Role of Gut Microecology in the Pathogenesis of Drug-Induced Liver Injury and Emerging Therapeutic Strategies.

Drug-induced liver injury (DILI) is a common clinical pharmacogenic disease. In the United States and Europe, DILI is the most common cause of acute liver failure. Drugs can cause hepatic damage either directly through inherent hepatotoxic properties or indirectly by inducing oxidative stress, immune responses, and inflammatory processes. These pathways can culminate in hepatocyte necrosis. The role of the gut microecology in human health and diseases is well recognized. Recent studies have revealed that the imbalance in the gut microecology is closely related to the occurrence and development of DILI. The gut microecology plays an important role in liver injury caused by different drugs. Recent research has revealed significant changes in the composition, relative abundance, and distribution of gut microbiota in both patients and animal models with DILI. Imbalance in the gut microecology causes intestinal barrier destruction and microorganism translocation; the alteration in microbial metabolites may initiate or aggravate DILI, and regulation and control of intestinal microbiota can effectively mitigate drug-induced liver injury. In this paper, we provide an overview on the present knowledge of the mechanisms by which DILI occurs, the common drugs that cause DILI, the gut microbiota and gut barrier composition, and the effects of the gut microbiota and gut barrier on DILI, emphasizing the contribution of the gut microecology to DILI.

Restricted Recruitment of NK Cells with Impaired Function Is Caused by HPV-Driven Immunosuppressive Microenvironment of Papillomas in Aggressive Juvenile-Onset Recurrent Respiratory Papillomatosis Patients.

Laryngopharynx epithelium neoplasia induced by HPV6/11 infection in juvenile-onset recurrent respiratory papillomatosis (JO-RRP) causes a great health issue characteristic of frequent relapse and aggressive disease progression. Local cell-mediated immunity shaped by the recruitment and activation of cytotoxic effector cells is critical for viral clearance. In this study, we found that NK cells in the papillomas of aggressive JO-RRP patients, in contrast to massive infiltrated T cells, were scarce in number and impaired in activation and cytotoxicity as they were in peripheral blood. Data from cell infiltration analysis indicated that the migration of NK cell to papilloma was restricted in aggressive JO-RRP patients. Further study showed that the skewed chemokine expression in the papillomas and elevated ICAM-1 expression in hyperplastic epithelia cells favored the T cell but not NK cell recruitment in aggressive JO-RRP patients. In parallel to the increased CD3+ T cells, we observed a dramatical increase in Tregs and Treg-promoting cytokines such as IL-4, IL-10 and TGFß in papillomas of aggressive JO-RRP patients. Our study suggested that likely initialized by the intrinsic change in neoplastic epithelial cells with persistent HPV infection, the aggressive papillomas built an entry barrier for NK cell infiltration and formed an immunosuppressive clump to fend off the immune attack from intra-papillomas NK cells. IMPORTANCE Frequent relapse and aggressive disease progression of juvenile-onset recurrent respiratory papillomatosis (JO-RRP) pose a great challenge to the complete remission of HPV 6/11 related laryngeal neoplasia. Local immune responses in papillomas are more relevant to the disease control considering the locale infected restriction of HPV virus in epitheliums. In our study, the restricted NK cell number and reduced expression of activating NKp30 receptor suggested one possible mechanism underlying impaired NK cell defense ability in aggressive JO-RRP papillomas. Meanwhile, the negative impact of HPV persistent infection on NK cell number and function represented yet another example of a chronic pathogen subverting NK cell behavior, affirming a potentially important role for NK cells in viral containment. Further, the skewed chemokine/cytokine expression in the papillomas and the elevated adhesion molecules expression in hyperplastic epithelia cells provided important clues for understanding blocked infiltration and antiviral dysfunction of NK cells in papilloma.

Application an internet facilitation in a community-based cervical cancer screening project.

