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IntroductionCancer-associated fibroblasts (CAFs) are a diverse group of cells that significantly impact the tumor microenvironment and therapeutic responses in breast cancer (BC). Despite their importance, the comprehensive profile of CAFs in BC remains to be fully elucidated.MethodsTo address this gap, we utilized single-cell RNA sequencing (scRNA-seq) to delineate the CAF landscape within 14 BC normal-tumor paired samples. We further corroborated our findings by analyzing several public datasets, thereby validating the newly identified CAF subtype. Additionally, we conducted coculture experiments with BC cells to assess the functional implications of this CAF subtype.ResultsOur scRNA-seq analysis unveiled eight distinct CAF subtypes across five tumor and six adjacent normal tissue samples. Notably, we discovered a novel subtype, designated as SFRP4+ CAFs, which was predominantly observed in normal tissues. The presence of SFRP4+ CAFs was substantiated by two independent scRNA-seq datasets and a spatial transcriptomics dataset. Functionally, SFRP4+ CAFs were found to impede BC cell migration and the epithelial-mesenchymal transition (EMT) process by secreting SFRP4, thereby modulating the WNT signaling pathway. Furthermore, we established that elevated expression levels of SFRP4+ CAF markers correlate with improved survival outcomes in BC patients, yet paradoxically, they predict a diminished response to neoadjuvant chemotherapy in cases of triple-negative breast cancer.ConclusionThis investigation sheds light on the heterogeneity of CAFs in BC and introduces a novel SFRP4+ CAF subtype that hinders BC cell migration. This discovery holds promise as a potential biomarker for refined prognostic assessment and therapeutic intervention in BC.

In recent years, a substantial body of research has demonstrated the close relationship between the built environment and urban nighttime vitality. While scholars have established slightly varied evaluation systems for the built environment, most have utilized the open-source nighttime light (NTL) data (2012 ∼ ) from the Visible Infrared Imaging Radiometer Suite (VIIRS) sensor on the Suomi National Polar-orbiting Partnership (NPP) Satellite to characterize nighttime vitality. However, with the release of the high spatial resolution NTL data from Glimmer Imager for Urbanization (GIU) sensor on the Sustainable Development Goals Satellite 1 (SDGSAT-1) by the Chinese Academy of Sciences (CAS), more options are now available for indicating nighttime vitality. Yet, no studies have so far measured the representational capability of this new NTL data. In this study, we selected Shanghai, one of the most urbanized cities in Asia, as our research area. We utilized both GIU NTL data and VIIRS NTL data to represent nighttime vitality and collected multidimensional geospatial big data as indicators of the built environment. Various regression models were employed to explore the differences in explanatory power when using different NTL data. To obtain more reliable conclusions, we have also divided the study area according to urban functional zone categories and conducted experiments on both the overall scale (entire study area) and local scale (different urban functional zones). The results showed that regression models using GIU NTL data had higher R2 values both at overall scale(0.529 > 0.268) and local scale (0.704 > 0.641, 0.701 > 0.408, 0.537 > 0.512, 0.674 > 0.589), indicating stronger explanatory power of GIU NTL data. Furthermore, we found that the use of GIU NTL data revealed an amplification effect, where the impact of certain representative built environment factors (such as road density, building height, and vegetation coverage) on nighttime vitality was magnified, demonstrating more pronounced spatial heterogeneity. Our study investigated the performance of the new open-source SDGSAT1/GIU NTL data in representing nighttime vitality and shows its potential application in research on the relationship between the built environment and nighttime vitality. Additionally, our study also reveals the differences in the impact of the built environment on nighttime vitality across different urban functional zones. All these results will provide more valuable references for city managers aspiring to enhance the nighttime vitality and help them to make more rational planning plans.

Patients of colorectal cancer (CRC) with BRAF V600E mutation obtain poor prognosis. This study aimed to explore the role and mechanism of BRAF V600E mutation in angiogenesis of tumor micro-environment (TME). It has been reported that CXCL16 expression in TME is closely related to BRAF mutation. Clinicopathological features of CRC with BRAF V600E mutant or wild type were collected in this study. Immunohistochemistry (IHC) assays were conducted to test the expressions of vascular endothelial growth factor (VEGF), CD31 and CXCL16. ROC curve was used to determine the optimal cut off values of CXCL16. A total of 680 patients including 141 BRAF V600E type and 679 wild type were included. BRAF V600E mutant tumors were presented with significant worse clinicopathological features and a shorter overall survival (OS) than wild-type. Besides, chemokines CXCL16 was up-regulated in BRAF V600E mutant tissues and was associated with poorer prognosis. In addition, VEGF levels and vascular endothelial cell density was significantly increased in BRAF mutation. At last, CXCL16 was positively correlated with VEGF expression and vascular endothelial cell density. In conclusion, BRAF V600E mutations may promote metastasis of CRC by regulating CXCL16 expression and promoting angiogenesis in the TME.

