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Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer, characterized by aggressive malignancy and a poor prognosis. Emerging nanomedicine-based combination therapy represents one of the most promising strategies for combating TNBC. Polypyrrole nanoparticles (PPY) are excellent drug delivery vehicles with outstanding photothermal performances. However, the impact of morphology on PPY's drug loading efficiency and photothermal properties remains largely unexplored. In this study, we propose that pluronic P123 can assist in the synthesis of polypyrrole nanoparticles with rough surfaces (rPPY). During the synthesis, P123 formed small micelles around the nanoparticle surface, which were later removed, resulting in small pits and cavities in rPPY. Subsequently, the rPPY was loaded with the chemotherapy drug gemcitabine (Gem@rPPY) for chemo-photothermal therapy against TNBCs. Our results demonstrate that rPPY exhibited superior photothermal performance and significantly enhanced drug loading efficiency by five times compared to smooth PPY nanoparticles. In vitro assessments confirmed Gem@rPPY's robust photothermal properties by efficiently converting light into heat. Cell culture experiments with 4T1 cells and a TNBC mice model revealed significant tumor suppression upon Gem@rPPY administration, emphasizing its efficacy in inducing apoptosis. Toxicity evaluations demonstrated minimal adverse effects both in vitro and in vivo, highlighting the biocompatibility of Gem@rPPY. Overall, this study introduces a promising combination therapy nanoplatform that underscores the importance of surface engineering to enhance therapeutic outcomes and overcome current limitations in TNBC therapy.
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BACKGROUND: Undergoing surgery for renal cell carcinoma can potentially compromise the mental well-being and overall quality of life of survivors. Long-term psychological education interventions that are delivered remotely through various modalities have shown promise in enhancing the psychological well-being and quality of life of cancer patients. This study investigates the effect of remote multimodal psychoeducational interventions on mental well-being and quality of life of renal cell carcinoma survivors. METHODS: A retrospective study was conducted to compare patients receiving remote psychological interventions (exposure group) with those receiving standard care (control group). Following the interventions, various data sets including general demographic information, and assessments from the Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), the Brief Fatigue Inventory-Chinese version (BFI-C), the Distress Thermometer (DT), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) were gathered and analysed for comparison. RESULTS: This study included 116 renal cell carcinoma survivors, with 52 in the exposure group and 64 in the control group. Baseline characteristics were not significantly different between the two groups (p > 0.05). After the intervention, the exposure group had significantly lower scores than the control group on HAMA (14.63 vs. 16.66, p < 0.001), HAMD (13.63 vs. 16.36, p < 0.001), BFI-C (52.31 vs. 57.65, p < 0.001), and DT (3.94 vs. 4.98, p < 0.001). Additionally, the exposure group had significantly higher total score of EORTC QLQ-C30 (69.22 vs. 65.59, p < 0.001) than the control group. CONCLUSIONS: Remote multimodal psychoeducational interventions demonstrate a notable impact in mitigating adverse emotions, exhaustion, and discomfort experienced by survivors of renal cell carcinoma. Such interventions should be actively promoted in clinical practice.
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Supervivientes de Cáncer , Carcinoma de Células Renales , Neoplasias Renales , Salud Mental , Educación del Paciente como Asunto , Calidad de Vida , Humanos , Estudios Retrospectivos , Masculino , Neoplasias Renales/psicología , Neoplasias Renales/cirugía , Femenino , Carcinoma de Células Renales/psicología , Carcinoma de Células Renales/cirugía , Persona de Mediana Edad , Supervivientes de Cáncer/psicología , Educación del Paciente como Asunto/métodos , Anciano , AdultoRESUMEN
OBJECTIVE: The objective is to evaluate the diagnostic effectiveness of contrast-enhanced spectral mammography (CESM) in the diagnosis of breast cancer. DESIGN: DATA SOURCES: PubMed, Embase and Cochrane libraries up to 18 June 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included trials studies, compared the results of different researchers on CESM in the diagnosis of breast cancer, and calculated the diagnostic value of CESM for breast cancer. DATA EXTRACTION AND SYNTHESIS: Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) evaluated the methodological quality of all the included studies. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses specification. In addition to sensitivity and specificity, other important parameters were explored in an analysis of CESM accuracy for breast cancer diagnosis. For overall accuracy estimation, summary receiver operating characteristic curves were calculated. STATA V.14.0 was used for all analyses. RESULTS: This meta-analysis included a total of 12 studies. According to the summary estimates for CESM in the diagnosis of breast cancer, the pooled sensitivity and specificity were 0.97 (95% CI 0.92 to 0.98) and 0.76 (95% CI 0.64 to 0.85), respectively. Positive likelihood ratio was 4.03 (95% CI 2.65 to 6.11), negative likelihood ratio was 0.05 (95% CI 0.02 to 0.09) and the diagnostic odds ratio was 89.49 (95% CI 45.78 to 174.92). Moreover, there was a 0.95 area under the curve. CONCLUSIONS: The CESM has high sensitivity and good specificity when it comes to evaluating breast cancer, particularly in women with dense breasts. Thus, provide more information for clinical diagnosis and treatment.
