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Hematopoietic stem cell (HSC) aging is accompanied by hematopoietic reconstitution dysfunction, including loss of regenerative and engraftment ability, myeloid differentiation bias, and elevated risks of hematopoietic malignancies. Gut microbiota, a key regulator of host health and immunity, has recently been reported to affect hematopoiesis. However, there is currently limited empirical evidence explaining the direct impact of gut microbiome on aging hematopoiesis. In this study, we performed fecal microbiota transplantation (FMT) from young mice to aged mice and observed a significant increment in lymphoid differentiation and decrease in myeloid differentiation in aged recipient mice. Furthermore, FMT from young mice rejuvenated aged HSCs with enhanced short-term and long-term hematopoietic repopulation capacity. Mechanistically, single-cell RNA sequencing deciphered that FMT from young mice mitigated inflammatory signals, upregulated the FoxO signaling pathway, and promoted lymphoid differentiation of HSCs during aging. Finally, integrated microbiome and metabolome analyses uncovered that FMT reshaped gut microbiota composition and metabolite landscape, and Lachnospiraceae and tryptophan-associated metabolites promoted the recovery of hematopoiesis and rejuvenated aged HSCs. Together, our study highlights the paramount importance of the gut microbiota in HSC aging and provides insights into therapeutic strategies for aging-related hematologic disorders.

High-performance red and NIR organic light-emitting diodes (OLEDs) have been achieved using highly robust and phosphorescent diplatinum(ii) complexes featuring strong intramolecular Pt–Pt and π–π interactions.

Background In vertebrates, hematopoietic stem and progenitor cells (HSPCs) emerge from hemogenic endothelium in the floor of the dorsal aorta and subsequently migrate to secondary niches where they expand and differentiate into committed lineages. Glia maturation factor γ (gmfg) is a key regulator of actin dynamics that was shown to be highly expressed in hematopoietic tissue. Our goal is to investigate the role and mechanism of gmfg in embryonic HSPC development. Methods In-depth bioinformatics analysis of our published RNA-seq data identified gmfg as a cogent candidate gene implicated in HSPC development. Loss and gain-of-function strategies were applied to study the biological function of gmfg. Whole-mount in situ hybridization, confocal microscopy, flow cytometry, and western blotting were used to evaluate changes in the number of various hematopoietic cells and expression levels of cell proliferation, cell apoptosis and hematopoietic-related markers. RNA-seq was performed to screen signaling pathways responsible for gmfg deficiency-induced defects in HSPC initiation. The effect of gmfg on YAP sublocalization was assessed in vitro by utilizing HUVEC cell line. Results We took advantage of zebrafish embryos to illustrate that loss of gmfg impaired HSPC initiation and maintenance. In gmfg-deficient embryos, the number of hemogenic endothelium and HSPCs was significantly reduced, with the accompanying decreased number of erythrocytes, myelocytes and lymphocytes. We found that blood flow modulates gmfg expression and gmfg overexpression could partially rescue the reduction of HSPCs in the absence of blood flow. Assays in zebrafish and HUVEC showed that gmfg deficiency suppressed the activity of YAP, a well-established blood flow mediator, by preventing its shuttling from cytoplasm to nucleus. During HSPC initiation, loss of gmfg resulted in Notch inactivation and the induction of Notch intracellular domain could partially restore the HSPC loss in gmfg-deficient embryos. Conclusions We conclude that gmfg mediates blood flow-induced HSPC maintenance via regulation of YAP, and contributes to HSPC initiation through the modulation of Notch signaling. Our findings reveal a brand-new aspect of gmfg function and highlight a novel mechanism for embryonic HSPC development.

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34+ cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34+ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.

Precisely regulating the key parameters associated with the thermally activated delayed fluorescence process is accomplished with optimized π-bridges or end-groups, affording improved maximum external quantum efficiencies of 18.9% (@630 nm).

