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Abstract Background Pulmonary tuberculosis is a chronic infectious disease of the respiratory system. It is still one of the leading causes of death from a single infectious disease, but it has been stuck in the study of a single pathogen. Recent studies have shown that many diseases are associated with disruption of the native microbiota. In this study we investigated the occurrence of tuberculosis and the correlation between drug resistance and respiratory flora. High-throughput 16 S rRNA gene sequencing was used to characterize the respiratory microbiota composition of 30 tuberculosis (TB) affected patients and compared with 30 healthy (H) controls. According to their Gene Xpert results, 30 pulmonary tuberculosis patients were divided into 12 persons in the drug-sensitive group (DS0) and 18 persons in the drug-resistant group (DR0). The microbial flora of the two were compared with the H group. Results The data generated by sequencing showed that Firmicutes, Proteus, Bacteroides, Actinomyces and Fusobacterium were the five main bacterial phyla detected, and they constituted more than 96% of the microbial community. The relative abundances of Fusobacterium, Haemophilus, Porphyromonas, Neisseria, TM7, Spirochetes, SR1, and Tenericutes in the TB group was lower than that of the H group, and Granulicatella was higher than the H group. The PcoA diagrams of the two groups had obvious clustering differences. The Alpha diversity of the TB group was lower than that of the H group, and the Beta diversity was higher than that of the H group (P

Bisecting N-acetylglucosamine (GlcNAc), a GlcNAc linked to the core β-mannose residue via a β1,4 linkage, is a special type of N-glycosylation that has been reported to be involved in various biological processes, such as cell adhesion and fetal development. This N-glycan structure is abundant in human trophoblasts, which is postulated to be resistant to natural killer cell-mediated cytotoxicity, enabling a mother to nourish a fetus without rejection. In this study, we hypothesized that the human amniotic membrane, which serves as the last barrier for the fetus, may also express bisected-type glycans. To test this hypothesis, glycomic analysis of the human amniotic membrane was performed, and bisected N-glycans were detected. Furthermore, our proteomic data, which have been previously employed to explore human missing proteins, were analyzed and the presence of bisecting GlcNAc-modified peptides was confirmed. A total of 41 glycoproteins with 43 glycopeptides were found to possess a bisecting GlcNAc, and 25 of these glycoproteins were reported to exhibit this type of modification for the first time. These results provide insights into the potential roles of bisecting GlcNAc modification in the human amniotic membrane, and can be beneficial to functional studies on glycoproteins with bisecting GlcNAc modifications and functional studies on immune suppression in human placenta.

Abstract Oxidative stress-induced dopaminergic neuronal loss and apoptosis play a crucial role in the pathogenesis of Parkinson’s disease (PD), and as a vital antioxidant protein, thioredoxin (Trx) exerts neuroprotection against PD. In this study, we investigated the effect of Schisanhenol (Sal), an active component from a traditional Chinese herb Schisandra rubriflora (Franch.), on MPP+-induced apoptosis and its association with thioredoxin-1 (Trx1) in SH-SY5Y cells. The protein levels of Trx1 and apoptosis-related proteins were detected by Western blot, the expression of Trx1 mRNA by real time qPCR, and apoptosis was detected by fluorescence microscopy and flow cytometry. Pretreatment with Sal (1 µM, 10 µM, and 50 µM) dose-dependently ameliorated MPP+-induced neuronal injury, confirmed by the improvement of the viability and morphological changes. Sal decreased the apoptosis rate of cells, suppressed the production of DNA ladder and sub-G1 peak, inhibited the Caspase-3 activity and the expression of apoptosis-related proteins. Sal enhanced the expression of Trx1 both in the protein and mRNA levels. However, the Trx1 inhibitor PX-12 suppressed the protective effects of Sal. In addition, Sal inhibited NF-κB translocation and activation. These results suggest that Sal has a protective effect against MPP+-induced apoptosis in SH-SY5Y cells via up-regulation of Trx1 expression and suppression of ASK1-P38-NF-κB pathway.

