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INTRODUCTION: The head and neck comprise vital organs and are apparent human body parts. Tumours here impair physical and sensory functions as well as appearance and social interactions, leading to body image distress (BID) and threatening mental health and quality of life. Acceptance and commitment therapy has shown effectiveness in improving BID in groups such as breast cancer patients. This study aims to apply this therapy to intervene in head and neck cancer (HNC) patients, aiming to improve BID and promote better psychological well-being. METHODS AND ANALYSIS: This study is a prospective, parallel-group, randomised controlled trial. A total of 64 HNC patients will be allocated to either an intervention group or a control group. The intervention group will engage in a 3 week, six-session group-based acceptance and commitment therapy programme, while the control group will receive standard treatment. The primary outcome is cancer-related BID, and secondary outcomes are HNC-related BID, psychological flexibility, coping style and psychological distress. These indicators will be measured at baseline, postintervention and 1 month following the intervention's completion. ETHICS AND DISSEMINATION: The trial has received approval from the Institutional Review Board of Shanghai Proton and Heavy Ion Hospital (2308-67-02). The study results will be shared through peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300077863.
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Terapia de Aceptación y Compromiso , Imagen Corporal , Neoplasias de Cabeza y Cuello , Calidad de Vida , Humanos , Terapia de Aceptación y Compromiso/métodos , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/psicología , China , Imagen Corporal/psicología , Estudios Prospectivos , Femenino , Masculino , Distrés Psicológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Adaptación Psicológica , Adulto , Persona de Mediana EdadRESUMEN
Blinatumomab has emerged as a promising component of first-line therapy for acute B-cell precursor lymphoblastic leukemia (BCP-ALL), bolstering treatment efficacy. To mitigate CD19 selection pressure and reduce the incidence of blinatumomab-associated toxicities, pre-treatment chemotherapy is recommended before administering blinatumomab. From September 2022 to December 2023, we conducted a single-arm, multicenter, phase 2 trial (NCT05557110) in newly diagnosed Philadelphia chromosome-negative BCP-ALL (Ph-negative BCP-ALL) patients. Participants received induction treatment with reduced-dose chemotherapy (RDC), comprising idarubicin, vindesine, and dexamethasone over 7 days, followed by 2 weeks of blinatumomab. Those failing to achieve composite complete remission (CRc) received an additional 2 weeks of blinatumomab. The primary endpoint was the CRc rate post initial induction treatment. Of the 35 enrolled patients, 33 (94%) achieved CRc after 2 weeks of blinatumomab, with 30 (86%) achieving measurable residual disease (MRD) negativity. Two patients extended blinatumomab to 4 weeks. With either 2 or 4 weeks of blinatumomab treatment, all patients achieved CR (35/35) and 89% (31/35) were MRD negativity. The median time to CR was 22 days. Immune effector cell-associated neurotoxicity syndrome was limited (14%, all grade 1). Non-hematological adverse events of grade 3 or higher included pneumonia (17%), sepsis (6%), and cytokine release syndrome (9%). With a median follow-up of 11.5 months, estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%, respectively. These findings affirm that RDC followed by blinatumomab is an effective and well-tolerated induction regimen for newly diagnosed Ph-negative BCP-ALL, supporting a shift towards less intensive and more targeted therapeutic approaches. Trial registration: https://www.clinicaltrials.Gov . Identifier NCT05557110.
