Cu-Catalyzed Carbocyclization for General Synthesis of N-Containing Heterocyclics Enabled by BrCF2COOEt as a C1 Source.

A practical and efficient copper-catalyzed carbocyclization of 2-functionalized anilines with ethyl bromodifluoroacetate has been developed. Ethyl bromodifluoroacetate is employed as the C1 source via quadruple cleavage in this transformation. This reaction can afford a variety of N-containing heterocyclics with satisfactory yields and excellent functional group compatibility.

Improved Water Collection from Short-Term Fog on a Patterned Surface with Interconnected Microchannels.

Fog harvesting is considered a promising freshwater collection strategy for overcoming water scarcity, because of its environmental friendliness and strong sustainability. Typically, fogging occurs briefly at night and in the early morning in most arid and semiarid regions. However, studies on water collection from short-term fog are scarce. Herein, we developed a patterned surface with highly hydrophilic interconnected microchannels on a superhydrophobic surface to improve droplet convergence driven by the Young-Laplace pressure difference. With a rationally designed surface structure, the optimized water collection rate from mild fog could reach up to 67.31 g m-2 h-1 (6.731 mg cm-2 h-1) in 6 h; this value was over 130% higher than that observed on the pristine surface. The patterned surface with interconnected microchannels significantly shortened the startup time, which was counted from the fog contact to the first droplet falling from the fog-harvesting surface. The patterned surface was also facilely prepared via a controllable strategy combining laser ablation and chemical vapor deposition. The results obtained in outdoor environments indicate that the rationally designed surface has the potential for short-term fog harvesting. This work can be considered as a meaningful attempt to address the practical issues encountered in fog-harvesting research.

The impact of the time factors on the exercise-based cardiac rehabilitation outcomes of the patients with acute myocardial infarction after percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Cardiac rehabilitation (CR) has been demonstrated to improve outcomes in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). However, the optimal CR initiation time and duration remain to be determined. This study aimed to explore the impact of the time factors on the CR outcomes in AMI patients who received PCI by the method of meta-regression analysis. METHODS: We searched five databases (PubMed, Embase, Cochrane Library, Web of Science and Google scholar) up to October 31, 2023. Meta-regression analysis was utilized to explore the impact of the time factors on the effect sizes. Subgroups with more than 3 studies were used for meta-regression analysis. RESULTS: Our analysis included 16 studies and a total of 1810 patients. The meta-regression analysis revealed that the initiation time and duration of CR had no significant impact on the occurrence of arrhythmia, coronary artery restenosis and angina pectoris. The initiation time and duration of CR also had no significant impact on the changes in left ventricular ejection fraction (LVEF, starting time: estimate = 0.160, p = 0.130; intervention time: estimate = 0.017, p = 0.149), left ventricular end-diastolic volume (LVEDV, starting time: estimate = - 0.191, p = 0.732; intervention time: estimate = - 0.033, p = 0.160), left ventricular end-systolic volume (LVESV, starting time: estimate = - 0.301, p = 0.464; intervention time: estimate = 0.015, p = 0.368) and 6-minute walk test (6MWT, starting time: estimate = - 0.108, p = 0.467; intervention time: estimate = 0.019, p = 0.116). CONCLUSION: Implementation of CR following PCI in patients with AMI is beneficial. However, in AMI patients, there is no significant difference in the improvement of CR outcomes based on different CR starting times within 1 month after PCI or different durations of the CR programs. It indicates that it is feasible for patients with AMI to commence CR within 1 month after PCI and continue long-term CR, but the time factors which impact CR are intricate and further clinical research is still needed to determine the optimal initiation time and duration of CR.

Morphological Analyses and QTL Mapping of Mottled Leaf in Zucchini (Cucurbita pepo L.).

