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The development of intelligent responsive reactive packaging materials with natural polymers shows excellent potential in food preservation. In this study, eco-friendly, pH-sensitive sodium alginate (SA)/hydroxyapatite (HA)/quaternary ammonium chitosan (HACC) composite microspheres loading curcumin (CUR) with excellent antibacterial and antioxidant activities were successfully synthesized. Scanning electron microscopy (SEM) and nitrogen adsorption/desorption tests indicated that the doping of HA substantially increased the specific surface area and pore volume of the microspheres. The loading experiments showed that the efficiency of the microspheres was significantly increased by 49.47 % and 55.10 %, respectively, when HA and HACC were incorporated into the SA network. The release test results suggested that the release rate of SA/HA/HACC microspheres loading CUR (SA/HA/HACC@CUR) increased as the pH decreased, demonstrating notable pH-responsive release characteristics. DPPH free radical scavenging experiments demonstrated that the SA/HA/HACC@CUR had excellent and long-lasting antioxidant capacity. The antibacterial experiments revealed that the SA/HA/HACC@CUR had excellent antibacterial properties, with inhibition rates of 88.73 % and 92.52 % against E. coli and S. aureus, respectively. Making coatings out of microspheres could effectively slow down the rotting and deterioration of cherry tomatoes during storage, suggesting that microspheres with intelligent responses have a broad application prospect in fruit preservation.
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BACKGROUND: Breakthrough cancer pain (BTcP) has a negative impact on patients' quality of life, general activities, and is related to worse clinical outcomes. Fentanyl inhalant is a hand-held combination drug-device delivery system providing rapid, multi-dose (25µg/dose) administration of fentanyl via inhalation of a thermally generated aerosol. This multicenter, randomized, placebo-controlled, multiple-crossover, double-blind study evaluated the efficacy, safety, and tolerability of fentanyl inhalant in treating BTcP in opioid-tolerant patients. METHODS: The trial was conducted in opioid-tolerant cancer patients with 1 ~ 4 BTcP outbursts per day. Each patient was treated and observed for 6 episodes of BTcP (4 with fentanyl inhalant, 2 with placebo). During each episode of targeted BTcP, patients were allowed up to six inhalations, with an interval of at least 4 min between doses. Primary outcome was the time-weighted sum of PID (pain intensity difference) scores at 30 min (SPID30). RESULTS: A total of 335 BTcP episodes in 59 patients were treated. The mean SPID30 was -97.4 ± 48.43 for fentanyl inhalant-treated episodes, and -64.6 ± 40.25 for placebo-treated episodes (p < 0.001). Significant differences in PID for episodes treated with fentanyl inhalant versus placebo was seen as early as 4 min and maintained for up to 60 min. The percentage of episodes reported PI (pain intensity) scores ≤ 3, a ≥ 33% or ≥ 50% reduction in PI scores at 30 min, PR30 (pain relief scores at 30 min) and SPID60 favored fentanyl inhalant over placebo. Only 4.4% of BTcP episodes required rescue medication in fentanyl inhalant group. Most AEs were of mild or moderate severity and typical of opioid drugs. CONCLUSION: Treatment with fentanyl inhalant was shown to be a promising therapeutic option for BTcP, with significant pain relief starting very soon after dosing. Confirmation of effectiveness requires a larger phase III trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05531422 registered on 6 September 2022 after major amendment, NCT04713189 registered on 14 January 2021.
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Analgésicos Opioides , Dolor Irruptivo , Dolor en Cáncer , Fentanilo , Humanos , Fentanilo/uso terapéutico , Fentanilo/farmacología , Fentanilo/administración & dosificación , Método Doble Ciego , Masculino , Persona de Mediana Edad , Femenino , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/administración & dosificación , Dolor Irruptivo/tratamiento farmacológico , Dolor Irruptivo/etiología , Anciano , Dolor en Cáncer/tratamiento farmacológico , Adulto , Administración por Inhalación , Estudios Cruzados , Dimensión del Dolor/métodos , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
Flexible conductive hydrogel-based electronic skin (E-skin) for simultaneous biotherapeutics and sensing applications is one of the current research directions. In this study, conductive and homogeneous silk fibroin/polyaniline/AgNP complexes (SPAg complexes) were prepared with the assistance of silk fibroin, which greatly optimized the compatibility of PANI with the hydrogel matrix. Then, SPAg was introduced into the covalently crosslinked polymer network to prepare poly(acrylamide-co-sulfobetaine methacrylate) - SPAg hydrogels (labeled as PSPAg hydrogels). The PSPAg hydrogels exhibit good biocompatibility, excellent mechanical properties, superb adhesive performance, and fantastic sensing capabilities. Being connected to a smartphone via a Bluetooth system, the SPAg hydrogel-based E-skin was employed to accurately monitor human movements including vigorous joint movements and subtle facial micro-expressions. Finally, benefiting from the synergistic effect of antimicrobial and exogenous electrical stimulation, through promoting angiogenesis and accelerating collagen production in diabetic wounds, PSPAg E-skin successfully facilitates rapid diabetic wound healing. Therefore, the multifunctional PSPAg hydrogel-based E-skin shows great promise for applications in wearable devices and bioelectronics.
