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Management of oligometastatic non-small cell lung cancer (OM-NSCLC) has changed considerably in recent years, as these patients were found to have better survival with systemic therapy followed by consolidative radiation. Stereotactic body radiotherapy (SBRT), characterized by high doses of radiation delivered in a limited number of fractions, has been shown to have improved local control compared to conventionally fractionated radiation in early-stage lung cancer, but its use in large tumors, ultra-central tumors, or mediastinal nodal regions is limited due to concerns of toxicity to nearby serial mediastinal structures. Recent improvements in image guidance and fast replanning allow adaptive radiotherapy to be used to personalize treatment to the patient's daily anatomy and ensure accurate dose delivery to the tumor while minimizing dose and toxicity to normal. Adaptive SBRT can expand its use into ultra-central tumors that otherwise may not be amenable to SBRT or enable alternative fractionation schedules such as personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR) with one-month intervals between fractions. In this case, we report a patient initially presenting with bulky OM-NSCLC of the left lung and mediastinum with an isolated left femur metastasis who was referred for consolidative radiotherapy after systemic therapy. We demonstrate how CT-guided online adaptive radiotherapy to the lung and mediastinum can be used despite the long time interval between treatments. In addition, adaptive plans lead to a substantial decrease in the heart dose, with moderate decreases in other organs compared to non-adaptive plans. This case demonstrates the feasibility of using adaptive radiotherapy for PULSAR of ultra-central OM-NSCLC.
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INTRODUCTION: Patients with advanced ALK-positive non-small cell lung cancer (NSCLC) typically have poor response to immunotherapy; the benefit of consolidation durvalumab in patients with unresectable stage III ALK-positive NSCLC remains unclear. Herein, we compare the efficacy and safety of consolidation ALK tyrosine kinase inhibitor (TKI) versus durvalumab or observation after concurrent chemoradiation (cCRT). METHODS: We conducted a retrospective study using a multi-center study of 17 institutions globally. Patients with unresectable stage III ALK-positive NSCLC treated between 2015-2022 were included. Patients received ALK TKI, durvalumab, or observation after cCRT. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated using Kaplan-Meier method. Treatment-related adverse events (trAE) were classified by Common Terminology Criteria for Adverse Events v5.0. Outcomes were assessed by multivariable Cox regression analysis. RESULTS: Sixty-seven patients were included, of whom 39 (58%) were female. Median age was 57 years (IQR: 49-67). Fifteen received consolidation ALK TKI, 30 received durvalumab, and 22 underwent observation. Baseline characteristics were similar across the 3 groups other than differences in race. After adjusting for stage, age, and nodal status, median rwPFS was significantly longer for ALK TKI (rwPFS not reached [NR], 95% CI 22.7-NR) versus durvalumab (11.3 months, 95% CI 8.9-18.5, hazard ratio [HR]=0.12, 95% CI: 0.026-0.5, p-adjusted=0.006) or observation (7.2 months, 95% CI 3.4-10.6, HR=0.04, 95% CI: 0.009-0.2, p-adjusted<0.0001). Durvalumab significantly improved median rwPFS compared to observation (HR=0.37, 95% CI: 0.19-0.71, p-adj = 0.002, p-adjusted=0.002). Median OS in the ALK TKI and durvalumab cohorts was significantly improved compared to patients on observation (ALK TKI-observation: p=0.04; durvalumab-observation: p=0.03). TrAE of any grade occurred in 8 (53%) and 11 (37%) patients treated with ALK-TKI and durvalumab, respectively. Grade ≥3 trAEs occurred in 27% (n=4) of patients treated with ALK TKI and 6.7% of patients treated with durvalumab. CONCLUSIONS: Patients with ALK-positive NSCLC experience significantly improved rwPFS when treated with consolidation ALK TKI therapy, surpassing outcomes seen with either durvalumab or observation. While both ALK TKI therapy and durvalumab offer an extension in OS compared to observation alone, it appears that ALK TKI therapy is the superior choice, underscoring its pivotal role in enhancing patient survival.
