Harnessing Large Language Models for Structured Reporting in Breast Ultrasound: A Comparative Study of Open AI (GPT-4.0) and Microsoft Bing (GPT-4).

OBJECTIVES: To assess the capabilities of large language models (LLMs), including Open AI (GPT-4.0) and Microsoft Bing (GPT-4), in generating structured reports, the Breast Imaging Reporting and Data System (BI-RADS) categories, and management recommendations from free-text breast ultrasound reports. MATERIALS AND METHODS: In this retrospective study, 100 free-text breast ultrasound reports from patients who underwent surgery between January and May 2023 were gathered. The capabilities of Open AI (GPT-4.0) and Microsoft Bing (GPT-4) to convert these unstructured reports into structured ultrasound reports were studied. The quality of structured reports, BI-RADS categories, and management recommendations generated by GPT-4.0 and Bing were evaluated by senior radiologists based on the guidelines. RESULTS: Open AI (GPT-4.0) was better than Microsoft Bing (GPT-4) in terms of performance in generating structured reports (88% vs. 55%; p < 0.001), giving correct BI-RADS categories (54% vs. 47%; p = 0.013) and providing reasonable management recommendations (81% vs. 63%; p < 0.001). As the ability to predict benign and malignant characteristics, GPT-4.0 performed significantly better than Bing (AUC, 0.9317 vs. 0.8177; p < 0.001), while both performed significantly inferior to senior radiologists (AUC, 0.9763; both p < 0.001). CONCLUSION: This study highlights the potential of LLMs, specifically Open AI (GPT-4.0), in converting unstructured breast ultrasound reports into structured ones, offering accurate diagnoses and providing reasonable recommendations.

Machine learning-based biomarker screening for acute myeloid leukemia prognosis and therapy from diverse cell-death patterns.

Acute myeloid leukemia (AML) exhibits pronounced heterogeneity and chemotherapy resistance. Aberrant programmed cell death (PCD) implicated in AML pathogenesis suggests PCD-related signatures could serve as biomarkers to predict clinical outcomes and drug response. We utilized 13 PCD pathways, including apoptosis, pyroptosis, ferroptosis, autophagy, necroptosis, cuproptosis, parthanatos, entotic cell death, netotic cell death, lysosome-dependent cell death, alkaliptosis, oxeiptosis, and disulfidptosis to develop predictive models based on 73 machine learning combinations from 10 algorithms. Bulk RNA-sequencing, single-cell RNA-sequencing transcriptomic data, and matched clinicopathological information were obtained from the TCGA-AML, Tyner, and GSE37642-GPL96 cohorts. These datasets were leveraged to construct and validate the models. Additionally, in vitro experiments were conducted to substantiate the bioinformatics findings. The machine learning approach established a 6-gene pan-programmed cell death-related genes index (PPCDI) signature. Validation in two external cohorts showed high PPCDI associated with worse prognosis in AML patients. Incorporating PPCDI with clinical variables, we constructed several robust prognostic nomograms that accurately predicted prognosis of AML patients. Multi-omics analysis integrating bulk and single-cell transcriptomics revealed correlations between PPCDI and immunological features, delineating the immune microenvironment landscape in AML. Patients with high PPCDI exhibited resistance to conventional chemotherapy like doxorubicin but retained sensitivity to dasatinib and methotrexate (FDA-approved drugs for other leukemias), suggesting the potential of PPCDI to guide personalized therapy selection in AML. In summary, we developed a novel PPCDI model through comprehensive analysis of diverse programmed cell death pathways. This PPCDI signature demonstrates great potential in predicting clinical prognosis and drug sensitivity phenotypes in AML patients.

Fabrication and performance of Zinc-based biodegradable metals: From conventional processes to laser powder bed fusion.

