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Abstract In this paper, we are concerned with the Kirchhoff-type variable-order fractional Laplacian problems involving critical exponents and logarithmic nonlinearity. By using the constraint variational method, we show the existence of one least energy sign-changing solution. Moreover, we show that this energy is strictly larger than twice the ground energy.

Background: Anaplastic Thyroid Carcinoma (ATC) is a rare and deadly malignant tumor in humans. It is prone to developing resistance to radiotherapy and chemotherapy. Molecular targeted therapy offers a novel way to treat ATC. The BRAF mutation is closely associated with many cancers, including thyroid carcinoma. Vemurafenib, a small-molecule inhibitor, is specifically designed to target the mutant serine/threonine kinase BRAF. The objective of this study is to elucidate the regulatory mechanisms underlying the effects of vemurafenib on human anaplastic thyroid carcinoma cell line FRO and to assess its potential therapeutic role. Methods: The effects of vemurafenib on the proliferation of FRO cells were assessed by the CCK-8 method and Colony-forming assay. Transwell chambers and scratch tests were employed to examine the impact of vemurafenib on the invasion and migration of FRO cells. Apoptosis and cycle distribution of FRO cells were analyzed by tunel assay and flow cytometry. The effects of vemurafenib on the expression of BRAF-activated non-protein coding RNA (BANCR), Bax, Bcl2, and E-cadherin were evaluated by qRT-PCR. Furthermore, the effects of vemurafenib on the expression of phosphoinositol-3-kinase (PI3K)/phosphoinositol-3-kinase (AKT) pathway-related proteins, BRAF, CyclinD1, Bcl-2, Bax, and E-cadherin proteins in FRO cells were investigated through the western-blot method. All experiments were conducted in three replicates. Results: Vemurafenib was observed to inhibit proliferation and induce apoptosis in a dose- and time-dependent manner (P

Natural disasters pose serious threats to human survival. With global warming, disaster chains related to extreme weather are becoming more common, making it increasingly urgent to understand the relationships between different types of natural disasters. However, there remains a lack of research on the frequent spatial-temporal intervals between different disaster events. In this study, we utilize textual records of natural disaster events to mine frequent spatial-temporal patterns of disasters in China. We first transform the discrete spatial-temporal disaster events into a graph structure. Due to the limit of computing power, we reduce the number of edges in the graph based on domain expertise. We then apply the GraMi frequent subgraph mining algorithm to the spatial-temporal disaster event graph, and the results reveal frequent spatial-temporal intervals between disasters and reflect the spatial-temporal changing pattern of disaster interactions. For example, the pattern of sandstorms happening after gales is mainly concentrated within 50 km and rarely happens at farther spatial distances, and the most common temporal interval is 1 day. The statistical results of this study provide data support for further understanding disaster association patterns and offer decision-making references for disaster prevention efforts.

Owing to the increased demand for autonomous driving and advanced driver assistant systems, autonomous parking configurations have been widely researched. In order to solve the problem of path tracking accuracy degradation, caused by ignoring the external interference in the actual parking process and the uncertainty of vehicle steering modeling, a parking path tracking algorithm, combining Sliding Model Control (SMC) and Extended State Observer (ESO), is proposed. First, the vehicle kinematics model is established, which includes many external interference factors, such as lateral position, speed, heading angle, uncertainty parameters and time delay of steering mechanism. Considering the vehicle physical constraints and boundary condition constraints, during the parking process, the parking reference path is designed according to reverse outbound driving, while the parking collision analysis and path smoothing are further carried out. Next, an ESO is designed to observe and compensate the external disturbances and model uncertainties, treating these as the total disturbances of the system. On this basis, a SMC for parallel parking path tracking is designed. The observed value of ESO is used as the compensation in the SMC, to weaken the influence of external interference. Finally, using Matlab simulation, the feasibility and effectiveness of the proposed path planning and tracking control method are verified. The simulation results show that, the maximum tracking error of lateral position is less than 0.01m, whereas the maximum tracking error of heading angle is less than 2.5°. Comparing two control strategies, the control effect of the designed SMC with ESO is better than that of the traditional SMC controller, while the ability of resisting external interference is stronger. In addition, real vehicle tests are carried out, to verify the effectiveness of the proposed control method. The test results show that, the vehicle can safely park in the parking space, quickly and accurately, even if there is external interference. The proposed method can produce the parking trajectory according to the given constraints and control the vehicle to complete the parking operation accurately along the planned path.

