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Abstract Background The development of alternative carbon sources is important for reducing the cost of heterotrophic microalgae cultivation. Among cheap feedstocks, galactose is one of the most abundant sugars and can be easily obtained from many natural biomasses. However, it is generally difficult to be utilized by microalgae. In addition, the mechanism of its low utilization efficiency in heterotrophic cultivation is still unknown. Results Among seven tested carbon sources, only glucose and acetate could be efficiently utilized by C. sorokiniana in heterotrophic cultivation while there were no apparent signs of utilization of other carbohydrates, including galactose, in regular heterotrophic cultivation. However, galactose could be utilized in cultures with high inoculation sizes. This confirmed that C. sorokiniana has a complete pathway for transporting and assimilating galactose under dark conditions, but the rate of galactose utilization is quite low. In addition, the galactose utilization was greatly enhanced in mixotrophic cultures, which indicated that galactose utilization could be enhanced by additional pathways that can enhance cell growth. Based on above results, a mixed carbon source culture strategy was proposed to improve the utilization rate of galactose, and a significant synergistic effect on cell growth was achieved in cultures using a mixture of galactose and acetate. Conclusions This study indicated that the galactose metabolism pathway may not be inherently deficient in Chlorophyta. However, its utilization rate was too low to be detected in regular heterotrophic cultivation. Mixed carbon source culture strategy was confirmed effective to improve the utilization rate of galactose. This study contributes to a deeper understanding of the utilization ability of difficultly utilized substrates in the heterotrophic cultivation of microalgae, which is of great significance for reducing the cost of heterotrophic cultivation of microalgae.

Abstract Background The growth and development of organism were dependent on the effect of genetic, environment, and their interaction. In recent decades, lots of candidate additive genetic markers and genes had been detected by using genome-widely association study (GWAS). However, restricted to computing power and practical tool, the interactive effect of markers and genes were not revealed clearly. And utilization of these interactive markers is difficult in the breeding and prediction, such as genome selection (GS). Results Through the Power-FDR curve, the GbyE algorithm can detect more significant genetic loci at different levels of genetic correlation and heritability, especially at low heritability levels. The additive effect of GbyE exhibits high significance on certain chromosomes, while the interactive effect detects more significant sites on other chromosomes, which were not detected in the first two parts. In prediction accuracy testing, in most cases of heritability and genetic correlation, the majority of prediction accuracy of GbyE is significantly higher than that of the mean method, regardless of whether the rrBLUP model or BGLR model is used for statistics. The GbyE algorithm improves the prediction accuracy of the three Bayesian models BRR, BayesA, and BayesLASSO using information from genetic by environmental interaction (G × E) and increases the prediction accuracy by 9.4%, 9.1%, and 11%, respectively, relative to the Mean value method. The GbyE algorithm is significantly superior to the mean method in the absence of a single environment, regardless of the combination of heritability and genetic correlation, especially in the case of high genetic correlation and heritability. Conclusions Therefore, this study constructed a new genotype design model program (GbyE) for GWAS and GS using Kronecker product. which was able to clearly estimate the additive and interactive effects separately. The results showed that GbyE can provide higher statistical power for the GWAS and more prediction accuracy of the GS models. In addition, GbyE gives varying degrees of improvement of prediction accuracy in three Bayesian models (BRR, BayesA, and BayesCpi). Whatever the phenotype were missed in the single environment or multiple environments, the GbyE also makes better prediction for inference population set. This study helps us understand the interactive relationship between genomic and environment in the complex traits. The GbyE source code is available at the GitHub website ( https://github.com/liu-xinrui/GbyE ).