Zinc (Zn)-based biodegradable metals (BMs) fabricated through conventional manufacturing methods exhibit adequate mechanical strength, moderate degradation behavior, acceptable biocompatibility, and bioactive functions. Consequently, they are recognized as a new generation of bioactive metals and show promise in several applications. However, conventional manufacturing processes face formidable limitations for the fabrication of customized implants, such as porous scaffolds for tissue engineering, which are future direction towards precise medicine. As a metal additive manufacturing technology, laser powder bed fusion (L-PBF) has the advantages of design freedom and formation precision by using fine powder particles to reliably fabricate metallic implants with customized structures according to patient-specific needs. The combination of Zn-based BMs and L-PBF has become a prominent research focus in the fields of biomaterials as well as biofabrication. Substantial progresses have been made in this interdisciplinary field recently. This work reviewed the current research status of Zn-based BMs manufactured by L-PBF, covering critical issues including powder particles, structure design, processing optimization, chemical compositions, surface modification, microstructure, mechanical properties, degradation behaviors, biocompatibility, and bioactive functions, and meanwhile clarified the influence mechanism of powder particle composition, structure design, and surface modification on the biodegradable performance of L-PBF Zn-based BM implants. Eventually, it was closed with the future perspectives of L-PBF of Zn-based BMs, putting forward based on state-of-the-art development and practical clinical needs.

A Transdiagnostic Network Analysis of Childhood Trauma and Psychopathology.

BACKGROUND AND HYPOTHESIS: Psychiatric comorbidities suggest that symptoms overlap across different diagnoses; the transdiagnostic network approach is valuable for studying psychopathology. Childhood trauma is a common transdiagnostic risk factor for psychiatric disorders, but the complex relationship between childhood trauma and psychopathology has seldom been investigated using a large cross-sectional transdiagnostic sample. STUDY DESIGN: This study recruited 869 patients with different diagnoses, including 418 schizophrenia, 215 bipolar disorder, and 236 major depressive disorder. Participants completed psychiatric interviews and self-report questionnaires. We constructed dimension- and item-level Least Absolute Shrinkage and Selection Operator-based (LASSO) networks to explore the relationship between childhood trauma, psychopathology, and duration of illness. Moreover, we constructed directed acyclic graphs (DAGs) to tentatively clarify the potential directions of associations among these variables. Network Comparison Tests (NCTs) were conducted for different diagnostic groups and gender-stratified groups. STUDY RESULTS: The transdiagnostic LASSO networks showed that different types of childhood trauma exerted distinct impacts on various psychopathological dimensions. Emotional abuse was linked to depressive symptoms, physical abuse to excited symptoms, sexual abuse to positive and disorganized symptoms, emotional neglect to depressive symptoms and motivation and pleasure (MAP) deficits factor of negative symptoms, and physical neglect to MAP factor. The DAG findings generally concurred with the LASSO network. The NCT showed comparable networks. CONCLUSIONS: Our findings suggest that childhood trauma is significantly associated with the development of psychopathology across different diagnostic groups. The affective pathway model suggests that early identification and tailored interventions would be needed for people with a history of childhood trauma.

Global research on emerging trends of obstetrics during the COVID-19 pandemic: A bibliometric analysis.

Coronavirus disease-2019 (COVID-19) has caused continuous effects on the global public, especially for susceptible and vulnerable populations like pregnant women. COVID-19-related studies and publications have shown blowout development, making it challenging to identify development trends and hot areas by using traditional review methods for such massive data. Aimed to perform a bibliometric analysis to explore the status and hotspots of COVID-19 in obstetrics. An online search was conducted in the Web of Science Core Collection (WOSCC) database from January 01, 2020 to November 31, 2022, using the following search expression: (((TS= ("COVID 19" OR "coronavirus 2019" OR "coronavirus disease 2019" OR "SARS-CoV-2" OR "2019-nCoV" OR "2019 novel coronavirus" OR "SARS coronavirus 2" OR "Severe Acute Respiratory Syndrome Coronavirus-2" OR "SARS-COV2")) AND TS= ("obstetric*" OR "pregnancy*" OR "pregnant" OR "parturition*" OR "puerperium"))). VOSviewer version 1.6.18, CiteSpace version 6.1.R6, R version 4.2.0, and Rstudio were used for the bibliometric and visualization analyses. 4144 articles were included in further analysis, including authors, titles, number of citations, countries, and author affiliations. The United States has contributed the most significant publications with the leading position. "Sahin, Dilek" has the largest output, and "Khalil, Asma" was the most influential author with the highest citations. Keywords of "Cov," "Experience," and "Neonate" with the highest frequency, and "Systematic Review" might be the new research hotspots and frontiers. The top 3 concerned genes included ACE2, CRP, and IL6. The new research hotspot is gradually shifting from the COVID-19 mechanism and its related clinical research to reviewing treatment options for pregnant women. This research uniquely delves into specific genes related to COVID-19's effects on obstetrics, a focus that has not been previously explored in other reviews. Our research enables clinicians and researchers to summarize the overall point of view of the existing literature and obtain more accurate conclusions.