The innate immune system is the first line of host defense sensing viral infection. Manganese (Mn) has recently been found to be involved in the activation of the innate immune DNA-sensing cGAS-STING pathway and subsequent anti-DNA virus function. However, it is still unclear whether Mn2+ mediates host defense against RNA viruses. In this study, we demonstrate that Mn2+ exhibited antiviral effects against various animal and human viruses, including RNA viruses such as PRRSVs and VSV, as well as DNA viruses such as HSV1, in a dose-dependent manner. Moreover, cGAS and STING were both investigated in the Mn2+ mediated antiviral roles using the knockout cells made by the CRISPR-Cas9 approach. Unexpectedly, the results revealed that neither cGAS knockout nor STING knockout had any effect on Mn2+-mediated antiviral functions. Nevertheless, we verified that Mn2+ promoted the activation of the cGAS-STING signaling pathway. These findings suggest that Mn2+ has broad-spectrum antiviral activities in a cGAS-STING pathway independent manner. This study also provides significant insights into redundant mechanisms participating in the Mn2+ antiviral functions, and also indicates a new target for Mn2+ antiviral therapeutics.

Nucleic acids with G4 elements play a role in the formation of aggregates involved in intracellular phase transitions. Our previous studies suggest that different forms of DNA could act as an accelerating template in Cu/Zn superoxide dismutase (SOD1) aggregation. Here, we examined the regulation of formation and cytotoxicity of the SOD1 aggregates by single-stranded 12-mer deoxynucleotide oligomers (dN)12 (N = A, T, G, C; ssDNAs) under acidic conditions. The ssDNAs can be divided into two groups based on their roles in SOD1 binding, exposure of hydrophobic clusters in SOD1, accelerated formation, morphology and cytotoxicity of SOD1 aggregates. G-quadruplexes convert SOD1 into fibrillar aggregates as a template, a fact which was observed for the first time in the nucleic acid regulation of protein aggregation. Moreover, the fibrillar or fibril-like SOD1 species with a G-quadruplex provided by (dG)12 were less toxic than the amorphous species with (dN)12 (N = A, T). This study not only indicates that both morphology and cytotoxicity of protein aggregates can be regulated by the protein-bound DNAs, but also help us understand roles of nucleic aid G-quadruplexes in the formation of aggregates and membraneless organelles involved in intracellular phase transitions.

Medicinal plants have incredibly high economic value, and a practical evaluation of their quality is the key to promoting industry development. The deep learning model based on residual convolutional neural network (ResNet) has the advantage of automatic extraction and the recognition of Fourier transform near-infrared spectroscopy (FT-NIR) features. Models are difficult to understand and interpret because of unknown working mechanisms and decision-making processes. Therefore, in this study, artificial feature extraction methods combine traditional partial least squares discriminant analysis (PLS-DA) and support vector machine (SVM) models to understand and compare deep learning models. The results show that the ResNet model has significant advantages over traditional models in feature extraction and recognition. Secondly, preprocessing has a great impact on the feature extraction and feature extraction, and is beneficial for improving model performance. Competitive adaptive reweighted sampling (CARS) and variable importance in projection (VIP) methods screen out more feature variables after preprocessing, but the number of potential variables (LVs) and successive projections algorithm (SPA) methods obtained is fewer. The SPA method only extracts two variables after preprocessing, causing vital information to be lost. The VIP feature of traditional modelling yields the best results among the four methods. After spectral preprocessing, the recognition rates of the PLS-DA and SVM models are up to 90.16% and 88.52%. For the ResNet model, preprocessing is beneficial for extracting and identifying spectral image features. The ResNet model based on synchronous two-dimensional correlation spectra has a recognition accuracy of 100%. This research is beneficial to the application development of the ResNet model in foods, spices, and medicinal plants.

