Nonaqueous Electroextraction with Tunable Selectivity for Direct, Fast, and Exhaustive Enrichment of Per- and Polyfluoroalkyl Acids from Oils and Food Contact Materials.

Widespread concerns have been raised due to the ever-increasing number of novel per- and polyfluoroalkyl acids (PFAAs) and the ever-decreasing level of legacy PFAAs. Most analytical methods for PFAAs suffer from a narrow range of analyzable PFAAs, insufficient sensitivity, poor performance for oil samples, and defective quantification without internal standards or blank matrices. To solve these challenges, a highly selective method for multiple PFAAs from oils and food contact materials (FCMs) was developed based on nonaqueous electroextraction (NE). Through theoretical derivation and experimental investigation, the selectivity of NE was discovered to be tunable, and the range of extractable analytes could be tuned by adjusting the dielectric constant of the sample solution. For PFAAs, the selectivity was attributed to the pKa-based differential migration mechanism, as PFAAs exhibited less variable pKa values in different solvents compared to interference components. The method achieved nonmatrix-matched calibration without internal standards and integration of sample cleanup, selective extraction, and exhaustive enrichment into a fast and convenient operation. The method provided low limits of detection (0.002-0.03 µg·kg-1), satisfactory accuracy (88.0-107.8%), and RSDs (<11.7%). Migration experiments from 33 FCMs to oils were further investigated. PFBS (<0.05-2.34 µg·kg-1) and PFBA (<0.2-0.398 µg·kg-1) were detected from most FCMs. This was the first attempt at PFAA analysis as well as oil sample analysis using an electric field-assisted extraction technique and also the first report on PFAA migration from FCMs into edible oils.

Beyond protein intake: does dietary fat intake in the year preceding pregnancy and during pregnancy have an impact on gestational diabetes mellitus?

PURPOSE: Studies regarding the association between dietary fat intake and gestational diabetes mellitus (GDM) are limited and provide conflicting findings. Thus, the study aims to examine the association of dietary fat intake in the year preceding pregnancy and during pregnancy with the risk of GDM, taking the relevance of dietary protein intake on GDM into consideration. METHODS: A prospective study was conducted in 6299 singleton pregnancies, using the data from the Nutrition in Pregnancy and Growth in Southwest China (NPGSC). A validated food frequency questionnaire was used to assess dietary fat intake in the year preceding pregnancy and during the first and second trimesters of pregnancy. Logistic regression analysis was used to assess the prospective associations of dietary fat intake and the type and source of dietary fats in different time windows with GDM risk. RESULTS: Higher intake of total fat [OR (95% CI): 2.21 (1.19-4.20), P = 0.02] during 12-22 weeks of gestation was associated with higher GDM risk. However, adjustment for animal protein intake greatly attenuated this association [OR (95% CI): 1.81 (0.93, 3.64), P = 0.11]. Total fat intake neither in the year preceding pregnancy nor during the early pregnancy was associated with GDM risk. Moreover, insignificant associations were observed between intakes of vegetable fat, animal fat, cholesterol, saturated fatty acid, monounsaturated fatty acid and polyunsaturated fatty acid one year before pregnancy and during the first and second trimesters and GDM risk. CONCLUSION: Our study indicated that dietary fat intake one year before pregnancy and across the two pregnancy trimesters preceding the diagnosis of GDM has no relevance on GDM risk among Chinese women, particularly those with normal BMI, low, or normal calorie intake.

Nutrition in Pregnancy and Growth in Southwest China (NPGSC) cohort: Design, implementation, and characteristics.

