Effect of Basalt/Steel Individual and Hybrid Fiber on Mechanical Properties and Microstructure of UHPC.

Ultra High-Performance Concrete (UHPC) is a cement-based composite material with great strength and durability. Fibers can effectively increase the ductility, strength, and fracture energy of UHPC. This work describes the impacts of individual or hybrid doping of basalt fiber (BF) and steel fiber (SF) on the mechanical properties and microstructure of UHPC. We found that under individual doping, the effect of BF on fluidity was stronger than that of SF. Moreover, the compressive, flexural, and splitting tensile strength of UHPC first increased and then decreased with increasing BF dosage. The optimal dosage of BF was 1%. At a low content of fiber, UHPC reinforced by BF demonstrated greater flexural strength than that reinforced by SF. SF significantly improved the toughness of UHPC. However, a high SF dosage did not increase the strength of UHPC and reduced the splitting tensile strength. Secondly, under hybrid doping, BF was partially substituted for SF to improve the mechanical properties of hybrid fiber UHPC. Consequently, when the BF replacement rate increased, the compressive strength of UHPC gradually decreased; on the other hand, there was an initial increase in the fracture energy, splitting tensile strength, and flexural strength. The ideal mixture was 0.5% BF + 1.5% SF. The fluidity of UHPC with 1.5% BF + 0.5% SF became the lowest with a constant total volume of 2%. The microstructure of hydration products in the hybrid fiber UHPC became denser, whereas the interface of the fiber matrix improved.

In vitro simulated digestion and fermentation characteristics of pectic polysaccharides from fresh passion fruit (Passiflora edulis f. flavicarpa L.) peel.

In this study, two pectic polysaccharides (PFP-T and PFP-UM) were extracted from fresh passion fruit peels using three-phase partitioning (TPP) and sequential ultrasound-microwave-assisted TPP methods, respectively, and their effects on the in vitro gastrointestinal digestion and fecal fermentation characteristics were examined. The results indicate that gastrointestinal digestion has a minimal effect on the physicochemical and structural characteristics of PFP-T and PFP-UM. However, during in vitro fecal fermentation, both undigested PFP-T and PFP-UM are significantly degraded and utilized by intestinal microorganisms, showing increased the total relative abundance of Firmicutes and Bacteroidota in the intestinal flora. Notably, compared with PFP-UM, PFP-T better promoted the reproduction of beneficial bacteria such as Prevotella, Megasphaera and Dialister, while suppressed the growth of harmful genera including Escherichia-Shigella, producing higher content of short-chain fatty acids. Therefore, our findings suggest that PFP-T derived from passion fruit peel has potential as a dietary supplement for promoting intestinal health.

Levothyroxine initiation and the risk of pregnancy loss among pregnant women with subclinical hypothyroidism: An observational study emulating a target trial.

BACKGROUND: While the benefits of levothyroxine are well-established for overt hypothyroidism, they are unclear for subclinical hypothyroidism (SCH) among pregnant women. OBJECTIVE: To estimate the effect of initiation of levothyroxine on pregnancy loss among women with SCH with an emulated target trial using observational data. METHODS: We emulated a target trial using the United Kingdom's Clinical Practice Research Datalink to account for the staggered timing of diagnosis and treatment of SCH and the time of entry of women into prenatal care. We emulated multiple nested trials (at each gestational week) and used an intention-to-treat approach to define levothyroxine use (≥1 prescription in the 7 days prior to trial entry), with eligible users matched to non-users (1:4) on time of diagnosis, gestational week of the first eligible trial and high-dimensional propensity score. Pregnancy losses included spontaneous abortion and stillbirth. A pooled logistic regression model with bootstrap resampling was used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Based on 159,177 eligible person-trials (5781 women), the matched cohort included 181 initiators and 640 non-initiators of levothyroxine, with 57 pregnancy losses occurring during follow-up. Overall, the mean age of women was 32.2 years (SD 5.4), 25% were obese, 8% had type 2 diabetes and about 50% were nulliparous. After matching, women who initiated levothyroxine versus not had higher thyroid-stimulating levels during pregnancy and were more likely to have a history of hypothyroidism. The cumulative incidence of pregnancy loss was lower in initiators versus non-initiators of levothyroxine. The adjusted HR for pregnancy loss was 0.87 (95% CI 0.22, 1.56). CONCLUSIONS: Although our assessment of the effect of initiation of levothyroxine for SCH in pregnancy precludes any definitive conclusions due to wide confidence intervals, this study illustrates the feasibility of using the target trial emulation framework to examine the effectiveness of medication use in pregnancy.