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Neoplasias de la Mama , Medios de Contraste , Mamografía , Sensibilidad y Especificidad , Humanos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico , Mamografía/métodos , Femenino , Curva ROCRESUMEN
Exposures to complex environmental chemical mixtures during pregnancy reach and target the feto-placental unit. This study investigates the influence of environmental chemical mixtures on placental bioenergetics. Recognizing the essential role of the epidermal growth factor receptor (EGFR) in placental development and its role in stimulating glycolysis and mitochondrial respiration in trophoblast cells, we explored the effects of chemicals known to disrupt EGFR signaling on cellular energy production. Human primary cytotrophoblasts (hCTBs) and a first-trimester extravillous trophoblast cell line (HTR-8/SVneo) were exposed to a mixture of EGFR-interfering chemicals, including atrazine, bisphenol S, niclosamide, PCB-126, PCB-153, and trans-nonachlor. An RNA sequencing approach revealed that the mixture altered the transcriptional signature of genes involved in cellular energetics. Next, the impact of the mixture on cellular bioenergetics was evaluated using a combination of mitochondrial and glycolytic stress tests, ATP production, glucose consumption, lactate synthesis, and super-resolution imaging. The chemical mixture did not alter basal oxygen consumption but diminished the maximum respiratory capacity in a dose-dependent manner, indicating a disruption of mitochondrial function. The respiratory capacity and ATP production were increased by EGF, while the Chem-Mix reduced both EGF- and non-EGF-mediated oxygen consumption rate in hCTBs. A similar pattern was observed in the glycolytic medium acidification, with EGF increasing the acidification, and the Chem-Mix blocking EGF-induced glycolytic acidification. Furthermore, direct stochastic optical reconstruction microscopy (dSTORM) imaging demonstrated that the Chem-Mix led to a reduction of the mitochondrial network architecture, with findings supported by a decrease in the abundance of OPA1, a mitochondrial membrane GTPase involved in mitochondrial fusion. In conclusion, we demonstrated that a mixture of EGFR-disrupting chemicals alters mitochondrial remodeling, resulting in disturbed cellular bioenergetics, reducing the capacity of human cytotrophoblast cells to generate energy. Future studies should investigate the mechanism by which mitochondrial dynamics are disrupted and the pathological significance of these findings.
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The growing concern over low-frequency noise pollution resulting from global industrialization has posed substantial challenges in noise attenuation. However, conventional acoustic metamaterials, with fixed geometries, offer limited flexibility in the frequency range adjustment once constructed. This research unveiled the promising potential of ionic electroactive polymers, particularly ionic polymer-metal composites (IPMCs), as a superior candidate to design tunable acoustic metamaterial due to its bidirectional energy conversion capabilities. The previously perceived limitations of the IPMC, including slow reaction and high energy expenditure, owning to its inherent sluggish intermediary ionic mass transport process, were astutely leveraged to expedite the attenuation of low-frequency sound energy. Both our experimental and simulation results elucidated that the IPMC can generate voltage potentials in response to acoustic pressure at frequencies significantly higher than those previously established. In addition, the peak absorption frequency can be effectively shifted by up to 45.7% with the application of a 4 V voltage. By further integration with a microperforated panel (MPP) structure, the developed metamaterial absorbers can achieve complete sound absorption, which was continuously tunable under minimal voltage stimulation across a wide frequency spectrum. In addition, a microslit structure IPMC metamaterial absorber was designed to realize modulation of the perforation rate, and the absorption peak can be shifted by up to 79.2%. These findings signify a pioneering application of ionic intelligent materials and may pave the way for further innovations of tunable low-frequency acoustic structures, ultimately advancing the pragmatic deployment of both soft intelligent materials and acoustic metamaterials.
