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Brassica juncea has adapted to diverse climate zones and latitudes, especially in the Yunnan–Guizhou Plateau with the complexity and diversity of the ecological types of western China. However, the genetic variations underlying the diversity of these ecotypes are poorly known. In this study, we resequenced the genome of 193 indigenous B. juncea accessions and obtained 1.04 million high-quality SNPs and 3.23 million InDels by mapping reads to the reference genomes of B. juncea var. timuda. Phenotype, population genetic, phylogenetic and principal component analyses showed considerable genetic variation including four distinct genetic groups. Selective sweep analysis and a genome-wide association study revealed the candidate genes for seed color and fatty acid biosynthesis. The results provide a comprehensive insight into the spread and improvement of B. juncea and laya foundation for accelerating rapeseed breeding by facilitating screenings of molecular markers.

Representative electrophoresis images for promoter hypermethylation and LOH of NISCH.

Figure S1. Representative electrophoresis images for promoter hypermethylation and LOH of NISCH.Figure S2. The flow cytometry profiles of cell cycle analysis with NISCH overexpressed or knockdown. Figure S3. The mRNA expression of NISCH in a panel of 45 ovarian cancer tissues in Lu's study.

The mRNA expression of NISCH in a panel of 45 ovarian cancer tissues in Lu's study.

PDF file, 19K, Line graph representing the mean change in eGFR for nine patients that received bardoxolone methyl treatment for at least six cycles. Error bars represent the SEM.

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PDF file, 63K, Changes in Serum Creatinine Following Treatment with Bardoxolone Methyl.

Purpose: Bardoxolone methyl, a novel synthetic triterpenoid and antioxidant inflammation modulator, potently induces Nrf2 and inhibits NF-κB and Janus-activated kinase/STAT signaling. This first-in-human phase I clinical trial aimed to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and appropriate dose for phase II studies; characterize pharmacokinetic and pharmacodynamic parameters; and assess antitumor activity.Experimental Design: Bardoxolone methyl was administered orally once daily for 21 days of a 28-day cycle. An accelerated titration design was employed until a grade 2–related adverse event occurred. A standard 3 + 3 dose escalation was then employed until the MTD was reached. Single dose and steady-state plasma pharmacokinetics of the drug were characterized. Assessment of Nrf2 activation was examined in peripheral blood mononuclear cells (PBMC) by measuring NAD(P)H:quinone oxidoreductase (NQO1) mRNA levels. Immunohistochemical assessment of markers of inflammation, cell cycle, and apoptosis was carried out on tumor biopsies.Results: The DLTs were grade 3 reversible liver transaminase elevations. The MTD was established as 900 mg/d. A complete tumor response occurred in a mantle cell lymphoma patient, and a partial response was observed in an anaplastic thyroid carcinoma patient. NQO1 mRNA levels increased in PBMCs, and NF-κB and cyclin D1 levels decreased in tumor biopsies. Estimated glomerular filtration rate (eGFR) was also increased.Conclusions: Bardoxolone methyl was well tolerated with an MTD of 900 mg/d. The increase in eGFR suggests that bardoxolone methyl might be beneficial in chronic kidney disease. Objective tumor responses and pharmacodynamic effects were observed, supporting continued development of other synthetic triterpenoids in cancer. Clin Cancer Res; 18(12); 3396–406. ©2012 AACR.

Object: Mycobacterium tuberculosis (MTB) is a bacterium that can cause zoonoses by aerosol transmission. Tuberculosis (TB) caused by MTB places a heavy burden on world public health security. The development of efficient, specific, convenient, and inexpensive MTB assays is important for the prevention and control of TB. Methods: Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) is a special DNA repeat family widely present in bacterial and archaeal genomes. In this study, we established a specific detection method for MTB using the CRISPR system, combined with recombinase mediated isothermal nucleic acid amplification (RAA) to improve the sensitivity of the detection system and achieve "two-level" amplification of the detection signal. The sensitivity and specificity of RAA combined with the CRISPR/Cas system were analyzed. Using BACTEC 960 culture as the gold standard for the detection of MTB, we established the TB-CRISPR technique by testing 504 samples from patients with suspected tuberculosis. Results: MTB H37Ra could be detected as low as 3.13 CFU/mL by the CRISPR-Cas12a system targeting IS6110. With BACTCE960 culture (120 positives and 384 negatives) as the gold standard, the sensitivity of the TB-CRISPR technique was 0.883 (0.809-0.932) and the specificity was 0.940 (0.910-0.961). According to the receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) reached 0.944 (0.914-0.975) within 95% CI. The positive likelihood ratio (PLR) was 14.747 (9.870-22.035) and the negative likelihood ratio (NLR) was 0.124 (0.076-0.203). The positive predictive value (PPV) was 0.822 (0.742-0.881) and the negative predictive value (NPV) was 0.963 (0.937-0.979). Conclusion: TB-CRISPR realizes the rapid screening and diagnosis of MTB. The whole detection time is less than 1.5h. It is easy to operate and does not need to rely on complex instruments. It is of great significance for the rapid detection of MTB and the clinical diagnosis of TB.