Porcine reproductive and respiratory syndrome virus (PRRSV) has a strict cell tropism. In addition to the primary alveolar macrophages, PRRSV is strictly cytotropic to African green monkey kidney cells, such as MARC-145 cells; however, MARC-145 cells are not infected by most NADC30-like and NADC34-like PRRSV strains. The essential scavenger receptor CD163 has been proved to mediate productive infection of PRRSV in various non-permissive cell lines. In this study, we systematically tested the porcine CD163 stably expressing 3D4/21 cells for infections with various PRRSV strains. The results showed that the porcine CD163-expressing macrophages support the infections of PRRSV2 of lineages 1, 5, and 8, as evidenced by Western blotting, immunofluorescence assay, quantitative PCR, and virus titration assay. Considering the current prevalence of NADC30-like and NADC34-like PRRSV2 of lineage 1 in China, the CD163-expressing macrophages are very useful for PRRSV research and disease management.

The innate immune DNA sensing cGAS-STING signaling pathway has been widely recognized for inducing interferons (IFNs) and subsequent antiviral state. In addition to IFN, the cGAS-STING pathway also elicits other cell autonomous immunity events including autophagy and apoptosis. However, the downstream signaling events of this DNA sensing pathway in livestock have not been well defined. Here, we systematically analyzed the porcine STING (pSTING) induced IFN, autophagy and apoptosis, revealed the distinct dynamics of three STING downstream events, and established the IFN independent inductions of autophagy and apoptosis. Further, we investigated the regulation of autophagy on pSTING induced IFN and apoptosis. Following TBK1-IRF3-IFN activation, STING induced Atg5/Atg16L1 dependent autophagy through LIR motifs. In turn, the autophagy likely promoted the pSTING degradation, inhibited both IFN production and apoptosis, and thus restored the cell homeostasis. Therefore, this study sheds lights on the molecular mechanisms of innate immunity in pigs.

Introduction: Numerous studies have investigated the use of Wechsler tests on individuals with visual impairments. However, few studies have examined the utilization of the fourth edition of the Wechsler Intelligence Scale for Children (WISC-IV) for such individuals. This study investigated the reliability and validity of the WISC-IV Verbal Scales’ (i.e., the Verbal Comprehension Index [VCI] and the Working Memory Index [WMI]) scores for children with blindness in China. Methods: One hundred children with blindness were assessed using the Chinese version of the WISC-IV Verbal and Nonverbal Cognitive Development Scales. Results: The results of this study generally support the internal consistency reliability and validity of WISC-IV Verbal Scale scores for Chinese children who are blind. The split-half reliability coefficients ranged from .79 to .97, while Cronbach’s alpha or KR-20 (KR-20 is a measure of internal consistency reliability for measures with dichotomous choices) reliability coefficients ranged from .83 to .97. In terms of construct validity through exploratory factor analysis, the subtests of the WISC-IV Verbal Scale were confirmed to belong to VCI or the WMI as intended by the original structure of the WISC-IV. The convergent validity showed that the VCI and WMI scores were moderately and positively correlated with the Nonverbal Cognitive Development Scale. Discussion: The WISC-IV VCI and WMI were found to be valuable instruments for assessing the cognitive abilities of students in China with blindness. Finally, the limitations and significance of the study were also discussed. Implications for practitioners: The WISC-IV Verbal Scales may be used to assess the cognitive abilities of the numerous students in China who are blind and may be used as one of many tests to provide reference information for educational placement, educational planning, employment, and project evaluation.

Multibody method is introduced into the FEM model of soft connected battery module as a novel simplified modeling method; FEM model of battery pack for modal analysis using this simplified method can significantly reduce the model size and save a lot of computing resource compared with the traditional simplified method.

