On approximating a new generalization of traveling salesman problem.

The current best-known performance guarantees for the extensively studied Traveling Salesman Problem (TSP) of determinate approximation algorithms is 32, achieved by Christofides' algorithm 47 years ago. This paper investigates a new generalization problem of the TSP, termed the Minimum-Cost Bounded Degree Connected Subgraph (MBDCS) problem. In the MBDCS problem, the goal is to identify a minimum-cost connected subgraph containing n=|V| edges from an input graph G=(V,E) with degree upper bounds for particular vertices. We show that for certain special cases of MBDCS, the aim is equivalent to finding a minimum-cost Hamiltonian cycle for the input graph, same as the TSP. To appropriately solve MBDCS, we initially present an integer programming formulation for the problem. Subsequently, we propose an algorithm to approximate the optimal solution by applying the iterative rounding technique to solution of the integer programming relaxation. We demonstrate that the returned subgraph of our proposed algorithm is one of the best guarantees for the MBDCS problem in polynomial time, assuming P≠NP. This study views the optimization of TSP as finding a minimum-cost connected subgraph containing n edges with degree upper bounds for certain vertices, and it may provide new insights into optimizing the TSP in future research.

Physiological and chaos effect on dynamics of neurological disorder with memory effect of fractional operator: A mathematical study.

BACKGROUND AND OBJECTIVE: To study the dynamical system, it is necessary to formulate the mathematical model to understand the dynamics of various diseases that are spread worldwide. The main objective of our work is to examine neurological disorders by early detection and treatment by taking asymptomatic. The central nervous system (CNS) is impacted by the prevalent neurological condition known as multiple sclerosis (MS), which can result in lesions that spread across time and place. It is widely acknowledged that multiple sclerosis (MS) is an unpredictable disease that can cause lifelong damage to the brain, spinal cord, and optic nerves. The use of integral operators and fractional order (FO) derivatives in mathematical models has become popular in the field of epidemiology. METHOD: The model consists of segments of healthy or barian brain cells, infected brain cells, and damaged brain cells as a result of immunological or viral effectors with novel fractal fractional operator in sight Mittag Leffler function. The stability analysis, positivity, boundedness, existence, and uniqueness are treated for a proposed model with novel fractional operators. RESULTS: Model is verified the local and global with the Lyapunov function. Chaos Control will use the regulate for linear responses approach to bring the system to stabilize according to its points of equilibrium so that solutions are bounded in the feasible domain. To ensure the existence and uniqueness of the solutions to the suggested model, it makes use of Banach's fixed point and the Leray Schauder nonlinear alternative theorem. For numerical simulation and results the steps Lagrange interpolation method at different fractional order values and the outcomes are compared with those obtained using the well-known FFM method. CONCLUSION: Overall, by offering a mathematical model that can be used to replicate and examine the behavior of disease models, this research advances our understanding of the course and recurrence of disease. Such type of investigation will be useful to investigate the spread of disease as well as helpful in developing control strategies from our justified outcomes.

Stability and bifurcation analysis of a discrete predator-prey system of Ricker type with refuge effect.

The refuge effect is critical in ecosystems for stabilizing predator-prey interactions. The purpose of this research was to investigate the complexities of a discrete-time predator-prey system with a refuge effect. The analysis investigated the presence and stability of fixed points, as well as period-doubling and Neimark-Sacker (NS) bifurcations. The bifurcating and fluctuating behavior of the system was controlled via feedback and hybrid control methods. In addition, numerical simulations were performed as evidence to back up our theoretical findings. According to our findings, maintaining an optimal level of refuge availability was critical for predator and prey population cohabitation and stability.

Highly Efficient Monolithic Perovskite/Perovskite/Silicon Triple-Junction Solar Cells.

Wide-bandgap metal halide perovskites have demonstrated promise in multijunction photovoltaic (PV) cells. However, photoinduced phase segregation and the resultant low open-circuit voltage (Voc) have greatly limited the PV performance of perovskite-based multijunction devices. Here, a alloying strategy is reported to achieve uniform distribution of triple cations and halides in wide-bandgap perovskites by doping Rb+ and Cl- with small ionic radii, which effectively suppresses halide phase segregation while promoting the homogenization of surface potential. Based on this strategy, a Voc of 1.33 V is obtained from single-junction perovskite solar cells, and a VOC approaching 3.0 V and a power conversion efficiency of 25.0% (obtained from reverse scan direction, certified efficiency: 24.19%) on an 1.04 cm2 photoactive area can be achieved in a perovskite/perovskite/c-Si triple-junction tandem cell, where the certification efficiency is by far the greatest performance of perovskite-based triple-junction tandem solar cells. This work overcomes the performance deadlock of perovskite-based triple-junction tandem cells by setting a materials-by-design paradigm.