OBJECTIVE: To evaluate the feasibility of an internet-facilitated community model for cervical cancer screening using self-collected HPV testing as primary screening. METHOD: A population-based cervical cancer screening program was conducted in the suburb of Shenzhen, China, from September 2014 to July 2017. Women with 25-60 years of age and no pregnancy were eligible for participation. Participants could register for screening by logging in a website by themselves or with the aids of local community workers. A unique barcode was issued to each applicant upon successful registration. After registration, women could get sampling kits from community screening site/study clinic, collect vaginal samples privately or in group, and provide their sample for Hr-HPV tests on Cobas4800 and SeqHPV assays. Testing reports were checkable through personal account for all participant and phone calls were given to all women positive of Hr-HPV. Participants positive of both or either the 2 assays were identified as the positives. The positives could return the study clinic for triage or search medical care in other clinics. Colposcopy directed or ramdom biopsies were performed on all positives who returned to the study clinics. RESULTS: A total of 10,792 community women registered for screening, among whom, 10,010 provided their vaginal samples for tests. 99.5% of the participants were confirmed to have correct personal identifiable information and samples, and 98.9% of them got HPV testing results from both or either assays. No adverse event was reported. CONCLUSION: When self-collected HPV testing is used as the primary testing, the internet-based data platform facilitates the screening in registration, data collection, and data tracking, and increases the screening coverage. Internet-facilitated community model is promising to cervical cancer control and applicable in regions with variety of resources.

Impaired HPV-specific T-cell response in juvenile-onset recurrent respiratory papillomatosis patients.

Immunologic dysfunction is one of the most important mechanisms underlying the initiation and development of JORRP. The study aimed to explore whether HPV-specific T-cell response was impaired in JORRP patients. We found JORRP patients had a Th2-biased cytokine profile correlated with disease severity in peripheral system. JORRP patients had an increased memory T cells and a reduced naive T cells in circulation. Upon HPV6/11 antigens stimulation, T cells from JORRP patients exhibited a greater activation profile. Of note, JORRP patients presented with a greater number of IL-10- and IL-4-secreting HPV6/11 antigen responding cells than that of IFN-γ and TNF-α secreting responders. Furthermore, in response to HPV6/11 antigen stimulation, JORRP patients showed a reduced level of cell proliferation, an increased level of apoptosis and higher percentage of the differentiated T cells expressing the replicative senescent cell marker CD57. Impaired HPV-specific T-cell responses could be partly responsible for JORRP development.

Antifouling Strategies for Selective In Vitro and In Vivo Sensing.

The ability to fabricate sensory systems capable of highly selective operation in complex fluid will undoubtedly underpin key future developments in healthcare. However, the abundance of (bio)molecules in these samples can significantly impede performance at the transducing interface where nonspecific adsorption (fouling) can both block specific signal (reducing sensitivity) and greatly reduce assay specificity. Herein, we aim to provide a comprehensive review discussing concepts and recent advances in the construction of antifouling sensors that are, through the use of chemical, physical, or biological engineering, capable of operating in complex sample matrix (e.g., serum). We specifically highlight a range of molecular approaches to the construction of solid sensory interfaces (planar and nanoparticulate) and their characterization and performance in diverse in vitro and in vivo analyte (e.g., proteins, nucleic acids, cells, neuronal transmitters) detection applications via derived selective optical or electrochemical strategies. We specifically highlight those sensors that are capable of detection in complex media or those based on novel architectures/approaches. Finally, we provide perspectives on future developments in this rapidly evolving field.

Genome sequencing sheds light on the contribution of structural variants to Brassica oleracea diversification.

BACKGROUND: Brassica oleracea includes several morphologically diverse, economically important vegetable crops, such as the cauliflower and cabbage. However, genetic variants, especially large structural variants (SVs), that underlie the extreme morphological diversity of B. oleracea remain largely unexplored. RESULTS: Here we present high-quality chromosome-scale genome assemblies for two B. oleracea morphotypes, cauliflower and cabbage. Direct comparison of these two assemblies identifies ~ 120 K high-confidence SVs. Population analysis of 271 B. oleracea accessions using these SVs clearly separates different morphotypes, suggesting the association of SVs with B. oleracea intraspecific divergence. Genes affected by SVs selected between cauliflower and cabbage are enriched with functions related to response to stress and stimulus and meristem and flower development. Furthermore, genes affected by selected SVs and involved in the switch from vegetative to generative growth that defines curd initiation, inflorescence meristem proliferation for curd formation, maintenance and enlargement, are identified, providing insights into the regulatory network of curd development. CONCLUSIONS: This study reveals the important roles of SVs in diversification of different morphotypes of B. oleracea, and the newly assembled genomes and the SVs provide rich resources for future research and breeding.

