Synthesis and evaluation of catecholamine derivatives as amyloid-beta aggregation inhibitors.

Effectively inhibition of amyloid ß (Aß) aggregation is considered an important method for treatment of the Alzheimer's disease. Herein, inspired by the ability of trans-clovamide to effectively inhibit Aß aggregation, we synthesized a series of structurally related catecholamine derivatives and tested them as Aß aggregation inhibitors using the Thioflavin T assay. The results show that they demonstrated a higher inhibitory rate against Aß aggregation. Furthermore, these compounds exhibited high water solubilities and low cytotoxicities. Additionally, transmission electron microscopy images and dynamic light scattering of their Aß aggregations were observed. Docking simulations revealed that the catechol moiety of the synthesized compounds can form hydrogen bonds with the key regions of Aß and thereby inhibit Aß aggregation.

Addition of α-1,3-glucan-binding domains to α-1,3-glucanase Agn1p from　 Schizosaccharomyces pombe enhances hydrolytic activity of insoluble α-1,3-glucan.

The glycoside hydrolase (GH) 71 α-1,3-glucanase (Agn1p) from Schizosaccharomyces pombe consists of an N-terminal signal sequence and a catalytic domain. Meanwhile, the GH87 α-1,3-glucanase (Agl-KA) from Bacillus circulans KA-304 consists of an N-terminal signal sequence, a first discoidin domain (DS1), a carbohydrate-binding module family 6 (CBM6), a threonine and proline repeat linker (TP), a second discoidin domain (DS2), an uncharacterized domain, and a catalytic domain. DS1, CBM6, and DS2 exhibit α-1,3-glucan binding activity. This study involved genetically fusing TP, DS1, CBM6, TP, and DS2 to the C-terminus of Agn1p, generating the fusion enzyme Agn1p-DCD. The fusion enzyme was then expressed in Escherichia coli and purified from the cell-free extract. Agn1p-DCD and Agn1p exhibited similar characteristics, such as optimal pH, optimal temperature, pH stability, and thermostability. Insoluble α-1,3-glucan (1%) hydrolyzing assay showed that Agn1p-DCD and Agn1p released approximately 7.6 and 5.0 mM of reducing sugars, respectively, after 48 h of reaction. Kinetic analysis and an α-1,3-glucan binding assay indicated that the addition of DS1, CBM6, and DS2 enhanced the affinity of Agn1p for α-1,3-glucan. Moreover, Agn1p-DCD contributed to enhancing the fungal growth inhibition activity when combined with a mixture of GH19 chitinase and GH16 ß-1,3-glucanase.

CAZymes-associated method to explore glycans that mitigate DSS-induced colitis via targeting Bacteroides cellulosilyticus.

Improving Bacteroides cellulosilyticus abundance is a feasible approach to treating inflammatory bowel disease (IBD). Although B. cellulosilyticus is responsive to dietary components, untargeted manipulation cannot focus on target microbe and lead to an increase in harmful bacteria in the microbiota. Breakthroughs in methods for regulating specific microbes, but the protocols are expensive, time-consuming, and difficult to follow. Glycans based on microbial-carbohydrate-active enzymes (CAZymes) would provide a potential solution. We propose a method based on CAZymes to explore polysaccharides that target specific gut microbes and alleviate diseases. The designed polysaccharides (Arabinogalactan, AG) enrich the abundance of B. cellulosilyticus in single-strain co-cultures, fermentation in vitro, and mouse models in vivo. Supplementation with AG relieved mice from colitis and clinical symptoms. We reveal that AG directly alters B. cellulosilyticus level and cooperative microbes, resulting in remission of colitis. Our glycan design pipeline is a promising way to improve disease through the targeted enhancement of specific microbes.

Identification of circulating miRNA as early diagnostic molecular markers in malignant glioblastoma base on decision tree joint scoring algorithm.