Abstract Background Heterogeneity of leukemia‐initiating cells (LICs) is a major obstacle in acute myeloid leukemia (AML) therapy. Accumulated evidence indicates that the coexistence of multiple types of LICs with different pathogenicity in the same individual is a common feature in AML. However, the functional heterogeneity including the drug response of coexistent LICs remains unclear. Therefore, this study aimed to clarify the intra‐heterogeneity in LICs that can help predict leukemia behavior and develop more effective treatments. Methods Spleen cells from the primary Setd2−/−‐AML mouse were transplanted into C57BL/6 recipient mice to generate a transplantable model. Flow cytometry was used to analyze the immunophenotype of the leukemic mice. Whole‐genome sequencing was conducted to detect secondary hits responsible for leukemia transformation. A serial transplantation assay was used to determine the self‐renewal potential of Setd2−/−‐AML cells. A limiting‐dilution assay was performed to identify the LIC frequency in different subsets of leukemia cells. Bulk and single‐cell RNA sequencing were performed to analyze the transcriptional heterogeneity of LICs. Small molecular inhibitor screening and in vivo drug treatment were employed to clarify the difference in drug response between the different subsets of LICs. Results In this study, we observed an aged Setd2−/− mouse developing AML with co‐mutation of NrasG12S and BrafK520E. Further investigation identified two types of LICs residing in the c‐Kit+B220+Mac‐1− and c‐Kit+B220+Mac‐1+ subsets, respectively. In vivo transplantation assay disclosed the heterogeneity in differentiation between the coexistent LICs. Besides, an intrinsic doxorubicin‐resistant transcriptional signature was uncovered in c‐Kit+B220+Mac‐1+ cells. Indeed, doxorubicin plus cytarabine (DA), the standard chemotherapeutic regimen used in AML treatment, could specifically kill c‐Kit+B220+Mac‐1− cells, but it hardly affected c‐Kit+B220+Mac‐1+ cells. Transcriptome analysis unveiled a higher activation of RAS downstream signaling pathways in c‐Kit+B220+Mac‐1+ cells than in c‐Kit+B220+Mac‐1− cells. Combined treatment with DA and RAS pathway inhibitors killed both c‐Kit+B220+Mac‐1− and c‐Kit+B220+Mac‐1+ cells and attenuated disease progression. Conclusions This study identified two cell subsets enriched for LICs in murine Setd2−/−‐AML and disclosed the transcriptional and functional heterogeneity of LICs, revealing that the coexistence of different types of LICs in this model brings about diverse drug response.

The color of light affects the reproductive performance of poultry, but it is not clear what efficient illumination strategy could be adopted to improve the reproductive performance of Zi-goose. Red light can increase the average weekly egg production rate, egg production, and qualified production. It can increase the serum GnRH level and decrease the serum PRL, MT, and T4 levels. In our study, red light for 12 h increased the average weekly laying rate, average qualified egg production, and hatching rate of Zi-goose eggs, and increased the serum levels of FSH, LH, P4, E2, MT, T3, and T4. Blue light at 14 h improved the average weekly egg production rate, average egg production, and average qualified egg production, and reduce serum PRL and MT levels to ensure the improvement of reproductive performance of goose. A total of 705,714 overlapping group sequences, 471,145 transcript sequences, and 268,609 single gene sequences were obtained from 18 sequencing samples, with a total length of 323.04, 668.53, and 247.88 M, respectively. About 176,416 unigenes were annotated successfully in six databases, accounting for 65.68% of the total unigenes obtained. 2,106, 2,142, and 8,892 unigenes were identified in the hypothalamus, pituitary gland, and ovary of the birds respectively, with different expressions of light regulation. The hypothalamus, ovary, and pituitary were involved in 279, 327, and 275 KEGG (Kyoto Encyclopedia of Genes and Genomes) metabolic pathways in response to light, respectively. Through further significance analysis and differential discovery rate control, a total of five metabolic pathways were obtained which were closely related to the reproductive hormones of goose. Ten candidate genes related to the reproductive performance of goslings were selected according to the identification results of differentially expressed genes of goslings under red light and white light conditions and the genes involved in metabolic pathways significantly related to the reproductive hormones of goslings. The expression levels of GnRh-1 in the hypothalamus, GnRH-R, FSHβ and LHβ in the pituitary gland, and FSH-R and LH-R candidate genes in the ovary were higher under the 12 h red light treatment than white light. However, the expression levels of VIP, PRL, and PRL-R candidate genes in the hypothalamus, pituitary and ovary were lower under 12 h red light than under 12 h white light.

The effects of Fe, Cr and thermal exposure on the microstructure and mechanical properties of Al-Si alloy were investigated in this work. The results indicated that the main phases of the Al-Si-Cu-Ni-Mg-(0.6–0.9%) Fe (wt. %) alloy were α-Al, Si, Al5Cu2Mg8Si6, Al3CuNi, Al7Cu4Ni, Al2Cu, and AlFeSi at room temperature. The size of the AlSiFe phase increased with increasing the weight fraction of Fe. The shape of Fe-rich phase changed from rod-like to star-like, followed by long needle-like with Fe varying from 0.6% to 0.9%. The mechanical properties of the studied alloys at elevated temperatures increased with Fe. The ultimate tensile strength of the three alloys at 350 °C was 111.2 MPa, 124 MPa, and 128.7 MPa, respectively. In addition, the ductility and strength of the studied alloys at room temperature decreased with increasing the Fe, due to the large size of the hard and brittle Fe-rich phase strictly cleaved the aluminum matrix. After thermal exposure, the properties of the alloy at room temperature and elevated temperature decreased obviously at the beginning of 0.5~8 h, and then tend to be stabilized during thermal exposure at 350 °C for approximately 32~64 h. Fe-rich was a thermal stable phase at 350 °C.