[Retracted] Chelerythrine chloride induces apoptosis in renal cancer HEK­293 and SW­839 cell lines.

[This retracts the article DOI: 10.3892/ol.2016.4520.].

Clinical application potential of large language model: a study based on thyroid nodules.

BACKGROUND: Limited data indicated the performance of large language model (LLM) taking on the role of doctors. We aimed to investigate the potential for ChatGPT-3.5 and New Bing Chat acting as doctors using thyroid nodules as an example. METHODS: A total of 145 patients with thyroid nodules were included for generating questions. Each question was entered into chatbot of ChatGPT-3.5 and New Bing Chat five times and five responses were acquired respectively. These responses were compared with answers given by five junior doctors. Responses from five senior doctors were regarded as gold standard. Accuracy and reproducibility of responses from ChatGPT-3.5 and New Bing Chat were evaluated. RESULTS: The accuracy of ChatGPT-3.5 and New Bing Chat in answering Q2, Q3, Q5 were lower than that of junior doctors (all P < 0.05), while both LLMs were comparable to junior doctors when answering Q4 and Q6. In terms of "high reproducibility and accuracy", ChatGPT-3.5 outperformed New Bing Chat in Q1 and Q5 (P < 0.001 and P = 0.008, respectively), but showed no significant difference in Q2, Q3, Q4, and Q6 (P > 0.05 for all). New Bing Chat generated higher accuracy than ChatGPT-3.5 (72.41% vs 58.62%) (P = 0.003) in decision making of thyroid nodules, and both were less accurate than junior doctors (89.66%, P < 0.001 for both). CONCLUSIONS: The exploration of ChatGPT-3.5 and New Bing Chat in the diagnosis and management of thyroid nodules illustrates that LLMs currently demonstrate the potential for medical applications, but do not yet reach the clinical decision-making capacity of doctors.

Furfural analysis of aqueous and oily foodstuffs using a single modified paper for combined headspace extraction, derivatization and paper spray mass spectrometry.

Furfurals, including 2-furaldehyde, 5-methylfurfural and 5-hydroxymethylfurfural, widely exist in carbohydrate-rich daily foods, and may have toxic effects on humans. Here, a new headspace extraction-paper spray mass spectrometry (HSPS-MS/MS) method was established for furfural detection, in which the extraction and derivatization of volatiles with pre-loaded derivatization agent on paper tips is combined with paper spray mass spectrometry for detection. By this simple and cheap approach, interference of non-volatile matrix compounds is prevented, and the derivatization agent improves electrospray-type ionization efficiency, thus increasing selectivity and sensitivity. The approach was optimized, by investigating positioning during extraction, extraction duration, derivatization agent, addition of internal standard for quantification and finally validated. For this, the developed method was benchmarked against HPLC-UV and could obtain detections limits of 0.32-0.40 µg mL-1 for 2-furaldehyde, 5-methylfurfural and 5-hydroxymethylfurfural in olive oil. Moreover, fast screening of free furfurals in soy sauce, coffees and teas was demonstrated with the HSPS-MS/MS method.

DHPS-Mediated Hypusination Regulates METTL3 Self-m6A-Methylation Modification to Promote Melanoma Proliferation and the Development of Novel Inhibitors.

Discovering new treatments for melanoma will benefit human health. The mechanism by which deoxyhypusine synthase (DHPS) promotes melanoma development remains elucidated. Multi-omics studies have revealed that DHPS regulates m6A modification and maintains mRNA stability in melanoma cells. Mechanistically, DHPS activates the hypusination of eukaryotic translation initiation factor 5A (eIF5A) to assist METTL3 localizing on its mRNA for m6A modification, then promoting METTL3 expression. Structure-based design, synthesis, and activity screening yielded the hit compound GL-1 as a DHPS inhibitor. Notably, GL-1 directly inhibits DHPS binding to eIF5A, whereas GC-7 cannot. Based on the clarification of the mode of action of GL-1 on DHPS, it is found that GL-1 can promote the accumulation of intracellular Cu2+ to induce apoptosis, and antibody microarray analysis shows that GL-1 inhibits the expression of several cytokines. GL-1 shows promising antitumor activity with good bioavailability in a xenograft tumor model. These findings clarify the molecular mechanisms by which DHPS regulates melanoma proliferation and demonstrate the potential of GL-1 for clinical melanoma therapy.