Comparative Analysis of Environment-Responsive Alternative Splicing in the Inflorescences of Cultivated and Wild Tomato Species.

Cultivated tomato (Solanum lycopersicum) is bred for fruit production in optimized environments, in contrast to harsh environments where their ancestral relatives thrive. The process of domestication and breeding has profound impacts on the phenotypic plasticity of plant development and the stress response. Notably, the alternative splicing (AS) of precursor message RNA (pre-mRNA), which is one of the major factors contributing to transcriptome complexity, is responsive to developmental cues and environmental change. To determine a possible association between AS events and phenotypic plasticity, we investigated environment-responsive AS events in the inflorescences of cultivated tomato and its ancestral relatives S. pimpinellifolium. Despite that similar AS frequencies were detected in the cultivated tomato variety Moneymaker and two S. pimpinellifolium accessions under the same growth conditions, 528 genes including splicing factors showed differential splicing in the inflorescences of plants grown in open fields and plastic greenhouses in the Moneymaker variety. In contrast, the two S. pimpinellifolium accessions, LA1589 and LA1781, had 298 and 268 genes showing differential splicing, respectively. Moreover, seven heat responsive genes showed opposite expression patterns in response to changing growth conditions between Moneymaker and its ancestral relatives. Accordingly, there were eight differentially expressed splice variants from genes involved in heat response in Moneymaker. Our results reveal distinctive features of AS events in the inflorescences between cultivated tomato and its ancestral relatives, and show that AS regulation in response to environmental changes is genotype dependent.

Effect of Substituents on the Homopolymerization Activity of Methyl Alkyl Diallyl Ammonium Chloride.

Among nitrogen-containing cationic electrolytes, diallyl quaternary ammonium salt is a typical monomer with the highest positive charge density, which has attracted the most attention, especially in the research on homopolymers and copolymers of dimethyl diallyl ammonium chloride (DMDAAC), which occupy a very unique and important position. In order to improve the lipophilicity of substituted diallyl ammonium chloride monomers under the premise of high cationic charge density, the simplest, most direct, and most efficient structure design strategy was selected in this paper. Only one of the substituents on DMDAAC quaternary ammonium nitrogen was modified by alkyl; the substituents were propyl and amyl groups, and their corresponding monomers were methyl propyl diallyl ammonium chloride (MPDAAC) and methyl amyl diallyl ammonium chloride (MADAAC), respectively. The effect of substituent structure on the homopolymerization activity of methyl alkyl diallyl ammonium chloride was illustrated by quantum chemical calculation and homopolymerization rate determination experiments via ammonium persulfate (APS) as the initiator system. The results of quantum chemistry simulation showed that, with the finite increase in substituted alkyl chain length, the numerical values of the bond length and the charge distribution of methyl alkyl diallyl ammonium chloride monomer changed little, with the activation energy of the reactions in the following order: DMDAAC < MPDAAC < MADAAC. The polymerization activities measured by the dilatometer method were in the order DMDAAC > MPDAAC > MADAAC. The activation energies Ea of homopolymerization were 96.70 kJ/mol, 97.25 kJ/mol, and 100.23 kJ/mol, and the rate equation of homopolymerization of each monomer was obtained. After analyzing and comparing these results, it could be easily found that the electronic effect of substituent was not obvious, whereas the effect of the steric hindrance was dominant. The above studies have laid a good foundation for an understanding of the polymerization activity of methyl alkyl diallyl ammonium chloride monomers and the possibility of preparation and application of these polymers with high molecular weight.

Tim-3 is a potential regulator that inhibits monocyte inflammation in response to intermittent hypoxia in children with obstructive sleep apnea syndrome.

