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PTEN is known as a tumor suppressor and plays essential roles in brain development. Here, we report that PTEN in primary sensory neurons is involved in processing itch and thermal information in adult mice. Deletion of PTEN in the dorsal root ganglia (DRG) is achieved in adult Drg11-Cre

Diagnosis of KBGS due to a high risk identified by early Down’s syndrome screening has not been reported in previous studies, and the prominent KBGS phenotype and absence of specificity on early ultrasound examination also pose a challenge for genetic diagnosis.

BackgroundThe success rates of in vitro fertilization (IVF) treatment are limited by the aneuploidy of human embryos. Pre-implantation genetic testing for aneuploidy(PGT-A) is often used to select embryos with normal ploidy but requires invasive embryo biopsy. MethodsWe performed chromosome sequencing of 345 paired blastocyst culture medium and whole blastocyst samples and developed a noninvasive embryo grading system based on the random forest machine-learning algorithm to predict blastocyst ploidy. The system was validated in 266 patients, and a blinded prospective observational study was performed to investigate clinical outcomes between machine learning-guided and traditional niPGT-A analyses. We graded embryos as A, B, or C using machine learning-guided niPGT-A analysis according to their euploidy probability levels predicted by noninvasive chromosomal screening. ResultsWe observed higher live birth rate in A- versus C-grade embryos (50.4% versus 27.1%, p=0.006) and B- versus C-grade embryos (45.3% versus 27.1%, p=0.022) and lower miscarriage rate in A- versus C-grade embryos (15.9% versus 33.3%, p=0.026) and B- versus C-grade embryos (14.3% versus 33.3%, p=0.021). The embryo utilization rate was significantly higher through machine learning strategy compared to the conventional dichotomic judgment of euploidy or aneuploidy in the niPGT-A analysis (78.8% versus 57.9%, p

Background: Despite their great disease burden, there have been few studies on the epidemiology of central nervous system tumours (CNSTs) in China. We used the latest data updated by GBD to analyse the trends of incidence, mortality, and disability-adjusted life years (DALYs) for CNSTs in China versus globally. Methods: Epidemiological data on CNSTs were extracted from GBD 2019. We used Joinpoint regression analysis to calculate the magnitude and direction of the trends and the age-period-cohort method to analyse the age, period, and cohort effects of the trend. Results: From 1990 to 2019, the 106.52% increase in Chinese incident cases was higher than the global increase (94.35%). The 67.32% increase in cancer deaths and 16.03% increase in DALYs were lower than the global increases (cancer death: 76.36%; DALYs: 40.06%). The age-standardized incidence rates (ASIRs) in China were higher than the global ASIRs, and the increase in China was higher than that globally. Although the age-standardized mortality rates and age-standardized DALY rates in China were higher, their increases in China were less than those globally. Both in China and globally, the number and incidence, mortality, and DALYs by age group showed a bimodal distribution (younger than 5 years and older), and the peak in the older age group showed a backwards trend. The proportion of incident cases, cancer deaths, and DALYs also increased in the older age group. In the age-period-cohort model, the local drifts in the older age group were above zero. Conclusions: The burden of CNSTs is very serious in China, and we should pay attention to the key populations, early diagnosis technology, improvements in medical technology, and ways to reduce medical costs. We believe our results could help policymakers allocate resources efficiently to reduce the burden of CNSTs.

Background and objectives The exosomes released by mesenchymal stromal cells (MSCs) in classical FBS-containing media have been demonstrated as an alternative, cell-free therapy in various diseases including inflammatory bowel disease (IBD). It has been found that the function of exosomes is affected by culture condition. We previously developed a serum-free, xeno-free and chemically defined medium, and umbilical cord-derived MSCs in this medium retained the immunosuppressive capability. Methods In this study, we evaluated the immunosuppressive function of exosomes from MSCs (MSC-Exo) in defined medium and their therapeutic effect on treating colitis. Results and conclusions In vitro studies indicated that MSC-Exo reduced the concentration of pro-inflammatory cytokines IFN-γ, TNF-α and IL-1β, and increased the secretion of anti-inflammatory cytokines TGF-β1 and IL-10, but no significant change of inhibitory effect on peripheral blood mononuclear cells proliferation was shown. In vivo experimental colitis showed that administration of MSC-Exo was able to significantly ameliorate the disease activity index score, weight loss, colon shortening, and the histological colitis score through up-regulation anti-inflammatory responses and down-regulation of inflammatory responses. Moreover, the use of MSC-Exo (200 µg) led to an improved therapeutic efficacy when compared with MSCs at a dose of 1×106 cells. Our findings indicate that the exosomes from MSCs in defined medium possess a certain degree of immunosuppressive effect in vitro and exhibit a therapeutic capability in a mouse model of DSS-induced colitis through suppressing inflammation mechanism.