Abstract Aim To analyze the changes of chronotypes in patients with depression before and after treatment, and explore the effects of different chronotypes on antidepressant treatment and the dimensions of common symptoms in patients with depression. Methods 180 patients with depression were selected from 10 tertiary psychiatric hospitals in Zhejiang province, according to the scores of morningness-eveningness questionnaire (MEQ), the patients were divided into three groups: early-type group, middle-type group and late-type group. The 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale anxiety Scale (HAMA), Snaith Hamilton Pleasure Scale (SHAPS), multidimensional fatigue inventory-20(MFI-20) and Pittsburgh sleep quality index (PSQI) were measured at baseline and at the end of the 2nd, 4th, 8th and 12th weeks, the variance analysis of repeated measures was used to analyze the change of each index in the study. The remission rate of depression at each time point was statistically analyzed. Results Of the 180 patients included in the study, 26 were lost to follow-up, and 154 were finally included in the analysis. At baseline, 14.93%, 56.5% and 28.57% of the subjects were diagnosed as middle-late type, middle-late type and early-late type respectively, the total scores of Shaps and MFI-20 in the early-type group were higher than those in the late-type group and the middle-type group (p 0.05) . Conclusion The disorder of chronotypes is common in patients with depression. The time effect of different time type on different symptom dimension of depression was affected, but the effect on remission rate of depression was not significant. To strengthen the management of biological chronotype rhythm in patients with depression may be of great significance in the treatment of depression.

Abstract Background Synchronization of follicles is key to improving ovulation stimulation with the gonadotropin-releasing hormone (GnRH) antagonist protocol. GnRH antagonist administration in the early follicular phase can quickly decrease gonadotrophin (Gn) levels and achieve downregulation before stimulation, which may improves synchronization. A previous small randomized controlled study (RCT) showed that pretreatment with a GnRH antagonist for 3 days before stimulation may increase oocyte retrieval but cannot increase the pregnancy rate. This study investigated whether the GnRH antagonist pretreatment protocol in ovulatory women can increase the synchronization of follicles and pregnancy outcomes compared with the conventional GnRH antagonist protocol. Methods This RCT included 136 normal ovulatory women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Both groups were treated with recombinant follicle-stimulating hormone (r-FSH) and a flexible GnRH antagonist protocol. The women were randomized into two equal groups with or without GnRH antagonist administration from day 2 of the menstrual cycle for 3 days before stimulation. Our primary outcome was the number of retrieved oocytes. Secondary outcomes included the pregnancy rate and live birth rate. Results Both groups had similar baseline characteristics. The number of retrieved oocytes in the study group was comparable to that in the control group (9.5 [8.0–13.0] vs. 11.0 [7.0–14.8], P = 0.469). There was no significant difference in the follicle size. The fertilization rate, number of good-quality embryos, implantation rate, pregnancy rate, ongoing pregnancy rate, live birth rate per embryonic transfer cycle, and miscarriage rate were similar between the two groups. Conclusion This large RCT analysed GnRH antagonist pretreatment with the GnRH antagonist protocol applied to normal ovulatory women undergoing IVF/ICSI. The number of retrieved oocytes and pregnancy outcomes did not significantly vary. Trial registration Chinese Clinical Trial Registry, ChiCTR1800019730 . Registered 26 November 2018.

Abstract Background Obsessive–compulsive and related disorders (OCRDs) are a group of intractable and chronic mental disorders. Trichotillomania (TTM) is a common type of OCRDs characterized by repetitive hair pulling, driven by escalating tension before the action and during the attempts to resist it. Binge eating disorder (BED) is a common type of eating disorder characterized by recurrent compulsive episodes of binge eating. Both have common psychological processes (tension or impulsion) and pathological manifestations (out of control), but the pathological mechanisms are still unclear and the current clinical treatments are often unsatisfactory for these two disorders. Case presentation A 25-year-old woman with TTM comorbid BED came to our hospital for treatment. She had accepted systematic cognitive behavioral therapy (CBT) and also monotherapy or multidrug therapy with sertraline, fluvoxamine, bupropion, risperidone in full dosage and duration for 2 years, but all of them did not work. We treated this case with N-acetylcysteine (NAC) as a synergist on the basis of recent treatment (fluvoxamine 150 mg/day and bupropion 300 mg/day). The pathological hair plucking behavior and binge eating symptoms were both significantly and rapidly improved, and the follow-up in next 14 weeks showed that the effect was still maintained. Conclusion To our knowledge, this may be the first case report of using NAC as a synergist to treat TTM comorbid BED successfully, which suggest that these two disorders may have a common pathophysiological mechanism. Moreover, NAC can be one choice as a synergistic treatment for OCRDs.