We incorporate social preferences, which are divided into relationship preferences and status preferences, and consumer low-carbon awareness into a supply chain with one manufacturer and one retailer ...under the cap-and-trade system. First, we suppress the price policies and investigate the manufacturer's carbon-emission reduction strategy and the leading retailer's low-carbon-related promotion strategy with and without the agents' social preferences. Then, we analyze the game dominated by the manufacturer with and without considering pricing policies. We prove that consumer low-carbon awareness improvement incentives channel members to invest in emission reduction and promotion and that this investment is beneficial to member profits and utilities. The channel members' utilities increase with their social preference value. However, their profits, emission-reduction level and promotion level might not necessarily do so. In the manufacturer-led supply chain, wholesale price increases with the retailer's social preference value and decreases with that of the manufacturer. The retail price decreases with the manufacturer's social preference value and increases with that of the retailer. The manners that the leader's decision affects the follower's decision-making and the channel members' social preferences affect their decision-making depend on who the dominator is in the supply chain. In addition, we design a new contract and coordinate the supply chain in the presence of the agents' social preferences. With the contract, the company's utility increment increases with its own social preference value and decreases with that of its cooperator.
Timely and faithful duplication of the entire genome depends on completion of replication. Replication forks frequently encounter obstacles that may cause genotoxic fork stalling. Nevertheless, ...failure to complete replication rarely occurs under normal conditions, which is attributed to an intricate network of proteins that serves to stabilize, repair and restart stalled forks. Indeed, many of the components in this network are encoded by tumour suppressor genes, and their loss of function by mutation or deletion generates genomic instability, a hallmark of cancer. Paradoxically, the same fork‐protective network also confers resistance of cancer cells to chemotherapeutic drugs that induce high‐level replication stress. Here, we review the mechanisms and major pathways rescuing stalled replication forks, with a focus on fork stabilization preventing fork collapse. A coherent understanding of how cells protect their replication forks will not only provide insight into how cells maintain genome stability, but also unravel potential therapeutic targets for cancers refractory to conventional chemotherapies.
This review examines mechanisms and pathways that stabilize stalled replication forks, and how these can be exploited for combinatorial treatments of cancer resistant to replication stress‐inducing drugs.
Summary
With advanced sequencing technology, dozens of complex polyploid plant genomes have been characterized. However, for many polyploid species, their diploid ancestors are unknown or extinct, ...making it impossible to unravel the subgenomes and genome evolution directly.
We developed a novel subgenome‐phasing algorithm, SubPhaser, specifically designed for a neoallopolyploid or a homoploid hybrid. SubPhaser first searches for the subgenome‐specific sequence (k‐mer), then assigns homoeologous chromosomes into subgenomes, and further provides tools to annotate and investigate specific sequences.
SubPhaser works well on neoallopolyploids and homoploid hybrids containing subgenome‐specific sequences like wheat, but fails on autopolyploids lacking subgenome‐specific sequences like alfalfa, indicating that SubPhaser can phase neoallopolyploid/homoploid hybrids with high accuracy, sensitivity and performance.
This highly accurate, highly sensitive, ancestral data free chromosome phasing algorithm, SubPhaser, offers significant application value for subgenome phasing in neoallopolyploids and homoploid hybrids, and for the subsequent exploration of genome evolution and related genetic/epigenetic mechanisms.
Industrial control systems (ICS) are applied in many fields. Due to the development of cloud computing, artificial intelligence, and big data analysis inducing more cyberattacks, ICS always suffers ...from the risks. If the risks occur during system operations, corporate capital is endangered. It is crucial to assess the security of ICS dynamically. This paper proposes a dynamic assessment framework for industrial control system security (DAF-ICSS) based on machine learning and takes an industrial robot system as an example. The framework conducts security assessment from qualitative and quantitative perspectives, combining three assessment phases: static identification, dynamic monitoring, and security assessment. During the evaluation, we propose a weighted Hidden Markov Model (W-HMM) to dynamically establish the system's security model with the algorithm of Baum-Welch. To verify the effectiveness of DAF-ICSS, we have compared it with two assessment methods to assess industrial robot security. The comparison result shows that the proposed DAF-ICSS can provide a more accurate assessment. The assessment reflects the system's security state in a timely and intuitive manner. In addition, it can be used to analyze the security impact caused by the unknown types of ICS attacks since it infers the security state based on the explicit state of the system.
Alzheimer’s disease (AD) is a neurodegenerative disease with increasing prevalence worldwide, while there are no effective drugs at present. Curcumin, a natural polyphenolic substance isolated from ...turmeric, is a promising natural compound to combat AD, but its pharmacology remains to be fully understood for its poor in vivo bioavalibility. Inspired by the recently reported associations between gut microbiota and AD development, the present study investigated the interactions of curcumin with gut microbiota of APP/PS1 double transgenic mice from two directions: (i) curcumin influences gut microbiota, and (ii) gut microbiota biotransform curcumin. It was found that curcumin administration tended to improve the spatial learning and memory abilities and reduce the amyloid plaque burden in the hippocampus of APP/PS1 mice. On the one hand, curcumin administration altered significantly the relative abundances of bacterial taxa such as
Bacteroidaceae
,
Prevotellaceae
,
Lactobacillaceae
, and
Rikenellaceae
at family level, and
Prevotella
,
Bacteroides
, and
Parabacteroides
at genus level, several of which have been reported to be key bacterial species associated with AD development. On the other hand, a total of 8 metabolites of curcumin biotransformed by gut microbiota of AD mice through reduction, demethoxylation, demethylation and hydroxylation were identified by HPLC-Q-TOF/MS, and many of these metabolites have been reported to exhibit neuroprotective ability. The findings provided useful clues to understand the pharmacology of curcumin and microbiome-targeting therapies for AD.