The mottled leaf is one of the agronomic traits of zucchini and can be applied as a marker trait in aggregation breeding. However, the genetic mechanism responsible for mottled leaf has yet to be elucidated. In the present study, we used two inbred lines (line '19': silver mottled leaf; line '113': normal leaf) as parents for the physiological and genetic analysis of mottled leaf. The synthesis and net photosynthetic rate of chlorophyll were not significantly affected in the mottled areas of leaves. However, we detected a large space between the palisade parenchyma in the leaf mottle area of line '19', which may have caused the mottled leaf phenotype. Light also plays an important role in the formation of mottled leaf, and receiving light during the early stages of leaf development is a necessary factor. Genetic analysis has previously demonstrated that mottled leaf is a quantitative trait that is controlled by multiple genes. Based on the strategy of quantitative trait locus sequencing (QTL-seq), two QTLs were identified on chromosomes 1 and 17, named CpML1.1 and CpML17.1, respectively. Two major loci were identified using R/qtl software version 1.66 under greenhouse conditions in April 2019 (2019A) and April 2020 (2020A) and under open cultivation conditions in May 2020 (2020M). The major QTL, CpML1.1, was located in a 925.2-kb interval on chromosome 1 and explained 10.51%-24.15% of the phenotypic variation. The CpML17.1 was located in a 719.7-kb interval on chromosome 17 and explained 16.25%-38.68% of the phenotypic variation. Based on gene annotation, gene sequence alignment, and qRT-PCR analysis, the Cp4.1LG01g23790 at the CpML1.1 locus encoding a protein of the TPX2 family (target protein of Xklp2) may be a candidate gene for mottled leaf in zucchini. Our findings may provide a theoretical basis for the formation of mottled leaf and provide a foundation for the fine mapping of genes associated with mottled leaf. Molecular markers closely linked to mottled leaf can be used in molecular-assisted selection for the zucchini mottled leaf breeding.

Fasting plasma glucose and fetal ultrasound predict the occurrence of neonatal macrosomia in gestational diabetes mellitus.

OBJECTIVE: The cause of fetal overgrowth during pregnancy is still unclear. This study aimed to analyze and predict the risk of macrosomia in pregnant women with gestational diabetes mellitus (GDM). METHODS: This study was a retrospective study collected from October 2020 to October 2021. A total of 6072 pregnant women with a routine 75-g oral glucose tolerance test (OGTT) during 24-28 gestational weeks were screened. Nearly equal numbers of pregnant women with gestational diabetes and with normal glucose tolerance (NGT) were included in the study. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve were performed to determine the index and inflection point for predicting macrosomia occurrence. RESULTS: The data of perinatal outcomes of 322 GDM and 353 NGT who had given birth to single live babies at term were analyzed. We found that significant cut-off values for the prediction of macrosomia are 5.13mmol/L in fasting plasma glucose (FPG), 12.25kg in gestational weight gain (GWG), 3,605g in ultrasound fetal weight gain (FWG) and 124mm in amniotic fluid index (AFI).The area under the ROC curve of this predictive model combined all variables reached 0.953 (95% CI: 0.914 ~ 0.993) with a sensitivity of 95.0% and a specificity of 85.4%. CONCLUSIONS: FPG is positively associated with newborn birth weight. An early intervention to prevent macrosomia may be possible by combining maternal GWG, FPG, FWG, and AFI in gestational diabetes.

Alterations of selenium level and speciation during milling and cooking in different wheat cultivars.

BACKGROUND: Selenium (Se) deficiency is a recognized problem that threatens the health of people worldwide, and wheat is grown worldwide and is one of the major sources of dietary Se. Since there are few studies that have investigated the changes in Se content and speciation of different varieties of Se-enriched wheat from primary to deep processing, we studied four naturally Se-enriched kinds of wheat and two Se-fertilized kinds of wheat. RESULTS: Glutenin- and albumin-bound Se accounted for the highest proportion of protein-bound Se in refined wheat flour (7.29 ± 0.19 to 10.82 ± 0.50% and 6.16 ± 0.34 to 8.45 ± 0.07%); water-soluble polysaccharide-bound Se accounted for the highest proportion of polysaccharide-bound Se in refined wheat flour (12.02 ± 0.54 to 24.62 ± 1.87%). Coarse bran Se content was significantly higher than refined wheat flour (137.94 ± 7.80 to 174.55 ± 5.09% for unpeeled wheat, 147.27 ± 10.96 to 187.72 ± 17.70% for peeled wheat). The peeling and processing of wheat into flour had different effects on Se the content and speciation dependent on the particular wheat variety. Whole wheat flour enabled better retention of selenomethionine (101.64 ± 2.32 to 138.41 ± 2.84% for unpeeled wheat, 158.59 ± 13.72 to 250.20 ± 4.94% for peeled wheat). The cooking process had no significant effect on Se content, but Se species were possibly interconverted. CONCLUSION: The organic Se content of different varieties of Se-enriched wheat was different, but the milling and cooking process retained the total Se and Se speciation better, which could be used for daily Se supplementation for Se-deficient people. © 2022 Society of Chemical Industry.