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Sleep problems significantly affect the quality of life of autism spectrum disorder (ASD) children. This study aimed to evaluate the effects of a 12-week ball combination exercise, continuous theta burst stimulation (cTBS) stimulation, and combined intervention on sleep problems in children with ASD. Forty-five ASD children were divided into three intervention groups (ball combination exercise(n = 12), cTBS stimulation(n = 10), combined (n = 12) and a control group (n = 11). The intervention groups underwent intervention, while the control group maintained daily activities. The effects were assessed using the Children's Sleep Habits Questionnaire (CSHQ) scale. The results revealed that after 12 weeks of intervention, three programs reduced sleep problems in children with ASD. The post-test scores of the cTBS group (p = 0.002) and the combined group (p < 0.001) were significantly lower than the baseline scores on the CSHQ scale. The exercise group (p = 0.002) and the combined group (p < 0.001) showed significant improvement in sleep anxiety, while there was no statistically significant difference in the effectiveness of the three interventions for sleep-onset delay. The combined group outperformed the single intervention groups in the CSHQ score and sleep anxiety sub-dimensions. The combined intervention group showed slightly superior performance in sleep onset latency, however, there was no significant difference. Three interventions alleviated sleep issues in ASD children, with the combined method proving more effective. This study validates non-pharmacologic and combined approaches for ASD sleep problems. Future research should delve deeper into the mechanisms of these interventions in ASD children's sleep improvement.
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The connectivity (valency) of building blocks for constructing 3D covalent organic frameworks (COFs) has long been limited to 4, 6, 8, and 12. Developing a higher connectivity remains a great challenge in the field of COF structural design. Herein, this work reports a hierarchical expansion strategy for making 16-connected building blocks to construct 3D COFs with sqc topology. The [16 + 2] construction achieved by condensation between a 16-connected carbazolyl dicyanobenzene-based building block (CzTPN) and linear diamino linkers (BD or Bpy) affords two 3D COFs (named CzBD COF and CzBpy COF). Furthermore, attributed to the well-organized donor-acceptor (D-A) heterojunction, the Ni chelated CzBpy COF (Ni@CzBpy COF) exhibits excellent performance for photoredox/Ni dual catalytic C(sp3)-C(sp2) cross-coupling of alkyltrifluoroborates with aryl halides, achieving a maximum 98% conversion and 94% yield for various substrates. This work developed the first case of high-connectivity COFs bearing 16-connected units, which is the highest connectivity reported until now, and achieved efficient photocatalysis applications, thus greatly enriching the possibilities of COFs.
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Bakanae disease, caused by Fusarium fujikuroi, poses a significant threat to rice production and has been observed in most rice-growing regions. The disease symptoms caused by different pathogens may vary, including elongated and weak stems, slender and yellow leaves, and dwarfism, as example. Bakanae disease is likely to cause necrosis of diseased seedlings, and it may cause a large area of infection in the field through the transmission of conidia. Therefore, early disease surveillance plays a crucial role in securing rice production. Traditional monitoring methods are both time-consuming and labor-intensive and cannot be broadly applied. In this study, a combination of hyperspectral imaging technology and deep learning algorithms were used to achieve in situ detection of rice seedlings infected with bakanae disease. Phenotypic data were obtained on the 9th, 15th, and 21st day after rice infection to explore the physiological and biochemical performance, which helps to deepen the research on the disease mechanism. Hyperspectral data were obtained over these same periods of infection, and a deep learning model, named Rice Bakanae Disease-Visual Geometry Group (RBD-VGG), was established by leveraging hyperspectral imaging technology and deep learning algorithms. Based on this model, an average accuracy of 92.2% was achieved on the 21st day of infection. It also achieved an accuracy of 79.4% as early as the 9th day. Universal characteristic wavelengths were extracted to increase the feasibility of using portable spectral equipment for field surveillance. Collectively, the model offers an efficient and non-destructive surveillance methodology for monitoring bakanae disease, thereby providing an efficient avenue for disease prevention and control. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00169-1.
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BACKGROUND: To report the diagnosis and treatment of a rare disease of intravenous leiomyomatosis (IVL) originating from the uterus, growing in the inferior vena cava (IVC) and extending into the right atrium (RA) associated with a pelvic arteriovenous fistula (AVF). This is the first reported case of IVL in the IVC and RA with pulmonary benign metastasizing leiomyoma (PBML) secondary to a pelvic AVF despite the use of GnRH agonists in a nonmenopausal woman. CASE PRESENTATION: The patient was a 50-year-old premenopausal woman with a history of surgical resection for and antiestrogen conservative drug for pulmonary benign metastasizing leiomyoma (PBML) 5 years. The patient nevertheless developed IVL in the IVC, internal iliac vein and RA accompanied by AVF. Vaginal ultrasound combined with echocardiography and computerized tomographic venography imaging assists in the diagnosis of IVL combined with AVF, with histopathology and immunohistochemistry ultimately confirming the diagnosis. The patient ultimately was performed with a combination of hysterectomy, bilateral adnexectomy, and resection of tumors in the IVC and RA without cardiopulmonary bypass and sternotomy. CONCLUSION: BML may be difficult to control with incomplete removal of the uterus and ovaries even with the use of antiestrogenic medications, and medically induced AVF resulting from fibroid surgery may accelerate this process and the development of IVL.