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Anticuerpos Biespecíficos , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia de Inducción , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Biespecíficos/efectos adversos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Adulto Joven , Quimioterapia de Inducción/métodos , Anciano , Adolescente , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Dexametasona/efectos adversos , Inducción de RemisiónRESUMEN
Angqu, positioned in the eastern expanse of the Tibet Plateau, claims the title of the largest tributary to the Lancang River. In October and December of 2018, in the sediment of Angqu, a comprehensive investigation was conducted on nine heavy metals-arsenic (As), manganese (Mn), chromium (Cr), cadmium (Cd), lead (Pb), mercury (Hg), copper (Cu), zinc (Zn), and nickel (Ni). This investigation aimed to scrutinize the spatial and temporal distribution patterns of these metals, assess the pollution status and ecological risks associated with the sediments, and delve into the sources contributing to their presence. The research results indicate that the average concentrations of As, Hg, and Cd in Angqu sediments exceed the soil background values of Tibet, while the concentrations of other heavy metals are below the soil background values of Tibet. Notably, arsenic poses potential ecological risks. In Angqu sediments, the concentrations of Mn, Cu, Ni, and Pb are generally higher in the wet season, but the seasonal variations of heavy metals in Angqu sediments are not significant. The sediments in the Angqu Basin are predominantly affected by mercury Hg, Cd, and As, with varying degrees of pollution at different sampling points. In the main stream of Angqu (City section), Hg pollution has reached above a moderate level, whereas As pollution near the tributary is only slightly polluted. The analysis of heavy metal sources reveals that there are five primary contributors to heavy metals in surface sediments of Angqu: parent material, agricultural activities, groundwater, atmospheric deposition, and other unidentified sources. Mn, Cr, Pb, and Ni are mainly derived from soil parent material, accounting for more than 50%. About 60.82% of As comes primarily from groundwater. Zn and Cd are mainly sourced from agricultural activities, accounting for 41.25% and 34.33%, respectively. Additionally, 20.6% of Hg originates from atmospheric deposition.
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Monitoreo del Ambiente , Sedimentos Geológicos , Metales Pesados , Ríos , Contaminantes Químicos del Agua , Metales Pesados/análisis , Sedimentos Geológicos/química , Medición de Riesgo , Tibet , Contaminantes Químicos del Agua/análisis , Ríos/química , Monitoreo del Ambiente/métodosRESUMEN
Primary breast Burkitt lymphoma (PB-BL) is an exceedingly rare form of primary breast lymphoma. Ultrasonography is the preferred modality for diagnosing breast diseases; however, the ultrasonic features of Burkitt lymphoma have rarely been reported. Herein, we report a case of ultrasonically diagnosed bilateral PB-BL in a lactating patient and present a literature review. A 28-year-old female patient experienced bilateral breast engorgement starting more than a month after childbirth. At three months postpartum, the patient experienced extreme bilateral breast engorgement, with the skin appearing dark purple and jaundiced. Based on the imaging diagnosis, pathological, immunohistochemical, and molecular biological findings, she was diagnosed with Burkitt lymphoma involves bilateral breasts, right adrenal glands, uterus, and multiple bones. After 4 cycles of combination chemotherapy, the tumor basically disappeared, and then after autologous stem cell transplantation and one cycle of combination chemotherapy, the patient is generally in good condition and is under follow-up. We found that the ultrasonic characteristics of PB-BL are different from those of common breast cancer or lactation mastitis. PB-BL lesions are often multiple, large masses, and even involve the whole breast. The characteristic reticular structures are common in lesions, and irregular hyperechoic masses can be seen around it. The mass has abundant peripheral and internal blood flow signals, but internal calcification and attenuated posterior echoes of masses are rarely observed. Thus, the ultrasonic features of breast Burkitt lymphoma are somewhat specific and understanding these features is conducive to its early identification.
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The recruitment of microorganisms by plants can enhance their adaptability to environmental stressors, but how root-associated niches recruit specific microorganisms for adapting to metalloid-metal contamination is not well-understood. This study investigated the generational recruitment of microorganisms in different root niches of Vetiveria zizanioides (V. zizanioides) under arsenic (As) and antimony (Sb) stress. The V. zizanioides was cultivated in As- and Sb-cocontaminated mine soils (MS) and artificial pollution soils (PS) over two generations in controlled conditions. The root-associated microbial communities were analyzed through 16S rRNA, arsC, and aioA gene amplicon and metagenomics sequencing. V. zizanioides accumulated higher As(III) and Sb(III) in its endosphere in MS in the second generation, while its physiological indices in MS were better than those observed in PS. SourceTracker analysis revealed that V. zizanioides in MS recruited As(V)- and Sb(V)-reducing microorganisms (e.g., Sphingomonales and Rhodospirillaceae) into the rhizoplane and endosphere. Metagenomics analysis further confirmed that these recruited microorganisms carrying genes encoding arsenate reductases with diverse carbohydrate degradation abilities were enriched in the rhizoplane and endosphere, suggesting their potential to reduce As(V) and Sb(V) and to decompose root exudates (e.g., xylan and starch). These findings reveal that V. zizanioides selectively recruits As- and Sb-reducing microorganisms to mitigate As-Sb cocontamination during the generational growth, providing insights into novel strategies for enhancing phytoremediation of metalloid-metal contaminants.