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Grafted chitosan materials show the characteristics of high stability, easy separation and recovery, and good heavy metal adsorption capacity, and have received much attention in the adsorption process. Therefore, in this work, novel grafted chitosan-based adsorbent CS-EHBSB@F-AE was prepared by a one-pot reaction of chitosan (CS), 3-ethoxy-4-hydroxybenzaldehyde (EHB), formaldehyde (F) and aminoethanol (F). The microstructure and morphology of the as-prepared composite CS-EHBSB@F-AE were characterized by FT-IR, TGA, DSC, FE-SEM, and BET analyses. The adsorption performance of the as-prepared CS-EHBSB@F-AE composite on Pb(II), Hg(II), and Cu(II) ions from aqueous was investigated using batch experiment and the effects of the initial pH of the solution, contact time, and initial metal ions concentration and temperature on the adsorption efficiency were investigated and discussed. At the best conditions, CS-EHBSB@F-AE exhibited remarkable adsorption capacity of 246.7â¯mg/g, 203.9â¯mg/g, and 234.4â¯mg/g in absorbing Pb(II), Hg(II), and Cu(II), respectively. The adsorption equilibrium and the kinetic studies confirmed that the ions adsorption process fits well with the Langmuir isotherm and pseudo-second-order (PSO) models. Additionally, the adsorption efficiency of Pb(II), Hg(II), and Cu(II) metal ions by the composite CS-EHBSB@F-AE was reduced by increasing the temperature from 298â¯K to 318â¯K. In addition, after the sixth ads/des cycles, the as-prepared adsorbent still exhibited high removal efficiency with a decrease in adsorption efficiency of Pb(II) (5.53â¯%), Hg(II) (15.43â¯%) and Cu(II) (8.27â¯%). Finally, we proposed that the ions adsorption by CS-EHBSB@F-AE has happened using the coordination of active groups containing nitrogen and oxygen atoms on the surface of the adsorbent with the Pb(II), Hg(II), and Cu(II) metal ions.
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The escalating costs and high failure rates have decelerated the pace of drug development, which amplifies the research interests in developing combinatorial/repurposed drugs and understanding off-target adverse drug reaction (ADR). In other words, it is demanded to delineate the molecular atlas and pharma-information for the combinatorial/repurposed drugs and off-target interactions. However, such invaluable data were inadequately covered by existing databases. In this study, a major update was thus conducted to the DrugMAP, which accumulated (a) 20831 combinatorial drugs and their interacting atlas involving 1583 pharmacologically important molecules; (b) 842 repurposed drugs and their interacting atlas with 795 molecules; (c) 3260 off-targets relevant to the ADRs of 2731 drugs and (d) various types of pharmaceutical information, including diverse ADMET properties, versatile diseases, and various ADRs/off-targets. With the growing demands for discovering combinatorial/repurposed therapies and the rapidly emerging interest in AI-based drug discovery, DrugMAP was highly expected to act as an indispensable supplement to existing databases facilitating drug discovery, which was accessible at: https://idrblab.org/drugmap/.
