Acyclic terpenes, commonly found in plants, are of high physiological importance and commercial value, and their diversity was controlled by different terpene synthases. During the screen of ...sesquiterpene synthases from Tripterygium wilfordii, we observed that Ses-TwTPS1-1 and Ses-TwTPS2 promiscuously accepted GPP, FPP, and GGPP to produce corresponding terpene alcohols (linalool/nerolidol/geranyllinalool). The Ses-TwTPS1-2, Ses-TwTPS3, and Ses-TwTPS4 also showed unusual substrate promiscuity by catalyzing GGPP or GPP in addition to FPP as substrate. Furthermore, key residues for the generation of diterpene product, (E, E)-geranyllinalool, were screened depending on mutagenesis studies. The functional analysis of Ses-TwTPS1-1:V199I and Ses-TwTPS1-2:I199V showed that Val in 199 site assisted the produce of diterpene product geranyllinalool by enzyme mutation studies, which indicated that subtle differences away from the active site could alter the product outcome. Moreover, an engineered sesquiterpene high-yielding yeast that produced 162 mg/L nerolidol in shake flask conditions was constructed to quickly identify the function of sesquiterpene synthases in vivo and develop potential applications in microbial fermentation. Our functional characterization of acyclic sesquiterpene synthases will give some insights into the substrate promiscuity of diverse acyclic terpene synthases and provide key residues for expanding the product portfolio.
In the social network, similar users are assumed to prefer similar items, so searching the similar users of a target user plays an important role for most collaborative filtering methods. Existing ...collaborative filtering methods use user ratings of items to search for similar users. Nowadays, abundant social information is produced by the Internet, such as user profiles, social relationships, behaviors, interests, and so on. Only using user ratings of items is not sufficient to recommend wanted items and search for similar users. In this paper, we propose a new collaborative filtering method using social information fusion. Our method first uses social information fusion to search for similar users and then updates the user rating of items for recommendation using similar users. Experiments show that our method outperforms the existing methods based on user ratings of items and using social information fusion to search similar users is an available way for collaborative filtering methods of recommender systems.
Objective
To examine the putative regulatory role of
TwDXR
in terpenoid biosynthesis and terpenoid biosynthetic pathway-related gene expression, through overexpression and RNA interference with
TwDXR
....
Results
We obtained 1410 and 454 bp
TwDXR
-specific fragments to construct overexpression and RNAi vectors. qRT-PCR was used to detect the expression of
TwDXR
and terpenoid biosynthesis pathway-related genes. The overexpression of
TwDXR
led to a 285% upregulation and the
TwDXR
RNAi led to a reduction to 26% of the control (empty vector-transformed cells) levels. However, pathway-related genes displayed different trends. When
TwDXR
was overexpressed,
TwDXS
expression decreased by 31% but increased to 198% when
TwDXR
expression was inhibited. The accumulation of terpenoids was also assayed. In the overexpression group, differences were not significant whereas the contents of triptolide and celastrol in the
TwDXR
RNAi samples were diminished by 27.3 and 24.0%, respectively.
Conclusion
The feedback regulation of gene transcription and the accumulation of terpenoids in terpenoid biosynthesis in
Tripterygium wilfordii
were verified by
TwDXR
overexpression and RNAi experiments.
Polybrominated diphenyl ethers (PBDEs) are extensively used as brominated flame retardants (BFRs) in different types of materials, which have been listed as Persistent Organic Pollutants (POPs) by ...the Stockholm Convention in 2009 and 2017. Due to their ubiquities in the environment and toxicities, PBDEs have posed great threat to both human health and ecosystems. The aim of this review is to offer a comprehensive understanding of the exposure pathways, levels and trends and associated health risks of PBDEs in human body in a global scale. We systematically reviewed and described the scientific data of PBDE researches worldwide from 2010 to March 2020, focusing on the following three areas: (1) sources and human external exposure pathways of PBDEs; (2) PBDE levels and trends in humans; (3) human data of PBDEs toxicity. Dietary intake and dust ingestion are dominant human exposure pathways. PBDEs were widely detected in human samples, especially in human serum and human milk. Data showed that PBDEs are generally declining in human samples worldwide as a result of their phasing out. Due to the common use of PBDEs, their levels in humans from the USA were generally higher than that in other countries. High concentrations of PBDEs have been detected in humans from PBDE production regions and e-waste recycling sites. BDE-47, -153 and -99 were proved to be the primary congeners in humans. Human toxicity data demonstrated that PBDEs have extensively endocrine disruption effects, developmental effects, and carcinogenic effects among different populations.
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•Dust ingestion is primary route of human external exposure.•PBDEs displayed higher values in humans from the USA, PBDE production and e-waste recycling regions.•PBDEs showed a declining trend, and BDE-47, -153, -99 were predominant congeners in humans.•Human toxicity studies have shown that PBDEs have endocrine disruption, developmental and carcinogenic effects.
There have been more than 2.2 million confirmed cases and over 120 000 deaths from the human coronavirus disease 2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome ...coronavirus (SARS-CoV-2), in the United States alone. However, there is currently a lack of proven effective medications against COVID-19. Drug repurposing offers a promising route for the development of prevention and treatment strategies for COVID-19. This study reports an integrative, network-based deep-learning methodology to identify repurposable drugs for COVID-19 (termed CoV-KGE). Specifically, we built a comprehensive knowledge graph that includes 15 million edges across 39 types of relationships connecting drugs, diseases, proteins/genes, pathways, and expression from a large scientific corpus of 24 million PubMed publications. Using Amazon’s AWS computing resources and a network-based, deep-learning framework, we identified 41 repurposable drugs (including dexamethasone, indomethacin, niclosamide, and toremifene) whose therapeutic associations with COVID-19 were validated by transcriptomic and proteomics data in SARS-CoV-2-infected human cells and data from ongoing clinical trials. Whereas this study by no means recommends specific drugs, it demonstrates a powerful deep-learning methodology to prioritize existing drugs for further investigation, which holds the potential to accelerate therapeutic development for COVID-19.