Evaluation of combined detection of multigene mutation and SDC2/SFRP2 methylation in stool specimens for colorectal cancer early diagnosis.

PURPOSE: Molecular diagnostics of colorectal cancer (CRC) can be used as an auxiliary approach for patients recommended for colonoscopy, providing more CRC supplemental diagnosis options. This study investigated whether combined detection of KRAS/BRAF/APC mutation and SDC2/SFRP2 methylation can serve as auxiliary diagnostics in clinical management. METHODS: KRAS/BRAF/APC mutation and SDC2/SFRP2 methylation in stool samples from healthy donors, patients with CRC, advanced adenoma (AA), non-advanced adenoma (NAA), or other gastroenterological diseases were evaluated using quantitative PCR (qPCR) or methylation-specific quantitative PCR (MSP). Test accuracy was determined by evaluating the tests' sensitivity, specificity, positive/negative predictive value (PPV/NPV), or positive/negative likelihood ratio (PLR/NLR). RESULTS: The combined fecal KRAS/BRAF/APC mutation and SFRP2/SDC2 methylation detection test achieved a sensitivity of 88.57% with a PPV of 93.64% and a PLR of 7.10 for CRC patients. In comparison, the corresponding parameters for multigene mutation were 46.67%, 92.59%, and 36.26 and 83.81%, 93.94%, and 7.47, for DNA methylation, separately. The sensitivity of the combined test, gene mutation test, and DNA methylation test approach was 75%, 28.26%, and 72.83%. Furthermore, the specificity of this approach in the NAA group was 79.49%. Meanwhile, the overall diagnostic specificity for the combined test in NAA, healthy control, and interference groups was 88.42%. In addition, the sensitivity of the combined detection method increased with the disease stage in CRC patients and elevated along with the lesion size (≥ 1 cm) in AA patients. CONCLUSION: Combined detection of fecal KRAS/BRAF/APC mutation and SFRP2/SDC2 methylation has potential application value for the auxiliary diagnosis of CRC and AA.

Pyrroloquinoline quinone ameliorates diabetic cardiomyopathy by inhibiting the pyroptosis signaling pathway in C57BL/6 mice and AC16 cells.

PURPOSE: Diabetic cardiomyopathy (DCM), a common complication of diabetes mellitus and is characterized by myocardial hypertrophy and myocardial fibrosis. Pyrroloquinoline quinone (PQQ), a natural nutrient, exerts strong protection against various myocardial diseases. Pyroptosis, a type of inflammation-related programmed cell death, is vital to the development of DCM. However, the protective effects of PQQ against DCM and the associated mechanisms are not clear. This study aimed to investigate whether PQQ protected against DCM and to determine the underlying molecular mechanism. METHODS: Diabetes was induced in mice by intraperitoneal injection of streptozotocin, after which the mice were administered PQQ orally (10, 20, or 40 mg/kg body weight/day) for 12 weeks. AC16 human myocardial cells were divided into the following groups and treated accordingly: control (5.5 mmol/L glucose), high glucose (35 mmol/L glucose), and HG + PQQ groups (1 and 10 nmol/L PQQ). Cells were treated for 24 h. RESULTS: PQQ reduced myocardial hypertrophy and the area of myocardial fibrosis, which was accompanied by an increase in antioxidant function and a decrease in inflammatory cytokine levels. Moreover, myocardial hypertrophy-(ANP and BNP), myocardial fibrosis-(collagen I and TGF-ß1), and pyroptosis-related protein levels decreased in the PQQ treatment groups. Furthermore, PQQ abolished mitochondrial dysfunction and the activation of NF-κB/IκB, and decreased NLRP3 inflammation-mediated pyroptosis in AC16 cells under high-glucose conditions. CONCLUSION: PQQ improved DCM in diabetic mice by inhibiting NF-κB/NLRP3 inflammasome-mediated cell pyroptosis. Long-term dietary supplementation with PQQ may be greatly beneficial for the treatment of DCM. Diagram of the underlying mechanism of the effects of PQQ on DCM. PQQ inhibits ROS generation and NF-κB activation, which stimulates activation of the NLRP3 inflammasome and regulates the expression of caspase-1, IL-1ß, and IL-18. The up-regulated inflammatory cytokines trigger myocardial hypertrophy and cardiac fibrosis and promote the pathological process of DCM.

