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Abstract Background The function of hematopoietic stem cells (HSC) is regulated by HSC internal signaling pathways and their microenvironment. Chemokines and chemokine ligands play important roles in the regulation of HSC function. Yet, their functions in HSC are not fully understood. Methods We established Cxcr3 and Cxcl10 knockout mouse models (Cxcr3 −/− and Cxcl10 −/− ) to analyze the roles of Cxcr3 or Cxcl10 in regulating HSC function. The cell cycle distribution of LT-HSC was assessed via flow cytometry. Cxcr3 −/− and Cxcl10 −/− stem/progenitor cells showed reduced self-renewal capacity as measured in serial transplantation assays. To study the effects of Cxcr3 or Cxcl10 deficient bone marrow microenvironment, we transplanted CD45.1 donor cells into Cxcr3 −/− or Cxcl10 −/− recipient mice (CD45.2) and examined donor-contributed hematopoiesis. Results Deficiency of Cxcl10 and its receptor Cxcr3 led to decreased BM cellularity in mice, with a significantly increased proportion of LT-HSC. Cxcl10 −/− stem/progenitor cells showed reduced self-renewal capacity in the secondary transplantation assay. Notably, Cxcl10 −/− donor-derived cells preferentially differentiated into B lymphocytes, with skewed myeloid differentiation ability. Meanwhile, Cxcr3-deficient HSCs demonstrated a reconstitution disadvantage in secondary transplantation, but the lineage bias was not significant. Interestingly, the absence of Cxcl10 or Cxcr3 in bone marrow microenvironment did not affect HSC function. Conclusions The Cxcl10 and Cxcr3 regulate the function of HSC, including self-renewal and differentiation, adding to the understanding of the roles of chemokines in the regulation of HSC function.

BackgroundMetagenomic next-generation sequencing (mNGS) has been widely reported to identify pathogens in infectious diseases (IDs). In this work, we intended to investigate the diagnostic value and clinical acceptance of paired-samples mNGS as compared to the culture method.MethodsA total of 361 patients with suspected infection were retrospectively included. With reference to the clinical diagnosis, we compared the diagnostic performance and clinical acceptance in pathogen detection between mNGS and culture tests. Moreover, the pathogen concordance of paired blood and respiratory tract (RT) samples in mNGS assay was investigated.ResultsAmong 511 samples, 62.04% were shown to be pathogen positive by mNGS, and that for clinical diagnosis was 51.86% (265/511). When compared to culture assay (n = 428), mNGS had a significantly higher positivity rate (51.87% vs. 33.18%). With reference to the clinical diagnosis, the sensitivity of mNGS outperformed that of culture (89.08% vs. 56.72%). Importantly, mNGS exhibited a clinically accepted rate significantly superior to that of culture. In addition, the mNGS result from 53 paired blood and RT samples showed that most pairs were pathogen positive by both blood and RT, with pathogens largely being partially matched.ConclusionThrough this large-scale study, we further illustrated that mNGS had a clinically accepted rate and sensitivity superior to those of the traditional culture method in diagnosing infections. Moreover, blood and paired RT samples mostly shared partial-matched positive pathogens, especially for pathogens with abundant read numbers in RT, indicating that both blood and RT mNGS can aid the identification of pathogens for respiratory system infection.

Geosynchronous synthetic aperture radar (GEO SAR) has the advantages of a short revisit time and a large beam footprint. Enhancing spatial resolution has become a hotspot in spaceborne SAR research areas. The existing designs of GEO SAR suffer from the problem of poor resolution (greater than 10 m) and cause low-precision observation in urban areas. First time, this article points out that GEO SAR has the ability to improve the two-dimensional (2-D) resolution of SAR images by spatial spectrum synthesis based on 2-D baselines, and proposes models and a signal processing method involved in GEO SAR spectrum synthesis. The 2-D spatial baselines of GEO SAR are analyzed and evaluated first based on satellite software and real ephemeris from Beidou Inclined Geosynchronous Orbit (IGSO) navigation satellites to demonstrate the potential of 2-D resolution improvement. Then the analytical models of the spectral shape and relative spectral shift between GEO SAR images are derived. Furthermore, a 2-D spectrum synthesis algorithm suitable for GEO SAR is also proposed, where we use deramping operation instead of the traditional spectrum shifting process. Nonideal factors are considered in the processing of synthesized. In addition, performances of the proposed algorithm, including the resolution improvement factor, the amplitude fluctuation, and the critical baseline, are constructed. Finally, computer simulations and equivalent experiments based on Beidou IGSO navigation satellites verify the proposed algorithm.

Geosynchronous (GEO) spaceborne-airborne bistatic synthetic aperture radar, consisting of a GEO transmitter and an airborne multichannel receiver, is a potential moving target indication (MTI) system. However, such systems encounter synchronization challenges due to noncooperative transmission and reception. Besides, the inaccurate GEO orbital position for the MTI processor construction results in a low output signal-to-noise ratio (SNR) and reduced target detection probability. To address this, this article proposes a synchronization and MTI method based on direct signal and clutter subspace, which can enhance the output SNR for target detection even if the GEO orbital position is inaccurate. This method utilizes the direct signal to compensate for time and frequency synchronization errors. In addition, the residual error caused by the imprecise GEO orbit is estimated by approximating the clutter subspace. Next, a modified MTI processor is employed to suppress clutter and focus moving targets by using the residual error. Finally, the effectiveness of the proposed method is verified by numerical simulation experiments based on real IGSO orbital parameters.

