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Abstract The ovary is crucial for female reproduction and health, as it generates oocytes and secretes sex hormones. Transplantation of mesenchymal stem cells (MSCs) has been shown to alleviate pathological ovarian aging. However, it is unclear whether MSCs could benefit the naturally aging ovary. In this study, we first examined the dynamics of ovarian reserve of Chinese women during perimenopause. Using a naturally aging cynomolgus monkey (Macaca fascicularis) model, we found that transplanting human embryonic stem cells-derived MSC-like cells, which we called M cells, into the aging ovaries significantly decreased ovarian fibrosis and DNA damage, enhanced secretion of sex hormones and improved fertility. Encouragingly, a healthy baby monkey was born after M-cell transplantation. Moreover, single-cell RNA sequencing analysis and in vitro functional validation suggested that apoptosis, oxidative damage, inflammation, and fibrosis were mitigated in granulosa cells and stromal cells following M-cell transplantation. Altogether, these findings demonstrate the beneficial effects of M-cell transplantation on aging ovaries and expand our understanding of the molecular mechanisms underlying ovarian aging and stem cell-based alleviation of this process.

Incident shortwave radiation can penetrate and heat the upper ocean water column, acting to modulate the stratification, vertical mixing and sea surface temperature. As a light-absorbing constituent, ocean chlorophyll (CHL) plays an important role in regulating these processes; however, its heating effect on the ocean state remains controversial and exhibits strong model dependence on ways the solar radiation transmission and the related CHL-induced heating are represented. In this study, we implement a chlorophyll-based two-way coupling between physical and ecological processes within the Regional Ocean Modeling System (ROMS). The bio-physics coupled model performs well in simulating the structure and variability of oceanic physical and ecological fields in the tropical Indo-Pacific region. Three CHL-related heating terms are analyzed based on the model output to diagnose the ocean biology-induced heating effects, namely the shortwave radiation part penetrating out of the base of the mixed layer (ML; Qpen), the portion absorbed within the ML (Qabs), and the rate of temperature change of the ML resulting from the Qabs effects (Rsr). Results show that the spatio-temporal distributions of the three heating terms are mainly determined by the ML depth (MLD). However, Qpen can also be regulated by the euphotic depth (ED), especially in the western-central equatorial Pacific. This moderating effect is particularly evident during El Niño when the ED tends to be greater than the MLD; positive ED anomalies act to enhance the positive Qpen anomalies caused by negative MLD anomalies. For the first time, the bio-heating effects are quantified within the ROMS-based two-way coupling context between the physical submodel and ecological submodel over the tropical Indo-Pacific Ocean, providing a basis for further understanding of the bio-effects and mechanisms. It is expected that the methodology and understanding developed in this study can help explore the chlorophyll-related processes in the ocean and the interactions with the atmosphere.

IntroductionThe implementation of ecological agriculture practices in Chinese tea gardens plays a vital role in mitigating N2O emissions and addressing environmental degradation. Nevertheless, a dearth of discourse exists regarding the intricacies surrounding farmers' adoption of tea garden ecological agriculture practices (TGEAP), particularly the complex interplay between adoption factors and outcomes.MethodsUsing data of 310 farmers, this study employed complexity theories and Stimulus-Organism-Response theories, and integrated Partial Least Squares Structural Equation Modeling and fuzzy-set Qualitative Comparative Analysis to explore the complex relationships between farmer characteristics, internal and external factors, and adoption of farmer.ResultsThe results show three influential paths in the Stimulus-Organism-Response model, and environmental protection attitude (EPA) and production expectation (PE) act as intermediaries. Notably, EPA exhibits a masking effect in one pathway. These paths linked closely to three farmer characteristics. Beyond the Stimulus-Organism-Response model, nine combinations lead to farmers' adoption, and four to non-adoption.DiscussionWe discover scenarios where opposing environmental states or age lead to adoption, explaining the masking effect. These combinations highlight how a favorable environment influences both adoption and non-adoption. We also discuss other combinations that lead to adoption or non-adoption. The study suggests that governments employ targeted incentives to facilitate tea farmers' transition in agriculture.

Abstract Triple-negative breast cancer (TNBC) is more aggressive and has a higher metastasis rate compared with other subtypes of breast cancer. Due to the lack of drug-targetable receptors, chemotherapy is now the only available systemic treatment for TNBC. However, some patients might still develop drug resistance and have poor prognosis. Therefore, novel molecular biomarkers and new treatment targets are urgently needed for patients with TNBC. To provide molecular insights into TNBC progression, we investigated the function and the underlying mechanism of Defective in cullin neddylation 1 domain containing 5 (DCUN1D5) in the regulation of TNBC. By TCGA dataset and surgical specimens with immunohistochemical (IHC) staining method, DCUN1D5 was identified to be significantly upregulated in TNBC tumor tissues and negatively associated with prognosis. A series of in vitro and in vivo experiments were performed to confirm the oncogenic role of DCUN1D5 in TNBC. Overexpression of FN1 or PI3K/AKT activator IGF-1 could restore the proliferative and invasive ability induced by DCUN1D5 knockdown and DCUN1D5 could act as a novel transcriptional target of transcription factor Yin Yang 1 (YY1). In conclusion, YY1-enhanced DCUN1D5 expression could promote TNBC progression by FN1/PI3K/AKT pathway and DCUN1D5 might be a potential prognostic biomarker and therapeutic target for TNBC treatment.

Abstract Based on observations from the Magnetospheric Multiscale mission, this study presents an analysis of a short large‐amplitude magnetic structures (SLAMS) event with simultaneous occurrence of low‐ and high‐frequency magnetosonic whistler waves. It was found that low‐frequency magnetosonic whistler waves around the lower‐hybrid frequency emerge in the presence of solar wind ions and local low‐energy ions in the trailing region of SLAMS. Additionally, counter‐propagating whistler waves (the high‐frequency branch of the magnetosonic whistler wave) are observed within SLAMS, coinciding with a perpendicular temperature anisotropy in the electron population. Instability analyses demonstrate that these low‐frequency waves are induced by the two‐stream instability associated with the cross‐field relative velocity between low‐energy ions and electrons, while whistler waves are locally generated by the whistler anisotropy instability. Our results shed light on the impact of SLAMS on particle and wave dynamics in the terrestrial foreshock.