Pterygium is a common ocular disease with high recurrence rate, characterized by hyperplasia of subconjunctival fibrovascular tissue. Autophagy, the important process to maintain cellular homeostasis, participates the pathogenic fibrosis of different organs. However, the exact role of autophagy in pterygium pathogenesis remains unknown. Here we found that autophagic activity was decreased in human pterygium tissues compared with adjacent normal conjunctival tissues. The in vitro model of fibrosis was successfully established using human primary conjunctival fibroblasts (ConFB) treated with TGF-β1, evidenced by increased fibrotic level and strong proliferative and invasive capability. The autophagic activity was suppressed during TGF-β1 or ultraviolet-induced fibrosis of ConFB. Activating autophagy dramatically retarded the fibrotic progress of ConFB, while blocking autophagy exacerbated this process. Furthermore, SQSTM1, the main cargo receptor of selective autophagy, was found to significantly promote the fibrosis of ConFB through activating PKCι–NF-κB signaling pathway. Knockdown of SQSTM1, PKCι, or p65 in ConFB delayed the TGF-β1-induced fibrosis. Over-expression of SQSTM1 drastically abrogated the inhibitory effect of rapamycin or serum starvation on the TGF-β1-induced fibrosis. Collectively, our data suggested that autophagy impairment of human ConFB facilitates fibrosis via activating SQSTM1–PKCι–NF-κB signaling cascades. This work was contributory to elucidating the mechanism of autophagy underlying pterygium occurrence.

Gelsenicine, mainly isolated from Gelsemium elegans Benth., is one of the most toxic alkaloids. The lack of information on gelsenicine leads to inaccurate risk and poisoning evaluation. In this study, the metabolic profiling and toxicokinetics of gelsenicine was studied by ultra-high performance liquid chromatography (UPLC) with quadrupole time-of-flight (Q-ToF) and tandem mass spectrometry in rats after intraperitoneal (i.p., 40 μg/kg) and intragastric (i.g., 60 μg/kg) administration. After i.p. administration, the area under the curve (AUC), the apparent volume of distribution (V), and the total body clearance (CL/F) of gelsenicine in plasma were 3.79 μg/L h, 38.47 L/kg, and 11.87 mL/h kg, respectively. After i.g. administration, the corresponding values were slightly increased (5.49 μg/L h; 53.10 mL/kg, and 12.66 mL/h kg). The toxicokinetic results indicated that the hepatic first-pass effect was predominant after i.p. administration. The UPLC-Q-ToF-MS data revealed nine metabolites in plasma, urine, and bile which were largely obtained by demethylation, hydroxylation, acetylation and glycine conjugation. Metabolites were mainly excreted through urine and bile, most of which in urine was basically eliminated in 24 h. Molecular docking and liver microsome experiments further showed that gelsenicine was metabolized by cytochrome P450 3A4 and 3A5. Summarizing, the present study provides metabolic and toxicokinetic information on gelsenicine which in turn may help in future risk assessment and forensic identification after poisonings.

Rice is a staple food for over half of the world’s population, and fungal spoilage in stored rice may occur when the moisture content and temperature are conducive. Aspergillus sp. and Penicillium sp. are the most harmful toxigenic species that produce harmful mycotoxins. Molds pose a potential threat to public health and cause a huge economic loss. Therefore, it is of great importance to find out how molds multiply in rice. This study focused on the isolation and identification of fungi presented in rice and their evolution in rice with different moisture contents stored for varying periods of time and under different temperatures. Mold community was detected every month using the culture-dependent and -independent method of polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). Significant differences were detected by the traditional culture method under different storage conditions. For potato dextrose agar (PDA) media, high temperature and moisture were suitable for the dominant strains including Penicillium aurantiogriseum and Penicillium oxalicum. In particular, P. oxalicum competitively inhibited the other fungi. For Rose Bengal medium, no difference was observed under different storage conditions, and only typical strains such as Aspergillus candidus and Alternaria were detected. PCR-DGGE identified some uncultured strains such as Trichoderma sp. and Cladosporium sp., the dominant strains and the flora diversity such as Aspergillus restrictus and Eurotium athecium. These results indicated that storage conditions greatly shape fungal growth. This study provides a foundation for the evolution of fungal flora in rice during storage in China and may help in developing biological control methods to prevent mold contamination in rice.

Engineering a tube-like architecture with bimetallic nanoparticles (NPs) has been considered an effective strategy for enhancing catalytic performance. Herein, we report a simple method for preparing one-dimensional (1D) carbon-based tubular composites incorporated with bimetallic active CoNi alloy NPs. CoNi alloy NPs were produced from the co-reduction of Co and Ni ions existing within a zeolitic imidazolate framework (ZIF)-based precursor and polydopamine (PDA) layer after N

Introduction: Premature infants are exceptionally vulnerable to nutrition-related diseases, and the utilization of standardized feeding guidelines may reduce nutritional practice variation, which can promote growth. Nutritional risk screening is the first step for standardized nutrition advice. However, risk screening tools specific for following up preterm infants are scarce. Hence, our study aimed to develop and evaluate a standardized Nutritional Risk Screening Tool for Preterm Infants (NRSP subscale 1) from birth to corrected age four months old . Methods: This study was a two-phase (the development phase and evaluation phase) study. Initially, we used the Delphi expert consultation method to create NRSP subscale 1. Then, a professional panel interviewed the participated preterm infants using the screening tool, measured anthropometric parameters, and conducted an intellectual development test on the interview day and remeasured anthropometric parameters 2 weeks or 1 month after the first interview. In the development phase, we cross-tabulated the responses to the screening tool with the classifications of z-scores of the body weight, length, or head circumference to identify significant predictors of underweight, stunting, or microcephaly. We then combined significant predictors to produce models for predicting underweight, stunting, or microcephaly by multivariate logistic regression analysis. In the evaluation phase, the area under the curve (AUC), sensitivity, specificity, and correlation coefficient by Spearman’s correlation analysis (rs) between the risk classifications by NRSP subscale 1 and the classifications of the z-scores of the body weight, length, or head circumference were calculated to assess the validity of the screening tool. Intellectual development levels between high and low nutritional risk infants were statistically compared. Results: A total of 219 and 244 preterm infants were included to two phases, respectively. AUC was 0.936 (95% CI: 0.860–1.000, p < 0.001), sensitivity was 0.667, specificity was 0.941, rs = 0.407 (p < 0.001); AUC was 0.794 (95% CI: 0.638–0.951, p = 0.002), sensitivity was 0.500, specificity was 0.953, rs = 0.339 (p < 0.001); AUC was 0.831 (95% CI: 0.737–0.925, p = 0.001), sensitivity was 0.889, specificity was 0.643, rs = 0.215 (p = 0.001) in predicting underweight, stunting, and microcephaly on the interview day, respectively. AUC was 0.905 (95% CI: 0.826–0.984, p = 0.006), sensitivity was 0.500, specificity was 0.905, rs = 0.504 (p < 0.001); AUC was 0.738 (95% CI: 0.515–0.960, p = 0.034), sensitivity was 0.429, specificity was 0.848, rs = 0.382 (p < 0.001); AUC was 0.664 (95% CI: 0.472–0.856, p = 0.071), sensitivity was 0.455, specificity was 0.809, rs = 0.169 (p = 0.037) in predicting underweight, stunting, and microcephaly 2 weeks or 1 month after the first interview, respectively. Gross motor development quotients (DQs) (95.85 [32.87] vs. 86.29 [17.19], p = 0.022), fine motor DQs (115.77 [46.03] vs. 102.12 [20.27], p = 0.010), and verbal DQs (110.73 [35.27] vs. 100.63 [21.28], p = 0.042) were higher in low nutritional risk infants than high-risk ones. Conclusion: NRSP subscale 1 was acceptable and reliable in predicting underweight, but the validity in predicting stunting or microcephaly was slightly mild. Further investigations are required to authenticate NRSP subscale 1’s effectiveness.