COVID-19 is a critical public health threat, but molecular characterizations of patients’ immunity is still lacking. Here the authors collected blood from patients with various disease severity, and prefiltered to exclude selected comorbidity, to obtain genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles to report a trans-omics landscape.

Rotating equipment often fails due to faults in the rolling element bearings. The remaining useful life (RUL) prediction of the bearings plays a critical role in prognostics and decision-makers. In this study, attention mechanism is integrated into the internal of just another network (JANET) unit, and a new improved version of JANET unit, namely, just another attention network (JAAN), is firstly presented. Firstly, root mean squares (RMS) of the test-to-failure datasets are calculated to characterize the degradation behavior of the bearings. Then, the prediction model is constructed by stacking multiple JAAN units to estimate the RUL values of rolling element bearings by existing RMS values. Extensive experiments on PRONOSTIA dataset are carried out to validate the superiority of the presented approach. The experiment results show that the proposed JAAN achieves good prediction results than other advanced technologies.

BackgroundLeukemic stem cell (LSC) is thought to be responsible for chronic myelogenous leukemia (CML) initiation and relapse. However, the inherent regulation of LSCs remains largely obscure. Herein, we integratedly analyzed miRNA and gene expression alterations in bone marrow (BM) Lin-Sca1+c-Kit+ cells (LSKs) of a tet-off inducible CML mouse model, Scl/tTA-BCR/ABL (BA).MethodsScl/tTA and TRE-BA transgenic mice were crossed in the presence of doxycycline to get double transgenic mice. Both miRNA and mRNA expression profiles were generated from BM LSKs at 0 and 3 weeks after doxycycline withdrawal. The target genes of differentially expressed miRNAs were predicted, followed by the miRNA-mRNA network construction. In vitro and in vivo experiments were further performed to elucidate their regulation and function in CML progression.ResultsAs a result of the integrated analysis and experimental validation, an anti-apoptotic pathway emerged from the fog. miR-142a was identified to be downregulated by enhanced ERK-phosphorylation in BA-harboring cells, thereby relieving its repression on Ciapin1, an apoptosis inhibitor. Moreover, miR-142a overexpression could partially rescue the abnormal anti-apoptotic phenotype and attenuate CML progression.ConclusionTaken together, this study explored the miRNA-mRNA regulatory networks in murine CML LSKs and demonstrated that ERK-miR-142a-Ciapin1 axis played an essential role in CML pathogenesis.

Abstract Similarity queries, including range queries and k nearest neighbor (kNN) queries, in metric spaces have applications in many areas such as multimedia retrieval, computational biology and location-based services. With the growing volumes of data, a distributed method is required. In this paper, we propose an Asynchronous Metric Distributed System (AMDS), to support efficient metric similarity queries in the distributed environment. AMDS uniformly partitions the data with the pivot-mapping technique to ensure the load balancing, and employs publish/subscribe communication model to asynchronous process large scale of queries. The employment of asynchronous processing model also improves robustness and efficiency of AMDS. In addition, we develop efficient similarity search algorithms using AMDS. Extensive experiments using real and synthetic data demonstrate the performance of metric similarity queries using AMDS. Moreover, the AMDS scales sublinearly with the growing data size.

Abstract A large number of current chemotherapeutic agents prevent the growth of tumors by inhibiting DNA synthesis of cancer cells. It has been found recently that many planar polycyclic aromatic hydrocarbons (PAHs) derivatives, previously known as carcinogenic, display anticancer activity through DNA cross‐linking. However, the practical use of these PAHs is substantially limited by their low therapeutic efficiency and selectivity toward most tumors. Herein, the anticancer property of a nonplanar PAH named [4]helicenium, which exhibits highly selective cytotoxicity toward liver, lung cancer, and leukemia cells compared with normal cells, is reported. Moreover, [4]helicenium effectively inhibits tumor growth in liver cancer‐bearing mice and shows little side effects in normal mice. RNA sequencing and confirmatory results demonstrate that [4]helicenium induces more DNA damage in tumor cells than in normal cells, resulting in tumor cell cycle arrest and apoptosis increment. This study reveals an unexpected role and molecular mechanism for PAHs in selectively killing tumor cells and provides an effective strategy for precision cancer therapies.