Differential synthetic aperture radar tomography (D-TomoSAR) uses multiple SAR acquisitions at different times to form an elevation-time 2-D synthetic aperture, enabling recovery of the target's 3-D structure and deformation velocity. However, the imaging performance of D-TomoSAR is influenced by the spatial-temporal baseline distribution, which is one of the crucial factors. Due to the difference in orbit altitude, the effects of various perturbation forces on geosynchronous SAR (GEO SAR) are significantly different from those on low Earth orbit SAR (LEO SAR), leading to different geometries in the spatial-temporal baseline distributions of GEO SAR and LEO SAR in the repeat-pass acquisitions. The spatial-temporal baseline distribution of LEO SAR is random, while that of GEO SAR is coupled. Although GEO SAR obtains a large number of acquisitions due to the short repeat-pass time, using data under all spatial-temporal baselines for D-TomoSAR does not necessarily provide the best imaging results. Therefore, how to select spatial-temporal baselines that can improve the estimation accuracy is important. In this article, the Cramér–Rao lower bound of GEO D-TomoSAR estimation accuracy is determined by considering multiple factors, including baseline decorrelation and spatial-temporal coupling. The optimal spatial-temporal baseline selection is modeled as a multiobjective problem and solved by the Nondominated Sorting Genetic Algorithm II (NSGA-II). Given the absence of in-orbit GEO SAR and the orbital similarity between GEO SAR and BeiDou Inclined Geosynchronous Orbit (IGSO) satellite, the real ephemeris of BeiDou IGSO satellite is used to simulate the baseline distribution of GEO SAR and verify the baseline optimization method.

Eucommiae Cortex (EC) is frequently used alone or in combination with other active ingredients to treat a range of illnesses. An efficient technical instrument for changing cheap or plentiful organic chemicals into rare or costly counterparts is biotransformation. It combines EC with biotransformation techniques with the aim of producing some novel active ingredients, using different strains of bacteria that were introduced to biotransform EC in an aseptic environment. The high-quality strains were screened for identification after the fermentation broth was found using HPLC, and the primary unidentified chemicals were separated and purified in order to be structurally identified. Strain 1 was identified as Aspergillus niger and strain 2 as Actinomucor elegans; the main transformation product A was identified as pinoresinol (Pin) and B as dehydrodiconiferyl alcohol (DA). The biotransformation of EC utilizing Aspergillus niger and Actinomucor elegans is reported for the first time in this study’s conclusion, resulting in the production of Pin and DA.

Direct conversion of syngas to aromatics (STA) over oxide-zeolite composite catalysts is promising as an alternative method for aromatics production. However, the structural effect of the oxide component in composite catalysts is still ambiguous. Herein, we investigate the size effect by selecting ZnCr2O4 spinel, as a probe oxide, mixing with H-ZSM-5 zeolite as a composite catalyst for STA reaction. The CO conversion, aromatics selectivity and space-time yield (STY) of aromatics are all significantly improved with the crystal size of ZnCr2O4 oxide decreases, which can mainly attribute to the higher oxygen vacancy concentration and thus the rapid generation of more C1 oxygenated intermediate species. Based on the understanding of the size–performance relationship, ZnCr2O4-400 with a smaller size mixing with H-ZSM-5 can achieve 32.6% CO conversion with 76% aromatics selectivity. The STY of aromatics reaches as high as 4.79 mmol gcat−1 h−1, which outperforms the previously reported some typical catalysts. This study elucidates the importance of regulating the size of oxide to design more efficient oxide-zeolite composite catalysts for conversion of syngas to value-added chemicals.

The food industry holds immense promise for 3D printing technology. Current research focuses mainly on optimizing food material composition, molding characteristics, and printing parameters. However, there is a notable lack of comprehensive studies on the shape changes of food products, especially in modeling and simulating deformations. This study addresses this gap by conducting a detailed simulation of the starch gel printing and deformation process using COMSOL Multiphysics 6.2 software. Additive manufacturing (AM) technology is widely acclaimed for its user-friendly operation and cost-effectiveness. The 3D printing process may lead to changes in part dimensions and mechanical properties, attributable to the accumulation of residual stresses. Studies require a significant amount of time and effort to discover the optimal composition of the printed material and the most effective deformed 3D structure. There is a risk of failure, which can lead to wasted resources and research delays. To tackle this issue, this study thoroughly analyzes the physical properties of the gel material through COMSOL Multiphysics 6.2 software, It simulates the heat distribution during the 3D printing process, providing important insights into how materials melt and solidify. Three-part models with varying aspect ratios were meticulously designed to explore shape changes during both the printing process and exposure to an 80 °C environment, employing NMR and rheological characterization. Using the generalized Maxwell model for material simulation in COMSOL Multiphysics, the study predicted stress and deformation of the parts by analyzing solid heat transfer and solid mechanics physical fields. Simulation results showed that among three models utilizing a gel-PET plastic membrane bilayer structure, Model No. 1, with the largest aspect ratio, exhibited the most favorable deformation under an 80 °C baking environment. It displayed uniform bending in the transverse direction without significant excess warpage in the edge direction. In contrast, Models No. 2 and No. 3 showed varying degrees of excess warpage at the edges, with Model No. 3 exhibiting a more pronounced warpage. These findings closely aligned with the actual printing outcomes.