C–CoNi/@Al2O3 nanosheets were well constructed with CoAl-LDH nanosheets as a precursor, and exhibited excellent performance as both a catalyst and an adsorbent.

Learning management system (LMS) is a web-based system used to develop, implement, and assess a specific learning process. When designing an administration learning system, it is important to understand the general architecture and roles of each level of the system. In this study, we propose a web-based English reading learning system to address the drawbacks of existing methods in English learning resource management that include login impact, system response time, and user satisfaction. English reading materials are integrated using a feature model, and the adaptive recommendation system is built using the ID3 method. The design of the proposed English reading learning system was intended to employ a hybrid of software and hardware that will benefit a wide variety of groups, especially universities, colleges, and organizations. The statistic results showed that the proposed model is capable of meeting the functional objectives of English learning resource management, as well as having a rapid and accurate response time with high user satisfaction.

Background: Artificial intelligence (AI) has been successfully applied to the screening tasks of fundus diseases. However, few studies focused on the potential of AI to aid medical teaching in the residency training program. This study aimed to evaluate the effectiveness of the AI-based pathologic myopia (PM) identification system in the ophthalmology residency training program and assess the residents’ feedback on this system.Materials and Methods: Ninety residents in the ophthalmology department at the Second Affiliated Hospital of Zhejiang University were randomly assigned to three groups. In group A, residents learned PM through an AI-based PM identification system. In group B and group C, residents learned PM through a traditional lecture given by two senior specialists independently. The improvement in resident performance was evaluated by comparing the pre-and post-lecture scores of a specifically designed test using a paired t-test. The difference among the three groups was evaluated by one-way ANOVA. Residents’ evaluations of the AI-based PM identification system were measured by a 17-item questionnaire.Results: The post-lecture scores were significantly higher than the pre-lecture scores in group A (p < 0.0001). However, there was no difference between pre-and post-lecture scores in group B (p = 0.628) and group C (p = 0.158). Overall, all participants were satisfied and agreed that the AI-based PM identification system was effective and helpful to acquire PM identification, myopic maculopathy (MM) classification, and “Plus” lesion localization.Conclusion: It is still difficult for ophthalmic residents to promptly grasp the knowledge of identification of PM through a single traditional lecture, while the AI-based PM identification system effectively improved residents’ performance in PM identification and received satisfactory feedback from residents. The application of the AI-based PM identification system showed advantages in promoting the efficiency of the ophthalmology residency training program.

Beige adipocytes have recently attracted attention for their potential as new therapeutic targets in the management of obesity and related metabolic disorders. MicroRNAs (miRNAs) have been reported as transcriptional regulators or biomarkers of brown and beige adipogenesis. Nevertheless, the effects of miRNAs involved in beige differentiation of human visceral adipocytes remain to be investigated. In this study, microarray screening showed that miR-1275 was significantly decreased during the differentiation of beige adipocytes induced by human omental adipose-derived stem cells (hASCs). Overexpression of miR-1275 suppressed the "brown-like" differentiation of hASCs by inhibiting the key transcriptional factor PR domain containing 16 (

Gestational diabetes mellitus (GDM) is a pathological condition of glucose intolerance associated with adverse pregnancy outcomes and increased risk of developing maternal type 2 diabetes later in life. Metabolomics is finding increasing use in the study of GDM. To date, GDM-specific metabolomic changes have not been completely elucidated.In this pilot study, metabolomics fingerprinting data, obtained by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS), of 54 healthy pregnant women and 49 patients with GDM at the second and third gestational trimesters were analyzed. Multilevel statistical methods were used to process complex metabolomic data from the retrospective cohorts.Using univariate analysis (p 0.05), 41 metabolites were identified as having the most significant differences between these two groups. Lipid metabolites, particularly glycerophospholipids, were the most prevalent class of altered compounds. In addition, metabolites with previously unknown connection to GDM - such as monoacylglycerol, dihydrobiopterin, and 13S-hydroxyoctadecadienoic acid - were identified with strong discriminative power. The main metabolic pathways affected by GDM included glycerophospholipid metabolism, linoleic acid metabolism, and D-arginine and D-ornithine metabolism.Our data provide a comprehensive overview of metabolite changes at different stages of pregnancy, which offers further insights into the pathogenesis of GDM.