Platelets are implicated in the pathophysiology of breast and other cancers through their role in exchanging biomolecules with tumor cells in the tumor microenvironment. Such exchange results in tumor‐educated platelets with altered RNA expression profiles. Multiple lines of evidence indicate that platelet RNA profiles may be suitable as diagnostic biomarkers for cancer‐related biological processes. In this study, we characterized the gene expression signatures of platelets in breast cancer (BC) by high‐throughput sequencing and quantitative real‐time RT‐PCR. Our results indicate that the expression of TPM3 (tropomyosin 3) mRNA is significantly elevated in platelets from patients with BC compared with age‐matched healthy control subjects. Furthermore, up‐regulation of TPM3 mRNA in platelets was found to be significantly correlated with metastasis in patients with BC. Finally, we report that platelet TPM3 mRNA is delivered into BC cells through microvesicles and leads to enhanced migrative phenotype of BC cells. In summary, our findings suggest that the transfer of platelet TPM3 mRNA into cancer cells via microvesicles promotes cancer cell migration, and thus platelet‐derived TPM3 mRNA may be a suitable biomarker for early diagnosis of metastatic BC., Platelets are implicated in the pathophysiology of breast and other cancers through their role in exchanging biomolecules with tumor cells in the tumor microenvironment. In this study, we found that platelet TPM3 (tropomyosin 3) mRNA can be delivered into cancer cells via microvesicles to promote cancer cell migration. Platelet‐derived TPM3 mRNA may be a suitable biomarker for early diagnosis of metastatic breast cancer.

A series of conjugated donor–acceptor (D–A) block copolymers (BCPs) were synthesised using a one-pot Stille coupling polycondensation reaction. This involved reaction between a series of mono-bromo-functionalised Poly3-hexylthiophene (P3HT) polymers (P3HT-Br, Mn : 17, 21 and 43 kg/mol) and [N, N′-bis(2-decyl-tetradecyl)-1,7-dibromo-3,4,9,10-perylene diimide (PBI) and [2,5-bis(trimethylstannyl)-thiophene] (T) monomers. Purification using preparative gel permeation chromatography (GPC) removed any excess P3HT and resulted in BCPs with low polydispersity index values. The P3HT-b-PBIT BCPs were characterised using 1H-NMR and Fourier-transform infrared spectroscopy. When compared to a P3HT/PBIT polymer blend, the D–A BCP films exhibited a remarkably fine structure with a nanoscale morphology. These results indicated that these D–A BCPs have the potential for use as nanostructured active layers in polymer solar cells.

All-conjugated donor-acceptor block copolymers (BCP) were synthesized in a one-pot reaction by a Stille coupling polycondensation through a terminal functional polymer copolymerization process. Mono bromo end-functionalized P3HT samples with various molecular weights (P3HT-Br, Mn: 5, 9, and 26 kg/mol) were copolymerized with AA (N,Nʹ-Bis(2-decyl-1-tetradecyl)-2,6-dibromonaphthalene-1,4,5,8-tetracarboxylic acid bisimide, NDI) and BB (5,5′-bis(trimethylstannyl)-2,2′-bithiophene) type monomers. Further purification by preparative GPC removed excess P3HT to yield block copolymers of low polydispersities with different donor and acceptor block chain lengths. The block copolymers were characterized by 1H-NMR and UV–vis absorption and FTIR spectroscopy. The optical properties, film morphologies, and optoelectronic properties of the block copolymer were strongly influenced by the donor and acceptor block chain lengths. Furthermore, the fully conjugated D-A block copolymer films exhibited fine structures, smooth film morphologies, and better OPV performance than those features of P3HT/PNDIT2 polymer blends. In polymer solar cells based on the various block copolymer as active layers, the device power convention efficiency was improved by maintaining the acceptor block content at 40–50 kg/mol and increasing the P3HT chain from 5 to 26 kg/mol.

Genghis Khan's lineage has attracted both academic and general interest because of its mystery and large influence. However, the truth behind the mystery is complicated and continues to confound the scientific study. In this study, we surveyed the molecular genealogy of Northwestern China's Lu clan who claim to be the descendants of the sixth son of Genghis Khan, Toghan. We also investigated living members of the Huo and Tuo clans, who, according to oral tradition, were close male relatives of Lu clan. Using network analysis, we found that the Y-chromosomal haplotypes of Lu clan mainly belong to haplogroup C2b1a1b1-F1756, widely prevalent in Altaic-speaking populations, and are closely related to the Tore clan from Kazakhstan, who claim to be the descendants of the first son of Genghis Khan, Jochi. The most recent common ancestor of the special haplotype cluster that includes the Lu clan and Tore clan lived about 1000 years ago (YA), while the Huo and Tuo clans do not share any Y lineages with the Lu clan. In addition to the reported lineages, such as C3*-Star Cluster, R1b-M343, and Q, our results indicate that haplogroup C2b1a1b1-F1756 might be another candidate of the true Y lineage of Genghis Khan.

Three sets of polyfluorenes grafting one/two orange emissive groups on central or terminal fluorene unit have been synthesized successfully through the catalyst-transfer polymerization. The molecular weights linearly increase with increase in the feed ratios of [monomer]/[catalyst] in a certain molecular weight range. The initiators with bis(2,6-diisopropylphenyl)imidazolin-2-ylidene) (IPr) as the ancillary ligand show better catalytic activity, leading to higher molecular weight of up to 126.3 kDa. All polymers in toluene have the similar absorption spectra to polyfluorene homopolymer, while the weak absorption bands of 420–500 nm are observed only in the polymers with low molecular weight. Photoluminescence spectra display a dominant blue emission from the polyfluorene backbone and a weak orange emission (508–661 nm) from the orange group. The clearly enhanced orange emission in the polymers with low molecular weight is mainly ascribed to the intramolecular Forster energy transfer from the polyfluorene segment to the orange group, which is further confirmed by the electroluminescent behavior of the polymers.