In this article, we consider the following fractional (p,q)-Laplacian problem (−Δ)ps1u+(−Δ)qs2u+V(x)(|u|p−2u+|u|q−2u)=f(u)+λ|u|r−2u, where x∈RN, (−Δ)ps1 is the fractional p-Laplacian operator ((−Δ)qs2 is similar), 00 is small.

Syndecan-1 (SDC1) modified lipid bilayer (LB)-coated mesoporous silica nanoparticles (MSN) to co-deliver gemcitabine (GEM) and honokiol (HNK) were prepared for the targeting treatment of pancreatic cancer. The encapsulation efficiencies of GEM and HNK in SDC1-LB-MSN-GEM/HNK were determined to be 60.3 ± 3.2% and 73.0 ± 1.1%. The targeting efficiency of SDC1-LB-MSN-GEM/HNK was investigated in BxPC-3 cells in vitro. The fluorescence intensity in the cells treated with SDC1-LB-MSN-Cou6 was 2-fold of LB-MSN-Cou6-treated cells, which was caused by SDC1/IGF1R-mediated endocytosis. As anticipated, its cytotoxicity was significantly increased. Furthermore, the mechanism was verified that SDC1-LB-MSN-HNK induced tumor cell apoptosis through the mitochondrial apoptosis pathway. Finally, the biodistribution, tumor growth inhibition, and preliminary safety studies were performed on BALB/c nude mice bearing BxPC-3 tumor models. The tumor growth inhibition index of SDC1-LB-MSN-GEM/HNK was 56.19%, which was 1.45-fold and 1.33-fold higher than that of the free GEM/HNK and LB-MSN-GEM/HNK treatment groups, respectively. As a result, SDC1-LB-MSN-GEM/HNK combined advantages of both GEM and HNK and simultaneously targeted and eliminated pancreatic cancerous and cancer-associated stromal cells. In summary, the present study demonstrated a new strategy of synergistic GEM and HNK to enhance the therapeutic effect of pancreatic cancer via the targeting depletion of tumor stroma.

Esophageal cancer which results in a relatively higher death rate is one of the most common cancers throughout the world. CT radiomics is a study to extract radiomics characteristics which are generalized from a large amount of CT images. These characteristics then underwent high-throughput quantitative analysis so that more heterogeneity information of the caner can be obtained. CT radiomics has been gradually used in forecast clinical stages and pathological differentiation of esophageal cancer in recent years, and applied in assessment of treatment effect and prognosis evaluation as well. This paper focuses on the application of CT radiomics in esophageal cancer and its progress.

IntroductionErectile dysfunction (ED), especially psychological ED (pED), is usually accompanied with psychological factors, which are related to abnormal activity in brain regions involved in sexual behavior. However, the mechanisms underlying functional changes in the brain of pED are still unclear. The present study aimed to explore the abnormalities of brain function, as well as their relationships with sexual behavior and emotion in pED patients.Materials and methodsResting state functional magnetic resonance imaging (rs-fMRI) data were collected from 31 pED patients to 31 healthy controls (HCs). The values of amplitude of fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) were calculated and compared between groups. In addition, the associations between abnormal brain regions and clinical features were evaluated by Pearson correlation analyses.ResultsCompared to HCs, pED patients demonstrated decreased fALFF values in the left medial superior frontal gyrus (had decreased FC values with the left dorsolateral superior frontal gyrus), the left lingual gyrus (had decreased FC values with the left parahippocamal gyrus and insula), the left putamen (had decreased FC values with the right caudate) and the right putamen (had decreased FC values with the left putamen and the right caudate). The fALFF values of the left medial superior frontal gyrus were negatively correlated with the fifth item scores of International Index of Erectile Function (IIEF-5). Negative relationships were found between fALFF values of the left putamen and the second item scores of Arizona Sexual Scale (ASEX). FC values between the right putamen and caudate were negatively related to the state scores of State-Trait Anxiety Inventory (STAI-S).ConclusionAltered brain function were found in the medial superior frontal gyrus and caudate-putamen of pED patients, which were associated with sexual function and psychological condition. These findings provided new insights into the central pathological mechanisms of pED.