Abstract Background Cyclic-dependent kinase (CDK) 4/6 kinases, as the critical drivers of the cell cycle, are involved in the tumor progression of various malignancies. Pharmacologic inhibitors of CDK4/6 have shown significant clinical prospects in treating hormone receptor-positive and human epidermal growth factor receptor-negative (HR + /HER2-) breast cancer (BC) patients. However, acquired resistance to CDK4/6 inhibitors (CDK4/6i), as a common issue, has developed rapidly. It is of great significance that the identification of novel therapeutic targets facilitates overcoming the CDK4/6i resistance. PARP1, an amplified gene for CDK4/6i-resistant patients, was found to be significantly upregulated during the construction of CDK4/6i-resistant strains. Whether PARP1 drives CDK4/6i resistance in breast cancer is worth further study. Method PARP1 and p-YB-1 protein levels in breast cancer cells and tissues were quantified using Western blot (WB) analysis, immunohistochemical staining (IHC) and immunofluorescence (IF) assays. Bioinformatics analyses of Gene Expression Profiling Interactive Analysis (GEPIA), Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE) datasets were applied to explore the relationship between YB-1/PARP1 protein levels and CDK4/6i IC50. Cell Counting Kit-8 (CCK-8) and crystal violet staining assays were performed to evaluate cell proliferation rates and drug killing effects. Flow cytometry assays were conducted to assess apoptosis rates and the G1/S ratio in the cell cycle. An EdU proliferation assay was used to detect the DNA replication ratio after treatment with PARP1 and YB-1 inhibitors. A ChIP assay was performed to assess the interaction of the transcription factor YB-1 and associated DNA regions. A double fluorescein reporter gene assay was designed to assess the influence of WT/S102A/S102E YB-1 on the promoter region of PARP1. Subcutaneous implantation models were applied for in vivo tumor growth evaluations. Results Here, we reported that PARP1 was amplified in breast cancer cells and CDK4/6i-resistant patients, and knockdown or inhibition of PARP1 reversed drug resistance in cell experiments and animal models. In addition, upregulation of transcription factor YB-1 also occurred in CDK4/6i-resistant breast cancer, and YB-1 inhibition can regulate PARP1 expression. p-YB-1 and PARP1 were upregulated when treated with CDK4/6i based on the WB and IF results, and elevated PARP1 and p-YB-1 were almost simultaneously observed during the construction of MCF7AR-resistant strains. Inhibition of YB-1 or PAPR1 can cause decreased DNA replication, G1/S cycle arrest, and increased apoptosis. We initially confirmed that YB-1 can bind to the promoter region of PARP1 through a ChIP assay. Furthermore, we found that YB-1 phosphorylated at S102 was crucial for PARP1 transcription according to the double fluorescein reporter gene assay. The combination therapy of YB-1 inhibitors and CDK4/6i exerted a synergistic antitumor effect in vitro and in vivo. The clinical data suggested that HR + /HER2- patients with low expression of p-YB-1/PARP1 may be sensitive to CDK4/6i in breast cancer. Conclusion These findings indicated that a ‘‘YB-1/PARP1’’ loop conferred resistance to CDK4/6 inhibitors. Furthermore, interrupting the loop can enhance tumor killing in the xenograft tumor model, which provides a promising strategy against drug resistance in breast cancer.

Antibiotic pollution in aqueous solutions seriously endangers the natural environment and public health. In this work, Mo-doped transition metal FeCo–Se metal aerogels (MAs) were investigated as bifunctional catalysts for the removal of sulfamethazine (SMT) in solution. The optimal Mo0.3Fe1Co3–Se catalyst can remove 97.7% of SMT within 60 min (SMT content: 10 mg/L, current intensity: 10 mA/cm2). The unique porous cross-linked structure of aerogel confered the catalyst sufficient active sites and efficient mass transfer channels. For the anode, Mo0.3Fe1Co3–Se MAs exhibits superior oxygen evolution reaction (OER) property, with an overpotential of only 235 mV (10 mA/cm2). Compared with Fe1Co3 MAs or Mo0.3Fe1Co3 MAs, density functional theory (DFT) demonstrated that the better catalytic capacity of Mo0.3Fe1Co3–Se MAs is attributed to the doping of Mo species and selenization lowers the energy barrier for the ∗OOH to O2 step in the OER process. Excellent OER performance ensures the self-oxygenation in this system, avoiding the addition of air or oxygen in the traditional electro-Fenton process. For the cathode, Mo doping can lead to the lattice contraction and metallic character of CoSe2, which is beneficial to accelerate electron transfer. The adjacent Co active sites effectively adsorb ∗OOH and inhibit the breakage of the O–O bond. Rotating ring disk electrode (RRDE) test indicated that Mo0.3Fe1Co3–Se MAs has an excellent 2e− ORR activity with H2O2 selectivity up to 88%, and the generated H2O2 is activated by the adjacent Fe site through heterogeneous Fenton process to generate ·OH.

