Search

Aucuba (Garryaceae), which includes approximately ten evergreen woody species, is a genus endemic to East Asia. Their striking morphological features give Aucuba species remarkable ornamental value. Owing to high levels of morphological divergence and plasticity, species definitions of Aucuba remain perplexing and problematic. Here, we sequenced and characterized the complete plastid genomes (plastomes) of three Aucuba species: Aucuba chlorascens, Aucuba eriobotryifolia, and Aucuba japonica. Incorporating Aucuba plastomes available in GenBank, a total of seven Aucuba plastomes, representing six out of ten species of Aucuba, were used for comparative plastome analysis, phylogenetic analysis and divergence time estimation in this study. Comparative analyses revealed that plastomes of Aucuba are highly conserved in size, structure, gene content, and organization, and exhibit high levels of sequence similarity. Phylogenetic reconstruction based on 68 plastid protein-coding genes strongly supported the monophyly of Garryales, Garryaceae and Aucuba. Aucuba eriobotryifolia was sister to the other Aucuba species examined, consistent with its unique fused anther locule. The divergence time of Aucuba was estimated to be approximately late Miocene. Extant Aucuba species derived from recent divergence events associated with the establishment of monsoonal climates in East Asia and climatic fluctuations.

As an important part of the second defense line of the power system, the Security and Stability Control System (SSCS) is of great significance to ensure the reliable operation of the power system. However, SSCS still lacks an effective security mechanism and is easily accessed by attackers, thus posing a threat to the stable and reliable operation of the power system. To tackle this issue, we propose a blockchain-based identity authentication scheme for Intelligent Electronic Devices (IEDs) of SSCS. We first propose an identity authentication system model for IEDs and design the deployment of consortium chain nodes on IEDs, with architectural characteristics of SSCS and the working scenario of IEDs taken into consideration. The consortium chain is used to store credentials required for authentication, ensuring that they are tamper-proof. We combine IP address, port number and physical ID, and propose the unique identification of IEDs, with a data structure designed for the identification. We also propose a lightweight identity authentication method based on renewable hash chains, with hash chains used as one-time authentication passwords, and introduce a renewal mechanism of hash chains. Further, the detailed processes of registration and authentication phase are designed. Finally, the security analysis shows that our identity authentication scheme can resist various attacks, and the feasibility of our scheme is verified by experiments.

Abstract Background Overweight or obesity has been evidenced as an important risk factor involved in the incidence, mortality, and therapy response of multiple malignancies. However, the differences between healthy and obesity tumor patients at the molecular and multi-omics levels remain unclear. Methods Our study performed a comprehensive and multidimensional analysis in fourteen tumor types of The Cancer Genome Atlas (TCGA) and found body mass index (BMI)-related genes in multiple tumor types. Furthermore, we compared composite expression between normal, overweight, and obese patients of each immune cell subpopulation and metabolism gene subset. Statistical significance was calculated via the Kruskal-Wallis rank-sum test. Results Our analysis revealed that BMI-related genes are enriched in multiple tumor-related biological pathways involved in intracellular signaling, immune response, and metabolism. We also found the different relationships between BMI and different immune cell infiltration and metabolic pathway activity. Importantly, we found that many clinically actionable genes were BMI-affect genes. Conclusion Overall, our data indicated that BMI-associated molecular characteristics involved in tumor immune and metabolic pathways, which may highlight the clinical importance of considering BMI-associated molecular signatures in cancer precision medicine.

Abstract Background Clinical outcome of adrenocortical carcinoma (ACC) varies because of its heterogeneous nature and reliable prognostic prediction model for adult ACC patients is limited. The objective of this study was to develop and externally validate a nomogram for overall survival (OS) prediction in adult patients with ACC after surgery. Methods Based on the data from the Surveillance Epidemiology, and End Results (SEER) database, adults patients diagnosed with ACC between January 1988 and December 2015 were identified and classified into a training set, comprised of 404 patients diagnosed between January 2007 and December 2015, and an internal validation set, comprised of 318 patients diagnosed between January 1988 and December 2006. The endpoint of this study was OS. The nomogram was developed using a multivariate Cox proportional hazards regression algorithm in the training set and its performance was evaluated in terms of its discriminative ability, calibration, and clinical usefulness. The nomogram was then validated using the internal SEER validation, also externally validated using the Cancer Genome Atlas set (TCGA, 82 patients diagnosed between 1998 and 2012) and a Chinese multicenter cohort dataset (82 patients diagnosed between December 2002 and May 2018), respectively. Results Age at diagnosis, T stage, N stage, and M stage were identified as independent predictors for OS. A nomogram incorporating these four predictors was constructed using the training set and demonstrated good calibration and discrimination (C-index 95% confidence interval [CI], 0.715 [0.679–0.751]), which was validated in the internal validation set (C-index [95% CI], 0.672 [0.637–0.707]), the TCGA set (C-index [95% CI], 0.810 [0.732–0.888]) and the Chinese multicenter set (C-index [95% CI], 0.726 [0.633–0.819]), respectively. Encouragingly, the nomogram was able to successfully distinguished patients with a high-risk of mortality in all enrolled patients and in the subgroup analyses. Decision curve analysis indicated that the nomogram was clinically useful and applicable. Conclusions The study presents a nomogram that incorporates clinicopathological predictors, which can accurately predict the OS of adult ACC patients after surgery. This model and the corresponding risk classification system have the potential to guide therapy decisions after surgery.

Hearing loss is a common disease due to sensory loss caused by the diseases in the inner ear. The development of delivery systems for inner ear disease therapy is important to achieve high efficiency and reduce side effects. Currently, traditional drug delivery systems exhibit the potential to be used for inner ear disease therapy, but there are still some drawbacks. As nanotechnology is developing these years, one of the solutions is to develop nanoparticle-based delivery systems for inner ear disease therapy. Various nanoparticles, such as soft material and inorganic-based nanoparticles, have been designed, tested, and showed controlled delivery of drugs, improved targeting property to specific cells, and reduced systemic side effects. In this review, we summarized recent progress in nanocarriers for inner ear disease therapy. This review provides useful information on developing promising nanocarriers for the efficient treatment of inner ear diseases and for further clinical applications for inner ear disease therapy.

Hearing loss is one of the most common disabilities affecting both children and adults worldwide. However, traditional treatment of hearing loss has some limitations, particularly in terms of drug delivery system as well as diagnosis of ear imaging. The blood–labyrinth barrier (BLB), the barrier between the vasculature and fluids of the inner ear, restricts entry of most blood-borne compounds into inner ear tissues. Nanoparticles (NPs) have been demonstrated to have high biocompatibility, good degradation, and simple synthesis in the process of diagnosis and treatment, which are promising for medical applications in hearing loss. Although previous studies have shown that NPs have promising applications in the field of inner ear diseases, there is still a gap between biological research and clinical application. In this paper, we aim to summarize developments and challenges of NPs in diagnostics and treatment of hearing loss in recent years. This review may be useful to raise otology researchers’ awareness of effect of NPs on hearing diagnosis and treatment.

In recent years, neural stem cell transplantation has received widespread attention as a new treatment method for supplementing specific cells damaged by disease, such as neurodegenerative diseases. A number of studies have proved that the transplantation of neural stem cells in multiple organs has an important therapeutic effect on activation and regeneration of cells, and restore damaged neurons. This article describes the methods for inducing the differentiation of endogenous and exogenous stem cells, the implantation operation and regulation of exogenous stem cells after implanted into the inner ear, and it elaborates the relevant signal pathways of stem cells in the inner ear, as well as the clinical application of various new materials. At present, stem cell therapy still has limitations, but the role of this technology in the treatment of hearing diseases has been widely recognized. With the development of related research, stem cell therapy will play a greater role in the treatment of diseases related to the inner ear.