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Background: The adjunctive therapeutic potential of simvastatin in schizophrenia treatment has generated interest due to its anti-inflammatory and neuroprotective properties. This meta-analysis aims to assess the efficacy of simvastatin as an adjunct treatment for schizophrenia, synthesizing results from various controlled trials. Methods: We performed a comprehensive search of databases including PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) evaluating the efficacy of simvastatin as an adjunct therapy in patients with schizophrenia. The primary outcome measures were improvements in the Positive and Negative Syndrome Scale (PANSS) scores. Secondary outcomes included changes in overall clinical condition and level of functioning. Data were pooled using random-effects models, and heterogeneity was assessed through I² statistics. Results: The four RCTs included in the analysis represented 425 participants. The combined results demonstrated no significant advantage of simvastatin over placebo in reducing PANSS total scores with a pooled effect size (Standard Mean Difference, SMD) of -0.36 (95% Confidence Interval, CI: -0.82 to 0.11) at 1 month, and -1.80 (95% Confidence Interval, CI: -4.82 to 1.21) at 3 months, indicating minimal to no effect. Similarly, analyses of secondary outcomes showed no significant improvements in overall clinical condition and level of functioning. The studies exhibited low heterogeneity (I² = 0%). Conclusion: This meta-analysis provides evidence that simvastatin, used as adjunctive therapy, does not significantly improve the symptomatic outcomes of schizophrenia compared to placebo. Although simvastatin is well-tolerated, its role in enhancing antipsychotic treatment efficacy in patients with schizophrenia appears limited. These findings suggest that simvastatin should not be recommended as an adjunctive treatment in the clinical management of schizophrenia. Further research may explore the potential subgroups that could benefit from such treatment or identify the biological reasons for the lack of efficacy.
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Mule ducks accumulate a large amount of fat in their livers when fed high-energy feed, which is predominantly used for producing fatty livers. Nevertheless, there is limited research on the molecular mechanisms underlying the formation of fatty liver in mule ducks. Fatty acid translocase (CD36) is a sensor for fatty acids and lipid metabolism regulator, which may play a crucial role in the accumulation of fat in the liver of mule ducks. In this study, Overexpression and CD36 gene interference for 24 h was followed by induction of liver cells with 400 µmol/L palmitic acid (PA) for 24 h. The results demonstrated that CD36 overexpression increased hepatic triglyceride content, lipid droplet deposition, oxidative stress, and cell apoptosis. However, interference with CD36 had the opposite effect. CD36 overexpression suppressed the expression of AMPK and CPT-1A genes but enhanced the expression of ACC1 and LKB1 genes, with interference yielding contrasting results. Additionally, the expression of CD36 inhibited the AMPK pathway, reduced AMPK phosphorylation, downregulated AMPK protein expression, and upregulated SREBP1 protein expression. This promoted palmitic acid-induced hepatocyte fat accumulation. In summary, CD36 promotes palmitic acid-induced fat accumulation in primary mule duck liver cells through the AMPK signaling pathway.
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Proteostasis and genomic integrity are respectively regulated by the endoplasmic reticulum-associated protein degradation (ERAD) and DNA damage repair signaling pathways, with both pathways essential for carcinogenesis and drug resistance. How these signaling pathways coordinate with each other remains unexplored. We found that ER stress specifically induces the DNA-PKcs-regulated nonhomologous end joining (NHEJ) pathway to amend DNA damage and impede cell death. Intriguingly, sustained ER stress rapidly decreased the activity of DNA-PKcs and DNA damage accumulated, facilitating a switch from adaptation to cell death. This DNA-PKcs inactivation was caused by increased KU70/KU80 protein degradation. Unexpectedly, the ERAD ligase HRD1 was found to efficiently destabilize the classic nuclear protein HDAC1 in the cytoplasm, by catalyzing HDAC1's polyubiquitination at lysine 74, at a late stage of ER stress. By abolishing HDAC1-mediated KU70/KU80 deacetylation, HRD1 transmits ER signals to the nucleus. The resulting enhanced KU70/KU80 acetylation provides binding sites for the nuclear E3 ligase TRIM25, resulting in the promotion of polyubiquitination and the degradation of KU70/KU80 proteins. Both in vitro and in vivo cancer models showed that genetic or pharmacological inhibition of HADC1 or DNA-PKcs sensitizes colon cancer cells to ER stress inducers, including the Food and Drug Administration-approved drug celecoxib. The antitumor effects of the combined approach were also observed in patient-derived xenograft models. These findings identify a mechanistic link between ER stress (ERAD) in the cytoplasm and DNA damage (NHEJ) pathways in the nucleus, indicating that combined anticancer strategies may be developed that induce severe ER stress while simultaneously inhibiting KU70/KU80/DNA-PKcs-mediated NHEJ signaling.