Dietary lipid oxidation is a lasting concern to aquafeed manufacturers and aquaculture farmers. Here, we determined if there was an association between oxidized fish oil (OFO) and hepatopancreatic injury in Chinese mitten crab, and evaluated the alleviating effects of a combination of vitamins C and E on hepatopancreatic injury. There were significant reductions in the body weight gain, hepatopancreatic index, and feed efficiency in crabs that received OFO. Diets with OFO also resulted in reduced crude fat contents in the hepatopancreas and muscle tissues, and alternations in the hepatopancreatic fatty acid compositions, especially a reduction in polyunsaturated fatty acids. Moreover, dietary OFO exposure reduced the antioxidant defense and non‐specific immune response, caused hepatopancreatic injury, and even apparent whitening. An ultrastructural examination of the whitened hepatopancreas revealed that hepatopancreatic cells were injured at varying degrees following OFO exposure. The combination of vitamins C and E could efficiently maintain a constant fatty acid profile in the hepatopancreas exposed to OFO, thus alleviating OFO‐induced hepatopancreatic injury. In addition, a biochemical analysis indicated that a combination of vitamins C and E not only improved the antioxidant status by mitigating the harmful effects of oxidized oil, but also modulated non‐specific immune responses in the crab that received OFO. Overall, OFO‐induced hepatopancreatic injury may be alleviated by a dietary combination of vitamins C and E, and the feeding of rancid forage fish or diets that contain highly oxidized oil is likely a cause of hepatopancreatic necrosis that is frequently observed in farmed crabs.

Glioma is the most common malignant tumor of the central nervous system, and it is characterized by high relapse and fatality rates and poor prognosis. Bufalin is one of the main ingredients of Chan-su, a traditional Chinese medicine (TCM) extracted from toad venom. Previous studies revealed that bufalin exerted inhibitory effects on a variety of tumor cells. To demonstrate the inhibitory effect of bufalin on glioma cells and glioma stem-like cells (GSCs) and discuss the underlying mechanism, the proliferation of glioma cells was detected by MTT and colony formation assays following treatment with bufalin. In addition, we investigated whether bufalin inhibits or kills GSCs using flow cytometry, Western blotting, and reverse transcription polymerase chain reaction analysis (RT-PCR). Finally, we investigated whether bufalin could improve the therapeutic effect of temozolomide (TMZ) and discussed the underlying mechanism. Taken together, our data demonstrated that bufalin inhibits glioma cell growth and proliferation, inhibits GSC proliferation, and kills GSCs. Bufalin was found to induce the apoptosis of GSCs by upregulating the expression of the apoptotic proteins cleaved caspase 3 and poly(ADP-ribose) polymerase (PARP) and by downregulating the expression of human telomerase reverse transcriptase, which is a marker of telomerase activity. Bufalin also improved the inhibitory effect of TMZ on GSCs by activating the mitochondrial apoptotic pathway. These results suggest that bufalin damages GSCs, induces apoptosis, and enhances the sensitivity of GSCs to TMZ.

To obtain more precise and rational calculation details of the loss and heat of a damper winding in a tubular hydro-generator, this study develops a three-dimensional, finite-element, electromagnetic-temperature field close-coupling model of the damper winding. On the basis of multi-physical field coupled theory, the model fully considers the temperature effects of the damper winding resistivities and heat conductivities, and the eddy current loss in the end region of the damper winding. The model was verified by direct tests of the damper winding temperature. Unlike the conventional weak-coupling model, the proposed close-coupling model fully captures the interaction between the electromagnetic and temperature fields. Therefore, of the model more accurately and reasonably calculates the loss and heat of the damper winding than the conventional model. The proposed calculation model can properly assess the loss and heat of damper windings in large hydro-generators, which is helpful for improving the design standards of hydro-generators.

Current ECG imaging (ECGi) systems deploy a large number of ECG sensors to provide the high-resolution body surface potential mapping (BSPM). The availability of BSPM was shown to substantially improve the early detection of life-threatening heart disease. However, most existing ECGi systems employ an approximately uniform distribution of hundreds of ECG sensors on the body surface. Very little has been done to investigate the optimal sensor placement for BSPM. In this article, we propose a new optimal sensing strategy to search the optimal number and locations of the sensors. First, we develop a greedy algorithm to sequentially place ECG sensor on the body surface, which will maximize the information gain at each step. Second, we leverage the available BSPM data to develop a spatiotemporal model of cardiac electrical activity. Third, we study the algorithmic convergence and stopping criteria by evaluating diminishing return of the placement of two sequential ECG sensors. Experimental results show that the optimal sensing strategy with 30 sensors yields large $R^2$ statistics ( $>$ 97%) for BSPM during the P, QRS, and T waves, as well as an average $R^2$ statistics of 97.71% for 12-lead ECG, and 99.44% for 3-lead VCG. The proposed methodology has strong potentials to help further improve the design of ECGi systems.

Understanding the high-temperature behaviors of two-dimensional (2D) transition metal dichalcogenides under different environments will provide a directive guide for the fabrication and application of their nanoelectronic devices. In this study, we investigate the high-temperature properties of chemical vapor deposition grown molybdenum disulfide (MoS2) in different atmospheres through the ex situ and in situ morphological and spectroscopical characterizations. When the MoS2 is exposed to Ar, dry O2, and wet O2 at the temperature of 500, 350, and 300 °C, the etching process starts at the edge and inner regions simultaneously, and the etched trenches are opposite to the outline of the MoS2 triangular shape. We observe a clear redshift of MoS2 in the Raman peak position and the photoluminescence peak position by in situ spectroscopical characterizations as the temperature increases. Moreover, a strong photoluminescence enhancement of 24-fold of MoS2 is observed when exposing to O2 at 300 °C . This should be due to the chemical and physical adsorbed oxygen on the MoS2 surface. Moreover, we find that physical adsorption can be eliminated after vacuum annealing. This study provides a real-time strategy to study the morphology and property evolution of 2D materials at high temperature in different atmospheres. These results will contribute to the applications in future electronic and optoelectronic functional devices of 2D materials.