BackgroundThe selection criteria for hepatic resection (HR) in intermediate-stage (IM) hepatocellular carcinoma (HCC) are still controversial. We used real-world data to evaluate the overall survival (OS) in treatment with HR or transarterial chemoembolization (TACE).MethodsIn total, 942 patients with IM-HCC were categorized into the HR group and the TACE group. OS was analyzed using the Kaplan–Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched (PSM) analysis. Curve smoothing was performed through the generalized additive model. The interaction test was performed to evaluate the impact of HR on OS concerning risk factors. Also, we used multiple imputation to deal with missing data.ResultsIn total, 23.0% (n = 225) of patients received HR. At a median OS of 23.7 months, HR was associated with improved OS in the multivariate analysis [hazard ratio (HzR) = 0.45, 95%CI = 0.35–0.58; after PSM: HzR = 0.56, 95%CI = 0.41–0.77]. Landmark analyses limited to long-term survivors of ≥6 months, ≥1 year, and ≥2 years demonstrated better OS with HR in all subsets (all p 192 U/L. Moreover, TACE might be suitable for patients with LDH levels ≤192 U/L.

Background: Alterations in the brain cortical structures of patients with chronic kidney disease (CKD) have been reported; however, the cause has not been determined yet. Herein, we used Mendelian randomization (MR) to reveal the causal effect of kidney damage on brain cortical structure. Methods: Genome-wide association studies summary data of estimated glomerular filtration rate (eGFR) in 480,698 participants from the CKDGen Consortium were used to identify genetically predicted eGFR. Data from 567,460 individuals from the CKDGen Consortium were used to assess genetically determined CKD; 302,687 participants from the UK Biobank were used to evaluate genetically predicted albuminuria. Further, data from 51,665 patients from the ENIGMA Consortium were used to assess the relationship between genetic predisposition and reduced eGFR, CKD, and progressive albuminuria with alterations in cortical thickness (TH) or surficial area (SA) of the brain. Magnetic resonance imaging was used to measure the SA and TH globally and in 34 functional regions. Inverse-variance weighted was used as the primary estimate whereas MR Pleiotropy RESidual Sum and Outlier, MR-Egger and weighted median were used to detect heterogeneity and pleiotropy. Findings: At the global level, albuminuria decreased TH (β = −0.07 mm, 95% CI: −0.12 mm to −0.02 mm, P = 0.004); at the functional level, albuminuria reduced TH of pars opercularis gyrus without global weighted (β = −0.11 mm, 95% CI: −0.16 mm to −0.07 mm, P = 3.74×10−6). No pleiotropy was detected. Interpretation: Kidney damage causally influences the cortex structure which suggests the existence of a kidney-brain axis. Funding: This study was supported by the Science and Technology Planning Project of Guangdong Province (Grant No. 2020A1515111119 and 2017B020227007), the National Key Research and Development Program of China (Grant No. 2018YFA0902803), the National Natural Science Foundation of China (Grant No. 81825016, 81961128027, 81772719, 81772728), the Key Areas Research and Development Program of Guangdong (Grant No. 2018B010109006), Guangdong Special Support Program (2017TX04R246), Grant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, and Grants from the Guangdong Science and Technology Department (2020B1212060018).

The modeling of the deformation and failure process of a cyclotetramethylene tetranitramine modified double-base (HMX-MDB) propellant based on the microstructure is of great importance for its manufacturing process and storage lifetime. In the present work, the debonding, nucleation, and crack propagation in an HMX-MDB propellant were investigated experimentally and numerically. Stress-strain responses and viscoelastic parameters were obtained through uniaxial tensile tests on the HMX-MDB propellant and stress relaxation tests on a nitrocellulose-nitroglycerine (NC-NG) propellant, respectively. A two-dimensional representative volume element (RVE) model was developed based on the molecular dynamics method by embedding HMX particles in the NC-NG matrix. A zero-thickness cohesive element was used to simulate the damage behavior of the matrix and the interface. A piecewise cohesive zone model (PCZM) was established to capture stress-strain responses resulted from the matrix rupture and the debonding process at the particle-matrix interface. The effects of matrix strength and interface strength on the mechanical properties of the HMX-MDB propellant were investigated by PCZM. The different ratio of matrix strength to interface strength revealed three kinds of HMX-MDB propellant’s damage patterns: matrix cracking, matrix cracking followed by particle-matrix interfacial debonding, and particle-matrix interfacial debonding followed by matrix cracking.

The abnormality of RNA-binding proteins (RBPs) is closely related to the tumorigenesis and development of esophageal squamous cell carcinoma (ESCC), and has been an area of interest for research recently. In this study, 162 tumors and 11 normal samples are obtained from The Cancer Genome Atlas database, among which 218 differentially expressed RBPs are screened. Finally, a prognostic model including seven RBPs (CLK1, DDX39A, EEF2, ELAC1, NKRF, POP7, and SMN1) is established. Further analysis reveals that the overall survival (OS) rate of the high-risk group is lower than that of the low-risk group. The area under the receiver operating characteristic (ROC) curve (AUC) of the training group and testing group is significant (AUCs of 3 years are 0.815 and 0.694, respectively, AUCs of 5 years are 0.737 and 0.725, respectively). In addition, a comprehensive analysis of seven identified RBPs shows that most RBPs are related to OS in patients with ESCC, among which EEF2 and ELCA1 are differentially expressed at the protein level of ESCC and control tissues. CLK1 and POP7 expressions in esophageal cancer tumor samples are undertaken using the tissue microarray, and show that CLK1 mRNA levels are relatively lower, and POP7 mRNA levels are higher compared with non-cancerous esophageal tissues. Survival analysis reveals that a higher expression of CLK1 predicts a significant worse prognosis, and a lower expression of POP7 predicts a worse prognosis in esophageal cancer. These results suggest that CLK1 may promote tumor progression, and POP7 may hinder the development of esophageal cancer. In addition, gene set enrichment analysis reveals that abnormal biological processes related to ribosomes and abnormalities in classic tumor signaling pathways such as TGF-β are important driving forces for the occurrence and development of ESCC. Our results provide new insights into the pathogenesis of ESCC, and seven RBPs have potential application value in the clinical prognosis prediction of ESCC.

The natural convection and anisotropic heat transfer of ferro-nanofluids in partially heated enclosures is studied for revealing the influence of the anisotropy of thermal conductivity, which is generated by the existence of external magnetic field. The viscosity of the ferro-nanofluid is assumed to vary with the nanoparticle concentration. The constitutive model of the anisotropic thermal conductivity is derived based on the principle of material frame indifference of Continuum Mechanics, and the numerical solver is built based on the library of OpenFOAM. Both problems of pure heat conduction and natural convection are investigated, and a series of numerical simulations are conducted for different relevant parameters such as the types of the magnetic field, nanoparticle concentration, Hartmann number and Rayleigh number. The numerical results show that the heat transfer along the magnetic field direction is apparently enhanced with Hartmann number of 0.1 and nanoparticle concentration of 0.05, which implies the feasibility of controlling the heat transfer of the ferro-nanofluids by adjusting the external magnetic field. Furthermore, for pure heat conduction, the increasing of the Hartmann number and nanoparticle concentration raises the anisotropic thermal conductivity; and in the natural convection case, increasing the intensity of magnetic field could also raises the Lorentz force resistance. In addition, the Nusselt number is larger with higher Rayleigh number and lower Hartmann number, as the Rayleigh number increases from 1×103 to 1×105, the average Nusselt number on the heater increases from 0.888 to 3.139, and it decreases from 3.789 to 2.866 when Hartmann number is 0 and 10.