Abstract Background The screening biomarkers for early detection of colorectal cancer (CRC) is lacking. The aim is to identify epigenetic silenced genes and clarify its roles and underlying mechanism in CRC. We conducted integrative analyses of epigenome-wide Human Methylation 450 K arrays and transcriptome to screen out candidate epigenetic driver genes with transcription silencing. Methylated silencing HAND2 were identified and verified in large CRC cohort. The mechanism of HAND2 expression by promoter inhibition were clarified both in vitro and vivo assays. Cell biofunctional roles of HAND2 methylation was investigated in CRC cells. HAND2 reconstitution were constructed by lentivirus plasmid and tumor xenograft model of HAND2 were built subcutaneously. Genomic mRNA analysis by RNA-sequencing and subsequent GSEA analysis were performed to identify potential target of HAND2 and qPCR/WB was conducted to identify the results. Results We firstly reported high frequency of HAND2 methylation in promoter in CRC and hypermethylation was negatively correlated with expression silencing and leaded to poor survival in several CRC cohort patients. 5-Aza treatment to demethylated HAND2 could revert its expression in CRC cells. Functionally, HAND2 reconstitution can inhibit cell proliferation, invasion and migration in vitro. In tumor xenograft, HAND2 reconstruction significantly repressed tumor growth when compared to control vector. Thousands of aberrant expressed genes were observed in the heatmap of RNA-sequencing data. HAND2 reconstitution could bind to ERK and reduce its phosphorylation by CoIP assay. These above results showed HAND2 reconstitution perturbed the activation of MAPK/ERK signaling by reduction of ERK phosphorylation. Conclusions HAND2 is one tumor suppressor by targeting ERK signaling and one potential epigenetic driver gene in CRC. Video Abstract

T cell large granular lymphocyte leukemia (T-LGLL) and the cellular phenotype underlying response to therapy is not well understood. Here the authors use single cell sequencing to better understand changes in T cell clonal frequency and gene expression before and after therapy in T-LGLL.

Abstract Background Although both copy number variations (CNVs) and single nucleotide variations (SNVs) detected by single-cell RNA sequencing (scRNA-seq) are used to study intratumor heterogeneity and detect clonal groups, a software that integrates these two types of data in the same cells is unavailable. Results We developed Clonal Architecture with Integration of SNV and CNV (CAISC), an R package for scRNA-seq data analysis that clusters single cells into distinct subclones by integrating CNV and SNV genotype matrices using an entropy weighted approach. The performance of CAISC was tested on simulation data and four real datasets, which confirmed its high accuracy in sub-clonal identification and assignment, including subclones which cannot be identified using one type of data alone. Furthermore, integration of SNV and CNV allowed for accurate examination of expression changes between subclones, as demonstrated by the results from trisomy 8 clones of the myelodysplastic syndromes (MDS) dataset. Conclusions CAISC is a powerful tool for integration of CNV and SNV data from scRNA-seq to identify clonal clusters with better accuracy than obtained from a single type of data. CAISC allows users to interactively examine clonal assignments.

BackgroundTo date, the value of hyperthermic intraperitoneal chemotherapy (HIPEC) following up-front resection for isolated synchronous colorectal peritoneal metastases seems controversial.Patients and MethodsThis retrospective cohort study was conducted from September 1, 2012, to September 1, 2019, at a tertiary medical center in China. Patients with isolated synchronous colorectal peritoneal metastases were included in CRS plus HIPEC group or CRS alone group based on the treatment history. Overall survival and relapse-free survival were estimated using Cox proportional hazards regression analysis and Kaplan–Meier method.Results78 patients with isolated synchronous colorectal peritoneal metastases were identified among 396 patients with synchronous colorectal peritoneal metastases. 43 were in the cytoreductive surgery plus HIPEC group and 35 were in the cytoreductive surgery alone group. Among them, 61 patients had relapse-free survival data. The median peritoneal cancer index was 4 in all patients. After a median follow-up of 46.0 months, 5-year overall survival was 66.8% and the median relapse-free survival was 36.0 (95% CI, 6.8-65.1) months in the CRS plus HIPEC group. 5-year overall survival was 31.2% and the median relapse-free survival was 12.0 (95% CI, 9.0-15.0) months in the CRS alone group. Cox regression analyses showed that HIPEC was the independent prognostic factor for overall survival (P = 0.004) and relapse-free survival (P = 0.049).ConclusionFindings of the present study suggest that HIPEC following up-front CRS could improve overall survival and relapse-free survival in patients with isolated synchronous colorectal peritoneal metastases.

BackgroundThe early diagnosis of occult peritoneal metastasis (PM) remains a challenge due to the low sensitivity on computed tomography (CT) images. Exploratory laparoscopy is the gold standard to confirm PM but should only be proposed in selected patients due to its invasiveness, high cost, and port-site metastasis risk. In this study, we aimed to develop an individualized prediction model to identify occult PM status and determine optimal candidates for exploratory laparoscopy.MethodA total of 622 colorectal cancer (CRC) patients from 2 centers were divided into training and external validation cohorts. All patients’ PM status was first detected as negative on CT imaging but later confirmed by exploratory laparoscopy. Multivariate analysis was used to identify independent predictors, which were used to build a prediction model for identifying occult PM in CRC. The concordance index (C-index), calibration plot and decision curve analysis were used to evaluate its predictive accuracy and clinical utility.ResultsThe C-indices of the model in the development and validation groups were 0.850 (95% CI 0.815-0.885) and 0.794 (95% CI, 0.690-0.899), respectively. The calibration curve showed consistency between the observed and predicted probabilities. The decision curve analysis indicated that the prediction model has a great clinical value between thresholds of 0.10 and 0.72. At a risk threshold of 30%, a total of 40% of exploratory laparoscopies could have been prevented, while still identifying 76.7% of clinically occult PM cases. A dynamic online platform was also developed to facilitate the usage of the proposed model.ConclusionsOur individualized risk model could reduce the number of unnecessary exploratory laparoscopies while maintaining a high rate of diagnosis of clinically occult PM. These results warrant further validation in prospective studies.Clinical Trial Registrationhttps://www.isrctn.com, identifier ISRCTN76852032