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Chewing areca nuts is popular in China. Areca alkaloids are the major toxic compounds in areca nuts. In this study, the levels of four areca alkaloids (i.e. arecoline, arecaidine, guvacoline and guvacine) in 119 areca nut samples were analyzed and 3030 areca nut consumption questionnaires were collected to investigate the exposure to areca alkaloids in the Chinese populations through areca nut chewing. The levels of arecoline, arecaidine, guvacoline and guvacine in different areca nut products were 0.46-4.97 mg/g, 0.57-7.51 mg/g, 0.08-1.44 mg/g and 0.03-8.48 mg/g, respectively. Chewing fresh areca fruits was the main source of arecoline and the total areca alkaloids exposure. The estimated daily intake (EDI) of arecoline and the total areca alkaloids for the Chinese populations were 1.126 and 2.625 mg/kg BW/day for average exposure, 4.411 and 9.739 mg/kg BW/day for high exposure (P95th). The EDI varied with age and gender. The young male population (≤ 34 years) had the highest EDI than other populations. Concentrated and focused efforts are required to educate the general public, especially the young male population, about the risks of areca nut chewing to reduce exposure to areca alkaloids of the Chinese population. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05966-6.
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Background: To identify the risk factors and construct a predictive model for early recurrence of hepatitis B virus(HBV-)- related hepatocellular carcinomas(HCCs) after radical resection. Data and methods: A total of 465 HBV-related HCC patients underwent radical resections between January 1, 2012 and August 31, 2018.Their data were collected through the inpatient information management system of the First Affiliated Hospital of University of Science and Technology of China. Survival and subgroup analyses of early recurrence among male and female patients were performed using Kaplan-Meier curves. The independent risk factors associated with early postoperative tumor recurrence were analyzed using multivariate Cox proportional hazards regression model. Based on these independent risk factors, a risk function model for early recurrence was fitted, and a column chart for the prediction model was drawn for internal and external validation. Results: A total of 181 patients developed early recurrences, including 156 males and 25 females. There was no difference in the early recurrence rates between males and females. Tumor diameters>5cm, microvascular invasion and albumin level<35 g/L were independent risk factors for early recurrence. A nomogram for the early recurrence prediction model was drawn; the areas under the curve for the model and for external verification were 0.638 and 0.655, respectively. Conclusion: Tumor diameter>5 cm, microvascular invasion, and albumin level<35 g/L were independent risk factors for early recurrence. The prediction model based on three clinical indicators could predict early recurrence, with good discrimination, calibration, and extrapolation.
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Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Recurrencia Local de Neoplasia , Nomogramas , Humanos , Masculino , Femenino , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/patología , Persona de Mediana Edad , Adulto , Factores de Riesgo , Virus de la Hepatitis B , Estudios Retrospectivos , Hepatitis B/complicaciones , China/epidemiología , Anciano , PronósticoRESUMEN
Retinal degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), initially manifest as dysfunction or death of the retinal pigment epithelium (RPE). Subretinal transplantation of human pluripotent stem cell (hPSC)-derived RPE cells has emerged as a potential therapy for retinal degeneration. However, RPE cells differentiated from hPSCs using current protocols are xeno-containing and are rarely applied in clinical trials. The development of hPSC-derived RPE cell differentiation protocols using xeno-free biomaterials is urgently needed for clinical applications. In this study, two protocols (the activin A and NIC84 protocols) were selected for modification and use in the differentiation of hiPSCs into RPE cells; the chetomin concentration was gradually increased to achieve high differentiation efficiency of RPE cells. The xeno-free extracellular matrix (ECM) proteins, laminin-511, laminin-521 and recombinant vitronectin, were selected as plate-coating substrates, and a Matrigel (xeno-containing ECM)-coated surface was used as a positive control. Healthy, mature hPSC-derived RPE cells were transplanted into 21-day-old Royal College of Surgeons (RCS) rats, a model of retinal degeneration disease. The visual function of RCS rats was evaluated by optomotor response (qOMR) and electroretinography after transplantation of hPSC-derived RPE cells. Our study demonstrated that hPSCs can be efficiently differentiated into RPE cells on LN521-coated dishes using the NIC84 protocol, and that subretinal transplantation of the cell suspensions can delay the progression of vision loss in RCS rats.