Abstract Early dysbiosis in the gut microbiota may contribute to the severity of acute pancreatitis (AP), however, a comprehensive understanding of the gut microbiome, potential pathobionts, and host metabolome in individuals with AP remains elusive. Hence, we employed fecal whole-metagenome shotgun sequencing in 82 AP patients and 115 matched healthy controls, complemented by untargeted serum metabolome and lipidome profiling in a subset of participants. Analyses of the gut microbiome in AP patients revealed reduced diversity, disrupted microbial functions, and altered abundance of 77 species, influenced by both etiology and severity. AP-enriched species, mostly potential pathobionts, correlated positively with host liver function and serum lipid indicators. Conversely, many AP-depleted species were short-chain fatty acid producers. Gut microflora changes were accompanied by shifts in the serum metabolome and lipidome. Specifically, certain gut species, like enriched Bilophila wadsworthia and depleted Bifidobacterium spp., appeared to contribute to elevated triglyceride levels in biliary or hyperlipidemic AP patients. Through culturing and whole-genome sequencing of bacterial isolates, we identified virulence factors and clinically relevant antibiotic resistance in patient-derived strains, suggesting a predisposition to opportunistic infections. Finally, our study demonstrated that gavage of specific pathobionts could exacerbate pancreatitis in a caerulein-treated mouse model. In conclusion, our comprehensive analysis sheds light on the gut microbiome and serum metabolome in AP, elucidating the role of pathobionts in disease progression. These insights offer valuable perspectives for etiologic diagnosis, prevention, and intervention in AP and related conditions.

The identification of genome-wide selection signatures can reveal the potential genetic mechanisms involved in the generation of new breeds through natural or artificial selection. In this study, we screened the genome-wide selection signatures of prolific Suffolk sheep, a new strain of multiparous mutton sheep, to identify candidate genes for reproduction traits and unravel the germplasm characteristics and population genetic evolution of this new strain of Suffolk sheep. Whole-genome resequencing was performed at an effective sequencing depth of 20× for genomic diversity and population structure analysis. Additionally, selection signatures were investigated in prolific Suffolk sheep, Suffolk sheep, and Hu sheep using fixation index (FST) and heterozygosity H) analysis. A total of 5,236.338 Gb of high-quality genomic data and 28,767,952 SNPs were obtained for prolific Suffolk sheep. Moreover, 99 selection signals spanning candidate genes were identified. Twenty-three genes were significantly associated with KEGG pathway and Gene Ontology terms related to reproduction, growth, immunity, and metabolism. Through selective signal analysis, genes such as ARHGEF4, CATIP, and CCDC115 were found to be significantly correlated with reproductive traits in prolific Suffolk sheep and were highly associated with the mTOR signaling pathway, the melanogenic pathway, and the Hippo signaling pathways, among others. These results contribute to the understanding of the evolution of artificial selection in prolific Suffolk sheep and provide candidate reproduction-related genes that may be beneficial for the establishment of new sheep breeds.

Abstract While overweight/obesity has become a major public health issue worldwide, any association between body mass index (BMI) and therapeutic response in neoadjuvant targeted therapy treated HER2 positive breast cancer patients remain unclear. The information from a total of four-hundred and ninety-one neoadjuvant targeted therapy treated HER2 positive breast cancer patients from four institutions were retrospectively collected. Univariate and multivariate logistic analysis was developed to determine the association between BMI and therapeutic response. A meta-analysis of published literature was then conducted to confirm the effect of overweight/obesity on pCR for patients treated with neoadjuvant targeted therapy. Restricted cubic spline (RCS) adjusted for confounding factors demonstrated a decrease pCR with increasing BMI (OR = 0.937, P = 0.045). Patients were then categorized into under/normal weight (n = 299) and overweight/obesity (n = 192). Overweight/obese patients were independently associated with a poor therapeutic response. In the subgroup analysis, a significant negative impact of overweight/obesity on pCR can be observed both in single-targeted (OR = 0.556; P = 0.02) and dual-targeted (OR = 0.392; P = 0.021) populations. Six eligible studies involving 984 neoadjuvant targeted therapy treated HER2 positive breast cancer patients were included in the meta-analysis. The meta-analysis also demonstrated that overweight/obesity was significantly associated with a poor response to neoadjuvant anti-HER2 therapy (OR = 0.68; P = 0.007). Our result show that overweight and obese HER2 positive breast cancer patients are less likely to achieve pCR after neoadjuvant targeted therapy.

Abstract Background Compelling evidence has indicated a significant association between leukocyte mitochondrial DNA copy number (mtDNAcn) and prognosis of several malignancies in a cancer-specific manner. However, whether leukocyte mtDNAcn can predict the clinical outcome of breast cancer (BC) patients has not been well investigated. Methods The mtDNA copy number of peripheral blood leukocytes from 661 BC patients was measured using a Multiplex AccuCopy™Kit based on a multiplex fluorescence competitive PCR principle. Kaplan–Meier curves and Cox proportional hazards regression model were applied to investigate the association of mtDNAcn with invasive disease-free survival (iDFS), distant disease-free survival (DDFS), breast cancer special survival (BCSS), and overall survival (OS) of patients. The possible mtDNAcn-environment interactions were also evaluated by the Cox proportional hazard regression models. Results BC patients with higher leukocyte mtDNA-CN exhibited a significantly worse iDFS than those with lower leukocyte mtDNAcn (5-year iDFS: fully-adjusted model: HR = 1.433[95%CI 1.038–1.978], P = 0.028). Interaction analyses showed that mtDNAcn was significantly associated with hormone receptor status (adjusted p for interaction: 5-year BCSS: 0.028, 5-year OS: 0.022), so further analysis was mainly in the HR subgroup. Multivariate Cox regression analysis demonstrated that mtDNAcn was an independent prognostic factor for both BCSS and OS in HR-positive patients (HR+: 5-year BCSS: adjusted HR (aHR) = 2.340[95% CI 1.163–4.708], P = 0.017 and 5-year OS: aHR = 2.446 [95% CI 1.218–4.913], P = 0.011). Conclusions For the first time, our study demonstrated that leukocyte mtDNA copy number might influence the outcome of early-stage breast cancer patients depending on intrinsic tumor subtypes in Chinese women.