Longan Polysaccharides with Covalent Selenylation Combat the Fumonisin B1-Induced Cell Toxicity and Barrier Disruption in Intestinal Epithelial (IEC-6) Cells.

In this study, the soluble, but non-digestible, longan (Dimocarpus longan Lour.) polysaccharides (LP) were extracted from dried longan fruits and then chemically selenylated to produce two selenylated products, namely SeLP1 and SeLP2, with different selenylation extents. The aim was to investigate their protective effects on rat intestinal epithelial (IEC-6) cells exposed to the food toxin fumonisin B1 (FB1). LP only contained total Se content of less than 0.01 g/kg, while SeLP1 and SeLP2 were measured with respective total Se content of up to 1.46 and 4.79 g/kg. The cell viability results showed that these two selenylated products were more efficient than LP in the IEC-6 cells in alleviating FB1-induced cell toxicity, suppressing lactate dehydrogenase (LDH) release, and decreasing the generation of intracellular reactive oxygen species (ROS). These two selenylated products were also more effective than LP in combating FB1-induced barrier disruption via increasing the transepithelial electric resistance (TEER), reducing the paracellular permeability, decreasing the mitochondrial membrane potential (MMP) loss, and maintaining cell barrier integrity by upregulating the tight-junction-related genes and proteins. FB1 caused cell oxidative stress and barrier dysfunction by activating the MAPK and mitochondrial apoptosis signaling pathways, while SeLP1 and SeLP2 could regulate the tMAPK- and apoptosis-related proteins to suppress the FB1-mediated activation of the two pathways. Overall, SeLP2 was observed to be more active than SeLP1 in the IEC-6 cells. In conclusion, the chemical selenylation of LP caused an activity enhancement to ameliorate the FB1-induced cell cytotoxicity and intestinal barrier disruption. Meanwhile, the increased selenylation of LP would endow the selenylated product SeLP2 with more activity.

Structure-evolution-designed amorphous oxides for dielectric energy storage.

Recently, rapidly increased demands of integration and miniaturization continuously challenge energy densities of dielectric capacitors. New materials with high recoverable energy storage densities become highly desirable. Here, by structure evolution between fluorite HfO2 and perovskite hafnate, we create an amorphous hafnium-based oxide that exhibits the energy density of ~155 J/cm3 with an efficiency of 87%, which is state-of-the-art in emergingly capacitive energy-storage materials. The amorphous structure is owing to oxygen instability in between the two energetically-favorable crystalline forms, in which not only the long-range periodicities of fluorite and perovskite are collapsed but also more than one symmetry, i.e., the monoclinic and orthorhombic, coexist in short range, giving rise to a strong structure disordering. As a result, the carrier avalanche is impeded and an ultrahigh breakdown strength up to 12 MV/cm is achieved, which, accompanying with a large permittivity, remarkably enhances the energy storage density. Our study provides a new and widely applicable platform for designing high-performance dielectric energy storage with the strategy exploring the boundary among different categories of materials.

Simultaneous Determination of 26 Pesticide Residues in Traditional Chinese Medicinal Leeches by Modified QuEChERS Coupled with HPLC-MS/MS.

A Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) pretreatment technique combined with HPLC-MS/MS was established to detect 26 pesticides in traditional Chinese medicinal leeches. The sample was extracted by acetonitrile solution with sodium acetate-0.1% (v/v) acetic acid as a buffer system, then cleaned up by a mixture of 750 mg of MgSO4, 150 mg of C18, and 150 mg of PSA, separated by an ACQUITY BEH C18 column, and determined in the dynamic multiple reaction mode. Under the optimized conditions, the peak areas of the 26 pesticides in leeches showed good linearity (r > 0.99) between their mass concentrations from 1 to 100 µg/L. At the spike levels of 10, 20, and 100 µg/kg, the recoveries of 26 pesticides in leeches were 72.9-101.6% with an RSD of 1.1-12.8%, an LOQ of 10 µg/kg, and an LOD of 0.1-5.4 µg/kg. This method is easy, rapid, sensitive, and practical and meets the requirements of pesticide residue detection standards.

Use of metformin and insulin among pregnant women with gestation diabetes in the United Kingdom: A population-based cohort study.

AIMS: The contemporary prescription patterns of antidiabetic drugs following guideline changes recommending metformin as first-line gestational diabetes (GDM) pharmacotherapy is underexplored. We aimed to examined use of metformin and insulin during pregnancy among women with GDM over 20 years in the United Kingdom. METHODS: We conducted a population-based cohort study using linked data from the Clinical Practice Research Datalink, its pregnancy register and Hospital Episode Statistics from 1998 to 2017. We included pregnancies of women without prior diabetes history who received GDM diagnosis or initiated an antidiabetic drug after 20 weeks gestation. Patient-level and practice-level characteristics were compared between metformin initiators and insulin initiators. We described trends of initiating metformin as first-line treatment and described time to initiation of rescue insulin overall, and by body mass index among metformin initiators. RESULTS: Our cohort included 5633 pregnancies from 5393 women with GDM, of whom 38.9% initiated pharmacotherapy (41% insulin, 59% metformin). Metformin prescriptions (as opposed to insulin) increased substantially, from <5% of pregnancies before 2007 to 42.5% in 2008. Over 85% of pregnancies that were prescribed pharmacotherapy were prescribed metformin as first-line treatment in 2015. Among metformin initiators, 16% initiated rescue insulin, typically occurring within 40 days of metformin initiation. Choice of GDM pharmacotherapy varied by characteristics, including smoking, obesity, race/ethnicity and general practice regions. CONCLUSIONS: Metformin was the most prescribed medication for GDM, with large increases over the past 2 decades. The increasing use of oral-antidiabetic drugs during pregnancy, consistent with other regions, highlights the need for future studies examining effectiveness and safety of antidiabetic drug use during pregnancy.

The impact of parental overprotection on the emotions and behaviors of pediatric hematologic cancer patients: a multicenter cross-sectional study.

Background: Parental overprotection may have an impact on children's emotional and behavioral problems (EBPs). As pediatric hematologic cancer patients have compromised immune systems, parents of such children often worry excessively, interfering with their daily lives. Therefore, avoiding overprotection is crucial for the overall physical and mental health of pediatric hematologic cancer patients. Aims: The aim of this study was to examine the current status of EBPs in pediatric hematologic cancer patients and analyze their associated risk factors. Design: This work was a multicenter cross-sectional observational and correlational study. We collected data anonymously through parental questionnaires from three pediatric hematologic oncology hospitals in China. The Strengths and Difficulties Questionnaire, the Parental Overprotection Measure (POM) scale, and a general information survey designed by the research team were employed to assess children's EBPs, the degree of parental overprotection, as well as basic demographic and disease-related information. Chi-square tests and generalized linear mixed-effects regression analysis were used to analyze the factors influencing EBPs among the pediatric hematologic cancer patients. Setting and participants: Using a convenience sampling method, a total of 202 participants' parents were selected. All participants were invited to complete the questionnaire through one-on-one guidance. Results: Emotional symptoms accounted for the highest proportion of abnormal EBPs in children (27.72%), followed by peer problems (26.24%), prosocial behavior (25.74%), behavioral problems (14.36%), and total difficulties (13.86%). A minority of children had abnormal hyperactivity scores (4.95%). The results of a generalized linear mixed regression analysis showed that age, duration of illness, and parental overprotection were significant factors influencing abnormal EBPs in children (p < 0.05). A POM score threshold of 37 exhibited good sensitivity (74%) and specificity (90%) in predicting abnormal EBPs in children. Conclusion: Pediatric hematologic cancer patients under excessive parental protection are more prone to experiencing EBPs. Healthcare professionals should guide parents to reduce this excessive protection, thus mitigating the occurrence of EBPs in children.