The newly reported associations between Alzheimer’s disease (AD) and gut microbiota indicate the potential of gut microbiota regulation–based therapeutic intervention for AD. Silymarin and its main ...active component, silibinin, are promising natural agents against AD, while their acting mechanisms remain to be explored. The present study investigated the effects of silibinin and silymarin administration on behavioral and histological manifestations, and regulation on the gut microbiota of transgenic APP/PS1 mice. First, silibinin and silymarin administration could alleviate memory deficits and reduce the amyloid plaque burden in the brain of APP/PS1 mice in comparison with controls. Second, silibinin and silymarin administration tended to decrease the microbiota diversity and exhibited regulative effect in abundances on several key bacterial species associated with AD development. This implied that gut microbiota regulation by silibinin and silymarin might be involved in their effects against AD. Further studies are warranted to fully elucidate the molecular mechanisms.
L. is a traditional Chinese medicine with various pharmacological properties, including anti-inflammatory, antibacterial, and detoxification effects. In this study, the mechanism of the hypoglycemic ...effect of purified anthraquinone-Glycoside from
L. (PAGR) in streptozotocin (STZ) and high-fat diet induced type 2 diabetes mellitus (T2DM) in rats was investigated. The rats were randomly divided into normal (NC), T2DM, metformin (Met), low, middle (Mid), and high (Hig) does of PAGR groups. After six weeks of continuous administration of PAGR, the serum indices and tissue protein expression were determined, and the pathological changes in liver, kidney, and pancreas tissues were observed. The results showed that compared with the type 2 diabetes mellitus group, the fasting blood glucose (FBG), total cholesterol (TC), and triglyceride (TG) levels in the serum of rats in the PAGR treatment groups were significantly decreased, while superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) levels were noticeably increased. The expression of Fas ligand (FasL), cytochrome C (Cyt-c), and caspase-3 in pancreatic tissue was obviously decreased, and the pathological damage to the liver, kidney, and pancreas was improved. These indicate that PAGR can reduce oxidative stress in rats with diabetes mellitus by improving blood lipid metabolism and enhancing their antioxidant capacity, thereby regulating the mitochondrial apoptotic pathway to inhibitβ-cell apoptosis and improve β-cell function. Furthermore, it can regulate Fas/FasL-mediated apoptosis signaling pathway to inhibit β-cell apoptosis, thereby lowering blood glucose levels and improving T2DM.
With the accelerated aging of human society Alzheimer's disease (AD) has become one of the most threatening diseases in the elderly. However, there is no efficient therapeutic agent to combat AD. ...Berberine is a natural isoquinoline alkaloid that possesses a wide range of pharmacological effects. In the present paper, we review the multiple activities of berberine, including antioxidant, acetylcholinesterase and butyrylcholinesterase inhibitory, monoamine oxidase inhibitory, amyloid-b peptide level-reducing and cholesterol-lowering activities, which suggest that berberine may act as a promising multipotent agent to combat AD.
In recent years, the associations between vitamin D status and Alzheimer's disease (AD) and dementia have gained increasing interests. The present meta-analysis was designed to estimate the ...association between vitamin D deficiency and risk of developing AD and dementia.
A literature search conducted until February 2015 identified 10 study populations, which were included in the meta-analysis. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated with a random-effect model using Stata software package.
Results of our meta-analysis showed that subjects with deficient vitamin D status (25(OH)D level < 50 nmol/L) were at increased risk of developing AD by 21% compared with those possessing 25(OH)D level > 50 nmol/L. Similar analysis also found a significantly increased dementia risk in vitamin D deficient subjects. There is no evidence for significant heterogeneity among the included studies.
Available data indicates that lower vitamin D status may be associated with increased risk of developing AD and dementia. More studies are needed to further confirm the associations and to evaluate the beneficial effects of vitamin D supplementation in preventing AD and dementia.
Wolbachia is a genus of maternally inherited endosymbionts that can affect reproduction of their hosts and influence metabolic processes. The pollinator, Valisia javana, is common in the male ...syconium of the dioecious fig Ficus hirta. Based on a high-quality chromosome-level V. javana genome with PacBio long-read and Illumina short-read sequencing, we discovered a sizeable proportion of Wolbachia sequences and used these to assemble two novel Wolbachia strains belonging to supergroup A. We explored its phylogenetic relationship with described Wolbachia strains based on MLST sequences and the possibility of induction of CI (cytoplasmic incompatibility) in this strain by examining the presence of cif genes known to be responsible for CI in other insects. We also identified mobile genetic elements including prophages and insertion sequences, genes related to biotin synthesis and metabolism. A total of two prophages and 256 insertion sequences were found. The prophage WOjav1 is cryptic (structure incomplete) and WOjav2 is relatively intact. IS5 is the dominant transposon family. At least three pairs of type I cif genes with three copies were found which may cause strong CI although this needs experimental verification; we also considered possible nutritional effects of the Wolbachia by identifying genes related to biotin production, absorption and metabolism. This study provides a resource for further studies of Wolbachia-pollinator-host plant interactions.
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