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Daño del ADN , Proteína Quinasa Activada por ADN , Estrés del Retículo Endoplásmico , Ubiquitina-Proteína Ligasas , Animales , Humanos , Ratones , Línea Celular Tumoral , Reparación del ADN por Unión de Extremidades , Reparación del ADN , Proteína Quinasa Activada por ADN/metabolismo , Proteína Quinasa Activada por ADN/genética , Retículo Endoplásmico/metabolismo , Histona Desacetilasa 1/metabolismo , Histona Desacetilasa 1/genética , Autoantígeno Ku/metabolismo , Autoantígeno Ku/genética , Proteolisis , Transducción de Señal , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , UbiquitinaciónRESUMEN
Objective: To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor (EGFR) 21L858R mutant non-small cell lung cancer (NSCLC) patients in China and to explore the factors influencing the efficacy and safety. Methods: A longitudinal, consecutive case-series, multicenter study with mixed prospective and retrospective data was conducted. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included duration of treatment (DOT), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Results: A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included. The median follow-up time for these patients was 20.4 months. Among 134 patients with evaluable lesions, the ORR was 70.9% and the DCR was 96.3%. The median PFS was 16.3 [95% confidence interval (95% CI), 13.7-18.9] months. Multivariate Cox regression analysis suggested that the baseline brain metastasis (BM) status [with vs. without BM: hazard ratio (HR), 1.331; 95% CI, 0.720-2.458; P=0.361] and initial doses (45 mg vs. 30 mg: HR, 0.837; 95% CI, 0.427-1.641; P=0.604) did not significantly affect the median PFS. The median DOT was 21.0 (95% CI, 17.5-24.6) months and the median OS was not reached. Genetic tests were performed in 64 patients after progression, among whom 29 (45.3%) patients developed the EGFR 20T790M mutation. In addition, among the 46 patients who discontinued dacomitinib treatment after progression, 31 (67.4%) patients received subsequent third-generation EGFR-tyrosine kinase inhibitors. The most common grade 3-4 adverse events were rash (10.4%), diarrhea (9.1%), stomatitis (7.1%) and paronychia (4.5%). The incidence of grade 3-4 rash was significantly higher in the 45 mg group than that in the 30 mg group (21.9% vs. 7.5%, P=0.042). Conclusions: First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.
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Spontaneous cerebellar hemorrhage (SCH) patients have a low success rate in extubation, but there are currently no guidelines establishing specifically for SCH patients extubation. The study included 68 SCH patients who received mechanical ventilation for more than 24 h, with 39 cases (57.3%) resulting in successful extubation. The multivariate analysis identified four factors significantly associated with extubation success: patient age under 66 years, an Intracerebral Hemorrhage (ICH) score less than 4 points, the presence of tissue shift, and a Glasgow Coma Scale (GCS) score (excluding language) above 6 points at extubation. By simplifying the prediction model, we obtained the Spontaneous Cerebellar Hemorrhage Extubation Success scoring system (SCHES-SCORE). Within the scoring system, 2 points were allocated for a GCS score (excluding language) above 6 at extubation, 1 point each for age under 66 years and an ICH score below 4, while tissue shift was assigned a negative point. A score of Grade A (SCHES-SCORE = 3-4) was found to correlate with a 92.9% success rate for extubation. The area under the receiver operating characteristic curve was 0.923 (95% CI, 0.863 to 0.983). Notably, successful extubation was significantly linked to reduced durations of mechanical ventilation, intensive care unit (ICU) stay, and total hospital stay. In conclusion, the scoring system developed for assessing extubation outcomes in SCH patients has the potential to enhance the rate of successful extubation and overall patient outcomes.
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Background: Chronic obstructive pulmonary disease (COPD) is a widespread respiratory condition characterized by chronic inflammation. Selenium, an essential trace element, possesses anti-inflammatory and antioxidant properties. However, the diet is often complex, and the absence of one nutrient may indicate a concurrent deficiency in others. Therefore, inadequate dietary selenium intake may suggest deficiencies in other elements. Despite its potential benefits, there is a scarcity of evidence regarding the association between dietary selenium intake and COPD. Purpose: This study aims to investigate the potential association between dietary selenium intake and COPD among American adults. Patients and Methods: This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey conducted in the United States from 1999 to 2018. Multivariate logistic regression, restricted cubic spline analyses, subgroup analysis, and sensitivity analysis were conducted to assess the correlation between dietary selenium intake and COPD. Results: A total of 39,654 participants were included in the study. The adjusted odds ratio (OR) for COPD in the highest selenium intake group (T3, > 122.0 µg/day) was 0.80 (95% CI: 0.71-0.91, p < 0.001) compared to the lowest intake group (T1, < 81.6 µg/day). Dietary selenium intake exhibited a linear negative correlation with COPD. Among participants reporting selenium supplementation, a similar negative association persisted. Conclusion: This study observed a negative correlation between dietary selenium intake and COPD among American adults, indicating a possible association between higher selenium intake and a lower risk of COPD.