This paper investigates global dynamics in fractional-order dual inertial neural networks with time lags. Firstly, according to some crucial features of Mittag-Leffler functions and Banach contracting mapping principle, the existence and uniqueness of S-asymptotically ω-periodic oscillation of the model are gained. Secondly, by using the comparison principle and the stability criteria of delayed Caputo fractional-order differential equations, global asymptotical stability of the model is studied. In the end, the feasibility and effectiveness of the obtained conclusions are supported by two numerical examples. There are few papers focus on S-asymptotically ω-periodic dynamics in fractional-order dual inertial neural networks with time-varying lags, apparently, the works in this paper fill some of the gaps.

This paper addresses the bifurcation control of a fractional-order Lokta-Volterra predator– prey model by using delay feedback control. By employing time delay as a bifurcation parameter, the conditions of bifurcation are gained for controlled systems. Then, it indications that the onset of bifurcation can be postponed as feedback gain decreases. An example numerical results are ultimately exploited to validate the correctness of the the proposed scheme.

Exponential Euler differences have got rapid development recently for integer-order differential equations. But there are few papers focusing on this difference to fractional differential equations. This paper establishes the basic structure of Mittag-Leffler implicit Euler scheme for fractional differential equations by using the constant variation methods in fractional calculus. More critically, since the acquired difference forms belong to the scope of implicit Euler differences and then the fractional PECE algorithms are proposed to solve these implicit differences in numerical calculations effectively. Besides, a novel nonlocal difference operator is proposed and some relative properties are presented. In the end, the existence and boundedness of a unique globally exponentially stable solution of some nonlocal difference system with short-term memory are investigated. Some calculative examples and numerical simulations are given to illustrate the primary research findings.

We studied the unique kinematic properties in massive filament G352.63-1.07 at 10 ^3 au spatial scale with the dense molecular tracers observed with the Atacama Large Millimeter/submillimeter Array. We find the central massive core M1 (12 M _⊙ ) being separated from the surrounding filament with a velocity difference of $v-{\overline{v}}_{\mathrm{sys}}=-2\,\mathrm{km}\,{{\rm{s}}}^{-1}$ and a transverse separation within 3″. Meanwhile, as shown in multiple dense-gas tracers, M1 has a spatial extension closely aligned with the main filament and is connected to the filament toward both its ends. M1 thus represents a very beginning state for a massive, young star-forming core escaping from the parental filament, within a timescale of ∼4000 yr. Based on its kinetic energy (3.5 × 10 ^44 erg), the core escape is unlikely solely due to the original filament motion or magnetic field but requires more energetic events such as a rapid intense anisotropic collapse. The released energy also seems to noticeably increase the environmental turbulence. This may help the filament to become stabilized again.

There is growing evidence that high-mass star formation and hub-filament systems (HFS) are intricately linked. The gas kinematics along the filaments and the forming high-mass star(s) in the central hub are in excellent agreement with the new generation of global hierarchical high-mass star formation models. In this paper, we present an observational investigation of a typical HFS cloud, G310.142+0.758 (G310 hereafter), which reveals unambiguous evidence of mass inflow from the cloud scale via the filaments onto the forming protostar(s) at the hub conforming with the model predictions. Continuum and molecular line data from the ATOMS and MALT90 surveys that cover different spatial scales are used. Three filaments (with a total mass of 5.7 ± 1.1 × 10 ^3 M _⊙ ) are identified converging toward the central hub region where several signposts of high-mass star formation have been observed. The hub region contains a massive clump (1280 ± 260 M _⊙ ) harboring a central massive core. Additionally, five outflow lobes are associated with the central massive core implying a forming cluster. The observed large-scale, smooth, and coherent velocity gradients from the cloud down to the core scale, and the signatures of infall motion seen in the central massive clump and core, clearly unveil a nearly continuous, multi-scale mass accretion/transfer process at a similar mass infall rate of ∼10 ^−3 M _⊙ yr ^−1 over all scales, feeding the central forming high-mass protostar(s) in the G310 HFS cloud.