PURPOSE: The lack of clinical markers prevents early diagnosis of glioblastoma (GBM). Many studies have found that circulating microRNAs (miRNAs) can be used as early diagnostic markers of malignant tumours. Therefore, the identification of novel circulating miRNA biomolecular markers could be beneficial to clinicians in the early diagnosis of GBM. METHODS: We developed a decision tree joint scoring algorithm (DTSA), systematically integrating significance analysis of microarray (SAM), Pearson hierarchical clustering, T test, Decision tree and Entropy weight score algorithm, to screen out circulating miRNA molecular markers with high sensitivity and accuracy for early diagnosis of GBM. RESULTS: DTSA was developed and applied for GBM datasets and three circulating miRNA molecular markers were identified, namely, hsa-miR-2278, hsa-miR-555 and hsa-miR-892b. We have found that hsa-miR-2278 and hsa-miR-892b regulate the GBM pathway through target genes, promoting the development of GBM and affecting the survival of patients. DTSA has better classification effect in all data sets than other classification algorithms, and identified miRNAs are better than existing markers of GBM. CONCLUSION: These results suggest that DTSA can effectively identify circulating miRNA, thus contributing to the early diagnosis and personalised treatment of GBM.

Cholecystectomy Significantly Alters Gut Microbiota Homeostasis and Metabolic Profiles: A Cross-Sectional Study.

Cholecystectomy (CCE) is a standard clinical treatment for conditions like gallstones and cholecystitis. However, its link to post-CCE syndrome, colorectal cancer, and nonalcoholic fatty liver disease has raised concerns. Additionally, studies have demonstrated the disruptive effects of CCE on gut microbiota homeostasis and bile acid (BA) metabolism. Considering the role of gut microbiota in regulating host metabolic and immune pathways, the use of dietary and probiotic intervention strategies to maintain a stable gut ecosystem after CCE could potentially reduce associated disease risks. Inter-study variations have made it challenging to identify consistent gut microbiota patterns after CCE, a prerequisite for targeted interventions. In this study, we first meta-analyzed 218 raw 16S rRNA gene sequencing datasets to determine consistent patterns of structural and functional changes in the gut microbiota after CCE. Our results revealed significant alterations in the gut microbiota's structure and function due to CCE. Furthermore, we identified characteristic gut microbiota changes associated with CCE by constructing a random model classifier. In the validation cohort, this classifier achieved an area under the receiver operating characteristic curve (AUC) of 0.713 and 0.683 when distinguishing between the microbiota of the CCE and healthy groups at the family and genus levels, respectively. Further, fecal metabolomics analysis demonstrated that CCE also substantially modified the metabolic profile, including decreased fecal short-chain fatty acid levels and disrupted BA metabolism. Importantly, dietary patterns, particularly excessive fat and total energy intake, influenced gut microbiota and metabolic profile changes post-CCE. These dietary habits were associated with further enrichment of the microbiota related to BA metabolism and increased levels of intestinal inflammation after CCE. In conclusion, our study identified specific alterations in gut microbiota homeostasis and metabolic profiles associated with CCE. It also revealed a potential link between dietary patterns and gut microbiota changes following CCE. Our study provides a theoretical basis for modulating gut microbiota homeostasis after CCE using long-term dietary strategies and probiotic interventions.

A High-Fat, High-Cholesterol Diet Promotes Intestinal Inflammation by Exacerbating Gut Microbiome Dysbiosis and Bile Acid Disorders in Cholecystectomy.

