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Background: Acute lymphoblastic leukemia with MLL/AF4 rearrangement remains a major hurdle to improving outcomes. Gene network and circRNAs have been found to participate in tumorigenesis, while their roles in leukemia still need to be explored. Recent patents have shown that circRNAs exhibit the markers for the children ALL, although the target and related mechanism remain to be elucidated. Objective: This study aims to explore the possible targets and mechanisms of ALL with MLLAF4 rearrangement. Methods: We first generated a gene network focusing on MLL-AF4 rearrangement. Cell viability was determined with Cell Counting Kit-8 assay. The cell apoptosis was tested by the Annexin V/PI assay. The RNA-protein complexes were analyzed by qRT-PCR, and the pathway proteins were analyzed by western blot. Results: This gene network was associated with biological processes, such as nucleic acid metabolism and immunity, indicating its key role in inflammation. We found that circ_0008012 was upregulated in MLL/AF4 ALL cells and regulated cell proliferation and apoptosis. Further computed simulation and RIP showed that IKKβ was the strongest protein in the NF-κB pathway binding with circ_0008012. As a result, possible regulation of circ_0008012 is suggested by binding IKKβ in the IKKα:IKKβ:IKKγ compound, which then phosphorylates IκB and activates NF- κB:p65:p300 compound in cell nucleus, thereby leading to leukemia. Conclusion: We identified a gene network for MLL/AF4 ALL. Moreover, circ_0008012 may be a therapeutic target for this subtype of ALL.

The application of electric vehicles (EVs) in the logistics industry has become more extensive. However, the mileage limitation of electric logistics vehicles (ELVs) and the long-distance distribution of ELVs have become urgent problems. Therefore, this paper proposes a long-distance distribution model for ELVs based on dynamic traffic information considering fleet mileage, distribution time and total distribution cost as the optimisation objectives, thus reasonably planning road selection and charging, and alleviating “mileage anxiety” in the long-distance distribution of ELVs. The model proposed in this paper comprehensively considers the characteristics of the high-speed and low-speed roads, the changes in road traffic flow on weekdays and non-weekdays, the time-of-use electricity price of electric vehicle charging stations (EVCSs) and uses the M/M/s queuing theory model to determine the charging waiting time. Finally, a real traffic network is taken as an example to verify the practicability and effectiveness of this model.

In the field of education, digital learning plays an important part. For each passing day, digital learning is displacing the traditional method of education. An accurate analysis of a student's qualities improves their academic performance. With the advancement of technology and big data, there are many applications for big data analytics, including education. Huge volumes of academic information are being generated, and discovering a technique to harness and analyze this information effectively is a challenging issue among many educational organizations. In this paper, educational clustering big data mining system (ECBDMS) has been proposed. The cognitive web service based learning analytic(CWS-LA) system is integrated to securely categorize and provide ease of access to the data. ECBDMS has been found to improve performance gains of 92.8%, prediction ratios of 88.6%, clustering error ratios of 2.3 percent, learning percentages of 94%, and forecasting accuracy of 97.1 percent when compared to other existing methods.

Delta(9)-tetrahydrocannabinolic acid (THCA) and delta(9)-tetrahydrocannabivarin (THCV) are phytocannabinoids with a similar structure derived from Cannabis sativa and possess a variety of biological activities. However, the relationship between the metabolic characterisation and bioactivity of THCA and THCV remains elusive.To explore the relationship between the metabolism of THCA and THCV and their underlying mechanism of activity, human/mouse liver microsomes and mouse primary hepatocytes were used to compare the metabolic maps between THCA and THCV through comparative metabolomics. A total of 29 metabolites were identified containing 7 previously undescribed THCA metabolites and 10 previously undescribed THCV metabolites. Of these metabolites, THCA was transformed into an active metabolite of delta(9)-tetrahydrocannabinol (THC) in these three systems, while THCV was transformed into THC and CBD.Bioactivity assays indicated that all of these phytocannabinoids exhibited anti-inflammatory activity, but the effects of THCA and THCV were slightly different in macrophages RAW264.7. Prediction of ADMET lab demonstrated that THCV and its metabolites were endowed with the advantage of blood–brain barrier (BBB) penetration compared to THCA.In conclusion, this study highlighted that metabolism plays a critical role in the biological activity of phytocannabinoids. Delta(9)-tetrahydrocannabinolic acid (THCA) and delta(9)-tetrahydrocannabivarin (THCV) are phytocannabinoids with a similar structure derived from Cannabis sativa and possess a variety of biological activities. However, the relationship between the metabolic characterisation and bioactivity of THCA and THCV remains elusive. To explore the relationship between the metabolism of THCA and THCV and their underlying mechanism of activity, human/mouse liver microsomes and mouse primary hepatocytes were used to compare the metabolic maps between THCA and THCV through comparative metabolomics. A total of 29 metabolites were identified containing 7 previously undescribed THCA metabolites and 10 previously undescribed THCV metabolites. Of these metabolites, THCA was transformed into an active metabolite of delta(9)-tetrahydrocannabinol (THC) in these three systems, while THCV was transformed into THC and CBD. Bioactivity assays indicated that all of these phytocannabinoids exhibited anti-inflammatory activity, but the effects of THCA and THCV were slightly different in macrophages RAW264.7. Prediction of ADMET lab demonstrated that THCV and its metabolites were endowed with the advantage of blood–brain barrier (BBB) penetration compared to THCA. In conclusion, this study highlighted that metabolism plays a critical role in the biological activity of phytocannabinoids.