The clinical pharmacodynamics of tacrolimus in renal transplant patients has significant interindividual variability. T lymphocytes were selected to study the pharmacodynamic response of tacrolimus, which was significantly correlated with renal function and the outcome of renal transplant patients. Ultra-performance liquid chromatography–quadrupole time-of-flight mass spectroscopy (UPLC/Q-TOF-MS) was performed to obtain the metabolic profiles of 109 renal transplant patients. A partial least squares (PLS) model was constructed to screen potential biomarkers that could predict the efficacy of tacrolimus. Multinomial logistic regression analysis established a bridge that could quantify the relationship between the efficacy of tacrolimus and biomarkers. The results showed a good correlation between endogenous molecules and the efficacy of tacrolimus. Metabolites such as serum creatinine, mesobilirubinogen, L-isoleucine, 5-methoxyindoleacetate, eicosapentaenoic acid, N2-succinoylarginine, tryptophyl-arginine, and butyric acid were indicated as candidate biomarkers. In addition, the key biomarkers could correctly predict the efficacy of tacrolimus with an accuracy of 82.5%. Finally, we explored the mechanism of individual variation by pathway analysis, which showed that amino acid metabolism was significantly related to the efficacy of tacrolimus. Moreover, orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there was no difference in key metabolites among different pharmacodynamic groups at 1 month and 3 months after dose adjustment, suggesting that pharmacometabonomics is a useful tool to predict individual differences in pharmacodynamics and thus to facilitate individualized drug therapy.

Experimental autoimmune uveitis (EAU) is a widely used animal model for uveitis research. The C57BL/6 mouse strain is the most commonly used mouse strain in the research of genetic modification, but C57BL/6 mice are not sufficiently susceptible to EAU induction, partly due to experimental factors. This work aims to optimize relevant factors to improve the efficiency of EAU induction in C57BL/6 mice.To induce EAU, mice were immunized via intraperitoneal injection with pertussis (PTX) and subcutaneous injection with interphotoreceptor retinoid-binding protein peptide 1-20 (IRBPUveitis occurred at 8-12 days after immunization and reached its peak at 18-20 days, while T helper type 17 (Th17) cells peaked earlier at 14-18 days after immunization. Based on clinical and histological scores, 500 µg of IRBP peptide was the optimal dose required to induce EAU. The PTX dose demonstrated no influence on EAU incidence, but potentially affected the severity of uveitis. A single injection of 1,000 ng of PTX induced the most severe EAU and the highest proportion of Th17 cells. Compared to extruded emulsion, sonicated emulsion produced a higher incidence, higher histological score, and a 2-day-earlier onset of EAU. Electron microscopy showed a significantly different microstructure between the 2 emulsions.This work optimized the protocols of EAU induction and obtained a high and stable induction rate with severe inflammation in the C57BL/6 mouse strain. Our results facilitate future experimental research involving uveitis.

The aim of this study is to evaluate morphological features of corneal flap/cap and the correlations with corneal higher-order aberrations (HOAs) changes after femtosecond laser in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE).This was a retrospective study. Pre- and postoperative (1 and 3 months) corneal HOAs were assessed with Pentacam HR. The corneal flap/cap thickness at 32 points (± 1.5 mm, ± 2 mm, ± 2.5 mm, and ± 3 mm from the corneal vertex on meridian 0°/45°/90°/135°) were measured using anterior segment optical coherence tomography at 3 months postoperatively. Morphological features of corneal flap/cap including predictability (P), uniformity (U), and symmetry (S) were calculated and used for correlation analysis with corneal HOAs changes.Eighty-six eyes (44 patients) and ninety-six eyes (50 patients) were involved in FS-LASIK and SMILE groups, respectively. Significant thicker corneal flap/cap than the predicted was observed at each measuring point and meridian in both groups (difference 2.225 μm, the within-subject standard deviation over 6-mm optical zone). There was no statistically significant difference in predictability of corneal flap/cap thickness, while UBoth FS-LASIK and SMILE had good predictability in flap or cap thickness, while the uniformity and symmetry of SMILE cap were better than FS-LASIK flap. The quality of flap/cap was closely associated with the changes of corneal HOAs.

Mammary epithelial cells (MECs) are specific target cells to study the underlying mechanism for mammary gland development and lactation, mammary gland bioreactor and breast cancer pathogenesis. However, the conventional isolation and purification methods of MECs have restricted the research and application of its related fields, because the isolated MECs population was always mixed with other cell types.In order to solve the problem of incomplete purification of MECs isolated in vitro, it is very necessary to establish the optimal culture method for its isolation and purification.In this study, a method were called the "selective secondary tissue attachment method", which were proved to be effective and accurate by the purity, cellular viability, biological characteristic, and transgenic efficiency of the purified MECs.The results showed that compared with traditional methods, this method could obtain 100% MECs population with high purity and high cell viability in vitro, and these purified cells showed high transgenic efficiency and a high number of positive clones. In addition, the early embryo development rate could significantly improve when the purified mammary epithelial cells were used as donor cells for nuclear transfer.Therefore, this study provides a versatile and effective method for the isolation of MECs with high purity, which can be used further for mammary-related research.It is most effective approach to isolate mammary epithelial cells by "selective secondary tissue attachment method".

Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine disease characterized by polycystic ovary. The aim of the study was to assess microRNA-21 regulates granulosa cell apoptosis and proliferation in polycystic ovary syndrome through target toll-like receptor 8. Granulosa cells were collected from 30 PCOS patients and 30 normal patients with tubal or male factor infertility (control) during in vitro fertilization-Embryo Transfer (IVF-ET) and were flash frozen with liquid nitrogen for storage for subsequent use. PCOS diagnosis was based on the revised standards of the American Society of Reproductive Medicine (ASRM) and the Rotterdam criteria PCOS granulosa cells and control granulosa cells were cultured in DMEM/F12 medium containing 10% fetal bovine serum and 1% antibiotic. After this RT-PCR, Western blot assessment and Detection of apoptosis by flow cytometry were conducted. The results of qPCR showed that the mRNA and protein expression of TLR8 in PCOS granulosa cells were significantly increased compared with the normal group. The results of Western blot also showed that the expression of TLR8, IFN-γ, TNF-α and IL-12 gene protein in the transfected cells was significantly higher than that in the control cells. Here, we show that miR-21 and TLR8 significantly increased in PCOS granulosa cell as compared with normal granulosa cells, and miR-21 enhances the TLR8 mRNA translation and then promotes the IFN-γ, TNF-α, and IL-12 secretion. Our study demonstrates that miR-21/ TLR8 involved in the PCOS inflammation, it provides profound insights into pathogenesis of PCOS.

BackgroundAntenatal corticosteroids (ACS) treatment is critical to support survival and lung maturation in preterm infants, however, its effect on feeding and growth is unclear. Prior preterm delivery, it remains uncertain whether ACS treatment should be continued if possible (repeated course ACS), until a certain gestational age is reached. We hypothesized that the association of single-course ACS with feeding competence and postnatal growth outcomes might be different from that of repeated course ACS in very-low-birth-weight preterm infants.MethodsA multicenter retrospective cohort study was conducted in very-low-birth-weight preterm infants born at 23–37 weeks’ gestation in South China from 2011 to 2014. Data on growth, nutritional and clinical outcomes were collected. Repeated course ACS was defined in this study as two or more courses ACS (more than single-course). Infants were stratified by gestational age (GA), including GA ResultsA total of 841 infants were recruited. The results, just in very-low-birth-weight preterm infants born at 28–32 weeks’ gestation, showed both single and repeated course of ACS regimens had shorter intubated ventilation time compared to non-ACS regimen. Single-course ACS promoted the earlier application of amino acid and enteral nutrition, and higher rate of weight increase (15.71; 95%CI 5.54–25.88) than non-ACS after adjusting for potential confounding factors. No associations of repeated course ACS with feeding, mean weight and weight increase rate were observed.ConclusionsSingle-course ACS was positively related to feeding and growth outcomes in very-low-birth-weight preterm infants born at 28–32 weeks’ gestation. However, the similar phenomenon was not observed in the repeated course of ACS regimen.

A low-loss broadband power splitter based on X-cut lithium niobate is proposed by utilizing the multimode interference coupler with a shallow-etched slot, wedge-shaped structure and SiO2 cladding. The multimode waveguide with a shallow-etch slot could reduce the sensitivity of multi-mode region on the wavelength and reach to high-quality imaging requirements. Results show that there is an excess loss around 0.01 dB at the operation wavelength of 1550 nm, a broad operation bandwidth of ∼ 1314 nm and large tolerance in the shallow-etching. Additionally, our proposed device has been compared with the published and conventional multimode interference coupler for presenting good low-loss and broad bandwidth.

Posterior reversible encephalopathy syndrome is a clinical-neuroradiological syndrome with typical neuroimaging features of posterior cerebral white matter changes that are usually reversible. However, there are only few reports of burns with posterior reversible encephalopathy syndrome in the literature. Hence, it is a clinical entity that many burn medicine physicians may be unfamiliar with. We report a case of severe burns complicated by posterior reversible encephalopathy syndrome in a 14-month-old male patient. On the eighth day of hospitalization, the child had persistent fever, occasional convulsions, eyes staring to the right, and high-pitched cry. Magnetic resonance imaging on day 10 showed the diagnosis is posterior reversible encephalopathy syndrome. We used hormone therapy to reduce cerebral oedema, oxcarbazepine to control convulsions, and multiple other drugs and physical measures to treat fever. The symptoms, signs, and imaging abnormalities of his posterior reversible encephalopathy syndrome were rapidly reversed in a short period of time. At the 1-year follow-up, the patient had recovered completely with no residual neurological signs and symptoms. To our knowledge, the patient may be the youngest recorded patient with both burns and posterior reversible encephalopathy syndrome. Careful observation, computed tomography, and magnetic resonance imaging can achieve early detection, early diagnosis, and early treatment of posterior reversible encephalopathy syndrome, which facilitates the achievement of desired therapeutic results. Further investigation is required to determine whether burns can serve as an independent posterior reversible encephalopathy syndrome causative factor and clarify the underlying pathogenesis mechanism.

China has started shifting from relying on supply management to demand management strategy in addressing its water shortage problems. Water option, a financial derivative for water commodity, has been utilized to manage water demands in the United States and Europe since the 1990s but is still novel to China. In this study we analyzed the pros and cons of China’s existing system for water rights transfers and proposed an alternative, flexible trading instrument-water options for China. Incorporating the uncertainty to water option pricing, this study first conducted an empirical analysis of the water option in the water-receiving area of the Hanjiang-Weihe River Transfer Project of China, and then evaluated the benefits of the water option applications. Results show that water option trading can bring water cost saving and increase the potential industrially added value for industrial enterprises in the receiving area, and trading of short-and-medium term water options is more favorable than the long-term water options trading. The novel water option trading proposed in this study, once verified through pilot studies, will be helpful in addressing water shortage problems in China.