The mechanism of the characteristic intermittent hypoxia (IH) of obstructive sleep apnea syndrome (OSAS) on monocyte remain unclear. Our study found that OSAS children had a significantly upregulated expression in circulating proinflammatory cytokines IL-6 and IL-12, and endothelial injury markers VEGF and ICAM1. Association analysis revealed that the plasma TNFα, IL-1ß, IL-6, IL-10 and IL-12 concentration were negatively associated with the minimal SpO2, a negative index for disease severity. OSAS monocytes presented an inflammatory phenotype with higher mRNA levels of inflammatory cytokines. Importantly, we noted a significant decrease in T-cell immunoglobulin and mucin domain (Tim)-3 expression in OSAS monocytes with the increase of the plasma proinflammatory cytokines. In vitro assay demonstrated that IH induced THP-1 cell overactivation via NF-κB dependent pathway was inhibited by the Tim-3 signal. Our results indicated that activation of monocyte inflammatory responses is closely related to OSAS-induced IH, and negatively mediated by a Tim-3 signaling pathway.

Bovine Serum Albumin-Cross-Linked Polyaniline Nanowires for Ultralow Fouling and Highly Sensitive Electrochemical Protein Quantification in Human Serum Samples.

Biofouling represents a serious challenge for the assaying of disease markers with various biosensors in complex biological samples due to the accompanied nonspecific protein adsorption. Herein, a highly sensitive and antifouling biosensing interface was constructed based on a cost-effective inert protein bovine serum albumin (BSA) cross-linked with polyaniline nanowires (PANI-NWs). Compared with the physically adsorbed BSA that was commonly used to block nonspecific adsorption or binding of proteins, the cross-linked BSA exhibited a significantly enhanced antifouling capability. The BSA/PANI-NW-modified electrode interface possessed excellent antifouling capability and electrochemical activity owing to the presence of the cross-linked BSA and the conducting polymer polyaniline. With further immobilization of the peptide aptamer for immunoglobulin G (IgG) recognition onto the BSA/PANI-NW interface, an electrochemical biosensor with excellent selectivity and sensitivity was prepared. The IgG biosensor possessed a linear range from 1.0 ng mL-1 to 10 µg mL-1 and a low detection limit of 0.27 ng mL-1, and it was capable of assaying IgG in complex human serum samples with acceptable accuracy when compared with the assay results obtained using commercial enzyme-linked immunosorbent assay kits. It is expected that the unique BSA-cross-linked conducting polymers can be used for the construction of various electrochemical sensors and biosensors that can be applied in complex biological media.

Vocal cord paralysis following lithium button battery ingestion in children.

This study reports on vocal cord paralysis caused by esophageal button battery (BB) ingestion in children. Medical records of children with vocal cord paralysis and esophageal BB ingestion treated at a tertiary referral institute between January 2016 and March 2020 were reviewed. Five patients aged 9-58 months were identified; three were male. Each patient had accidentally swallowed a 20-mm-diameter lithium battery (3 CR2032 type and 2 CR2025 type). One battery was removed within 4 h after ingestion, and three batteries were removed within 12 h. Removal of the battery was achieved with rigid esophagoscopy in four patients and direct laryngoscopy in one patient. Four patients had bilateral, and one had unilateral vocal cord paralysis. Three patients underwent tracheotomy; two were tracheotomy-dependent until follow-up, while the third patient died of multiple organ dysfunction syndrome a month after surgery. The two cases without tracheotomy remain under close follow-up.Conclusion: Accidentally ingested button batteries should be removed promptly to avoid severe complications. Respiratory support and neurotrophic treatment in the early stage of vocal cord paralysis may be beneficial for recovery of vocal cord movement. What is Known: • Button battery ingestion in children is extremely harmful, especially when the diameter of the button battery exceeds 20 mm. • Esophageal button battery impaction can cause serious complications such as esophageal perforation, mediastinal infection, tracheoesophageal fistula, vocal cord paralysis, and life-threatening bleeding. What is New: • Vocal cord paralysis in children with button battery ingestion plays an early warning role for identifying the severity of the disease. • Early neurotrophic drugs and glucocorticoid therapy may be helpful for the recovery of vocal cord movement, thereby avoiding tracheotomy.