For overcoming possibly attacks from super-computers and quantum computers, we proposed the Integer-Decomposing Topological Authentication Problem (IDTAP) in Topological Coding: Decompose an even integer m to form a number-based string m 1 m 2 ⋯m p (as a public key) holding m = m 1 + m 2 + ⋯+ m p , such that d = (m 1 ,m 2 ,…,m p ) is just the degree-sequence of a graph G (as a private key). For the goal of answering IDTAP, we investigate some operations on graph degree-sequences, and show particular degree-sequences, such as perfect degree-sequence, unique graph degree-sequence corresponds, right-angled degree sequence base, degree-sequence homomorphism. We define degree-sequence lattices, degree-sequence accompany graphic lattices, and present: "A degree-sequence lattice is equivalent to a non-negative integer lattice", and our star-tree lattices can describe graphs.

For letting graphic lattices approaching lattices, we define imaginary graphs and the leaf-splitting operation and the leaf-coinciding operation, and show an equivalent property: The leaf-splitting connectivity of a connected im-graph is equivalent to its edge connectivity. Using im-graphs produce complex degree-sequence lattices, graphic lattices, im-graphs in the integer decomposition problem, topological IoT-networks and data-functional IoT-networks. Each integer m with |m| ≥ 2 corresponds at least a graph or an im-graph. We try to build some connections between popular lattices and our lattices, and moreover propose some problems on Hanzi-writings lattices constructed by Chinese character coding.

Understanding the functional consequence of noncoding variants is of great interest. Though genome-wide association studies or quantitative trait locus analyses have identified variants associated with traits or molecular phenotypes, most of them are located in the noncoding regions, making the identification of causal variants a particular challenge. Existing computational approaches developed for prioritizing noncoding variants produce inconsistent and even conflicting results. To address these challenges, we propose a novel statistical learning framework, which directly integrates the precomputed functional scores from representative scoring methods. It will maximize the usage of integrated methods by automatically learning the relative contribution of each method and produce an ensemble score as the final prediction. The framework consists of two modes. The first ‘context-free’ mode is trained using curated causal regulatory variants from a wide range of context and is applicable to predict regulatory variants of unknown and diverse context. The second ‘context-dependent’ mode further improves the prediction when the training and testing variants are from the same context. By evaluating the framework via both simulation and empirical studies, we demonstrate that it outperforms integrated scoring methods and the ensemble score successfully prioritizes experimentally validated regulatory variants in multiple risk loci.

Preimplantation genetic testing for aneuploidy (PGT-A) is widely used to select embryos having normal ploidy for transfer, but they require an invasive embryo biopsy procedure that may cause harm to the embryos and offspring. Therefore, a non-invasive approach to select embryos with normal ploidy for implantation is highly demanded. Non-invasive chromosome screening (NICS) methods have been proposed and applied in clinical practices, but a large-scale validation versus invasive preimplantation genetic testing (PGT) and the whole embryo ploidy has not yet been reported. In this study, by using the whole embryo as a gold standard, we validated NICS assay in a total of 265 donated human embryos and compared its performance with conventional trophectoderm (TE) biopsy PGT. The NICS assay showed promising performance, which is comparable to PGT-TE [sensitivity: 87.36 versus 89.66%; specificity: 80.28 versus 82.39%; negative predictive value (NPV): 91.2 versus 92.86%; positive predictive value (PPV): 73.08 versus 75.73%]. Additionally, NICS provides a scoring system for prioritizing embryo: embryos can be categorized into three groups with euploid prediction probabilities of 90.0, 27.8, and 72.2% for group euploid (A), aneuploid (B), and multiple abnormal chromosomes (MAC) (C), respectively. When an addition of TE assay is provided as a secondary validation, the accuracy significantly increases from 72.2 to 84.3% for group B and from 27.8 to 83.3% for group C. Our results suggest that NICS is a good rule in assay for identifying chromosomal normal embryos for transfer and might serve as a non-invasive approach for prioritizing embryos instead of preventing transfer of aneuploid and MAC embryos. It will help to ensure the safety of offspring and efficient utilization of embryos.

Complex networks have become a powerful tool to describe the structure and evolution in a large quantity of real networks in the past few years, such as friendship networks, metabolic networks, protein–protein interaction networks, and software networks. While a variety of complex networks have been published, dense networks sharing remarkable structural properties, such as the scale-free feature, are seldom reported. Here, our goal is to construct a class of dense networks. Then, we discover that our networks follow the mixture degree distribution; that is, there is a critical point above which the cumulative degree distribution has a power-law form and below which the exponential distribution is observed. Next, we also prove the networks proposed to show the small-world property. Finally, we study random walks on our networks with a trap fixed at a vertex with the highest degree and find that the closed form for the mean first-passage time increases logarithmically with the number of vertices of our networks.