Patients with post-cholecystectomy (PC) often experience adverse gastrointestinal conditions, such as PC syndrome, colorectal cancer (CRC), and non-alcoholic fatty liver disease (NAFLD), that accumulate over time. An epidemiological survey further revealed that the risk of cholecystectomy is associated with high-fat and high-cholesterol (HFHC) dietary intake. Mounting evidence suggests that cholecystectomy is associated with disrupted gut microbial homeostasis and dysregulated bile acids (BAs) metabolism. However, the effect of an HFHC diet on gastrointestinal complications after cholecystectomy has not been elucidated. Here, we aimed to investigate the effect of an HFHC diet after cholecystectomy on the gut microbiota-BA metabolic axis and elucidate the association between this alteration and the development of intestinal inflammation. In this study, a mice cholecystectomy model was established, and the levels of IL-Iß, TNF-α, and IL-6 in the colon were increased in mice fed an HFHC diet for 6 weeks. Analysis of fecal BA metabolism showed that an HFHC diet after cholecystectomy altered the rhythm of the BA metabolism by upregulating liver CPY7A1, CYP8B1, and BSEP and ileal ASBT mRNA expression levels, resulting in increased fecal BA levels. In addition, feeding an HFHC diet after cholecystectomy caused a significant dysbiosis of the gut microbiota, which was characterized by the enrichment of the metabolic microbiota involved in BAs; the abundance of pro-inflammatory gut microbiota and related pro-inflammatory metabolite levels was also significantly higher. In contrast, the abundance of major short-chain fatty acid (SCFA)-producing bacteria significantly decreased. Overall, our study suggests that an HFHC diet after cholecystectomy promotes intestinal inflammation by exacerbating the gut microbiome and BA metabolism dysbiosis in cholecystectomy. Our study also provides useful insights into the maintenance of intestinal health after cholecystectomy through dietary or probiotic intervention strategies.

Meta-analysis reveals gut microbiome and functional pathway alterations in response to resistant starch.

Resistant starch (RS) has the ability to improve the structure of the gut microbiota, regulate glucolipid metabolism and maintain the health of the human body, and has been extensively studied by many scholars in recent years. However, previous studies have provided a wide range of results on the differences in the gut microbiota after RS intake. In this article, we performed a meta-analysis of a total of 955 samples of 248 individuals from the seven studies included to compare the gut microbiota of the baseline and the end-point of RS intake. At the end-point, RS intake was related to a lower gut microbial α-diversity and higher relative abundance of Ruminococcus, Agathobacter, Faecalibacterium and Bifidobacterium, and the functional pathways of the gut microbiota related to the carbohydrate metabolism, lipid metabolism, amino acid metabolism and genetic information processing were higher. Different types of resistant starch and different populations led to varied responses on the gut microbiome. The altered gut microbiome may contribute to improve the blood glucose level and insulin resistance, which may be a potential treatment route for diabetes, obesity and other metabolic diseases.

Effect of psychotropics on the risk of COVID-19 in middle-aged and older adults.

Older adults have been markedly impacted by the coronavirus disease 19 (COVID-19) pandemic, and many reports have cited concerns regarding potential psychiatric sequelae of coronavirus disease (COVID-19), but the actual effects of psychotropics on the COVID-19 are unclear. In this study, multivariate logistic regression was used to evaluate associations between the prescription of psychotropics and the risk of SARS-CoV-2 infection, and COVID-19-related death among the participants who were tested for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) before October 18, 2021, in UK Biobank. The psychotropics included 18 types of medications. Among 168,173 participants who underwent testing for SARS-CoV-2 RNA, 30,577 (18.2%) were positive, and 14,284 (8.5%) participants used psychotropics. Among 30,577 participants who were infected with SARS-CoV-2, 1,181 (3.9%) were COVID-19-related deaths, and 2,542 (8.3%) participants used psychotropics. In multivariate logistic regression, psychotropics use was significantly associated with the risk of SARS-CoV-2 infection (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.88-0.98), and COVID-19-related death (OR, 0.78; 95% CI, 0.64-0.98). Interestingly, the use of diazepam was significantly associated with a 31% lower risk of SARS-CoV-2 infection (OR, 0.69; 95% CI, 0.53-0.88). The use of sertraline was significantly associated with a 89% lower risk of COVID-19-related death (OR, 0.11; 95% CI, 0.02-0.39). In conclusion, our findings suggested that the use of psychotropics was associated with a lower risk of SARS-CoV-2 infection and COVID-19-related deaths.

A nucleotide signature for the identification of Pinelliae Rhizoma (Banxia) and its products.