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Fístula Arteriovenosa , Atrios Cardíacos , Leiomiomatosis , Neoplasias Pulmonares , Neoplasias Uterinas , Neoplasias Vasculares , Vena Cava Inferior , Humanos , Femenino , Vena Cava Inferior/patología , Vena Cava Inferior/cirugía , Vena Cava Inferior/diagnóstico por imagen , Persona de Mediana Edad , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugía , Fístula Arteriovenosa/cirugía , Fístula Arteriovenosa/etiología , Fístula Arteriovenosa/diagnóstico por imagen , Fístula Arteriovenosa/patología , Atrios Cardíacos/patología , Atrios Cardíacos/cirugía , Atrios Cardíacos/diagnóstico por imagen , Leiomiomatosis/patología , Leiomiomatosis/cirugía , Leiomiomatosis/diagnóstico por imagen , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/patología , Neoplasias Vasculares/patología , Neoplasias Vasculares/cirugía , Neoplasias Vasculares/diagnóstico por imagen , Neoplasias Cardíacas/secundario , Neoplasias Cardíacas/patología , Neoplasias Cardíacas/cirugía , Neoplasias Cardíacas/complicaciones , Resultado del Tratamiento , Histerectomía , Vena Ilíaca/patología , Vena Ilíaca/diagnóstico por imagenRESUMEN
Blood transcriptomics has emerged as a vital tool for tracking the immune system and supporting disease diagnosis, prognosis, treatment, and research. The present study was conducted to analyze the gene expression profile and potential biomarker candidates using the whole blood of mandarin fish (Siniperca chuatsi) infected with LPS or poly (I:C) at 0 h, 3 h, 6 h, and 12 h. Our data suggest that 310 shared differentially expressed genes (DEGs) were identified among each comparison group after LPS infection, and 137 shared DEGs were identified after poly (I:C) infection. A total of 62 shared DEGs were differentially expressed in all compared groups after LPS or poly (I:C) infection. Pathways analysis for DEGs in all different compared groups showed that cytokine-cytokine receptor interaction was the most enrichment pathway. The expression levels of genes C-X-C chemokine receptor type 2-like (cxcr2), chemokine (C-C motif) receptor 9a (ccr9a), chemokine (C-C motif) receptor 9b (ccr9b), chemokine (C-X-C motif) receptor 4b (cxcr4b), and interleukin 10 receptor alpha (il10ra) were significantly different in all compared groups and most enriched in cytokine-cytokine receptor interaction pathway. The protein-protein interactions analysis among all shared DEGs showed that cxcr4 was the hub gene with the highest degree. The biomarker candidates discovered in this study may, following validation, prove effective as diagnostic tools in monitoring mandarin fish diseases.
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Biomarcadores , Enfermedades de los Peces , Proteínas de Peces , Lipopolisacáridos , Perciformes , Poli I-C , Transcriptoma , Animales , Enfermedades de los Peces/inmunología , Poli I-C/farmacología , Biomarcadores/sangre , Lipopolisacáridos/farmacología , Perciformes/genética , Perciformes/inmunología , Perciformes/sangre , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Proteínas de Peces/sangre , Perfilación de la Expresión Génica/veterinaria , Inmunidad Innata/genética , Regulación de la Expresión Génica/inmunología , Regulación de la Expresión Génica/efectos de los fármacosRESUMEN
The association between built environment and physical activity has been recognized. However, how and to what extent microscale streetscapes are related to running activity remains underexplored, partly due to the lack of running data in large urban areas. Moreover, few studies have examined the interactive effects of macroscale built environment and microscale streetscapes. This study examines the main and interactive effects of the two-level environments on running intensity, using 9.73 million fitness tracker data from Keep in Shanghai, China. Results of spatial error model showed that: 1) the explanatory power of microscale streetscapes was higher than that of macroscale built environment with R2 of 0.245 and 0.240, respectively, which is different from the prior finding that R2 is greater for macroscale built environment than for microscale streetscape; 2) sky and green view indexes were positively associated with running intensity, whereas visual crowdedness had a negative effect; 3) there were negative interactions of land use Herfindahl-Hirschman index with sky and green view indexes, while a positive interaction was observed for visual crowdedness. To conclude, greener, more open and less visually crowded streetscapes, can promote running behavior and enhance the benefits of land use mix as well. The findings highlight the importance of streetscapes in promoting running behavior, instead of a supplement to macroscale built environment.