This paper gives some results on almost automorphic strong solutions to time-fractional partial differential equations by employing a mix o thef Galerkin method, Fourier series, and Picard iteration. As an application, the existence, uniqueness, and global Mittag–Leffler convergence of almost automorphic strong solution are discussed to a concrete time-fractional parabolic equations. To the best of our knowledge, this is the first study on almost automorphic strong solutions on this subject.

In this paper, we consider the following Kirchhoff problem −a+b∫R3∇u2dxΔu+λVxu=up−2u, in R3u∈H1R3 where a,b>0 are constants, λ is a positive parameter, and 4

In this article, a novel semi-discrete model for stochastic competitive neural networks (SCNNs) is proposed. At first, taking advantage of some famous inequalities and fixed point theory, a few conditions are obtained for the existence of 2p-th mean almost periodic sequence (MAPS) of the semi-discrete stochastic model. In the next palace, 2p-th moment global exponential stability (MGES) of the above model is discussed as well. The research findings exhibit the stochastic and delayed effects on the mean dynamics of the semi-discrete stochastic networks. In the end, some numerical illustrations are presented to visually expound the feasibility of the works in this paper. The methods in this article could be applied to investigate other models in the areas of science and engineering.

Abstract An enzyme-responsive colon-specific delivery system was developed based on hollow mesoporous silica spheres (HMSS) to which biodegradable chitosan (CS) was attached via cleavable azo bonds (HMSS–N=N–CS). Doxorubicin (DOX) was encapsulated in a noncrystalline state in the hollow cavity and mesopores of HMSS with the high loading amount of 35.2%. In vitro drug release proved that HMSS–N=N–CS/DOX performed enzyme-responsive drug release. The grafted CS could increase the biocompatibility and stability and reduce the protein adsorption on HMSS. Gastrointestinal mucosa irritation and cell cytotoxicity results indicated the good biocompatibility of HMSS and HMSS–N=N–CS. Cellular uptake results indicated that the uptake of DOX was obviously increased after HMSS–N=N–CS/DOX was preincubated with a colonic enzyme mixture. HMSS–N=N–CS/DOX incubated with colon enzymes showed increased cytotoxicity, and its IC50 value was three times lower than that of HMSS–N=N–CS/DOX group without colon enzymes. The present work lays the foundation for subsequent research on mesoporous carriers for oral colon-specific drug delivery.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide. Mitochondrial dysfunction is thought to be an early event in the onset and progression of AD; however, the precise underlying mechanisms remain unclear. In this study, we investigated mitochondrial proteins involved in organelle dynamics, morphology and energy production in the medial prefrontal cortex (mPFC) and hippocampus (HIPP) of young (1∼2 months), adult (4∼5 months) and aged (9∼10, 12∼18 months) APP/PS1 mice. We observed increased levels of mitochondrial fission protein, Drp1, and decreased levels of ATP synthase subunit, ATP5A, leading to abnormal mitochondrial morphology, increased oxidative stress, glial activation, apoptosis, and altered neuronal morphology as early as 4∼5 months of age in APP/PS1 mice. Electrophysiological recordings revealed abnormal miniature excitatory postsynaptic current in the mPFC together with a minor connectivity change between the mPFC and HIPP, correlating with social deficits. These results suggest that abnormal mitochondrial dynamics, which worsen with disease progression, could be a biomarker of early-stage AD. Therapeutic interventions that improve mitochondrial function thus represent a promising approach for slowing the progression or delaying the onset of AD.

In this paper, we consider the nonlinear impulsive generalized fractional differential equations with (p,q)-Laplacian operator for 1