Association between SII and markers of liver injury: A cross-sectional study from the NHANES (2017-2020).

INTRODUCTION: A novel indicator of inflammation is the systemic immune-inflammation index (SII), and liver dysfunction is linked to the advancement of inflammation. In light of this, this study aims to look into any potential connections between SII and markers of liver injury. METHODS: A cross-sectional study was conducted using the National Health and Nutrition Examination (NHANES) dataset for 2017-2020. The linear relationship between SII and markers of liver injury was examined using multiple linear regression models. Examining threshold effects and fitted smoothed curves were utilized to describe nonlinear connections. RESULTS: A total of 8213 adults aged 18-80 years participated in this population-based study. In the fully adjusted model, SII maintained a negative association with ALT(ß = -0.003, 95%CI:-0.005, -0.002, P<0.00001), AST(ß = -0.004, 95% CI:-0.005, -0.002, P<0.00001), and GGT(ß = -0.004, 95% CI:-0.007, -0.000, P = 0.03791) and a positive association with ALP (ß = 0.005, 95% CI:0.003, 0.007, P<0.00001). In subgroup analyses, it was found that SII remained negatively correlated with ALT, AST and GGT in gender, age and body mass index. SII was positively correlated with ALP at BMI≥25(kg/m2)(ß = 0.005, 95% CI:0.003, 0.008, P = 0.00001), and was negatively correlated with ALT(ß = -0.004, 95% CI:-0.005, -0.002, P<0.00001), AST(ß = -0.004, 95% CI:-0.005, -0.003, P<0.00001) and GGT(ß = -0.004, 95% CI:-0.008, -0.000, P = 0.02703) at BMI≥25, whereas no significant correlation was observed at BMI<25 (all P-values>0.05). Furthermore, the association between SII and markers of liver injury was nonlinear. By using a two-stage linear regression model for analysis, a U-shaped relationship was found to exist between SII and ALT with a turning point of 818.40(1,000 cells/µl). The inflection points of SII with AST and GGT were 451.20 (1,000 cells/µl) and 443.33 (1,000 cells/µl), respectively, and no significant inflection point with ALP was observed. Interaction tests demonstrated that SII correlation with ALT, AST, ALP, and GGT was not significantly different between strata (all p for interaction>0.05). CONCLUSIONS: The research findings suggested that there was a negative correlation between SII and ALT, AST and GGT, and a positive correlation with ALP. However, larger prospective investigations are still greatly needed to confirm the findings.

The circular RNA circSLC16A10 alleviates diabetic retinopathy by improving mitochondrial function via the miR-761-5p/MFN2 axis.

It has been demonstrated that circular RNAs (circRNAs) are associated with the development of diabetic retinopathy (DR). Nevertheless, the function of circSLC16A10 in the development of DR remains unclear. In order to investigate the role of circSLC16A10, we employed cell and animal models of DR. An analysis of a public database revealed that hsa_circSLC16A10 was expressed at lower levels in DR patients than in diabetic patients without DR or healthy controls. Additionally, the level of hsa_circSLC16A10 was lower in high glucose (HG)-exposed ARPE-19 cells and diabetic mice. hsa_circSLC16A10 was observed to be mainly distributed in the cytoplasm. Moreover, overexpression of hsa_circSLC16A10 alleviated HG-induced endoplasmic reticulum stress and cell apoptosis in vitro. Furthermore, overexpression of hsa_circSLC16A10 ameliorated HG-induced mitochondrial dysfunction, as evidenced by improvements in mitochondrial structure and function. hsa_circSLC16A10 acted as a hsa-miR-761-5p sponge to increase MFN2 expression. MFN2 knockdown or hsa-miR-761-5p overexpression partially reversed the protective effect of hsa_circSLC16A10 in vitro. The protective effect of mmu_circSLC16A10 against DR was confirmed in an animal model of DR. These findings indicate that circSLC16A10 may regulate DR progression by improving mitochondrial function via the miR-761-5p/MFN2 axis.