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Electrosynthesis of adipic acid (a precursor for nylon-66) from KA oil (a mixture of cyclohexanone and cyclohexanol) represents a sustainable strategy to replace conventional method that requires harsh conditions. However, its industrial possibility is greatly restricted by the low current density and competitive oxygen evolution reaction. Herein, we modify nickel layered double hydroxide with vanadium to promote current density and maintain high faradaic efficiency (>80%) within a wide potential window (1.5 ~ 1.9 V vs. reversible hydrogen electrode). Experimental and theoretical studies reveal two key roles of V modification, including accelerating catalyst reconstruction and strengthening cyclohexanone adsorption. As a proof-of-the-concept, we construct a membrane electrode assembly, producing adipic acid with high faradaic efficiency (82%) and productivity (1536 µmol cm-2 h-1) at industrially relevant current density (300 mA cm-2), while achieving >50 hours stability. This work demonstrates an efficient catalyst for adipic acid electrosynthesis with high productivity that shows industrial potential.
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OBJECTIVE: To investigate the association between atherogenic index of plasma (AIP) and kidney stones (KS) occurrence and recurrence. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2014. Non-pregnant adults who provided complete information on AIP and KS were included in the analyses. AIP was calculated as log (triglyceride/high-density lipoprotein cholesterol). KS was ascertained with questionnaires. Weighted multivariable logistic regression model and restricted cubic spline (RCS) were applied to examine the associations between AIP and KS occurrence and recurrence. RESULTS: A total of 6488 subjects (weighted mean age 43.19 years and 49.26% male) with a weighted mean AIP of 0.66 were included in this study. The multivariable-adjusted OR for nephrolithiasis occurrence across consecutive tertiles was 1.00 (reference), 1.21 (95% CI: 0.90-1.62), and 1.85 (95% CI: 1.39-2.48), respectively. Moreover, each SD increment of AIP was associated with a 50% (OR:1.50, 95% CI: 1.25-1.81) higher risk of nephrolithiasis recurrence. RCSs showed significant and linear dose-response relationships between AIP and nephrolithiasis occurrence (p-overall = 0.006, p-nonlinear = 0.689) and recurrence (p-overall = 0.001, p-nonlinear = 0.848). The positive associations between AIP and nephrolithiasis occurrence and recurrence persisted in sensitivity analyses, suggesting the robustness of the results. CONCLUSION: In the current US nationally representative cross-sectional study, AIP was positively associated with KS occurrence and recurrence.
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Aterosclerosis , Cálculos Renales , Encuestas Nutricionales , Humanos , Masculino , Femenino , Estudios Transversales , Adulto , Cálculos Renales/epidemiología , Cálculos Renales/sangre , Persona de Mediana Edad , Prevalencia , Aterosclerosis/epidemiología , Aterosclerosis/sangre , Aterosclerosis/etiología , Triglicéridos/sangre , Factores de Riesgo , Recurrencia , HDL-Colesterol/sangre , Estados Unidos/epidemiología , Modelos LogísticosRESUMEN
Persistent truncus arteriosus (PTA) is a rare congenital heart malformation. A 4-year-old girl was diagnosed with type I PTA through echocardiography and confirmed by cardiac CTA.