This study introduces a novel organosilicon-modified polysaccharide (Si-AP) synthesized via grafting and comprehensively evaluates its performance in water-based drilling fluids (WBDFs). The molecular structure of Si-AP was characterized using Fourier-transform infrared spectroscopy (FTIR) and 1H-NMR experiments. Thermalgravimetric analysis (TGA) confirmed the good thermal stability of Si-AP up to 235 °C. Si-AP significantly improves the rheological properties and fluid loss performance of WBDFs. With increasing Si-AP concentration, system viscosity increases, API filtration rate decreases, clay expansion is inhibited, and drilling cuttings hydration dispersion is suppressed, especially under high-temperature conditions. Additionally, mechanistic analysis indicates that the introduction of siloxane groups can effectively inhibit the thermal degradation of AP chains and enhance their high-temperature resistance. Si-AP can form a lubricating film by adsorbing on the surface of clay particles, improving mud cake quality, reducing the friction coefficient, and significantly enhancing the lubricating performance of WBDFs. Overall, Si-AP exhibits a higher temperature-resistance limit compared to AP and more effectively optimizes the lubrication, inhibition, and control of the filtration rate of WBDFs under high-temperature conditions. While meeting the requirements of drilling fluid systems under high temperatures, Si-AP also addresses environmental concerns and holds promise as an efficient solution for the exploitation of deep-seated oil and gas resources.

Summary: Oocyte maturation is vital to attain full competence required for fertilization and embryogenesis. NLRP14 is preferentially expressed in mammalian oocytes and early embryos. Yet, the role and molecular mechanism of NLRP14 in oocyte maturation and early embryogenesis are poorly understood, and whether NLRP14 deficiency accounts for human infertility is unknown. Here, we found that maternal loss of Nlrp14 resulted in sterility with oocyte maturation defects and early embryonic arrest (EEA). Nlrp14 ablation compromised oocyte competence due to impaired cytoplasmic and nuclear maturation. Importantly, we revealed that NLRP14 maintained cytoplasmic UHRF1 abundance by protecting it from proteasome-dependent degradation and anchoring it from nuclear translocation in the oocyte. Furthermore, we identified compound heterozygous NLRP14 variants in women affected by infertility with EEA, which interrupted the NLRP14-UHRF1 interaction and decreased UHRF1 levels. Our data demonstrate NLRP14 as a cytoplasm-specific regulator of UHRF1 during oocyte maturation, providing insights into genetic diagnosis for female infertility.

The high cost of laser powder bed fusion (LPBF) fabricated high-strength Sc containing aluminium alloy hinders its applications. To reduce the cost, we reported a LPBF fabricated strong and ductile Al–Mn–Mg–Sc–Zr alloy using large layer thicknesses to improve the fabrication efficiency on coarse powder particles. A high relative density exceeding 99.2% was achieved at layer thicknesses up to 120 μm. In post-process heat-treated specimens, the yield strength only had a slight 6% decrease from layer thickness of 30 to 120 μm; such a decrease in strength was attributed to the larger grain size resulted from the adopted larger layer thickness. The fabricated sample at layer thickness of 120 μm still exhibited high tensile yield strength of 472 MPa and fracture strain of ∼10%. This work showed a successful application of improving the LPBF fabrication efficiency of high-strength Al–Mn–Mg–Sc–Zr alloy using large layer thickness in LPBF process.

Abstract Background Bilateral breast cancer (BBC), as well as ovarian cancer, are significantly associated with germline deleterious variants in BRCA1/2, while BRCA1/2 germline deleterious variants carriers can exquisitely benefit from poly (ADP-ribose) polymerase (PARP) inhibitors. However, formal genetic testing could not be carried out for all patients due to extensive use of healthcare resources, which in turn results in high medical costs. To date, existing BRCA1/2 deleterious variants prediction models have been developed in women of European or other descent who are quite genetically different from Asian population. Therefore, there is an urgent clinical need for tools to predict the frequency of BRCA1/2 deleterious variants in Asian BBC patients balancing the increased demand for and cost of cancer genetics services. Methods The entire coding region of BRCA1/2 was screened for the presence of germline deleterious variants by the next generation sequencing in 123 Chinese BBC patients. Chi-square test, univariate and multivariate logistic regression were used to assess the relationship between BRCA1/2 germline deleterious variants and clinicopathological characteristics. The R software was utilized to develop artificial neural network (ANN) and nomogram modeling for BRCA1/2 germline deleterious variants prediction. Results Among 123 BBC patients, we identified a total of 20 deleterious variants in BRCA1 (8; 6.5%) and BRCA2 (12; 9.8%). c.5485del in BRCA1 is novel frameshift deleterious variant. Deleterious variants carriers were younger at first diagnosis (P = 0.0003), with longer interval between two tumors (P = 0.015), at least one medullary carcinoma (P = 0.001), and more likely to be hormone receptor negative (P = 0.006) and HER2 negative (P = 0.001). Area under the receiver operating characteristic curve was 0.903 in ANN and 0.828 in nomogram modeling individually (P = 0.02). Conclusion This study shows the spectrum of the BRCA1/2 germline deleterious variants in Chinese BBC patients and indicates that the ANN can accurately predict BRCA deleterious variants than conventional statistical linear approach, which confirms the BRCA1/2 deleterious variants carriers at the lowest costs without adding any additional examinations.