Exploring main soil drivers of vegetation succession in abandoned croplands of Minqin Oasis, China.

Background: The Minqin Oasis, which is located in Wuwei City, Gansu Province, China, faces a very serious land desertification problem, with about 94.5% of its total area desertified. Accordingly, it is crucial to implement ecological restoration policies such as cropland abandonment in this region. In abandoned croplands, abiotic factors such as soil properties may become more important than biotic factors in driving vegetation succession. However, the connections between soil properties and vegetation succession remain unclear. To fill this knowledge gap, this study investigated these connections to explore major factors that affected vegetation succession, which is meaningful to designing management measures to restore these degraded ecosystems. Methods: This study investigated seven 1-29-year-old abandoned croplands using the "space for time" method in Minqin Oasis. Vegetation succession was classified into different stages using a canonical correlation analysis (CCA) and two-way indicator species analysis (Twinspan). The link between soil properties and vegetation succession was analyzed using CCA. The primary factors shaping community patterns of vegetation succession were chosen by the "Forward selection" in CCA. The responses of dominant species to soil properties were analyzed using generalized additive models (GAMs). Results: Dominant species turnover occurred obviously after cropland abandonment. Vegetation succession can be classified into three stages (i.e., early, intermediate, and late successional stages) with markedly different community composition and diversity. The main drivers of vegetation succession among soil properties were soil salinity and saturated soil water content and they had led to different responses of the dominant species in early and late successional stages. During the development of vegetation succession, community composition became simpler, and species diversity decreased significantly, which was a type of regressive succession. Therefore, measures should be adopted to manage these degraded, abandoned croplands.

Safety of embryo cryopreservation: insights from mid-term placental transcriptional changes.

BACKGROUND: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms. METHODS: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET). RESULTS: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups. CONCLUSION: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.

Botensilimab, an Fc-enhanced anti-CTLA-4 antibody, is effective against tumors poorly responsive to conventional immunotherapy.

Conventional immune checkpoint inhibitors (ICI) targeting CTLA-4 elicit durable survival, but primarily in patients with immune-inflamed tumors. Although the mechanisms underlying response to anti-CTLA-4 remain poorly understood, Fc-gamma receptor (FcγR) IIIA co-engagement appears critical for activity, potentially explaining the modest clinical benefits of approved anti-CTLA-4 antibodies. We demonstrate that anti-CTLA-4 engineered for enhanced FcγR affinity leverages FcγR-dependent mechanisms to potentiate T cell responsiveness, reduce intratumoral Tregs, and enhance antigen presenting cell activation. Fc-enhanced anti-CTLA-4 promoted superior efficacy in mouse models and remodeled innate and adaptive immunity versus conventional anti-CTLA-4. These findings extend to patients treated with botensilimab, an Fc-enhanced anti-CTLA-4 antibody, with clinical activity across multiple poorly immunogenic and ICI treatment-refractory cancers. Efficacy was independent of tumor neoantigen burden or FcγRIIIA genotype. However, FcγRIIA and FcγRIIIA expression emerged as potential response biomarkers. These data highlight the therapeutic potential of Fc-enhanced anti-CTLA-4 antibodies in cancers unresponsive to conventional ICI therapy.

Inhibition of Indoleamine 2,3-Dioxygenase Exerts Antidepressant-like Effects through Distinct Pathways in Prelimbic and Infralimbic Cortices in Rats under Intracerebroventricular Injection with Streptozotocin.