Background: Cordyceps is a precious Chinese herbal medicine with rich bio-active ingredients and is used for regulating arrhythmia alongside routine treatments. However, the efficacy and potential mechanisms of Cordyceps on patients with arrhythmia remain unclear.Methods: Randomized controlled trials of bradycardia treatment with Cordyceps were retrieved from diverse databases and available data. Dichotomous variables were expressed as a risk ratio (RR) with a 95% confidence interval (CI). Continuous variables were expressed as a standardized mean difference (SMD) with a 95% CI. Network pharmacology was used to identify potential targets of Cordyceps for arrhythmia. Metascape was used for gene ontology (GO) and genome (KEGG) pathway enrichment analysis.Results: Nineteen trials included 1,805 patients with arrhythmia, of whom 918 were treated with Ningxinbao capsule plus routine drugs, and, as a control, 887 were treated with only routine drugs. Six trials reported on bradycardia and the other 13 on tachycardia. Treatment with Cordyceps significantly improved the total efficacy rate in both bradycardia (RR = 1.24; 95% CI, 1.15 to 1.35; Pz z Conclusion: This study confirmed that Cordyceps has a certain positive effect on the treatment of arrhythmia and that its main mechanism may be through the regulation of adrenergic signaling in cardiomyocytes and the PI3K-Akt signaling pathway.

The highway system is an important component of the modern society as it allows an efficient intercity communication. However, with the increase in the number of cars, the traffic congestion becomes a widespread problem around the world. Here, we study the traffic conditions in Hsuehshan tunnel in Taiwan. When there is traffic congestion, there is a remarkable fraction of vehicles choosing an alternative path, even if it cost more time than jamming on the highway. In addition, we evaluate through statistics and the government’s policy to improve the road condition of the tunnel.

G2 porcine epidemic diarrhea virus (G2 PEDV) and highly pathogenic porcine reproductive and respiratory syndrome virus 2 (HP-PRRSV2) are two of the most prevalent swine pathogens in China's swine herds, and their coinfection occurs commonly. Several PED and PRRS vaccines have been utilized in China for decades, and systemic homologous neutralizing antibodies (shnAbs) in serum are frequently used to evaluate the protective efficacy of PED and PRRS vaccines. To develop a vaccine candidate against G2 PEDV and HP-PRRSV2 coinfection, in this study, we generated a chimeric virus (rJSTZ1712-12-S) expressing S protein of G2 PEDV using an avirulent HP-PRRSV2 rJSTZ1712-12 infectious clone as the viral vector. The rJSTZ1712-12-S strain has similar replication efficacies as the parental rJSTZ1712-12 virus. In addition, animal inoculation indicated that rJSTZ1712-12-S is not pathogenic to piglets and can induce shnAbs against both G2 PEDV and HP-PRRSV2 isolates after prime-boost immunization. However, passive transfer study in neonatal piglets deprived of sow colostrum showed that rJSTZ1712-12-S-induced shnAbs may only decrease PEDV and PRRSV viremia but cannot confer sufficient protection against dual challenge of high virulent G2 PEDV XJ1904-34 strain and HP-PRRSV2 XJ17-5 isolate. Overall, this study provides the first evidence that shnAbs confer insufficient protection against PEDV and PRRSV coinfection and are inadequate for the evaluation of protective efficacy of PED and PRRS bivalent vaccine (especially for the PED vaccine).

Complete Multi-lingual Neural Machine Translation (C-MNMT) achieves superior performance against the conventional MNMT by constructing multi-way aligned corpus, i.e., aligning bilingual training examples from different language pairs when either their source or target sides are identical. However, since exactly identical sentences from different language pairs are scarce, the power of the multi-way aligned corpus is limited by its scale. To handle this problem, this paper proposes "Extract and Generate" (EAG), a two-step approach to construct large-scale and high-quality multi-way aligned corpus from bilingual data. Specifically, we first extract candidate aligned examples by pairing the bilingual examples from different language pairs with highly similar source or target sentences; and then generate the final aligned examples from the candidates with a well-trained generation model. With this two-step pipeline, EAG can construct a large-scale and multi-way aligned corpus whose diversity is almost identical to the original bilingual corpus. Experiments on two publicly available datasets i.e., WMT-5 and OPUS-100, show that the proposed method achieves significant improvements over strong baselines, with +1.1 and +1.4 BLEU points improvements on the two datasets respectively., Comment: Accepted as a long paper at ACL 2022