Forkhead box O (FoxO) protein, a major downstream transcription factor of insulin/insulin-like growth factor signaling/target of rapamycin pathway (IIS/TOR), is involved in the regulation of larval growth and the determination of organ size. FoxO also interacts with 20-hydroxyecdysone (20E) and juvenile hormone (JH) signal transduction pathways, and hence is critical for larval development in holometabolans. However, whether FoxO plays a critical role during larval metamorphosis needs to be further determined in Leptinotarsa decemlineata. We found that 20E stimulated the expression of LdFoxO. RNA interference (RNAi)-aided knockdown of LdFoxO at the third-instar stage repressed 20E signaling and reduced larval weight. Although the resultant larvae survived through the third-fourth instar ecdysis, around 70% of the LdFoxO depleted moribund beetles developmentally arrested at prepupae stage. These LdFoxO depleted beetles were completely wrapped in the larval exuviae, gradually darkened and finally died. Moreover, approximately 12% of the LdFoxO RNAi beetles died as pharate adults. Ingestion of either 20E or JH by the LdFoxO depletion beetles excessively rescued the corresponding hormonal signals, but could not alleviate larval performance and restore defective phenotypes. Therefore, FoxO plays an important role in regulation of larval-pupal-adult transformation in L. decemlineata, in addition to mediation of IIS/TOR pathway and stimulation of ecdysteroidogenesis.

Focusing on low biogas yields in the anaerobic co-digestion of waste activated sludge and food waste, the enhancing effects and mechanisms of microscale zero valent iron (mZVI) on anaerobic co-digestion was investigated. The results indicated that the addition of mZVI enhanced the methanogenesis stage of co-digestion but had no significant effect on the solubilization, hydrolysis, and acidification stages. With a dosage of 10 g·L

A new method for judging degree sequence is shown by means of perfect ice-flower systems made by operators - stars (particular complete bipartite graphs), and moreover this method can be used to build up degree sequences and perfect ice-flower systems. Graphic lattice, graph-graphic lattice, caterpillar-graphic lattice and topological coding lattice are defined. We establish some connections between traditional lattices and graphic lattices trying to provide new techniques for Lattice-based cryptosystem and post-quantum cryptography, and trying to enrich the theoretical knowledge of topological coding.

Based on the problems that quantum computer is not good at computing, various anti-quantum-computing ciphers have been designed to resist the threat of the forthcoming quantum computing to the public key cryptosystem. We design several topological authentications on number-based strings and degree-sequences in topological coding by sequence-type operations, leaf-type operations, vertex-type operations, cycle-type operations, where number-based strings are considered as public keys in topological authentications. The decomposition of degree-sequences of graphs are determined completely, and we build up the connections between degree-sequences and various graphic lattices, as well as the complexity of decomposing a number-based string into a degree-sequence is NP-hard.

For answering the similarity authentication problem: "For a given public key-graph G colored by a coloring , find a private key-graph H admitting a coloring such that G and H admit one of some similarities, and a particular text-based string induced from a Topcode-matrix of G is authenticated with another particular text-based string induced from a Topcode-matrix of H". For new new encryption techniques and measuring various similarities between graphs, we define some particular W-similarities, such as: isomorphic subgraph similarity, subgraph Topcode-matrix similarity, isomorphic colored subgraph similarity, subgraph degree-sequence e-distance similarity, subgraph m-editable similarity, graphic base H-similarity, etc. Moreover, we introduce several graph operations, graph-splitting group matchings and graphic lattices an so on, such that our topological encryption techniques can be used in the calculating era of supercomputer and quantum computer.

Depressive phenotypes induced by paternal stress can be transferred from one generation to the next via small RNAs in the sperm., Evidence that offspring traits can be shaped by parental life experiences in an epigenetically inherited manner paves a way for understanding the etiology of depression. Here, we show that F1 offspring born to F0 males of depression-like model are susceptible to depression-like symptoms at the molecular, neuronal, and behavioral levels. Sperm small RNAs, and microRNAs (miRNAs) in particular, exhibit distinct expression profiles in F0 males of depression-like model and recapitulate paternal depressive-like phenotypes in F1 offspring. Neutralization of the abnormal miRNAs in zygotes by antisense strands rescues the acquired depressive-like phenotypes in F1 offspring born to F0 males of depression-like model. Mechanistically, sperm miRNAs reshape early embryonic transcriptional profiles in the core neuronal circuits toward depression-like phenotypes. Overall, the findings reveal a causal role of sperm miRNAs in the inheritance of depression and provide insight into the mechanism underlying susceptibility to depression.

When we are fatigued, we feel that our performance is worse than when we are fresh. Yet, for over 100 years, researchers have been unable to identify an objective, behavioral measure that covaries with the subjective experience of fatigue. Previous work suggests that the metrics of signal detection theory (SDT)—response bias (criterion) and perceptual certainty (d’)—may change as a function of fatigue, but no work has yet been done to examine whether these metrics covary with fatigue. Here, we investigated cognitive fatigue using SDT. We induced fatigue through repetitive performance of the n-back working memory task, while functional magnetic resonance imaging (fMRI) data was acquired. We also assessed cognitive fatigue at intervals throughout. This enabled us to assess not only whether criterion and d’ covary with cognitive fatigue but also whether similar patterns of brain activation underlie cognitive fatigue and SDT measures. Our results show that both criterion and d’ were correlated with changes in cognitive fatigue: as fatigue increased, subjects became more conservative in their response bias and their perceptual certainty declined. Furthermore, activation in the striatum of the basal ganglia was also related to cognitive fatigue, criterion, and d’. These results suggest that SDT measures represent an objective measure of cognitive fatigue. Additionally, the overlap and difference in the fMRI results between cognitive fatigue and SDT measures indicate that these measures are related while also separate. In sum, we show the relevance of SDT measures in the understanding of fatigue, thus providing researchers with a new set of tools with which to better understand the nature and consequences of cognitive fatigue.