Comparison of percutaneous permeation profiles of flurbiprofen enantiomers.

Flurbiprofen is clinically effective for the treatment of acute or long-term rheumatoid arthritis and osteoarthritis. Studies showed that S-flurbiprofen had better anti-inflammatory effect than R-flurbiprofen. As flurbiprofen racemates are usually used in the form of transdermal preparations, such as Flurbiprofen Cataplasms (Zepolas), it is of great significance to investigate the percutaneous permeation profiles of flurbiprofen enantiomers for considering whether it is necessary to develop the transdermal preparation with single optical enantiomer. Taking the economy into consideration, the flurbiprofen enantiomers as the mode drug and the CHIRALPAKAAGP column we had as instrument were used to perform the following experiments. On the basis of experiences provided by predecessors, we made some improvements to the analytical conditions, and method validation was developed to verify the feasibility of the method. The results showed that the established method could be used to analyze the percutaneous permeation profiles of flurbiprofen enantiomers in the flurbiprofen cataplasms accurately and effectively, and the percutaneous permeation profiles of flurbiprofen enantiomers had no significantly difference no matter under what conditions (P > 0.05).

Evaluation of Combined use of Fecal Multigene Mutation Test and Fecal Immunochemical Test for Colorectal Cancer Screening.

BACKGROUND: The aim was to investigate the value of concomitant use of fecal KRAS-APC-p53-BRAF mutation test and a fecal immunochemical test (FIT) for colorectal cancer (CRC) screening. METHODS: Stool samples of 279 subjects were collected from the Fujian provincial hospital and divided into five groups: CRC (n = 82); advanced adenoma (AA, n = 76); non-advanced adenoma (NAA, n = 24); healthy control (n = 85); and interference group (n = 12). All stool samples were tested using a fecal multigene mutation (KRAS-APC-p53-BRAF) Kit and FIT. RESULTS: The sensitivity of combined use of fecal multigene mutation test and FIT for detecting CRC [84.15% (69/ 82)] was significantly higher than that of fecal multigene mutation test [47.56% (39/82), p < 0.001] or FIT [71.95% (59/82), p < 0.001] alone. The sensitivity of combined use for detection of AA [48.68% (37/76)] was also significantly higher than that of multigene mutation test [26.32% (20/76), p < 0.001] or FIT [28.95% (22/76), p < 0.001] alone. The specificity of combined use for detection of NAA and healthy control was 87.16%. CONCLUSIONS: The combination of fecal multigene (KRAS-APC-p53-BRAF) mutation test and FIT has greater sensitivity than alone and may be a useful noninvasive method for CRC screening.

Application of Fe3O4@CNFs combined with deep eutectic solvent-based dual microextraction: a novel and green strategy for rapid determination of pesticides in edible oil samples.

A novel, green, and effective strategy employing Fe3O4-modified carbon nanofibers (CNFs) combined with deep eutectic solvent (DES) is proposed as an extraction agent to extract five pesticides in edible oil samples via dual microextraction modes, followed by high-performance liquid chromatography for determination. The Fe3O4@CNFs nanomaterial and a sequence of hydrophilic DES were prepared at first and then characterized by multiple techniques. Subsequently, the extraction performance of DES and Fe3O4@CNFs-DES was compared and Fe3O4@CNFs-DES exhibited better extraction ability. After that, several influencing parameters such as the composition of DES, the amount of Fe3O4@CNFs-DES, the dispersion methods, and the extraction time were investigated and optimized. Eventually, Fe3O4@CNFs as the solid adsorbent combined with tetrabutylammonium chloride-lactic acid-based DES as the extraction solvent were selected to extract target pesticides from oil samples. The established method received good linearity in the range 25-1000 ng·g-1. The limits of detection for all analytes were in the range 2.25-7.50 ng·mL-1. Satisfactory recoveries of target pesticides were obtained (ranging from 82 to 117%) with a relative standard deviation of 0.26-9.46%. The proposed method has been successfully applied to the rapid detection of target pesticides in oil samples, demonstrating its great potential for quick screening and analysis.