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Entorno Construido , Ciudades , Carrera , Humanos , China , Entorno Construido/estadística & datos numéricos , Carrera/estadística & datos numéricos , Masculino , Femenino , Adulto , Planificación Ambiental , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Gliomas are highly invasive brain tumors that evade accurate geographic assessment by conventional MRI due to microscopic invasion along white matter (WM) tracts. Advanced diffusion MRI techniques are needed to assess occult WM involvement. PURPOSE: To evaluate peak width of skeletonized mean diffusivity (PSMD) and peak width of skeletonized free water (PSFW), and axonal water fraction (AWF) for assessing glioma-induced alterations in normal-appearing WM and their relationship with isocitrate dehydrogenase 1 (IDH1) mutation. STUDY TYPE: Retrospective. POPULATION: One hundred five glioma patients (46 ± 13 years), 53 healthy controls (HCs) (46 ± 9 years). FIELD STRENGTH/SEQUENCE: 3.0 T, T1WI, T1-CE, T2WI, T2FLAIR, and DKI. ASSESSMENT: PSMD and PSFW were compared between lesion and contralateral sides in glioma patients and between patients and HCs. The associations between these metrics and clinical variables, including IDH1 mutation, was assessed. Corpus callosum (CC) injury, quantified by the AWF, was evaluated for its mediated effect of IDH1 mutation on contralesional PSMD and PSFW. STATISTICAL TESTS: Paired-t tests, ANCOVA, univariate and multivariate linear regression, and mediation analysis with significance set at P < 0.05. RESULTS: Contralateral PSMD and PSFW were significantly higher in left-sided gliomas (PSMD: 0.206 ± 0.027 vs. 0.193 ± 0.023; PSFW: 0.119 ± 0.019 vs. 0.106 ± 0.020) than in HCs, with similar increases in right-sided gliomas (PSMD: 0.219 ± 0.036 vs. 0.195 ± 0.023; PSFW: 0.129 ± 0.031 vs. 0.109 ± 0.020). IDH1 wild-type gliomas were associated with higher contralateral PSMD and PSFW (ß = -0.302 and -0.412). AWF of CC mediated the impact of IDH1 mutations on contralesional PSMD and PSFW (mediated proportion: 42.7% and 53.7%). DATA CONCLUSION: PSMD and PSFW are effective biomarkers for assessing WM integrity in gliomas, significantly associated with IDH1 mutation status. AWF of CC mediates the relationship between IDH1 mutation and contralesional PSMD and PSFW. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.
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Background: Most ovarian tumors exhibit a pure histological characteristic. Nevertheless, a combination of tumors with the same histogenetic origin but different histologic subtypes is relatively common. Additionally, co-occurrence of tumors with different histogenetic origins is very rare. Typically, these mixed tumors include mixed epithelial tumors, mixed epithelial-stromal tumors, mixed germ cell-sex cord-stromal tumors, and mixed germ cell tumors. However, mixed epithelial-sex cord stromal-lymphohematopoietic system tumors are rare. Currently, clinicians have limited knowledge of this type of tumor, and the epidemiology, diagnosis, and treatment of this disease are yet to be established. Case presentation: We report a case of a 73-year-old woman with abdominal distension and pain for three months. Imaging evaluation revealed a large pelvic mass, with ultrasound suggesting a benign ovarian cyst along with leiomyoma. Furthermore, computed tomography (CT) and magnetic resonance imaging (MRI) revealed a malignant tumor. Blood tests showed significant increases in CA125 and CA199 levels. The patient underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. During the surgery, a large multinodular cystic solid mass was observed in the right ovary, and the maximum nodular diameter was 14.2 cm. The solid areas of the mass appeared gray-white and taupe, whereas the cystic areas contained clear liquid with smooth walls 0.2 cm thick and no intracystic solid areas. The left ovary had solitary nodules, the largest being 4 cm in diameter. Microscopic examination of the right ovary revealed three different cell types. The first type of cell area was analogous, round, fusiform, and staggered mixed cells with unclear boundaries and rare nucleolus or mitosis. The second type of cell area was the cystic dilatation area. The cyst wall was covered with a single layer of flat epithelium, rich eosinophilic cytoplasm, uniform nuclear chromatin, and no papillary structures. The third type was a diffuse lymphoid region with uniform medium-sized cells, rough nuclear chromatin and evident nucleoli and mitosis. The morphology of the left ovarian cell was single, which was consistent with the first type of cell area in the right ovary. Immunohistochemistry of the right ovary indicated that the first region expressed vimentin, inhibin-α, calretinin, SF-1, WT-1 and CD56, with Ki-67 at 5 %, and no CKpan expression. The second region expressed CKpan, with Ki-67 at 1 %. The third region expressed CD20, Pax-5, Bcl-6, Bcl-2, MUM1, CD45, and C-myc, with Ki-67 at 70 %, and positive IGH clonal gene rearrangement. Lastly, the pathological diagnosis was a mixed ovarian tumor in the right ovary, comprising thecoma-fibroma, serous cystadenoma, diffuse large B-cell lymphoma, and a thecoma-fibroma in the left ovary. A follow-up examination of the patient after 15 months showed no mass or lymph node enlargement in other parts of the body, and no recurrence or metastasis was observed. Conclusions: We present a case of a postmenopausal woman with a rare combination of thecoma-fibroma, serous cystadenoma and diffuse large B-cell lymphoma in the ovary. To the best of our knowledge, this is the first reported case of such a combination. Typical pathological morphology and immunohistochemistry are crucial for the diagnosis of this disease. Owing to the limited knowledge of the disease, its pathogenesis and tissue origin are unknown. Clinicians should be careful about such patients. We believe this case report may provide some novel insights into the diagnosis and therapy of patients with this type of tumor.