Abstract Excessive protein synthesis upon enhanced cell proliferation frequently results in an increase of unfolded or misfolded proteins. During hematopoietic regeneration, to replenish the hematopoietic system, hematopoietic stem cells (HSCs) are activated and undergo a rapid proliferation. But how the activated HSCs respond to the proliferation pressure is still ambiguous; The proper control of the functional reservoir in the activated HSCs remains poorly understood. Here, we show a significant upregulation of EVA1A protein associated with the increase of ER stress during hematopoietic regeneration. Deletion of Eva1a significantly enhances the regeneration capacity of HSCs by inhibiting the ER stress-induced apoptosis. Mechanistically, the expression of EVA1A protein was upregulated by CHOP, and thereby promoted the ER-mitochondria interlinking via MCL1, which resulted in mitochondria-mediated apoptosis. These findings reveal a pathway for ER stress responses of HSCs by the EVA1A mediated apoptosis, which play an important role in HSCs regeneration.

Abstract Age-related macular degeneration (AMD) is a major vision-threatening disease. Although mesenchymal stem cells (MSCs) exhibit beneficial neural protective effects, their limited differentiation capacity in vivo attenuates their therapeutic function. Therefore, the differentiation of MSCs into retinal pigment epithelial (RPE) cells in vitro and their subsequent transplantation into the subretinal space is expected to improve the outcome of cell therapy. Here, we transdifferentiated human umbilical cord MSCs (hUCMSCs) into induced RPE (iRPE) cells using a cocktail of five transcription factors (TFs): CRX, NR2E1, C-MYC, LHX2, and SIX6. iRPE cells exhibited RPE specific properties, including phagocytic ability, epithelial polarity, and gene expression profile. In addition, high expression of PTPN13 in iRPE cells endows them with an epithelial-to-mesenchymal transition (EMT)-resistant capacity through dephosphorylating syntenin1, and subsequently promoting the internalization and degradation of transforming growth factor-β receptors. After grafting into the subretinal space of the sodium iodate-induced rat AMD model, iRPE cells demonstrated a better therapeutic function than hUCMSCs. These results suggest that hUCMSC-derived iRPE cells may be promising candidates to reverse AMD pathophysiology.

BackgroundEpidemiological evidence on alpha (α)-tocopherol intake and cognitive performance in older individuals is controversial and the effect of periodontitis in this chain is sparse and limited. The goal of this study was to characterize the association between α-tocopherol intake and cognitive performance and the mediating role of periodontitis in a nationally representative sample of older adults.MethodsData from the National Health and Nutrition Examination Survey (NHANES), 2011–2014, were used. Multivariate logistic regression analysis was performed to explore the association of α-tocopherol intake, periodontal measures (mean attachment loss [AL] and mean probing depth [PD]), and clinical periodontitis defined by the European Workshop in Periodontology with poor cognitive performance evaluated by Consortium to Establish a Registry for Alzheimer’s disease (CERAD); the animal fluency test (AFT); and the Digit Symbol Substitution test (DSST) and the correlation between α-tocopherol intake and clinical periodontitis. Multiple linear regression analysis was used to explore the relationship between α-tocopherol intake and periodontal measures. Mediation analysis was used to test the effects of periodontal measures on the association between α-tocopherol intake and cognitive measures.ResultsA total of 1,749 older participants (≥60 years of age) with complete periodontal diagnosis, dietary retrospective survey, and cognitive tests were included. In the fully adjusted model, the odds ratio (OR) with 95% confidence interval (CI) of CERAD score, AFT score and DSST score were 0.214 (0.137–0.327), 0.378 (0.241–0.585) and 0.298 (0.169–0.512) for the highest versus lowest tertile of α-tocopherol intake, respectively. And participants with clinical periodontitis were more likely to exhibit lower DSST score (OR = 1.689; 95 CI%: 1.018–2.771) than those without periodontitis. Mean AL (OR = 1.296; 95 CI%: 1.102–1.524) and PD (OR = 1.667; 95 CI%: 1.18–2.363) were negatively correlated with DSST, and were estimated to mediate 9.1 and 8.2% of the total association between α-tocopherol intake and cognitive performance, respectively.ConclusionFinding of the present study suggested that participants with low α-tocopherol intake were at higher risk for developing cognitive decline. Moreover, periodontitis mediated the association between α-tocopherol intake and cognitive performance.