Abstract We fabricated sulfur and nitrogen codoped cyanoethyl cellulose‐derived carbons (SNCCs) with state‐of‐the‐art electrochemical performance for potassium ion battery (PIB) and potassium ion capacitor (PIC) anodes. At 0.2, 0.5, 1, 2, 5, and 10 A g−1, the SNCC shows reversible capacities of 369, 328, 249, 208, 150, and 121 mA h g−1, respectively. Due to a high packing density of 1.01 g cm−3, the volumetric capacities are also uniquely favorable, being 373, 331, 251, 210, 151, and 122 mA h cm−3 at these currents, respectively. SNCC also shows promising initial Coulombic efficiency of 69.0% and extended cycling stability with 99.8% capacity retention after 1000 cycles. As proof of principle, an SNCC‐based PIC is fabricated and tested, achieving 94.3 Wh kg−1 at 237.5 W kg−1 and sustaining over 6000 cycles at 30 A g−1 with 84.5% retention. The internal structure of S and N codoped SNCC is based on highly dilated and defective graphene sheets arranged into nanometer‐scale walls. Using a baseline S‐free carbon for comparison (termed NCC), the role of S doping and the resultant dilated structure was elucidated. According to galvanostatic intermittent titration technique and electrochemical impedance spectroscopy analyses, as well as COMSOL simulations, this structure promotes rapid solid‐state diffusion of potassium ions and a solid electrolyte interphase that is stable during cycling. X‐ray diffraction was used to probe the ion storage mechanisms in SNCC, establishing the role of reversible potassium intercalation and the presence of KC36, KC24, and KC8 phases at low voltages.

Abstract Background Potato (Solanum tuberosum) is the fourth most important food crop in the world and plays an important role in food security. Drought stress has a significantly negative impact on potato growth and production. There are several publications involved drought stress in potato, this research contributes to enrich the knowledge. Results In this study, next-generation sequencing (NGS) and single-molecule real-time (SMRT) sequencing technology were used to study the transcription profiles in potato in response to 20%PEG6000 simulates drought stress. The leaves of the variety “Désirée” from in vitro plantlets after drought stress at six time points from 0 to 48 hours were used to perform NGS and SMRT sequencing. According to the sequencing data, a total of 12,798 differentially expressed genes (DEGs) were identified in six time points. The real-time (RT)-PCR results are significantly correlated with the sequencing data, confirming the accuracy of the sequencing data. Gene ontology and KEGG analysis show that these DEGs participate in response to drought stress through galactose metabolism, fatty acid metabolism, plant-pathogen interaction, glutathione metabolism and other pathways. Through the analysis of alternative splicing of 66,888 transcripts, the functional pathways of these transcripts were enriched, and 51,098 transcripts were newly discovered from alternative splicing events and 47,994 transcripts were functionally annotated. Moreover, 3445 lncRNAs were predicted and enrichment analysis of corresponding target genes was also performed. Additionally, Alternative polyadenylation was analyzed by TADIS, and 26,153 poly (A) sites from 13,010 genes were detected in the Iso-Seq data. Conclusion Our research greatly enhanced potato drought-induced gene annotations and provides transcriptome-wide insights into the molecular basis of potato drought resistance.

BackgroundMyositis-specific autoantibodies (MSAs) are clinically used to diagnose and define idiopathic inflammatory myopathy (IIM) subsets. However, the underlying pathogenic mechanisms of patients with different MSAs remain unclear.MethodsA total of 158 Chinese patients with IIM and 167 gender- and age-matched healthy controls (HCs) were enrolled. Transcriptome sequencing (RNA-Seq) was performed with peripheral blood mononuclear cells (PBMCs), followed by the identification of differentially expressed genes (DEGs) and analysis of gene set enrichment analysis, immune cell infiltration, and WGCNA. Monocyte subsets and related cytokines/chemokines were quantified. The expressions of interferon (IFN)-related genes were validated using qRT-PCR and Western blot in both PBMCs and monocytes. We also performed correlation analysis and ROC analysis to explore the potential clinical significance of the IFN-related genes.ResultsThere were 1,364 genes altered in patients with IIM, including 952 upregulated and 412 downregulated genes. The type I interferon (IFN-I) pathway was remarkably activated in patients with IIM. Compared with patients with other MSAs, IFN-I signatures were significantly activated in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibodies. In total, 1,288 hub genes associated with IIM onset were identified using WGCNA, including 29 key DEGs associated with IFN signaling. The patients had more CD14brightCD16- classical, CD14brightCD16+ intermediate, and fewer CD14dimCD16+ non-classical monocyte subsets. Plasma cytokines like IL-6 and TNF and chemokines including CCL3 and MCPs increased. The validation of IFN-I-related gene expressions was consistent with the findings from RNA-Seq. The IFN-related genes were correlated with laboratory parameters and helpful for IIM diagnosis.ConclusionGene expressions were remarkably altered in the PBMCs of IIM patients. Anti-MDA5+ IIM patients had a more pronounced activated IFN signature than others. Monocytes exhibited a proinflammatory feature and contributed to the IFN signature of IIM patients.

Background: The quantitative relationship between HER2 copy number and prognosis in HER2 positive adjuvant setting remain controversial, and few studies have focused on adjuvant setting to illustrate the potential clinical relevance of HER2 in cfDNA. Our study aim to develop a novel method in HER2 quantification and explore the relationship between HER2 copy number in primary tumors or cfDNA and prognosis in HER2 positive early breast cancer. Methods: Two hundred and two patients with early breast cancer were prospectively included in a study where primary tumors, matching non-cancer breast tissue, corresponding plasma, and the plasma from 20 healthy volunteers were collected. Cox proportional hazard analysis was employed to determine the prognostic value of HER2 gene copy number in tissue and cfDNA. Tissue based nomograms and time-dependent decision curve analysis were used to evaluate the practicality of HER2 copy number stratification. Results: HER2 amplification by CNVplex demonstrated a robust concordance with FISH (concordance 89.2%). A three-tiered system of tissue and a two-tiered system of cfDNA classification were shown to be independent prognostic factors. A tissue copy number-based nomogram was fitted and further evaluation revealed a good performance in discrimination (c statistic 0.801) and calibration. Conclusions: We first report CNVplex as a viable alternative for HER2 detection. Quantitative evaluation of HER2 presents tremendous potential for use in risk stratification. We also uncover the potential for using HER2 copy number in cfDNA as a biomarker for prognosis in a HER2 positive adjuvant setting.