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Encuestas Nutricionales , Enfermedad Pulmonar Obstructiva Crónica , Selenio , Humanos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Selenio/administración & dosificación , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Estados Unidos/epidemiología , Anciano , Factores de Riesgo , Adulto , Medición de Riesgo , Dieta/efectos adversos , Estado Nutricional , Factores Protectores , Factores de TiempoRESUMEN
Sarcopenia, a multifactorial systemic disorder, has attracted extensive attention, yet its pathogenesis is not fully understood, partly due to limited research on the relationship between lipid metabolism abnormalities and sarcopenia. Lipidomics offers the possibility to explore this relationship. Our research utilized LC/MS-based nontargeted lipidomics to investigate the lipid profile changes as-sociated with sarcopenia, aiming to enhance understanding of its underlying mechanisms. The study included 40 sarcopenia patients and 40 control subjects matched 1:1 by sex and age. Plasma lipids were detected and quantified, with differential lipids identified through univariate and mul-tivariate statistical analyses. A weighted correlation network analysis (WGCNA) and MetaboAna-lyst were used to identify lipid modules related to the clinical traits of sarcopenia patients and to conduct pathway analysis, respectively. A total of 34 lipid subclasses and 1446 lipid molecules were detected. Orthogonal partial least squares discriminant analysis (OPLS-DA) identified 80 differen-tial lipid molecules, including 38 phospholipids. Network analysis revealed that the brown module (encompassing phosphatidylglycerol (PG) lipids) and the yellow module (containing phosphati-dylcholine (PC), phosphatidylserine (PS), and sphingomyelin (SM) lipids) were closely associated with the clinical traits such as maximum grip strength and skeletal muscle mass (SMI). Pathway analysis highlighted the potential role of the glycerophospholipid metabolic pathway in lipid me-tabolism within the context of sarcopenia. These findings suggest a correlation between sarcopenia and lipid metabolism disturbances, providing valuable insights into the disease's underlying mechanisms and indicating potential avenues for further investigation.
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Metabolismo de los Lípidos , Lipidómica , Lípidos , Sarcopenia , Humanos , Sarcopenia/metabolismo , Lipidómica/métodos , Masculino , Femenino , Cromatografía Liquida/métodos , Anciano , Lípidos/sangre , Lípidos/análisis , Persona de Mediana Edad , Espectrometría de Masas/métodos , Músculo Esquelético/metabolismo , Estudios de Casos y ControlesRESUMEN
To investigate the effects of health education combined with biofeedback electrical stimulation on maternal postpartum pelvic floor function and psychology. The clinical data of 80 patients with postpartum pelvic floor dysfunction (PFD) from May 2020 to May 2022 were selected as retrospective study subjects, and 40 cases were divided into the comparison group and the observation group according to the different intervention methods. Among them, the comparison group implemented biofeedback electrical stimulation and guidance, and the observation group implemented Greene health education and Kegel pelvic floor rehabilitation training intervention based on the comparison group. The differences in pelvic floor muscle strength, sexual quality of life, anxiety, and depression in the 2 groups with postpartum PFD were compared. Comparison of pelvic floor muscle strength: before the intervention (Pâ >â .05) and after the intervention, the anterior resting mean electromyography (EMG), slow muscle mean EMG, fast muscle maximum EMG, and mixed muscle mean EMG values of patients in the observation group were higher than those in the comparison group, and the posterior resting mean EMG values were lower than those in the comparison group (Pâ <â .05). There was no statistically significant difference in the Hospital Anxiety and Depression Scale (HADS) scores and anxiety and depression subscale scores between the 2 groups of patients before intervention (Pâ >â .05). After the intervention, the HADS scores and anxiety and depression subscale scores were lower than those before the intervention in both groups, and the differences were statistically significant in the intervention group than in the comparison group (Pâ <â .05). There was no statistically significant difference between The Chinese Female Sexual Life Quality Questionnaire scores of both groups before the intervention (Pâ >â .05). Sexual desire, vaginal lubrication, sexual arousal, sexual satisfaction, orgasm, and painful intercourse improved in both groups after the intervention, and the scores in the intervention group were higher than those in the comparison group (Pâ <â .05). Health education combined with biofeedback electrical stimulation can effectively improve the quality of patients' sexual life, improve the pelvic floor muscle strength of patients with postpartum PFD, enhance patients' confidence, reduce patients' anxiety and depression, and effectively improve patients' psychological status.