The growing concerns about the quality and safety of herbs and spices among consumers have increased the demand for technical testing. Recently, non-destructive analysis techniques have been widely studied and applied. Generally, a single technology has certain limitations, which are not enough to fully describe the characteristics of complex products (dynamic or complex structure). Combining non-destructive analysis technology (multi-source information) can overcome the above problems. The present review focused on applying multi-source and non-destructive information on herbs and spices quality authentication, including vibration spectroscopy and electronic sensor technologies. Then summarized and analyzed the authentication process for issues such as adulteration, contents prediction, geographical traceability, process and products analysis, and identification variety. Additionally, we presented trends in quality authentication, discussed the challenges and prospects, and made recommendations. This investigation provided clear evidence for the superiority of the quality authentication methods for herbs and spices based on multi-source and non-destructive information.

Background. Our previous study showed that interleukin-22 (IL-22) levels were increased in patients with aortic dissection (AD). This study evaluated the effects of IL-22 on AD/abdominal aortic aneurysm (AAA) formation in angiotensin II (Ang II)-infused ApoE-/- mice. Methods. ApoE-/- mice were treated with Ang II for 28 days, and IL-22 expression was examined. In addition, the effects of IL22 deficiency on AAA/AD formation induced by Ang II infusion in ApoE-/- mice were investigated. ApoE-/-IL-22-/- mice were transplanted with bone marrow cells isolated from ApoE-/- mice or ApoE-/-IL-22-/- mice, and AAA/AD formation was observed. Results. IL-22 expression was increased in both the aortas and serum of ApoE-/- mice after Ang II infusion and was mainly derived from aortic CD4+ T lymphocytes (CD4+ TCs). IL-22 deficiency significantly reduced the AAA/AD formation as well as the maximal aortic diameter in Ang II-infused ApoE-/- mice. Decreased elastin fragmentation and reduced fibrosis were observed in the aortas of ApoE-/-IL-22-/- mice compared with ApoE-/- mice. The deletion of IL-22 also decreased aortic M1 macrophage differentiation, alleviated M1 macrophage-induced oxidative stress, and reduced aortic smooth muscle cell loss. Furthermore, M1 macrophage-induced oxidative stress was worsened and AAA/AD formation was promoted in ApoE-/-IL-22-/- mice that received transplanted bone marrow cells from ApoE-/- mice compared with those that were transplanted with bone marrow cells isolated from ApoE-/-IL-22-/- mice. Conclusions. IL-22 deficiency inhibits AAA/AD formation by inhibiting M1 macrophage-induced oxidative stress. IL-22 potentially represents a promising new target for preventing the progression of AAA/AD.

Non-alcoholic fatty liver disease (NAFLD) is becoming the most predominant burden of chronic liver disease worldwide. Non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, can develop into cirrhosis and hepatocellular cancer. Unfortunately, current options for therapeutic treatment of NASH are very limited. Among multiple pathways in NASH, farnesoid X receptor (FXR), a nuclear bile acid receptor, is well-recognized as an important effective target. Here we report the synthesis and characterization of compound HEC96719 a novel tricyclic FXR agonist based on a prior high-affinity nonsteroidal molecule GW4064. HEC96719 exhibits excellent potency superior to GW4064 and obeticholic acid in in vitro and in vivo assays of FXR activation. It also shows higher FXR selectivity and more favorable tissue distribution dominantly in liver and intestine. Preclinical data on pharmacokinetic properties, efficacy, and safety profiles overall indicate that HEC96719 is a promising drug candidate for NASH treatment.