Challenges in evaluating treatments for COVID-19: The case of in-hospital anticoagulant use and the risk of adverse outcomes.

Anticoagulants are a potential treatment for the thrombotic complications resulting from COVID-19. We aimed to determine the association between anticoagulant use and adverse outcomes among hospitalized patients with COVID-19. We used data from the COVID-19 International Collaborative Research Project in South Korea from January to June 2020. We defined exposure using an intention-to-treat approach, with person-time classified as use or non-use of anticoagulants at cohort entry, and a time-varying approach. The primary outcome was all-cause, in-hospital mortality; the secondary outcome was a composite including respiratory outcomes, cardiovascular outcomes, venous thromboembolism, major bleeding, and intensive care unit admission. Cox proportional hazards models estimated adjusted hazard ratios (HRs) of the outcomes comparing use versus non-use of anticoagulants. Our cohort included 2,677 hospitalized COVID-19 patients, of whom 24 received anticoagulants at cohort entry. Users were older and had more comorbidities. The crude incidence rate (per 1,000 person-days) of mortality was 5.83 (95% CI: 2.80, 10.72) among anticoagulant users and 1.36 (95% CI: 1.14, 1.59) for non-users. Crude rates of the composite outcome were 3.20 (95% CI: 1.04, 7.47) and 1.80 (95% CI: 1.54, 2.08), respectively. Adjusted HRs for mortality (HR: 1.12, 95% CI: 0.48, 2.64) and the composite outcome (HR: 0.79, 95% CI: 0.28, 2.18) were inconclusive. Although our study was not able to draw conclusions on anticoagulant effectiveness for COVID-19 outcomes, these results can contribute to future knowledge syntheses of this important question. Our study demonstrated that the dynamic pandemic environment may have important implications for observational studies of COVID-19 treatment effectiveness.

Optimizing Film Companies' Marketing Strategy Using Blockchain and Recurrent Neural Network Model.

With the growing scale of the domestic film industry, the output of domestic films is also increasing. The design and execution problems in ticket marketing strategies adversely affect the revenue of domestic films. This paper aims to propose solutions to optimize film companies' marketing strategies by analyzing the marketing environment and current situation to increase the income of domestic films. Firstly, the current situation of BJ's marketing is analyzed, and the main problems are clarified. Secondly, the necessity and feasibility of applying blockchain technology to the operation and management of film companies are introduced. New marketing strategies and safeguards have been developed by analyzing the target market and optimizing the program. A quantitative method is used to predict a new movie's box office in its premiere month. The proposed method introduces three factors affecting the box office: new film positioning, film marketing, and film prerating, as input variables. Besides, a Recurrent Neural Network (RNN) is implemented to predict the monthly box office of the premiere of new films. The results show that the predicted monthly box office of the movie adopting the optimized marketing strategy is 1,451,718.6 CNY, which is smaller than the target box office of 1414029.8. The Mean Absolute Error (MAE) is only 0.026. The proposed model's Root Mean Square Error (RMSE) is 0.45 for the long-term prediction of a single movie price. The MAE is 0.106, and the accuracy is 0.80. The model proposed beats the unimproved Long Short-Term Memory (LSTM) model and the Autoregressive Moving Average (ARMA) model. This paper provides a reference for optimizing the film company's marketing system.