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ETHNOPHARMACOLOGICAL RELEVANCE: Blossom of Citrus aurantium L. var. amara Engl. (CAVA) has been popularly consumed as folk medicine and dietary supplement owing to its various beneficial effects and especially anti-obesity potential. Our previous study predicted that eriodictyol was probably one of the key active compounds of the total flavonoids from blossom of CAVA. However, effects of eriodictyol in anti-obesity were still elusive. AIM OF THE STUDY: This study was performed to explore the precise role of eriodictyol in white adipose tissue (WAT) browning and hepatic lipid metabolism, and simultaneously, to verify the impact of eriodictyol on the total flavonoids of CAVA in losing weight. MATERIALS AND METHODS: The pancreas lipase assay was conducted and oleic acid-induced HepG2 cells were established to preliminarily detect the lipid-lowering potential of eriodictyol. Then, high fat diet-induced obesity (DIO) mouse model was established for in vivo studies. The biochemical indicators of mice were tested by commercial kits. The histopathological changes of WAT and liver in mice were tested by H&E staining, Oil Red O staining and Sirius Red staining. Immunohistochemical, Western blot assay, as well as RT-qPCR analysis were further performed. Additionally, molecular docking assay was used to simulate the binding of eriodictyol with potential target proteins. RESULTS: In vitro studies showed that eriodictyol intervention potently inhibited pancreatic lipase activity and reversed hepatic steatosis in oleic acid-induced HepG2 cells. Consistently, long-term medication of eriodictyol also effectively prevented obesity and improved lipid and glucose metabolism in diet-induced obesity mice. Obesity-induced histopathological changes in iWAT, eWAT and BAT, and abnormal expression levels of IL-10, IL-6 and TNF-α in iWAT of DIO mice were also significantly reversed by eriodictyol treatment. Eriodictyol administration significantly and potently promoted browning of iWAT by increasing expression levels of thermogenic marker protein of UCP1, as well as brown adipocyte-specific genes of PGC-1α, SIRT1 and AMPKα1. Further assays revealed that eriodictyol enhanced mitochondrial function, as shown by an increase in compound IV activity and the expression of tricarboxylic acid cycle-related genes. Besides, eriodictyol addition markedly reversed hepatic damages and hepatic inflammation, and enhanced hepatic lipid metabolism in DIO mice, as evidenced by its regulation on p-ACC, CPT1-α, UCP1, PPARα, PGC-1α, SIRT1 and p-AMPKα expression. Molecular docking results further validated that AMPK/SIRT1 pathway was probably the underlying mechanisms by which eriodictyol acted. CONCLUSION: Eriodictyol exhibited significant anti-obesity effect, which was comparable to that of the total flavonoids from blossom of CAVA. These findings furnished theoretical basis for the application of eriodictyol in weight loss.
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BACKGROUND: Obesity is a major public health issue in China and around the world. While acupuncture is often used in clinical practice, there is a lack of conclusive evidence for its weight-loss effect. Thus we will conduct a parallel, randomised, sham-controlled trial to evaluate the efficacy and safety of acupuncture for treating obesity. METHODS AND ANALYSIS: A total of 160 eligible participants with obesity will be randomly assigned to the verum acupuncture group or sham acupuncture group at a ratio of 1:1. All participants will be treated three times a week for a duration of 12 weeks, and followed up for another 16 weeks. The primary outcome is the percentage change in body weight from baseline to Week 12. The secondary outcomes include body mass index (BMI), waist circumference (WC), body fat percentage (BF%), blood pressure, fasting blood glucose, insulin, glycosylated haemoglobin A1c, blood lipids, and physical functioning score on the Short Form 36 Health Survey. Other secondary outcomes including psychological and social functions will also be evaluated using the body image scale, psychological function scale, and social function scale of the BODY-Q, Rosenberg Self-Esteem Scale, Patient Health Questionnaire-9, and Dutch Eating Behaviour Questionnaire. BMI, WC, BF% and blood pressure will be evaluated at Week 0, 4, 8, 12 and 28. Other secondary outcomes will be measured at Week 0, 12 and 28, respectively. Adverse events will be recorded in detail during the trial. ETHICS AND DISSEMINATION: Ethical approval of this trial was granted by the Ethics Committee of Chengdu Sport University (2023-102). Written informed consent will be obtained from study participants before enrolment. The findings will be disseminated through peer-reviewed journals. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2200062092).