Early pregnancy loss (EPL) is a common event worldwide. Previous studies show that mitochondrial DNA (mtDNA) copy number (CN) is associated with semen parameters and preimplantation embryo viability, indicating the predictive potential of mtDNA CN for ongoing pregnancy outcomes. However, no relevant study has assessed the relationship between mtDNA CN and EPL. Thus, we aimed to determine whether mtDNA CN and mtDNA 4977-bp deletion rate (DR) in chorionic villous tissue are associated with EPL. Chorionic villous tissue total DNA was extracted from 75 EPL cases and 75 healthy controls. Chromosomal analysis was conducted using copy number variation (CNV) sequencing. The mtDNA CN and DR were measured in samples without pathogenic CNVs. The association between mtDNA CN or DR and EPL risk were estimated using logistic regression. The EPL group had a significantly different mtDNA CN (P 0.001) and DR (P = 0.005) compared to the control group. Both biomarkers were independent risk factors for EPL (CN odds ratio 1.71, 95% confidence interval 1.17 to 2.49, P = 0.005; DR odds ratio 1.07, 95% confidence interval 1.02 to 1.12, P = 0.006). These results suggest that higher mtDNA CN and DR levels are strongly associated with EPL and represent independent risk factors for EPL. Further studies validating these findings and exploring the underlying biological mechanisms are warranted.

Hand-foot syndrome (HFS) is a major adverse reaction to capecitabine (CAP). The exact pathogenesis of this disease remains unclear. In this study, metabolomics combined with cell RNA sequencing was used to study the mechanisms of CAP-induced HFS. The murine model of HFS was constructed by intragastric administration of CAP or its metabolites. Quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to verify the mechanisms. Metabolomics showed the phosphatidylinositol signaling pathway and amino acid and fatty acid metabolism to be the major metabolic alterations related to the occurrence of HFS. Transcriptomics profiles further revealed that the cytokine-cytokine receptor interaction, IL17 signaling pathway, Toll-like receptor signaling pathway, arachidonic acid metabolism, MAPK signaling pathway, and JAK-STAT3 signaling pathway were the vital steps in skin toxicity induced by CAP or its metabolites. We also verified that the inflammation mechanisms were primarily mediated by the abnormal expression of interleukin (IL) 6 or IL8 and not exclusively by COX-2 overexpression. Finally, the P38 MAPK, NF-κB, and JAK-STAT3 signaling pathways, which mediate high levels of expression of IL6 or IL8, were identified as potential pathways underlying CAP-induced HFS.

Background A complementary feeding (CF) period is necessary for nutritional and developmental reasons. Preterm children encounter more feeding problems than their term counterparts in the CF period. The goal of this study was to develop a nutritional risk screening tool specific to preterm children (the NRSP) in outpatient settings in the CF period, with the expectation of providing a standardised process to determine feeding problems and subsequently offering targeted nutritional advice. Methods This study was a 2-phase study consisting of the development and evaluation phases. In the development phase, the items of the NRSP were initially developed based on references and the Delphi expert consultation method. Second, 329 preterm individuals with corrected ages from 5 to 36 months were enrolled. The participating preterm children were interviewed with the NRSP and anthropometric measurements, and underwent intellectual developmental tests and biochemistry detection (haemoglobin, red blood cell count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, serum iron, vitamin D). Third, preterm children’s anthropometric parameters were remeasured 1 month (for infants whose corrected age was 5–11 months) or 3 months (for children whose corrected age was 12–36 months) after the interview. Data in the development phase were analysed via univariate and binary logistic regression analysis sequentially to assign scores for items of the NRSP and to generate the models to predict underweight, stunting, and microcephaly of the NRSP. In the evaluation phase, another 605 preterm individuals were recruited to undergo the interview, anthropometric measurements, intellectual developmental tests, and biochemistry detection as in the development phase. Interrater reliability, test-retest reliability, area under the curve (AUC), accuracy, sensitivity, specificity, the positive/negative predictive value (P/NPV), the positive/negative likelihood ratio (LR+/−), and the correlation coefficient by Spearman’s correlation analysis (rs) were used to assess the reliability and validity of the NRSP. Finally, anthropometric parameters, biochemistry levels, and intellectual development quotients (DQs) from the development and evaluation phases between the high- and low-risk groups classified by the NRSP were compared using a t-test. Results The κ coefficients of the interrater and test-retest reliability of the NRSP were all above 0.600, which meant that the reliability of the NRSP was moderate to substantial. The NRSP exhibited relatively higher efficiency in predicting underweight and stunting, with AUCs, accuracies, specificities, and NPVs near to or greater than 0.900, sensitivities above 0.600, PPVs above 0.400, LR + s near to or greater than 10, and rss above 0.400. On the other hand, the NRSP manifested a weaker ability in predicting microcephaly, with most of the values of validity indicators lower than those of underweight and stunting prediction. Z scores of body weight, body length and head circumference, as well as DQs, were all higher in the low-risk groups than in the high-risk groups. There were no significant differences with respect to biochemistry levels between the high- and low-risk groups. Conclusion The NRSP shows moderate to substantial reliability and validity in predicting underweight, stunting, and microcephaly. Health care staff should shed light on improving the feeding practices of preterm children with high nutritional risk classified by the NRSP to facilitate their physical growth and intellectual development. More research is expected to promote the NRSP models.

Early non-chromosome-related missed abortion (MA) is commonly associated with an altered immunological environment during pregnancy. Human decidual natural killer (dNK) cells, the most abundant lymphocyte population within the first-trimester maternal-fetal interface, are vital maternal regulators of immune tolerance mediating successful embryo implantation and placentation. Previous studies have shown that dNK cells may play a role in MA. However, the gene expression status and specific altered manifestations of dNK cells in patients with early MA remain largely unknown. Here, we show that MA dNK cells have distinct mRNA and lncRNA expression profiles through RNA sequencing, with a total of 276 mRNAs and 67 lncRNAs being differentially expressed compared with controls. Protein-protein interaction analysis of differentially expressed mRNAs was performed to identify hub genes and key modules. An lncRNA-mRNA regulatory network characterized by the small-world property was constructed to reveal the regulation of mRNA transcription by differential hub lncRNAs. Functional annotation of differentially expressed mRNAs and lncRNAs was performed to disclose their potential roles in MA pathogenesis. Our data highlight several enriched biological processes (immune response, inflammatory response, cell adhesion, and extracellular matrix [ECM] organization) and signaling pathways (cytokine-cytokine receptor interaction, ECM-receptor interaction, Toll-like receptor signaling pathway, and phosphatidylinositol signaling system) that may influence MA. This study is the first to demonstrate the involvement of altered mRNA and lncRNA expression profiles in the dNK cell pathogenesis of early MA, facilitating a better understanding of the underlying molecular mechanisms and the development of novel MA therapeutic strategies targeting key mRNAs and lncRNAs.

