Tea is the world's oldest and most popular caffeine-containing beverage with immense economic, medicinal, and cultural importance. Here, we present the first high-quality nucleotide sequence of the ...repeat-rich (80.9%), 3.02-Gb genome of the cultivated tea tree Camellia sinensis. We show that an extraordinarily large genome size of tea tree is resulted from the slow, steady, and long-term amplification of a few LTR retrotransposon families. In addition to a recent whole-genome duplication event, lineage-specific expansions of genes associated with flavonoid metabolic biosynthesis were discovered, which enhance catechin production, terpene enzyme activation, and stress tolerance, important features for tea flavor and adaptation. We demonstrate an independent and rapid evolution of the tea caffeine synthesis pathway relative to cacao and coffee. A comparative study among 25 Camellia species revealed that higher expression levels of most flavonoid- and caffeinebut not theanine-related genes contribute to the increased production of catechins and caffeine and thus enhance tea-processing suitability and tea quality. These novel findings pave the way for further metabolomic and functional genomic refinement of characteristic biosynthesis pathways and will help develop a more diversified set of tea flavors that would eventually satisfy and attract more tea drinkers worldwide.
Camellia is an economically and phylogenetically important genus in the family Theaceae. Owing to numerous hybridization and polyploidization, it is taxonomically and phylogenetically ranked as one ...of the most challengingly difficult taxa in plants. Sequence comparisons of chloroplast (cp) genomes are of great interest to provide a robust evidence for taxonomic studies, species identification and understanding mechanisms that underlie the evolution of the Camellia species.
The eight complete cp genomes and five draft cp genome sequences of Camellia species were determined using Illumina sequencing technology via a combined strategy of de novo and reference-guided assembly. The Camellia cp genomes exhibited typical circular structure that was rather conserved in genomic structure and the synteny of gene order. Differences of repeat sequences, simple sequence repeats, indels and substitutions were further examined among five complete cp genomes, representing a wide phylogenetic diversity in the genus. A total of fifteen molecular markers were identified with more than 1.5% sequence divergence that may be useful for further phylogenetic analysis and species identification of Camellia. Our results showed that, rather than functional constrains, it is the regional constraints that strongly affect sequence evolution of the cp genomes. In a substantial improvement over prior studies, evolutionary relationships of the section Thea were determined on basis of phylogenomic analyses of cp genome sequences.
Despite a high degree of conservation between the Camellia cp genomes, sequence variation among species could still be detected, representing a wide phylogenetic diversity in the genus. Furthermore, phylogenomic analysis was conducted using 18 complete cp genomes and 5 draft cp genome sequences of Camellia species. Our results support Chang's taxonomical treatment that C. pubicosta may be classified into sect. Thea, and indicate that taxonomical value of the number of ovaries should be reconsidered when classifying the Camellia species. The availability of these cp genomes provides valuable genetic information for accurately identifying species, clarifying taxonomy and reconstructing the phylogeny of the genus Camellia.
Numerous protocols for viral enrichment and genome amplification have been created. However, the direct identification of viral genomes from clinical specimens using next-generation sequencing (NGS) ...still has its challenges. As a selected viral nucleic acid extraction method may determine the sensitivity and reliability of NGS, it is still valuable to evaluate the extraction efficiency of different extraction kits using clinical specimens directly.
In this study, we performed qRT-PCR and viral metagenomic analysis of the extraction efficiency of four commonly used Qiagen extraction kits: QIAamp Viral RNA Mini Kit (VRMK), QIAamp MinElute Virus Spin Kit (MVSK), RNeasy Mini Kit (RMK), and RNeasy Plus Micro Kit (RPMK), using a mixed respiratory clinical sample without any pre-treatment. This sample contained an adenovirus (ADV), influenza virus A (Flu A), human parainfluenza virus 3 (PIV3), human coronavirus OC43 (OC43), and human metapneumovirus (HMPV). The quantity and quality of the viral extracts were significantly different among these kits. The highest threshold cycle(Ct)values for ADV and OC43 were obtained by using the RPMK. The MVSK had the lowest Ct values for ADV and PIV3. The RMK revealed the lowest detectability for HMPV and PIV3. The most effective rate of NGS data at 67.47% was observed with the RPMK. The other three kits ranged between 12.1-26.79% effectiveness rates for the NGS data. Most importantly, compared to the other three kits the highest proportion of non-host reads was obtained by the RPMK. The MVSK performed best with the lowest Ct value of 20.5 in the extraction of ADV, while the RMK revealed the best extraction efficiency by NGS analysis.