BACKGROUND: Pregnancy and birth cohorts addressing maternal nutrition and its impact on health outcomes have been rare in China, especially in Southwest China. OBJECTIVES: To describe the design, implementation, baseline characteristics, and initial results of the Nutrition in Pregnancy and Growth in Southwest China (NPGSC) cohort. POPULATION: Pregnant women with their children in Southwest China. DESIGN: NPGSC participants have been prospectively recruited since 2014. Pregnant women were invited to participate in the study at their first routine ultrasound examination in gestational weeks 9-11. Data were assessed three times during pregnancy (9-11, 20-22, and 33-35 gestation weeks), and eight times in infants and toddlers. METHODS: Pre-pregnancy body weight and height were self-reported; gestational weight gain was measured at regular intervals. Both food frequency questionnaires (FFQ) and 24-hour dietary recalls were used to collect dietary intakes during pregnancy, and FFQ for diet before pregnancy. Information on pregnancy outcomes was extracted from the medical birth registry. Anthropometry of children in the first 3 years of life was measured by trained investigators. Other child outcomes, including feeding practices (self-reported by mothers) and cognitive development (assessed by the Chinese version of Ages and Stages Questionnaire), were recorded. PRELIMINARY RESULTS: Between 2014 and 2018, 12 989 pregnant women were enrolled, and 2296 children completed the 3 years follow-up. Among them, 115 pregnancies ended in stillbirth. Mean maternal pre-pregnancy BMI was 21.1 kg/m2 and mean gestational weight gain was 13.5 kg 18.6% of mothers developed gestational diabetes and 1.5% of mothers were diagnosed with preeclampsia. Mean birthweight and birth length of children were, respectively, 3329 g and 49.4 cm. CONCLUSION: We built a prospective cohort in Southwest China, which can provide valuable data to investigate the relevance of nutrition for the health of mothers and children.

Monetary diet cost is positively associated with diet quality and obesity: an analysis of school-aged children in Southwest China.

BACKGROUND: Little is known about the relationships between diet cost, dietary intake and obesity in Chinese populations. This study explored how diet cost was related to diet quality and obesity among school-aged children in Southwest China. METHODS: Data from a cross-sectional study was analysed. Diet cost was estimated based on dietary intake assessed with 24-h dietary recalls and retail food prices. Diet quality was measured using the Chinese Children Dietary Index. Body height, weight, waist circumference and skinfold thicknesses were measured, and their body mass index standard deviation score (BMISDS), waist-to-height ratio (WHtR), fat mass index (FMI) and fat-free mass index (FFMI) were calculated. Multivariate regression models were used to explore the relevance of diet cost to diet quality and obesity. RESULTS: After adjustment for potential confounders, a positive association was observed between diet quality and energy-adjusted diet cost (ß = 0.143, 95% confidence interval, CI: 0.014-0.285, Pfor-trend = 0.0006). Energy-adjusted diet cost also showed a positive association with FMI (ß = 0.0354, 95% CI: 0.0001-0.0709, Pfor-trend = 0.01), BMISDS (ß = 0.0200, 95% CI: 0.0006-0.0394, Pfor-trend = 0.002) and WHtR (ß = 0.0010, 95% CI: 0.0003-0.0017, Pfor-trend = 0.02). CONCLUSIONS: Energy-adjusted diet cost was independently and positively associated with diet quality and obesity among Chinese school-aged children.

Higher serum 25(OH)D level is associated with decreased risk of impairment of glucose homeostasis: data from Southwest China.