This paper focuses on the fatigue reliability analysis and the development of a new life model of reliability and crack growth mechanisms in FV520B-I (high strength martensitic-type stainless steels) in the very-high cycle fatigue (VHCF) regime, which haven’t been studied well. First, the fatigue test was carried out to clarify the fatigue failure mechanism in the very-high cycle regime. Based on the test results and fatigue reliability theory, the fatigue life distribution and P-S-N curves were modeled. A new fatigue life evaluation model for FV520B-I is proposed according to the fracture mechanics and classic life evaluation method. With the comprehensive application of P-S-N curves and a new proposed fatigue life evaluation model, a new assumption of a P-Sc-N curve is developed and verified, to quantitatively express the relationship between fatigue life, reliability and fatigue cracking. This is novel and valuable for further fatigue study of FV520B-I.

Prognostics and health management technology (PHM), a measure to ensure the reliability and safety of the operation of industrial machinery, has attracted attention and application adequately. However, how to use the monitored information to evaluate the degradation of rolling bearings is a significant issue for its predictive maintenance and autonomic logistics. This work presents a reliable health prognosis approach to estimate the health indicator (HI) and remaining useful life (RUL) of rolling bearings. Firstly, to accurately capture the degradation process, a novel health index (HI) is constructed based on correlation kurtosis for different iteration periods and a Gaussian process latency variable model (GPLVM). Then, a multiple convolutional long short-term memory (MCLSTM) network is proposed to predict HI values and RUL values. Finally, we perform experimental datasets of rolling bearings, demonstrating that the presented method surpasses other state-of-the-art prognosis approaches. The results also confirm the feasibility of the presented method in industrial machinery.

Setd2 is known as a histone-H3K36-specific methyltransferase. However, its role in physiological function remains unclear. In this study, we show that Setd2 mainly regulates differentiation of murine embryonic stem cells (mESCs) toward primitive endoderm. Furthermore, we show that downregulated endoderm-related genes in Setd2−/− mESCs are associated with an aberrantly low level of Erk activity and that enforced expression of Fgfr3 can rescue the defective Erk pathway in Setd2−/− mESCs. Interestingly, the transcriptional initiation of Fgfr3 is directly regulated through histone H3K36me3 modification in its distal promoter region by Setd2. These results indicate that Setd2 controls the primitive endoderm differentiation of mESCs by regulating the Fgfr3-Erk signaling.

The present study aimed to investigate the effects of epigallocatechin-3-gallate (EGCG) on the in vitro development of porcine oocytes, parthenogenetic activation embryos (PA), and somatic cell nuclear transfer (SCNT) embryos. In Experiment 1, 0 (control), 10, 30, and 50 μg/mL EGCG were added to in vitro maturation (IVM) medium to explore the effect of EGCG on IVM of pig oocytes. The matured oocytes were then used to produce PA and SCNT embryos. Either for nuclear maturation of oocytes or for the rates of cleavage and blastocyst of PA and SCNT embryos, no significant difference was found among all groups. However, the total cell number per cloned blastocyst was significantly lower in blastocysts derived from oocytes matured in 50 μg/mL EGCG (Pin vitro development of pig cloned embryos.

In this study, 285 Chinese core journal papers involving early childhood sports in the CNKI (China National Knowledge Infrastructure) database from 1993 to 2022 were selected as samples. Text mining and data statistical analysis tools, such as BICOMB2.0, SPSS22.0, UCINET6.0, EXCEL2016, and other research methods in bibliometrics, such as word frequency analysis, co word clustering analysis, multidimensional scale analysis, and strategic coordinate map analysis, were used to explore the status and evolutionary trends of early childhood sports in China. The results are as follows: Since 2011, the annual number of documents has indicated a wave-like increasing trend every year, reaching its peak in 2020. In total, 237 institutions participated in this study. The journal distribution of papers in this field was close to the 1:4:16 ratio of Bradford's law. A relatively stable periodic group was formed. 12 cluster themes have been formed in the field of children's sports in China.

In the field of new environmental energy harvesting technology, wind energy and piezoelectric energy harvesting have become research hotspots. By utilizing wind energy into vibration energy, i.e., wind-induced vibration effect is a research hotspot in the field of environmental energy harvesting. This article comprehensively analyzes the research status and development trend of piezoelectric energy harvesters based on wind-induced vibration effects at home and abroad. It was found that the conversion process of wind energy to vibration energy is mainly based on flutter, galloping, and acoustic resonance. The conversion of vibration energy into electrical energy is mainly piezoelectric power generation, supplemented by magnetic induction power generation and friction power generation. For high power density and small volume application scenarios, resonant cavity type wind vibration energy collection is the main development trend. [ABSTRACT FROM AUTHOR]