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Ecocardiografía , Tronco Arterial Persistente , Humanos , Femenino , Tronco Arterial Persistente/diagnóstico por imagen , Preescolar , Ecocardiografía/métodos , Diagnóstico Diferencial , Angiografía Coronaria/métodosRESUMEN
Grain weight and grain shape are important traits that determine rice grain yield and quality. Mining more quantitative trait loci (QTLs) that control grain weight and shape will help to further improve the molecular regulatory network of rice grain development and provide gene resources for high-yield and high-quality rice varieties. In the present study, a QTL for grain length (GL) and grain width (GW), qGL5.2, was firstly fine-mapped into a 21.4 kb region using two sets of near-isogenic lines (NILs) derived from the indica rice cross Teqing (TQ) and IRBB52. In the NIL populations, the GL and ratio of grain length to grain width (RLW) of the IRBB52 homozygous lines increased by 0.16-0.20% and 0.27-0.39% compared with the TQ homozygous lines, but GW decreased by 0.19-0.75%. Then, by analyzing the grain weight and grain shape of the knock-out mutant, it was determined that the annotation gene Os05g0551000 encoded a RING-type E3 ubiquitin ligase, which was the cause gene of qGL5.2. The results show that GL and RLW increased by 2.44-5.48% and 4.19-10.70%, but GW decreased by 1.69-4.70% compared with the recipient. Based on the parental sequence analysis and haplotype analysis, one InDel variation located at -1489 in the promoter region was likely to be the functional site of qGL5.2. In addition, we also found that the Hap 5 (IRBB52-type) increased significantly in grain length and grain weight compared with other haplotypes, indicating that the Hap 5 can potentially be used in rice breeding to improve grain yield and quality.
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Pulmonary fibrosis (PF) is an interstitial lung disease characterized by inflammation and fibrotic changes, with an unknown cause. In the early stages of PF, severe inflammation leads to the destruction of lung tissue, followed by upregulation of fibrotic factors like Transforming growth factor-ß (TGF-ß) and connective tissue growth factor (CTGF), which disrupt normal tissue repair. Geniposide, a natural iridoid glycoside primarily derived from the fruits of Gardenia jasminoides Ellis, possesses various pharmacological activities, including liver protection, choleretic effects, and anti-inflammatory properties. In this study, we investigated the effects of Geniposide on chronic inflammation and fibrosis induced by bleomycin (BLM) in mice with pulmonary fibrosis (PF). PF was induced by intratracheal instillation of bleomycin, and Geniposide(100/50/25mgâ¢kg-1) was orally administered to the mice once a day until euthanasia(14 day/28 day). The Raw264.7 cell inflammation induced by LPS was used to evaluate the effect of Geniposide on the activation of macrophage. Our results demonstrated that Geniposide reduced lung coefficients, decreased the content of Hydroxyproline, and improved pathological changes in lung tissue. It also reduced the number of inflammatory cells and levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) of bleomycin-induced PF mice. At the molecular level, Geniposide significantly down-regulated the expression of TGF-ß1, Smad2/3, p38, and CTGF in lung tissues of PF mice induced by bleomycin. Molecular docking results revealed that Geniposide exhibited good binding activity with TGF-ß1, Smad2, Smad3, and p38. In vitro study showed Geniposide directly inhibited the activation of macrophage induced by LPS. In conclusion, our findings suggest that Geniposide can ameliorate bleomycin-induced pulmonary fibrosis in mice by inhibiting the TGF-ß/Smad and p38MAPK signaling pathways.
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Bleomicina , Iridoides , Fibrosis Pulmonar , Factor de Crecimiento Transformador beta , Proteínas Quinasas p38 Activadas por Mitógenos , Animales , Bleomicina/efectos adversos , Bleomicina/toxicidad , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Iridoides/farmacología , Ratones , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Transducción de Señal/efectos de los fármacos , Masculino , Células RAW 264.7 , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Proteínas Smad/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones Endogámicos C57BLRESUMEN
Background: Medical security work for the 2022 Beijing Winter Olympic and Paralympics faced enormous challenges under COVID-19. This study aimed to investigate the mental status of those medical team members to provide a reference for scientifically implementing medical security services for large-scale events. Methods: In this prospective cohort study, the Patient Health Questionnaire-9, Self-rating Anxiety Scale, General Self-Efficacy Scale, and Psychological Questionnaire for Emergent Events of Public Health (PQEEPH) were administered to 145 members of the medical team. A generalized mixed linear model was used to analyze the impact of work duration, position, on/off rotation, and gender on psychological status. Results: Work duration significantly impacted depression, anxiety, self-efficacy, and all dimensions of PQEEPH. Women scored higher than men in the PQEEPH dimensions of depression, neurasthenia, fear, and total score. Working status affected the dimensions of depression, neurasthenia, and total score. Deterioration in emotional state became apparent in the fourth week and recovered 1 week after the task concluded, while self-efficacy decreased from beginning to end. Conclusion: All the medical team members experienced emotional deterioration and decreased self-efficacy in medical security tasks. To maintain a medical team's psychological wellbeing during large-scale activities, rotation times should be set reasonably, and adequate mental health services should be provided.