BackgroundN6-methyladenosine (m6A) modification is known to impact many aspects of RNA metabolism, including mRNA stability and translation, and is highly prevalent in the brain.ResultsWe show that m6A modification displays temporal and spatial dynamics during neurodevelopment and aging. Genes that are temporally differentially methylated are more prone to have mRNA expression changes and affect many pathways associated with nervous system development. Furthermore, m6A shows a distinct tissue-specific methylation profile, which is most pronounced in the hypothalamus. Tissue-specific methylation is associated with an increase in mRNA expression and is associated with tissue-specific developmental processes. During the aging process, we observe significantly more m6A sites as age increases, in both mouse and human. We show a high level of overlap between mouse and human; however, humans at both young and old ages consistently show more m6A sites compared to mice. Differential m6A sites are found to be enriched in alternative untranslated regions of genes that affect aging-related pathways. These m6A sites are associated with a strong negative effect on mRNA expression. We also show that many Alzheimer-related transcripts exhibit decreased m6A methylation in a mouse model of Alzheimer’s disease, which is correlated with reduced protein levels.ConclusionsOur results suggest that m6A exerts a critical function in both early and late brain development in a spatio-temporal fashion. Furthermore, m6A controls protein levels of key genes involved in Alzheimer’s disease-associated pathways, suggesting that m6A plays an important role in aging and neurodegenerative disease.

The problem of determining the number of spanning trees of graph having interesting structural properties such as the scale-free feature is attractive in science community. In this paper, we first present a class of outer-planar and self-similar graphs N(t) by using vertex-edge-growth operation. According to specific topological structure, we calculate the average degree, and show that the model N(t) is sparse. Then, we develop a series of iterative methods in order to obtain an exact solution of the total number of spanning trees of the model N(t), and also illustrate the corresponding spanning tree entropy. The calculation method used can be suitable for enumerating spanning trees of other graphs with similar properties.

Background: Approximately 15% of all solid tumors harbor deletions in methylthioadenosine phosphorylase (MTAP) (1). MTAP deficiencies have been reported to sensitize tumor cells to methionine adenosyltransferase 2A (MAT2A) modulation (2). MAT2A synthesizes the universal methyl donor and PRMT5 substrate S-adenosylmethionine (SAM) from methionine. PRMT5 symmetrically di-methylates arginine (SDMA) residues on proteins that are key to genomic integrity and proteostasis. We evaluated the anti-tumor activity of the small molecule MAT2A inhibitor IDE397 in multiple CDX models and in an ongoing study of 45 MTAP-deleted PDX models to inform clinical strategy for a First-in-Human clinical trial evaluating IDE397. Methods: CDX models utilized included the HCT116 isogenic pair and endogenous MTAP-deleted models. A series of dose response and time-course studies were performed to inform the efficacy-PD relationship. SAM was quantified by LC-MS and SDMA was visualized by western blot (WB) and further quantified by immunohistochemistry (IHC). PDX models with MTAP homozygous deletions were selected from bladder, esophageal, gastric, head and neck, NSCLC and pancreatic cancers. MTAP deletion was determined by WES and/or SNP 6.0 microarray and verified by absence of significant mRNA. Tumors were subcutaneously implanted into immunocompromised mice by serial transplantation of tumor fragments. Each PDX model included a vehicle control and an IDE397-treated group (n=5/group). IDE397 was administered orally once per day (QD). Tumor growth inhibition (TGI) was calculated using the formula TGI = (TV controlfinal - TV treatedfinal)/(TV controlfinal - TV controlinitial) x 100. Results: Administration of IDE397 resulted in TGI and/or tumor regression in MTAP-deleted CDX and PDX models. The HCT116 MTAP-deleted CDX model was more sensitive to IDE397 compared to the HCT116 MTAP-WT model. IDE397 produced a dose- and time-dependent modulation of the proximal and distal PD biomarkers SAM and SDMA. SAM was decreased in plasma and tumors irrespective of MTAP status. In contrast, SDMA was selectively modulated in MTAP-null models only. In a NSCLC CDX model, a dose dependent TGI was observed, with the higher doses leading to tumor regression. Anti-tumor activity is observed in MTAP-deleted PDX models, where IDE397 administration has resulted in TGI and tumor regressions. Conclusion: Xenograft studies indicate that IDE397 exhibits anti-tumor activity as a single agent in MTAP-deleted CDX models and in MTAP-deleted PDX models of NSCLC, pancreatic, bladder, head and neck, esophageal and gastric cancer. This data supports the clinical evaluation of IDE397 across a wide range of solid tumor types with MTAP-deletion. References: (1) Beroukhim, R. et al. Nature 2010 Feb 18;463(7283):899-905. (2) Marjon, K. et al. Cell Rep 2016 Apr 19;15(3):574-587. Citation Format: Marcus M. Fischer, Neil Bhola, John Faulhaber, Yevgeniy Freyman, Bing Yao, Zineb Mounir, Mark R. Lackner, Claire Neilan. MAT2A inhibitor, IDE397, displays broad anti-tumor activity across a panel of MTAP-deleted patient-derived xenografts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1278.

