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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.

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

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.

The rapid developments in advanced sensing and imaging bring about a data-rich environment, facilitating the effective modeling, monitoring, and control of complex systems. For example, the body-sensor network captures multi-channel information pertinent to the electrical activity of the heart (i.e., electrocardiograms (ECG)), which enables medical scientists to monitor and detect abnormal cardiac conditions. However, the high-dimensional sensing data are generally complexly structured and realizing the full data potential depends to a great extent on advanced analytical and predictive methods. This paper presents a physics-constrained deep learning (P-DL) framework for high-dimensional inverse ECG modeling. This method integrates the physical laws of the complex system with the advanced deep learning infrastructure for effective prediction of the system dynamics. The proposed P-DL approach is implemented to solve the inverse ECG model and predict the time-varying distribution of electric potentials in the heart from the ECG data measured by the body-surface sensor network. Experimental results show that the proposed P-DL method significantly outperforms existing methods that are commonly used in current practice.

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.

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.

The mean first-passage time of random walks on a network has been extensively applied in the theory and practice of statistical physics, and its application effects depend on the behavior of first-passage time. Here, we firstly define a graphic operation, namely, rectangle operation, for generating a scale-free network. In this paper, we study the topological structures of our network obtained from the rectangle operation, including degree distribution, clustering coefficient, and diameter. And then, we also consider the characteristic quantities related to the network, including Kirchhoff index and mean first-passage time, where these characteristic quantities can not only be used to evaluate the properties of our network, but also have remarkable applications in science and engineering.

A variety of labelings on trees have emerged in order to attack the Graceful Tree Conjecture, but lack showing the connections between two labelings. In this paper, we propose two new labelings: vertex image-labeling and edge image-labeling, and combine new labelings to form matching-type image-labeling with multiple restrictions. The research starts from the set-ordered graceful labeling of the trees, and we give several generation methods and relationships for well-known labelings and two new labelings on trees.

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.

Non-obstructive azoospermia (NOA) severely affects male infertility, however, the deep mechanisms of this disease are rarely interpreted. In this study, we find that undifferentiated spermatogonial stem cells (SSCs) still exist in the basal compartment of the seminiferous tubules and the blood–testis barrier (BTB) formed by the interaction of neighbor Sertoli cells (SCs) is incomplete in NOA patients with spermatogenic maturation arrest. The adhesions between SCs and germ cells (GCs) are also broken in NOA patients. Meanwhile, the expression level of geranylgeranyl diphosphate synthase (Ggpps), a key enzyme in mevalonate metabolic pathway, is lower in NOA patients than that in obstructive azoospermia (OA) patients. After Ggpps deletion specifically in SCs, the mice are infertile and the phenotype of the SC-Ggpps−/− mice is similar to the NOA patients, where the BTB and the SC–GC adhesions are severely destroyed. Although SSCs are still found in the basal compartment of the seminiferous tubules, fewer mature spermatocyte and spermatid are found in SC-Ggpps−/− mice. Further examination suggests that the defect is mediated by the aberrant protein isoprenylation of RhoA and Ras family after Ggpps deletion. The exciting finding is that when the knockout mice are injected with berberine, the abnormal cell adhesions are ameliorated and spermatogenesis is partially restored. Our data suggest that the reconstruction of disrupted BTB is an effective treatment strategy for NOA patients with spermatogenic maturation arrest and hypospermatogenesis.

Graphene nanoribbons are ideal candidates to serve as highly conductive, flexible, and transparent interconnections, or the active channels for nanoelectronics. However, patterning narrow graphene nanoribbons to 30%, while carrying stable and repeatable electronic transport. We suggest that this convenient scalable nanowire lithography technology has great potential to establish a general and efficient strategy to batch-pattern or integrate various two-dimensional materials as active channels and interconnections for emerging flexible electronic applications.

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.

SUMMARY 5-hydroxymethylcytosine (5hmC) is enriched in brain and has been recognized as an important DNA modification. However, the roles of 5hmC and its writers, ten-eleven translocation (Tet) proteins, in stress-induced response have yet to be elucidated. Here, we show that chronic restraint stress (CRS) induced depression-like behavior in mice and resulted in a 5hmC reduction in prefrontal cortex (PFC). We found that loss of Tet1 (Tet1 KO) led to resistance to CRS, whereas loss of Tet2 (Tet2 KO) increased the susceptibility of mice to CRS. Genome-wide 5hmC profiling identified the phenotype-associated stress-induced dynamically hydroxymethylated loci (PA-SI-DhMLs), which are strongly enriched with hypoxia-induced factor (HIF) binding motifs. We demonstrated the physical interaction between TET1 and HIF1α induced by CRS and revealed that the increased HIF1α binding under CRS is associated with SI-DhMLs. These results suggest that TET1 could regulate stress-induced response by interacting with HIFIα., Graphical Abstract, In Brief The roles of 5-hydroxymethylcytosine (5hmC) and its writers, Tet proteins, in stress-induced response remain unclear. Cheng et al. show that Tet1 knockout mice exhibit resistance, whereas Tet2 knockout mice have increased susceptibility to stress. Biochemical and genome-wide analyses suggest that Tet1 could regulate stress-induced response by interacting with Hif1α.