Abstract Background Cytidine nucleotide triphosphate synthase 1 (CTPS1) is a CTP synthase which play critical roles in DNA synthesis. However, its biological regulation and mechanism in triple-negative breast cancer (TNBC) has not been reported yet. Methods The expression of CTPS1 in TNBC tissues was determined by GEO, TCGA databases and immunohistochemistry (IHC). The effect of CTPS1 on TNBC cell proliferation, migration, invasion, apoptosis and tumorigenesis were explored in vivo and in vitro. In addition, the transcription factor Y-box binding protein 1 (YBX1) was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. Pearson correlation analysis was utilized to assess the association between YBX1 and CTPS1 expression. Results CTPS1 expression was significantly upregulated in TNBC tissues and cell lines. Higher CTPS1 expression was correlated with a poorer disease-free survival (DFS) and overall survival (OS) in TNBC patients. Silencing of CTPS1 dramatically inhibited the proliferation, migration, invasion ability and induced apoptosis of MDA-MB-231 and HCC1937 cells. Xenograft tumor model also indicated that CTPS1 knockdown remarkably reduced tumor growth in mice. Mechanically, YBX1 could bind to the promoter of CTPS1 to promote its transcription. Furthermore, the expression of YBX1 was positively correlated with CTPS1 in TNBC tissues. Rescue experiments confirmed that the enhanced cell proliferation and invasion ability induced by YBX1 overexpression could be reversed by CTPS1 knockdown. Conclusion Our data demonstrate that YBX1/CTPS1 axis plays an important role in the progression of TNBC. CTPS1 might be a promising prognosis biomarker and potential therapeutic target for patients with triple-negative breast cancer.

Abstract Signals from gyros and accelerometers in an inertial navigation system (INS) can be processed to obtain navigation information while its errors accumulate with time. A path with long‐term characteristics is more likely to encounter unpredictable dynamic conditions. To deal with such problems, this work improves the global static path‐planning algorithm based on the A* algorithm, and the local dynamic path‐planning algorithm based on dynamic window approach (DWA). In the global planning algorithm, the gravity index and the heading index are incorporated into the cost function of the A* algorithm to consider the mismatches and the deflection of the path. Furthermore, the search method of the A* algorithm is also improved. In the local planning algorithm, the motion model of the DWA algorithm is improved to a high‐precision model and expressed in a geographic coordinate system. Finally, the improved global static planning and local dynamic planning are combined as the global dynamic path‐planning algorithm of an underwater vehicle. The simulation results show that the global dynamic path‐planning algorithm proposed can realise obstacle‐free navigation of the underwater vehicle.

IntroductionTissue-resident macrophages (TRMs) are highly heterogeneous and have a complex and important role in tissue support, homeostasis, and function. The heterogeneity, maintenance, and function of TRMs, as one of the major immune cells in the ovary, are not well understood.MethodsApplication of flow cytometry, Parabiosis, Fate mapping, Macrophage depletion, etc.ResultsHere, we described two distinct macrophage subsets, F4/80hiCD11bint and F4/80intCD11bhi, with different phenotypic characteristics in the ovary of mice. The F4/80hiCD11bint population contained a distinct CD206+ subgroup and highly expressed CD81, while the F4/80intCD11bhi subset showed higher expression of CCR2 and TLR2. Notably, Ly6c+ macrophages were present almost exclusively in the F4/80intCD11bhi subpopulation. Combining in vivo fate mapping and parabiotic mouse models, we characterized the longevity and replenishment of the two macrophage populations. We found that both the F4/80hiCD11bint and F4/80intCD11bhi subsets were ovary-resident. Importantly, the F4/80hiCD11bint macrophages acted as a self-maintaining and long-lived population with a modest monocyte contribution at a steady state, and the F4/80intCD11bhi subpopulation had a relatively short lifespan with a greater contribution from monocytes. After macrophage ablation, disturbance of estradiol secretion and ovarian hemorrhage due to damaged vascular integrity was observed in mice.DiscussionOur data provide critical insights into ovarian macrophage heterogeneity and highlight the strategic role of TRMs in ovarian homeostasis and physiology.

The interdiffusion and atomic structure of the interface between metallic glass Cu50Zr50 and crystalline Cu were investigated using molecular dynamics simulations. We show that the interdiffusion of atoms at the amorphous/crystalline interface is mainly manifested as the diffusion of crystalline Cu atoms into amorphous atoms, and only a very small amount of amorphous atoms diffuse into crystalline Cu. And the temperature and diffusion time are proportional to the thickness of the diffusion layer. The H-A bond index and Voronoi polyhedron distribution method were used to analyze the structure type and cluster distribution of the interface atoms. the results show that the diffusion will cause the amorphization of the atoms on the crystal side of the interface, and the higher the temperature and the longer the diffusion time, the higher the degree of amorphization of the interface atoms. And the size of the amorphized region is related to the temperature, and the dividing plane between the amorphized atoms and the crystal atoms gradually moves to the crystal side with the increase of temperature. In addition, the diffusion behavior of atoms at the amorphous/crystal interface with different crystal orientations exhibits anisotropy, and some atoms at the interface between the 〈110〉 oriented crystal and amorphous are transformed from FCC structure to HCP structure during the diffusion process.

Due to their exceptional all-around performance, steel/aluminum-alloy composite plates have been frequently utilized in many different industries. However, when steel/aluminum-alloy composite plates are prepared by the rolling process, they will scarcely bond with high bonding strength under a lower reduction rate due to the inconsistent deformation the of steel/aluminum-alloy. Therefore, a method of adding a pure-aluminum interlayer by differential temperature rolling with induction heating was proposed to prepare steel/aluminum-alloy composite plates. The results showed that when the induction heating time was 10–18 s, the pure-aluminum interlayer became molten, and the temperature difference between the steel and aluminum alloy reached 350–500 °C. The interface shear strength of the composite plate reached more than 68 MPa under a 31% reduction rate. The shear fracture of the composite plate occurred in the pure-aluminum layer, and the steel/aluminum interface diffusion layer was 0.83–0.99 μm thick. There was no obvious compound formation at the bonding interface, however, the steel and aluminum alloy could not bond without the addition of an interlayer under the same conditions.