Background/Aims: Diabetic foot ulcers (DFUs) present a major challenge in clinical practice, and hyperglycemia-induced angiogenesis disturbance and endothelial dysfunction likely exacerbate DFUs. The long-acting glucagon-like peptide-1 (GLP-1) analog liraglutide (Lira) is a potential activator of AMP-activated protein kinase (AMPK) that appears to enhance endothelial function and have substantial pro-angiogenesis and antioxidant stress effects. Therefore, in this study, we aimed to investigate whether the protective role of Lira in diabetic wound healing acts against the mechanisms underlying hyperglycemia-induced endothelial dysfunction and angiogenesis disturbance.Methods: Accordingly, db/db mice were assessed after receiving subcutaneous Lira injections. We also cultured human umbilical vein endothelial cells (HUVECs) in either normal or high glucose (5.5 or 33 mM glucose, respectively) medium with or without Lira for 72 h.Results: An obvious inhibition of hyperglycemia-triggered endothelial dysfunction and angiogenesis disturbance was observed; follow by a promotion of diabetic wound healing under Lira treatment combined with restored hyperglycemia-impaired AMPK signaling pathway activity. AMPKα1/2 siRNA and Compound C (Cpd C), an inhibitor of AMPK, abolished both Lira-mediated endothelial protection and pro-angiogenesis action, as well as the diabetic wound healing promoted by Lira. Furthermore, hypoxia inducible factor-1α (Hif-1α; transcription factors of AMPK substrates) knockdown in HUVECs and db/db mice demonstrated that Lira activated AMPK to prevent hyperglycemia-triggered endothelial dysfunction and angiogenesis disturbance, with a subsequent promotion of diabetic wound healing that was Hif-1α–heme oxygenase-1 (HO-1) axis-dependent. Taken together, these findings reveal that the promotion of diabetic wound healing by Lira occurs via its AMPK-dependent endothelial protection and pro-angiogenic effects, which are regulated by the Hif-1α–HO-1 axis.

Cardiovascular complications are a well-documented limitation of conventional cancer chemotherapy. As a notable side effect of cisplatin, cardiotoxicity represents a major obstacle to the treatment of cancer. Recently, it has been reported that cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) signaling pathway was associated with the occurrence and development of cardiovascular diseases. However, the effect of STING on cardiac damage caused by cisplatin remains unclear. In this study, cisplatin was shown to activate the cGAS-STING signaling pathway, and deficiency of STING attenuated cisplatin-induced cardiotoxicity in vivo and in vitro. Mechanistically, the STING-TNF-α-AP-1 axis contributed to cisplatin-induced cardiotoxicity by triggering cardiomyocyte apoptosis. In conclusion, our results indicated that STING might be a critical regulator of cisplatin-induced cardiotoxicity and be considered as a potential therapeutic target for preventing the progression of chemotherapy-associated cardiovascular complications.

ObjectiveThe adoption of hearts from donation after circulatory death (DCD) is a promising approach for the shortage of suitable organs in heart transplantation. However, DCD hearts suffer from serious ischemia/reperfusion injury (IRI). Recent studies demonstrate that nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-mediated pyroptosis is a novel target to ameliorate myocardial IRI. Melatonin is shown to inhibit NLRP3 inflammasome-mediated pyroptosis. Therefore, this study is designed to verify the hypothesis that melatonin can protect the heart graft preserved with ex vivo heart perfusion (EVHP) against myocardial IRI via inhibiting NLRP3 inflammasome-mediated pyroptosis in a rat model of DCD.MethodsDonor-heart rats were randomly divided into three groups: (1) Control group: non-DCD hearts were harvested from heart-beating rats and immediately preserved with allogenic blood-based perfusate at constant flow for 105 min in the normothermic EVHP system; (2) DCD-vehicle group; and (3) DCD-melatonin group: rats were subjected to the DCD procedure with 25 min of warm ischemia injury and preserved by the normothermic EVHP system for 105 min. Melatonin (200 μmol/L) or vehicle was perfused in the cardioplegia and throughout the whole EVHP period. Cardiac functional assessment was performed every 30 min during EVHP. The level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis of heart grafts submitted to EVHP were evaluated.ResultsTwenty five-minute warm ischemia injury resulted in a significant decrease in the developed pressure (DP), dP/dtmax, and dP/dtmin of left ventricular of the DCD hearts, while the treatment with melatonin significantly increased the DP, dP/dtmax of the left ventricular of DCD hearts compared with DCD-vehicle group. Furthermore, warm ischemia injury led to a significant increase in the level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis in the hearts preserved with EVHP. However, melatonin added in the cardioplegia and throughout the EVHP period significantly attenuated the level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis compared with DCD-vehicle group.ConclusionEVHP combined with melatonin post-conditioning attenuates myocardial IRI in DCD hearts by inhibiting NLRP3 inflammasome-mediated pyroptosis, which might expand the donor pool by the adoption of transplantable DCD hearts.

Gel fuel potentially combines the advantages of solid fuel and liquid fuel due to its special rheological properties, which have essential impacts on the application of gel fuel in propulsion systems. In this paper, we study the rheological property of organic kerosene gel through a series of measurements on its viscosity as a function of the shear rate, temperature, and shear history. The measured datasets are then fitted with constitutive relationships between the viscosity and shear rate at three different levels: the power law shear-thinning model, the power law dependency on both the temperature and shear rate, and the thixotropic property. It is found that intense pre-shear could exhaust thixotropy and reduce viscosity of the kerosene gel. For the power law shear-thinning model, the consistency index increases with the gellant mass fraction, whereas the power law exponent remains constant. The dependence of viscosity on temperature could be well approximated by an empirical power law relationship. As for the thixotropic property of the kerosene gel, the fitted second-order kinetic model corresponds accurately to the viscosity at different shear rates and shear times. The constitutive models fitted in this work at different levels are consistent with each other and provide useful tools for further applications of organic kerosene gel fuel.

Alternative splicing (AS) is a key mechanism involved in regulating gene expression and is closely related to tumorigenesis. The incidence of thyroid cancer (THCA) has increased during the past decade, and the role of AS in THCA is still unclear. Here, we used TCGA and to generate AS maps in patients with THCA. Univariate analysis revealed 825 AS events related to the survival of THCA. Five prognostic models of AA, AD, AT, ES, and ME events were obtained through lasso and multivariate analyses, and the final prediction model was established by integrating all the AS events in the five prediction models. Kaplan–Meier survival analysis revealed that the overall survival rate of patients in the high-risk group was significantly shorter than that of patients in the low-risk group. The ROC results revealed that the prognostic capabilities of each model at 3, 5, and 8 years were all greater than 0.7, and the final prognostic capabilities of the models were all greater than 0.9. By reviewing other databases and utilizing qPCR, we verified the established THCA gene model. In addition, gene set enrichment analysis showed that abnormal AS events might play key roles in tumor development and progression of THCA by participating in changes in molecular structure, homeostasis of the cell environment and in cell energy. Finally, a splicing correlation network was established to reveal the potential regulatory patterns between the predicted splicing factors and AS event candidates. In summary, AS should be considered an important prognostic indicator of THCA. Our results will help to elucidate the underlying mechanism of AS in the process of THCA tumorigenesis and broaden the prognostic and clinical application of molecular targeted therapy for THCA.

