve green, low-carbon, and high-quality development of society. The spatial-temporal differentiation, coupling coordination, and driving factors of the compactness and carbon emission intensity of the Chengdu-Chongqing urban agglomeration from 2010 to 2020 were analyzed by using the methods of comprehensive evaluation, carbon emission identical equality, coupling coordination, and the Geo-detector model. The results showed that:① The compactness of the Chengdu-Chongqing urban agglomeration continued to rise from 0.18 in 2010 to 0.22 in 2020, with an overall increase of 22.22 %, in which the contribution rate of economic compactness to urban compactness increased yearly. There were significant regional differences in the compactness of cities. The high-value areas were concentrated in Chengdu, Deyang, and Mianyang in the northwest and Zigong, Neijiang, and Luzhou in the southwest, whereas the low-value areas were distributed in the middle. Ya'an was always the area with the lowest compactness of urban agglomeration. ② The carbon emission intensity of the Chengdu-Chongqing urban agglomeration was decreasing yearly, with a decrease rate of 39.57 % during the study period. The carbon emission intensity in the southern part of the urban agglomeration was higher than that in other regions as a whole, whereas Chengdu and Chongqing were low-value areas all the year round, and the regional differences of carbon emission intensity were gradually narrowing. ③ The coupling degree between urban compactness and carbon emission intensity changed from the antagonistic stage to the running-in stage; the coupling coordination degree increased notably, from 0.21 in 2010 to 0.69 in 2020; and the two systems gradually moved towards benign and coordinated development. The coupling coordination between the northwest of the urban agglomeration (Chengdu, Deyang, and Mianyang) and the south of Sichuan (Zigong and Luzhou) was generally high. Industrial structure, scientific and technological innovation, urbanization level, government intervention, and environmental livability all had significant effects on the coupling and coordination of the two systems. ④ Optimizing industrial structure, strengthening scientific and technological support, improving the quality of urbanization development, implementing active policy guidance, and building green barriers were effective ways to promote the coordinated development of compactness and low carbon in the Chengdu-Chongqing urban agglomeration.

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Type 2 diabetes mellitus combined with metabolic dysfunction-associated steatotic liver disease (MASLD) leads to an increasing incidence of liver injury year by year, and patients are at a significantly higher risk of developing cirrhosis or even liver failure. No drugs have emerged to specifically treat this disease. The aim of this study is to investigate the mechanisms and causative hub genes of type 2 diabetes combined with MASLD. The data were obtained through the GEO platform for bioinformatics analysis and validated by in vitro experiments to find the causative targets of type 2 diabetes mellitus combined with MASLD, which will provide some theoretical basis for the development of future therapeutic drugs. GSE23343 and GSE49541 were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) in type 2 diabetes mellitus combined with MASLD for functional enrichment analysis. And STRING database and Cytoscape software were used to construct Protein-Protein Interaction (PPI) and hub gene networks. And GO (gene ontology, GO) analysis and KEGG (Kyoto encyclopedia of genes and genomes, KEGG) enrichment analysis were performed on target genes. A total of 185 co-expressed DEGs were obtained by differential analysis, and 20 key genes involved in the development and progression of type 2 diabetes were finally screened. These 20 key genes were involved in 529 GO enrichment results and 20 KEGG enrichment results, and were mainly associated with ECM-receptor interaction, Focal adhesion, Human papillomavirus infection, PI3K-Akt signaling pathway, and the Toll-like receptor signaling pathway. A total of two target genes (SPP1, collagen IV) were found to be highly correlated with type 2 diabetes mellitus combined with MASLD. Real time PCR results showed that there was a significant difference in SPP1 and collagen IV mRNA expression among the three groups (P < 0.05). SPP1 and Collagen IV may be candidate biomarkers for type 2 diabetes mellitus combined with MASLD, as verified by bioinformatics screening and in vitro experiments. Our findings provide new targets for the treatment of type 2 diabetes combined with MASLD.

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Colágeno Tipo IV , Diabetes Mellitus Tipo 2 , Osteopontina , Mapas de Interacción de Proteínas , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Animales , Ratas , Colágeno Tipo IV/genética , Colágeno Tipo IV/metabolismo , Osteopontina/genética , Osteopontina/metabolismo , Redes Reguladoras de Genes , Modelos Animales de Enfermedad , Biología Computacional/métodos , Perfilación de la Expresión Génica , Masculino , Humanos , Ontología de Genes , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Transducción de Señal

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In our previous study, a new fermented food (PWF) created by utilizing pineapple by-products and whey proteins as a matrix via co-fermentation with lactic acid bacteria and yeast was developed, and, in the current study, we examined the impact of a pineapple-whey protein fermentation product on a cefixime-induced dysbiosis model in mice using 16S sequencing and untargeted metabolomics techniques. The results indicated that the pineapple-whey protein fermentation product played a positive role in restoring the intestinal flora. In this study, cefixime reduced the overall abundance of intestinal flora and decreased the relative abundance of probiotics in the gut, while also inhibiting amino acid metabolism. The addition of PWF normalized the intestinal flora to a steady state, significantly increasing the populations of Weissella, Lactococcus, Faecalibaculum, and Bacteroides acidophilus, while decreasing the numbers of Akkermansia and Escherichia-Shigella. Additionally, PWF modulated microbial metabolites, such as L-glutamate and L-threonine, and upregulated amino-acid-related metabolic pathways, including those involving glycine, serine, and threonine. In conclusion, PWF can alleviate intestinal flora dysbiosis and metabolic disturbances induced by antibiotic interventions. It is suggested that PWF could be a potential dietary strategy for patients with antibiotic-associated diarrhea.

