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Abstract Background Lanping black-boned sheep (LPB) represent a distinctive mammalian species characterized by hyperpigmentation, resulting in black bone and muscle features, in contrast to their conventional counterparts exhibiting red muscle and white bone. The genetic basis underlying LPB hyperpigmentation has remained enigmatic. Methods In this study, we conducted whole-genome sequencing of 100 LPB and 50 Lanping normal sheep (LPN), and integrated this data with 421 sequenced datasets from wild and domestic sheep, shedding light on the genetic backdrop and genomic variations associated with LPB. Furthermore, we performed comparative RNA-Seq analysis using liver sample to pinpoint genes implicated in the pigmentation process. We generated a comprehensive dataset comprising 97,944,357 SNPs from 571 sheep, facilitating an in-depth exploration of genetic factors. Results Population genetic structure analysis revealed that the LPB breed traces its origin back to LPN, having evolved into a distinct breed. The integration of positively selected genes with differentially expressed genes identified two candidates, ERBB4 and ROR1, potentially linked to LPB hyperpigmentation. Comparative analysis of ERBB4 and ROR1 mRNA relative expression levels in liver, spleen, and kidney tissues of LPB, in comparison to Diqing sheep, revealed significant upregulation, except for ERBB4 in the liver. Gene expression heatmaps further underscored marked allelic frequency disparities in different populations. Conclusion Our findings establish the evolutionary lineage of the LPB breed from LPN and underscore the involvement of ERBB4 and ROR1 genes in melanin synthesis. These results enhance our comprehension of the molecular basis of hyperpigmentation and contribute to a more comprehensive depiction of sheep diversity.

Abstract Background Beneficial associations between plants and soil microorganisms are critical for crop fitness and resilience. However, it remains obscure how microorganisms are assembled across different root compartments and to what extent such recruited microbiomes determine crop performance. Here, we surveyed the root transcriptome and the root and rhizosphere microbiome via RNA sequencing and full-length (V1–V9) 16S rRNA gene sequencing from genetically distinct monogenic root mutants of maize (Zea mays L.) under different nutrient-limiting conditions. Results Overall transcriptome and microbiome display a clear assembly pattern across the compartments, i.e., from the soil through the rhizosphere to the root tissues. Co-variation analysis identified that genotype dominated the effect on the microbial community and gene expression over the nutrient stress conditions. Integrated transcriptomic and microbial analyses demonstrated that mutations affecting lateral root development had the largest effect on host gene expression and microbiome assembly, as compared to mutations affecting other root types. Cooccurrence and trans-kingdom network association analysis demonstrated that the keystone bacterial taxon Massilia (Oxalobacteraceae) is associated with root functional genes involved in flowering time and overall plant biomass. We further observed that the developmental stage drives the differentiation of the rhizosphere microbial assembly, especially the associations of the keystone bacteria Massilia with functional genes in reproduction. Taking advantage of microbial inoculation experiments using a maize early flowering mutant, we confirmed that Massilia-driven maize growth promotion indeed depends on flowering time. Conclusion We conclude that specific microbiota supporting lateral root formation could enhance crop performance by mediating functional gene expression underlying plant flowering time in maize. Video Abstract

Objectives: About 90 % of all colorectal cancer (CRC) fatalities are caused by the metastatic spread of primary tumors, which is closely correlated with patient survival and spreads by circulating tumor cells (CTCs). The epithelial-mesenchymal transition (EMT) that characterizes CTCs is associated with a poor prognosis. Organotropic metastasis is dictated by the transmission of miRNAs by cancer-derived exosomes. The purpose of this research is to examine PKS + E's function. Coli in CRC metastases and exosomal miR-885-5p suppression. Methods: A cohort of 100 patients (50 CRC, 50 healthy) underwent colonoscopy screenings from February 2018 to August 2021. Exosomes were isolated using ultracentrifugation, and exosomal miRNA was analyzed using sequencing and qPCR. Results: Among the patients, 40 tested positive for E. coli (12 CRC, 23 healthy). Serotyping revealed that 68.57 % harbored the PKS gene. Exosomal miR-885-5p levels were significantly altered in CRC patients with PKS + E. coli. Intriguingly, our findings indicate that exosomes derived from EMT-CRC cells did not affect miR-885-5p synthesis in HUVECs. Moreover, we observed that the levels of miR-885-5p in both exosomes and the total CRC-conditioned medium were comparable upon isolation of exosomes from CRC cells. What's more, an increased expression of miR-558-5p within the tumors, and the group that received exosome treatment, as well as the EMT-HCT116 group, exhibited a higher occurrence of distant metastasis. Conclusion: PKS + E. By inhibiting exosomal miR-885-5p, coli is linked to CRC metastases, offering a possible target for therapeutic intervention.