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Biorretroalimentación Psicológica , Fuerza Muscular , Trastornos del Suelo Pélvico , Diafragma Pélvico , Calidad de Vida , Humanos , Femenino , Estudios Retrospectivos , Adulto , Biorretroalimentación Psicológica/métodos , Diafragma Pélvico/fisiopatología , Fuerza Muscular/fisiología , Trastornos del Suelo Pélvico/terapia , Trastornos del Suelo Pélvico/psicología , Trastornos del Suelo Pélvico/rehabilitación , Ansiedad/terapia , Educación en Salud/métodos , Depresión/terapia , Electromiografía , Terapia por Estimulación Eléctrica/métodos , Periodo Posparto/psicologíaRESUMEN
EDITORIAL: The invention of organic light emitting diodes (LEDs) led to enormous excitement in both academe and industry in the late 1980's. Flexibility, large area solution processability, roll-to-roll printing, low cost, and environmentally friendly are some of the advantages of organic semiconductor materials, which brought a new horizon for optoelectronics. Together with the achievement of organic solar cells, transistors, lasers, and amplifiers, this has demonstrated potential applications of organic semiconductors in displays, lighting, solar energy generation, electronics, sensing and imaging, and many aspects of photonics. In an enlightened conversation with Light: Science & Applications, Prof. Donal Bradley (FRS), a pioneer in the field, shared his deep insights on past, current, and future exciting developments of organic optoelectronic materials and devices. In particular, he expressed his opinion on the hot topics related to organic optoelectronics research and application, such as the relationship between organic and inorganic semiconductors and the challenge of electrically pumped organic lasers. As a successful scientist, Donal has also been co-founder of several organic optoelectronics innovation companies and research centers and a long-term academic administrator serving as a Head of Department, Centre Director, and Vice-Rector for Research at Imperial College, Head of the Mathematical, Physical, and Life Sciences Division at the University of Oxford, Vice-President for Research at King Abdullah University of Science and Technology and now Vice-President for Research and Innovation at NEOM U and Executive Director of the NEOM Education, Research and Innovation Foundation. Through this interview, we also explore the major roles and events in Donal's career experience from the invention of the first conjugated polymer LED in the world to the set-up of entrepreneurial companies, from Cambridge to Sheffield, Imperial College, and Oxford, from the UK to overseas, and from the establishment of the Centre for Plastic Electronics in Imperial College to the set-up of the Oxford Suzhou Centre for Advanced Research (OSCAR). Before the end of the conversation, he also shares his interesting story of identifying a new species of Sea Bream, Acanthopagrus oconnorae (Bev Bradley's Bream), named after his mother and wife, while fishing in the Red Sea.
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BACKGROUND: This study aimed to use artificial intelligence (AI) to integrate various radiological and clinical pathological data to identify effective predictors of contralateral cervical lymph node metastasis (CCLNM) in patients with papillary thyroid carcinoma (PTC) and to establish a clinically applicable model to guide the extent of surgery. METHODS: This prospective cohort study included 603 patients with PTC from three centers. Clinical, pathological, and ultrasonographic data were collected and utilized to develop a machine learning (ML) model for predicting CCLNM. Model development at the internal center utilized logistic regression along with other ML algorithms. Diagnostic efficacy was compared among these methods, leading to the adoption of the final model (random forest). This model was subject to AI interpretation and externally validated at other centers. RESULTS: CCLNM was associated with multiple pathological factors. The Delphian lymph node metastasis ratio, ipsilateral cervical lymph node metastasis number, and presence of ipsilateral cervical lymph node metastasis were independent risk factors for CCLNM. Following feature selection, a Delphian lymph node-CCLNM (D-CCLNM) model was established using the Random forest algorithm based on five attributes. The D-CCLNM model demonstrated the highest area under the curve (AUC; 0.9273) in the training cohort and exhibited high predictive accuracy, with AUCs of 0.8907 and 0.9247 in the external and validation cohorts, respectively. CONCLUSIONS: We developed a new, effective method that uses ML to predict CCLNM in patients with PTC. This approach integrates data from Delphian lymph nodes and clinical characteristics, offering a foundation for guiding surgical decisions, and is conveniently applicable in clinical settings.