BACKGROUND: Ensuring the authenticity of raw materials is a key step prior to producing Chinese patent medicines. Pinellia ternata (Thunb.) Breit. is the botanical origin of Pinelliae Rhizoma (Banxia), a traditional Chinese medicine used to treat cough, insomnia, nausea, inflammation, epilepsy, and so on. Unfortunately, authentic Pinelliae Rhizoma is often adulterated by morphologically indistinguishable plant material due to the insufficient regulatory procedures of processed medicinal plant products. Thus, it is important to develop a molecular assay based on species-specific nucleotide signatures and primers to efficiently distinguish authentic Pinelliae Rhizoma from its adulterants. METHODS AND RESULTS: The ITS2 region of 67 Pinelliae Rhizoma and its common adulterants were sequenced. Eight single nucleotide polymorphisms within a 28-43 bp stretch of ITS2 were used to develop six primer pairs to amplify these species-specific regions. We assayed 56 Pinelliae Rhizoma products sold on the Chinese market, including medicinal slices, powder and Chinese patent medicines, which revealed that about 66% of products were adulterated. The most common adulterants were Pinellia pedatisecta (found in 57% of the assayed products), Arisaema erubescens (9%), Typhonium giganteum (2%) and Typhonium flagelliforme (2%). CONCLUSIONS: A severe adulteration condition was revealed in the traditional medicine market. The species-specific nucleotide assays developed in this study can be applied to reliably identify Pinelliae Rhizoma and its adulterants, aiding in the authentication and quality control of processed products on the herbal market.

Design, synthesis, and evaluation of the self-assembled antimicrobial peptides based on the ovalbumin-derived peptide TK913.

The preparation, self-assembly, and antimicrobial activity of peptides based on TK913 is described. TK9Z4 incorporating a Pro-Pro motif exhibited self-assembly but no cytotoxicity. However, peptide TKZ3 (obtained by changing the amino acid sequence of TK9Z4) showed morphological changes at different concentrations, potent antimicrobial activity, low cytotoxicity, and trypsin resistance. Accordingly, TKZ3 is proposed as new AMP derived from ovalbumin-derived peptides.

Association of comprehensive mental health with incident cardiovascular disease: A prospective cohort study.

BACKGROUND: Evidence is limited regarding the impact of comprehensive mental health on the risk of subsequent cardiovascular events. OBJECTIVES: To investigate the association of mental health status with cardiovascular disease (CVD) in the UK Biobank. METHODS: This prospective study included 339,616 participants aged 40 to 69 years who were enrolled between 2006 and 2010 and were followed up to 2020, without CVD at baseline. A mental health score was created using information about depressive symptoms, anxiety, loneliness, and neuroticism. Cardiovascular disease events ascertained through hospital inpatient. Cox models were used to estimate hazard ratios and 95% confidence intervals across mental health score. RESULTS: During a median follow-up of 11.3 years (3.7 million person-years), we documented 22,688 CVD cases including 18,460 CHD cases and 5,070 stroke cases (some individuals were diagnosed as having both CHD and stroke). A statistically significantly increased risk of incident CVD was observed for the four mental factors individually, with adjusted hazard ratios ranging from 1.03 to 1.44. The composite score of such four mental factors was also positively associated with CVD risk in a dose-response manner, with the highest scores associated with a 1.56-fold (95% confidence interval 1.47 to 1.65), 1.61-fold (1.51 to 1.72), and 1.44-fold (1.25 to 1.67) higher CVD, CHD, and stroke risk, respectively. CONCLUSIONS: In this large prospective study, poor mental health status was associated with an increased risk of CVD. Our results highlight the importance to jointly investigate the mental health factors in relation to the risk of CVD.

Sex Differences in Association Between Anti-Hypertensive Medications and Risk of COVID-19 in Middle-Aged and Older Adults.