The application of intracerebroventricular injection of streptozotocin (ICV-STZ) is considered a useful animal model to mimic the onset and progression of sporadic Alzheimer's disease (sAD). In rodents, on day 7 of the experiment, the animals exhibit depression-like behaviors. Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme catalyzing the conversion of tryptophan (Trp) to kynurenine (Kyn), is closely related to depression and AD. The present study aimed to investigate the pathophysiological mechanisms of preliminary depression-like behaviors in ICV-STZ rats in two distinct cerebral regions of the medial prefrontal cortex, the prelimbic cortex (PrL) and infralimbic cortex (IL), both presumably involved in AD progression in this model, with a focus on IDO-related Kyn pathways. The results showed an increased Kyn/Trp ratio in both the PrL and IL of ICV-STZ rats, but, intriguingly, abnormalities in downstream metabolic pathways were different, being associated with distinct biological effects. In the PrL, the neuroprotective branch of the Kyn pathway was attenuated, as evidenced by a decrease in the kynurenic acid (KA) level and Kyn aminotransferase II (KAT II) expression, accompanied by astrocyte alterations, such as the decrease in glial fibrillary acidic protein (GFAP)-positive cells and increase in morphological damage. In the IL, the neurotoxicogenic branch of the Kyn pathway was enhanced, as evidenced by an increase in the 3-hydroxy-kynurenine (3-HK) level and kynurenine 3-monooxygenase (KMO) expression paralleled by the overactivation of microglia, reflected by an increase in ionized calcium-binding adaptor molecule 1 (Iba1)-positive cells and cytokines with morphological alterations. Synaptic plasticity was attenuated in both subregions. Additionally, microinjection of the selective IDO inhibitor 1-Methyl-DL-tryptophan (1-MT) in the PrL or IL alleviated depression-like behaviors by reversing these different abnormalities in the PrL and IL. These results suggest that the antidepressant-like effects linked to Trp metabolism changes induced by 1-MT in the PrL and IL occur through different pathways, specifically by enhancing the neuroprotective branch in the PrL and attenuating the neurotoxicogenic branch in the IL, involving distinct glial cells.

Temperature-Responsive "Nano-to-Micro" Transformed Polymersomes for Enhanced Ultrasound/Fluorescence Dual Imaging-Guided Tumor Phototherapy.

The perfect integration of microbubbles for efficient ultrasound imaging and nanocarriers for intelligent tumor-targeting delivery remains a challenge in precise tumor theranostics. Herein, we exquisitely fabricated laser-activated and targeted polymersomes (abbreviated as FIP-NPs) for simultaneously encapsulating the photosensitizer indocyanine green (ICG) and the phase change agent perfluorohexane (PFH). The formulated FIP-NPs were nanosize and effectively accumulated into tumors as observed by ICG fluorescence imaging. When the temperature rose above 56 °C, the encapsulated PFH transformed from liquid to gas and the FIP-NPs underwent balloon-like enlargement without structure destruction. Impressively, the enlarged FIP-NPs fused with adjacent polymersomes to form even larger microparticles. This temperature-responsive "nano-to-micro" transformation and fusion process was clearly demonstrated, and FIP-NPs showed greatly improved ultrasound signals. More importantly, FIP-NPs achieved dramatic antitumor efficacy through ICG-mediated phototherapy. Taken together, the novel polymersomes achieved excellent ultrasound/fluorescence dual imaging-guided tumor phototherapy, providing an optimistic candidate for the application of tumor theranostics.

Quercetin intervention reduced hepatic fat deposition in patients with nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled crossover clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become a growing public health problem worldwide. However, there is still lack of effective treatment strategies except lifestyle intervention. OBJECTIVES: To evaluate whether quercetin improves intrahepatic lipid content in patients with NAFLD. METHODS: In this randomized, double-blind, placebo-controlled crossover trial, 41 patients with NAFLD were randomly assigned to receive the quercetin (500 mg) or placebo capsules for 12 wk, then switched interventions for another 12 wk after a 4-wk washout period. The primary outcome was intrahepatic lipid content evaluated by magnetic resonance imaging estimated proton density fat fraction. The secondary outcomes were liver function measurements, etc. Safety outcomes included blood routine. RESULTS: A total of 36 patients completed the trial. In intention-to-treat analyses, the quercetin intervention moderately decreased the intrahepatic lipid contents from 11.5% ± 6.4% to 9.6% ± 5.8%, compared with the placebo intervention (decreased by 0.1% ± 2.6%, P = 0.013 and adjusted P value is 0.028). Body weight and body mass index were mildly reduced by 1.5 ± 2.6 kg and 0.5 ± 0.9 kg/m2 after the quercetin intervention (P < 0.05 and both adjusted P values are 0.038), whereas the reductions were only 0.2 ± 1.8 kg and 0.1 ± 0.7 kg/m2 after the placebo intervention. The intrahepatic lipid content reductions were noticeably positively associated with the body weight losses after the quercetin and placebo interventions (r = 0.557 and 0.412, P < 0.001 and P = 0.007, respectively). Subgroup analyses found that the reduction of intrahepatic lipid contents in females (3.0% ± 3.7%) was about twice as large as that in males (1.4% ± 2.5%) with a trend of statistical significance (P = 0.113 and adjusted P value is 0.061). There were no significant differences in other secondary and safety outcomes. No adverse events associated with study intervention were found. CONCLUSIONS: Twelve weeks treatment of quercetin could reduce intrahepatic lipid contents in patients with NAFLD, possibly explained by a slightly larger body weight loss in the quercetin group. TRIAL REGISTRATION: The trial is registered at www.chictr.org.cn as ChiCTR2100047904.