Background: Diabetes mellitus (DM) is among the most common chronic diseases, and diabetic enteropathy (DE), which is a complication caused by DM, is a serious health condition. Long noncoding RNAs (lncRNAs) are regulators of DE progression. Objective: However, the mechanisms of action of multiple lncRNAs involved in DE remain poorly understood. Methods: Reverse transcription-quantitative PCR (RT–qPCR) and in situ hybridization were used to analyze terminal differentiation-induced lncRNA (Tincr) expression in intestinal epithelial cells (IECs) in the DM state. Microarray analysis, bioinformatics analysis, and luciferase reporter assays were used to identify the genes targeted by Tincr. The role of miR-668-3p was then explored by up- and down-regulating its expression in vitro and in vivo. Results: In this study, we observed that the level of lncRNA Tincr was increased in IECs in the DM state. More importantly, Tincr was associated with abnormal intestinal epithelial stem cell (IESC) differentiation in DM. Our mechanistic study demonstrated that Tincr is a major marker of Lgr5+ stem cells in DM. In addition, we investigated whether Tincr directly targets miR-668-3p and whether miR-668-3p targets Klf3. Our findings showed that Tincr sponged miR-668-3p, which attenuated abnormal IESC differentiation in DM by regulating Klf3 expression. Conclusion: This study presents evidence of an essential role for Tincr in IESC differentiation in DM.

Two unusual novel iridoid glycosides, cornsecoside A (1) and cornsecoside B (2), were isolated from a 40% ethanol elution fraction of a 50% ethanol extract of Cornus officinalis fruit. Their structures were determined by spectroscopic data analysis combined with hydrolysis and ECD spectroscopy. In addition, compounds 1 and 2 exhibited cytotoxic activity against Bel-7402 cells with IC50 values of 8.12 and 9.31 µM, and were neuroprotective against H2O2-induced SH-SY5Y cell injure at a concentration of 10 µM.

Breast cancer is one of the most frequent malignancies in females. The molecular mechanism of how breast cancer development and recurrence still need to be explored. Peroxisome gamma coactivator-1β (PGC-1β) was engaged in cancer energy metabolism and tumor genesis. However, the mechanisms of PGC-1β in breast cancer have not been fully understood. In this study, PCG-1β overexpressed and knockdown vectors were transferred into MCF-7 cells. With the association-quantitative connection analysis, the different expressions of mRNAs and proteins were examined. Additionally, the terms on differentially expressed mRNAs and proteins were enriched by GO and KEGG. Based on the results, 1872 differentially expressed genes were identified in the up-regulated of PGC-1β group, and 1318 genes were found in the down-regulated of PGC-1β cells. With the label-free technique, 221 differentially expressed proteins were screened in PGC-1β up-regulated group, and 459 proteins were identified in PGC-1β down-regulated group. Correlation analysis showed that 49 significantly expressed mRNA-protein pairs in OV vs CT groups and 25 paired in SI vs CT groups. Combined analysis of transcriptome and proteome demonstrated that PGC-1β plays a important role in cancer energy metabolism and boosting the pace of chemical processes in the proliferation of breast cancer cells. Additional investigation about PGC-1β and energy metabolism in cancer cells may shed fresh light on the growth and treatment of breast cancer cells.

Here, we describe a new species of the genus Polionemobius from Wuyanling Nature Reserve, Zhejiang Province of China. Meanwhile, we have confirmed two new synonyms. The genus Polycomus is a junior synonym of the genus Zilingxi, and Polycomus exspiravit He & Ma, 2022 is a junior synonym of Zilingxi dian He, 2022.