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BACKGROUND: This study aimed to compare the effects of two 12-week training intervention experimental ball games combined with standard behavioral rehabilitation against a control group solely utilizing standard behavioral rehabilitation on social communication impairments (SCI) in preschool children with Autism Spectrum Disorder (ASD). METHODS: A multi-arm controlled study design was implemented, involving 41 children diagnosed with ASD (mean age: 4.99 ± 0.76 years). 41 participants were randomized assigned to two experimental groups and a control group, The experimental group carried out ball combination training program group (BCTP) and mini-basketball training program group (MBTP) on the basis of routine behavioral rehabilitation, which underwent 12-week training interventions 5 times a week. The control group (n = 14) received only standard behavioral rehabilitation. Evaluations were conducted before and after interventions using the Social Responsiveness Scale, Second Edition (SRS-2). RESULTS: The results suggest that both 12-week interventions, BCTP, and MBTP, led to significant improvements in social communication impairment among children with ASD (p < 0.05). Despite enhancing the overall scores on the SRS-2, these interventions displayed varying impacts across different sub-dimensions. BCTP primarily exhibited significant enhancements in social awareness and behavior pattern (p < 0.05), whereas MBTP significantly improved social cognition and social communication (p < 0.05). Both interventions showed slight improvements in social motivation. CONCLUSIONS: The utilization of recreational ball games has showed to be effective in decreasing the impairment levels of children with ASD, while the control group experienced a worsening of outcomes. This suggests that irrespective of the specific ball game strategy employed, both can be employed on a weekly basis to complement standard behavioral rehabilitation and enhance the ability to improve the quality of life for children diagnosed with ASD. TRIAL REGISTRATION: The trial is retrospectively registered on the Chinese Clinical Trial Registry (ChiCTR1900024973;August 5, 2019).
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Limu smoked chicken is a traditional Chinese delicacy; however, polycyclic aromatic hydrocarbons (PAHs) are generated during the smoking process. We developed a pyrolysis process for pear wood liquid smoke with minimal PAH generation. Pear wood liquid smoke products were prepared under different pyrolysis conditions in a self-made pyrolysis reactor, and the total phenol, carbonyl compound, total acid, and PAH contents and PAH toxicity risk were evaluated. With increasing temperatures, the toxicity equivalent ΣPAH of the smoke liquid reached 3.004 µg/kg. With increasing particle sizes, the total phenol content reached 1.6 mg/mL; the phenol content was 5.95 mg/mL. With increasing particle sizes, the toxicity equivalent ΣPAHs of the smoke liquor reached 2.441 µg/kg. The optimal parameters for treating pear wood smoke liquid in the thermal reaction device were a pyrolysis temperature of pear wood of >350 °C, particle size of S2, and sucrose content of 8%.
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Phosphogypsum is a solid waste with great environmental stockpile pressure produced by the wet production of phosphoric acid. Although there are various methods to purify and utilize phosphogypsum, the means for environmentally friendly, low energy consumption, and high value-added utilization still need to be further explored. Here, CaSO4·2H2O crystal was directly purified and regulated from phosphogypsum by using the anti-solvent method. The antisolvent can be adsorbed in the c-axis direction of the crystal and further inhibit the growth rate in this direction, resulting in a change in the morphology of the crystal. By adjusting the polarity and chain length of the anti-solvent, the morphology of CaSO4·2H2O crystal can change from butterfly-like flake crystals to hexagonal prism-like crystals. When n-propanol with long chain was used as the anti-solvent, the morphology of the CaSO4·2H2O crystal showed a hexagonal prism with a specific surface area of 19.98 m2/g and a Cu2+ loading efficiency of 52.67%. The encouraging results open up new possibilities for the application of phosphogypsum.