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The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes. The structural basis for their inhibitory potency was elucidated through the crystallographic study of RORγ LBD complex with 13e. Both 13e and 14a demonstrated reasonable antiproliferative activity, potently inhibited colony formation and the expression of AR, AR regulated genes, and other oncogene in AR positive prostate cancer cell lines. Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer.

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Antineoplásicos , Proliferación Celular , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Neoplasias de la Próstata , Quinolinas , Masculino , Animales , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Quinolinas/farmacología , Quinolinas/química , Quinolinas/uso terapéutico , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/agonistas , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/antagonistas & inhibidores , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Agonismo Inverso de Drogas , Ratones , Ratones Desnudos , Descubrimiento de Drogas , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Endogámicos BALB C

RESUMEN

BACKGROUND: There are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical characteristics of the participants with variable obstruction and determine the relationship between variable obstruction and the development of chronic obstructive pulmonary disease (COPD) and the decline of lung function in a community-dwelling study of Chinese, especially among never smokers and different variable obstruction subtypes. METHODS: Participants with preserved spirometry (postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.70) at baseline from the Early COPD cohort were included in our analysis. Participants with variable obstruction (prebronchodilator FEV1/FVC <0.70) were compared with those without variable obstruction (prebronchodilator FEV1/FVC ≥0.70). We performed subgroup analyses in never smokers, former and current smokers, and different variable obstruction types (postbronchodilator FVC

Asunto(s)

Enfermedad Pulmonar Obstructiva Crónica , Espirometría , Humanos , Masculino , Femenino , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Persona de Mediana Edad , China/epidemiología , Anciano , Volumen Espiratorio Forzado , Capacidad Vital , Fumar/epidemiología , Fumar/efectos adversos , Pulmón/fisiopatología , Pronóstico

RESUMEN

BACKGROUND: Congenital thrombotic thrombocytopenic purpura (TTP) results from severe hereditary deficiency of ADAMTS13. The efficacy and safety of recombinant ADAMTS13 and standard therapy (plasma-derived products) administered as routine prophylaxis or on-demand treatment in patients with congenital TTP is not known. METHODS: In this phase 3, open-label, crossover trial, we randomly assigned patients in a 1:1 ratio to two 6-month periods of prophylaxis with recombinant ADAMTS13 (40 IU per kilogram of body weight, administered intravenously) or standard therapy, followed by the alternate treatment; thereafter, all the patients received recombinant ADAMTS13 for an additional 6 months. The trigger for this interim analysis was trial completion by at least 30 patients. The primary outcome was acute TTP events. Manifestations of TTP, safety, and pharmacokinetics were assessed. Patients who had an acute TTP event could receive on-demand treatment. RESULTS: A total of 48 patients underwent randomization; 32 completed the trial. No acute TTP event occurred during prophylaxis with recombinant ADAMTS13, whereas 1 patient had an acute TTP event during prophylaxis with standard therapy (mean annualized event rate, 0.05). Thrombocytopenia was the most frequent TTP manifestation (annualized event rate, 0.74 with recombinant ADAMTS13 and 1.73 with standard therapy). Adverse events occurred in 71% of the patients with recombinant ADAMTS13 and in 84% with standard therapy. Adverse events that were considered by investigators to be related to the trial drug occurred in 9% of the patients with recombinant ADAMTS13 and in 48% with standard therapy. Trial-drug interruption or discontinuation due to adverse events occurred in no patients with recombinant ADAMTS13 and in 8 patients with standard therapy. No neutralizing antibodies developed during recombinant ADAMTS13 treatment. The mean maximum ADAMTS13 activity after recombinant ADAMTS13 treatment was 101%, as compared with 19% after standard therapy. CONCLUSIONS: During prophylaxis with recombinant ADAMTS13 in patients with congenital TTP, ADAMTS13 activity reached approximately 100% of normal levels, adverse events were generally mild or moderate in severity, and TTP events and manifestations were rare. (Funded by Takeda Development Center Americas and Baxalta Innovations; ClinicalTrials.gov number, NCT03393975.).

Asunto(s)

Proteína ADAMTS13 , Púrpura Trombocitopénica Trombótica , Proteínas Recombinantes , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Proteína ADAMTS13/administración & dosificación , Proteína ADAMTS13/efectos adversos , Proteína ADAMTS13/deficiencia , Proteína ADAMTS13/genética , Estudios Cruzados , Púrpura Trombocitopénica Trombótica/congénito , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Púrpura Trombocitopénica Trombótica/genética , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Preescolar

RESUMEN

Dry-cured hams contain abundant bioactive peptides with significant potential for the development of functional foods. However, the limited bioavailability of food-derived bioactive peptides has hindered their utilization in health food development. Moreover, there is insufficient regulatory information regarding bioactive peptides and related products globally. This review summarizes diverse bioactive peptides derived from dry-cured ham and by-products originating from various countries and regions. The bioactivity, preparation techniques, bioavailability, and metabolic stability of these bioactive peptides are described, as well as the legal and regulatory frameworks in various countries. The primary objectives of this review are to dig deeper into the functionality of dry-cured ham and provide theoretical support for the commercialization of bioactive peptides from food sources, especially the dry-cured ham.

Asunto(s)

Manipulación de Alimentos , Productos de la Carne , Péptidos , Animales , Productos de la Carne/análisis , Manipulación de Alimentos/métodos , Disponibilidad Biológica , Porcinos , Humanos , Alimentos Funcionales , Estabilidad Proteica