Objective: Atrial fibroblasts are the main component of atrial fibrosis. Data in previous studies proved the implication of miRNAs in AF progression and the association of miR-205 with cancer associated-fibroblasts, while no evidence supported the implication of miR-205 in atrial fibrosis. Therefore, this study aims to explore the effect and mechanism of miR-205/P4HA3 axis on atrial fibrosis.Methods: Angiotensin II (Ang II) was used to induce atrial fibrosis model in rats, which was verified by H&E staining and Masson staining. qRT-PCR and Western blot were applied to measure the expressions of miR-205, P4HA3, collagen I, and α-SMA. The rat atrial fibroblasts were isolated and then subjected to Ang II treatment or cell transfection for determination of cell biological functions using CCK-8, BrdU assay, TUNEL staining, and cell scratch assay. qRT-PCR and Western blot was applied to analyze the expressions of miR-205, P4HA3, collagen I, α-SMA, JNK, and p-JNK in atrial fibroblasts. Dual-luciferase reporter gene assay and RNA immune-precipitation experiment was employed to verify the binding relationship between miR-205 and P4HA3.Results: Ang II induced rats had disordered arrangement of atrial muscles with uneven nuclear sizes and necrotic atrial myocytes, and increased collagen deposition, in which elevated expressions of P4HA3, collagen I, and α-SMA as well as suppressed expression level of miR-205 were found. In vitro, Ang II treatment in atrial fibroblasts with overexpression of P4HA3 facilitated cellular migration and proliferation, with the induction of JNK signaling pathway. However, these trends were reversed after transfection with miR-205 mimic. P4HA3 is a target gene of miR-205.Conclusion: The miR-205/P4HA3 axis is implicated in atrial fibrosis by inhibition of rat fibroblast proliferation and migration and the inactivation of JNK signaling pathway.

Molybdenum disulfide (MoS2), a typical member of the transition metal dichalcogenides (TMDs) group, is known for its excellent electronic performance and is considered a candidate next-generation semiconductor. The preparation of MoS2 nanoflakes for use as the core of semiconducting devices depends on mechanical exfoliation, but its quality has not yet been optimized. In this paper, a novel exfoliation method of achieving MoS2 nanoflakes is proposed. We find that the size and yield of the exfoliated flakes are improved after thermal treatment for 2 h at a temperature of 110°C followed by precooling for 10 min in ambient air. The new method has the advantage of a 152-fold larger size of obtained MoS2 flakes than traditional mechanical exfoliation. This phenomenon may be attributable to the differences in van Der Waals force and the increase in surface free energy at the interface induced by thermal treatment. In addition, a field-effect transistor (FET) was fabricated on the basis of multilayer MoS2 prepared according to a new process, and the device exhibited a typical depleted-FET performance, with an on/off ratio of ~105 and a field-effect mobility of 24.26 cm2/Vs in the saturated region when VG is 10 V, which is generally consistent with the values for devices reported previously. This implies that the new process may have potential for the standard preparation of MoS2 and even other 2D materials as well.

Tampering, forgery and theft of the measurement and control messages in a smart grid could cause one breakdown in the power system. However, no security measures are employed for communications in intelligent substations. Communication services in an intelligent substation have high demands for real-time performance, which must be considered when deploying security measures. This paper studies the security requirements of communication services in intelligent substations, analyzes the security capabilities and shortages of IEC 62351, and proposes a novel security scheme for intelligent substation communications. This security scheme covers internal and telecontrol communications, in which the real-time performance of each security measure is considered. In this scheme, certificateless public key cryptography (CLPKC) is used to avoid the latency of certificate exchange in certificate-based cryptosystem and the problem of key escrow in identity-based cryptosystem; the security measures of generic object-oriented substation event, sampled measure value and manufacturing message specification in IEC 62351 are improved to meet the real-time requirements of the messages as well as to provide new security features to resist repudiation and replay attacks; and the security at transport layer is modified to fit CLPKC, which implements mutual authentication by exchanging signatures. Furthermore, a deployment of CLPKC in an intelligent substation is presented. We also evaluate the security properties of the scheme and analyze the end-to-end delays of secured services by combining theoretical calculation and simulation in this paper. The results indicate that the proposed scheme meets the requirements of security and real-time performance of communications in intelligent substations.

Pancreatic adenocarcinoma is by far the deadliest type of cancer. Inflammation is one of the important risk factors in tumor development. However, it is not yet clear whether deterioration in pancreatic cancer patients is related to inflammation, as well as the underlying mechanism. In addition, JNK is abnormally activated in pancreatic cancer cells and the JNK inhibitor C66 reduces the inflammatory microenvironment in the tumor. Therefore, the aim of this study was to evaluate the role of C66 in the proliferation and migration of pancreatic cancer. Our results showed that various inflammatory cytokines, such as IL-1β, IL-6, IL-8, and IL-15, were more expressed in pancreatic cancer than in the matching normal tissue. Furthermore, C66, a curcumin analogue with good anti-inflammatory activity, inhibited the proliferation and migration of pancreatic cancer cells in a dose-dependent manner, and effectively inhibited the expression of the above inflammatory factors. Our previous research demonstrated that C66 prevents the inflammatory response by targeting JNK. Therefore, in this study, JNK activity in pancreatic cancer cells was investigated, revealing that JNK was highly activated, and the treatment with C66 inhibited the phosphorylation of JNK. Next, shJNK was used to knockdown JNK expression in pancreatic cancer cells to further confirm the role of JNK in the proliferation and migration of this tumor, as well as in the inflammatory tumor microenvironment (TME). The results demonstrated that JNK knockdown could significantly inhibit the proliferation and migration of pancreatic cancer. Moreover, the low JNK expression in pancreatic cancer cells significantly inhibited the expression of various inflammatory factors. These results indicated that C66 inhibited the progression of pancreatic cancer through the inhibition of JNK-mediated inflammation.

Abstract Background Obstructive sleep apnea-hypopnea syndrome (OSAHS) is prone to being complicated with various cardiovascular, cerebrovascular and metabolic conditions. OSAHS, due to its multifactorial nature, entails individualized and comprehensive treatment. So far, no well-established diagnostic criteria for the disease are available. In recent years, miRNA has been shown to be a sensitive biomarker suggestive of the progression and prognosis of many diseases. In this study, we examined some serum miRNAs in healthy OSAHS (OSAHS patients without complication) and OSAHS with arterial hypertension, with an attempt to understand the potential effects on the disease, improve the diagnosis of OSAHS and find OSAHS-related diagnostic markers. Methods Against various diagnostic criteria, participants were divided into three groups: healthy OSAHS, OSAHS with arterial hypertension and healthy controls. Their serum miRNA profiles were assessed by microarray technology, and then differentially expressed miRNAs were verified by quantitative real-time PCR (qRT-PCR). The receiver operating characteristic (ROC) curves of miRNAs were constructed and the areas under the curve (AUC) were calculated. Meanwhile, the miRNAs were subjected to logistic regression analysis. The target genes were bioinformatically assessed, their functions and signaling pathways further determined and eventually an miRNA-gene network was established. Results Analysis with the miRNA array exhibited that, compared with the control group, 12 differentially expressed miRNAs were found in healthy OSAHS, and 33 were found in OSAHS with arterial hypertension. The expression of miR-126-3p, let-7d-5p, miR-7641 and miR-1233-5p, miR-320b, miR-145-5p, miR-107, miR-26a-5p were validated by using qRT-PCR. Bioinformatics analysis predicted that the potential target genes of these miRNAs might be involved in metabolism, and the regulation of endothelial cells and nervous system. Moreover, the ROC analysis showed that the using miR-145-5p and let-7d-5p in combination can identify the healthy OSAHS, presence of miR-126-3p, miR-26a-5p and miR-107 was well indicative of OSAHS with arterial hypertension. Conclusions A cluster of dysregulation miRNAs have been found to be involved in the development of OSAHS patients. Moreover, these miRNAs might be used to be potential diagnostic and early warning markers.