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COVID-19 , Humanos , COVID-19/psicología , Masculino , Femenino , Estudios Prospectivos , Adulto , Autoeficacia , Encuestas y Cuestionarios , Depresión/psicología , Ansiedad/psicología , SARS-CoV-2 , China , Salud Mental , Persona de Mediana Edad , Deportes/psicología , Personal de Salud/psicología , Personal de Salud/estadística & datos numéricosRESUMEN
The antimicrobial and pro-healing properties remain critical clinical objectives for skin wound management. However, the escalating problem of antibiotic overuse and the corresponding rise in bacterial resistance necessitates an urgent shift towards an antibiotic-free approach to antibacterial treatment. The quest for antimicrobial efficacy while accelerating wound healing without antibiotic treatment have emerged as innovative strategies in skin wound treatment. Here, a dual-function hydrogel with antimicrobial and enhanced tissue-healing properties was developed by utilizing cyclodextrin, ferrocene, polyethyleneimine (PEI), and Bletilla striata polysaccharide (BSP), through multiple non-covalent interactions, which can intelligently release BSP by recognizing the wound inflammatory microenvironment through the cyclodextrin-ferrocene unit. Moreover, the porosity (65 % - 85 %), Young's modulus (400 KPa - 140 KPa), and DPPH scavenge rate (18 % - 40 %) of the hydrogel are modulated by varying the BSP content. The hydrogel exhibits outstanding antibacterial properties (98.3 % reduction of Escherichia coli observed after exposure to HTFC@BSP-20 for 24 h) and favorable biocompatibility. Furthermore, in a rat full-thickness skin wound model, the dual-function hydrogel significantly accelerates wound healing, increased CD31 expression promotes vascular regeneration, reduced TNF-α express and inhibited the inflammation. This multifunctional ROS responsive hydrogel provides a new perspective for antibiotics-free treatment of skin injuries.
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Antibacterianos , Vendajes , Hidrogeles , Polisacáridos , Especies Reactivas de Oxígeno , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Animales , Polisacáridos/química , Polisacáridos/farmacología , Ratas , Especies Reactivas de Oxígeno/metabolismo , Antibacterianos/farmacología , Antibacterianos/química , Inflamación/tratamiento farmacológico , Orchidaceae/química , Escherichia coli/efectos de los fármacos , Humanos , Piel/efectos de los fármacos , Ciclodextrinas/química , Ciclodextrinas/farmacología , Ratas Sprague-Dawley , Masculino , Compuestos Ferrosos/química , Compuestos Ferrosos/farmacología , MetalocenosRESUMEN
Obesity increases the risk of kidney injury, involving various pathological events such as inflammation, insulin resistance, lipid metabolism disorders, and hemodynamic changes, making it a significant risk factor for the development and progression of chronic kidney disease. Diosmin, a natural flavonoid glycoside, exhibits anti-inflammatory, antioxidant, anti-lipid, and vasodilatory effects. However, whether diosmin has a protective effect on obesity-related kidney injury remains unclear. The molecular formula of diosmin was obtained, and diosmin and target genes related to obesity-related kidney injury were screened. The interaction between overlapping target genes was analyzed. GO functional enrichment and KEGG pathway enrichment analyses were performed on overlapping target genes. Molecular docking was employed to assess the binding strength between overlapping target genes. Palmitic acid-induced damage to HK-2 cells, which were then treated with diosmin. Subsequently, the expression levels of relevant mRNAs and proteins were measured. Network analysis identified 219 potential diosmin target genes, 6800 potential target genes related to obesity-related kidney injury, and 93 potential overlapping target genes. Protein-protein interaction networks and molecular docking results revealed that AKT1, TNF-α, SRC, EGFR, ESR1, CASP3, MMP9, PPAR-γ, GSK-3ß, and MMP2 were identified as key therapeutic targets, and they exhibited stable binding with diosmin. GO analysis indicated that these key targets may participate in inflammation, chemical stress, and protein phosphorylation. KEGG revealed that pathways in cancer, AGE-RAGE signaling pathway, PI3K-AKT signaling pathway, PPAR signaling pathway, and insulin resistance as crucial in treating obesity-related kidney injury. CCK-8 assay showed that diosmin significantly restored the viability of HK-2 cells affected