BACKGROUND: There is ongoing debate about the associations between drug therapies targeting the renin-angiotensin-aldosterone system (RAAS) and adverse outcomes in coronavirus disease 2019 (COVID-19). OBJECTIVE: This study aims to examine the associations between using medications for the cardiovascular system and the risks associated with COVID-19 in middle-aged and older adults. METHODS: A total of 77,221 participants (aged 50-86 years) from UK Biobank were tested for SARS-CoV-2 RNA. The medications included angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), ß-blockers, calcium channel blockers (CCB), statins, and aspirin. COVID-19 outcomes comprised a positive test result and severity of COVID-19 (defined as mild, hospitalization or death). We evaluated the risk among total participants and for sub-groups based on sex. Propensity score matching was performed 1:1 and logistic regression models were used. RESULTS: Among the middle- and older aged participants, no significant associations between any class of medications and the likelihood of COVID-19 infection were observed. ACEI were associated with a higher mortality risk from COVID-19 (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01-1.32) and CCB were associated with a lower hospitalization risk for COVID-19 (OR 0.87, 95% CI 0.79-0.96) among the male patients with COVID-19, while a lower mortality risk from COVID-19 (OR 0.67, 95% CI 0.47-0.96) was observed with ARB among the female patients with COVID-19. CONCLUSIONS: The study suggested sex differences in the risk of death from COVID-19 with the use of ACEI and ARB among middle-aged and older adults. Sex differences in the risk of hospitalization for COVID-19 with the use of CCB was observed as well. It is of clinical importance that clinicians adopt different CVD treatment approaches for female and male patients with COVID-19.

Associations of sleep duration and quality with incident cardiovascular disease, cancer, and mortality: a prospective cohort study of 407,500 UK biobank participants.

OBJECTIVE: Few studies have investigated the associations of sleep duration and sleep quality with incident cardiovascular diseases (CVDs), cancer, and mortality in the same large population. This study aimed at estimating the independent risk factors of long or short sleep durations and several typical characteristics of poor sleep quality for incident CVDs, cancer, and mortality. METHODS: In this prospective cohort study, 407 500 individuals were enrolled. Cox proportional hazards models were used to calculate the adjusted hazard ratios and 95% confidence intervals (HR, 95%CI) of associations of sleep duration and quality with incident CVDs, cancer, and mortality. RESULTS: Compared with the sleep duration of 7 h, sleep duration of ≤5 h and ≥9 h were both associated with higher risk of all-cause mortality (HR = 1.25, 95% CI: 1.16-1.34 and HR = 1.30, 95% CI: 1.22-1.38, respectively), CVD mortality (HR = 1.27, 95% CI: 1.09-1.49 and HR = 1.32, 95% CI: 1.16-1.50, respectively), and CVD incidence (HR = 1.23, 95% CI: 1.16-1.31 and HR = 1.08, 95% CI: 1.02-1.15, respectively). Additionally, long sleep duration (≥9 h) was associated with a higher risk of cancer mortality (HR = 1.19, 95% CI: 1.10-1.30) and cancer incidence (HR = 1.08, 95% CI: 1.04-1.12). Moreover, CVD incidence was significantly associated with snoring, insomnia and narcolepsy, increasing the risk by 7%, 26%, and 20%, respectively. CONCLUSION: Long sleep durations may substantially increase the risk of mortality and morbidity. Snoring, insomnia, and narcolepsy were independent risk factors for incident CVD.

Metabolic Healthy Obesity, Vitamin D Status, and Risk of COVID-19.

Aging and obesity-related conditions seem to worsen the effect of Coronavirus Disease 2019 (COVID-19). This study assessed the possible roles of metabolic/obesity phenotypes and vitamin D status in increasing the greater severity of COVID-19. We studied 353,299 UK Biobank participants from England with a mean age of 67.7 years. Metabolic/obesity phenotypes were defined as a combination of metabolic components (hypertension, high cholesterol, and diabetes) and obesity. Multivariate logistic regression analysis was performed to test whether the addition of metabolic disorders and vitamin D insufficiency increased obesity associations with COVID-19 hospitalization, confirmed COVID-19, and severe COVID-19. Metabolically unhealthy obesity (MUHO) represented 12.3% of the total analytic samples, and 21.5%, 18.5%, and 19.8% of the included subpopulations with COVID-19 hospitalization, confirmed COVID-19, and severe COVID-19, respectively. Vitamin D insufficiency phenotypes represented 53.5% of the total analytic samples, and 59.5%, 61.7%, and 61.5% of the included subpopulations with COVID-19 hospitalization, confirmed COVID-19, and severe COVID-19, respectively. In multivariate logistic regression, MUHO and vitamin D insufficiency and their combination were significantly associated with COVID-19 illness severity (odds ratio [OR] for COVID-19 hospitalization = 2.33, 95% confidence interval [CI], 2.02-2.70; OR for confirmed COVID-19 = 2.06, 95% CI, 1.58-2.70; OR for severe COVID-19 = 2.06, 95% CI, 1.47-2.87). Elderly men were prone to have a higher risk of COVID-19 than women. Our findings showed that MUHO and vitamin D insufficiency are associated with a significantly increased risk of COVID-19 severity, especially for adults 65 years and older. Susceptible individuals should be aware of their conditions and avoid contact with new coronavirus.