Abstract Background Presently, there is no comprehensive analysis of the transcription regulation network in hematopoiesis. Comparison of networks arising from gene co-expression across species can facilitate an understanding of the conservation of functional gene modules in hematopoiesis. Results We used single-cell RNA sequencing to profile bone marrow from human and mouse, and inferred transcription regulatory networks in each species in order to characterize transcriptional programs governing hematopoietic stem cell differentiation. We designed an algorithm for network reconstruction to conduct comparative transcriptomic analysis of hematopoietic gene co-expression and transcription regulation in human and mouse bone marrow cells. Co-expression network connectivity of hematopoiesis-related genes was found to be well conserved between mouse and human. The co-expression network showed “small-world” and “scale-free” architecture. The gene regulatory network formed a hierarchical structure, and hematopoiesis transcription factors localized to the hierarchy’s middle level. Conclusions Transcriptional regulatory networks are well conserved between human and mouse. The hierarchical organization of transcription factors may provide insights into hematopoietic cell lineage commitment, and to signal processing, cell survival and disease initiation.

Abstract A pot experiment was used to explore the distribution of fertilizer N and agronomic effects in a paddy soil-rice (Oryza sativa L.) system. Five treatments were set: without nitrogen, straw and inhibitor (C), urea (U), urea + straw (US), urea + urease + nitrification inhibitor (UI) and urea + urease + nitrification inhibitor + straw (UIS). Soil and urea-derived microbial biomass N increased significantly in US and UIS compared with straw-free treatments at seedling and tillering, indicating that biotic process play an important role in the retention of fertilizer N with straw addition. About 10% urea-N was recovered as fixed ammonium (FA) at seedling stage, subsequently released at tillering and maturation regardless of treatments, which emphasizes the importance of FA in the retention and supply of fertilizer N in paddy soils. Compared with U, rice yield and N uptake in US decreased by 7.8% and 25.2% respectively, while inhibitors (UIS) alleviated the reduction by 16.4% and 31.6%. The current research indicated UIS is recommended as the most appropriate management strategy in paddy soils of Northeast China based on N dynamics. But the economic effect as well as the field-scale validation need to be further evaluated.

BackgroundMicrosatellite has been proved to be an important prognostic factor and a treatment reference in colon cancer. The transcriptome profile and tumor microenvironment of different microsatellite statuses are different. Metastatic colon cancer patients with microsatellite instability-high (MSI-H) are sensitive to immune checkpoint inhibitors (ICIs), but not fluorouracil. Efforts have been devoted to identify the predictive factors of immunotherapy.MethodsWe analyzed the transcriptome profile of different microsatellite statuses in colon cancer by using single-cell and bulk transcriptome data from publicly available databases. The immune cells in the tumor microenvironment were analyzed by the ESTIMATION algorithm. The microsatellite-related gene signature (MSRS) was constructed by the least absolute shrinkage and selection operator (LASSO) Cox regression based on the differentially expressed genes (DEGs) and its prognostic value and predictive value of response to immunotherapy were assessed. The prognostic value of the MSRS was also validated in another cohort.ResultsThe MSI-H cancers cells were clustered differentially in the dimension reduction plot. Most of the immune cells have a higher proportion in the tumor immune microenvironment, except for CD56 bright natural killer cells. A total of 238 DEGs were identified. Based on the 238 DEGs, a neural network was constructed with a Kappa coefficient of 0.706 in the testing cohort. The MSRS is a favorable prognostic factor of overall survival, which was also validated in another cohort (GSE39582). Besides, MSRS is correlated with tumor mutation burden in MSI-H colon cancer. However, the MSRS is a barely satisfactory factor in predicting immunotherapy with the area under the curve (AUC) of 0.624.ConclusionWe developed the MSRS, which is a robust prognostic factor of overall survival in spite of a barely satisfactory immunotherapy predictor. Further studies may need to improve the predictive ability.

Abstract Objective Single cell methodology enables detection and quantification of transcriptional changes and unravelling dynamic aspects of the transcriptional heterogeneity not accessible using bulk sequencing approaches. We have applied single-cell RNA-sequencing (scRNA-seq) to fresh human bone marrow CD34+ cells and profiled 391 single hematopoietic stem/progenitor cells (HSPCs) from healthy donors to characterize lineage- and stage-specific transcription during hematopoiesis. Results Cells clustered into six distinct groups, which could be assigned to known HSPC subpopulations based on lineage specific genes. Reconstruction of differentiation trajectories in single cells revealed four committed lineages derived from HSCs, as well as dynamic expression changes underlying cell fate during early erythroid-megakaryocytic, lymphoid, and granulocyte-monocyte differentiation. A similar non-hierarchical pattern of hematopoiesis could be derived from analysis of published single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), consistent with a sequential relationship between chromatin dynamics and regulation of gene expression during lineage commitment (first, altered chromatin conformation, then mRNA transcription). Computationally, we have reconstructed molecular trajectories connecting HSCs directly to four hematopoietic lineages. Integration of long noncoding RNA (lncRNA) expression from the same cells demonstrated mRNA transcriptome, lncRNA, and the epigenome were highly homologous in their pattern of gene activation and suppression during hematopoietic cell differentiation.