BackgroundObservational studies have shown an association of increased iron status with a higher risk of amyotrophic lateral sclerosis (ALS). Iron status might be a novel target for ALS prevention if a causal relationship exists. We aimed to reveal the causality between iron status and ALS incidence using a large two-sample Mendelian randomization (MR).MethodsSingle nucleotide polymorphisms (SNPs) for iron status were identified from a genome-wide association study (GWAS) on 48,972 individuals. The outcome data came from the largest ALS GWAS to date (20,806 cases; 59,804 controls). We conducted conservative analyses (using SNPs with concordant change of biomarkers of iron status) and liberal analyses (using SNPs associated with at least one of the biomarkers of iron status), with inverse variance weighted (IVW) method as the main analysis. We then performed sensitivity analyses including weighted median, MR-Egger and MR-pleiotropy residual sum and outlier, as well as leave-one-out analysis to detect pleiotropy.ResultsIn the conservative analyses, we found no evidence of association between four biomarkers of iron status and ALS using IVW method with odds ratio (OR) 1.00 [95% confidence interval (CI): 0.90–1.11] per standard deviation (SD) increase in iron, 0.96 (95% CI: 0.77–1.21) in ferritin, 0.99 (95% CI: 0.92–1.07) in transferrin saturation, and 1.04 (95% CI: 0.93–1.16) in transferrin. Findings from liberal analyses were similar, and sensitivity analyses suggested no pleiotropy detected (all p > 0.05).ConclusionOur findings suggest no causal effect between iron status and risk of ALS. Efforts to change the iron status to decrease ALS incidence might be impractical.

2-Phenylethanol (2-PE) is an important flavouring ingredient with a persistent rose-like odour, and it has been widely utilized in food, perfume, beverages, and medicine. Due to the potential existence of toxic byproducts in 2-PE resulting from chemical synthesis, the demand for “natural” 2-PE through biotransformation is increasing. L-Phenylalanine (L-Phe) is used as the precursor for the biosynthesis of 2-PE through the Ehrlich pathway by Saccharomyces cerevisiae. The regulation of L-Phe metabolism in S. cerevisiae is complicated and elaborate. We reviewed current progress on the signal transduction pathways of L-Phe sensing, uptake of extracellular L-Phe and 2-PE synthesis from L-Phe through the Ehrlich pathway. Moreover, the anticipated bottlenecks and future research directions for S. cerevisiae biosynthesis of 2-PE are discussed.

ObjectivesTumor enucleation (TE) optimizes parenchymal preservation with promising short-term oncologic outcomes compared with standard partial nephrectomy (SPN). However, researches/literatures about long-term oncologic outcomes for TE after minimally invasive surgery are scarce. We aim to analyze long-term oncologic outcomes after laparoscopic and robotic tumor enucleation for renal cell carcinoma (RCC).Patients and MethodsWe retrospectively analyzed 146 patients who underwent TE with either laparoscopic or robotic approach for localized RCC in our center. Local recurrence, cancer specific survival (CSS), recurrence free survival (RFS), and overall survival (OS) were the main outcomes. Survival curves were generated using a Kaplan-Meier method. Perioperative outcomes and pathological outcomes were also analyzed.ResultsOverall, 98 male and 48 female patients were eligible for the study. The median tumor size was 3.4 cm with a median R.E.N.A.L. score of seven. Warm ischemia was used in 143 patients with a median ischemia time of 20 min and three patients had zero ischemia. Five patients (3.4%) had major complications (> Clavien IIIa) and only two were related to urinary system. The median global glomerular filtration rate (GFR) preserved after surgery was 93%. Pseudocapsule invasion was reported in 50 tumors (34%) and positive surgical margins were found in 3/146 (2.1%) tumors. At a median follow-up of 66 months, local recurrence happened in two patients (1.4%), and systemic recurrence happened in six patients (4.2%). The 5-year CSS, RFS, OS were 95.7, 89.6, and 91.9%, and the 10-year CSS, RFS, OS were 93.8, 89.6, and 90.0%, respectively.ConclusionThis study indicates that tumor enucleation with laparoscopic or robotic approach in experienced hands for the treatment of RCC appears oncologically safe with a median follow-up of more than 5 years. Prospective studies with more patients and longer follow-up will be required to further evaluate oncologic safety after TE.

Wide Area Protection System (WAPS) undertakes the important task of maintaining system reliability and stability when the power system is subject to abnormal or predetermined unstable conditions. The existing WAPS adopts a centralized mechanism to record and audit communication messages, which faces the risk of excessive authority and tampering with communication records and audit logs, thus making it impossible to achieve true transparency and fairness. Due to the involvement of multiple parties and equipment maintained by different manufacturers in the communication of WAPS, there are difficulties in tracing the cause of the accident and determining the at-fault party following misoperations and miss trips. To address this issue, we propose a semi-centralized blockchain system with multi-chain for auditing communications of WAPS. We first propose a semi-centralized system architecture according to the system architecture and management requirements of WAPS. Then, we utilize the blockchain network as a self-recording channel to achieve tamper-proof and non-repudiation verification interaction. We also design a multi-chain structure and classification node mechanism to meet the communication auditing requirements of multiple WAPS. We have designed a new block structure that conforms to the communication protocol of WAPS. To reduce the storage burden caused by the ever-expanding blockchain ledger, we propose a deletable blockchain scheme while maintaining the integrity and security of blockchain. Analysis and experiments show that the proposed blockchain system can support the secure, transparent, tamper-proof and traceable communication recording and auditing of WAPS along with high performance.

With the development of distributed networks, the remote controllability of the distributed energy objects and the vulnerability of user-side information security protection measures make distributed energy objects extremely vulnerable to malicious control by attackers. Hence, the large-scale loads may produce abnormal operation performance, such as load casting/dropping synchronously or frequent and synchronous casting and dropping, and hence, it can threaten the security and stable operation of the distribution networks. First, we analyze the security threats faced by industrial controllable load, civil controllable load, and the gains and losses of attacks on the distribution networks. Considering the factors of cyber attacks, we propose a control model and cyber attack model in active distribution networks (ADNs). And, three types of attacks that the target suffered are defined on the basis of “on” and “off” modes for control. Then, the controllable load was maliciously controlled as the research object, and a suitable scenario is selected. The impact of malicious control of the controllable load on the power supply reliability and power quality of the distribution networks are simulated and analyzed, and risk consequences for different types of attacks are provided.