[Shenling Baizhu Powder alleviates chronic inflammation to prevent type 2 diabetes of ZDF rats via intestinal flora].

This study explored the mechanism of Shenling Baizhu Powder(SLBZP) in the prevention and treatment of type 2 diabetes from the perspective of flora disorder and chronic inflammation. Fifty rats were randomly divided into normal control group, model control group, low-dose SLBZP group, medium-dose SLBZP group, and high-dose SLBZP group, with 10 rats in each group. The rats of 5 weeks old were administrated by gavage with ultrapure water and different doses of SLBZP decoction. The basic indicators such as body weight and blood glucose were monitored every week, and stool and intestinal contents were collected from the rats of 9 weeks old for 16 S rRNA sequencing and metabolomic analysis. An automatic biochemical analyzer was used to measure the serum biochemical indicators, ELISA to measure serum insulin, and chipsets to measure leptin and inflammatory cytokines. The results showed that SLBZP reduced the body weight as well as blood glucose, glycosylated hemoglobin, and lipid levels. In the rats of 9 weeks, the relative abundance of Anaerostipes, Turicibacter, Bilophila, Ochrobactrum, Acinetobacter, and Prevotella decreased significantly in the model control group, which can be increased in the high-dose SLBZP group; the relative abundance of Psychrobacter, Lactobacillus, Roseburia and Staphylococcus significantly increased in the model control group, which can be down-regulated in the high-dose SLBZP group. The differential metabolites of intestinal flora included 4-hydroxyphenylpyruvic acid, phenylpyruvic acid, octanoic acid, 3-indolepropionic acid, oxoglutaric acid, malonic acid, 3-methyl-2-oxovaleric acid, and methylmalonic acid. Moreover, SLBZP significantly lowered the levels of free insulin, insulin resistance and leptin resistance in rats. The variations in the serum levels of interleukin 1ß(IL-1ß) and monocyte chemoattractant protein-1(MCP-1) showed that SLBZP could alleviate chronic inflammation in rats. In conclusion, SLBZP can regulate intestinal flora and metabolites and relieve chronic inflammation to control obesity and prevent type 2 diabetes.

HIF-1α is necessary for activation and tumour-promotion effect of cancer-associated fibroblasts in lung cancer.

Cancer-associated fibroblasts (CAFs) activation is crucial for the establishment of a tumour promoting microenvironment, but our understanding of CAFs activation is still limited. In this study, we found that hypoxia-inducible factor-1α (HIF-1α) was highly expressed in CAFs of human lung cancer tissues and mouse spontaneous lung tumour. Accordingly, enhancing the expression of HIF-1α in fibroblasts via hypoxia induced the conversion of normal fibroblasts into CAFs. HIF-1α-specific inhibitor or HIF-1α knockout (KO) significantly attenuated CAFs activation, which was manifested by the decreased expression of COL1A2 and α-SMA. In vivo, during tumour formation, the expression of Ki-67 and proliferating cell nuclear antigen (PCNA) in the tumour tissue with HIF-1α KO fibroblasts was significantly lower than that of normal fibroblasts. Moreover, HIF-1α in fibroblasts could activate the NF-κB signalling pathway and enhance a subsequent secretion of CCL5, thus promoting the tumour growth. In conclusion, our results suggest that HIF-1α is essential for the activation and tumour-promotion function of CAFs in lung cancer (LC). And targeting HIF-1α expression on CAFs may be a promising strategy for LC therapy.

Fluoride-Triggered Self-Degradation of Poly(2,4-disubstitued 4-hydroxybutyric acid) Derivatives.