Abstract Background Clear cell renal cell carcinoma (ccRCC) is associated with a high prevalence of cancer-related deaths. The survival rates of patients are significantly lower in late-stage ccRCC than in early-stage ccRCC, due to the spread and metastasis of late-stage ccRCC, surgery has not reached the goal of radical cure, and the effect of traditional radiotherapy and chemotherapy is poor. Thus, it is crucial to accurately assess the prognosis and provide personalized treatment at an early stage in ccRCC. This study aims to develop an efficient nomogram model for stratifying and predicting the survival of ccRCC patients based on tumor stage. Methods We first analyzed the microarray expression data of ccRCC patients from the Gene Expression Omnibus (GEO) database and categorized them into two groups based on the disease stage (early and late stage). Subsequently, the GEO2R tool was applied to screen out the genes that were highly expressed in all GEO datasets. Finally, the clinicopathological data of the two patient groups were obtained from The Cancer Genome Atlas (TCGA) database, and the differences were compared between groups. Survival analysis was performed to evaluate the prognostic value of candidate genes (PSAT1, PRAME, and KDELR3) in ccRCC patients. Based on the screened gene PSAT1 and clinical parameters that were significantly associated with patient prognosis, we established a new nomogram model, which was further optimized to a single clinical variable-based model. The expression level of PSAT1 in ccRCC tissues was further verified by qRT-PCR, Western blotting, and immunohistochemical analysis. Results The datasets GSE73731, GSE89563, and GSE150404 identified a total of 22, 89, and 120 over-expressed differentially expressed genes (DEGs), respectively. Among these profiles, there were three genes that appeared in all three datasets based on different stage groups. The overall survival (OS) of late-stage patients was significantly shorter than that of early-stage patients. Among the three candidate genes (PSAT1, PRAME, and KDELR3), PSAT1 was shown to be associated with the OS of patients with late-stage ccRCC. Multivariate Cox regression analysis showed that age, tumor grade, neoadjuvant therapy, and PSAT1 level were significantly associated with patient prognosis. The concordance indices were 0.758 and 0.725 for the 3-year and 5-year OS, respectively. The new model demonstrated superior discrimination and calibration compared with the single clinical variable model. The enhancer PSAT1 used in the new model was shown to be significantly overexpressed in tissues from patients with late-stage ccRCC, as demonstrated by the mRNA level, protein level, and pathological evaluation. Conclusion The new prognostic prediction nomogram model of PSAT1 and clinicopathological variables combined was thus established, which may provide a new direction for individualized treatment for different-stage ccRCC patients.

This paper deals with the following fractional Schrödinger–Poisson system: (−Δ)su + u − K(x)ϕ|u|2s∗−3u = f λ(x)|u|q−2u,x ∈ ℝ3,(−Δ)sϕ = K(x)|u|2s∗−1, x ∈ ℝ3 with multiple competing potentials and a critical nonlocal term, where [Formula: see text], [Formula: see text] or [Formula: see text], and [Formula: see text] is the fractional critical exponent. By combining the Nehari manifold analysis and the Ljusternik–Schnirelmann category theory, we establish how the coefficient [Formula: see text] of the nonlocal critical nonlinearity affects the number of positive solutions. We propose a new relation between the number of positive solutions and the category of the global maximal set of [Formula: see text].

In Beyond the Fifth Generation (B5G) heterogeneous edge networks, numerous users are multiplexed on a channel or served on the same frequency resource block, in which case the transmitter applies coding and the receiver uses interference cancellation. Unfortunately, uncoordinated radio resource allocation can reduce system throughput and lead to user inequity, for this reason, in this paper, channel allocation and power allocation problems are formulated to maximize the system sum rate and minimum user achievable rate. Since the construction model is non-convex and the response variables are high-dimensional, a distributed Deep Reinforcement Learning (DRL) framework called distributed Proximal Policy Optimization (PPO) is proposed to allocate or assign resources. Specifically, several simulated agents are trained in a heterogeneous environment to find robust behaviors that perform well in channel assignment and power allocation. Moreover, agents in the collection stage slow down, which hinders the learning of other agents. Therefore, a preemption strategy is further proposed in this paper to optimize the distributed PPO, form DP-PPO and successfully mitigate the straggler problem. The experimental results show that our mechanism named DP-PPO improves the performance over other DRL methods.