In this work, 2D numerical RANS (Reynolds Average Navier-Stokes) simulations were carried out to investigate the thermodynamic performance of a solid fuel ramjet (SFRJ) with different inlet conditions. This is achieved by using an in-house FORTRAN code to simulate a 2D turbulent, reacting, unsteady flow in the ramjet engine. The inlet conditions are characterized by three key parameters: (1) swirl number (SN), (2) mass flow rate (ṁair), and (3) inlet temperature (Tin). With the code numerically validated by benchmarking with a number of computed cases, it is applied to perform systematic studies on the turbulent flow recirculation, combustion, and heat transfer characteristics. It is found that increasing SN, ṁair, or Tin can dramatically enhance the combustion heat release rate, regression rate, and combustor average temperature. Furthermore, the analysis on the chemical reaction intermediate (CO) reveals that the chemical reaction is more sufficient with increased ṁair, but SN=0. In addition, a secondary vortex is generated at the corner of the backward facing step in the presence of a swirl flow resulting from the instability of the shear layer. Finally, the nonlinear correlations between the heat transfer, combustion characteristics, and flow field characteristics and the corresponding inlet thermodynamic parameters are identified.

To describe the effect of confining pressure on the mechanical responses of N15 propellant, a constitutive model considering the confining pressure effect was first established for N15 propellant based on the elastic-viscoelastic correspondence principle. Then, the mechanical properties of N15 solid propellant under different confining pressures were obtained using confining pressure test system, and the obtained results indicate that the initial modulus of propellant did not change with confining pressure, but the maximum tensile strength, rupture strength, the maximum elongation, and elongation at break increased with increasing confining pressure. In conjunction with propellants’ mesoscopic structure and cross-section analysis, the mechanical mechanism of confining pressure effect on propellant was initially disclosed. Due to confining pressure, the particle dewetting inside the propellant was reduced, the hole propagation was delayed, and crack extension inhibited germination, proving that confining pressure has a strengthening impact on the propellant. Finally, assuming that the model parameters were dependent on pressure, the model parameters acquisition and validation were conducted. The results demonstrated that constitutive model can describe confining pressure influence on the mechanical properties of N15 propellant accurately.

Pasty rocket engines have broad application prospects in the aerospace field. To study the internal ballistic characteristics of the pasty propellant rocket engine, the burning surface change model of pasty propellant was built. The calculation program was developed to calculate the pressure evolution in the combustion chamber, and the experiment was carried out based on a pasty propellant rocket test system. The data calculated by the program are in good agreement with the experiment, the error of the initial pressure peak is only 4.02%, and the internal ballistic characteristics of the rocket engine at each stage were analyzed detailly. The effects of ignition delay time, transport pipeline structure, free volume of the combustion chamber, mass flow rate, and flow velocity of the pasty propellant on internal ballistic characteristics of the pasty propellant rocket engine are investigated. The results indicate that when the ignition delay time increases, the pressure rises faster and the initial pressure peak increases obviously. The transport pipe diameter changes from 11.3 mm to 7.4 mm, and the initial combustion time and residual propellant combustion time decreased by 41.3% and 36.0%. The reduction of the free volume of the combustion chamber can reduce the initial pressure peak and the time to reach the equilibrium pressure. The initial pressure spike and equilibrium pressure rise with the increase of the pasty propellant flow velocity. While the ignition transient decreased with the increase of the pasty propellant flow velocity. The internal ballistic properties can be improved by reducing the ignition delay time, the diameter of the transport pipeline, and the free volume of the combustion chamber, or by increasing the mass flow rate of the pasty propellant rocket engine.

Glaux maritima Linnaeus (1753), the monotypic species of the genus Glaux in Primulaceae, with unique physiological characteristics-salt gland, is a typical salt-secreting plant. We sequenced and assembled the complete chloroplast genome of Glaux maritima with a length of 154,939 bp, consisting of a large single-copy region (LSC) of 84,808 bp, a small single-copy region (SSC) of 18,031 bp, and two inverted repeats (IR) region of 26,050 bp. The chloroplast genome contained 111 genes, including 77 protein-coding genes, 4 rRNA genes, and 30 tRNA genes. The phylogenetic tree exhibited that Glaux maritima is nested in the monophyletic clade of Lysimachia hemsleyana, L. congestiflora.

Objectives To explore the non-linear relationship between platelet count (PLT) and hepatocellular carcinoma (HCC) overall survival (OS).Setting The study was done in Sun Yat-sen University Cancer Center (SYSUCC) from January 2007 to May 2012, a total of 5005 consecutive participants at SYSUCC were retrospectively reviewed, and 979 patients with Barcelona clinic liver cancer (BCLC) stage B were selected for the final analysis.Participants A total of 979 newly diagnosed patients with HCC with BCLC stage B were identified for the secondary analysis. Eight cases were excluded for missing data of PLT.Main outcome measures Cox proportional hazard regression models were used to calculate multivariable-adjusted HRs and 95% CIs for HCC. The non-linear relationship was estimated through a restricted cubic spline regression, and a two-piecewise Cox proportional hazards model was further performed to calculate the threshold effect. We used multiple imputation to deal with the missing data.Results In the multivariate analysis, Log PLT was associated with a 91% risk increase in death (HR 1.91; 1.28 to 2.85) with adjustment for gender, Child-Pugh class, age × diameter of main tumour, both lobe with lesions × number of the intrahepatic lesions, alpha-fetoprotein (10.83 after adjusting for potential confounders. The core results were consistent with those from the sensitivity analysis. Besides, a significantly higher hazard risk was found in the patients with age 50, haemoglobin ≥120 and C reactive protein >10.Conclusion PLT was nonlinearly associated with HCC OS.

We isolated an aromatic strain of yeast (M2013310) from chili sauce. Assembly, annotation, and phylogenetic analysis based on genome sequencing, identified M2013310 as an allodiploid yeast that was closely related to Zygosaccharomyces rouxii. During fermentation, M2013310, produced an aromatic alcohol with a rose-honey scent; gas chromatography tandem mass spectrometry identified this alcohol as 2-phenylethanol. The concentration of 2-phenylethanol reached 3.8 mg/L, 1.79 g/L, and 3.58 g/L, in M3 (NH4+), M3 (NH4+ + Phe), and M3 (Phe) culture media, after 72 h of fermentation, respectively. The mRNA expression levels of ARO8 encoding aromatic aminotransferases I and ARO10 encoding phenylpyruvate decarboxylase by M2013310 in M3 (Phe) were the lowest of the three different forms of media tested. These results indicated that M2013310 can synthesize 2-phenylethanol via the Shikimate or Ehrlich pathways and the production of 2-phenylethanol may be significantly improved by the over-expression of these two genes. Our research identified a promising strain of yeast (M2013310) that could be used to improve the production of 2-phenylethanol.

SnP3 has a great prospect in electronic and thermoelectric device applications due to its moderate band gap, high carrier mobility, absorption coefficients, and dynamical and chemical stability. Doping in two-dimensional semiconductors is likely to display various anomalous behaviors when compared to doping in bulk semiconductors due to the significant electron confinement effect. By introducing foreign atoms from group III to VI, we can successfully modify the electronic properties of two-dimensional SnP3. The interaction mechanism between the dopants and atoms nearby is also different from the type of doped atom. Both Sn7BP24 and Sn7NP24 systems are indirect bandgap semiconductors, while the Sn7AlP24, Sn7GaP24, Sn7PP24, and Sn7AsP24 systems are metallic due to the contribution of doped atoms intersecting the Fermi level. For all substitutionally doped 2D SnP3 systems considered here, all metallic systems are nonmagnetic states. In addition, monolayer Sn7XP24 and Sn8P23Y may have long-range and local magnetic moments, respectively, because of the degree of hybridization between the dopant and its adjacent atoms. The results complement theoretical knowledge and reveal prospective applications of SnP3-based electrical nanodevices for the future.