Medicinal plants have incredibly high economic value, and a practical evaluation of their quality is the key to promoting industry development. The deep learning model based on residual convolutional neural network (ResNet) has the advantage of automatic extraction and the recognition of Fourier transform near-infrared spectroscopy (FT-NIR) features. Models are difficult to understand and interpret because of unknown working mechanisms and decision-making processes. Therefore, in this study, artificial feature extraction methods combine traditional partial least squares discriminant analysis (PLS-DA) and support vector machine (SVM) models to understand and compare deep learning models. The results show that the ResNet model has significant advantages over traditional models in feature extraction and recognition. Secondly, preprocessing has a great impact on the feature extraction and feature extraction, and is beneficial for improving model performance. Competitive adaptive reweighted sampling (CARS) and variable importance in projection (VIP) methods screen out more feature variables after preprocessing, but the number of potential variables (LVs) and successive projections algorithm (SPA) methods obtained is fewer. The SPA method only extracts two variables after preprocessing, causing vital information to be lost. The VIP feature of traditional modelling yields the best results among the four methods. After spectral preprocessing, the recognition rates of the PLS-DA and SVM models are up to 90.16% and 88.52%. For the ResNet model, preprocessing is beneficial for extracting and identifying spectral image features. The ResNet model based on synchronous two-dimensional correlation spectra has a recognition accuracy of 100%. This research is beneficial to the application development of the ResNet model in foods, spices, and medicinal plants.

Relapses of CD19-expressing leukemia in patients who achieved initial remission after CART cell treatment have been reported to correlate with poor CART cells persistence. Sustained tonic signaling or strong activation drives CART cell differentiation and exhaustion, which limit the therapeutic efficacy and persistence of CART cells. Here, we identified dasatinib as the optimal candidate to prevent or reverse both CD28/CART and 4-1BB/CART cell differentiation and exhaustion during ex vivo expansion, which profoundly enhanced the therapeutic efficacy and in vivo persistence. Moreover, strong activation-induced CART cells differentiation, exhaustion and apoptosis driven by CD3/CD28 stimulation or antigen exposure were dramatically prevented or reversed by dasatinib treatment. Mechanistically, dasatinib markedly reduced the phosphorylation of Src and Lck, and downregulated the expression of genes involved in CAR signaling pathways, which resulted in the optimization of cell differentiation, exhaustion and apoptosis-related gene expression. Our study proposes a promising pharmacological approach for optimizing CART cells manufacture, and provides an experimental basis for reinvigorating CART cells in clinical application. Supplementary Information The online version contains supplementary material available at 10.1186/s13045-021-01117-y.

Both in situ and ex situ conservation are important strategies for protecting threatened plant species. Nevertheless, the success of conservation depends on whether the plant species can naturally regenerate and accomplish its life cycle over a long-term. Here we studied the pollination biology of the threatened species Hibiscus aridicola, Amorphophallus albus, Stemona parviflora and S. japonica aiming to get data about pollination strategies, pollinators as well as mating systems. These experiments were performed at Kunming Botanical Garden (KBG) for ex situ and the plant species’ natural habitat for in situ conservation. The results indicated that H. aridicola is self-compatible and had pollinators under both ex situ and in situ conditions. The other three species are all self-incompatible and a limited number of pollinators for S. parviflora and S. japonica were observed at cultivated and natural habitats. Amorphophallus albus had no pollinators at KBG but a large number of rove beetles (Atheta sp.) could be observed in the plant species’ natural habitat. This resulted in a high fruit set under natural conditions (73.3%, n = 30). The results showed clearly, that appropriate pollinators for the four plant species are not present all the time and all localities, which further influences the reproduction success of a plant species. Hence, for a successful conservation, it is vital to assess the species reproduction strategy prior deciding whether in situ and/or ex situ conservation should be carried out.

Environmentally persistent free radicals (EPFRs) are emerging pollutants in contaminated soils and have attracted significant attention. Chinese coke production making a great contribution to the globe is increasingly identified as the non-ignorable source of EPFRs. However, the distribution level, influence factors, and biotoxicity of EPFRs at coking sites remain poorly understood. Herein, a typical coking plant in Tangshan, China, featuring two functional regions (the reconstructed project (RP) and elimination engineering (EE)) was used to study the existence of EPFRs. The spin density of the EPFRs in coking soils was 3.20 × 10

During software maintenance, developers may need to migrate an already in-use library to another library with similar functionalities. However, it is difficult to make the optimal migration decision with limited information, knowledge, or expertise. In this paper, we present MigrationAdvisor, an evidence-based tool to recommend library migration targets through intelligent analysis upon a large number of GitHub repositories and Java libraries. The migration advisories are provided through a search engine style web service where developers can seek migration suggestions for a specific library. We conduct systematic evaluations on the correctness of results, and evaluate the usefulness of the tool by collecting usage feedback from industry developers. Video: https://youtu.be/4I75W22TqwQ.