BACKGROUND: Recent epidemiological studies have suggested inverse associations between vitamin D status and metabolic diseases including type 2 diabetes (T2DM). The aim of this study was to examine whether a higher serum 25-hydroxyvitamin D (25(OH)D) was associated with a more favorable glucose homeostasis among adults without diabetes in Southwest China. METHODS: Serum 25(OH)D concentration was measured in a cross-sectional sample of 1514 adults without diabetes aged 25-65 years recruited from Southwest China. Indices describing glucose homeostasis included fasting plasma glucose (FPG), fasting insulin, glycated hemoglobin (HbA1c), the homeostatic model assessment 2-insulin resistance (HOMA2-IR) and odds of pre-diabetes. Data were analyzed by multivariable-adjusted regression models. RESULTS: The average serum 25(OH)D was 22.66 ng/ml, and percentages of vitamin D deficiency [25(OH)D < 20 ng/ml], insufficiency [20 ≤ 25(OH)D ≤ 30 ng/ml] were 47.6 and 32.2%, respectively. Serum 25(OH)D was inversely associated with fasting insulin (P = 0.0007), HbA1c (P = 0.0001) and HOMA2-IR (P = 0.0007), but not with FPG, after adjusting for age, gender, monthly personal income, smoking status, energy intake, moderate-to-vigorous physical activity (MVPA) and waist circumference (WC). Compared with the lowest 25(OH)D tertile, the odds ratio for pre-diabetes in the highest tertile was 0.68 (95%CI: 0.47-0.99) after adjustment for cofounders. In the following stratified analyses according to weight status, we only observed this inverse association between serum 25(OH)D and pre-diabetes in overweight or obese adults (n = 629, P = 0.047), but not in their counterparts with BMI < 24 kg/m2. CONCLUSIONS: Our results advocate that a higher serum 25(OH)D level is associated with decreased risk of impairment of glucose homeostasis among adults without diabetes in Southwest China. Further studies are warranted to determine the role of vitamin D in glucose homeostasis.

Association between dietary inflammatory index and all-cause mortality in US adults with dermatitis: a population-based cohort study.

Background: While dermatitis management is primarily symptomatic, the role of diet in symptom exacerbation and improvement is increasingly recognized. The dietary inflammatory index (DII), a quantitative assessment tool for dietary inflammatory potential, has been associated with various chronic diseases but remains understudied in dermatitis. This cohort study investigated the association between DII scores and all-cause mortality among patients with dermatitis. Methods: The study included 1,074 patients with dermatitis and complete dietary intake records from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. The DII scores were calculated using two 24-h dietary recalls and dietary supplement intakes and the consumption of 28 foods with known pro- or anti-inflammatory properties. All-cause mortality information was from the National Death Index, censored on December 31, 2019. Multivariable Cox hazards regression models, restricted cubic spline (RCS) models, and subgroup analyses were employed to evaluate the association of DII with all-cause mortality, adjusting for potential confounders. Results: The 1,074 patients were divided into DII tertiles (T1: n = 358, median age 40 years, DII -3.91, 0.06; T2: n = 296, median age 40 years, DII 0.06, 1.88; T3: n = 237, median age 39 years, DII 1.88, 4.39). The study revealed a positive correlation between higher DII scores and increased all-cause mortality risk among patients with dermatitis (fully-adjusted model, HR = 1.13, 95% CI 1.02, 1.27, p = 0.026). This association was more pronounced in adults over 45 years, with the highest DII tertile indicating a 2.42-fold increased mortality risk (95% CI 1.15, 5.07, p = 0.019) compared with the lowest tertile. The RCS model confirmed a linear dose-response trend (p for non-linear = 0.183), validating the relationship. Conclusion: Elevated DII scores are associated with an increased risk of all-cause mortality in patients with dermatitis, suggesting that the dietary inflammatory potential may impact health outcomes in this population. The findings underscore the importance of dietary interventions in dermatitis management, especially for middle-aged and older adults. Future research with larger cohorts and a longer follow-up is warranted to validate the findings.

Plasmon-Assisted Trapping of Single Molecules in Nanogap.

The manipulation of single molecules has attracted extensive attention because of their promising applications in chemical, biological, medical, and materials sciences. Optical trapping of single molecules at room temperature, a critical approach to manipulating the single molecule, still faces great challenges due to the Brownian motions of molecules, weak optical gradient forces of laser, and limited characterization approaches. Here, we put forward localized surface plasmon (LSP)-assisted trapping of single molecules by utilizing scanning tunneling microscope break junction (STM-BJ) techniques, which could provide adjustable plasmonic nanogap and characterize the formation of molecular junction due to plasmonic trapping. We find that the plasmon-assisted trapping of single molecules in the nanogap, revealed by the conductance measurement, strongly depends on the molecular length and the experimental environments, i.e., plasmon could obviously promote the trapping of longer alkane-based molecules but is almost incapable of acting on shorter molecules in solutions. In contrast, the plasmon-assisted trapping of molecules can be ignored when the molecules are self-assembled (SAM) on a substrate independent of the molecular length.