Objective: The relationship between diabetes and all- and cause-specific mortality in individuals with common cancers (breast, colorectal, and prostate) remains both under-researched and poorly understood.Methods: Cancer survivors (N = 37,993) from the National Health Interview Survey with linked data retrieved from the National Death Index served as our study participants. Cox proportional-hazards models were used to assess associations between pre- and post-diabetes and all-cause and cause-specific mortality.Results: Over a median follow-up period of 13 years, 2,350 all-cause, 698 cancer, and 506 CVD deaths occurred. Among all cancer survivors, patients with diabetes had greater risk of: all-cause mortality [hazard ratio (HR) 1.35, 95% CI = 1.27–1.43], cancer-specific mortality (HR: 1.14, 95% CI = 1.03–1.27), CVD mortality (HR: 1.36, 95% CI = 1.18–1.55), diabetes related mortality (HR: 17.18, 95% CI = 11.51–25.64), and kidney disease mortality (HR: 2.51, 95% CI = 1.65–3.82), compared with individuals without diabetes. The risk of all-cause mortality was also higher amongst those with diabetes and specific types of cancer: breast cancer (HR: 1.28, 95% CI = 1.12–1.48), prostate cancer (HR: 1.20, 95% CI = 1.03–1.39), and colorectal cancer (HR: 1.29, 95% CI = 1.10–1.50). Diabetes increased the risk of cancer-specific mortality among colorectal cancer survivors (HR: 1.36, 95% CI = 1.04–1.78) compared to those without diabetes. Diabetes was associated with higher risk of diabetes-related mortality when compared to non-diabetic breast (HR: 9.20, 95% CI = 3.60–23.53), prostate (HR: 18.36, 95% CI = 6.01–56.11), and colorectal cancer survivors (HR: 12.18, 95% CI = 4.17–35.58). Both pre- and post-diagnosis diabetes increased the risk of all-cause mortality among all cancer survivors. Cancer survivors with diabetes had similar risk of all-cause and CVD mortality during the second 5 years of diabetes and above 10 years of diabetes as compared to non-diabetic patients.Conclusions: Diabetes increased the risk of all-cause mortality among breast, prostate, and colorectal cancer survivors, not for pre- or post-diagnosis diabetes. Greater attention on diabetes management is warranted in cancer survivors with diabetes.

PurposeWe performed this systematic review and meta-analysis to assess the incidence of fatal adverse events that were associated with the use of programmed cell death ligand 1 (PD-L1) inhibitors, to describe them and to statistically depict factors that were associated with these events.MethodPubMed, Embase, and Cochrane Library were completely searched based on the following terms or relevant Medical Subject Heading ones: “atezolizumab”, “durvalumab”, “avelumab”, and “cemiplimab”.ResultsA total of 26 eligible studies were identified, incorporating 6,896 unique participants. The overall incidence was 1.24% (95% CI: 0.93–1.65%). The incidence and odds were higher in patients with non-squamous non-small cell lung cancer (NSCLC) than those with urothelial carcinoma [(2.25 vs. 0.85, p = 0.04), (odds ratio [OR]: 2.69; 95% CI: 1.04–6.97, p = 0.04)], higher in the middle-aged group than the young group [(1.74 vs. 0.89, p = 0.01), (OR: 2.13; 95% CI: 1.26–3.61, p = 0.01)], and higher in the trial phase I than the trial phase II [(1.76 vs. 0.60, p = 0.01), (OR: 0.31; 95% CI: 0.13–0.75, p = 0.01)]. Notably, the trial phase I had a higher incidence than trial phase II or III following regulating for cancer types and average age (OR: 0.28; 95% CI: 0.11–0.71, p = 0.01, OR: 0.48; 95% CI: 0.24–0.95, p = 0.04, respectively). In terms of organ-specific fatal adverse events, interstitial lung disease (ILD) was frequently documented. A variety of respiratory system-related fatal adverse events were recorded, including but not limited to pneumonia and respiratory failure. As for organ-unspecific fatal adverse events, substantial cases of sepsis and neutropenia were recorded.ConclusionThis study firstly provided a comprehensive incidence and the spectrum of fatal adverse events associated with PD-L1 inhibitors, and identified three potential susceptible factors of that, yielding a capability for clinicians to distinguish high-risk populations from relatively low-risk ones, and facilitating to improve the safety of PD-L1 inhibitors broadly used in the clinical setting.

Summary: Skeletal mandibular hypoplasia (SMH), one of the common types of craniofacial deformities, seriously affects appearance, chewing, pronunciation, and breathing. Moreover, SMH is prone to inducing obstructive sleep apnea syndrome. We found that brain and muscle ARNT-like 1 (BMAL1), the core component of the molecular circadian oscillator, was significantly decreased in mandibles of juvenile SMH patients. Accordingly, SMH was observed in circadian-rhythm-disrupted or BMAL1-deficient mice. RNA sequencing and protein chip analyses suggested that matrix metallopeptidase 3 (MMP3) is the potential target of BMAL1. Interestingly, in juvenile SMH patients, we observed that MMP3 was obviously increased. Consistently, MMP3 was upregulated during the whole growth period of 3–10 weeks in Bmal1−/− mice. Given these findings, we set out to characterize the underlying mechanism and found BMAL1 deficiency enhanced Mmp3 transcription through activating p65 phosphorylation. Together, our results provide insight into the mechanism by which BMAL1 is implicated in the pathogenesis of SMH.

Whilst researches elucidating a diversity of intracellular mechanisms, platinum-resistant epithelial ovarian cancer (EOC) remains a major challenge in the treatment of ovarian cancer. Here we report that Exo70, a key subunit of the exocyst complex, contributes to both innate and acquired cisplatin resistance of EOC. Upregulation of Exo70 is observed in EOC tissues and is related to platinum resistance and progression-free survival of EOC patients. Exo70 suppressed the cisplatin sensitivity of EOC cells through promoting exocytosis-mediated efflux of cisplatin. Moreover, cisplatin-induced autophagy-lysosomal degradation of Exo70 protein by modulating phosphorylation of AMPK and mTOR, thereby reducing the cellular resistance. However, the function was hampered during prolonged cisplatin treatment, which in turn stabilized Exo70 to facilitate the acquired cisplatin resistance of EOC cells. Knockdown of Exo70, or inhibiting exocytosis by Exo70 inhibitor Endosidin2, reversed the cisplatin resistance of EOC cells both in vitro and in vivo. Our results suggest that Exo70 overexpression and excessive stability contribute to innate and acquired cisplatin resistance through the increase in cisplatin efflux, and targeting Exo70 might be an approach to overcome cisplatin resistance in EOC treatment.

O-GlcNAcylation is an important post-translational modification (PTM) jointly controlled by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Aberrant hyper-O-GlcNAcylation is reported to yield hepatocellular carcinoma (HCC) malignancy, but the underlying mechanisms of the OGT/OGA imbalance responsible for HCC tumorigenesis remain largely unknown. Here, we report that RAN-binding protein 2 (RANBP2), one of the small ubiquitin-like modifier (SUMO) E3 ligases, contributed to malignant phenotypes in HCC. RANBP2 was found to facilitate CCAAT/enhancer-binding protein alpha (CEBPα) SUMOylation and degradation by direct interplay with CEBPα. As a transcriptional factor, CEBPα was verified to augment OGA transcription, and further experiments demonstrated that RANBP2 enhanced the O-GlcNAc level by downregulating OGA transcription while not affecting OGT expression. Importantly, we provided in vitro and in vivo evidence of HCC malignant phenotypes that RANBP2 triggered through an imbalance of OGT/OGA and subsequent higher O-GlcNAcylation events for oncogenic proteins such as peroxisome proliferative-activated receptor gamma coactivator 1 alpha (PGC1α) in a CEBPα-dependent manner. Altogether, our results show a novel molecular mechanism whereby RANBP2 regulates its function through CEBPα-dependent OGA downregulation to induce a global change in the hyper-O-GlcNAcylation of genes, such as PGC1α, encouraging the further study of promising implications for HCC therapy.