Abstract Purposes The aim of this study was to construct a lateral classification system for nontraumatic osteonecrosis of femoral head (NONFH) through three-dimensional reconstruction of the necrotic area to assist in evaluating the prognosis of patients with JIC type C1. Methods Retrospective analysis of patients with JIC type C1 NONFH from January 2018 to December 2020. All patients were followed up for more than 3.5 years. The patients were divided into collapse group and non-collapse group according to whether the femoral head collapsed during the follow-up.Lateral classification system for femoral head necrosis is constructed through three-dimensional reconstruction of the necrotic area.Comparison of lateral classification system,midsagittal necrosis angle(MNA)and general data between the two groups.Furthermore, ROC curve analysis and survival analysis were performed. Results 318 patients were included in this study.There was a significant difference between the two groups in the lateral classification system (P

Many UAVs today have an S-bend inlet for the sake of stealth; however, the majority of them have a relatively gentle transition of the flow channel. This study presents an experimental investigation of the aerodynamic performance and swirl flow characteristics of a UAV inlet with double 90° bends, which is also integrated with an aircraft fuselage as well as a volute. The influences of angle of attack, sideslip angle, AIP Mach number and freestream speed are explored in detail. The influences of the deflectors installed ahead of the first 90° bend of the inlet and the baffle installed at the bottom of the volute are revealed. It is found that both the deflectors and the baffle are beneficial in enhancing the aerodynamic performance of the inlet and alleviating the intensity of the swirl flow inside the volute.

Conclusion: Quercetin can improve cognitive impairment and AD-like pathology in APP/PS1 double transgenic mice, potentially related to quercetin’s activation of the Keap1/Nrf2/HO-1 pathway and reduction of cell apoptosis.

In the context of the advancing construction engineering field in China, there has been a significant increase in the adoption of building information modeling (BIM) technology within engineering–procurement–construction (EPC) projects. This emerging technology is expected to significantly influence the decision-making practices of professionals in the construction and engineering domain. Consequently, there is an urgent need for comprehensive research focused on construction management specifically pertaining to the effectiveness of construction developer management. This study examines seven representative EPC projects where BIM technology was implemented and it considers various factors that have the potential to influence project decision-making while taking into account time and cost considerations. A comprehensive multidimensional evaluation method that combines the analytic hierarchy process (AHP) and the fuzzy comprehensive evaluation method is introduced in this study. The results of this study emphasize that the efficiency enhancement strategies derived from the judgment indicator method demonstrate favorable practical outcomes. This research highlights the importance of a comprehensive evaluation method combining the AHP and the fuzzy comprehensive evaluation method to enhance decision-making efficiency for construction developer management staff.

In the vertical take-off and landing (VTOL) state of tiltrotor aircraft, the inlet entrance encounters the incoming airflow at a 90° attack angle, resulting in highly complex internal flow characteristics that are extremely susceptible to gusts. Meanwhile, the flow quality at the inlet exit directly affects the performance of the aircraft’s engine. This work made use of an unsteady numerical simulation method based on sliding meshes to investigate the internal flow characteristics of the inlet during the hover state of a typical tiltrotor aircraft and the effects of head-on gusts on the inlet’s aerodynamic characteristics. The results show that during the hover state, the tiltrotor aircraft inlet features three pairs of transverse vortices and one streamwise vortex at the aerodynamic interface plane (AIP). The transverse vortices generated due to the rotational motion of the air have the largest scale and exert the strongest influence on the inlet’s performance, which is characterized by pronounced unsteady features. Additionally, strong unsteady characteristics are present within the inlet. Head-on gusts mainly affect the mechanical energy and non-uniformity of the air sucked into the inlet by influencing the direction of the rotor’s induced slipstream, thereby impacting the performance of the inlet. The larger head-on gusts have beneficial effects on the performance of the inlet. When the gust velocity reaches 12 m/s, there is a 1.01% increase in the total pressure recovery (σ) of the inlet, a 25.72% decrease in the circumferential distortion index (DC60), and a reduction of 62.84% in the area where the swirl angle |α| exceeds 15°. Conversely, when the gust velocity of head-on gusts reaches 12 m/s in the opposite direction, the inlet’s total pressure recovery decreases by 1.13%, the circumferential distortion index increases by 14.57%, and the area where the swirl angle exceeds 15° increases by 69.59%, adversely affecting the performance of the inlet. Additionally, the presence of gusts alters the unsteady characteristics within the inlet.

Introduction: Body measurement traits are integral in cattle production, serving as pivotal criteria for breeding selection. Wenshan cattle, a local breed in China’s Yunnan province, exhibit remarkable genetic diversity. However, the molecular mechanisms regulating body measurement traits in Wenshan cattle remain unexplored.Methods: In this study, we performed a genome-wide association method to identify genetic architecture for body height body length hip height back height (BAH), waist height and ischial tuberosity height using the Bovine 50 K single nucleotide polymorphism Array in 1060 Wenshan cattles.Results: This analysis reveals 8 significant SNPs identified through the mixed linear model (MLM), with 6 SNPs are associated with multiple traits and 4 SNPs are associated with all 6 traits. Furthermore, we pinpoint 21 candidate genes located in proximity to or within these significant SNPs. Among them, Scarb1, acetoacetyl-CoA synthetase and HIVEP3 were implicated in bone formation and rarely encountered in livestock body measurement traits, emerge as potential candidate genes regulating body measurement traits in Wenshan cattle.Discussion: This investigation provides valuable insights into the genetic mechanisms underpinning body measurement traits in this unique cattle breed, paving the way for further research in this domain.