Chromosome engineering has been attempted successfully in yeast but remains challenging in higher eukaryotes, including mammals. Here, we report programmed chromosome ligation in mice that resulted in the creation of new karyotypes in the lab. Using haploid embryonic stem cells and gene editing, we fused the two largest mouse chromosomes, chromosomes 1 and 2, and two medium-size chromosomes, chromosomes 4 and 5. Chromatin conformation and stem cell differentiation were minimally affected. However, karyotypes carrying fused chromosomes 1 and 2 resulted in arrested mitosis, polyploidization, and embryonic lethality, whereas a smaller fused chromosome composed of chromosomes 4 and 5 was able to be passed on to homozygous offspring. Our results suggest the feasibility of chromosome-level engineering in mammals.

PAN-based carbon fiber was surface-modified with silane coating, and a composite material was prepared using a PI resin as a matrix. The structure and surface properties of carbon fibers were studied by means of X-ray photoelectron spectroscopy (XPS) and SEM. The tensile strength of the composite was measured by a tensile tester, and the friction properties of the composite were measured by a micro-nano mechanics comprehensive test system. The results show that treatment with silane coating can improve the surface roughness and chemical activity of carbon fiber, improve the interface between carbon fiber and PI resin matrix, and improve the tensile strength and wear rate of the composite.

Due to the worldwide epidemic of allergic disease and a cure nowhere in sight, there is a crucial need to explore its pathophysiological mechanisms. As allergic disease has been associated with gut dysbiosis, we searched for a possible mechanism from the perspective of the molecular interface between host and microbiota with concurrent metabolomics and microbiome composition analysis. Sprague-Dawley rats were injected with Artemisia pollen extract to stimulate a hyper reaction to pollen. This hyper reaction decreased the circulation of valine, isoleucine, aspartate, glutamate, glutamine, indole-propionate (IPA), and myo-inositol, and reduced short-chain fatty acids (SCFAs) in feces. Several beneficial genera belonging to Ruminococcaceae, Lachnospiraceae, and Clostridiales declined in the model group, whereas Helicobacter and Akkermansia were only expressed in the model group. Furthermore, the expression of intestinal claudin-3 and liver fatty acid binding protein was downregulated in the model group and associated with metabolic changes and bacteria. Our results suggest that alterations in amino acids as well as their derivatives (especially valine, and IPA which is the reductive product of tryptophan) , SCFAs, and the gut microbiome (specifically Akkermansia and Helicobacter) may disrupt the intestinal barrier function by inhibiting the expression of claudin proteins and affecting the mucus layer, which further results in hay fever.

Examining the coexisting policies for mandatory and voluntary disclosure of environmental information, this paper focuses on the unique background for such disclosure in the context of domestic companies in heavy pollution industries (EHPIs), a topic thus far overlooked by the literature. We aim to identify, in regard to compulsory environmental information disclosure in financial reports, whether adding further voluntary information disclosure to corporate social responsibility (CSR) results in an extra discount from investors during an equity financing. We evaluate a sample of 4390 A-share listed companies in EHPIs operating in China between 2010 and 2018. Specifically, linguistic analysis and image recognition are conducted with Python, and a regression model is applied to test our hypotheses. The positive impact of the following variables on the cost reduction in equity capital is thus demonstrated: (a) CSR disclosure, (b) higher quality CSR reports, (c) increased environmental information disclosure in CSR reports (CSR_E), (d) more accurate environmental investment information, and (e) additional graphs and text. Moreover, the degree of CSR_E disclosure's reduction in the cost of equity is 30 times that of CSR disclosure, while charts have specific positive effects that text does not. Therefore, we identify a new path for remitting information asymmetry in a financial market by extending information manipulation research, especially studies of nonfinancial information. Overall, information disclosure should be taken seriously by both firms and supervisors. Hence, this study offers guidelines for regulatory authorities to explore the coordination effect of mandatory and voluntary disclosure policies, i.e., to achieve environmental governance and the sustainable development of enterprises by improving corporate governance.