Abstract Background Harnessing helminth-based immunoregulation is a novel therapeutic strategy for many immune dysfunction disorders, including inflammatory bowel diseases (IBDs). We previously identified a small molecule peptide from Schistosoma japonicum and named it SJMHE1. SJMHE1 can suppress delayed-type hypersensitivity, collagen-induced arthritis and asthma in mice. In this study, we assessed the effects of SJMHE1 on dextran sulfate sodium (DSS)-induced acute and chronic colitis. Methods Acute and chronic colitis were induced in C57BL/6 mice by DSS, following which the mice were injected with an emulsifier SJMHE1 or phosphate-buffered saline. The mice were then examined for body weight loss, disease activity index, colon length, histopathological changes, cytokine expression and helper T (Th) cell subset distribution. Results SJMHE1 treatment significantly suppressed DSS-induced acute and chronic colitis, improved disease activity and pathological damage to the colon and modulated the expression of pro-inflammatory and anti-inflammatory cytokines in splenocytes and the colon. In addition, SJMHE1 treatment reduced the percentage of Th1 and Th17 cells and increased the percentage of Th2 and regulatory T (Treg) cells in the splenocytes and mesenteric lymph nodes of mice with acute colitis. Similarly, SJMHE1 treatment upregulated the expression of interleukin-10 (IL-10) mRNA, downregulated the expression of IL-17 mRNA and modulated the Th cell balance in mice with chronic colitis. Conclusions Our data show that SJMHE1 provided protection against acute and chronic colitis by restoring the immune balance. As a small molecule, SJMHE1 might be a novel agent for the treatment of IBDs without immunogenicity concerns. Graphical abstract

Background: Triple-negative breast cancer (TNBC) is characterized by a more aggressive biological behavior and unfavorable outcome. Circulating and histological expression of THBS2 has been demonstrated to be a novel diagnostic and prognostic biomarker in patients with various types of tumors. However, few studies have evaluated the predictive and prognostic value of THBS2 in TNBC specifically.Methods: In total, 185 triple-negative breast cancer patients (TNBC) with preoperative neoadjuvant chemotherapy were enrolled in this study. Serum THBS2 (sTHBS2) level was measured both prior to the start of NAC and at surgery by enzyme-linked immunosorbent assay (ELISA). Histological THBS2 (hTHBS2) expression in patients with residual tumors was evaluated by immunohistochemistry (IHC) staining method. Correlations between variables and treatment response were studied. Kaplan-Meier plots and Cox proportional hazard regression model were applied for survival analysis. Functional activities of THBS2 in TNBC cells were determined by CCK-8 assay, colony formation, wound healing, and transwell assay.Results: Of the 185 patients, 48 (25.9%) achieved pathological complete response (pCR) after completion of NAC. Elevated pCR rates were observed in patients with a lower level of sTHBS2 at surgery and higher level of sTHBS2 change (OR = 0.88, 95%CI: 0.79–0.98, p = 0.020 and OR = 1.12, 95%CI: 1.02–1.23, p = 0.015, respectively). In survival analysis, hTHBS2 expression in residual tumor was of independent prognostic value for both disease-free survival (HR = 2.21, 95%CI = 1.24–3.94, p = 0.007) and overall survival (HR = 2.07, 95%CI = 1.09–3.92, p = 0.026). For functional studies, THBS2 was indicated to inhibit proliferation, migration, and invasion abilities of TNBC cells in vitro.Conclusion: Our findings confirmed the value of serum THBS2 level to predict pCR for TNBC patients and the prognostic performance of histological THBS2 expression in non-pCR responders after NAC. THBS2 might serve as a promising functional biomarker for patients with triple-negative breast cancer.

We describe the case of a 4-month-old boy who presented with bilateral congenital cataract and high intraocular pressure (IOP) in the left eye, followed by mental retardation and delayed motor development. Genetic investigation revealed the boy had a splicing variant (c.940-11G>A) of the oculocerebrorenal syndrome of Lowe (OCRL) gene. The boy underwent a lensectomy for congenital cataract in his right eye, and lensectomy combined with a 360° suture trabeculotomy to remove the clouded lens and to control IOP of the left eye. During postoperative one-and-a-half-year follow-up, the boy exhibited an improved visual acuity and a well-controlled IOP without the use of topical IOP-lowering medications. Lowe syndrome is a rare multisystemic disorder that is diagnosed through clinical manifestation and genetic testing. The possibility of Lowe syndrome should be considered in patients presenting with typical triad, and genetic analysis should be performed in time to confirm the diagnosis. We recommend combined cataract surgery and minimally invasive glaucoma surgery (MIGS) as a safe, feasible, and efficient method to treat congenital cataract and glaucoma in Lowe syndrome patients.

The yield and quality of potatoes, an important staple crop, are seriously threatened by high temperature and drought stress. In order to deal with this adverse environment, plants have evolved a series of response mechanisms. However, the molecular mechanism of potato’s response to environmental changes at the translational level is still unclear. In this study, we performed transcriptome- and ribosome-profiling assays with potato seedlings growing under normal, drought, and high-temperature conditions to reveal the dynamic translational landscapes for the first time. The translational efficiency was significantly affected by drought and heat stress in potato. A relatively high correlation (0.88 and 0.82 for drought and heat stress, respectively) of the fold changes of gene expression was observed between the transcriptional level and translational level globally based on the ribosome-profiling and RNA-seq data. However, only 41.58% and 27.69% of the different expressed genes were shared by transcription and translation in drought and heat stress, respectively, suggesting that the transcription or translation process can be changed independently. In total, the translational efficiency of 151 (83 and 68 for drought and heat, respectively) genes was significantly changed. In addition, sequence features, including GC content, sequence length, and normalized minimal free energy, significantly affected the translational efficiencies of genes. In addition, 28,490 upstream open reading frames (uORFs) were detected on 6463 genes, with an average of 4.4 uORFs per gene and a median length of 100 bp. These uORFs significantly affected the translational efficiency of downstream major open reading frames (mORFs). These results provide new information and directions for analyzing the molecular regulatory network of potato seedlings in response to drought and heat stress.