Musk deer (Moschidae), whose secretion is an expensive and irreplaceable component of traditional medicine, have become endangered in the wild due to habitat fragmentation and over-exploitation. In recent years, China has had success in the artificial breeding of forest musk deer, thus relieving the pressure on wild populations. However, many farmed populations are experiencing degradation, and little genetic information is available for conservation management. In this study, we selected 274 individuals from three typical captive populations (originated from the Ta-pa Mountains (Tp), the midrange of the Qinling Mountains (Ql) and the Western Sichuan Plateau (WS), respectively) to evaluate the genetic variations. A total of more than 3.15 billion high-quality clean reads and 4.37 million high-quality SNPs were generated by RAD sequencing. Based on the analysis, we found that captive forest musk deer populations exhibit a relatively low level of genetic diversity. Ql displayed a higher level of genetic diversity than the Tp and WS populations. Tp and WS had experienced population bottlenecks in the past as inferred from the values of Tajima’s D. There were high levels of heterozygote deficiency caused by inbreeding within the three populations. Population structure analysis suggested that the three populations have evolved independently, and a moderate amount of genetic differentiation has developed, although there was a low level of gene flow between the Ql and Tp populations. Furthermore, the average quantities of musk secreted by musk deer in the Tp and WS populations were significantly higher than that in the Ql population. The present genetic information should be considered in management plans for the conservation and utilization of musk deer from captive breeding.

The existing of avidity cancer stem cells (CSCs) made it an optical strategy to kill cancer cells and CSCs at the same time. Here, we constructed a CSCs specific nanocarrier naming T-S-NLC using the CD133+ targeting peptide TISWPPR (TR) as the targeting moiety attached to the distal end of PEG on salinomycin (Sal) loaded nanostructured lipid carriers (NLC), its pharmaceutical characteristics proved it 128.73 ± 2.09 nm, anionic spheroid with sustained release profile. It's in vitro targeting effect in CD133+ CSCs indicated that it exhibited superior CSCs internalization over non-modified NLC or free drug. Afterwards, it was used in combination with previously designed EGFR specific A-P-NLC (AEYLR peptide-PEG-modified paclitaxel loaded NLC) to achieve the goal to kill the cancer cells and CSCs, simultaneously. The in vitro tumor targeting effect of T-S-NLC + A-P-NLC was affirmed by cellular uptake and proliferation inhibition effect in NCI-H1299 and S180 cell lines showing advanced results over single preparation groups. In vivo tumor targeting effect in S180 tumor-bearing mice also validated the better tumor accumulative effect of the combined group. Last but not least, the in vivo antitumor effect strongly identified the greater tumor suppression effect of T-S-NLC + A-P-NLC than single preparation groups or combined use of free drugs while maintaining a good living state of the mice. To sum up, the combined usage of PTX and Sal active targeting NLC naming A-P-NLC + T-S-NLC which killed cancer cells and CSCs at the same time was a promising drug delivery system.

This paper discusses a kind of coupled nonlocal Laplacian evolution equation with Caputo time-fractional derivatives and proportional delays. Green function and mild solution are firstly established by employing the approach of eigenvalues’ expansions and Fourier analysis technique. By the properties of eigenvalues and Mittag–Leffler functions, several vital estimations of Green functions are presented. In view of these estimations and some appropriate assumptions, the existence and uniqueness of the mild solution are studied by utilizing the Leray–Schauder fixed-point theorem and the Banach fixed-point theorem. Finally, an example is provided to illustrate the effectiveness of our main results.

In the present paper, we consider the following Hamiltonian elliptic system with Choquard’s nonlinear term −Δu+Vxu=∫ΩGvy/x−yβdygv in Ω,−Δv+Vxv=∫ΩFuy/x−yαdyfu in Ω,u=0,v=0 on ∂Ω,where Ω⊂ℝN is a bounded domain with a smooth boundary, 0

In this paper, we show the existence of solutions for an indefinite fractional Schrödinger equation driven by the variable-order fractional magnetic Laplace operator involving variable exponents and steep potential. By using the decomposition of the Nehari manifold and variational method, we obtain the existence results of nontrivial solutions to the equation under suitable conditions.

Using conformable fractional calculus on time scales, we first introduce fractional Sobolev spaces on time scales, characterize them, and define weak conformable fractional derivatives. Second, we prove the equivalence of some norms in the introduced spaces and derive their completeness, reflexivity, uniform convexity, and compactness of some imbeddings, which can be regarded as a novelty item. Then, as an application, we present a recent approach via variational methods and critical point theory to obtain the existence of solutions for a p-Laplacian conformable fractional differential equation boundary value problem on time scale T: Tα(Tαup-2Tα(u))(t)=∇F(σ(t),u(σ(t))), Δ-a.e. t∈a,bTκ2, u(a)-u(b)=0, Tα(u)(a)-Tα(u)(b)=0, where Tα(u)(t) denotes the conformable fractional derivative of u of order α at t, σ is the forward jump operator, a,b∈T, 01, and F:[0,T]T×RN→R. By establishing a proper variational setting, we obtain three existence results. Finally, we present two examples to illustrate the feasibility and effectiveness of the existence results.