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Small-sized microplastics (MPs) pose greater ecological toxicity due to their larger surface area, which makes them more likely to act as carriers for other pollutants and to be ingested by aquatic organisms. However, traditional visual analysis often neglects small-sized MPs and their associated ecological risk. This study utilized Laser Direct Infrared (LDIR) spectroscopy and traditional visual analysis to examine MPs in 31 sediment samples from Jinzhou Bay, a typical semi-enclosed bay located at the economic center of Dalian, China. The results showed significant heterogeneity in MP distribution, with averages of 1192 and 2361 items/kg dry weight reported by visual analysis and LDIR spectroscopy, respectively. LDIR spectroscopy identified MPs as small as 10 µm, with the majority of MPs (89.21 %) within the 10-250 µm range, and a significant proportion (46.45 %) between 10 and 50 µm among them. However, visual analysis was limited to detecting MPs >50 µm, and significant portions were identified between 50 and 100 µm (49.36 %) and 100-250 µm (31.01 %), missing a substantial fraction of smaller MPs. The predominant polymers identified were polyamide (PA), polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), and acrylonitrile butadiene styrene (ABS). LDIR spectroscopy demonstrated a strong positive correlation between MP abundance and clay content, a relationship not observed with traditional visual analysis. The Potential Ecological Risk Index (PERI) indicated that over 87 % of sites posed an extremely high risk according to LDIR spectroscopy, compared to 51 % by traditional visual analysis. These discrepancy underscores the underestimation of ecological risks by traditional methods, particularly for small-sized MPs. High-risk polymers such as polyvinyl chloride (PVC), ABS, and polyurethane (PUR) significantly influenced PERI values. These findings highlight the critical need for precise identification and thorough risk assessment of small-sized MPs in environmental studies and offer insights for understanding of MP vertical migration in aquatic environments, particularly in the context of co-settlement with sediments.
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ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herb pairs are the most basic and compressed examples of Chinese herbal combinations and can be used to effectively explain the fundamental concepts of traditional Chinese medicine prescriptions. These pairings have gained significant interest due to their subtle therapeutic benefits, minimal side effects, and efficacy in treating complicated chronic conditions. The Banxia-Xiakucao Chinese herb pair (BXHP) consists of Pinellia ternata (Thunb.) Breit. (Banxia) and Prunella vulgaris L. (Xiakucao). This formula was documented in The Medical Classic of the Yellow Emperor approximately 2000 years agoï¼and clinical research has demonstrated that BXHP effectively treats insomnia. AIM OF THE STUDY: This study aimed to evaluate the efficacy and therapeutic mechanism of the BXHP through a comprehensive strategy involving network pharmacology, molecular docking, transcriptomics, and molecular biology experimental validation. MATERIALS AND METHODS: The composition of BXHP was characterized using the UPLC-Q-TOF-MS. The active compounds were screened to find drug-likeness compounds by analyzing the ADME data. To predict the molecular mechanism of BXHP in sleep deprivation (SD) by network pharmacology and molecular docking. We established a rat model of SD and the in vivo efficacy of BXHP was verified through the pentobarbital sodium righting reflex test, behavioral assays, enzyme-linked immunosorbent assay, transmission electron microscopy, HE staining, and Nissl staining, and the underlying molecular mechanism of BXHP in SD was revealed through transcriptomic and bioinformatic analyses in conjunction with quantitative real-time PCR, Western blot, and immunofluorescence staining. RESULTS: In the present study, we showed for the first time that BXHP reduced sleep latency, prolongs sleep duration, and improves anxiety; lowered serum CORT, IL6, TNF-α and MDA levels; decreased hypothalamic Glu levels; and elevated hypothalamic GABA and 5-HT levels in SD rats. We found 16 active compounds that acted on 583 targets, 145 of which are related to SD. By modularly dissecting the PPI network, we discovered three critical targets, Akt1, CREB1, and PRKACA, all of which play important roles in the effects of BXHP on SD. Molecular docking resulted in the identification of 16 active compounds that strongly bind to key targets. The results of GO and KEGG enrichment analyses of network pharmacology and transcriptomics focused on both the regulation of circadian rhythm and the cAMP signaling pathway, which strongly demonstrated that BXHP affects SD via the cAMP-PKA-CREB-Circadian rhythm pathway. Molecular biology experiments verified this hypothesis. Following BXHP administration, PKA and CREB phosphorylation levels were elevated in SD rats, the cAMP-PKA-CREB signaling pathway was activated, the expression levels of the biological clock genes CLOCK, p-BMAL1/BMAL1, and PER3 were increased, and the rhythmicity of the biological clock was improved. CONCLUSIONS: The active compounds in BXHP can activate the cAMP-PKA-CREB-Circadian rhythm pathway, improve the rhythmicity of the biological clock, promote sleep and ameliorate anxiety, which suggests that BXHP improves SD through a multicomponent, multitarget, multipathway mechanism. This study is important for the development of herbal medicines and clinical therapies for improving sleep deprivation.