by palmitic acid. Oil Red O staining demonstrated that diosmin significantly improved lipid deposition in HK-2 cells induced by palmitic acid. PCR results showed that diosmin inhibited the mRNA levels of AKT1, TNF-α, EGFR, ESR1, CASP3, MMP9, GSK-3ß, and MMP2 while promoting the mRNA level of PPAR-γ. Western blot analysis revealed that diosmin restored PPAR-γ protein expression, inhibited NF-kB p-p65 protein expression, and reduced TNF-α protein expression. Diosmin demonstrated multi-target and multi-pathway effects in the treatment of obesity-associated renal injury, with key targets including AKT1, TNF-α, EGFR, ESR1, CASP3, MMP9, PPAR-γ, GSK-3ß, and MMP2. The mechanism may be through the modulation of the PPAR-γ/NF-κB signaling pathway, which can attenuate inflammatory responses and protect the kidney.
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Background: Limited epidemiological evidence suggests that exposure to trace elements adversely impacts the development of gastric precancerous lesions (GPL) and gastric cancer (GC). This study aimed to estimate the association of individual urinary exposure to multiple elements with GPL and GC. Methods: A case-control investigation was conducted in Anhui Province from March 2021 to December 2022. A total of 528 subjects (randomly sampled from 1,020 patients with GPL, 200 patients with GC, and 762 normal controls) were included in our study. Urinary levels of iron (Fe), copper (Cu), zinc (Zn), nickel (Ni), strontium (Sr), and Cesium (Cs) were measured using inductively coupled plasma mass spectrometry (ICP-MS). Four different statistical approaches were employed to explore the risk of GPL and GC with mixed exposure, including multivariate logistic regression, weighted quantile regression (WQS), quantile g-computation (Qgcomp), and the Bayesian kernel machine regression (BKMR) model. Results: The WQS model indicated that urinary exposure to a mixture of elements is positively correlated with both GPL and GC, with ORs for the mixture exposure of 1.34 (95% CI: 1.34-1.61) for GPL and 1.38 (95% CI: 1.27-1.50) for GC. The Qgcomp and BKMR models also demonstrated a statistically significant positive correlation between the mixture and both GPL and GC. Conclusion: Considering the limitations of case-control studies, future prospective studies are warranted to elucidate the combined effects and mechanisms of trace elements exposure on human health.
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Lesiones Precancerosas , Neoplasias Gástricas , Oligoelementos , Humanos , Neoplasias Gástricas/orina , Neoplasias Gástricas/epidemiología , China/epidemiología , Masculino , Oligoelementos/orina , Femenino , Estudios de Casos y Controles , Persona de Mediana Edad , Lesiones Precancerosas/orina , Anciano , AdultoRESUMEN
OBJECTIVE: This study investigated the clinical importance of long noncoding RNA myocardial infarction-associated transcript (MIAT) in periodontitis and its impact on the functional regulation of human periodontal ligament fibroblasts (hPDLFs). METHODS: Ninety-eight periodontitis patients and 74 healthy controls were enrolled. In vitro cellular models were created using Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) to stimulate hPDLFs. Real-time quantitative polymerase chain reaction was used to measure mRNA levels of MIAT and osteogenic factors. Inflammation factor concentration was assessed using an enzyme-linked immunosorbent assay. Cell viability and apoptosis were examined by cell counting kit -8 and flow cytometry assay. The targeting relationship was verified by the dual-luciferase reporter and RNA Immunoprecipitation assay. RESULTS: Highly expressed MIAT and Dicckopf-1 (DDK1), and lowly expressed miR-204-5p were found in the gingival crevicular fluid of periodontitis patients and Pg-LPS induced hPDLFs. MIAT has a sensitivity of 76.53 % and a specificity of 86.49 % for identifying patients with periodontitis among healthy individuals. MIAT acts as a sponge for miR-204-5p and upregulates DDK1 mRNA expression. Silencing of MIAT diminished the promotion of apoptosis and inflammation in hPDLFs by Pg-LPS and enhanced osteogenic differentiation. However, a miR-204-5p inhibitor significantly reversed the effect of silenced MIAT. CONCLUSIONS: MIAT may act as a promising biomarker for periodontitis. It modulates apoptosis, inflammation, and osteogenic differentiation of PDLFs by focusing on the miR-204-5p/DKK1 axis, indicating its potential as a new therapeutic target for treating periodontitis.