Activities of the soluble and non-digestible longan (Dimocarpus longan Lour.) polysaccharides against HCT-116 cells as affected by a chemical selenylation.

The soluble and non-digestible longan (Dimocarpus longan Lour.) polysaccharides (LP) with Se content less than 0.01 g/kg were extracted and selenylated chemically with the HNO3-Na2SeO3 system, to prepare two selenylated products namely SeLP1 and SeLP2 with enhanced Se contents of 1.46 and 4.79 g/kg, respectively. LP, SeLP1, and SeLP2 were then measured and compared for their saccharide features and bioactivity in human colon carcinoma HCT-116 cells. Compared with LP, both SeLP1 and SeLP2 contained more neutral saccharides, but showed reduced uronic acid content and undetectable sulfate. Moreover, SeLP1 and especially SeLP2 in the cells showed higher activities than LP, reflected by their enhanced capacity to inhibit cell growth, alter cell morphology, and suppress cell colony formation. Compared with LP, SeLP1 and especially SeLP2 were also more capable of promoting intracellular reactive oxygen species and Ca2+ levels, causing mitochondrial membrane potential loss, or inducing cell apoptosis via up- and down-regulating the eight apoptosis-related genes and proteins. Overall, the performed chemical selenylation of LP resulted in obvious changes in these saccharide features and simultaneously enhanced the anti-cancer activity of the selenylated products against the cells clearly, while a higher selenylation extent of the selenylated products consistently caused higher activity towards the cells. The results of this study thus highlighted that this chemical selenylation is applicable when aiming to enhance the bioactivities of natural polysaccharides.

Information Dissemination Model in Rural Live Broadcasting under Blockchain in the Era of Artificial Intelligence.

This work aims to improve the information dissemination atmosphere of rural live broadcasting and ensure its long-term development. First, it studies and analyzes the current situation and characteristics of rural live broadcasting. Then, it discusses the blockchain (BC) technology and information dissemination mode in the era of artificial intelligence (AI). Finally, the characteristics of BC technology (BT) and the information dissemination model are discussed. A BT-optimized susceptible exposed infected recovered (SEIR) information dissemination model is proposed. The results show that the BT-optimized SEIR model has no effect on the traditional information transmission characteristics and can ensure the conventional transmission of all information. Additionally, BT can effectively improve the overall transmission efficiency of the SEIR model for false information and accurate information and effectively shorten the duration. Specifically, the BT-optimized SEIR model's maximum false information transmission proportion is reduced by about 13%. The duration is reduced by 15 days over the traditional model. By comparison, in positive information dissemination, the maximum transmission proportion of the proposed BT-optimized SEIR model is about 19% higher than the traditional model. The duration is about 30 days longer. The research provides technical support for controlling and improving the current situation and atmosphere of rural live broadcasting information dissemination.

Niacin skin flush and membrane polyunsaturated fatty acids in schizophrenia from the acute state to partial remission: a dynamic relationship.

Despite the consistent finding of an attenuated niacin-induced flush response in schizophrenia, its long-term stability and relationship to the membrane polyunsaturated fatty acid (PUFA) levels remain unknown. We conducted niacin skin tests and measured the membrane PUFAs using gas chromatography among 46 schizophrenia inpatients and 37 healthy controls at the baseline and the 2-month follow-up. Attenuated flush responses were persistently observed in schizophrenia patients in both acute and partial remission states, whereas an increased flush response was found in the controls. A persistent decrease in both dihomo-gamma-linolenic acid and docosahexaenoic acid and an increased turnover of arachidonic acid (ARA) via endogenous biosynthesis were found in schizophrenia patients. A composite niacin flush score by combining those with a control-to-case ratio of >1.4 (i.e., scores at 5 min of 0.1 M, 0.01 M, and 0.001 M + 10 min of 0.01 M and 0.001 M + 15 min of 0.001 M) at the baseline was correlated positively with ARA levels among controls but not among schizophrenia patients, whereas the flush score at the 2-month follow-up was correlated positively with ARA levels among patients. The 2-month persistence of attenuated niacin-induced flush response in schizophrenia patients implies that the niacin skin test might tap a long-term vulnerability to schizophrenia beyond acute exacerbation.