Abstract Background As one of the main functional forms of mesenchymal stem cells (MSCs), MSC-derived extracellular vesicles (MSC-EVs) have shown an alternative therapeutic option in experimental models of allergic asthma. Oxygen concentration plays an important role in the self-renewal, proliferation, and EV release of MSCs and a recent study found that the anti-asthma effect of MSCs was enhanced by culture in hypoxic conditions. However, the potential of hypoxic MSC-derived EVs (Hypo-EVs) in asthma is still unknown. Methods BALB/c female mice were sensitized and challenged with ovalbumin (OVA), and each group received PBS, normoxic human umbilical cord MSC-EVs (Nor-EVs), or Hypo-EVs weekly. After treatment, the animals were euthanized, and their lungs and bronchoalveolar lavage fluid (BALF) were collected. With the use of hematoxylin and eosin (HE), periodic acid-Schiff (PAS) and Masson’s trichrome staining, enzyme-linked immune sorbent assay (ELISA), Western blot analysis, and real-time PCR, the inflammation and collagen fiber content of airways and lung parenchyma were investigated. Results Hypoxic environment can promote human umbilical cord MSCs (hUCMSCs) to release more EVs. In OVA animals, the administration of Nor-EVs or Hypo-EVs significantly ameliorated the BALF total cells, eosinophils, and pro-inflammatory mediators (IL-4 and IL-13) in asthmatic mice. Moreover, Hypo-EVs were generally more potent than Nor-EVs in suppressing airway inflammation in asthmatic mice. Compared with Nor-EVs, Hypo-EVs further prevented mouse chronic allergic airway remodeling, concomitant with the decreased expression of pro-fibrogenic markers α-smooth muscle actin (α-SMA), collagen-1, and TGF-β1-p-smad2/3 signaling pathway. In vitro, Hypo-EVs decreased the expression of p-smad2/3, α-SMA, and collagen-1 in HLF-1 cells (human lung fibroblasts) stimulated by TGF-β1. In addition, we showed that miR-146a-5p was enriched in Hypo-EVs compared with that in Nor-EVs, and Hypo-EV administration unregulated the miR-146a-5p expression both in asthma mice lung tissues and in TGF-β1-treated HLF-1. More importantly, decreased miR-146a-5p expression in Hypo-EVs impaired Hypo-EV-mediated lung protection in OVA mice. Conclusion Our findings provided the first evidence that hypoxic hUCMSC-derived EVs attenuated allergic airway inflammation and airway remodeling in chronic asthma mice, potentially creating new avenues for the treatment of asthma.

ObjectiveTo characterize the status of ovarian reserve and ART outcomes in BPES women and provide informative reference for clinical diagnosis and treatment.MethodsTwenty-one women with BPES were screened for mutations in the FOXL2 gene and underwent assisted reproductive technology (ART) treatment. Indicators for ovarian reserve and ART outcomes were compared between patients with and without FOXL2 mutations. Additionally, ART outcomes were compared among patients with different subtypes of FOXL2 mutations.ResultsA total of 13 distinct heterozygous variants in the FOXL2 gene were identified in 80.95% of BPES women, including 4 novel mutations with plausible pathogenicity (c.173_175dup, c.481C>T, c.576del and c.675_714del). Compared to non-mutation group, patients with FOXL2 mutations had elevated levels of FSH (P=0.007), decreased AMH levels (P=0.012) and less AFC (P=0.015). They also had worse ART outcomes with large amount of Gn dosage (P=0.008), fewer oocytes (P=0.001), Day3 good quality embryos (P=0.001) and good quality blastocysts (P=0.037), and a higher cancellation rate (P=0.272). High heterogeneity of ART outcomes existed in BPES patients with different FOXL2 mutation types.ConclusionsBPES patients with FOXL2 mutations had diminished ovarian reserve and adverse ART outcomes. The genotype-reproductive phenotype correlations were highly heterogeneous and cannot be generalized. Genetic counseling for fertility planning and preimplantation or prenatal genetic diagnosis to reduce offspring inheritance are recommended.

The wellbore instability in the horizontal sections of continental shale gas wells in the Ordos Basin is a major engineering and technical problem that restricts the exploration and development of the shale gas resources in the Yanchang Formation of Upper Triassic of Mesozoic in the Yanchang Block. To solve this problem, this paper analyzed the characteristics of mineral components in shale by means of X-ray diffraction. In addition, its physical and chemical characteristics, specific surface area and microstructure were analyzed. On this basis, a shale water-based drilling fluid system (PSW-2) of low free water activity based on nano plugging was developed. And it was applied on site at five horizontal wells in continental shale gas reservoirs to ensure the wellbore stability of their long horizontal sections. And the following research results were obtained. First, the Yanchang Formation shale in this area has a high content of clay mineral, and it is a fractured formation of weak expansion, easy dispersion and multiple bedding, so the wellbore instability here is the result of the comprehensive action of mechanical factors, physical and chemical factors, drilling mechanical disturbance, etc. Second, the shale has average pore diameter is 4.494–8.502 nm and is characterized by obvious capillary action, strong water absorption capacity and uneven hydration, which result in the decrease of local shale strength, so sudden collapse tends to happen easily. Third, the API loss of PSW-2 system is less than 2.8 mL, the rolling recovery rate is 95.15% (close to the recovery rate of oil-based drilling fluid 98.25%), the linear expansion rate is as low as 1.38%, and the wetting angle increases from 26° of dry rock samples to 56.5°. Fourth, the compressive strength of the system after immersion increases to 95.806 MPa, which is close to the original rock strength (110.70 MPa). It is concluded that this water-based drilling fluid system can effectively ensure wellbore stability by blocking the pores of shale with micro nano components, reducing the activity of liquid phase to increase the inhibition, and weakening the multi-element collaboration of the capillary imbibition effect of shale.

A new fossil genus and species is described from the Middle Jurassic of China. The type of Sinoelcana minuta gen. et sp. nov. has body and legs preserved. It is distinguished from all other elcanids by the unique combination of wing venation and stout ovipositor. The sickle-shaped ovipositor suggests that the new species had a preference for oviposition on plant material. A world key to the genera of Elcanidae is provided based on the wing venation.

Great progress has been made in the field of pedestrian detection, but the following two problems have not yet been well addressed. One problem is the missed detection of small scale pedestrain as false negative failure, and the other one is confusion with anthropomorphic negative samples like vertical structures as false positive failure. In this paper, to tackle the above two problems, we use the light-field camera to capture pedestrian images for the following reasons: (i) the light-field camera can obtain multi-depth refocused images in a single exposure using one sensor, (ii) compared with 2D images, these refocused images can provide different key representations for different parts of the image. We further establish a light-field pedestrian dataset with 1766 images for pedestrian detection. A multi-focus detection network proposed in this work consists of multiple-branch detection models and takes multiple refocused images as inputs. In order to select the appropriate candidate proposal bounding box as final detection results, we design a cumulative probability selection (CPS) layer to combine each refocused image branch and accumulate the probability of each candidate neighboring proposal. Experimental results demonstrate that the proposed method outperforms state-of-the-art methods on our light-field pedestrian dataset.