Increasing evidence highlights a robust correlation between the gut microbiota and bone diseases; however, the existence of a causal relationship between them remains unclear. In this study, we thoroughly examined the correlation between gut microbiota and skeletal diseases using genome-wide association studies. Linkage disequilibrium score regression and Mendelian randomization were used to probe genetic causality. Furthermore, the potential mediating role of neuropsychological states (i.e., cognition, depression, and insomnia) between the gut microbiota and bone diseases was evaluated using mediation analysis, with genetic colocalization analysis revealing potential targets. These findings suggest a direct causal relationship between Ruminococcaceae and knee osteoarthritis (OA), which appears to be mediated by cognitive performance and insomnia. Similarly, a causal association was observed between Burkholderiales and lumbar pelvic fractures, mediated by cognitive performance. Colocalization analysis identified a shared causal variant (rs2352974) at the TRAF-interacting protein locus for cognitive ability and knee OA. This study provides compelling evidence that alterations in the gut microbiota can enhance cognitive ability, ameliorate insomnia, and potentially reduce the risk of site-specific fractures and OA. Therefore, strategies targeting gut microbiota optimization could serve as novel and effective preventive measures against fractures and OA.

Summary: The hostile microenvironment of the retina in patients with age-related macular degeneration (AMD) may trigger epithelial-to-mesenchymal transition (EMT) of grafted retinal pigment epithelial (RPE) cells, thus attenuating the therapeutic outcome. Here, we transformed human dedifferentiated induced pluripotent stem cell-derived RPE (iPSC-RPE) cells into induced RPE (iRPE) cells using a cocktail of four transcription factors (TFs)—CRX, MITF-A, NR2E1, and C-MYC. These critical TFs maintained the epithelial property of iRPE cells by regulating the expression of bmp7, forkhead box f2, lin7a, and pard6b, and conferred resistance to TGF-β-induced EMT in iRPE cells by targeting ppm1a. The iRPE cells with Tet-on system-regulated c-myc expression exhibited EMT resistance and better therapeutic function compared with iPSC-RPE cells in rat AMD model. Our study demonstrates that endowing RPE cells with anti-EMT property avoids the risk of EMT after cells are grafted into the subretinal space, and it may provide a suitable candidate for AMD treatment.

Abstract Remarkable progress in ageing research has been achieved over the past decades. General perceptions and experimental evidence pinpoint that the decline of physical function often initiates by cell senescence and organ ageing. Epigenetic dynamics and immunometabolic reprogramming link to the alterations of cellular response to intrinsic and extrinsic stimuli, representing current hotspots as they not only (re-)shape the individual cell identity, but also involve in cell fate decision. This review focuses on the present findings and emerging concepts in epigenetic, inflammatory, and metabolic regulations and the consequences of the ageing process. Potential therapeutic interventions targeting cell senescence and regulatory mechanisms, using state-of-the-art techniques are also discussed.

Based on its ability to obtain two-dimensional (2D) high-resolution images in all-time and all-weather conditions, spaceborne synthetic aperture radar (SAR) has become an important remote sensing technique and the study of such systems has entered a period of vigorous development. Advanced imaging modes such as radar interferometry, tomography, and multi-static imaging, have been demonstrated. However, current in-orbit spaceborne SARs, which all operate in low Earth orbits, have relatively long revisit times ranging from several days to dozens of days, restricting their temporal sampling rate. Geosynchronous SAR (GEO SAR) is an active research area because it provides significant new capability, especially its much-improved temporal sampling. This paper reviews the research progress of GEO SAR technologies in detail. Two typical orbit schemes are presented, followed by the corresponding key issues, including system design, echo focusing, main disturbance factors, repeat-track interferometry, etc, inherent to these schemes. Both analysis and solution research of the above key issues are described. GEO SAR concepts involving multiple platforms are described, including the GEO SAR constellation, GEO-LEO/airborne/unmanned aerial vehicle bistatic SAR, and formation flying GEO SAR (FF-GEO SAR). Due to the high potential of FF-GEO SAR for three-dimensional (3D) deformation retrieval and coherence-based SAR tomography (TomoSAR), we have recently carried out some research related to FF-GEO SAR. This research, which is also discussed in this paper, includes developing a formation design method and an improved TomoSAR processing algorithm. It is found that GEO SAR will continue to be an active topic in the aspect of data processing and multi-platform concept in the near future.

Abstract Liver fibrosis occurs in response to any etiology of chronic liver injury. Lack of appropriate clinical intervention will lead to liver cirrhosis or hepatocellular carcinoma (HCC), seriously affecting the quality of life of patients, but the current clinical treatments of liver fibrosis have not been developed yet. Recent studies have shown that hypoxia is a key factor promoting the progression of liver fibrosis. Hypoxia can cause liver fibrosis. Liver fibrosis can, in turn, profoundly further deepen the degree of hypoxia. Therefore, exploring the role of hypoxia in liver fibrosis will help to further understand the process of liver fibrosis, and provide the theoretical basis for its diagnosis and treatment, which is of great significance to avoid further deterioration of liver diseases and protect the life and health of patients. This review highlights the recent advances in cellular and molecular mechanisms of hypoxia in developments of liver fibrosis.