Self-immolative polymers are a special kind of degradable polymers that depolymerize into small molecules through a cascade of reactions upon stimuli-triggered cleavage of the polymer chain ends. This work reports the design and synthesis of a fluoride-triggered self-immolative polyester. A 2,4-disubstitued 4-hydroxy butyrate is first confirmed to quickly cyclize in solution to form a γ-butyrolactone derivative. Then, the Passerini three component reaction (P-3CR) of an AB dimer (A: aldehyde, B: carboxylic acid) with tert-butyl isocyanide or oligo(ethylene glycol) isocyanide affords two poly(2,4-disubstitued 4-hydroxybutyrate) derivatives (P2 and P3). Two silyl ether end-capped polymers (P4 and P5) are abtained from P2 and P3, and their degradation in solution is examined by NMR spectrum and size exclusion chromatography. Polymers P4 and P5 are stable in the absence of tetrabutylammonium fluoride (TBAF), while in the presence of TBAF, the molar masses of P4 and P5 gradually decrease with time together with the increase of the amount of formed 2,4-disubstitued γ-butyrolactone. The depolymerization mechanism is proposed. The first step is the fast removal of the silyl ether by fluoride. Then, the released hydroxyl group initiates the quick head-to-tail depolymerization of the polyester via intramolecular cyclization.

Transcriptomic Analysis Reveals Key Genes Involved in Oil and Linoleic Acid Biosynthesis during Artemisia sphaerocephala Seed Development.

Artemisia sphaerocephala seeds are rich in polysaccharides and linoleic acid (C18:2), which have been widely used as traditional medicine and to improve food quality. The accumulation patterns and molecular regulatory mechanisms of polysaccharides during A. sphaerocephala seed development have been studied. However, the related research on seed oil and C18:2 remain unclear. For this study, A. sphaerocephala seeds at seven different development stages at 10, 20, 30, 40, 50, 60, and 70 days after flowering (designated as S1~S7), respectively, were employed as experimental samples, the accumulation patterns of oil and fatty acids (FA) and the underlying molecular regulatory mechanisms were analyzed. The results revealed that oil content increased from 10.1% to 20.0% in the early stages of seed development (S1~S2), and up to 32.0% in mature seeds, of which C18:2 accounted for 80.6% of the total FA. FA and triacylglycerol biosynthesis-related genes jointly involved in the rapid accumulation of oil in S1~S2. Weighted gene co-expression network analysis showed that transcription factors FUS3 and bHLH played a critical role in the seed oil biosynthesis. The perfect harmonization of the high expression of FAD2 with the extremely low expression of FAD3 regulated the accumulation of C18:2. This study uncovered the gene involved in oil biosynthesis and molecular regulatory mechanisms of high C18:2 accumulation in A. sphaerocephala seeds; thus, advancing research into unsaturated fatty acid metabolism in plants while generating valuable genetic resources for optimal C18:2 breeding.

Supplementation with embryo chicken egg extract improves exercise performance and exerts anti-fatigue effects via AMPK/mTOR signalling pathway in mice.

BACKGROUND: Embryo chicken egg is a nutritional supplement that has been used to enhance physical fitness and promote wound healing according to traditional Chinese medicine for many years. In this study, we evaluated the effects of embryo chicken egg extract (ECE) on the exercise performance and fatigue in mice and the underlying mechanisms. RESULTS: The results indicated that ECE can prolong the exhaustive swimming time, decrease lactic acid, blood urea nitrogen, creatine kinase, and malondialdehyde levels, and increase superoxide dismutase, glutathione peroxidase, and glycogen levels. Additionally, ECE can also regulate the balance of oxidative stress via the adenosine monophosphate activated protein kinase/mammalian target of rapamycin signalling pathway. CONCLUSION: Taken together, these results showed that ECE can improve exercise performance and reduce physical fatigue in mice, which indicates that ECE can be used as a potential supplement to reduce physical fatigue. © 2020 Society of Chemical Industry.

An imperialist competition algorithm using a global search strategy for physical examination scheduling.

The outbreak of the novel coronavirus clearly highlights the importance of the need of effective physical examination scheduling. As treatment times for patients are uncertain, this remains a strongly NP-hard problem. Therefore, we introduce a complex flexible job shop scheduling model. In the process of physical examination for suspected patients, the physical examiner is considered a job, and the physical examination item and equipment correspond to an operation and a machine, respectively. We incorporate the processing time of the patient during the physical examination, the transportation time between equipment, and the setup time of the patient. A unique scheduling algorithm, called imperialist competition algorithm with global search strategy (ICA_GS) is developed for solving the physical examination scheduling problem. A local search strategy is embedded into ICA_GS for enhancing the searching behaviors, and a global search strategy is investigated to prevent falling into local optimality. Finally, the proposed algorithm is tested by simulating the execution of the physical examination scheduling processes, which verify that the proposed algorithm can better solve the physical examination scheduling problem.