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Terapia por Acupuntura , Índice de Masa Corporal , Obesidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Obesidad/terapia , Terapia por Acupuntura/métodos , Adulto , Femenino , Masculino , Circunferencia de la Cintura , Persona de Mediana Edad , Pérdida de Peso , Adulto Joven , China , Glucemia/metabolismo , Glucemia/análisis , Presión Sanguínea , Resultado del TratamientoRESUMEN
BACKGROUND: The paucity of evidence on longitudinal and consecutive recordings of physical activity (PA) and blood pressure (BP) under real-life conditions and their relationships is a vital research gap that needs to be addressed. OBJECTIVE: This study aims to (1) investigate the short-term relationship between device-measured step volume and BP; (2) explore the joint effects of step volume and variability on BP; and (3) examine whether the association patterns between PA and BP varied across sex, hypertension status, and chronic condition status. METHODS: This study used PA data of a prospective cohort of 3070 community-dwelling older adults derived from a mobile health app. Daily step counts, as a proxy of step volume, were derived from wearable devices between 2018 and 2022 and categorized into tertiles (low, medium, and high). Step variability was assessed using the SD of daily step counts. Consecutive daily step count recordings within 0 to 6 days preceding each BP measurement were analyzed. Generalized estimation equation models were used to estimate the individual and joint associations of daily step volume and variability with BP. Stratified analyses by sex, the presence of hypertension, and the number of morbidities were further conducted. RESULTS: A total of 3070 participants, with a median age of 72 (IQR 67-77) years and 71.37% (2191/3070) women, were included. Participants walked a median of 7580 (IQR 4972-10,653) steps and 5523 (IQR 3590-7820) meters per day for a total of 592,597 person-days of PA monitoring. Our results showed that higher levels of daily step volume were associated with lower BP (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure). Compared with participants with low step volume (daily step counts <6000/d) and irregular steps, participants with high step volume (≥9500/d) and regular steps showed the strongest decrease in systolic BP (-1.69 mm Hg, 95% CI -2.2 to -1.18), while participants with medium step volume (6000/d to <9500/d) and regular steps were associated with the lowest diastolic BP (-1.067 mm Hg, 95% CI -1.379 to -0.755). Subgroup analyses indicated generally greater effects on women, individuals with normal BP, and those with only 1 chronic disease, but the effect pattern was varied and heterogeneous between participants with different characteristics. CONCLUSIONS: Increased step volume demonstrated a substantial protective effect on BP among older adults with chronic conditions. Furthermore, the beneficial association between step volume and BP was enhanced by regular steps, suggesting potential synergistic protective effects of both increased step volume and step regularity. Targeting both step volume and variability through PA interventions may yield greater benefits in BP control, particularly among participants with hypertension and a higher chronic disease burden.
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Presión Sanguínea , Hipertensión , Dispositivos Electrónicos Vestibles , Humanos , Anciano , Femenino , Masculino , Estudios Longitudinales , Hipertensión/fisiopatología , Estudios Prospectivos , Ejercicio Físico , China , Persona de Mediana Edad , Anciano de 80 o más Años , Aplicaciones Móviles , Pueblos del Este de AsiaRESUMEN
INTRODUCTION: The current treatment regimens for Hodgkin's lymphoma (HL) are associated with high incidences of adverse events. PURPOSE: This study aimed to compare the efficacy and safety of doxorubicin + bleomycin + vincristine + dacarbazine (ABVD) and standard bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine + prednisone (BEACOPP) chemotherapy in the treatment of advanced stage HL. METHODS: This multicenter, randomized, parallel, open, positive control noninferiority trial was conducted from 2016 to 2019 and comprised 93 subjects who were randomized in a 1:1 ratio between the treatment (BEACOPP; n = 44) and control (ABVD; n = 49) groups. RESULTS: The primary efficacy endpoint of this trial was the objective response rate (ORR) after eight cycles of chemotherapy, which was 100.00% (36/36) in the treatment group and 95.74% (45/49) in the control group. The incidence of adverse reactions was 100% in both groups. Significant differences (P < 0.05) in the incidences of grade 3 (39/44 [88.64%] vs. 23/49 [46.94%]) and grade 4 (27/44 [61.36%] vs. 8/49 [16.94%]) adverse events were observed between the treatment and control groups, respectively. However, most of these reactions were manageable, with no serious consequences, and were reversible after discontinuation of the treatment. CONCLUSION: Both regimens had a similar ORR and were associated with a high number of adverse events. The ABVD regimen was better tolerated and safer than the standard BEACOPP regimen. This study indicates that the standard BEACOPP regimen may be considered as a treatment option for patients with advanced HL.