We previously demonstrated that Tetraticopeptide 4 (TTC4) inhibited apoptosis in vascular endothelial cells (VEC) deprived of serum and fibroblast growth factor 2 (FGF-2). In this study, we aimed to resolve the mechanism of TTC4 inhibiting VEC apoptosis. TTC4, predicted as a HSP70 co-chaperone protein, may regulate the fate of cells by affecting the activity of HSP70, however, there is no experimental evidence showing the interaction of TTC4 and HSP70. Using Co-immunoprecipitation (Co-IP), we demonstrated that TTC4 interacted with HSP70. If HSP70 was knockdown, TTC4 no longer suppressed apoptosis. Furthermore, we found ABO, an inhibitor of annexin A7 (ANXA7) GTPase, could promote the interaction of TTC4 and HSP70 and the translocation of ANXA7 to lysosome. At the same time, ABO inhibited the interaction of HSP70 and ANXA7. Moreover, Akt, as a downstream effector of HSP70 was upregulated, and ANXA7 translocating to lysosome protected the stability of lysosomal membrane. Here, we discovered a special mechanism by which TTC4 inhibited apoptosis via HSP70 in VECs. On the one hand, increasing TTC4 and HSP70 interaction upregulated Akt that inhibited apoptosis. On the other hand, decreasing HSP70 and ANXA7 interaction promoted the translocation of ANXA7 to lysosome, which inhibited apoptosis through protecting the lysosomal membrane stability.

Studies have shown that the use of artificial intelligence can reduce errors in medical image assessment. The diagnosis of breast cancer is an essential task; however, diagnosis can include ‘detection’ and ‘interpretation’ errors. Studies to reduce these errors have shown the feasibility of using convolution neural networks (CNNs). This narrative review presents recent studies in diagnosing mammographic malignancy investigating the accuracy and reliability of these CNNs. Databases including ScienceDirect, PubMed, MEDLINE, British Medical Journal and Medscape were searched using the terms ‘convolutional neural network or artificial intelligence’, ‘breast neoplasms [MeSH] or breast cancer or breast carcinoma’ and ‘mammography [MeSH Terms]’. Articles collected were screened under the inclusion and exclusion criteria, accounting for the publication date and exclusive use of mammography images, and included only literature in English. After extracting data, results were compared and discussed. This review included 33 studies and identified four recurring categories of studies: the differentiation of benign and malignant masses, the localisation of masses, cancer‐containing and cancer‐free breast tissue differentiation and breast classification based on breast density. CNN's application in detecting malignancy in mammography appears promising but requires further standardised investigations before potentially becoming an integral part of the diagnostic routine in mammography., This article explores the current research and developments in using convolutional neural networks for mammography diagnosis. Current developments are focused on four distinct categories; however, limitations of this artificial intelligence withhold it from clinical implementation.

Silicon anodes are a key component for high-energy lithium-ion batteries (LIBs). Electrode binder engineering for Si anodes has been calling increasing awareness. Here, we report a series of molecu...

A new mitochondria-targeted fluorescent probe RBC, constructed using a coumarin moiety which was selected as the donor and a benzothiazole derivative as the acceptor, for SO2 derivatives (HSO3-/SO32-) was presented. The probe designed on a new FRET platform showed high selectivity and a low detection limit. Importantly, the probe could respond to HSO3-/SO32- within 35 s. Furthermore, the probe could target mitochondria and was successfully used for fluorescence imaging of endogenous bisulfite in HepG2 with low cytotoxicity, which significantly assisted in cancer diagnosis.

In order to reduce the fluctuations of traffic flow and the impacts of traffic flow fluctuations, thereby increasing the level of service of roads and constructing the Internet of Things-based traffic system, based on the various causes of traffic flow fluctuations, the countermeasures were taken, such as the optimization of lanes, the management of intersections, the improvement and perfection of slow-vehicle lanes and bus stops, the timely renewal of traffic signs and marks, the rational arrangements of road operations, and the removal of visual obstacles, etc. The research results showed that these countermeasures could effectively reduce the hidden peril of accidents and improve the road capacity, thereby improving the level of service of roads, which provided a theoretical foundation and basis for road engineering design and traffic management. It can be seen that improving urban traffic through rational management and control measures can effectively improve the level of service of urban traffic.

Graphene and hBN as two-dimensional materials with excellent optical properties can be combined with other materials. In this paper, graphene and hBN is sequentially deposited on the surface of the silicon-core fiber to serve as transverse magnetic (TM) or transverse electric (TE) mode polarizer alternatively depending on the input wavelength and the diameter of the silicon-core. The Gr/hBN stack structure on the surface silicon-core microfiber is used not only for enlarging the wavelength bandwidth, such as from 350 nm (TM) and 670 nm (TE) for double Gr/hBN stack to 300 nm (TM) and 550 nm (TE) for single Gr/hBN stack, but also enhancing the light-graphene interaction to multiply the polarization extinction ratio, as compared with that of monolayer graphene. Small radius silicon core could provide large light-graphene interaction for flat extinction ratio with different thickness of the hBN.