BackgroundObstructive sleep apnea-hypopnea syndrome (OSA) may cause liver fibrosis, and liver fibrosis serum biomarkers plays an important role on the diagnosis of liver fibrosis. In addition, this study aimed to observe the changes of 4 serum markers and Chitinase 3-like protein 1 (CHII3L1) levels in OSA patients with different disease severity and explore their interactions. And then, we examined whether intermittent hypoxia (IH) exposure can activate hepatic stellate cell.Methods74 OSA patients in Second Xiangya hospital from January 2021 to October 2021 was selected and categorized into mild, moderate, and severe groups according to AHI. In addition, 20 subjects were selected as the control group. Serum levels of liver fibrosis markers were determined by electrochemiluminescence immunoassay. Hepatic stellate cells were exposed to intermittent IH or normoxia (RA). Results were analyzed using the SPSS software.ResultsThere was a significant increase in serum hyaluronic acid (HA), collagen type IV (CIV) and CHI3L1 levels in OSA patients compared with control group. Specifically, serum liver fibrosis markers HA, CIV and CHI3L1 levels were positively correlated with apnea-hypopnea index (AHI), but negatively correlated with the lowest saturation oxygen (LSaO2) respectively. The LX-2 cells (human hepatic stellate cell line) exposed to IH showed significant increases in fibrotic protein expression.ConclusionOSA might either directly or indirectly trigger or exacerbate liver fibrosis, possibly via IH-related pathways.

Biological invasion is a serious threat to biodiversity and ecosystem function in nature reserves. However, the knowledge of the spatial patterns and underlying mechanisms of plant invasions in nature reserves is still limited. Based on a recent dataset on both invasive and native plants in 67 nature reserves of China, we used correlation, regression, and variation partitioning methods to statistically assess the relative roles of the “human activity,” “biotic acceptance,” and “environmental heterogeneity” hypotheses in explaining the geographic pattern of plant invasion. A total of 235 invasive plant species were compiled from 67 nature reserves. The high explanatory power of the human activity variables supported the human activity hypothesis. The biotic acceptance hypothesis was weakly supported since no significant correlations between climatic variables and invasion levels were found when the effects of the other factors were controlled. The environmental heterogeneity hypothesis was partially supported, since the number of native plants, representing environmental heterogeneity at fine-scale explained remarkable proportion of spatial variance of invasive plants but not that of the proportion of invasive plants. We predict that nature reserves with high plant diversity affected by rapid economic development and increasing temperature will face a serious threat of exotic plant invasion. In conclusion, our results provide crucial clues for understanding geographic variance of plant invasion in China’s nature reserves and spatial risk assessment.

Antibiotics are broadly restricted in modern husbandry farming, necessitating the need for efficient and low-cost immunomodulatory preparations in antibiotic-free and healthful farming. As is known to all, CpG oligonucleotides (CpG-ODNs, an effective innate immunostimulatory agent) recognized by TLR9 in mammals (while TLR21 in avians) could collaborate with some united agent to induce stronger immune responses, but the cost is prohibitively expensive for farmers. Here, considering the coordination between TLR2 and TLR9/TLR21, we firstly proposed the idea that the well-fermented Lactococcus lactis could be utilized as a CpG-plasmid carrier (LACpG10) to enhance the host’s innate immunity against pathogenic invasion. In the present study, after obtaining LACpG10-HL from homogenized and lyophilized recombinant strain LACpG10, we treated primary chicken lymphocytes, two cell lines (HD11 and IPEC-J2), and chickens with LACpG10-HL, CpG plasmids (pNZ8148-CpG10), and other stimulants, and respectively confirmed the effects by conducting qRT-PCR, bacterial infection assays, and a zoological experiment. Our data showed that LACpG10-HL could induce excellent innate immunity by regulating autophagy reactions, cytokine expression, and motivating PRRs. Interestingly, despite having no direct antiseptic effect, LACpG10-HL improved the antibacterial capacities of lymphocytes and enterocytes at the first line of defense. Most importantly, water-supplied LACpG10-HL treatment reduced the average adverse event rates, demonstrating that LACpG10-HL maintained its excellent immunostimulatory and protective properties under farming conditions. Our research not only contributes to revealing the satisfactory effects of LACpG10-HL but also sheds new light on a cost-effective solution with optimal immune effects in green, antibiotic-free, and healthful husbandry farming.

Due to the short revisit time and large coverage of Geosynchronous synthetic aperture radars (GEO SARs) and the increasing number of low earth orbit synthetic aperture radar (LEO SAR) constellations, radio frequency interference (RFI) between GEO SARs and LEO SARs may occur, deteriorating the quality of SAR images. Traditional methods only simplify RFI to noise-like interference without considering the signal characteristics. In this paper, to accurately evaluate the impacts of GEO-to-LEO RFI and LEO-to-GEO RFI on imaging quantitatively, an RFI-impact quantitative analysis model is established. Taking account of the chirp signal form of SAR systems, the RFI power and image Signal-to-Interference-plus-Noise Ratio (SINR) are theoretically deduced and validated by numerical experiments. Based on the proposed method, the SAR image quality under different system parameters and bistatic configurations is estimated, and the probability of different configurations is also given. The results show that specular bistatic scattering RFI between GEO SARs and LEO SARs has serious effects on imaging, and the probability can approach 2% for certain orbital parameters and will become higher as LEO SAR constellations increase in the future, implying the necessity to suppress the RFI between the GEO SAR and the LEO SAR system.