Enhanced Growth Inhibition and Apoptosis Induction in Human Colon Carcinoma HT-29 Cells of Soluble Longan Polysaccharides with a Covalent Chemical Selenylation.

The selenylated polysaccharides chemically belong to the organic Se-conjugated macromolecules and have recently been attracting more and more attention due to their potential to promote body health or prevent cancers. Longan (Dimocarpus longan L.), as a subtropical fruit, contains soluble and non-digestible polysaccharides that are regarded with health care functions in the body. In this study, the longan polysaccharides (LP) were obtained via enzyme-assisted water extraction, and then chemically selenylated using a reaction system composed of HNO3-Na2SeO3 to yield two selenylated products, namely, SeLP1 and SeLP2, with Se contents of 1.46 and 4.79 g/kg, respectively. The anti-cancer effects of the three polysaccharide samples (LP, SeLP1, and SeLP2) were thus investigated using the human colon cancer HT-29 cells as the cell model. The results showed that SeLP1 and SeLP2 were more able than LP to inhibit cell growth, alter cell morphology, cause mitochondrial membrane potential loss, increase intracellular reactive oxygen and [Ca2+]i levels, and induce apoptosis via regulating the eight apoptosis-related genes and proteins including Bax, caspases-3/-8/-9, CHOP, cytochrome c, DR5, and Bcl-2. It was thereby proven that the selenylated polysaccharides could induce cell apoptosis via activating the death receptor, mitochondrial-dependent, and ER stress pathways. Collectively, both SeLP1 and SeLP2 showed higher activities than LP in HT-29 cells, while SeLP2 was consistently more active than SeLP1 in exerting these assessed anti-cancer effects on the cells. In conclusion, this chemical selenylation covalently introduced Se into the polysaccharide molecules and caused an enhancement in their anti-cancer functions in the cells, while higher selenylation extent was beneficial to the activity enhancement of the selenylated products.

Nasopharyngeal cancer cell-derived exosomal PD-L1 inhibits CD8+ T-cell activity and promotes immune escape.

Programmed cell death ligand 1 (PD-L1) is an immune surface protein that binds to programmed cell death 1 (PD-1) and allows tumors to evade T-cell immunity. This study aims to define the role of PD-L1 shuttled by tumor cell-derived exosomes in the immune escape of nasopharyngeal carcinoma (NPC). PD-L1 expression was determined in the exosomes isolated from the plasma of NPC patients or from NPC cells. It was found that PD-L1 was highly expressed in the exosomes from the plasma of NPC patients and also in the exosomes from NPC cells. PD-L1/PD-1 binding was identified in the presence or absence of interferon-gamma (IFN-γ) or anti-PD-L1 antibody. PD-L1 expression was elevated following IFN-γ treatment. Binding of PD-L1 to PD-1 was augmented by IFN-γ and blocked by anti-PD-L1 antibody. Following this, CD8+ T cells were sorted out from peripheral blood samples to assess the binding between exosomal PD-L1 and PD-1 on the CD8+ T-cell surface, and to measure the percentage of Ki-67-positive T cells. The results indicated that exosomal PD-L1 bound to the PD-1 on CD8+ T-cell surface, leading to a reduced percentage of Ki-67-positive CD8+ T cells and downregulated production of cytokines. In vivo data confirmed that exosomal PD-L1 promoted NPC tumor growth in mice by suppressing CD8+ T-cell activity. In conclusion, NPC cell-derived exosomes deliver PD-L1 to bind to PD-1 on the CD8+ T-cell surface, through which cytotoxic CD8+ T-cell function was attenuated and the immune escape was thus promoted in NPC.