Transcriptome-wide N6-methyladenosine methylation profile of atherosclerosis in mice.

BACKGROUND: Atherosclerosis (AS) is a critical pathological event during the progression of cardiovascular diseases. It exhibits fibrofatty lesions on the arterial wall and lacks effective treatment. N6-methyladenosine (m6A) is the most common modification of eukaryotic RNA and plays an important role in regulating the development and progression of cardiovascular diseases. However, the role of m6A modification in AS remains largely unknown. Therefore, in this study, we explored the transcriptome distribution of m6A modification in AS and its potential mechanism. METHODS: Methylation Quantification Kit was used to detect the global m6A levels in the aorta of AS mice. Western blot was used to analyze the protein level of methyltransferases. Methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were used to obtain the first transcriptome range analysis of the m6A methylene map in the aorta of AS mice, followed by bioinformatics analysis. qRT-PCR and MeRIP-qRT-PCR were used to measure the mRNA and m6A levels in target genes. RESULTS: The global m6A and protein levels of methyltransferase METTL3 were significantly increased in the aorta of AS mice. However, the protein level of demethylase ALKBH5 was significantly decreased. Through MeRIP-seq, we obtained m6A methylation maps in AS and control mice. In total, 26,918 m6A peaks associated with 13,744 genes were detected in AS group, whereas 26,157 m6A peaks associated with 13,283 genes were detected in the control group. Peaks mainly appeared in the coding sequence (CDS) regions close to the stop codon with the RRACH motif. Moreover, functional enrichment analysis demonstrated that m6A-containing genes were significantly enriched in AS-relevant pathways. Interestingly, a negative correlation between m6A methylation abundance and gene expression level was found through the integrated analysis of MeRIP-seq and RNA-seq data. Among the m6A-modified genes, a hypo-methylated but up-regulated (hypo-up) gene Fabp5 may be a potential biomarker of AS. CONCLUSIONS: Our study provides transcriptome-wide m6A methylation for the first time to determine the association between m6A modification and AS progression. Our study lays a foundation for further exploring the pathogenesis of AS and provides a new direction for the treatment of AS.

A Multiobjective Evolutionary Algorithm Based on Objective-Space Localization Selection.

This article proposes a simple yet effective multiobjective evolutionary algorithm (EA) for dealing with problems with irregular Pareto front. The proposed algorithm does not need to deal with the issues of predefining weight vectors and calculating indicators in the search process. It is mainly based on the thought of adaptively selecting multiple promising search directions according to crowdedness information in local objective spaces. Concretely, the proposed algorithm attempts to dynamically delete an individual of poor quality until enough individuals survive into the next generation. In this environmental selection process, the proposed algorithm considers two or three individuals in the most crowded area, which is determined by the local information in objective space, according to a probability selection mechanism, and deletes the worst of them from the current population. Thus, these surviving individuals are representative of promising search directions. The performance of the proposed algorithm is verified and compared with seven state-of-the-art algorithms [including four general multi/many-objective EAs and three algorithms specially designed for dealing with problems with irregular Pareto-optimal front (PF)] on a variety of complicated problems with different numbers of objectives ranging from 2 to 15. Empirical results demonstrate that the proposed algorithm has a strong competitiveness power in terms of both the performance and the algorithm compactness, and it can well deal with different types of problems with irregular PF and problems with different numbers of objectives.

Tetramethylpyrazine Improves Cognitive Function of Alzheimer's Disease Mice by Regulating SSTR4 Ubiquitination.