// Bing Yao 1, * , Bingqian Liu 1, * , Lei Shi 1, * , Xiang Li 2 , Chuanchuan Ren 1 , Mingbo Cai 3 , Wen Wang 3 , Jianhua Li 1 , Yongde Sun 1 , Yudong Wu 1 , Jianguo Wen 1 1 Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 2 Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 3 Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China * These authors contributed equally to this work Correspondence to: Yudong Wu, email: yudongwu_zhd@163.com Jianguo Wen, email: wenjg_zhdu@163.com Keywords: platelet activating factor receptor, prostatic neoplasms, radiotherapy, autophagy, drug sensitivity Received: July 22, 2016 Accepted: January 03, 2017 Published: January 14, 2017 ABSTRACT Platelet-activating factor receptor (PAFR) promotes tumorigenesis, angiogenesis and metastasis. Here, we defined the PAFR as a yielding new inhibiting target to selectively enhance the sensitivity of prostate cancer (PCa) cells to radiation. The selective responding to PAFR inhibiter may be caused by the differential expression pattern of PAFR in PCa cells. In this study, we also determined PAFR as a molecular basis by which the radiation induces autophagy suppression independent of activating mTOR pathway. PAFR can bind to the autophagy-indispensable protein Beclin 1, leading to the disability in its serine phosphorylation. The PAFR antagonist Ginkgolide B (GB) can sensitize radiotherapy by disrupting the formation of PAFR/Beclin 1 complex in PC3 and LNCaP cells, which have elevated PAFR expression after radiation exposure. Most importantly, GB efficiently radiosensitized PC3 and LNCaP tumor xenografts in vivo , and significantly reduced tumor burden. Overall, our results elucidated a significant role of GB in selectively improving the outcomes of PCa receiving radiation therapy.

Topological cryptography wants number of new colorings of graphs for resisting attack from supercomputer and quantum computers in the near future. Needless to say, one want random text-based strings as passwords or crypt digital files, also, want such forms of “one public key vs two or more private keys” and “one private key vs two or more public keys”. We define some sequence-type colorings and set-ordered sequence-type colorings defined on number sequences, also, these colorings are parameterized colorings with certain randomness. An algorithm, called LEAF-adding algorithm, is designed for proving “Each tree admits a set-ordered graceful total coloring”, which helps us to show trees admitting graceful sequence total colorings. Moreover, we discuss colorings based on abstract sequences, and construct connections between sequence-type colorings by the abstract substitution and the mapping homomorphism. At the end of the article we present “Text-Based String Partition Problem” for proving our sequence-type colorings having “provable security”.

In order to serve the need of resisting full-scale attacks and sabotage by supercomputers and quantum computers in the future, we make two systems of linear equations for optimizing network models such that they can simulate and approximate to high quality networks such as BA-models, tree-like network models, network models containing blockchain. We will design two algorithms for encrypting randomly growing network models wholly in dynamic evolution of the networks. These network models mentioned here produce network-network lattices, graphic group lattices, infinite every-zero graphic group homomorphism, mutually equivalent infinite every-zero graphic groups, and relate to mathematical problems.

Information security is a long-term and relative problem. Since dynamic networks change with time, the coding (coloring or labeling) of dynamic networks is far different from graph colorings/labelings of graph theory. Various distinguishing colorings of graph theory can help us to encrypt dynamic networks wholly, although it is a new topic of network security. We use ice-flower systems to construct lattices (colored star-graphic lattices, star Topcode-matrix lattices) containing networks encrypted wholly by the distinguishing colorings with many restrictions, and propose a difficult problem called Number String Decomposition.

In topological authentication for encrypting networks wholly we define matchings of dual-type and image-type labellings/colorings, such as totally-dual $(W_{f},\ W_{g})$-type total-image labellings/colorings, uniformly dual-image $(W_{f},\ W_{g})$-type labellings/colorings; and moreover we define graph edge-homomorphism from a graph to another graph, graph edge-homomorphism, dual-image graph base-homomorphism, matching of $(W_{f},\ W_{g})$-type number strings. The Number String Decomposition Problem is proposed for resisting possibly the attack of supercomputers and quantum computing.

This paper proposes a reactive power coordination control scheme between voltage source converter based HVDC (VSC-HVDC) system and filter switching of line commutated converter based HVDC (LCC-HVDC) system for a hybrid multi-infeed VSC/LCC HVDC system. The conventional reactive power control strategies of filter switching of LCC-HVDC system and VSC-HVDC system are analyzed, and the limitations of them are pointed out. To reduce the filter switching, a control module is designed for the coordination control scheme. A hybrid multi-infeed system model was built in PSCAD/EMTDC for simulation verification. The simulation results showed that the performance of the reactive power coordinated control is better than that of the reactive power independent control between VSC-HVDC system and LCC-HVDC system.

Understanding the functional consequence of noncoding variants is of great interest. Though genome-wide association studies (GWAS) or quantitative trait locus (QTL) analyses have identified variants associated with traits or molecular phenotypes, most of them are located in the noncoding regions, making the identification of causal variants a particular challenge. Existing computational approaches developed for for prioritizing non-coding variants produce inconsistent and even conflicting results. To address these challenges, we propose a novel statistical learning framework, which directly integrates the precomputed functional scores from representative scoring methods. It will maximize the usage of integrated methods by automatically learning the relative contribution of each method and produce an ensemble score as the final prediction. The framework consists of two modes. The first “context-free” mode is trained using curated causal regulatory variants from a wide range of context and is applicable to predict noncoding variants of unknown and diverse context. The second “context-dependent” mode further improves the prediction when the training and testing variants are from the same context. By evaluating the framework via both simulation and empirical studies, we demonstrate that it outperforms integrated scoring methods and the ensemble score successfully prioritizes experimentally validated regulatory variants in multiple risk loci.