To retrospectively explore the characteristics of plasma amino acids (PAAs) in children with autism spectrum disorder and their clinical association via case-control study. A total of 110 autistic and 55 healthy children were recruited from 2014 to 2018. The clinical phenotypes included severity of autism, cognition, adaptability, and regression. Compared with the control group, autistic children had significantly elevated glutamate, [gamma]-Amino-n-butyric acid, glutamine, sarcosine, [delta]-aminolevulinic acid, glycine and citrulline. In contrast, their plasma level of ethanolamine, phenylalanine, tryptophan, homocysteine, pyroglutamic acid, hydroxyproline, ornithine, histidine, lysine, and glutathione were significantly lower. Elevated neuroactive amino acids (glutamate) and decreased essential amino acids were mostly distinct characteristics of PAAs of autistic children. Increased level of tryptophan might be associated with severity of autism.

With economic growth, the demand for power systems is increasingly large. Short-term load forecasting (STLF) becomes an indispensable factor to enhance the application of a smart grid (SG). Other than forecasting aggregated residential loads in a large scale, it is still an urgent problem to improve the accuracy of power load forecasting for individual energy users due to high volatility and uncertainty. However, as an important variable that affects the power consumption pattern, the influence of weather factors on residential load prediction is rarely studied. In this paper, we review the related research of power load forecasting and introduce a short-term residential load forecasting model based on a long short-term memory (LSTM) recurrent neural network with weather features as an input.

Salix polaris is a dwarf species of the genus Salix which distribute in harsh arctic environment. In this study, we sequenced and assembled whole mitochondrial genome of S. polaris for the first time. The complete mitochondrial genome sequence of this species is a circular molecule of 562920 bp in size, encoding 23 CDS, 21 tRNA genes, and 3 rRNA genes. Mitogenome based phylogenetic tree showed that Salix polaris clustered in the robust clade consist of all Salix species sampled in this study. The complete mitochondrial genome of Salix polaris adds new data into the whole mitochondrial genome of Salix, which is still scarce so far, and we anticipate the accumulation of mitogenome of Salix will facilitate phylogenetic study for this systematic difficult genus.

Salix cardiophylla was a member of the genus of Salix in family Salicaceae with unique morphological traits, and once recognized as a separate genus, Toisusu Kimura. Here, we sequenced and assembled the complete mitochondrial genome of S. cardiophylla, which was 735,173 bp in length, including 56 genes, 28 protein-coding genes, 3 rRNA genes, 25 tRNA genes, and one large inverted repeat regions with length of 13,603 bp. Phylogenetic analysis based on 26 mitochondrial CDS confirmed that S. cardiophylla is a member of Salix, and support its merge into Salix in aspect of our new insights on mitogenome phylogenomics.

Primula helodoxa Balf.f. is a species endemic to southeastern China distributed in Tengchong county of Yunnan Province. Here is the first time to report the complete chloroplast genome sequence of P. helodoxa. The complete chloroplast genome was 151,909 bp in length, containing a large single-copy (LSC) region of 83192 bp, a small single-copy (SSC) region of 17,797 bp, and a pair of inverted repeats (IRs) regions of 25,460 bp. There are 137 genes in total, 91 protein-coding genes, eight rRNA genes, and 38 transfer RNA genes. The phylogenetic tree showed relative relationship of P. helodoxa and P. chrysochlora.

Primula beesiana Forrest is a perennial rosette alpine species in the Sect. Proliferae of family Primulaceae. Here, the first complete chloroplast genome of P. beesiana was determined. The size of the complete chloroplast genome of P. beesiana is 150873 bp with GC content of 37.1%. The assembled genome has a typical quadripartite structure, containing a large single-copy (LSC) region was 82850 bp, a small single-copy (SSC) region was 17,651 bp, and a pair of inverted repeats (IRs) regions was 25,186 bp. There are 137 genes are annotated in the whole cp genome with 91 protein-coding genes, 8 rRNA genes, and 38 transfer RNA (tRNA) genes, including 115 unique genes, 81 unique CDSs, 30 unique tRNAs, and 4 unique rRNAs. The phylogenetic tree showed that P. beesiana is closely related to P. bulleyana.

IntroductionObstructive sleep apnoea-hypopnea syndrome (OSAHS) is characterised by recurring episodes of complete or partial upper airway collapse during sleep. Persistent OSAHS is associated with long-term consequences, such as growth failure, cardiovascular and neurocognitive problems in children. Different from the aetiology of OSAHS in adults, the most common cause of paediatric OSAHS is adenotonsillar hypertrophy. Adenotonsillectomy (AT) has been recommended as the first-line treatment of paediatric OSAHS. Several studies have suggested that retarded growth caused by OSAHS can improve after AT during the prepubertal period. This review will systematically search and summarise the available evidence on the effects of AT on children’s growth.Methods and analysisWe will conduct electronic searches in MEDLINE (via PubMed), Embase, Google Scholar and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) or cohort studies that included a control group. Additional records will be searched by checking the references included in the selected studies and relevant reviews. At least two authors will undertake selection of studies and data extraction independently and in duplicate. The Cochrane Risk of Bias tool and Risk Of Bias In Non-randomised Studies—of Interventions will be used to assess the risk of bias of RCT and cohort studies, respectively. A random-effects model will be used for meta-analyses. Data synthesis and other analyses will be carried out using the RevMan V.5.3 software. The Grades of Recommendation, Assessment, Development and Evaluation will be used to assess the quality of the supporting evidence behind each main comparison.Ethics and disseminationThere is no ethical issue in this systematic review given that we will only include published studies. The results will be disseminated via peer-reviewed publications and social networks.PROSPERO registration numberCRD42019125882

Progestins has been used widely for endometrial cancer (EC) patients. However, long term use of high dose progestin often lead to progestin resistance. Our previous studies have demonstrated that metformin reversed progestin resistance through the downregulation of the expression of glyoxalase I (GLOI) in type I endometrial cancer. Recent studies have demonstrated the role of Ten-eleven translocation 1 (TET1) in endometrial cancer, but the physiological role of TET1 in GLOI-mediated progestin resistance has been poorly addressed. Immunohistochemistry was used to detect the expression of TET1, GLOI and 5hmC in various endometrium. Western blot was carried out to analyses TET1 and GLOI expression with different treatment. Cell counting kit-8 was used to evaluate cell proliferation after various treatment. Dot blot assay and HMeDIP assay were performed to detect global hydroxmethylation levels and hydroxymethylation levels in GLOI gene respectively. In current study, we found that metformin effectively sensitized progestin in endometrial cancer cell lines through the down regulation of the expression of TET1 and GLOI. Interestingly, the exogenous increase of TET1 expression enhanced total 5hmC level and hydroxymethylation modification in glyoxalase I promoter region. This effect was abated by metformin treatment. Moreover, the expression profile of TET1 and glyoxalase I in various endometrial tissue parallelized with 5hmC level. Therefore, this finding suggests that metformin sensitized progestin in endometrial cancer through the TET1-5hmC-GLOI signaling pathway.