Subsets of cancer cells expressing CX3CR1 are endowed with metastasis-initiating properties and resistance to chemotherapy.

Metastasis-initiating cells (MICs) display stem cell-like features, cause metastatic recurrences and defy chemotherapy, which leads to patients' demise. Here we show that prostate and breast cancer patients harbor contingents of tumor cells with high expression of CX3CR1, OCT4a (POU5F1), and NANOG. Impairing CX3CR1 expression or signaling hampered the formation of tumor spheroids by cell lines from which we isolated small subsets co-expressing CX3CR1 and stemness-related markers, similarly to patients' tumors. These rare CX3CR1High cells show transcriptomic profiles enriched in pathways that regulate pluripotency and endowed with metastasis-initiating behavior in murine models. Cancer cells lacking these features (CX3CR1Low) were capable of re-acquiring CX3CR1-associated features over time, implying that MICs can continuously emerge from non-stem cancer cells. CX3CR1 expression also conferred resistance to docetaxel, and prolonged treatment with docetaxel selected CX3CR1High phenotypes with de-enriched transcriptomic profiles for apoptotic pathways. These findings nominate CX3CR1 as a novel marker of stem-like tumor cells and provide conceptual ground for future development of approaches targeting CX3CR1 signaling and (re)expression as therapeutic means to prevent or contain metastasis initiation.

[Clinical observation of refined moxibustion for sequelae of pelvic inflammatory disease with qi stagnation and blood stasis].

OBJECTIVE: To compare the curative effect of refined moxibustion, traditional moxa box moxibustion and Chinese patent medicine on the sequelae of pelvic inflammatory disease with qi stagnation and blood stasis. METHODS: A total of 150 patients with sequelae of pelvic inflammatory disease with qi stagnation and blood stasis were randomized into a refined moxibustion group (50 cases), a box-moxibustion group (50 cases) and a Chinese medication group (50 cases, 2 cases dropped off). The patients in the refined moxibustion group were treated with refined moxibustion at Qihai (CV 6), Guanyuan (CV 4), Zigong (EX-CA 1) and Shuidao (ST 28), 2 moxa-cones for each acupoint. The patients in the box-moxibustion group were treated with box-moxibustion on the lower abdomen and Shenque (CV 8), and the patients in the Chinese medication group were treated with penyanqing capsules orally. All groups started treatment after menstruation, moxibustion was applied once every 4 days, twice a week, and medication was taken 3 times a day for a total of 2 menstrual cycles. The TCM symptoms and body signs scores of each group were observed before and after treatment. The short form health survey (SF-36) scores of each group were observed before and after treatment and during follow-up 12 weeks after treatment. RESULTS: After treatment, the TCM symptoms, body signs and comprehensive scores of each group were lower than those before treatment (P<0.05), and those in the refined moxibustion group were lower than the box-moxibustion group and the Chinese medication group (P<0.05). The SF-36 scores of each group after treatment and during follow-up were higher than before treatment (P<0.05); during follow-up, the SF-36 scores of the box-moxibustion group and the Chinese medication group were lower than after treatment (P<0.05), while that in the refined moxibustion group was higher than after treatment (P<0.05); the SF-36 scores after treatment and during follow-up in the refined moxibustion group were higher than the box-moxibustion group and the Chinese medication group (P<0.05, P<0.01). CONCLUSION: Compared with traditional moxa box moxibustion and Chinese patent medicine treatment, refined moxibustion can better improve the symptoms, body signs and quality of life in patients with the sequelae of pelvic inflammatory disease of qi stagnation and blood stasis, and the effect is longer.