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Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Ciclofosfamida , Dacarbazina , Doxorrubicina , Etopósido , Enfermedad de Hodgkin , Prednisona , Procarbazina , Vincristina , Humanos , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Bleomicina/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Vincristina/efectos adversos , Vincristina/uso terapéutico , Vincristina/administración & dosificación , Masculino , Procarbazina/administración & dosificación , Procarbazina/efectos adversos , Procarbazina/uso terapéutico , Adulto , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Femenino , Etopósido/administración & dosificación , Etopósido/efectos adversos , Etopósido/uso terapéutico , Prednisona/administración & dosificación , Prednisona/efectos adversos , Prednisona/uso terapéutico , Dacarbazina/efectos adversos , Dacarbazina/administración & dosificación , Dacarbazina/uso terapéutico , Persona de Mediana Edad , Adulto Joven , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vinblastina/uso terapéutico , Adolescente , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
Objective: To retrospectively analyze clinical features in adolescent Menière's disease (MD). Methods: The medical records of adolescents with MD (11-17 years old) from May 2014 to March 2023 in Shandong Provincial ENT Hospital were retrospectively analyzed, including clinical features, a battery of auditory and vestibular function tests, sensory organization test, and imaging assessments. Patients with recurrent vertigo of childhood (RVC) were as controls. Results: Compared with RVC, adolescent MD showed higher pure tone average threshold (p < .001), lower speech discrimination score (p = .014), and lower otoacoustic emission pass rates (p = .005). Adolescents with MD exhibited significant reduction in equilibrium score (Conditions 1, 5, and 6; p1 = .035; p5 = .033; p6 = .003), composite sensory score (p = .014), and vestibular sensory score (p = .029). Adolescents with bilateral MD exhibited worse performance in equilibrium score and strategy score compared to adolescents with unilateral MD. For the affected ear, the more severe endolymphatic hydrops detected by gadolinium-enhanced magnetic resonance imaging, the higher the auditory brainstem response threshold (r = .850, p = .007), and the lower the otoacoustic emission pass rate (r = -.976, p < .001). Conclusion: Adolescent MD has similar vestibular information inputs with that of RVC, but the ability for the nerve center to use these clues to maintain balance is worse in adolescents with MD. There were potential differences in vestibular weights in adolescents with unilateral and bilateral MD, also potential effects on vision and proprioception. Level of Evidence: Level 4.
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Atopic dermatitis (AD), a recurrent inflammatory systemic skin disease, is difficult to cure. In the present study, several ethylenediamine-derived dehydrocostuslactone (DHCL) derivatives were prepared to assess their in vitro and in vivo anti-inflammatory activities. The results indicated that DHCL derivatives inhibited NO generation with low cytotoxicity. In particular, compound 5d exhibited the best anti-inflammatory activity. Subsequent experiments revealed that 5d not only inhibited the LPS-induced inflammatory response in RAW264.7 cells via the MAPK-NF-κB signaling pathway inhibition but also significantly decreased Th2-type cytokine levels and inhibited the NF-κB signaling pathway activation in mice with MC903-induced AD. Therefore, DHCL derivatives may be considered as new agents for the treatment of AD.
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Diatoms, a group of prevalent marine algae, contribute significantly to global primary productivity. Their substantial biomass is linked to enhanced absorption of blue-green light underwater, facilitated by fucoxanthin chlorophyll (Chl) a/c-binding proteins (FCPs), which exhibit oligomeric diversity across diatom species. Using mild clear native PAGE analysis of solubilized thylakoid membranes, we displayed monomeric, dimeric, trimeric, tetrameric, and pentameric FCPs in diatoms. Mass spectrometry analysis revealed that each oligomeric FCP has a specific protein composition, and together they constitute a large Lhcf family of FCP antennas. In addition, we resolved the structures of the Thalassiosira pseudonana FCP (Tp-FCP) homotrimer and the Chaetoceros gracilis FCP (Cg-FCP) pentamer by cryoelectron microscopy at 2.73-Å and 2.65-Å resolution, respectively. The distinct pigment compositions and organizations of various oligomeric FCPs affect their blue-green light-harvesting, excitation energy transfer pathways. Compared with dimeric and trimeric FCPs, the Cg-FCP tetramer and Cg-FCP pentamer exhibit stronger absorption by Chl c, redshifted and broader Chl a fluorescence emission, and more robust circular dichroism signals originating from Chl a-carotenoid dimers. These spectroscopic characteristics indicate that Chl a molecules in the Cg-FCP tetramer and Cg-FCP pentamer are more heterogeneous than in both dimers and the Tp-FCP trimer. The structural and spectroscopic insights provided by this study contribute to a better understanding of the mechanisms that empower diatoms to adapt to fluctuating light environments.