Background Decades of efforts have attempted to differentiate the pluripotent stem cells (PSCs) into truly functional hematopoietic stem cells (HSCs), yet the problems of low differentiation efficiency in vitro and poor hematopoiesis reconstitution in vivo still exist, mainly attributing to the lack of solid, reproduced, or pursued differentiation system. Methods In this study, we established an in vitro differentiation system yielding in vivo hematopoietic reconstitution hematopoietic cells from mouse PSCs through a 3D induction system followed by coculture with OP9 stromal cells. The in vivo hematopoietic reconstitution potential of c-kit+ cells derived from the mouse PSCs was evaluated via m-NSG transplantation assay. Flow cytometry analysis, RNA-seq, and cell cycle analysis were used to detect the in vitro hematopoietic ability of endothelial protein C receptor (EPCR, CD201) cells generated in our induction system. Results The c-kit+ cells from 3D self-assembling peptide induction system followed by the OP9 coculture system possessed apparently superiority in terms of in vivo repopulating activity than that of 3D induction system followed by the 0.1% gelatin culture. We interestingly found that our 3D+OP9 system enriched a higher percentage of CD201+c-kit+cells that showed more similar HSC-like features such as transcriptome level and CFU formation ability than CD201-c-kit+cells, which have not been reported in the field of mouse PSCs hematopoietic differentiation. Moreover, CD201+ hematopoietic cells remained in a relatively slow cycling state, consistent with high expression levels of P57 and Ccng2. Further, we innovatively demonstrated that notch signaling pathway is responsible for in vitro CD201+ hematopoietic cell induction from mouse PSCs. Conclusions Altogether, our findings lay a foundation for improving the efficiency of hematopoietic differentiation and generating in vivo functional HSC-like cells from mouse PSCs for clinical application.

The wide adoption of third-party libraries in software projects is beneficial but also risky. An already-adopted third-party library may be abandoned by its maintainers, may have license incompatibilities, or may no longer align with current project requirements. Under such circumstances, developers need to migrate the library to another library with similar functionalities, but the migration decisions are often opinion-based and sub-optimal with limited information at hand. Therefore, several filtering-based approaches have been proposed to mine library migrations from existing software data to leverage "the wisdom of crowd," but they suffer from either low precision or low recall with different thresholds, which limits their usefulness in supporting migration decisions.In this paper, we present a novel approach that utilizes multiple metrics to rank and therefore recommend library migrations. Given a library to migrate, our approach first generates candidate target libraries from a large corpus of software repositories, and then ranks them by combining the following four metrics to capture different dimensions of evidence from development histories: Rule Support, Message Support, Distance Support, and API Support. We evaluate the performance of our approach with 773 migration rules (190 source libraries) that we borrow from previous work and recover from 21,358 Java GitHub projects. The experiments show that our metrics are effective to help identify real migration targets, and our approach significantly outperforms existing works, with MRR of 0.8566, top-1 precision of 0.7947, top-10 NDCG of 0.7702, and top-20 recall of 0.8939. To demonstrate the generality of our approach, we manually verify the recommendation results of 480 popular libraries not included in prior work, and we confirm 661 new migration rules from 231 of the 480 libraries with comparable performance. The source code, data, and supplementary materials are provided at: https://github.com/hehao98/MigrationHelper.