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.

Background Immune checkpoint inhibitors blocking programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) have emerged as effective treatment options for cancer. However, immunotherapy is only effective in a subset of patients. Identifying effective biomarkers to predict the treatment response to PD-1/PD-L1 inhibitors remains an unmet clinical need. Methods This study retrospectively analyzed clinical information and genetic profiling results of 16,013 samples from Chinese patients with various cancer types in order to investigate the prevalence of CD274 (also known as PD-L1) amplification in various cancer types and its association with existing PD-1/PD-L1 biomarkers, including tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 expression. Results Amplification of CD274 was identified in 174 samples with an overall prevalence of 1.09% among all cancer types in the cohort. The prevalence of CD274 amplification in different cancer types and histological subtypes of lung cancer was varied, with cervical cancer having the highest prevalence. Distinct distributions of TMB, MSI, and PD-L1 expression between CD274-amplified and wild-type samples were observed in several cancer types as well as among different histological subtypes of lung cancer. Conclusions Although CD274 amplification was only observed in a small proportion of patients, it demonstrated an association with TMB, MSI, and PD-L1 expression in several common cancer types. The molecular features of CD274 in different cancer types are heterogeneous. The role of CD274 amplification as a novel biomarker of PD-1/PD-L1 inhibitors remains to be characterized in future prospective clinical studies.

Gliomas are the most invasive and fatal primary malignancy of the central nervous system that have poor prognosis, with maximal safe resection representing the gold standard for surgical treatment. To achieve gross total resection (GTR), neurosurgery relies heavily on generating continuous, real-time, intraoperative glioma descriptions based on image guidance. Given the limitations of currently available equipment, developing a real-time image-guided resection technique that provides reliable functional and anatomical information during intraoperative settings is imperative. Nowadays, the application of intraoperative ultrasound (IOUS) has been shown to improve resection rates and maximize brain function preservation. IOUS, which presents an attractive option due to its low cost, minimal operational flow interruptions, and lack of radiation exposure, is able to provide real-time localization and accurate tumor size and shape descriptions while helping distinguish residual tumors and addressing brain shift. Moreover, the application of new advancements in ultrasound technology, such as contrast-enhanced ultrasound, three-dimensional ultrasound, navigable ultrasound, ultrasound elastography, and functional ultrasound, could help to achieve GTR during glioma surgery. The current review describes current advancements in ultrasound technology and evaluates the role and limitation of IOUS in glioma surgery.

Background Aberrant changes in epigenetic mechanisms such as histone modifications play an important role in cancer progression. PRMT1 which triggers asymmetric dimethylation of histone H4 on arginine 3 (H4R3me2a) is upregulated in human colorectal cancer (CRC) and is essential for cell proliferation. However, how this dysregulated modification might contribute to malignant transitions of CRC remains poorly understood. Methods In this study, we integrated biochemical assays including protein interaction studies and chromatin immunoprecipitation (ChIP), cellular analysis including cell viability, proliferation, colony formation, and migration assays, clinical sample analysis, microarray experiments, and ChIP-Seq data to investigate the potential genomic recognition pattern of H4R3me2s in CRC cells and its effect on CRC progression. Results We show that PRMT1 and SMARCA4, an ATPase subunit of the SWI/SNF chromatin remodeling complex, act cooperatively to promote colorectal cancer (CRC) progression. We find that SMARCA4 is a novel effector molecule of PRMT1-mediated H4R3me2a. Mechanistically, we show that H4R3me2a directly recruited SMARCA4 to promote the proliferative, colony-formative, and migratory abilities of CRC cells by enhancing EGFR signaling. We found that EGFR and TNS4 were major direct downstream transcriptional targets of PRMT1 and SMARCA4 in colon cells, and acted in a PRMT1 methyltransferase activity-dependent manner to promote CRC cell proliferation. In vivo, knockdown or inhibition of PRMT1 profoundly attenuated the growth of CRC cells in the C57BL/6 J-ApcMin/+ CRC mice model. Importantly, elevated expression of PRMT1 or SMARCA4 in CRC patients were positively correlated with expression of EGFR and TNS4, and CRC patients had shorter overall survival. These findings reveal a critical interplay between epigenetic and transcriptional control during CRC progression, suggesting that SMARCA4 is a novel key epigenetic modulator of CRC. Our findings thus highlight PRMT1/SMARCA4 inhibition as a potential therapeutic intervention strategy for CRC. Conclusion PRMT1-mediated H4R3me2a recruits SMARCA4, which promotes colorectal cancer progression by enhancing EGFR signaling.

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.