Top-down proteomics can provide unique insights into the biological variations of protein biomarkers but detecting low-abundance proteins in body fluids remains challenging. Here, the authors develop a nanoparticle-based top-down proteomics approach enabling enrichment and detailed analysis of cardiac troponin I in human serum.

A long time-series land surface temperature (LST) product is useful for ecological and environmental studies. However, current LST products cannot provide a global coverage at a fine spatial resolution (~100 m) over a long period (>30 years). Landsat series satellites that have been launched since 1972 provide a unique opportunity to fill the gap. Here, we proposed a single-channel framework for producing global long time-series Landsat LST retrievals on a Google earth engine (GEE) cloud computing platform. This framework unifies the LST, land surface emissivity (LSE) and atmospheric water vapor (AWV) estimation algorithms, as well as the emissivity and atmospheric input data for the Landsat LST retrievals from the entire Landsat thermal infrared image archive. In situ LST measurements and the MODIS LST products were employed to evaluate Landsat LST retrievals using the proposed framework over land and water surfaces, respectively. In total, 1317 clear-sky LST samples were collected from the Landsat 5-8 series after spatiotemporal registration with seven sites, and the average bias and root-mean-square error (RMSE) were 0.33 and 2.01 K, respectively. Intercomparison between Landsat and MODIS LST retrievals based on 100 clear-sky scenes over 12 inland lakes showed an average bias of 0.17 K and RMSE of 1.11 K. We conclude that the proposed single-channel framework can produce Landsat LST with high accuracy following a simple yet robust way. Implementation of the single-channel method on GEE shows promise in providing the community with freely accessible and global long time-series (>30 years) LST data.

Application of nitrification inhibitors (NIs) with nitrogen (N) fertilizer is one of the most efficient ways to improve nitrogen use efficiency (NUE). To fully understand the efficiency of NIs with N fertilizer on soil nitrification, yield and NUE of maize (Zea mays L.), an outdoor pot experiment with different NIs in three soils with different pH was conducted. Five treatments were established: no fertilizer (Control); ammonium sulfate (AS); ammonium sulfate + 3, 4-dimethyl-pyrazolate phosphate (DMPP) (AD); ammonium sulfate + nitrogen protectant (N-GD) (AN); ammonium sulfate + 3, 4-dimethyl-pyrazolate phosphate + nitrogen protectant (ADN). The results showed that NIs treatments (AD, AN and ADN) significantly reduced soil nitrification in the brown and red soil, especially in AD and ADN, which decreased apparent nitrification rate by 28% - 44% (P < 0.05). All NIs treatments significantly increased yield and NUE of maize in three soils, especially ADN in the cinnamon soil and AD in the red soil were more efficiency, which significantly increased maize yield and apparent nitrogen recovery by 5.07 and 6.81 times, 4.39 and 8.16 times, respectively. No significant difference on maize yield was found in the brown soil, but AN significantly increased apparent nitrogen recovery by 70%. Given that the effect of NIs on both soil nitrification and NUE of maize, DMPP+N-GD was more efficient in the cinnamon soil, while N-GD and DMPP was the most efficiency in the brown and red soil, respectively. In addition, soil pH and soil organic matter play important role in the efficiency of NIs.

This paper introduces some experimental data measured from 63 impact tests of pre−stressed strand cables. The test specimens consist of seven steel wires that have a length equivalent to 100 times the outside diameter. To ensure consistency with the engineering service status, the strand cables are fully installed in a specially designed device and are axially pre−stretched to 0% to 40% of the ultimate bearing capacity before being subjected to lateral impact. The mass of the indenter is 50.34 kg, and the maximum impact velocity reaches 13 m/s. Two dimensionless variables, axial force and input kinetic energy, are used to control the experimental parameters. The recorded test data show that input energy and pre−stress level are the key factors governing the impact behavior, which is mainly characterized by plastic deformation controlled by the combination of tension and flexure, and the dynamic fracture concentrated in the impact zone is controlled by the joint effects of compression, tension and shear. As the impact energy increases, the dynamic mode of the test specimen changes from elastic rebound to plastic deformation, and finally evolves into fracture of some or all steel wires, which correspond to slight, partial and total loss of pre−tension, respectively. An increase in the level of pre−stress will significantly reduce the critical displacement of the structural failure but has little effect on the critical failure energy. The present paper provides a basic experimental data and mechanical analysis framework for the analysis, design and evaluation of the mechanical behavior of strands under accidental lateral impact.