Relevance of dietary glycemic index, glycemic load and fiber intake before and during pregnancy for the risk of gestational diabetes mellitus and maternal glucose homeostasis.

BACKGROUND & AIMS: To date, the prevalence of Gestational diabetes mellitus (GDM) in China was 17.5%. Given the substantial relevance of GDM for medium- and long-term health of both mother and offspring and the paucity of existing data on the link between maternal diet and glucose homeostasis during pregnancy in Asian population, additional studies are needed. To examine the relevance of dietary glycemic index (GI), glycemic load (GL) and fiber intake before and during pregnancy for the development of GDM and glucose homeostasis over the course of pregnancy. METHODS: Cox proportional hazards analysis and linear mixed effects regressions were performed on data from 9317 women for whom three food frequency questionnaires (pre-pregnancy, 1st and 2nd trimesters) and biochemical measures during pregnancy were available. Investigated outcome variables included GDM risk, fasting plasma glucose (FPG), glycated hemoglobin (HbA1C), and homeostasis model assessment insulin resistance (HOMA-IR) in the 1st, 2nd and 3rd trimesters. RESULTS: Women in the highest tertile of dietary GI (or GL) before pregnancy, in the 1st, or the 2nd trimester respectively had a 12% (15%), 25% (23%) or 29% (25%) higher risk of developing GDM than those in the lowest tertile (all p for trend ≤ 0.02). Women with the highest dietary fiber intake before pregnancy, in the 1st or 2nd trimester had a 11%, 17% or 18% lower GDM risk (all p for trend ≤ 0.03). Moreover, increases in GI or GL and decreases in fiber intake over the course of pregnancy (1st to 3rd trimesters) were independently associated with adverse concurrent developments in FPG, HbA1C and HOMA-IR (p ≤ 0.03). CONCLUSIONS: Our study indicates that dietary GI, GL and fiber intake before and during pregnancy affects glucose homeostasis of pregnant Chinese women.

Corrigendum: Heparan Sulfate Induces Necroptosis in Murine Cardiomyocytes: A Medical-in-Silico Approach Combining In Vitro Experiments and Machine Learning.

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Icariside II induces cell cycle arrest and differentiation via TLR8/MyD88/p38 pathway in acute myeloid leukemia cells.

Acute myeloid leukemia (AML) is a devastating hematological malignancy, characterized by differentiation arrest and unscheduled proliferation of immature cells of the myeloid lineage. Inducing AML cell differentiation has emerged as a promising therapeutic strategy for the therapy of AML. Icariside II, an active component of Herba Epimedii, has been well defined to promote osteogenic differentiation. However, the differentiation-inducing effect of Icariside II on AML cells has not been explored. In this study, we investigated the differentiation-inducing effect and underlying mechanism of Icariside II in AML HL-60 and THP-1 cell lines. Icariside II induced G1 phase cell cycle arrest by down-regulating Cyclin-dependent kinases (CDK2, CDK4 and CDK6) and up-regulating Cyclin-dependent kinase inhibitor (p21 and p27). Importantly, Icariside II could induce differentiation of AML cells, accompanied by the up-regulation of Toll-like receptor 8 (TLR8), myeloid differentiation factor 88 (MyD88) and phosphorylated p38. Further study indicated the cell cycle arrest and differentiation induced by Icariside II could be abrogated by TLR8-specific inhibitor CU-CPT9a. Collectively, these findings firstly demonstrate Icariside II induces cell cycle arrest and differentiation of AML cells via activation of TLR8/MyD88/p38 pathway, suggesting Icariside II could be developed into a novel differentiation-inducing agent for AML.