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Trichosanthes truncata C. B. Clarke, an important medicinal plant, is a dioecious plant belonging to the Cucurbitaceae family. This study presents a chromosomal-level reference genome assembly for T. truncata. Through the integration of PacBio high-fidelity sequencing and high-throughput chromosome conformation capture technology, a final genome sequence of 637.41 Mb was assembled, with an N50 of 57.24 Mb and consisting of 11 pseudochromosomes. Additionally, 97.21 Mb of repetitive sequences and 36,172 protein-coding genes were annotated. This high-quality genome assembly is of utmost significance for studying the molecular mechanisms underlying the biosynthesis of bioactive compounds. Furthermore, this study provided valuable insights into plant comparative genomics research.
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Cromosomas de las Plantas , Genoma de Planta , Trichosanthes , Trichosanthes/genética , Cromosomas de las Plantas/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Evolución MolecularRESUMEN
BACKGROUND: Growing evidence suggests that elective induction of labor at 39 weeks' gestation may lead to more favorable perinatal outcomes than expectant management, however, how to weigh the pros and cons of elective labor induction at 39 weeks, the expectation of spontaneous delivery at 40 or 41 weeks, or delayed labor induction at 40 or 41 weeks on neonatal and maternal outcomes remains a practical challenge in clinical decision-making. OBJECTIVE: We compared the neonatal and maternal outcomes between elective induction of labor at 39 weeks' gestation and expectant management in a real-world setting. We also divided the expectantly managed group and compared outcomes of the spontaneous delivery at 40 or 41 weeks' gestation group and the induced group at 40 or 41 weeks' gestation with those of the elective induction at 39 weeks' gestation group. STUDY DESIGN: This retrospective cohort study included 21,282 participants who delivered between January 1, 2019, and June 30, 2022. Participants were initially categorized into 3 groups at 39 weeks' gestation, namely elective induction of labor, spontaneous delivery, and expectant management, for the primary analysis in which elective induction was compared with expectant management. Subsequently, the expectant management group at 39 weeks' gestation was divided into 3 groups at 40 weeks, and participants who underwent expectant management at 40 weeks were then divided into 2 groups at 41 weeks' gestation, namely elective induction and spontaneous delivery. In total, 6 groups were compared in the secondary analysis with the elective induction at 39 weeks' gestation group serving as the reference group. RESULTS: At 39 weeks' gestational age, participants who underwent elective induction of labor had a significantly lower risk for the primary composite outcomes than participants who were managed expectantly (adjusted odds ratio, 0.72; 95% confidence interval, 0.55-0.95), and there was no significant difference in the risk for cesarean delivery between the 2 groups. After further dividing the expectantly managed group and comparing them with participants who underwent elective induction of labor at 39 weeks' gestation, those who underwent spontaneous delivery at 40 weeks' gestation had significantly lower risks for cesarean delivery (0.61; 0.52-0.71) and chorioamnionitis (0.78; 0.61-1.00) but a higher risk for fetal distress (1.39; 1.22-1.57); those with spontaneous delivery at 41 weeks' gestation had a significantly higher risk for fetal distress (1.44; 1.16-1.79), postpartum hemorrhage (1.83; 1.26-2.66), and prolonged or arrested labor (1.61; 1.02-2.54). Moreover, when compared with participants who underwent elective induction of labor at 39 weeks' gestation, participants who were induced later in gestation had significantly higher risks for adverse neonatal and maternal outcomes, especially at 40 weeks' gestation. CONCLUSION: Our findings indicate that elective induction of labor at 39 weeks' gestation was significantly associated with lower risks for adverse short-term neonatal and maternal outcomes when compared with expectant management. Moreover, our study highlights the nuanced trade-offs in risks and benefits between elective induction at 39 weeks' gestation and waiting for spontaneous labor or delayed induction at 40 or 41 weeks' gestation, thus providing valuable insights for clinical decision-making in practice.
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Brain microstructural alterations possibly occur in the normal-appearing white matter (NAWM) and grey matter of small vessel disease (SVD) patients, and may contribute to cognitive impairment. The aim of this study was to explore cognitive related microstructural alterations in white matter and deep grey matter nuclei in SVD patients using magnetic resonance (MR) quantitative susceptibility mapping (QSM). 170 SVD patients, including 103 vascular mild cognitive impairment (VaMCI) and 67 no cognitive impairment (NCI), and 21 healthy control (HC) subjects were included, all underwent a whole-brain QSM scanning. Using a white matter and a deep grey matter atlas, subregion-based QSM analysis was conducted to identify and characterize microstructural alterations occurring within white matter and subcortical nuclei. Significantly different susceptibility values were revealed in NAWM and in several specific white matter tracts including anterior limb of internal capsule, corticospinal tract, medial lemniscus, middle frontal blade, superior corona radiata and tapetum among VaMCI, NCI and HC groups. However, no difference was found in white matter hyperintensities between VaMCI and NCI. A trend toward higher susceptibility in the caudate nucleus and globus pallidus of VaMCI patients compared to HC, indicating elevated iron deposition in these areas. Interestingly, some of these QSM parameters were closely correlated with both global and specific cognitive function scores, controlling age, gender and education level. Our study suggested that QSM may serve as a useful imaging tool for monitoring cognitive related microstructural alterations in brain. This is especially meaningful for white matter which previously lacks of attention.