BackgroundAs the most aggressive tumors in the central nervous system, gliomas have poor prognosis and limited therapy methods. Immunotherapy has become promising in the treatment of gliomas. Here, we explored the expression pattern of APOBEC3B, a genomic mutation inducer, in gliomas to assess its value as an immune biomarker and immunotherapeutic target.MethodsWe mined transcriptional data from two publicly available genomic datasets, TCGA and CGGA, to investigate the relevance between APOBEC3B and clinical characterizations including tumor classifications, patient prognosis, and immune infiltrating features in gliomas. We especially explored the correlation between APOBEC3B and tumor mutations. Samples from Xiangya cohort were used for immunohistochemistry staining.ResultsOur findings demonstrated that APOBEC3B expression level was relatively high in advanced gliomas and other cancer types, which indicated poorer prognosis. APOBEC3B also stratified patients’ survival in Xiangya cohort. APOBEC3B was significantly associated with infiltrating immune and stromal cell types in the tumor microenvironment. Notably, APOBEC3B was involved in tumor mutation and strongly correlated with the regulation of oncogenic genes.ConclusionOur findings identified that APOBEC3B could be a latent molecular target in gliomas.

Summary: Hematopoietic stem cells (HSCs) regenerate blood cells upon hematopoietic injuries. During homeostasis, HSCs are maintained in a low reactive oxygen species (ROS) state to prevent exhaustion. However, the role of nitric oxide (NO) in controlling HSC regeneration is still unclear. Here, we find increased NO during HSC regeneration with an accumulation of protein aggregation. S-nitrosoglutathione reductase (GSNOR)-deleted HSCs exhibit a reduced reconstitution capacity and loss of self-renewal after chemotherapeutic injury, which is resolved by inhibition of NO synthesis. Deletion of GSNOR enhances protein S-nitrosylation, resulting in an accumulation of protein aggregation and activation of unfolded protein response (UPR). Treatment of taurocholic acid (TCA), a chemical chaperone, rescues the regeneration defect of Gsnor−/− HSCs after 5-fluorouracil (5-FU) treatment. Deletion of C/EBP homologous protein (Chop) restores the reconstitution capacity of Gsnor−/− HSCs. These findings establish a link between S-nitrosylation and protein aggregation in HSC in the context of blood regeneration.

Blasting is currently the most important method for rock fragmentation in metal mines. However, blast-induced ground vibration causes many negative effects, including great damage to surrounding rock masses and projects and even casualties in severe cases. Therefore, prediction of the peak particle velocity (PPV) caused by blasting plays an important role in reducing safety threats. In this paper, a genetic algorithm (GA) and an artificial neural network (ANN) algorithm were jointly used to construct a neural network model with a 4-5-1 topology to predict the PPV. For this model, the ANN parameters were optimized using the GA, and the deviating direction, horizontal distance, vertical distance, Euclidean distance, explosive type, burden, hole spacing, and maximum charge per delay were used as input information. Moreover, principal component analysis (PCA) was used to extract the first four principal components from the eight input factors as the four inputs of the ANN model. The model was successfully applied to protect an underground crushing cave from blasting vibration damage by adjusting the blasting parameters. Compared with several widely used empirical equations, the GA-ANN PPV prediction model produced significantly better results, while the Ambraseys–Hedron method was the best of the empirical methods. Therefore, the improved GA-ANN model can be used to predict the PPV on site and provide a reference for the control of blasting vibration in field production.

BackgroundStroke remains a leading cause of adult disability and the demand for stroke rehabilitation services is growing, and Astragaloside IV (As IV), a primary bioactive compound of Radix Astragali : Astragalus mongholicus Bunge (Fabaceae), may be a promising stroke therapy.MethodsTo access the effect of As IV on adult mice after ischemic stroke, a photochemical ischemia model was established on C57BL/6 mice, which were intravenously administered As IV for three consecutive days later. And then the cognitive benefits and hippocampal neurogenesis were evaluated by Morris Water Maze (MWM) test, Golgi staining, and immunohistochemical staining in vivo and in vitro. Furthermore, to find out the underlying mechanism, interleukin-17 (IL-17) knockout (KO) mice were used, through RNA sequence (RNA-seq) analysis and immunohistochemistry. Then the mechanism of neurogenesis promoted by As IV was observed by western blot both in vivo and in vitro. Specifically, As IV, recombinant mouse IL-17A and IL-17F, and Wingless/integrated (Wnt)-expressing virus was administered respectively in neural stem cells (NSCs), and then their diameters and protein expression of Nestin, IL-17, and Wnt pathway relevant protein, were measured in vitro.ResultsAdministering As IV resulted in significant amelioration of stroke-induced cognitive deficits. And more hippocampal neurons with normal morphology, significant increments in the length of the apical dendrites, and the density of their spines were observed in As IV-treated mice. Furthermore, the immunohistochemistry staining of DCX/BrdU and Sox2/Nestin showed As IV could promote hippocampal neurogenesis and NSC proliferation after ischemic stroke, as well as in vitro. For the mechanism underlying, IL-17 expression was downregulated significantly by As IV treatment and knocking out IL-17 was associated with nervous regeneration and synapse repair according to the analysis of RNA-seq. Consistent to As IV treatment, knocking out IL-17 showed some promotion on hippocampal neurogenesis and proliferation of NSCs, with activating Wnt pathway after stoke. Finally, in vitro, NSCs’ diameters and protein expression of Nestin, IL-17, and Wnt pathway were regulated by either administering As IV or inhibiting IL-17.ConclusionAs IV stimulates hippocampal neurogenesis after stroke, thus potentially facilitates brain to remodel and repair by downregulating IL-17 expression via Wnt pathway.