[Pharmacoeconomic evaluation of Shexiang Tongxin Dropping Pills combined with conventional Western medicine treatment for coronary heart disease by Markov model].

This research was to evaluate the economics of Shexiang Tongxin Dropping Pills combined with conventional therapy for patients with coronary heart disease(CHD) in Chinese medical environment. From the perspective of medical insurance, a Markov model was established in this study based on the results of Meta-analysis comparing the effectiveness and safety of Shexiang Tongxin Dripping Pills combined with conventional treatment and conventional treatment alone. The experimental group was treated with She-xiang Tongxin Dropping Pills combined with conventional Western medicine treatment, while the control group was treated with conventional Western medicine treatment alone. The cost-utility analysis and sensitivity analysis were performed for the two regimens using Treeage pro. After 30 cycles of model simulation, according to the results of Markov model, the total cost and health output were CNY 237 795.73 and 16.36 QALYs(the quality adjusted life years, QALYs), respectively for Shexiang Tongxin Dropping Pills combined with conventional Western medicine treatment, CNY 247 396.55 and 16.36 QALYs respectively for the conventional Western medicine treatment alone. Compared with the conventional treatment alone, the Shexiang Tongxin Dropping Pills combined with conventional treatment had lower long-term cost and higher health output, with advantages of cost-utility and pharmacoeconomic advantages. The sensitivity analysis results showed that the conclusion was relatively stable. Based on the above results, it is considered that compared with the conventional Western medicine alone, Shexiang Tongxin Dropping Pill combined with conventional Western medicine is a treatment regimen with pharmacoeconomic advantages for the treatment of CHD.

Tumour-derived exosomal miR-3473b promotes lung tumour cell intrapulmonary colonization by activating the nuclear factor-κB of local fibroblasts.

Tumour-derived exosomes have been shown to induce pre-metastatic niche formation, favoring metastatic colonization of tumour cells, but the underlying molecular mechanism is still not fully understood. In this study, we showed that exosomes derived from the LLC cells could indeed significantly enhance their intrapulmonary colonization. Circulating LLC-derived exosomes were mainly engulfed by lung fibroblasts and led to the NF-κB signalling activation. Further studies indicated that the exosomal miR-3473b was responsible for that by hindering the NFKB inhibitor delta's (NFKBID) function. Blocking miR-3473b could reverse the exosome-mediated NF-κB activation of fibroblasts and decrease intrapulmonary colonization of lung tumour cells. Together, this study demonstrated that the miR-3473b in exosomes could mediate the interaction of lung tumour cells and local fibroblasts in metastatic sites and, therefore, enhance the metastasis of lung tumour cells.

Molecular mapping of major QTL conferring resistance to orange wheat blossom midge (Sitodiplosis mosellana) in Chinese wheat varieties with selective populations.

KEY MESSAGE: Two novel midge resistance QTL were mapped to a 4.9-Mb interval on chromosome arm 4AL based on the genetic maps constructed with SNP markers. Orange wheat blossom midge (OWBM) is a devastating insect pest affecting wheat production. In order to detect OWBM resistance genes and quantitative trait loci (QTL) for wheat breeding, two recombinant inbred line (RIL) populations were established and used for molecular mapping. A total of seven QTL were detected on chromosomes 2D, 4A, 4D and 7D, respectively, of which positive alleles were all from the resistant parents except for the QTL on 7D. Two stable QTL (QSm.hbau-4A.2-1 and QSm.hbau-4A.2-2) were detected in both populations with the LOD scores ranging from 5.58 to 29.22 under all three environments, and they explained a combined phenotypic variation of 24.4-44.8%. These two novel QTL were mapped to a 4.9-Mb physical interval. The single-nucleotide polymorphism (SNP) markers AX-109543456, AX-108942696 and AX-110928325 were closely linked to the QTL and could be used for marker-assisted selection (MAS) for OWBM resistance in wheat breeding programs.