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Enfermedades de los Pequeños Vasos Cerebrales , Disfunción Cognitiva , Sustancia Gris , Imagen por Resonancia Magnética , Sustancia Blanca , Humanos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Masculino , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Anciano , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Persona de Mediana Edad , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/patología , Imagen por Resonancia Magnética/métodosRESUMEN
Plastic pollution is an emerging environmental issue, with microplastics and nanoplastics raising health concerns due to bioaccumulation. This work explored the impact of polystyrene nanoparticle (PS-NPs) exposure during prepuberty on male reproductive function post maturation in rats. Rats were gavaged with PS-NPs (80 nm) at 0, 3, 6, 12 mg/kg/day from postnatal day 21 to 95. PS-NPs accumulated in the testes and reduced sperm quality, serum reproductive hormones, and testicular coefficients. HE staining showed impaired spermatogenesis. PS-NPs disrupted the blood-testis barrier (BTB) by decreasing junction proteins, inducing inflammation and apoptosis. Transcriptomics identified differentially expressed genes related to metabolism, lysosome, apoptosis, and TLR4 signaling. Molecular docking revealed Cordycepin could compete with polystyrene for binding to TLR4. Cordycepin alleviated oxidative stress and improved barrier function in PS-NPs treated Sertoli cells. In conclusion, prepubertal PS-NPs exposure induces long-term reproductive toxicity in male rats, likely by disrupting spermatogenesis through oxidative stress and BTB damage. Cordycepin could potentially antagonize this effect by targeting TLR4 and warrants further study as a protective agent. This study elucidates the mechanisms underlying reproductive toxicity of PS-NPs and explores therapeutic strategies.
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Barrera Hematotesticular , Desoxiadenosinas , Nanopartículas , Poliestirenos , Espermatogénesis , Testículo , Animales , Masculino , Desoxiadenosinas/farmacología , Barrera Hematotesticular/efectos de los fármacos , Poliestirenos/toxicidad , Nanopartículas/toxicidad , Espermatogénesis/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Células de Sertoli/efectos de los fármacos , Células de Sertoli/metabolismo , Simulación del Acoplamiento Molecular , Microplásticos/toxicidad , Receptor Toll-Like 4/metabolismo , Apoptosis/efectos de los fármacos , Maduración Sexual/efectos de los fármacos , Sustancias Protectoras/farmacologíaRESUMEN
Background: Ulcerative colitis (UC) is an intestinal inflammatory disease that is strongly associated with mitochondrial damage and dysfunction as well as mitophagy and lacks of satisfactory treatments. Hair follicle mesenchymal stem cell (HF-MSC)-derived exosomes owe benefit effectiveness on inflammatory therapies. Hypoxia-preconditioned HF-MSCs exhibit enhanced proliferation and migration abilities, and their exosomes exert stronger effects than normal exosomes. However, the therapeutic function of Hy-Exos in UC is unknown. Methods: The inflammation model was established with LPS-treated MODE-K cells, and the mouse UC model was established by dextran sulfate sodium (DSS) administration. The therapeutic effects of HF-MSC-derived exosomes (Exos) and hypoxia-preconditioned HF-MSC-derived exosomes (Hy-Exos) were compared in vitro and in vivo. Immunofluorescence staining and western blotting were used to explore the effects of Hy-Exos on mitochondrial function, mitochondrial fission and fusion and mitophagy. MiRNA sequencing analysis was applied to investigate the differences in components between Exos and Hy-Exos. Results: Hy-Exos had a better therapeutic effect on LPS-treated MODE-K cells and DSS-induced UC mice. Hy-Exos promoted colonic tight junction proteins expression, suppressed the oxidative stress response, and reduced UC-related inflammatory injury. Hy-Exos may exert these effects via miR-214-3p-mediated inhibition of the PI3K/AKT/mTOR signaling pathway, maintenance of mitochondrial dynamic stability, alleviation of mitochondrial dysfunction and enhancement of mitophagy. Conclusion: This study revealed a vital role for Hy-Exos in suppressing inflammatory progression in UC and suggested that miR-214-3p is a potential critical target for Hy-Exos in alleviating UC.