Sucrose phosphorylase (SPase) is capable of specifically catalysing transglucosylation reactions and can be employed in the enzymatic synthesis of α-D-glycosides. In the present study, a putative Thermobacillus SPase gene (TSPase) was synthesised with optimised codons and overexpressed in Escherichia coli. The 1467 bp gene encodes a 488-amino acid protein with a calculated molecular mass of 55.8 kDa. The specific activity of the recombinant TSPase (rTSPase) was 6.42 U/mg for sucrose, and the optimum temperature and pH were 65 °C and pH 7.0. The T1/2 value of the rTSPase was 212 h at 50 °C and 98 h at 60 °C. A stimulating effect on the activity of the rTSPase was observed in the presence of 5 mM Co2+. The rTSPase showed increased stability against DMSO as organic co-solvent at 50 °C. The Km and kcat of the rTSPase with sucrose were determined as 6.24 mM and 5.73 s−1 respectively. The rTSPase produced 2-O-α-D-Glucopyranosyl-L-ascorbic acid (AA-2 G) from ascorbic acid in both crude extract and whole-cell forms. A maximum yield of 19.7% (39.94 ± 0.17 g/L) was achieved after incubation of ascorbic acid sodium salt and sucrose (1:2) with 19.76 U/mL of the rTSPase at pH 7.0 and 50 °C for 24 h.

Our previous study revealed that Homeobox containing 1 (HMBOX1), essential for the survival of vascular endothelial cells (VECs), was involved in the progression of atherosclerosis. Knockdown of HMBOX1 promoted apoptosis and inhibited autophagy through regulating intracellular free zinc level in cultured VECs. In current study, in order to investigate the roles of HMBOX1 in vivo and in endothelium, we generated a knockout (KO) mouse for HMBOX1 by using transcription activator-like effector nucleases (TALENs) technology. Herein, we reported that the protein level of HMBOX1 was gradually increased during mouse development. The HMBOX1 KO mouse was viable and fertile. There existed no differences in apoptosis and autophagy of aortic endothelial cells between wild type and KO mouse. Whereas, loss of HMBOX1 promoted apoptosis and inhibited autophagy of aortic endothelial cells under lipopolysaccharide (LPS) stimulation in mouse. We also demonstrated that HMBOX1 deletion had no influence on the secretion of inflammatory cytokines TNF-α and IL-6. Moreover, overexpression or knockdown of HMBOX1 failed to regulate multiple pro-apoptotic genes expression in vitro. In conclusion, HMBOX1 participated in the functional maintenance of mouse aortic endothelial cells, the aortic endothelial cells of HMBOX1 KO mouse showed increased apoptosis and decreased autophagy with LPS treatment.

A coupled equivalent circuit for high-speed Si photodiodes is proposed, which is composed of a traditional resistance-capacitance-limited equivalent circuit and a carrier transit-limited equivalent circuit connected by a voltage controlled current source. All the resistances and capacitances in the carrier transit-limited equivalent circuit have physical meaning according to Laplace Transform. The proposed coupled equivalent circuit was applied to the Si p-i-n photodiodes and agreed well with the measured reflection coefficients and frequency response curves. Again, the minority carrier lifetime, diffusivity and interface state is verified to be the main limiting factors to the frequency response. This improved modeling can provide an effective way to design high speed photodiodes.

Anemia is associated with neurodevelopmental delays and brain injury in infants and toddlers, but whether early anemia has a similar effect in neonatal preterm infants is largely unknown. Thus, this study aimed to determine the relationship of early anemia with neurodevelopment and brain injury in very-low-birth-weight (VLBW) preterm infants within the neonatal period. A prospective cohort study including 110 VLBW preterm infants was conducted in Southern China from 2016 to 2018. All participants were followed from birth to 1 month corrected age. Early anemia is defined as hemoglobin of ≤145 g/L within the first week after birth. The non-anemic group (control group, N = 55) was 1:1 matched with the early anemia group (N = 55) according to birth weight and gestational age. Neurodevelopment at 1 month corrected age and brain injury within 1 month corrected age were measured by neonatal behavioral neurological assessments (NBNA) and cranial ultrasound, respectively. Compared to the control group, the early anemia group had a lower score in behavioral ability in the NBNA test [11 (10–12) vs. 10 (9.5–11), p = 0.033]. Early anemia was negatively associated with the NBNA total score (β= −0.680, 95% CI: −1.300, −0.059), especially with the behavioral ability score (β= −0.504, 95% CI: −0.941, −0.067) after adjusting for the confounders. However, no association between early anemia and brain injury was observed. In conclusion, in VLBW preterm infants, early anemia is negatively correlated with neurodevelopment, especially with behavioral ability.

Age-related cell loss underpins many senescence-associated diseases. Apoptosis of lens epithelial cells (LECs) is the important cellular basis of senile cataract resulted from prolonged exposure to oxidative stress, although the specific mechanisms remain elusive. Our data indicated the concomitance of high autophagy activity, low SQSTM1/p62 protein level and apoptosis in the same LEC from senile cataract patients. Meanwhile, in primary cultured LECs model, more durable autophagy activation and more obvious p62 degradation under oxidative stress were observed in LECs from elder healthy donors, compared with that from young healthy donors. Using autophagy-deficiency HLE-B3 cell line, autophagy adaptor p62 was identified as the critical scaffold protein sustaining the pro-survival signaling PKCι-IKK-NF-κB cascades, which antagonized the pro-apoptotic signaling. Moreover, the pharmacological inhibitor of autophagy, 3-MA, significantly inhibited p62 degradation and rescued oxidative stress-induced apoptosis in elder LECs. Collectively, this study demonstrated that durable activation of autophagy promoted age-related cell death in LECs. Our work contributes to better understanding the pathogenesis of senescence-associated diseases.