PURPOSE: Many researches have investigated the functions of tetramethylpyrazine (TMP) in Alzheimer's disease (AD). This study aimed to discuss the underlying mechanism of TMP in AD mice. METHODS: TMP (200 mg/kg) was administered to 6-month-old APP/PS1 transgenic mice, and behavioral changes and hippocampal nerve injury in AD mice were detected. Apoptosis and autophagy-related protein levels were detected. Changes in gene expression before and after TMP treatment were compared using transcriptome sequencing. The effects of Cullin 4B (CUL4B) overexpression and somatostatin receptor 4 (SSTR4) silencing on AD symptoms and SSTR4 ubiquitination in APP/PS1 mice were observed. SH-SY5Y and PC12 cells were treated with 25 µmol/L Aß25-35 and TMP to observe cell viability, apoptosis, and autophagy. Cell viability and apoptosis were measured again after treatment with proteasome inhibitor MG132 or lysosomal inhibitor 3-mA. RESULTS: TMP treatment improved the behavioral cognition of APP/PS1 mice and improved the neuronal apoptosis and damage in brain tissue. CUL4B was significantly upregulated in APP/PS1 mouse brain tissue, and SSRT4 protein was downregulated, and the levels of CUL4B and SSRT4 were negatively correlated. TMP treatment downregulated CUL4B, inhibited SSRT4 ubiquitination and upregulated SSRT4 protein level in APP/PS1 mouse brain tissue, while CUL4B overexpression or SSRT4 silencing reversed the effect of TMP. TMP and MG132 improved the decreased activity, increased apoptosis and increased SSRT4 protein in SH-SY5Y and PC12 cells treated with Aß25-35, but not 3-mA. CUL4B overexpression promoted the ubiquitination of SSTR4 in cells, which partially reversed the effect of TMP. CONCLUSION: TMP could improve the cognitive ability of AD mice by inhibiting CUL4B expression and the ubiquitination degradation of SSTR, and alleviating neuronal apoptosis and injury. This study may offer a new therapeutic option for AD treatment.

Running Time Analysis of MOEA/D on Pseudo-Boolean Functions.

Decomposition-based multiobjective evolutionary algorithms (MOEAs) are a class of popular methods for solving the multiobjective optimization problems (MOPs), and have been widely studied in numerical experiments and successfully applied in practice. However, we know little about these algorithms from the theoretical aspect. In this paper, we present running time analysis of a simple MOEA with mutation and crossover based on the MOEA/D framework (MOEA/D-C) on five pseudo-Boolean functions. Our rigorous theoretical analysis shows that by properly setting the number of subproblems, the upper bounds of expected running time of MOEA/D-C obtaining a set of solutions to cover the Pareto fronts (PFs) of these problems are apparently lower than those of the one with mutation-only (MOEA/D-M). Moreover, to effectively obtain a set of solutions to cover the PFs of these problem, MOEA/D-C only needs to decompose these MOPs into several subproblems with a set of simple weight vectors while MOEA/D-M needs to find Ω(n) optimally decomposed weight vectors. This result suggests that the use of crossover in decomposition-based MOEA can simplify the setting of weight vectors for different problems and make the algorithm more efficient. This paper provides some insights into the working principles of MOEA/D and explains why some existing decomposition-based MOEAs work well in computational experiments.

Sitagliptin promotes mitochondrial biogenesis in human SH-SY5Y cells by increasing the expression of PGC-1α/NRF1/TFAM.

Mitochondrial dysfunction has been associated with the pathogenesis of a variety of neurodegenerative diseases. Sitagliptin is a dipeptidyl-peptidase-4 (DPP-4) inhibitor that has been approved for the treatment of type 2 diabetes (T2DM). In the current study, we report that sitagliptin increased the expression of PGC-1α, NRF1, and TFAM in human SH-SY5Y neuronal cells. Notably, our data indicate that sitagliptin promoted mitochondrial biogenesis by increasing the amount of mtDNA, the levels of mitochondria-related genes such as TOMM20, TOMM40, TIMM9, NDUFS3, ATP5C1, and the expression of oxidative phosphorylation subunits complex I and complex IV. Additionally, we found that sitagliptin induced a "gain of mitochondrial function" in SH-SY5Y cells by increasing the mitochondrial respiratory rate and adenosine triphosphate (ATP) production. Significantly, our results demonstrate that sitagliptin activated the transcriptional factor CREB by inducing its phosphorylation at Ser133. Inhibition of CREB using its specific inhibitor H89 abolished the effects of sitagliptin on the expression of PGC-1α, NRF1, and TFAM, as well as an increase in mtDNA amount and ATP production. These findings suggest that sitagliptin could become a potential agent for the treatment of neurological disorders.

Formononetin may protect aged hearts from ischemia/reperfusion damage by enhancing autophagic degradation.

Myocardial infarction is a leading cause of mortality worldwide, and timely blood/oxygen reperfusion may substantially improve the outcome of infarction. However, ischemia/reperfusion (I/R) may cause severe side effects through excess reactive oxygen species generation. To develop novel methods to relieve I/R induced cell damage, the present study used a component of traditional Chinese medicine. In the present study, isolated heart tissue from aged mice and H9C2 cells with chemically­induced aging were used as experimental subjects, and it was demonstrated that formononetin was able to alleviate I/R­induced cell or tissue apoptosis. By applying formononetin to I/R­damaged tissue or cells, it was demonstrated that formononetin was able to enhance autophagy and thus alleviate I/R­induced cell damage. Furthermore, it was observed that I/R was able to inhibit lysosomal degradation processes in aged tissues or cells by impairing the lysosome acidification level, and formononetin was able to reverse this process via the re­acidification of lysosomes. In conclusion, the present study demonstrated that formononetin was able to alleviate I/R­induced cellular apoptosis in aged cells by facilitating autophagy.