Psychological stress of university students in the hardest-hit areas at different stages of the COVID-19 epidemic.

BACKGROUND: The outbreak of COVID-19 has caused extremely many serious consequences for the country and the world. In fact, it has seriously affected people's mental health. The purpose of this study is to understand the psychological stress among college students in different stages of epidemics in hard-hit areas such as Hubei. Moreover, to highlight the factors that influencing, their psychological conditions with the emphasis of further corresponding suggestions. METHODS: This study includes self-designed questionnaires in order to assess and analyze the psychological state of over 17,000 college students during the outbreak period in January and home quarantine in February. The questionnaire contains three aspects and six dimensions: pressure responses: stress susceptibility (SS), stress adjustment (SA), risk cognition: cognition of danger (CD), cognition of illness (CI) and stress reactions: emotional responses (ER), somatic responses (SR). This survey was done by an online questionnaire (www.wjx.cn) to investigate the psychological stress information of college students, and analyzed the data by SPSS 22.0 for Windows. RESULTS: Regarding the stress susceptibility, participants were more likely stressed in February than in January. Regarding the stress adjustment, the number of participants requiring pressure regulation or release in the February survey was significantly lower than that the effective in the January survey. The mean of the cognition of danger reduced significantly in February than in January, in other words, participants were highly worried about the epidemic in January than in February. Regarding the cognition of illness, participants in January had a more pessimistic attitude towards the epidemic than those in February. The emotional responses of the participants in February were more severe than those in January, while the somatic responses reduced significantly in February compared with January. Furthermore, females have stronger stress reactions than males. However, the SR doesn't have significant differences between females and males. CONCLUSION: After two surveys in January and February, it was found that the psychological stress of college students in Hubei was significantly different at different stages of the epidemic, where the epidemic developed, the psychological stress of college students become more severe. The psychological stress of the college students in Hubei Province, as a severely affected area, should be paid more attention.

ChIP-cloning analysis uncovers centromere-specific retrotransposons in Brassica nigra and reveals their rapid diversification in Brassica allotetraploids.

Centromeres are indispensable functional units of chromosomes. The evolutionary mechanisms underlying the rapid evolution of centromeric repeats, especially those following polyploidy, remain unknown. In this study, we isolated centromeric sequences of Brassica nigra, a model diploid progenitor (B genome) of the allopolyploid species B. juncea (AB genome) and B. carinata (BC genome) by chromatin immunoprecipitation of nucleosomes containing the centromere-specific histone CENH3. Sequence analysis detected no centromeric satellite DNAs, and most B. nigra centromeric repeats were found to originate from Tyl/copia-class retrotransposons. In cytological analyses, six of the seven analyzed repeat clusters had no FISH signals in A or C genomes of the related diploid species B. rapa and B. oleracea. Notably, five repeat clusters had FISH signals in both A and B subgenomes in the tetraploid B. juncea. In the tetraploid B. carinata, only CL23 displayed three pairs of signals in terminal or interstitial regions of the C-derived chromosome, and no evidence of colonization of CLs onto C-subgenome centromeres was found in B. carinata. This observation suggests that centromeric repeats spread and proliferated between genomes after polyploidization. CL3 and CRB are likely ancient centromeric sequences arising prior to the divergence of diploid Brassica which have detected signals across the genus. And in allotetraploids B. juncea and B. carinata, the FISH signal intensity of CL3 and CRB differed among subgenomes. We discussed possible mechanisms for centromeric repeat divergence during Brassica speciation and polyploid evolution, thus providing insights into centromeric repeat establishment and targeting.

Electrochemical Biosensors Capable of Detecting Biomarkers in Human Serum with Unique Long-Term Antifouling Abilities Based on Designed Multifunctional Peptides.