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Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Farmacología en Red , Pinellia , Ratas Sprague-Dawley , Privación de Sueño , Transcriptoma , Animales , Privación de Sueño/tratamiento farmacológico , Privación de Sueño/metabolismo , Masculino , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/química , Ratas , Pinellia/química , Transcriptoma/efectos de los fármacos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Sueño/efectos de los fármacos , Pentobarbital/farmacologíaRESUMEN
The rampant hepatitis B virus (HBV) seriously endangers human health, and hepatitis B surface antigen (HBsAg) is its early diagnostic marker. Therefore, it is crucial to construct a fast and highly sensitive HBsAg detection method. Based on high-efficiency magnetic separation technology and fluorescent composite material labelling technology, an accurate, fast and sensitive fluorescent immunosensing system for HBsAg detection was developed. Immunomagnetic beads constructed from carboxyl-functionalized Fe3O4 nanoparticles (Fe3O4-COOH) with excellent magnetic response performance were used as efficient capture carriers for HBsAg. Immunofluorescence composite microspheres constructed based on ultra-stable polystyrene-coated CsPbBr3 perovskite nanocrystals (CPB@PSAA) with high hydrophilic properties, were excellent fluorescent markers for HBsAg. Using this sensitive sandwich fluorescence sensing system a good linear relationship within the range of 0.2-15 ng/mL was established between HBsAg concentration and fluorescence intensity with a limit of detection (LOD) of 0.05 ng/mL. The system obtained satisfactory results when tested on real human serum samples. The magnetic-assisted fluorescence immune-sandwich sensor system has broad application prospects in biomedicine such as rapid and early diagnosis and effective prevention of infectious diseases.
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Compuestos de Calcio , Antígenos de Superficie de la Hepatitis B , Interacciones Hidrofóbicas e Hidrofílicas , Límite de Detección , Óxidos , Titanio , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/análisis , Humanos , Óxidos/química , Titanio/química , Compuestos de Calcio/química , Colorantes Fluorescentes/química , Nanopartículas de Magnetita/química , Microesferas , Anticuerpos Inmovilizados/inmunología , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/aislamiento & purificación , Inmunoensayo/métodosRESUMEN
BACKGROUND Cryptococcosis is an opportunistic fungal infection that typically occurs in patients with compromised immune systems, primarily affecting the respiratory and central nervous systems. However, cryptococcal osteomyelitis is a rare manifestation of cryptococcal infection, characterized by nonspecific clinical features. Here, we present a case of vertebral cryptococcal osteomyelitis in a middle-aged woman and discuss diagnostic approaches. CASE REPORT A 56-year-old woman presented with lower back pain and limited mobility, without fever, and with a history of pulmonary tuberculosis. Physical examination revealed enlarged lymph nodes and tenderness in the thoracic vertebrae. A computed tomography-guided biopsy confirmed granulomatous inflammation caused by Cryptococcus, with abundant 10 µm spherical microbial spores. After 4 weeks of treatment with amphotericin B and fluconazole, symptoms and lesions improved. Upon discharge, the patient was prescribed oral fluconazole. Follow-up examinations showed a stable condition and a negative serum cryptococcal capsular polysaccharide antigen test. CONCLUSIONS Given the rarity and lack of specificity of clinical features of cryptococcal spondylitis, clinicians encountering similar presentations should consider tuberculous spondylitis and spinal tumors as differential diagnoses. Additionally, tissue biopsy of the affected vertebral bodies should be performed early to establish the type of vertebral infection, aiding in diagnosis, treatment, and prognosis.