The Anthraquinone Derivative C2 Enhances Oxaliplatin-Induced Cell Death and Triggers Autophagy via the PI3K/AKT/mTOR Pathway.

Chemotherapy resistance in cancer is an essential factor leading to high mortality rates. Tumor multidrug resistance arises as a result of the autophagy process. Our previous study found that compound 1-nitro-2 acyl anthraquinone-leucine (C2) exhibited excellent anti-colorectal cancer (CRC) activity involving autophagy and apoptosis-related proteins, whereas its underlying mechanism remains unclear. A notable aspect of this study is how C2 overcomes the multidrug susceptibility of HCT116/L-OHP, a colon cancer cell line that is resistant to both in vitro and in vivo oxaliplatin (trans-/-diaminocyclohexane oxalatoplatinum; L-OHP). In a xenograft tumor mouse model, we discovered that the mixture of C2 and L-OHP reversed the resistance of HCT116/L-OHP cells to L-OHP and inhibited tumor growth; furthermore, C2 down-regulated the gene expression levels of P-gp and BCRP and decreased P-gp's drug efflux activity. It is important to note that while C2 re-sensitized the HCT116/L-OHP cells to L-OHP for apoptosis, it also triggered a protective autophagic pathway. The expression levels of cleaved caspase-3 and Beclin 1 steadily rose. Expression of PI3K, phosphorylated AKT, and mTOR were decreased, while p53 increased. We demonstrated that the anthraquinone derivative C2 acts as an L-OHP sensitizer and reverses resistance to L-OHP in HCT116/L-OHP cells. It suggests that C2 can induce autophagy in HCT116/L-OHP cells by mediating p53 and the PI3K/AKT/mTOR signaling pathway.

Reduced Health-Related Quality of Life Due to Mobile Phone Dependence in a Sample of Chinese College Students: The Mediating Role of Chronotype and Sleep Quality.

PURPOSE: Presenting a chain mediation model to investigate whether mobile phone dependence results in a reduction in health-related quality of life (HRQoL) among Chinese college students, through the mediating effect of chronotype and sleep quality. DESIGN AND SETTING: A cross-sectional survey was conducted on students from a Chinese university using a validated structured questionnaire. SAMPLE: 2014 freshmen. MEASURES: The study measured the students' level of mobile phone dependence using the Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use. Chronotype and sleep quality were measured by the Chinese version of the Morningness-Eveningness Questionnaire (MEQ) and the Pittsburgh Sleep Quality Index (PSQI), respectively. HRQoL was evaluated using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L), including a descriptive system and a visual analog scale (VAS). ANALYSIS: Descriptive statistical analysis, correlation analysis, and mediation analysis. RESULTS: Mobile phone dependence had a significant negative effect on HRQoL as indicated by both the EQ-5D-5L index score and EQ-VAS score (P < .001 for both). Additionally, it was found to significantly predict chronotype (MEQ score) (ß = -.546, P < .001) and sleep quality (PSQI score) (ß = .163, P < .001). Chronotype negatively predict sleep quality (ß = -.058, P < .001), and sleep quality was a significant negative predictor of HRQoL (EQ-5D-5L index score, ß = -.008, P < .001; EQ-VAS score, ß = -1.576, P < .001). CONCLUSION: Mobile phone dependence negatively impacts students' HRQoL through chronotype and sleep quality, and there is a chain mediating effect. Students should consider making lifestyle changes to improve their HRQoL and promote health.