An electrochemical sensing platform for biomarker detection in complex serum samples with unique long-term antifouling performance was constructed, based on newly designed multifunctional peptides containing anchoring, doping, linking, and antifouling sequences. The designed peptides were first attached onto an electrode surface with the assistance of the anchoring sequences, and the negatively charged doping sequences as dopants for conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) were then precisely doped into the electropolymerized PEDOT to form a conducting and stable substrate, leaving the linking and antifouling sequences exposed on the PEDOT substrate surface. The linking sequence of the peptide between the doping and antifouling parts was designed to be beneficial for enhancing the antifouling performance. After the biorecognizing probe immobilization, the obtained biosensor was able to detect targets with a low limit of detection of 2.3 fM and high specificity in complex biological fluids. More importantly, the electrochemical biosensor exhibited incomparable long-term antifouling performances over previous reports and retained their antifouling capabilities for 20 days, indicating a promising feasibility of this design strategy for the construction of biosensors and bioelectronics to be used or implanted in real biological systems.

Psychological stress of medical staffs during outbreak of COVID-19 and adjustment strategy.

COVID-19 has a significant impact on public health and poses a challenge to medical staffs, especially to front-line medical staffs who are exposed to and in direct contact with patients. To understand the psychological stress status of medical staffs during the outbreak of COVID-19, random sample questionnaire survey was conducted among 2110 medical staffs and 2158 college students in all provinces of China through a questionnaire, which was compiled and completed through the Questionnaire Star platform relying on Wechat, QQ, and other social software. The differences in psychological stress status of different groups were compared through the analysis of the questionnaire. Results revealed that in all provinces of China, medical staffs scored significantly higher on all items of psychological stress than college students (P < .001). In Wuhan, medical staffs scored significantly higher than college students in all items of psychological stress (P < .001). While among medical staffs, the group in Wuhan area scored significantly higher than the group outside Wuhan on the following items: "Thought of being in danger," "The possibility of self-illness," "Worrying about family infection" (P < .05), "Poor sleep quality," "Needing psychological guidance," and "Worrying about being infected" (P < .01) in the Psychological Stress Questionnaire, but on the item "Confidence in the victory of the epidemic," the group in Wuhan area scored significantly lower than the group outside Wuhan (P < .05). The emotion, cognition, physical, and mental response of front-line medical staff showed obvious "exposure effect", which calls for a psychological crisis intervention strategy that can be helpful.

Attractiveness-related recognition bias captures the memory of the beholder.

Earlier electroencephalographic studies have compared attractive and unattractive faces and between faces with other objects, such as flowers, without revealing if a recognition memory bias toward faces and flowers exists or whether humans exhibit enhanced specific components toward all attractive objects or only toward attractive faces. For objects with similar degrees of attractiveness, we sought to determine if the N170, P1, and N250 reflect upon the attractiveness of faces and flowers and demonstrated by comparing event-related potentials of humans' different perceptual mechanisms recognizing high attractive faces and high attractive flowers. The repeated high attractive faces tended to elicit a larger N170. Simultaneously, the P1 was preferentially associated with the repeated high attractive flowers, but both indicated that the repetitive enhancement effect only occurred on repeated attractive faces. Thus, differences existed in the perceptual mechanisms for processing repeated high attractive faces and repeated high attractive flowers. However, there was no significant difference in N250 between repeated faces and repeated flowers or between high attractive faces and high attractive flowers. Consequently, high attractive faces and high attractive flowers capture the beholder's memory bias in different processing stages. The N170 and P1 components are affected by attractiveness, thereby demonstrating the differences between human perceptual mechanisms in recognizing high attractive faces and objects.

Minimally invasive procedure for diagnosis and treatment of vallecular cysts in children: review of 156 cases.