A field experiment was conducted to study the effects of stabilized nitrogen fertilizer combined with pig manure on rice yield and nitrous oxide (N2O) and methane (CH4) emissions. Four treatments were established: urea (U); pig manure (PM); PM and urea (PM + U); PM and stabilized nitrogen fertilizer (urea plus 1% NBPT (N-(n-butyl) thiophosphoric triamide), 1% PPD (phenylphosphorodiamidate) and 2% DMPP (3,4-dimethylpyrazole phosphate)) (PM + U + I). In this study, compared with PM, PM + U significantly increased cumulative N2O emission, but PM + U + I showed no significant difference from PM on N2O cumulative emission, indicating that stabilized nitrogen fertilizer combined with PM is effective at reducing N2O emissions. The cumulative emission of CH4 from PM + U + I treatment was significantly lower than that from PM and PM + U, indicating that stabilized nitrogen fertilizer combined with PM can effectively reduce CH4 emissions as well. The yields of PM + U and PM + U + I were not significantly different from those of U and PM, indicating that local conventional nitrogen application and returns of PM can provide sufficient nitrogen for rice growth. For yield-scaled emissions (YSE), PM was the highest, while PM + U + I significantly decreased YSE. Concomitant application of stabilized nitrogen fertilizer can achieve the goal of reducing YSE when PM is returned to the field.

Heterocyclic nitrogen compounds containing two adjacent nitrogen atoms generally have a significant effect on soil nitrification inhibition, and 3,5-dimethylpyrazole (DMP) is a typical representative of this structure. However, the inhibitory effect and the regulatory mechanism of DMP on soil N transformation are unclear. In this study, a microcosm with different concentrations of DMP was carried out in brown soil to detect the dynamic changes of soil NH4+–N, NO3–N and related soil enzyme activities. Results showed that DMP inhibited soil nitrification effectively and decreased soil nitrate reductase activity, while increasing nitrite reductase and dehydrogenase activities. The inhibition effects were dose dependent, and DMP at the rate of 0.025 g kg−1 dry soil showed the strongest inhibitory effect on N transformation in brown soil. The soil dehydrogenase activity was increased with an increasing DMP application rate. The changes in the soil’s chemical and biological properties caused by DMP application provided a new idea for systematically explaining how DMP participated in the soil N transformation process. This study further implied that DMP would play positive roles in alleviating environmental pressure by delaying nitrate-N formation and decreasing the activity of nitrate reductase.

The application of nitrification inhibitors (NIs) based on ammonium (NH4+) is considered to be an efficient way to reduce nitrogen (N) loss by delaying the nitrification process through influencing ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). However, the inhibition mechanisms of NIs on AOA and AOB in different soils remain unclear. Hence, we explored the two commonly used NIs (3, 4-dimethylepyrazole phosphate (DMPP) and dicyandiamide (DCD) and their combination (DMPP + DCD) on the soil nitrification and abundance of ammonia oxidizers (AOA and AOB) in three black soils (HLJ, NA, and DA) with different physicochemical properties using a 120-day incubation experiment. The results demonstrated that NIs significantly increased NH4+-N concentrations and decreased NO3−-N concentrations in all three tested soils. There was no significant difference in inhibiting nitrification in HLJ among all NI treatments, while DCD was more efficient in NA, DMPP + DCD had better efficiency in DA. The potential nitrification rate (PNR) was greatly decreased by NIs addition, and PNR was significantly positively correlated with AOB (p < 0.05). AOA was dominant in the acid soil. All NI treatments significantly inhibited soil nitrification through inhibiting the growth of AOB in the two soils with higher pH. The abundance of AOA and AOB was significantly correlated with different soil types (positively correlated with soil pH, and negatively correlated with organic matter). Moreover, soil pH and soil organic matter were considered to be the most important factors influencing the inhibition efficiency of NIs and the abundance of AOA and AOB. The application of the NIs combination (DMPP + DCD) was considered to be the most cost-effective way to inhibit soil nitrification in soil with higher pH and lower SOM, which provides a theoretical basis for a field experiment.

The application of nitrification inhibitors (NIs) is considered to be an efficient way to delay nitrification, but the effect of NIs combinations on soil nitrification and ammonia (NH3) volatilization are not clear in soils with different pH values. In this study, we explored the effect of nitrapyrin (CP) and its combinations with 3, 4-dimethylepyrazole phosphate (DMPP), dicyandiamide (DCD) on the transformation of nitrogen, potential nitrification rate (PNR), and ammonia (NH3) volatilization in a 120-day incubation experiment with three different pH values of black soil. Treatments included no fertilizer (Control), ammonium sulfate (AS), AS+CP (CP), AS+CP+DMPP (CP+DMPP), and AS+CP+DCD (CP+DCD). The application of NIs significantly decreased NO3−-N contents and potential nitrification rate (p < 0.05), while significantly increased NH4+-N contents (p < 0.05), especially CP+DCD and CP+DMPP were the most effective in the neutral and alkaline soils, respectively. In the acid soil, CP significantly increased total NH3 volatilization by 31%, while CP+DCD significantly reduced by 28% compared with AS. However, no significant difference was found in NH3 volatilization with and without NIs treatments (p > 0.05) in the neutral and alkaline soils. In conclusion, the combined nitrification inhibitors had the better efficiency in all three tested soils. CP+DCD and CP+DMPP are the most effective in inhibiting soil nitrification in the clay soils with higher pH value and lower organic matter, while CP+DCD had the potential in mitigating environment pollution by reducing N loss of NH3 volatilization in the loam soil with lower pH value and higher organic matter. It provided a theoretical basis for the application of high efficiency fertilizer in different soils. Further studies under field conditions are required to assess the effects of these nitrification inhibitors.