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Context: Presently, there is a paucity of prospective clinical trials investigating neoadjuvant therapy for locally advanced thyroid cancer. Objective: This study was a multicenter, open-label, single-arm, phase II trial evaluating the efficacy and safety of apatinib as neoadjuvant therapy in patients with local advanced differentiated thyroid cancer (DTC). Methods: Patients were treated with preoperative apatinib over a course of 2 to 4 cycles, culminating in surgical resection. The primary endpoints were objective response rate (ORR) and disease control rate (DCR); the secondary endpoints were the rate of R0 surgery, alterations in serum thyroglobulin levels, disease-free survival, and adverse events (AEs). Results: A total of 14 patients who met the inclusion criteria were administered neoadjuvant apatinib. Among these, 13 patients underwent surgical procedures following apatinib treatment and were enrolled in the ITT population. The ORR was 53.8% and the DCR was 100%. Of the patients, 84.6% received R0 surgery, while the remaining 15.4% underwent R1 resection. Predominant among the observed AEs were hypertension, hand-foot syndrome, hepatic dysfunction, proteinuria, and hypothyroidism, with no instances of grade 4 or 5 AEs reported. Subsequent to surgery, patients were followed up for a median period of 34 months, during which disease progression occurred in 5 individuals (35.7%), encompassing 3 cases of locoregional recurrences and 2 cases of distant metastases. Conclusion: Apatinib may be an effective agent in the use of neoadjuvant therapy for locally advanced DTC. Patients may therefore benefit from surgical outcomes and their long-term prognosis.
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Measurements of gene expression or signal transduction activity are conventionally performed using methods that require either the destruction or live imaging of a biological sample within the timeframe of interest. Here we demonstrate an alternative paradigm in which such biological activities are stably recorded to the genome. Enhancer-driven genomic recording of transcriptional activity in multiplex (ENGRAM) is based on the signal-dependent production of prime editing guide RNAs that mediate the insertion of signal-specific barcodes (symbols) into a genomically encoded recording unit. We show how this strategy can be used for multiplex recording of the cell-type-specific activities of dozens to hundreds of cis-regulatory elements with high fidelity, sensitivity and reproducibility. Leveraging signal transduction pathway-responsive cis-regulatory elements, we also demonstrate time- and concentration-dependent genomic recording of WNT, NF-κB and Tet-On activities. By coupling ENGRAM to sequential genome editing via DNA Typewriter1, we stably record information about the temporal dynamics of two orthogonal signalling pathways to genomic DNA. Finally we apply ENGRAM to integratively record the transient activity of nearly 100 transcription factor consensus motifs across daily windows spanning the differentiation of mouse embryonic stem cells into gastruloids, an in vitro model of early mammalian development. Although these are proof-of-concept experiments and much work remains to fully realize the possibilities, the symbolic recording of biological signals or states within cells, to the genome and over time, has broad potential to complement contemporary paradigms for how we make measurements in biological systems.
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ADN , Edición Génica , Transducción de Señal , Transcripción Genética , Animales , Ratones , Diferenciación Celular/genética , ADN/genética , ADN/metabolismo , Elementos de Facilitación Genéticos/genética , Edición Génica/métodos , Genómica , Células Madre Embrionarias de Ratones/citología , FN-kappa B/metabolismo , Reproducibilidad de los Resultados , ARN Guía de Sistemas CRISPR-Cas/genética , ARN Guía de Sistemas CRISPR-Cas/metabolismo , Transducción de Señal/genética , Factores de Tiempo , Factores de Transcripción/metabolismo , Transcripción Genética/genética , Vía de Señalización Wnt/genética , Motivos de Nucleótidos , Secuencia de Consenso/genética , Biología Evolutiva , Prueba de Estudio ConceptualRESUMEN
Background: There have been studies on the role of sperm-associated antigen 6 (SPAG6) in cytoskeleton formation and growth cone stability, but it is also unknown how spag6 affect tumor growth and development. The aim of this study was to clarify the role of SPAG6 in pan-cancer, with some findings about thyroid carcinoma (THCA) validated through experiments. Methods: We examined the role of SPAG6 in pan-cancer, with the data being collected from databases. Further analysis was conducted to assess its correlations with prognosis, gene heterogeneity, stemness, and tumor immunity. The interacting proteins of SPAG6 were also identified, and gene ontology enrichment analysis was performed to determine its biological function. We preliminarily confirmed the role of SPAG6 via in vitro experiments and immunofluorescence staining. Results: This study found that SPAG6 expression was differentially expressed in cancers and at various tumor stages and grades. In stomach and esophageal carcinoma (STES), stomach adenocarcinoma (STAD), kidney renal clear cell carcinoma (KIRC), lung squamous cell carcinoma (LUSC), and adrenocortical carcinoma (ACC), SPAG6 expression was correlated with gender. SPAG6 expression was also found to be correlated with prognostic value, with low expression being associated with poor prognosis. Furthermore, SPAG6 expression was positively linked with immune-related cells in HNSC, chemokine receptors in LUSC, and immune checkpoint genes in THCA. Furthermore, SPAG6 overexpression suppressed the malignant phenotypes of THCA cells, manifested by slower proliferation and decreased migration. The different SPAG6 expression in THCA led to different malignant phenotypes, which are involved in the upregulation of DNA repair, MYC targets, peroxisome, and G2M checkpoint. Conclusions: SPAG6 plays a significant role as an oncogene and can be used as a marker to predict the prognosis of cancer. SPAG6 influences both the tumor immune infiltration and microenvironment, making it a promising immunotherapeutic target for tumor therapy.