Adipose-derived stem cells (ASCs) have shown a strong protective effect on retinal degenerative diseases (RDD) after being transplanted into the subretinal space in an animal model. Recently, several clinical trials have been conducted to treat RDD with intravitreal transplantation of stem cells, including ASCs. However, the outcomes of the clinical trials were not satisfactory. To investigate if the transplantation site alters the outcome of stem cell-based therapy for RDD, we isolated rat ASCs (rASCs) and labeled them with green fluorescent protein. Autologous rASCs were grafted into the vitreous chamber or subretinal space in a rat RDD model induced by sodium iodate (SI). The electric response was recorded by ERG. The anatomic structure of the retina was observed in cryosections of rat eyes at posttransplantation weeks 1, 2, and 4. Neural retina apoptosis and epiretinal membrane- (ERM-) like structure formation were investigated by immunostaining. The intravitreal transplantation of rASCs resulted in an extinguished electric response, although the rosette formation and apoptosis of neural retina were reduced. However, the rASCs that grafted in the subretinal space protected the retina from the damage caused by SI, including a partial recovering of the electric response and a reduction in rosette formation. Intravitreally grafted rASCs formed a membrane, resulting in retina folding at the injection site. Müller cells, retinal pigment epithelial cells, and microglial cells migrated from the retina to the rASC-formed membrane and subsequently formed an ERM-like structure. Furthermore, vitreous fluid promoted rASC migration, and rASC-conditioned medium enhanced Müller cell migration as indicated by in vitro studies. These data suggested that the vitreous chamber is not a good transplantation site for ASC-based therapy for RDD and that a deliberate decision should be made before transplantation of stem cells into the vitreous chamber to treat RDD in clinical trials.

A geosynchronous spaceborne-airborne bistatic synthetic aperture radar (GEO SA-BSAR) system is an important technique to achieve long-time moving target monitoring over a wide area. However, due to special bistatic configuration of GEO SA-BSAR, two major challenges, i.e., severe range migration and space-variant Doppler parameters for moving targets, hinder the moving target indication (MTI) processing. Traditional SAR MTI methods, which do not take the challenges into consideration, will defocus the moving targets, leading to a loss of the signal-to-noise ratio (SNR). To focus moving targets and estimate motion parameters accurately, long-time coherent integration space-time adaptive processing (LTCI-STAP) is proposed for GEO SA-BSAR MTI in this paper. First, a modified adaptive spatial filtering based on the bistatic signal model is performed to suppress the clutter. Then, an LTCI filter bank is constructed to achieve range migration correction and moving target focusing, which yields the optimal output signal and filtering parameters. Finally, constant false alarm rate (CFAR) detection is carried out to determine the targets, and the space-variant Doppler parameters, solved from the filtering parameters, are used for estimating moving target positions and velocities. Simulations verify the effectiveness of our method.

Selective conversion of CO2 and H2 into aromatics remains challenging due to the high unsaturation degree and complex structure of aromatics. Here the authors report a composite catalyst of ZnAlOx and H-ZSM-5 which promotes the formation of aromatics with high selectivity while inhibiting CO and CH4 formation in CO2 hydrogenation reactions.

Abstract. Hematopoietic stem cells (HSCs) are responsible for generating all blood cells throughout life. Apart from the role of HSCs in maintaining the homeostasis of blood cell production process, they must respond quickly to hematopoietic challenges, such as infection or blood loss. HSCs can be directly/indirectly activated and engage in blood formation for the acute needs in response to inflammation. Recent findings highlight the emerging role of inflammation signaling on HSC fate decision and shaping the hematopoietic system during aging. Here, we summarize recent studies identifying the changes in inflammation and their role in modulation of HSC function and discuss the interaction between inflammation and HSC biology in the contexts of aging and hematological malignancy.

The abundant space, time, frequency and code resources of distributed multiple-input multiple-output (MIMO) synthetic aperture radar (SAR) enables it to bring various applications. The generalised ambiguity function (GAF) of distributed MIMO SAR is analysed. By equating the bistatic SAR to equivalent phase centre (EPC), the GAF can be expressed as sum of that of mostatic SAR. The influence of EPC's position on GAF is analysed, including its effects on amplitude items in range direction, in azimuth direction and phase item, and the boundary conditions of formation scale within which the envelope items are not affected are deduced. Furthermore, the phase in GAF is expressed as linear combinations of EPC position related to formation centre. The simulation results verify the negligibility of formation scale and show that the linear combination expression is accurate enough to evaluate the resolution.