Torreya plants produce dry fruits with assorted functions. Here, we report the 19-Gb chromosome-level genome assembly of T. grandis. The genome is shaped by ancient whole-genome duplications and ...recurrent LTR retrotransposon bursts. Comparative genomic analyses reveal key genes involved in reproductive organ development, cell wall biosynthesis and seed storage. Two genes encoding a C
Δ
-elongase and a C
Δ
-desaturase are identified to be responsible for sciadonic acid biosynthesis and both are present in diverse plant lineages except angiosperms. We demonstrate that the histidine-rich boxes of the Δ
-desaturase are crucial for its catalytic activity. Methylome analysis reveals that methylation valleys of the T. grandis seed genome harbor genes associated with important seed activities, including cell wall and lipid biosynthesis. Moreover, seed development is accompanied by DNA methylation changes that possibly fuel energy production. This study provides important genomic resources and elucidates the evolutionary mechanism of sciadonic acid biosynthesis in land plants.
Cancer cells need to generate large amounts of glutathione (GSH) to buffer oxidative stress during tumor development. A rate-limiting step for GSH biosynthesis is cystine uptake via a ...cystine/glutamate antiporter Xc
. Xc
is a sodium-independent antiporter passively driven by concentration gradients from extracellular cystine and intracellular glutamate across the cell membrane. Increased uptake of cystine via Xc
in cancer cells increases the level of extracellular glutamate, which would subsequently restrain cystine uptake via Xc
. Cancer cells must therefore evolve a mechanism to overcome this negative feedback regulation. In this study, we report that glutamate transporters, in particular SLC1A1, are tightly intertwined with cystine uptake and GSH biosynthesis in lung cancer cells. Dysregulated SLC1A1, a sodium-dependent glutamate carrier, actively recycled extracellular glutamate into cells, which enhanced the efficiency of cystine uptake via Xc
and GSH biosynthesis as measured by stable isotope-assisted metabolomics. Conversely, depletion of glutamate transporter SLC1A1 increased extracellular glutamate, which inhibited cystine uptake, blocked GSH synthesis, and induced oxidative stress-mediated cell death or growth inhibition. Moreover, glutamate transporters were frequently upregulated in tissue samples of patients with non-small cell lung cancer. Taken together, active uptake of glutamate via SLC1A1 propels cystine uptake via Xc
for GSH biosynthesis in lung tumorigenesis. SIGNIFICANCE: Cellular GSH in cancer cells is not only determined by upregulated Xc
but also by dysregulated glutamate transporters, which provide additional targets for therapeutic intervention.
A series of well-defined azobenzene-functionalized ionomers were produced via ring-opening metathesis polymerization of norbornene-dicarboximide tethered to an ionic group further connected with an ...azobenzene unit in ionic liquid. The corresponding azobenzene-containing non-ionic polymers were also synthesized by the similar method. All the polymerizations were confirmed to be the characteristic of living based on the linear relationship between molecular weight and feed ratio. As expected, the distinct photoresponsive properties from azobenzene units in ionomers were observed under alternating irradiation of UV and visible light, which cannot be achieved by traditional azobenzene-containing non-ionic polymers. The ability and efficiency of trans−cis photoisomerization was depressed to some extent due to the presence of ionic groups nearby azobenzene units. Moreover, the sizes and morphologies of these ionomers can be modulated through changing the number of the methylene spacer to generate regular and uniform spherical nanostructures, ultimately leading to the unique photoisomerization behaviors. All these interesting results will not only provide a facile and efficient method for constructing photosensitive ionic metathesis polymers, but also expand the optical properties and application prospect of azobenzene-containing polymers.
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•The azobenzene-functionalized ionomers were produced in ionic liquid via directly ROMP of ionic monomers.•All the polymerizations were confirmed to be the characteristic of living.•The ionomers displayed the confined photoisomerization process and reduced the efficiency of photoisomerization.•The ionomers can self-assemble into the spherical nanostructures with uniform aggregate sizes.
Aiming at the problem that the accuracy and economy of the traditional off-line batching method are not high, the online batching system (BSMLIA) based on machine learning and intelligent algorithms ...was put forward from three aspects: real-time, technical requirements and economic benefits. The accurate solution and on-line fast calculation of sintering raw material ratio under the influence of multiple factors are solved. Specifically, a BSMLIA architecture with three levels of data communication layer (DCL), parameter prediction and batching optimization layer (PPBOL), and diagnostic decision layer (DDL) was first designed to realize online monitoring and abnormal diagnosis of sinter performance. Then, the sintering batching adjustment and optimization module (SBAOM) was elaborated. The mixture performance prediction model was developed by MLR and LightGBM algorithm, the model can be based on sinter composition and quality index requirements and current sintering production process parameters to calculate the appropriate mixture performance. In addition, the pre-batching model and the sintering batching model were established to achieve the solution of the lowest raw material cost ratio for a given mixture performance. Finally, the actual production data was used to verify the SBAOM. The results proved that the online batching system can not only quickly calculate the batching plan that meets the requirements, but also reduce the batching cost by RMB 29.54/ton.
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