Delayed callose degradation restores the fertility of multiple P/TGMS lines in Arabidopsis.

Photoperiod/temperature-sensitive genic male sterility (P/TGMS) is widely applied for improving crop production. Previous investigations using the reversible male sterile (rvms) mutant showed that slow development is a general mechanism for restoring fertility to P/TGMS lines in Arabidopsis. In this work, we isolated a restorer of rvms-2 (res3), as the male sterility of rvms-2 was rescued by res3. Phenotype analysis and molecular cloning show that a point mutation in UPEX1 l in res3 leads to delayed secretion of callase A6 from the tapetum to the locule and tetrad callose wall degradation. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis demonstrated that the tapetal transcription factor ABORTED MICROSPORES directly regulates UPEX1 expression, revealing a pathway for tapetum secretory function. Early degradation of the callose wall in the transgenic line eliminated the fertility restoration effect of res3. The fertility of multiple known P/TGMS lines with pollen wall defects was also restored by res3. We propose that the remnant callose wall may broadly compensate for the pollen wall defects of P/TGMS lines by providing protection for pollen formation. A cellular mechanism is proposed to explain how slow development restores the fertility of P/TGMS lines in Arabidopsis.

Floridean Starch and Floridoside Metabolic Pathways of Neoporphyra haitanensis and Their Regulatory Mechanism under Continuous Darkness.

Floridean starch and floridoside are the main storage carbohydrates of red algae. However, their complete metabolic pathways and the origin, function, and regulatory mechanism of their pathway genes have not been fully elucidated. In this study, we identified their metabolic pathway genes and analyzed the changes in related gene expression and metabolite content in Neoporphyra haitanensis under continuous dark conditions. Our results showed that genes from different sources, including eukaryotic hosts, cyanobacteria, and bacteria, were combined to construct floridean starch and floridoside metabolic pathways in N. haitanensis. Moreover, compared with those in the control, under continuous dark conditions, floridean starch biosynthesis genes and some degradation genes were significantly upregulated with no significant change in floridean starch content, whereas floridoside degradation genes were significantly upregulated with a significant decrease in floridoside content. This implies that floridean starch content is maintained but floridoside is consumed in N. haitanensis under dark conditions. This study elucidates the "floridean starch-floridoside" metabolic network and its gene origins in N. haitanensis for the first time.

Use of levothyroxine among pregnant women with subclinical hypothyroidism in the United Kingdom: A population-based assessment.

Our study aimed to describe levothyroxine prescription patterns and trends over time among pregnant women with subclinical hypothyroidism (SCH) in the United Kingdom. We used data from the Clinical Practice Research Datalink linked to its Pregnancy Register and the Hospital Episode Statistics database from 1998 to 2017. The study population included women with a diagnosis of SCH or an abnormal thyroid-simulated hormone (TSH) level one year prior to or during pregnancy. We compared characteristics between women who received a prescription for levothyroxine during pregnancy and those who did not. We further described the timing, dose, duration, and temporal trends of levothyroxine prescriptions. Our cohort included 6,757 pregnancies from 6,287 women with SCH, of whom 10% received levothyroxine during pregnancy. Among women who received levothyroxine, most received their first prescription during the first trimester (median gestational age: 7 weeks; interquartile range [IQR]: 0, 16) with a median daily dosage of 50 mcg (IQR: 50, 73). Levothyroxine prescription varied over time, decreasing from 23% of pregnant women in 1998 to 7.5% in 2003, remaining stable until 2014, and increasing to 12.5% in 2016. Smoking, diabetes, polycystic ovary syndrome, infertility, timing of SCH diagnosis, age, TSH level at diagnosis, and general practice regions were associated with prescription. Few women with SCH received levothyroxine during pregnancy, and treatment varied by patient characteristics and geographical regions. These results highlight the need to increase awareness among healthcare providers and will guide future studies that explore barriers to initiating levothyroxine treatment for women with SCH during pregnancy.