Associations of BMI and Serum Urate with Developing Dementia: A Prospective Cohort Study.

CONTEXT: Recent studies have suggested that a higher body mass index (BMI) and serum urate levels were associated with a lower risk of developing dementia. However, these reverse relationships remain controversial, and whether serum urate and BMI confound each other is not well established. OBJECTIVES: To investigate the independent associations of BMI and urate, as well as their interaction with the risk of developing dementia. DESIGN AND SETTINGS: We analyzed a cohort of 502 528 individuals derived from the UK Biobank that included people aged 37-73 years for whom BMI and urate were recorded between 2006 and 2010. Dementia was ascertained at follow-up using electronic health records. RESULTS: During a median of 8.1 years of follow-up, a total of 2138 participants developed dementia. People who were underweight had an increased risk of dementia (hazard ratio [HR] = 1.91, 95% confidence interval [CI]: 1.24-2.97) compared with people of a healthy weight. However, the risk of dementia continued to fall as weight increased, as those who were overweight and obese were 19% (HR = 0.81, 95%: 0.73-0.90) and 22% (HR = 0.78, 95% CI: 0.68-0.88) were less likely to develop dementia than people of a healthy weight. People in the highest quintile of urate were also associated with a 25% (HR = 0.75, 95% CI: 0.64-0.87) reduction in the risk of developing dementia compared with those who were in the lowest quintile. There was a significant multiplicative interaction between BMI and urate in relation to dementia (P for interaction = 0.004), and obesity strengthens the protective effect of serum urate on the risk of dementia. CONCLUSION: Both BMI and urate are independent predictors of dementia, and there are inverse monotonic and dose-response associations of BMI and urate with dementia.

Association of obesity status and metabolic syndrome with site-specific cancers: a population-based cohort study.

BACKGROUND: Obesity and metabolic syndrome (MetS) appear in clusters and are both associated with an increased risk of cancer. However, it remains unknown whether obesity status with or without MetS increases the risk of site-specific cancers. METHODS: We used data derived from 390,575 individuals (37-73 years old) from the UK Biobank who were enrolled from 2006-2016 with a median of 7.8 years of follow-up. Obesity was defined by BMI ≥ 30 kg/m2 and MetS was defined by the criteria of the Adult Treatment Panel-III (ATP-III). Cox proportional hazards models were used to investigate the associations of BMI and MetS with 22 cancers. RESULTS: Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) phenotypes represented 6.7% and 17.9% of the total analytic samples and 27.1% and 72.9% of the included subpopulation with obesity, respectively. Obesity was independently associated with higher risks of 10 of 22 cancers. Stratified by metabolic status, the MUO phenotype was consistently associated with 10 obesity-related cancers. In contrast, the MHO phenotype was only associated with increased risks of five cancers: endometrium, oesophagus, kidney, pancreas and postmenopausal breast cancers. CONCLUSION: Even in metabolically healthy individuals, obesity was associated with increased risks of five cancers, whereas we did not find that these individuals were associated with increased risks of several other obesity-related cancers.

Complete chloroplast genome sequence determination of Rheum species and comparative chloroplast genomics for the members of Rumiceae.