Nano-TATB was developed in microchannels by physical method and chemical method, respectively. The effects of total flow rate, number of microreactor plates, solvent/non-solvent ratio and temperature on the particle size of TATB in the physical method were studied. Prepared TATB were characterized by Nano Sizer, Scanning Electron Microscopy, Specific surface aperture analyzer, X-ray diffraction, Fourier transform infrared spectroscopy and Differential Scanning Calorimetry. The results show that the TATB obtained by physical method and chemical method are spherical, with average particle size of 130.66 nm and 108.51 nm, respectively. Specific surface areas of TATB obtained by physical and chemical methods are 21.37 m2/g and 21.91 m2/g, respectively. Compared with the specific surface area of micro-TATB (0.0808 m2/g), the specific surface area of nano-TATB is significantly increased. DSC test results show that the smaller the particle size of TATB, the lower the thermal decomposition temperature. In addition, by simulating the mixing state of fluid in microchannels and combining with the classical nucleation theory, the mechanism of preparing nano-TATB by microchannels was proposed.

Polysaccharides derived from plants, algae, or fungi serve as the major components of some human diets. Polysaccharides have been shown to exhibit diverse biological activities in improving human health, and have also been proposed to function as potent modulators of gut microbiota composition, thus playing a bi-directional regulatory role in host health. Here, we review a variety of polysaccharide structures potentially linked to biological functions, and cover current research progress in characterizing their pharmaceutical effects in various disease models, including antioxidant, anticoagulant, anti-inflammatory, immunomodulatory, hypoglycemic, and antimicrobial activities. We also highlight the effects of polysaccharides on modulating gut microbiota via enrichment for beneficial taxa and suppression of potential pathogens, leading to increased microbial expression of carbohydrate-active enzymes and enhanced short chain fatty acid production. This review also discusses polysaccharide-mediated improvements in gut function by influencing interleukin and hormone secretion in host intestinal epithelial cells.

Pecan (Carya illinoinensis) is an important oilseed nut and is rich in fatty acids and flavonols. Pecan fatty acid has significantly edible, industrial, and clinical value. To investigate the dynamic patterns and compositions of fatty acid, and the molecular mechanism that controls fatty acid accumulation in pecan, lipidomic and transcriptomic analyses were performed to determine lipid profiles and gene expression in pecan’s fatty acid biosynthesis pathway. In the present study, compared to cultivars ‘Caddo’ and ‘Y-01’, ‘Mahan’ formed larger and heavier embryos and accumulated higher oil content. Lipidomic analysis showed that fatty acid and (O-acyl)-1-hydroxy fatty acid contents were higher in ‘Mahan’ at the mature stage. Based on full-length and comparative RNA-Seq, differential expression gene enrichment analysis revealed that many functional genes participated in the pathways of ‘fatty acid biosynthesis’, ‘fatty acid metabolism’, and ‘linoleic acid metabolism’. High fatty acid accumulation model from ‘Mahan’ demonstrated that key enzyme encoding genes played an important role in regulating fatty acid biosynthesis. Co-expression module analysis indicated that several transcription factors (MYB, TCP, bHLH, Dof, ERF, NAC) were involved in fatty acid accumulation by regulating the expression of functional genes, and real-time quantitative PCR verification proved that these transcription factors had a high correlation with pecan fatty acid accumulation pattern. These findings provided an insight into the molecular mechanism of fatty acid accumulation in C. illinoinensis embryo, which contributes to pecan oil yielding and pecan molecular breeding.

BackgroundOvarian cancer (OC) is highly heterogeneous and has a poor prognosis. A better understanding of OC biology could provide more effective therapeutic paradigms for different OC subtypes.MethodsTo reveal the heterogeneity of T cell-associated subclusters in OC, we performed an in-depth analysis of single-cell transcriptional profiles and clinical information of patients with OC. Then, the above analysis results were verified by qPCR and flow cytometry examine.ResultsAfter screening by threshold, a total of 85,699 cells in 16 ovarian cancer tissue samples were clustered into 25 major cell groups. By performing further clustering of T cell-associated clusters, we annotated a total of 14 T cell subclusters. Then, four distinct single-cell landscapes of exhausted T (Tex) cells were screened, and SPP1 + Tex significantly correlated with NKT cell strength. A large amount of RNA sequencing expression data combining the CIBERSORTx tool were labeled with cell types from our single-cell data. Calculating the relative abundance of cell types revealed that a greater proportion of SPP1 + Tex cells was associated with poor prognosis in a cohort of 371 patients with OC. In addition, we showed that the poor prognosis of patients in the high SPP1 + Tex expression group might be related to the suppression of immune checkpoints. Finally, we verified in vitro that SPP1 expression was significantly higher in ovarian cancer cells than in normal ovarian cells. By flow cytometry, knockdown of SPP1 in ovarian cancer cells could promote tumorigenic apoptosis.ConclusionThis is the first study to provide a more comprehensive understanding of the heterogeneity and clinical significance of Tex cells in OC, which will contribute to the development of more precise and effective therapies.