Let $mathbb{T}$ be a periodic time scale. We use Krasnoselskii's fixed point theorem to show that the neutral functional differential equation with impulses $$displaylines{ x^{Delta}(t)=-A(t)x^sigma(t)+g^Delta(t,x(t-h(t)))+f(t,x(t),x(t-h(t))),quad teq t_j,;tinmathbb{T},cr x(t_j^+)= x(t_j^-)+I_j(x(t_j)), quad jin mathbb{Z}^+ }$$ has a periodic solution. Under a slightly more stringent conditions we show that the periodic solution is unique using the contraction mapping principle.

By means of a three critical points theorem proposed by Brezis and Nirenberg and a general version of Mountain Pass Theorem, we obtain some multiplicity results for periodic solutions of a fourth-order discrete Hamiltonian system Δ4u(t-2)+∇ F(t,u(t))=0 for all t∈ Z.

Gliomas are the most common and aggressive primary tumors in the central nervous system. Recently, Max interactor-1 (MXI1), an antagonist of c-Myc that is involved in brain tumor progression, has been reported to be deregulated in a variety of tumors including glioma. However, the mechanism of MXI1 deregulation in gliomas remains unclear. In this study, we show that the relative expression level of MXI1 is markedly down-regulated in glioma cell lines. Using integrated bioinformatic analysis and experimental confirmation, we identified several miRNAs by screening a panel of predicted miRNAs that may regulate the MXI1 3'UTR. The strongest inhibitory miRNA, miR-155, can attenuate the activity of a luciferase reporter gene that is fused with the MXI1 3'UTR and decrease the expression levels of MXI1 mRNA and protein in U87 glioma cells. The potential role of miR-155 in promoting glioma cell proliferation by targeting MXI1 was confirmed in various glioma cell lines by rescue experiments using MTT assays, EdU incorporation assay, and cell counting experiments. In addition, we determined that the level of MXI1 mRNA was inversely correlated with the expression of miR-155 in 18 sets of glioblastoma multiforme specimens. These findings reveal for the first time that the targeting of MXI1 by miR-155 may result in a reduction in MXI1 expression and promote glioma cell proliferation; this result suggests a novel function of miR-155 in targeting MXI1 in glioma-genesis.

Animal microRNA (miRNA) target prediction is still a challenge, although many prediction programs have been exploited. MiRNAs exert their function through partially binding the messenger RNAs (mRNAs; likely at 3' untranslated regions [3'UTRs]), which makes it possible to detect the miRNA-mRNA interactions in vitro by co-transfection of miRNA and a luciferase reporter gene containing the target mRNA fragment into mammalian cells under a dual-luciferase assay system. Here, we constructed a human miRNA expression library and used a dual-luciferase assay system to perform large-scale screens of interactions between miRNAs and the 3'UTRs of seven genes, which included more than 3,000 interactions with triplicate experiments for each interaction. The screening results showed that the 3'UTR of one gene can be targeted by multiple miRNAs. Among the prediction algorithms, a Bayesian phylogenetic miRNA target identification algorithm and a support vector machine (SVM) presented a relatively better performance (27% for EIMMo and 24.7% for miRDB) against the average precision (17.3%) of the nine prediction programs used here. Additionally, we noticed that a relatively high conservation level was shown at the miRNA 3' end targeted regions, as well as the 5' end (seed region) binding sites.