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Fibroblastos , Péptidos y Proteínas de Señalización Intercelular , MicroARNs , Ligamento Periodontal , Periodontitis , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/metabolismo , ARN Largo no Codificante/genética , Ligamento Periodontal/citología , Ligamento Periodontal/metabolismo , MicroARNs/metabolismo , Periodontitis/metabolismo , Masculino , Fibroblastos/metabolismo , Femenino , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Adulto , Apoptosis , Reacción en Cadena en Tiempo Real de la Polimerasa , Ensayo de Inmunoadsorción Enzimática , Persona de Mediana Edad , Porphyromonas gingivalis , Líquido del Surco Gingival/metabolismo , Células Cultivadas , Supervivencia Celular , Estudios de Casos y Controles , Lipopolisacáridos/farmacología , Citometría de FlujoRESUMEN
All-polymer photodetectors possess unique mechanical flexibility and are ideally suitable for the application in next-generation flexible, wearable short-wavelength infrared (SWIR, 1000-2700 nm) photodetectors. However, all-polymer photodetectors commonly suffer from low sensitivity, high noise, and low photoresponse speed in the SWIR region, which significantly diminish their application potential in wearable electronics. Herein, two polymer acceptors with absorption beyond 1000 nm, namely P4TOC-DCBT and P4TOC-DCBSe, were designed and synthesized. The two polymers possess rigid structure and good conformational stability, which is beneficial for reducing energetic disorder and suppressing dark current. Owing to the efficient charge generation and ultralow noise current, the P4TOC-DCBT-based all-polymer photodetector achieved a specific detectivity () of over 1012 Jones from 650 (visible) to 1070 nm (SWIR) under zero bias, with a response time of 1.36 µs. These are the best results for reported all-polymer SWIR photodetectors in photovoltaic mode. More significantly, the all-polymer blend films exhibit good mechanical durability, and hence the P4TOC-DCBT-based flexible all-polymer photodetectors show a small performance attenuation (<4%) after 2000 cycles of bending to a 3 mm radius. The all-polymer flexible SWIR organic photodetectors are successfully applied in pulse signal detection, optical communication and image capture.
RESUMEN
Arthropods harbor complex microbiota that play a pivotal role in host fitness. While multiple factors, like host species and diet, shape microbiota in arthropods, their impact on community assembly in wild insects remains largely unknown. In this study, we surveyed bacterial and fungal community assembly in nine sympatric wild insect species that share a common citrus fruit diet. Source tracking analysis suggested that these insects acquire some bacteria and fungi from the citrus fruit with varying degrees. Although sharing a common diet led to microbiota convergence, the diversity, composition, and network of both bacterial and fungal communities varied significantly among surveyed insect groups. Null model analysis indicated that stochastic processes, particularly dispersal limitation and drift, are primary drivers of structuring insect bacterial and fungal communities. Importantly, the influence of each community assembly process varied strongly depending on the host species. Thus, we proposed a speculative view that the host specificity of the microbiome and mycobiome assembly is widespread in wild insects despite sharing the same regional species pool. Overall, this research solidifies the importance of host species in shaping microbiomes and mycobiomes, providing novel insights into their assembly mechanisms in wild insects. IMPORTANCE: Since the microbiome has been shown to impact insect fitness, a mechanistic understanding of community assembly has potentially significant applications but remains largely unexplored. In this paper, we investigate bacterial and fungal community assembly in nine sympatric wild insect species that share a common diet. The main findings indicate that stochastic processes drive the divergence of microbiomes and mycobiomes in nine sympatric wild insect species. These findings offer novel insights into the assembly mechanisms of microbiomes and mycobiomes in wild insects.