A large guide-field (∼1.1 B _o ) reconnection X -line, observed by the Magnetospheric Multiscale spacecraft during an outbound magnetopause crossing, is studied for Alfvén waves. Here B _o is the reconnecting field magnitude. The current sheet thickness of the magnetopause was ∼2.6 ion inertial lengths (∼269 km), where field-aligned counter-streaming electrons were observed and Hall electromagnetic fields were identified. A remarkable finding was that a kinetic Alfvén wave (KAW) was seen in the magnetopause upstream region after a shear Alfvén wave (SAW) was encountered in the magnetopause layer. The presence of both the SAW and KAW near the reconnection X -line is for the first time reported. In the spacecraft frame of reference, the SAW has a dominant frequency at ∼0.74 Hz, while the KAW has two dominant frequencies at ∼0.38 and ∼0.64 Hz. The wave energy for KAW and SAW was mostly carried away from the reconnection site by the Poynting flux parallel to the magnetic field. The parallel temperatures for ions and electrons were increased at KAW. The peaks of T _∥ / T _⊥ for ions were located near the wave peaks, while the ratio peaks for electrons were near the wave troughs. Our findings suggest that KAWS and SAWs can be generated by asymmetric reconnection with a large guide field.

Emerging quantum technologies, such as quantum computations and precise sensing, provide new opportunities in the fields of science and engineering. While energy consumption is a major concern for modern industry and society, it is rarely taken into consideration for quantum technologies. Especially, the potential of quantum technologies directly powered by renewable energy has long been neglected. The initialization, manipulation, and readout of quantum systems generally require high-power-consuming equipment, such as a dilution refrigerator, a microwave-power amplifier, and a high-power laser. Here, we discover a direct utilization path for solar energy to steer the quantum states of negatively charged nitrogen-vacancy centers in diamond, which is one of the most promising solid-state quantum systems in the past decades. Following this method, we demonstrate sunlight-driven quantum magnetometry. The initialization and readout of this quantum magnetometry are achieved directly by sunlight, and conventional microwave manipulation can be removed by using a microwave-free scheme. By utilizing ambient energy directly, our method brings potential solutions to the energy-consumption issue of quantum technologies. This technique can be further extended to multiple quantum systems, and thus opens the door to environmentally sustainable quantum technologies and self-powered quantum sensing in the future.

Abstract Objective To identify the plasma protein biomarkers related to the chemoresistance of postoperative recurrence of epithelial ovarian cancers. Methods Forty plasma samples from patients in chemotherapy-sensitive and chemotherapy-resistant groups (20 for each group) were collected at Gynecology Department in the Fourth Hospital of Hebei Medical University from September 2013 to September 2014. The differentially expressed proteins between two groups were screened with two-dimensional gel electrophoresis (2-DE) and further analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF–MS). Results Thirty-four differentially expressed spots were identified between the two groups. Compared with the chemo-sensitive group, 21 protein spots were up-regulated and 13 were down-regulated in the chemoresistant group, in which 14 differentially expressed proteins were identified by the Mass spectrometry and Mascot search. Among the 14 proteins, complement C4-A, IgJ chain, clusterin, α-1-antitrypsin and carbonic anhydrase 1 were up-regulated, and transthyretin, haptoglobin, β-2-glycoprotein, Ig γ-2 chain C region, Ig γ-1 chain C region, complement factor I light chain, Igκ chain C region, complement C3 and apolipoprotein E were down-regulated in the chemoresistant group when compared with the chemosensitive group. Conclusion The up-regulated proteins including transthyretin, apolipoprotein E and haptoglobin proteins and the down-regulated proteins such as clusterin, carbonic anhydrase 1, alpha-1-antitrypsin were differentially expressed in the plasma between the chemo-sensitive group and the chemoresistant group, which may be potential biomarkers for predicting the chemotresistance of epithelial ovarian cancer patients.

Slickwater fracturing can create complex fracture networks in shale. A uniform proppant distribution in the network is preferred. However, proppant transport mechanism in the fracture network is still uncertain, which restricts the optimization of sand addition schemes. In this study, slot flow experiments are conducted to analyze the proppant placement in the complex fracture system. Dense discrete phase method is used to track the particle trajectories to study the transport mechanism into the branch. The effects of the pumping rate, sand ratio, sand size, and branch angle and location are discussed in detail. Results demonstrate that: (1) under a low pumping rate or coarse proppant conditions, the dune development in the branch depends on the dune geometry in the primary fracture, and a high proportion of sand can transport into the branch; (2) using a high pumping rate or fine proppants is beneficial to the uniform placement in the fracture system; (3) sand ratio dominates the proppant placement in the branch and passing-intersection fraction of a primary fracture; (4) more proppants may settle in the near-inlet and large-angle branch due to the size limit. Decreasing the pumping rate can contribute to a uniform proppant distribution in the secondary fracture. This study provides some guidance for the optimization of proppant addition scheme in the slickwater fracturing in unconventional resources.

Real-time collaborative programming is an emerging approach that supports a team of programmers to view and edit shared source code at the same time. Each programmer can edit any part of the source code, and changes become instantly visible at other collaborating sites. With a broad range of application scenarios and benefits, real-time collaborative programming has attracted increasing interest from academia and industry. Lightweight integrated development environments (lightweight IDEs) have rapidly grown in popularity in the recent years, but there are serious problems and limitations with existing real-time collaboration support for lightweight IDEs. In this study, we contribute a novel real-time collaborative programming environment named CoVSCode that supports unconstrained and flexible real-time collaboration based on Visual Studio Code, one of the most popular and widely used lightweight IDEs. We present design objectives and rationales, the workflow and functional design from collaborating programmers’ perspectives, major technical issues and solutions, and prototype implementation, as well as a set of experimental evaluations that have demonstrated the technical feasibility and good performance of the prototype system. All approaches, techniques and solutions derived in this work are generic, which can also be applied in building real-time collaborative programming environments for other lightweight IDEs.