Long noncoding RNAs (lncRNAs) are regulators of cell differentiation and development. The lncRNA transcriptome in human hematopoietic stem and progenitor cells is not comprehensively defined. We investigated lncRNAs in 979 human bone marrow-derived CD34+ cells by single cell RNA sequencing followed by de novo transcriptome reconstruction. We identified 3,173 lncRNAs in total, among which 2,365 were previously unknown, and we characterized lncRNA stem, differentiation, and maturation signatures. lncRNA expression exhibited high cell-to-cell variation, which was only apparent in single cell analysis. lncRNA expression followed a lineage-specific and highly dynamic pattern during early hematopoiesis. lncRNAs in hematopoietic cells closely correlated with protein-coding genes of known functions in the regulation of hematopoiesis and cell fate decisions, and the potential regulatory roles of lncRNAs in hematopoiesis were imputed by projection from protein-coding genes with a “guilt-by-association” approach. We characterized lncRNAs preferentially expressed in hematopoietic stem cells and in various downstream differentiated lineage progenitors. We also profiled lncRNA expression in single cells from patients with myelodysplastic syndromes and in aneuploid cells in particular. Our study provides a global view of lncRNAs in human hematopoietic stem and progenitor cells. We observed a highly ordered pattern of lncRNA expression and participation in regulation of early hematopoiesis, and coordinate aberrant messenger RNA and lncRNA transcriptomes in dysplastic hematopoiesis. (Registered at clinicaltrials.gov with identifiers: 00001620, 00001397)

(1) Background: mouse models are fundamental to the study of hematopoiesis, but comparisons between mouse and human in single cells have been limited in depth. (2) Methods: we constructed a single-cell resolution transcriptomic atlas of hematopoietic stem and progenitor cells (HSPCs) of human and mouse, from a total of 32,805 single cells. We used Monocle to examine the trajectories of hematopoietic differentiation, and SCENIC to analyze gene networks underlying hematopoiesis. (3) Results: After alignment with Seurat 2, the cells of mouse and human could be separated by same cell type categories. Cells were grouped into 17 subpopulations; cluster-specific genes were species-conserved and shared functional themes. The clustering dendrogram indicated that cell types were highly conserved between human and mouse. A visualization of the Monocle results provided an intuitive representation of HSPC differentiation to three dominant branches (Erythroid/megakaryocytic, Myeloid, and Lymphoid), derived directly from the hematopoietic stem cell and the long-term hematopoietic stem cells in both human and mouse. Gene regulation was similarly conserved, reflected by comparable transcriptional factors and regulatory sequence motifs in subpopulations of cells. (4) Conclusions: our analysis has confirmed evolutionary conservation in the hematopoietic systems of mouse and human, extending to cell types, gene expression and regulatory elements.

Cover crop management during the fallow season may play a relevant role in improving crop productivity and soil quality, by increasing nitrogen (N) and soil organic carbon (SOC) accumulation, but has the possibility of increasing greenhouse gas (GHG) emissions from the soil. A year-long consistency experiment was conducted to examine the effects of various winter covering crops on annual nitrous oxide (N2O) together with methane (CH4) emissions in the mono-rice planting system, including direct emissions in the cover crop period and the effects of incorporating these crops on gaseous emissions during the forthcoming rice (Oryza Sativa L.) growing period, to improve the development of winter fallow paddy field with covering crops and to assess rice cultivation patterns. The experiment included three treatments: Chinese milk vetch-rice (Astragalus sinicus L.) with cover crop residue returned (T1), ryegrass (Lolium multiflorum L.)-rice with cover crop residue returned (T2), and rice with winter fallow (CK). Compared with CK, the two winter cover crop treatments significantly increased rice yield, soil organic carbon (SOC) and total nitrogen (TN) by 6.9–14.5%, 0.8–2.1% and 3.4–5.4%, respectively. In all cases, the fluxes of CH4 and N2O could increase with the incorporation of N fertilizer application and cover crop residues. Short-term peaks of these two gas fluxes were monitored after all crop residues were incorporated in the soil preparation period, the early vegetative growth period and the midseason drainage period. The winter cover crop residue application greatly enhanced CH4 and N2O cumulative emissions compared with CK (by 193.6–226.5% and 37.5–43.7%, respectively) during rice growing season and intercropping period. Meanwhile, the mean values of global warming potentials (GWPs) from paddy fields with different cropping crops were T2 > T1 > CK. Considering the advantages of crop productivity together with environmental safety and soil quality, Chinese milk vetch-rice with cover crop residue returned would be the most practicable and sustainable cultivation pattern for the mono-rice cropping systems.