With the popularity of automated vehicles, the future mixed traffic flow contains automated vehicles with different degrees of intelligence developed by other manufacturers. Therefore, simulating the interaction behavior of automated vehicles with varying levels of intelligence is crucial for testing and evaluating autonomous driving systems. Since the algorithm of traffic vehicles with various intelligence levels is difficult to obtain, it leads to hardships in quantitatively characterizing their interaction behaviors. Therefore, this paper designs a new automated vehicle test platform to solve the problem. The intelligent vehicle testbed with multiple personalized in-vehicle control units in the loop consists of three parts: 1. Multiple controllers in the loop to simulate the behavior of traffic vehicles；2. The central console applies digital twin technology to share the same traffic scenario between the tested vehicle and the traffic vehicle, creating a mixed traffic flow. 3. The tested vehicle can be either a virtual or an actual vehicle, i.e., an actual vehicle in the loop used to represent the effects of vehicle dynamics, actuators, and other characteristics.

Submarine pipelines play an important role in offshore oil and gas development. A touchy issue in pipeline design and application is how to avoid the local collapse of pipelines under external pressure. The pipe diameter-thickness ratio D/t is one of the key factors that determine the local critical collapse pressure of the submarine pipelines. Based on the pipeline collapse experiment and finite element simulation, this paper explores the pressure-bearing capacity of the pipeline under external pressure in a wide range of diameter-thickness ratio D/t. Some interesting and important phenomena have been observed and discussed. In the range of 16

IntroductionWithin the context of the yearly improvement of particulate matter (PM) pollution in Chinese cities, Surface ozone (O3) concentrations are increasing instead of decreasing and are becoming the second most important air pollutant after PM. Long-term exposure to high concentrations of O3 can have adverse effects on human health. In-depth investigation of the spatiotemporal patterns, exposure risks, and drivers of O3 is relevant for assessing the future health burden of O3 pollution and implementing air pollution control policies in China.MethodsBased on high-resolution O3 concentration reanalysis data, we investigated the spatial and temporal patterns, population exposure risks, and dominant drivers of O3 pollution in China from 2013 to 2018 utilizing trend analysis methods, spatial clustering models, exposure-response functions, and multi-scale geographically weighted regression models (MGWR).ResultsThe results show that the annual average O3 concentration in China increased significantly at a rate of 1.84 μg/m3/year from 2013 to 2018 (160 μg/m3) in China increased from 1.2% in 2013 to 28.9% in 2018, and over 20,000 people suffered premature death from respiratory diseases attributed to O3 exposure each year. Thus, the sustained increase in O3 concentrations in China is an important factor contributing to the increasing threat to human health. Furthermore, the results of spatial regression models indicate that population, the share of secondary industry in GDP, NOx emissions, temperature, average wind speed, and relative humidity are important determinants of O3 concentration variation and significant spatial differences are observed.DiscussionThe spatial differences of drivers result in the spatial heterogeneity of O3 concentration and exposure risks in China. Therefore, the O3 control policies adapted to various regions should be formulated in the future O3 regulation process in China.

DNA methylation is an important epigenetic modification that regulates many biological processes. The sea cucumber Apostichopus japonicus often suffers from heat stress that affects its growth and leads to significant economic losses. In this study, the mRNA expression patterns and DNA methylation characteristics in the body wall of A. japonicus under heat stress were analyzed by whole-genome bisulfite sequencing (WGBS) and transcriptome sequencing (RNA-seq). We found that CpG was the main DNA methylation type, and heat stress caused a significant increase in the overall methylation level and methylation rate, especially in the intergenic region of the A. japonicus genome. In total, 1,409 differentially expressed genes (DEGs) and 17,927 differentially methylated genes (DMGs) were obtained by RNA-seq and WGBS, respectively. Association analysis between DNA methylation and transcription identified 569 negatively correlated genes in both DMGs and DEGs, which indicated that DNA methylation affects on transcriptional regulation in response to heat stress. These negatively correlated genes were significantly enriched in pathways related to energy metabolism and immunoregulation, such as the thyroid hormone signaling pathway, renin secretion, notch signaling pathway and microRNAs in cancer. In addition, potential key genes, including heat shock protein (hsp70), calcium-activated chloride channel regulator 1(clca1), and tenascin R (tnr), were obtained and their expression and methylation were preliminarily verified. The results provide a new perspective for epigenetic and transcriptomic studies of A. japonicus response to heat stress, and provide a reference for breeding sea cucumbers resistant to high temperatures.