PURPOSE: Vallecular cyst is an uncommon but potentially life-threatening disease. The aim of this study was to review the presentation, evaluation, and treatment of vallecular cysts in children. METHODS: Medical records of 156 patients treated for vallecular cysts between 2013 and 2016 were retrospectively reviewed. The patients were divided into four age groups for comparison of clinical data: A, < 1 month; B, 1-6 months; C, 7-12 months; and D, > 1 year. RESULTS: The median age of all patients (98 males and 58 females) was 12.1 months (range 1 day-11 years), including 21, 86, 21, and 28 patients in group A, B, C, and D, respectively. A diagnosis of vallecular cysts was made for 135 patients using a combination of flexible laryngoscopy and ultrasound, and ten patients (all in group A) required pre-surgery ventilation support. The most common symptoms were wheezing (59.6%) and stridor (36.5%). Ten patients experienced difficulty with intubation. Endoscopic-assisted transoral coblation marsupialization was performed for all patients, combined with supraglottoplasty for 41 out of 68 patients with concurrent laryngomalacia. Patients in group D had a longer operation time and higher incidence of intraoperative bleeding, two of whom experienced post-operation recurrence, and symptoms resolved after a second operation in both cases. CONCLUSIONS: Flexible laryngoscopy and ultrasound are recommended for a diagnosis in suspected cases of vallecular cysts. Coblation marsupialization has advantages of minor damage, low recurrence rate, and suitability for all age groups.

Identification and differential expression analysis of anthocyanin biosynthetic genes in leaf color variants of ornamental kale.

BACKGROUND: Anthocyanins perform diverse biological functions in plants and are beneficial to human health. Leaf color is the most important trait of ornamental kale and the characteristics of changes in leaf color make it an ideal material to elucidate genetic mechanisms of anthocyanins accumulation in Brassica oleracea. To elucidate the anthocyanin distribution, metabolic profiles and differentially expressed anthocyanin biosynthetic genes between different colored accessions can pave the way for understanding the genetic regulatory mechanisms of anthocyanin biosynthesis and accumulation in ornamental kale. RESULTS: In this study, anthocyanin distributions in red- and white-leaved ornamental kale accessions were determined. Thirty-four anthocyanins were detected in the red-leaved accession. The complete set of anthocyanin biosynthetic genes in the B. oleracea reference genome was identified and differential expression analysis based on RNA-seq was conducted. Eighty-one anthocyanin biosynthetic genes were identified in the B. oleracea reference genome. The expression patterns and differential expressions of these genes in different leaf types indicated that late biosynthetic genes (BoDFR1, BoANS1 and 2, and BoUGT79B1.1), positive regulatory genes (BoTTG1, BoTT8, and Bol012528), a negative regulatory gene (BoMYBL2.1), and transport genes (BoTT19.1 and BoTT19.2) may play roles in anthocyanin accumulation in ornamental kale. A genetic regulatory network of anthocyanin accumulation in ornamental kale was constructed. CONCLUSIONS: The distribution of pigments and anthocyanin profiles explained the leaf color phenotypes of ornamental kales. The identification of key genes and construction of genetic regulatory network in anthocyanin accumulation in ornamental kale elucidated the genetic basis of leaf color variants. These findings enhance the understanding of the genetic mechanisms and regulatory network of anthocyanin accumulation in B. oleracea, and provide a theoretical basis for breeding new cultivars of Brassica vegetables with enhanced ornamental and nutritional value.

Synthesis of two new gem-fluoronitro containing tetranitroadamantanes and property comparison with their nitro and gem-dinitro analogues.

Two new fluorinated tetranitroadamantanes, 2,6-difluoro-2,4,4,6-tetranitroadamantane and 2,4,6,8-tetrafluoro-2,4,6,8-tetranitroadamantane, were synthesized. 2,6-Difluoro-2,4,4,6-tetranitroadamantane was prepared from 4,4-dinitroadamantane-2,6-dione by a three-step route with an overall yield of 40%. It has a slightly higher crystal density (1.787 g cm-3) than its analogue 2,2,4,4,6,6-tetranitroadamantane (1.777 g cm-3). 2,4,6,8-Tetrafluoro-2,4,6,8-tetranitroadamantane was prepared from 4,8-dihydroxyadamantane-2,6-dione by an eight-step route with an overall yield of 8%. It is notable that the replacement of one nitro group in the gem-dinitro functionality with fluorine might slightly reduce the detonation performance but improve the density and inherent steric hindrance, which makes it possible to introduce more nitro functionalities on the adamantane backbone.