This study investigated the influence of nitrogen (N) fertilizer and straw on intact amino acid N uptake by soil microorganisms and the relationship between amino acid turnover and soil properties during the wheat growing season. A wheat pot experiment was carried out with three treatments: control (CK), N fertilizer (NF) and N fertilizer plus rice straw (NS). We used stable isotope compound-specific analysis to determine the uptake of 13C,15N-glycine by soil microorganisms. In the NF treatment, microbial 13C,15N-glycine uptake was lower compared with CK, suggesting that inorganic N was the preferred N source for soil microorganisms. However, The application of straw with N fertilizer (in NS treatment) increased microbial 13C,15N-glycine uptake even with the same amount of N fertilizer application. In this treatment, enzyme activities, soil microbial biomass C and microbial biomass N increased simultaneously because more C was available. Soil mineral N and plant N contents all decreased substantially. The increased uptake of intact 13C,15N-glycine in the NS treatment can be attributed to direct assimilation by soil microorganisms to satisfy the demand for N when inorganic N was consumed.

A field experiment was carried out to evaluate the effect of organic amendments on soil organic carbon, total nitrogen, bulk density, aggregate stability, field capacity and plant available water in a representative Chinese Mollisol. Four treatments were as follows: no fertilization (CK), application of inorganic fertilizer (NPK), combined application of inorganic fertilizer with maize straw (NPK+S) and addition of biochar with inorganic fertilizer (NPK+B). Our results showed that after three consecutive years of application, the values of soil bulk density were significantly lower in both organic amendment-treated plots than in unamended (CK and NPK) plots. Compared with NPK, NPK+B more effectively increased the contents of soil organic carbon, improved the relative proportion of soil macro-aggregates and mean weight diameter, and enhanced field capacity as well as plant available water. Organic amendments had no obvious effect on soil C/N ratio or wilting coefficient. The results of linear regression indicated that the improvement in soil water retention could be attributed to the increases in soil organic carbon and aggregate stability.

Soil β-glucosidase participates in the final step of cellulose biodegradation. It is significant in the soil C cycle and is used as an indicator of the biological fertility of soil. However, the response of its kinetic parameters to environmental temperature and moisture regimes is not well understood. This study tested the β-glucosidase response in the main agricultural soils (black soil, albic soil, brown soil, and cinnamon soil) of Northeast China. Incubation tests were conducted to measure the kinetic parameters Km, Vmax or Vmax/Km of soil β-glucosidase at environmental temperatures of 10, 20 and 30 ºC and at 10, 20 and 30 % soil moisture content. The insensitive response of the kinetic parameters to temperature changes indicates that soil β-glucosidase was present primarily in immobilized form. The significant response of the kinetic parameters of soil β-glucosidase to soil moisture rather than to environmental temperatures suggests that the catalytic ability of soil β-glucosidase was sensitive to changing soil moisture regimes.

Near surface air temperature (NSAT) is a primary descriptor of terrestrial environmental conditions. In recent decades, many efforts have been made to develop various methods for obtaining spatially continuous NSAT from gauge or station observations. This study compared three spatial interpolation (i.e., Kriging, Spline, and Inversion Distance Weighting (IDW)) and two regression analysis (i.e., Multiple Linear Regression (MLR) and Geographically Weighted Regression (GWR)) models for predicting monthly minimum, mean, and maximum NSAT in China, a domain with a large area, complex topography, and highly variable station density. This was conducted for a period of 12 months of 2010. The accuracy of the GWR model is better than the MLR model with an improvement of about 3 °C in the Root Mean Squared Error (RMSE), which indicates that the GWR model is more suitable for predicting monthly NSAT than the MLR model over a large scale. For three spatial interpolation models, the RMSEs of the predicted monthly NSAT are greater in the warmer months, and the mean RMSEs of the predicted monthly mean NSAT for 12 months in 2010 are 1.56 °C for the Kriging model, 1.74 °C for the IDW model, and 2.39 °C for the Spline model, respectively. The GWR model is better than the Kriging model in the warmer months, while the Kriging model is superior to the GWR model in the colder months. The total precision of the GWR model is slightly higher than the Kriging model. The assessment result indicated that the higher standard deviation and the lower mean of NSAT from sample data would be associated with a better performance of predicting monthly NSAT using spatial interpolation models.

In order to discover the advantages and disadvantages of different fertilization regimes and identify the best management practice of fertilization in greenhouse fields, soil enzyme activities involved in carbon (C) transformations, soil chemical characteristics, and crop yields were monitored after long-term (20-year) fertilization regimes, including no fertilizer (CK), 300 kg N ha-1 and 600 kg N ha-1 as urea (N1 and N2), 75 Mg ha-1 horse manure compost (M), and M with either 300 or 600 kg N ha-1 urea (MN1 and MN2). Compared with CK, fertilization increased crop yields by 31% (N2) to 69% (MN1). However, compared with CK, inorganic fertilization (especially N2) also caused soil acidification and salinization. In the N2 treatment, soil total organic carbon (TOC) decreased from 14.1±0.27 g kg-1 at the beginning of the long-term experiment in 1988 to 12.6±0.11 g kg-1 (P