The evaluation of viral nucleic acid extraction efficiency is different between NGS and qRT-PCR analysis. The RPMK was most applicable for the metagenomic analysis of viral RNA and enabled more sensitive identification of the RNA virus genome in respiratory clinical samples. In addition, viral RNA extraction kits were also applicable for metagenomic analysis of the DNA virus. Our results highlighted the importance of nucleic acid extraction kit selection, which has a major impact on the yield and number of viral reads by NGS analysis. Therefore, the choice of extraction method for a given viral pathogen needs to be carefully considered.
Comparative genomic analyses among closely related species can greatly enhance our understanding of plant gene and genome evolution. We report de novo-assembled AA-genome sequences for Oryza nivara , ...Oryza glaberrima , Oryza barthii , Oryza glumaepatula , and Oryza meridionalis . Our analyses reveal massive levels of genomic structural variation, including segmental duplication and rapid gene family turnover, with particularly high instability in defense-related genes. We show, on a genomic scale, how lineage-specific expansion or contraction of gene families has led to their morphological and reproductive diversification, thus enlightening the evolutionary process of speciation and adaptation. Despite strong purifying selective pressures on most Oryza genes, we documented a large number of positively selected genes, especially those genes involved in flower development, reproduction, and resistance-related processes. These diversifying genes are expected to have played key roles in adaptations to their ecological niches in Asia, South America, Africa and Australia. Extensive variation in noncoding RNA gene numbers, function enrichment, and rates of sequence divergence might also help account for the different genetic adaptations of these rice species. Collectively, these resources provide new opportunities for evolutionary genomics, numerous insights into recent speciation, a valuable database of functional variation for crop improvement, and tools for efficient conservation of wild rice germplasm.
Significance Asian rice ( Oryza sativa ) is among the world’s most important crops. The genus Oryza has become a model for the study of plant genome structure, function, and evolution. We have undertaken de novo, full-genome sequence analysis of five diploid AA-genome species that are closely related to O. sativa . These species are native to quite different environments, representing four continents, thus exhibiting very different adaptations. Our studies identify specific genetic changes, in both gene copy number and the degree of diversifying natural selection, that indicate specific genes responsible for these adaptations, particularly in genes related to defense against pathogens and reproductive diversification. This genome discovery and comparative analysis provide a powerful tool for future Oryza study and rice improvement.
Background
PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China’s registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively ...explored its value over multiple cycles of chemotherapy.
Methods
In this open-label, randomized, multicenter phase 3 study, breast cancer patients (
n
= 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2–4, the incidence of febrile neutropenia, and the safety.
Results
A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3–4, reaching a statistical significance at cycle 4 in either incidence (
P
= 0.0309) or duration (
P
= 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (
P
= 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (
P
= 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan–Meier analysis (
n
= 49,
P
= 0.153).
Conclusions
PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.
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•A hierarchical Co3O4@Co3O4/Fe3O4 yolk-shell nanoreactor was designed and prepared.•The confinement effect and bimetallic cycles were integrated in this nanoreactor.•This nanoreactor ...could activate PMS for various organic pollutants degradation.•DFT calculations and MD simulations disclosed the confined reaction mechanisms.
It is still a challenging task to reasonably design an efficient Co3O4-based nanoreactor for persulfate activation and accurately disclose the confined reaction mechanism. Herein, we design and prepare a hierarchical Co3O4@Co3O4/Fe3O4 yolk-shell nanoreactor (CT@CT/MG). In this yolk-shell structured nanoreactor, a Co3O4 solid sphere is the yolk and a flower-like Co3O4 hollow sphere wrapped by Fe3O4 nanoparticles is the shell. The void between them constitutes a confined space. Various instrumental techniques are used to characterize the structure and compositions of this nanoreactor. Degradation experiments show that CT@CT/MG have powerful capability to activate peroxymonosulfate (PMS) for the degradation and mineralization of various organic pollutants and even their mixture. Radical quenching experiments and EPR results confirm that •OH and SO4•− are the dominant reactive oxygen species in the CT@CT/MG-PMS system. Electrochemical measurements indicate that CT@CT/MG have better electron transfer ability and lower charge transfer resistance. In-situ characterization techniques including in-situ FT-IR and in-situ Raman are employed for deep insights into the potential reaction mechanisms. XPS analyses prove that Fe2+ promote the cycling regeneration of the reactive Co2+. MD simulations and DFT calculations disclose the confined reaction mechanisms by the means of comparative investigations in a confined space and under the unrestricted environment.