[Preparation and in vitro evaluation of forsythoside A-loaded exosomes].

A drug delivery system of forsythoside A-loaded exosomes(FTA-Exos) with high biocompatibility and low immunogenicity was established to investigate its impact on the migration of human lung epithelial adenocarcinoma A549 cells. The exosomes from A549 cells were extracted and purified by ultra-high speed centrifugation and ultrafiltration. FTA-Exos were prepared by ultrasonic incubation, and characterized by particle size analysis, transmission electron microscopy, and Western blot assay. The uptake of FTA-Exos by A549 cells was observed under the laser confocal microscope, and the impact of FTA-Exos on the migration of A549 cells was investigated by cell scratch assay. The results showed that the average particle size of the prepared FTA-Exos was(138.90±2.37) nm, which increased slightly after drug loading. The PDI was 0.291±0.013, and the average potential was(-10.1±0.66) mV. The FTA-Exos were spheroidal in appearance as observed by transmission electron microscope, with an obvious saucer-like double-layer membrane. Western blot assay indicated that the specific proteins CD63 and Alix were both expressed in exosomes. The laser confocal microscopy suggested that FTA-Exos were taken up by A549 cells and stably maintained in the cell for 4-8 h, and the fluorescence was significantly enhanced at 4 h. The scratch assay showed that the inhibitory effect of FTA-Exos on the migration of A549 cells was significantly stronger than that of forsythoside A(P < 0.05). In conclusion, the drug delivery system of FTA-Exos established in this study had good stability, reliable preparation process, and potent inhibitory effect on the migration of A549 cells in vitro, which can provide an important reference for subsequent in-depth research and application.

A Randomized Controlled Trial Comparing Two Different Schedules for Cisplatin Treatment in Patients with Locoregionally Advanced Nasopharyngeal Cancer.

PURPOSE: Previous studies suggest that a cumulative cisplatin dose of 200 mg/m2 might be adequate in the intensity-modulated radiation therapy (IMRT) era for locoregionally advanced nasopharyngeal carcinoma (LANPC). However, two cycles of once-every-3-weeks cisplatin at 100 mg/m2 has never been prospectively compared with standard once-a-week cisplatin regimen. PATIENTS AND METHODS: This trial was conducted at three hospitals from 2011 to 2016. Patients who met the eligibility criteria were recruited (ChiCTR-TRC-12001979) and randomly assigned (1:1) via a computer-generated sequence to receive once-every-3-weeks cisplatin at 100 mg/m2 for two cycles or once-a-week cisplatin at 40 mg/m2 for six cycles concurrently with IMRT. Primary endpoint was failure-free survival and between-group absolute difference of 10% as the noninferiority margin. RESULTS: A total of 510 patients were enrolled. Median follow-up time was 58.3 months with 85.4% of 3-year failure-free survival in the once-every-3-weeks group and 85.6% in the once-a-week group. An absolute difference of -0.2% (95% confidence interval, -6.3 to 5.9; P noninferiority = 0.0016). Acute toxicities of grade 3 or higher occurred in 55.8% in the once-every-3-weeks group and 66.3% in the once-a-week group (P = 0.015). The most common acute toxicities were hematologic abnormalities, including leukopenia (16% vs. 27%; P = 0.0022) and thrombocytopenia (1% vs. 5%; P = 0.015). The late grade 3-4 auditory loss rate was significantly lower in the once-every-3-weeks group than the once-a-week group (6% vs. 13%; P = 0.0039). CONCLUSIONS: Once-every-3-weeks cisplatin as concurrent chemoradiotherapy is noninferior to once-a-week cisplatin in the treatment efficacy in the LANPC. Although both regimens are well tolerated, severe acute toxicities and late-onset auditory loss are higher in the once-a-week group.