Arctiin Prevents LPS-Induced Acute Lung Injury via Inhibition of PI3K/AKT Signaling Pathway in Mice.

Arctiin is a lignin isolated from Arctium lappa which has been known to have anti-viral and anti-inflammatory effects. The aim of this study is to explore the protective effect of arctiin on lipopolysaccharide (LPS)-induced inflammatory responses in acute lung injury (ALI) model of mice. Male BALB/c mice were pretreated with commercial arctiin (10, 20, and 40 mg/kg) 1 h prior to LPS challenge. Twelve hours later, airway inflammation was assessed. We assessed the effects of arctiin on the LPS-induced production of TNF-α, IL-6, and IL-1ß in the bronchoalveolar lavage fluid (BALF). The lung wet-to-dry weight ratio, myeloperoxidase (MPO) activity, and inflammatory signaling pathway were also detected. Our results showed that arctiin not only significantly ameliorated LPS-stimulated lung histopathological changes but also reduced the lung MPO activity. Arctiin also dramatically decreased the production of TNF-α, IL-1ß, and IL-6 in the BALF. In addition, arctiin significantly inhibited LPS-induced PI3K/Akt phosphorylation as well as NF-κB activation. In conclusion, our results suggested that arctiin protected against LPS-induced ALI through inhibiting PI3K/AKT/NF-κB signaling pathway.

Association of Achilles tendon thickness and LDL-cholesterol levels in patients with hypercholesterolemia.

BACKGROUND: Achilles tendons are the most common sites of tendon xanthomas that are commonly caused by disturbance of lipid metabolism. Achilles tendon thickening is the early characteristic of Achilles tendon xanthomas. The relationship between Achilles tendon thickness (ATT) and LDL-C levels, and risk factors of ATT in patients with hypercholesterolemia, have thus far been poorly documented. METHODS: A total of 205 individuals, aged 18-75 years, were enrolled from March 2014 to March 2015. According to the LDL-C levels and the "Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults", all subjects were divided into 3 groups: normal group (LDL-C < 3.37 mmol/L, n = 51); borderline LDL-C group (3.37 mmol/L ≤ LDL-C ≤ 4.12 mmol/L, n = 50); and hypercholesterolemia group (LDL ≥ 4.14 mmol/L, n = 104). ATT was measured using a standardized digital radiography method and the results were compared among the 3 groups. The correlation between ATT and serum LDL-C levels was analyzed by Pearson's correlation, and the risk factors of ATT were determined by the logistic regression model. RESULTS: ATT in borderline LDL-C group was 8.24 ± 1.73 mm, markedly higher than 6.05 ± 0.28 mm of normal group (P < 0.05). ATT in hypercholesterolemia group was 9.42 ± 3.63 mm which was significantly higher than that of normal group (P < 0.005) and that of borderline LDL-C group (P < 0.05). There was a positive correlation between the serum LDL-C levels and ATT (r = 0.346, P < 0.001). The serum LDL-C level was a risk factor (OR = 1.871, 95% CI: 1.067-3.280) while the levels of HDL-C (OR = 0.099, 95% CI: 0.017-0.573) and Apo AI (OR = 0.035, 95% CI: 0.003-0.412) were protective factors of ATT. CONCLUSIONS: ATT might serve as a valuable auxiliary diagnostic index for hypercholesterolemia and used for the assessment and management of cardiovascular disease.

The design of formatted report language and its applications in medical information systems.

The extensible markup language (XML) is gaining attention in medicine because of its flexibility. Since most XML documents convey information only on content, it has been difficult for medical applications to present and edit them in the precise format, as required in many clinical circumstances. This article offers a design of formatted report (FR) language to meet almost all medical-oriented requirements of presenting and editing data items such as text, image, scheme and video in the precise format. As FR language could be converted to and from other XML-based languages, it's suitable for almost all XML application environments. A set of components and tools have also been built to promote the application of FR language in the medical fields. These components and tools have established a development platform and could cover almost all application fields of XML. The FR language together with the set of components and tools has already been used in image diagnostic system to present and edit image report in the clinical environment.