Abstract The influence of marriage on the long-term outcomes of schizophrenia is largely unknown. This study was to examine the impact of marriage on the 14-year outcomes and identify the correlates ...of marriage among persons with schizophrenia in rural community. All study participants with schizophrenia ( n = 510) were identified in 1994 in an epidemiological investigation of 123,572 people aged 15 years and older and followed up in 2004 and 2008 in Xinjin County, Chengdu, China. The Patients Follow-up Schedule (PFS) was used in 2004 and 2008. The rate of follow-up in 2008 was 95.9%. Unmarried individuals in 1994 had higher rates of homelessness and suicide, and lower rate of survival in 2004 and 2008 than those married. In 14-year follow-up, unmarried individuals were more likely to be male, to have higher level of psychiatric symptoms and lower rate of full remission of illness, and to report lower level of work functioning, as well as with fewer family members and caregiver, and lower family economic status. The predictors of being married in 2008 included being married in 1994, shorter duration of illness, being female, and lower level of education. Being married is predictive of more favorable 14-year outcomes of persons with schizophrenia in the rural community. Given that marriage can be instrumental for enhancing family-based support and caregiving, as well as improving the community tenure of persons with schizophrenia, it is important to develop programs to enhance opportunity for persons with schizophrenia to get and stay married.
The course, tempo and mode of chloroplast genome evolution remain largely unknown, resulting in limited knowledge about how plant plastome gene and genome evolve during the process of recent plant ...speciation. Here, we report the complete plastomes of 22 closely related
species in chronologically ordered stages and generate the first precise map of genomic structural variation, to our knowledge. The occurrence rapidity was estimated on average to be ~7 insertions and ~15 deletions per Myr. Relatively fewer deletions than insertions result in an increased repeat density that causes the observed growth of
chloroplast genome sizes. Genome-wide scanning identified 14 positively selected genes that are relevant to photosynthesis system, eight of which were found independently in shade-tolerant or sun-loving rice species.
seemed positively selected in both shade-tolerant and sun-loving rice species. The results show that adaptive evolution of chloroplast genes makes rice species adapt to diverse ecological habitats related to sunlight preferences.
Curcumin is a polyphenol substance considered to be effective in the treatment of a number of neurodegenerative diseases. However, details regarding the exact mechanisms for the protective effects of ...curcumin in neuropsychiatric disorders, like depression, remain unknown. In the pathogenesis of major depressive disorder (MDD) it appears that dysregulation of oxidative stress and immune systems, particularly within the hippocampal region, may play a critical role. Here, we show that pre-treatment with curcumin (40 mg kg
−1
) alleviates depression-like behaviors in a LPS-induced rat model of depression, effects which were accompanied with suppression of oxidative stress and inflammation and an inhibition of neuronal apoptosis in the hippocampal CA1 region, and results from ultramicrostructure electrophysiological experiments revealed that the curcumin pre-treatment significantly prevented excessive synaptic loss and enhanced synaptic functioning in this LPS-induced rat model. In addition, curcumin attenuated the increases in levels of miR-146a-5p and decreases in the expression of p-ERK signaling that would normally occur within CA1 regions of these depressed rats. Taken together, these results demonstrated that curcumin exerts neuroprotective and antidepressant activities by suppressing oxidative stress, neural inflammation and their related effects upon synaptic dysregulation. One of the mechanisms for these beneficial effects of curcumin appears to involve the miR-146a-5p/ERK signaling pathway within the hippocampal CA1 region. These findings not only elucidated some of the mechanisms underlying the neuroprotective/antidepressant effects of curcumin, but also suggested a role of curcumin as a potential therapeutic strategy for depression.
Curcumin is a polyphenol substance considered to be effective in the treatment of a number of neurodegenerative diseases.
In this work, Fe
3
O
4
nanoparticles (NPs) loaded inside and outside halloysite nanotubes (HNTs) were prepared and developed as the heterogeneous Fenton-like catalysts for the removal of ...representative organic pollutants. Characterization results indicated that the samples with Fe
3
O
4
NPs loaded outside the HNTs lumen (Fe
3
O
4
/HNTs) and inside the HNTs lumen (Fe
3
O
4
@HNTs) were successfully prepared. Both samples had typical magnetic hysteresis loops, while Fe
3
O
4
@HNTs exhibited higher magnetization intensity. The comparative experiments showed that Fe
3
O
4
@HNTs had better Fenton-like catalytic ability than that of Fe
3
O
4
/HNTs in the degradation of various organic pollutants. Taking Rhodamine B (RhB) as an example, the adsorption thermodynamics and kinetics of RhB onto Fe
3
O
4
/HNTs and Fe
3
O
4
@HNTs were also investigated. The comparative results demonstrated that the adsorption ability of Fe
3
O
4
/HNTs was better than that of Fe
3
O
4
@HNTs. Moreover, the dissolved concentration of Fe
2+
and production amount of hydroxyl radical (·OH) in the Fe
3
O
4
@HNTs-H
2
O
2
system were significantly higher than those in the Fe
3
O
4
/HNTs-H
2
O
2
system. Based on aforementioned comparison, the nano-confinement effect in the Fe
3
O
4
@HNTs-H
2
O
2
system was verified. This work provides meaningful guidance for the cheap and convenient design of nanoreactors for Fenton-like applications.