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Criptococosis , Osteomielitis , Tuberculosis de la Columna Vertebral , Humanos , Femenino , Persona de Mediana Edad , Osteomielitis/diagnóstico , Osteomielitis/microbiología , Osteomielitis/tratamiento farmacológico , Criptococosis/diagnóstico , Criptococosis/tratamiento farmacológico , Diagnóstico Diferencial , Tuberculosis de la Columna Vertebral/diagnóstico , Vértebras Torácicas , Antifúngicos/uso terapéutico , Fluconazol/uso terapéutico , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Shift work was associated with elevated dementia risk. Definitive guidelines for sleep duration among shift workers have not been proposed. We aimed to identify sleep durations associated with elimination of excess dementia risk in shift workers. METHODS: 285,213 dementia-free UK Biobank participants at baseline, aged 38-71 years, were enrolled between 2006 and 2010 and followed up through 2022 in this cohort study. Cox proportional hazards models were used to examine the associations between shift work, sleep duration, and risk of dementia. RESULTS: The 285,213 participants included 49,079 shift workers and 236,134 non-shift workers. Over a median follow-up of 13.8 years, 1887 dementia cases were documented. Current shift workers had significantly higher dementia risk than non-shift workers (hazard ratio [HR] 1.26; 95% CI 1.11-1.42). However, this excess risk was eliminated in shift workers with 8 h of sleep (HR 1.02; 95% CI 0.80-1.29). Analysis of shift work frequency indicated that "sometimes" and "usually/always" shift work were associated with increased dementia risk compared to that of non-shift workers, but excess dementia risk was eliminated in members of either frequency group receiving 8 h of sleep ("sometimes", HR 1.05; 95% CI 0.75-1.48; "usually/always", HR 0.98; 95% CI 0.70-1.35). Both "non-night shift" and "night shift" workers showed increased dementia risk compared to non-shift workers. Workers with 8 h of sleep mitigated the excess risk (HR 1.13; 95% CI 0.84-1.53 and HR 0.86; 95% CI 0.59-1.26, respectively). CONCLUSION: 8-h sleep may eliminate excess dementia risk among shift workers, suggesting a potentially effective dementia prevention guideline for shift workers.
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Bancos de Muestras Biológicas , Demencia , Horario de Trabajo por Turnos , Sueño , Humanos , Demencia/epidemiología , Demencia/etiología , Persona de Mediana Edad , Masculino , Femenino , Reino Unido/epidemiología , Anciano , Adulto , Sueño/fisiología , Estudios de Cohortes , Horario de Trabajo por Turnos/efectos adversos , Factores de Tiempo , Factores de Riesgo , Duración del Sueño , Biobanco del Reino UnidoRESUMEN
Phototherapy utilizing bacterial carriers has demonstrated efficacy in anti-tumor therapy, while the poor delivery of phototherapeutic agents and immunogenicity of microbial substances remain problematic. Herein, we develop a nanocoated bacterial delivery system (IF-S.T) that in situ forms the efficient photothermal agents via biomineralization and improves the intracellular oxygenation, thus triggering the self-enhanced photothermal therapy (PTT) and photodynamic therapy (PDT) on tumor. We densely coat self-assembled IF (ICG-Fe2+) nanocomplex onto the surface of LT2, weakly virulent strain of Salmonella typhimurium (S.T), by bioadaptive nanocoating techniques, masking bacterial virulence factors and reducing the potential immune adverse effects. Upon penetrating into the tumor environment, IF-S.T responds to H2O2 to trigger the removal of the IF coating, where S.T produces excess hydrogen sulfide (H2S). H2S reacts with Fe2+, yielding ferrous sulfide (FeS) for PTT, and inhibits mitochondrial respiration to enhance tumor cell oxygenation for PDT. Consequently, IF-S.T plus laser irradiation exhibits direct tumor cells killing and elicits robust antitumor immune responses, leading to the complete tumor elimination. Thus, IF-S.T represents a promising platform for effective tumor delivery of photoactive agents for improved PTT/PDT efficacy.
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Neoplasias de la Mama , Sulfuro de Hidrógeno , Ratones Endogámicos BALB C , Fotoquimioterapia , Salmonella typhimurium , Animales , Fotoquimioterapia/métodos , Femenino , Sulfuro de Hidrógeno/química , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Salmonella typhimurium/efectos de los fármacos , Línea Celular Tumoral , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Verde de Indocianina/administración & dosificación , Humanos , Terapia Fototérmica/métodos , Ratones , Peróxido de Hidrógeno , Fototerapia/métodosRESUMEN
Meat consumption is increasing globally. The safety and quality of meat are considered important issues for human health. During evaluations of meat quality and freshness, microbiological parameters are often analyzed. Counts of indicator cells can provide important references for meat quality. In order to eliminate the error of manual operation and improve detection efficiency, this paper proposed a Convolutional Neural Network (CNN) with a backbone called Detect-Cells-Rapidly-Net (DCRNet), which can identify and count stained cells automatically. The DCRNet replaces the single channel of residual blocks with the aggregated residual blocks to learn more features with fewer parameters. The DCRNet combines the deformable convolution network to fit flexible shapes of stained animal cells. The proposed CNN with DCRNet is self-adaptive to different resolutions of images. The experimental results indicate that the proposed CNN with DCRNet achieves an Average Precision of 81.2% and is better than traditional neural networks for this task. The difference between the results of the proposed method and manual counting is less than 0.5% of the total number of cells. The results indicate that DCRNet is a promising solution for cell detection and can be equipped in future meat quality monitoring systems.