KEY MESSAGE: Complete plastomes of Rheum species facilitated to clarify the phylogeny of Polygonaceae, and comparative chloroplast genomics contributed to develop genetic markers for the authentication of Rheum species. Rheum (Polygonaceae) is widely distributed throughout the temperate and subtropical areas of Asian interior. Rheum species are usually perennial herbs, and half of them are endemic to China with important medicinal properties. On account of similar morphological characteristics, species delimitation of Rheum still remains unclear. Chloroplast genomes of eight Rheum species, Rumex crispus and Oxyria digyna were characterized. Based on the comparison of genome structure of these species and the two published Rheum species, it is shown that plastome sequences of these species are relatively conserved with the same gene order, and three Sect. Palmata species remarkably showed high sequence similarities. Some hotspots could be used to discriminate the Rheum species, and 17 plastid genes were subject to positive selection. The phylogenetic analyses indicated that all the Polygonaceae species were clustered in the same group and showed that Rheum species, except for Rheum wittrockii, formed a monophyletic group with high maximum parsimony/maximum likelihood bootstrap support values and Bayesian posterior probabilities. The molecular dating based on plastomes indicated that the divergences within Polygonaceae species were dated to the Upper Cretaceous period [73.86-77.99 million years ago (Ma)]. The divergence of Sect. Palmata species was estimated to have occurred around 1.60 Ma, indicating that its diversification was affected by the repeated climatic fluctuation in the Quaternary.

The Complete Chloroplast Genome of Euphrasia regelii, Pseudogenization of ndh Genes and the Phylogenetic Relationships Within Orobanchaceae.

Euphrasia (Orobanchaceae) is a genus which is widely distributed in temperate regions of the southern and northern hemisphere. The taxonomy of Euphrasia is still controversial due to the similarity of morphological characters and a lack of genomic resources. Here, we present the first complete chloroplast (cp) genome of this taxonomically challenging genus. The cp genome of Euphrasia regelii consists of 153,026 bp, including a large single-copy region (83,893 bp), a small single-copy region (15,801 bp) and two inverted repeats (26,666 bp). There are 105 unique genes, including 71 protein-coding genes, 30 tRNA and 4 rRNA genes. Although the structure and gene order is comparable to the one in other angiosperm cp genomes, genes encoding the NAD(P)H dehydrogenase complex are widely pseudogenized due to mutations resulting in frameshifts, and stop codon positions. We detected 36 dispersed repeats, 7 tandem repeats and 65 simple sequence repeat loci in the E. regelii plastome. Comparative analyses indicated that the cp genome of E. regelii is more conserved compared to other hemiparasitic taxa in the Pedicularideae and Buchnereae. No structural rearrangements or loss of genes were detected. Our analyses suggested that three genes (clpP, ycf2 and rps14) were under positive selection and other genes under purifying selection. Phylogenetic analysis of monophyletic Orobanchaceae based on 45 plastomes indicated a close relationship between E. regelii and Neobartsia inaequalis. In addition, autotrophic lineages occupied the earliest diverging branches in our phylogeny, suggesting that autotrophy is the ancestral trait in this parasitic family.

Heterogeneous Prolinamide-Catalyzed Atom-Economical Synthesis of ß-Thioketones from Bio-Based Enones.

Sulfur-containing compounds are a class of important motifs extensively applied in pharmaceutical and pesticidal industries as well as in electrochemistry, toxicant separation, and organic syntheses. Herein, we describe a novel and efficient metal-free catalytic strategy for the rapid synthesis of ß-thioketones from sustainable enone derivatives and thiols via thia-Michael addition enabled by heterogeneous prolinamide. At room temperature, up to 98% yield of ß-thioketones could be obtained over the solid UiO-66-NH-proline catalyst facilely prepared by the covalent immobilization of proline onto UiO-66-NH2 (a well-known metal-organic framework) via a stable amido linkage. A cooperative effect of proline (amino group) and UiO-66-NH2 (in situ-derived amide species) was observed to play a promotional role in the proceeding of thia-Michael addition, resulting in a high TOF value of 1124.3 h-1. A three-component "iminium" intermediate was illustrated to the key species approaching the product ß-thioketone. Moreover, the UiO-66-NH-proline could be easily recovered from the reaction mixture and recycled for at least five times with a slight loss of activity.