This paper considers a class of Caputo fractional-order genetic regulatory networks with time-varying lags in biomedicine and life sciences. Applying some features of Mittag-Leffler function and contraction mapping principle, the sufficient conditions are gained to ensure the existence and uniqueness of S-asymptotically co-periodic solution of the model. Based on comparison principle and stability theorem of linear delayed Caputo fractional-order differential equations, global asymptotical stability of the model is also investigated. The work of this article can improve and expand some existing results. [ABSTRACT FROM AUTHOR]

Using time-scale calculus and construction of a suitable Lyapunov functional, the permanence and uniform asymptotical stability of a ratio-dependent Leslie model with feedback control on time scales are studied. The results of this paper extend some recent research results. An illustrative example with numerical simulations is employed to visually manifest the theoretical findings. [ABSTRACT FROM AUTHOR]

Mitophagy is an important quality-control mechanism in eukaryotic cells, and defects in mitophagy correlate with aging phenomena and neurodegenerative disorders. It is known that different mitochondrial matrix proteins undergo mitophagy with very different rates but, to date, the mechanism underlying this selectivity at the individual protein level has remained obscure. We now present evidence indicating that protein phosphorylation within the mitochondrial matrix plays a mechanistic role in regulating selective mitophagic degradation in yeast via involvement of the Aup1 mitochondrial protein phosphatase, as well as 2 known matrix-localized protein kinases, Pkp1 and Pkp2. By focusing on a specific matrix phosphoprotein reporter, we also demonstrate that phospho-mimetic and nonphosphorylatable point mutations at known phosphosites in the reporter increased or decreased its tendency to undergo mitophagy. Finally, we show that phosphorylation of the reporter protein is dynamically regulated during mitophagy in an Aup1-dependent manner. Our results indicate that structural determinants on a mitochondrial matrix protein can govern its mitophagic fate, and that protein phosphorylation regulates these determinants. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the diagnostic value of interleukin-18 (IL-18) and troponin (TnI) in sepsis.Methods: This retrospective analysis included 117 patients with sepsis (patient group) and 92 subjects who attended regular physical examinations (control group). We compared IL-18 and TnI expressions before treatment (T1) and on day 5 (T2), day 10 (T3) and day 15 (T4) of treatment. Acute Physiology and Chronic Health Evaluation II (APACHE II) guidelines were used to analyse the correlation between IL-18, TnI and APACHE II scores.Results: At T1, T2, T3 and T4, the IL-18 and TnI levels were all higher in the patient group than in the control group (p<0.001). In the patient group, peak IL-18 and TnI levels were noted at T1, followed by T2, T3 and T4 (p<0.001). The linear correlation analysis revealed positive correlations between IL-18 and TnI levels and APACHE II score (r =0.759, 0.866, p <0.001). The 3-year survival rates of subjects with high IL-18 or TnI expression levels were all lower than of those with low expression levels (p=0.047, 0.048). In patients with sepsis, the expression of TnI and IL-18 is high and is positively correlated with APACHE II scores.Conclusions: Monitoring TnI and IL-18 levels can effectively evaluate the severity and recovery of patients with sepsis. [ABSTRACT FROM AUTHOR]

Esophageal cancer is one of the most common type of malignancies. Telomerase activity, which is absent or weakly detected in the majority of human somatic cells, is elevated in esophageal cancer. Although azidothymidine (AZT), a reverse transcriptase inhibitor, has been utilized as a treatment for tumors, its role in treating esophageal cancer has not been confirmed. The aim of the present study was to determine the effect of AZT on telomerase activity and the proliferation of the human esophageal cancer cell line TE‑11. A telomeric repeat amplification assay was utilized to detect telomerase activity following treatment of TE‑11 cells with AZT. The effect of AZT on TE‑11 cell cycle distribution was determined by flow cytometry. Cellular DNA damage was evaluated by a comet assay and an MTT assay demonstrated that AZT significantly inhibited the viability of TE‑11 cells, in a time‑and dose‑dependent manner. In addition, TE‑11 cells treated with various concentrations of AZT exhibited a significant reduction in telomerase activity and percentage of cells in the G1/G0 phase, and an increase in the percentage of cells in the S phase. High doses of AZT caused DNA damage, and enhanced the expression levels of γ‑H2A histone family member X and phosphorylated checkpoint kinase 2 in TE‑11 cells. These results demonstrated that AZT effectively inhibits proliferation of the TE‑11 human esophageal cancer cell line in vitro. The growth inhibitory effects were associated with a reduction in telomerase activity, S and G2/M phase cell cycle arrest, and enhanced DNA damage, suggesting that AZT may be utilized in the clinic for the treatment of esophageal cancer. [ABSTRACT FROM AUTHOR]