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To alleviate the problems of environmental pollution and energy crisis, aggressive development of clean and alternative energy technologies, in particular, water splitting, metal-air batteries, and fuel cells involving two key half reactions comprising hydrogen evolution reaction (HER) and oxygen reduction (ORR), is crucial. In this work, an innovative hybrid comprising heterogeneous Cu/Co bimetallic nanoparticles homogeneously dispersed on a nitrogen-doped carbon layer (Cu/Co/NC) was constructed as a bifunctional electrocatalyst toward HER and ORR via a hydrothermal reaction along with post-solid-phase sintering technique. Thanks to the interfacial coupling and electronic synergism between the Cu and Co bimetallic nanoparticles, the Cu/Co/NC catalyst showed improved catalytic ORR activity with a half-wave potential of 0.865 V and an excellent stability of more than 30 h, even compared to 20 wt% Pt/C. The Cu/Co/NC catalyst also exhibited excellent HER catalytic performance with an overpotential of below 149 mV at 10 mA/cm2 and long-term operation for over 30 h.
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Background: Right ventricular involvement in hypertrophic cardiomyopathy is uncommon. This study aimed to evaluate clinical outcomes of the modified septal myectomy in patients diagnosed with biventricular hypertrophic cardiomyopathy (BHCM), a subject seldom explored in the literature. Methods: We conducted a retrospective cohort study from January 2019 to January 2023, enrolling 12 patients with BHCM. Each patient underwent a modified septal myectomy and was followed postoperatively. Clinical data and echocardiographic parameters, including the ventricular outflow tract peak pressure gradient and maximum interventricular septum thickness, were collected and analyzed. Results: The study cohort had a median age of 43.0 (interquartile range 14.5-63.0) years at surgery, with four patients (33.3%) being children. Two patients (16.7%) previously underwent percutaneous transluminal septal myocardial ablation. Surgical relief of biventricular outflow tract obstruction (BVOTO) was achieved in five patients (41.7%), aside from those managed solely for left ventricular outflow tract obstruction. In five instances, three-dimensional (3D) printing technology assisted in surgical planning. The postoperative interventricular septum thickness was significantly reduced (21.0 mm preoperative vs. 14.5 mm postoperative, p < 0.001), effectively eliminating residual ventricular outflow tract obstruction. There were no severe complications, such as septal perforation or third-degree atrioventricular block. During a mean follow up of 21.2 ± 15.3 months, no sudden deaths, residual outflow tract obstruction, permanent pacemaker implantation, recurrent systolic anterior motion, or reoperations were reported. Conclusions: Our findings affirm that the modified septal myectomy remains the gold standard treatment for BHCM, improving patient symptoms and quality of life. BVOTO relief can be safely and effectively achieved through septal myectomy via transaortic and pulmonary valve approaches in selected patients. For intricate cases, the application of 3D printing technology as a preoperative planning tool is advised to optimize surgical precision and safety.