Bibliometric analysis on research hotspots and evolutionary trends of artificial intelligence application in traditional Chinese medicine diagnosis / 数字中医药（英文）

@#【Objective】  To explore the development and research hotspots on the application of artificial intelligence (AI) in traditional Chinese medicine (TCM) diagnosis and predict research trends in the area. 【Methods】  All articles were retrieved from China National Knowledge Infrastructure (CNKI), Wanfang Data (Wanfang), China Science and Technology Journal Database (VIP), and Web of Science Core Collection (WoSCC). All related papers published in journals from the foundation of the databases to December 31, 2022 were included. NoteExpress, Co-Occurrence(COOC), VOSviewer, and CiteSpace were used to visualize data about publication volumes, journals, authors, research institutions, and keywords as well as to analyze hotspots trending topics in the field. 【Results】  A total of 686 articles were retrieved from the databases, among which 610 papers were published in Chinese and 76 in English. In terms of the journals in which these papers were published, 238 of them were Chinese journals and 52 were English ones. The number of the papers published in journals presented a slow growth. According to the results from Chinese article analysis, WANG Yiqin from Shanghai University of Traditional Chinese Medicine published the most papers in the field. The authors of Chinese papers belonged to six long-term research teams, led by WANG Yiqin and XU Jiatuo (Shanghai University of Traditional Chinese Medicine), WEI Yuke (Guangdong University of Technology), LI Gang (Tianjin University), XI Guangcheng (Institute of Automation of the Chinese Academ of Sciences), and NIU Xin (Beijing University of Chinese Medicine), respectively. In accordance with results from English paper analysis, four authors equally publishing the most papers were YAN Haixia, HU Xiaojuan, and JIANG Tao (Shanghai University of Traditional Chinese Medicine), and WEN Chuanbiao (Chengdu University of Traditional Chinese Medicine). The authors of English papers were from two major research teams in the field of Shanghai University of Traditional Chinese Medicine. Currently, research hotspots on AI such as neural networks, data mining, machine learning, feature recognition, image processing, and expert systems, have been centered on tongue diagnosis, pulse diagnosis, and syndrome research in TCM. Additionally, it was found that research on the topic was gradually evolving from explorations of a single diagnosis method to investigations on the combination of multiple TCM diagnosis methods. 【Conclusion】  Research on AI application in TCM diagnosis is still in a slowly growing stage. As technology develops, AI has been applied to many aspects of TCM diagnosis. Therefore, how to combine the two for improving TCM diagnosis is something worthy of our brainstorming and exploring.

Heparan Sulfate Induces Necroptosis in Murine Cardiomyocytes: A Medical-In silico Approach Combining In vitro Experiments and Machine Learning.

Life-threatening cardiomyopathy is a severe, but common, complication associated with severe trauma or sepsis. Several signaling pathways involved in apoptosis and necroptosis are linked to trauma- or sepsis-associated cardiomyopathy. However, the underling causative factors are still debatable. Heparan sulfate (HS) fragments belong to the class of danger/damage-associated molecular patterns liberated from endothelial-bound proteoglycans by heparanase during tissue injury associated with trauma or sepsis. We hypothesized that HS induces apoptosis or necroptosis in murine cardiomyocytes. By using a novel Medical-In silico approach that combines conventional cell culture experiments with machine learning algorithms, we aimed to reduce a significant part of the expensive and time-consuming cell culture experiments and data generation by using computational intelligence (refinement and replacement). Cardiomyocytes exposed to HS showed an activation of the intrinsic apoptosis signal pathway via cytochrome C and the activation of caspase 3 (both p < 0.001). Notably, the exposure of HS resulted in the induction of necroptosis by tumor necrosis factor α and receptor interaction protein 3 (p < 0.05; p < 0.01) and, hence, an increased level of necrotic cardiomyocytes. In conclusion, using this novel Medical-In silico approach, our data suggest (i) that HS induces necroptosis in cardiomyocytes by phosphorylation (activation) of receptor-interacting protein 3, (ii) that HS is a therapeutic target in trauma- or sepsis-associated cardiomyopathy, and (iii) indicate that this proof-of-concept is a first step toward simulating the extent of activated components in the pro-apoptotic pathway induced by HS with only a small data set gained from the in vitro experiments by using machine learning algorithms.