Among the different antibiotics, tetracycline hydrochloride (TCH) is one of the most commonly used. In this study, the activated sodium persulfate (SPS) process induced by microwave (MW) energy was used to treat TCH. The effect of different operational parameters of MW/SPS-treated TCH, such as SPS concentration, TCH concentration, initial pH, and MW power, was investigated. The concentration changes of TCH were determined using a spectrophotometer. The results of radical scavenger experiments indicated that the sulfate radical () was stronger than the hydroxyl radical (·OH). On the basis of high performance liquid chromatography–mass spectrometry (HPLC–MS) analysis, a possible degradation pathway of TCH was proposed. This research indicates that the MW/SPS system is a promising prospect for the treatment of TCH.

Since encrypting networks wholly by graphic groups, we will define a new labelling, called modular- $2q$ mixed odd-graceful labelling, and build up various graphic groups based on the modular- $2q$ mixed odd-graceful labelling. We will show: the necessity and sufficiency of subgroup of a graphic group; a ( $p, q$ ) -graph $G$ admitting a modular- $2q$ mixed(negative) odd-graceful labelling can generate a graphic group, and moreover these graphs form an Abelian additive graphic group. A ( $p, q$ ) -graph $G$ admits a modular- $2q$ odd-graceful labelling $f$ generate $2q$ vertex-modular graphs, each of them generates $2q$ edge-modular graphs, which form an Abelian additive graphic group, similar results can be obtained for modular- $2q$ negative odd-graceful graph and modular- $2q$ mixed odd-graceful graph.

New security methods based on lattice cryptography emerge today. It has been shown that topological coding made by topological structures and mathematical restrictions can be used to serve information security, since the Number String Decomposition Problem of topological coding is NP-hard. We aim to producing topological coding, encrypting networks wholly and finding matching of twin graphic groups, multiple-graphic groups for serving the construction of graphic lattices. New coloring/labellings, matching-type graphic groups and infinite graphic groups will be discussed, a new Wait-filling Topcode-matrices Problem will be proposed.

In the field of information security, there are many public-key cryptographies, such as the RSA algorithm, EIGamal cryptography, Rabin algorithm and so on, these encryption algorithms are based on difficult algebraic problems. We propose a new encryption algorithm from the perspective of topology, which combine topological structures of graphs with matching-type image-labellings to generate public and private keys, and the new algorithm is based on the difficulty of judging the graph isomorphism problem. We construct two types of leaf self-similar trees, and our large-scale passwords can be generated on this basis, in addition, leaf self-similar tree increases the length and difficulty of the passwords for resisting the attack of supercomputers and quantum computers.

A new type of total colorings is defined, we call them n-dimension total colorings such that the vertices and edges of graphs are colored with $n$ -dimension digital-based strings $a_{1}a_{2}\cdots a_{n}$ , and hold some restrictive conditions between the colors of vertices and edges of the graphs. We show that All trees admit 2-dimension proper total colorings by the ADDING-leaves algorithm. By trees admitting 2-dimension proper total colorings, we present tree-graphic lattices and 2-dimension Topcode-matrices for building topological cryptography in topological coding. Some mathematical problems for future research are proposed at the end of this article.

Long noncoding RNAs (lncRNAs) have emerged as important regulators in cancers, including breast cancer. However, the overall biological roles and clinical significance of most lncRNAs are not fully understood. This study aimed to elucidate the potential role of a novel lncRNA FGF14-AS2 and the mechanisms underlying metastasis in breast cancer. The lncRNA FGF14-AS2 was significantly downregulated in breast cancer tissues; patients with lower FGF14-AS2 expression had advanced clinical stage. In vitro and in vivo assays of FGF14-AS2 alterations revealed a complex integrated phenotype affecting breast cancer cell migration, invasion, and tumor metastasis. Mechanistically, FGF14-AS2 functioned as a competing endogenous RNA of miR-370-3p, thereby leading to the activation of its coding counterpart, FGF14. Clinically, we observed increased miR-370-3p expression in breast cancer tissues, whereas FGF14 expression was decreased in breast cancer tissues compared to the adjacent normal breast tissues. FGF14-AS2 expression was significantly negatively correlated with miR-370-3p expression, and correlated positively to FGF14 expression. Collectively, our findings support a model in which the FGF14-AS2/miR-370-3p/FGF14 axis is a critical regulator in breast cancer metastasis, suggesting a new therapeutic direction in breast cancer.

Gliomas are the most common primary malignant brain tumors associated with a low survival rate. Even after surgery, radiotherapy, and chemotherapy, gliomas still have a poor prognosis. Extracellular vesicles are a heterogeneous group of cell-derived membranous structures. Exosomes are a type of extracellular vesicles, their size ranges from 30 nm to 100 nm. Recent studies have proved that glioma cells could release numerous exosomes; therefore, exosomes have gained increasing attention in glioma-related research. Recent studies have confirmed the importance of extracellular vesicles, particularly exosomes, in the development of brain tumors, including gliomas. Exosomes mediate intercellular communication in the tumor microenvironment by transporting biomolecules (proteins, lipids, deoxyribonucleic acid, and ribonucleic acid); thereby playing a prominent role in tumor proliferation, differentiation, metastasis, and resistance to chemotherapy or radiation. Given their nanoscale size, exosomes can traverse the blood-brain barrier and promote tumor progression by modifying the tumor microenvironment. Based on their structural and functional characteristics, exosomes are demonstrating their value not only as diagnostic and prognostic markers, but also as tools in therapies specifically targeting glioma cells. Therefore, exosomes are a promising therapeutic target for the diagnosis, prognosis, and treatment of malignant gliomas. More research will be needed before exosomes can be used in clinical applications. Here, we describe the exosomes, their morphology, and their roles in the diagnosis and progression of gliomas. In addition, we discuss the potential of exosomes as a therapeutic target/drug delivery system for patients with gliomas.