Objective: This study aimed to determine the rates of different fetal chromosomal abnormalities among women of advanced maternal age in China and to discuss the possible misdiagnosis risks of newer molecular techniques, for selection of appropriate prenatal screening and diagnostic technologies. Materials and Methods: Second trimester amniocentesis and fetal karyotype results of 46,258 women were retrospectively reviewed. All women were ≥ 35 years old with singleton pregnancies. The rates of clinically significant chromosomal abnormalities (CSCAs), incidence of chromosomal abnormalities, and correlations with age were determined. Results: From 2001 to 2010, the proportion of women of advanced maternal age undergoing prenatal diagnosis increased from 20% to 46%. The mean age was 37.4 years (range, 35–46 years). A total of 708 cases of CSCAs, with a rate of 1.53% were found. Trisomy 21 was the most common single chromosome abnormality and accounted for 55.9% of all CSCAs with an incidence of 0.86%. Trisomy 13, trisomy 18, and trisomy 21, the most common chromosome autosomal aneuploidies, accounted for 73.6% of all CSCAs, with a rate of 1.13%. As a group, the most common chromosomal aneuploidies (13/18/21/X/Y) accounted for 93.9% of all abnormalities, with a rate of 1.44%. The incidence of trisomy 21, trisomy 13/18/21 as a group, and 13/18/21/X/Y as a group was significantly greater in women aged 39 years and older (p

The single-pass geosynchronous synthetic aperture radar interferometry (GEO InSAR) adopts the formation of a slave satellite accompanying the master satellite, which can reduce the temporal decorrelation caused by atmospheric disturbance and observation time gap between repeated tracks. Current formation design methods for spaceborne SAR are based on the Relative Motion Equation (RME) in the Earth-Centered-Inertial (ECI) coordinate system (referred to as ECI-RME). Since the Earth rotation is not taken into account, the methods will lead to a significant error for the baseline calculation while applied to formation design for GEO InSAR. In this paper, a formation design method for single-pass GEO InSAR based on Coordinate Rotational Transformation (CRT) is proposed. Through CRT, the RME in Earth-Centered-Earth-Fixed (ECEF) coordinate system (referred to as ECEF-RME) is derived. The ECEF-RME can be used to describe the accurate baseline of close-flying satellites for different orbital altitudes, but not limited to geosynchronous orbit. Aiming at the problem that ECEF-RME does not have a regular geometry as ECI-RME does, a numerical formation design method based on the minimum baseline error criterion is proposed. Then, an analytical formation design method is proposed for GEO InSAR, based on the Minimum Along-track Baseline Criterion (MABC) subject to a fixed root mean square of the perpendicular baseline. Simulation results verify the validity of the ECEF-RME and the analytical formation design method. The simulation results also show that the proposed method can help alleviate the atmospheric phase impacts and improve the retrieval accuracy of the digital elevation model (DEM) compared with the ECI-RME-based approach.

In this paper, low-heat Portland cement (LHC) clinkers were prepared by calcining raw materials at 1350°C for 2.0 hours, 1400°C for 1.0 hour, 1400°C for 1.5 hours, 1400°C for 2.0 hours, 1450°C for 1.0 hour, and 1450°C for 2.0 hours. The clinkers were ground with gypsum to produce LHC. The particle size of periclase was analysed by BSEM. Expansion of LHC pastes due to hydration of periclase was measured. The hydration degree of periclase in LHC pastes was quantitatively determined by XRD internal standard method and BSEM. The results showed that the particle size of periclase was larger when clinkers were calcined at higher temperatures or for longer time. Smaller periclase (2.60 μm) in LHC pastes tended to hydrate faster. As a result, expansion of LHC pastes develops relatively faster. Smaller particle of periclase in clinker tends to result in higher hydration degree of periclase in pastes cured at 20°C for 240 days, and there is a small amount of brucite appearing around periclase. The hydration rate of 4.00 μm periclase particle in cement paste cured at 80°C is obviously faster than that in paste cured at 20°C and 40°C. When cement paste was cured at 80°C for 7 days, the periclase was hydrated for 32.56%. The smaller size periclase (1–3 μm) had fully hydrated when the curing age was 240 days, and a large amount of brucite was produced around the larger periclase particle.

To promote the application of MgO-type expansive agents (MEAs), the expansion stresses produced by compacted MEAs with different activities cured in water at 40 °C were measured using a self-designed expansion stress test apparatus. Based on these, different MEAs were divided into the early-type MgO expansive agent and the late-type MgO expansive agent classifications according to the stress curves of compacted MEAs. The two types of MEAs were blended with each other at different ratios and added into cement pastes. Results indicated that the expansion of the cement pastes added with blended MEAs lasted from the beginning to 200 days later, and the expansion characteristics can be regulated by adjusting the blending ratio of MEAs and the choice of types of MEAs. The results suggest that the expansion of MEAs can be improved by using blended MEAs in practical applications.