Background Clinical management of triple-negative breast cancer (TNBC) patients remain challenging because of the development of chemo-resistance. Identification of biomarkers for risk stratification of chemo-resistance and therapeutic decision-making to overcome such resistance is thus necessary. Methods Retrospective analysis was performed to identify potential stratification biomarkers. The levels of ceramide kinase (CERK) was determined in breast cancer patients. The roles of CERK and its downstream signaling pathways were analysed using cellular and biochemical assays. Results CERK upregulation was identified as a biomarker for chemotherapeutic response in TNBC. A > 2-fold change in CERK (from tumor)/CERK (from normal counterpart) was significantly associated with chemo-resistance (OR = 2.66, 95% CI 1.18–7.34), P = 0.04. CERK overexpression was sufficient to promote TNBC growth and migration, and confer chemo-resistance in TNBC cell lines, although this resistance could be overcome via CERK inhibition. Mechanistic studies suggest that CERK mediates intrinsic resistance and inferior response to chemotherapy in TNBC by regulating multiple oncogenic pathways such as Ras/ERK, PI3K/Akt/mTOR, and RhoA. Conclusions Our work provides an explanation for the heterogeneity of chemo-response across TNBC patients and demonstrates that CERK inhibition offers a therapeutic strategy to overcome treatment resistance.

In order to solve the problem that the attribute reduction algorithm of neighborhood rough set only considers the influence of a single attribute on the decision attributes, but fails to consider the correlation between the attributes, this paper proposes an attribute reduction algorithm of neighborhood rough set based on chi-square test (ChiS-NRS). Firstly, the chi-square test is used to calculate the correlation, and the influence of related attributes is considered when selecting important attributes, which reduces the time complexity and improves the classification accuracy. Then, he improved algorithm uses the Gradient Boosting Decision Tree (GBDT) algorithm to build a classification model, and the model is verified on the UCI data set. Finally, the model is applied to predict the existence of intracranial aneurysms. The experimental results show that the proposed model can better predict the existence of intracranial aneurysms and assist doctors to make more accurate diagnosis.

Additional file 1: Fig. S1. Transfection alone does not affect TNBC cell growth, migration and survival. Proliferation (A), migration (B) and apoptosis (C) of TNBC parental cells and cells transfected with Neg siRNA or pCMV3. Fig. S2. CERK knockdown augments cytotoxicity of chemotherapeutic agents in TNBC cells. CERK depletion significantly augments the anti-migratory (A), anti-proliferative (B) and pro-apoptotic (C) effects of cisplatin and paclitaxel in BT-549 and Hs 578T cells. Paclitaxel at 100 nM and cisplatin at 1 μM were added to the cell medium at 24 h post-transfection. *P

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34+ cells. Further, 3DCS-expanded cHSPCs exhibited 1.65-fold increase in the reconstitution rate compared to CD34+ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF-α to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.

The bionic robotic arm has the characteristics of high safety, lightweight and portability, which can assist humans in completing various daily activities in life. Based on the research background of human-machine collaboration and simulating its experimental environment, a vision-assisted grasping framework for collaborative robots serving humans is proposed, and a discrimination scheme based on the combination of the shortest path and gIOU is designed. We can interact with the robotic grasping system by directly gazing at the object of interest. The gaze coordinates are provided by an eye tracker, which is matched with the image of the target detection algorithm to obtain the grasping information, and the signal is transmitted to the grasping system. The grasping system executes the grasping operation through the robotic arm after calculating the target pose, and implements the automatic grasping target by gazing at the target object. The experimental results show that this framework has good positioning accuracy and can effectively complete daily grasping tasks.

As the global aging and climbing rate of aging diseases causing more and more attention to elderly illness, a systematic review explores the part eye-tracking plays in reflecting cognitive status and being an indicator and assistive tool for diagnosis of neurological diseases. Neuropsychological tests are commonly seen in current clinical diagnostic process, while massive labor and equipment support are a must. To look for alternatives, various eye movement parameters have been investigated covering smooth saccade pursuit, inhibitory gaze, fixation of duration, pupil diameter, saccade length, scan path and ROI using diverse visual stimuli. Nonetheless, existing limitations in studies are presented. Overall, current research validated that eye movements reflect cognitive impairment based on different distinct manifestation and provide a contact-free and efficient methodology for pre-diagnostic domain.