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Background and aims: In recent years, the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and colorectal cancer (CRC) or colorectal adenoma (CRA) has gained widespread attention. Previous meta-analyses on this subject either incorporated numerous cross-sectional studies, which were susceptible to bias, or concentrated solely on a restricted number of cohort studies. Moreover, with the release of a substantial number of high-quality cohort studies on this subject in the past two years, the findings continue to be debated and contradictory. Therefore, we conducted an updated systematic review and meta-analysis of cohort studies to quantitatively evaluate the magnitude of the association between them. Methods: Comprehensive searches of PubMed, Web of Science, and Embase were conducted without language restrictions from the time of their creation up to December, 2023. The pooled hazard ratios (HRs) with 95% confidence interval (CIs) were calculated by the generic inverse variance based on the random-effects model. Moreover, subgroup and sensitivity analyses were performed. Results: A total of 15 cohort studies were analyzed in this meta-analysis, which included 9,958,412 participants. The meta-analysis of 13 cohort studies showed that MASLD was linked to a higher risk of CRC (HR=1.25, 95% CI: 1.15-1.36, P < 0.00001). Additionally, further subgroup analysis indicated that the combined HR remained consistent regardless of the study location, nomenclature of fatty liver disease (FLD), confirmation methods for FLD, sample size, follow-up time, and study quality. Furthermore, the meta-analysis of four cohort studies demonstrated that MASLD was correlated with an increased risk of CRA (HR=1.38, 95% CI: 1.17-1.64, P = 0.0002). The sensitivity analysis results further validated the robustness of the aboved findings. Conclusion: The results of our meta-analysis indicated that MASLD was associated with an increased risk of incident CRC/CRA. In the future, it is necessary to conduct more prospective cohort studies to thoroughly assess potential confounding factors, particularly in individuals from Europe and North America. Furthermore, related mechanism studies should be conducted to enhance our understanding of the link between MASLD and CRC/CRA. Systematic review registration: Open Science Framework registries (https://osf.io/m3p9k).
RESUMEN
Coronary artery disease (CAD) is a common comorbidity of type 2 diabetes mellitus (T2DM). However, the pathophysiology connecting these two phenotypes remains to be further understood. Combined analysis in multi-ethnic populations can help contribute to deepening our understanding of biological mechanisms caused by shared genetic loci. We applied genetic correlation analysis and then performed conditional and joint association analyses in Chinese, Japanese, and European populations to identify the genetic variants jointly associated with CAD and T2DM. Next, the associations between genes and the two traits were also explored. Finally, fine-mapping and functional enrichment analysis were employed to identify the potential causal variants and pathways. Genetic correlation results indicated significant genetic overlap between CAD and T2DM in the three populations. Over 10,000 shared signals were identified, and 587 were shared by East Asian and European populations. Fifty-six novel shared genes were found to have significant effects on both CAD and T2DM. Most loci were fine-mapped to plausible causal variant sets. Several similarities and differences of the involved genes in GO terms and KEGG pathways were revealed across East Asian and European populations. These findings highlight the importance of immunoregulation, neuroregulation, heart development, and the regulation of glucose metabolism in shared etiological mechanisms between CAD and T2DM.
RESUMEN
BACKGROUND AND AIM: The introduction of the latest nomenclature, metabolic associated steatotic liver disease (MASLD), proposed by the multi-society without Asian society consensus statement, aims to redefine the diagnostic criteria for metabolic associated fatty liver disease (MAFLD). However, its effect on the epidemiology in Asia remains unclear. METHOD: We conducted a population-based cross-sectional survey on fatty liver disease using multistage stratified random sampling of participants from Guangzhou, a representative area in China (ChiCTR2000033376). Demographic, socioeconomic, lifestyle, and laboratory data were collected. Hepatic steatosis and the severity of fibrosis were assessed using FibroScan. RESULTS: A total of 7388 individuals were recruited, the proportion of which meeting the definitions for nonalcoholic fatty liver disease (NAFLD), MAFLD, and MASLD were 2359 (31.9%), 2666 (36.1%), and 2240 (30.3%), respectively. One hundred and twenty (1.6%) patients had cryptogenic SLD, and 537 (7.3%) patients were diagnosed with MetALD. MASLD did not significantly differ from NAFLD and MAFLD, except that MAFLD patients had a lower proportion of males, hypertension, and diabetes and were less likely to consume tea (P < 0.05). Both cryptogenic SLD and MASLD non-MAFLD patients exhibited milder hepatic steatosis and a lower frequency of liver injury than NAFLD, MAFLD, or MASLD patients (all P < 0.05). An increased HOMA-IR (adjusted OR: 1.33, 95% CI: 1.10-2.03) was associated with higher risk of moderate-to-severe steatosis for MASLD non-MAFLD patients, while consuming more cups of tea (P for trend = 0.015) showed inverse associations. CONCLUSION: Irrespective of terminology used is that fatty liver disease is highly prevalent in the Han Chinese population. Differences in insulin resistance and lifestyle risk factors are associated with redefinition disparities.