Background Tetanus remains a significant public health issue in China, with the approach of anti-tetanus prophylaxis in the emergency department resulting in both overuse, particularly of human tetanus immune globulin (TIG), and underuse with the tetanus vaccine. This is largely due to the absence of updated guidelines on tetanus prophylaxis before 2018. Our study aimed to evaluate the effects of the 2018 Chinese tetanus guidelines on the knowledge and practices of emergency physicians about tetanus prevention in trauma patients. Methods From November 2019 to April 2020, we conducted a web-based survey involving 499 emergency physicians. The survey included a questionnaire covering knowledge, attitudes, and practices related to tetanus. We assessed the influence of the 2018 tetanus guidelines on the knowledge and practices of emergency physicians related to tetanus prevention for patients with trauma using multiple regression analysis. Results The survey results showed that only 45.3% of the participants had received formal training on tetanus immunization, despite 53.3% reporting the availability of tetanus vaccines at their institutions. Physicians typically prescribed tetanus antitoxin or human TIG instead of tetanus toxoid (TT) to treat injuries, regardless of the patient’s TT vaccination history. Among the respondents, those who were aware of the 2018 tetanus guidelines had higher mean scores on the general knowledge, risk knowledge, and treatment knowledge scales, with increases of 6%, 13%, and 9%, respectively, compared to those who were unaware of the guidelines. Awareness of the 2018 tetanus guidelines was associated with a high level of knowledge, as indicated by the general knowledge score, recommendation knowledge score, and total knowledge score, after adjusting for the effects of all variables on the knowledge, attitudes, and practices of the participants. A high level of education was also associated with a high level of knowledge indicated by the recommendation knowledge score and total knowledge score. Conclusions Our study highlights a substantial gap in the attitudes, knowledge, and practices of emergency physicians in China regarding tetanus immunization. The results suggest an urgent need to promote the Chinese Expert Consensus Guidelines on tetanus to improve emergency physicians’ knowledge and competence in tetanus prophylaxis. The findings underscore the importance of enhancing physicians’ awareness of the latest guidelines to ensure appropriate and effective treatment for patients with tetanus-prone injuries.

Cryosurgery can represent a therapeutic option for breast cancer treatment. Here the authors report a strategy combining cryosurgery with cold-responsive nanoparticles loaded with the chemotherapeutic drug irinotecan and PD-L1-targeting siRNA, inducing anti-tumor immune responses in preclinical breast cancer models.

The conventional approach for fabricating polydimethylsiloxane (PDMS) microfluidic devices is a lengthy and inconvenient procedure and may require a clean-room microfabrication facility often not readily available. Furthermore, living cells can't survive the oxygen-plasma and high-temperature-baking treatments required for covalent bonding to assemble multiple PDMS parts into a leak-free device, and it is difficult to disassemble the devices because of the irreversible covalent bonding. As a result, seeding/loading cells into and retrieving cells from the devices are challenging. Here, we discovered that decreasing the curing agent for crosslinking the PDMS prepolymer increases the noncovalent binding energy of the resultant PDMS surfaces without plasma or any other treatment. This enables convenient fabrication of leak-free microfluidic devices by noncovalent binding for various biomedical applications that require high pressure/flow rates and/or long-term cell culture, by simply hand-pressing the PDMS parts without plasma or any other treatment to bind/assemble. With this method, multiple types of cells can be conveniently loaded into specific areas of the PDMS parts before assembly and due to the reversible nature of the noncovalent bonding, the assembled device can be easily disassembled by hand peeling for retrieving cells. Combining with 3D printers that are widely available for making masters to eliminate the need of photolithography, this facile yet rigorous fabrication approach is much faster and more convenient for making PDMS microfluidic devices than the conventional oxygen plasma-baking-based irreversible covalent bonding method.

Change detection in remote sensing enables identifying alterations in surface characteristics over time, underpinning diverse applications. However, conventional pixel-based algorithms encounter constraints in terms of accuracy when applied to medium- and high-resolution remote sensing images. Although object-oriented methods offer a step forward, they frequently grapple with missing small objects or handling complex features effectively. To bridge these gaps, this paper proposes an unsupervised object-oriented change detection approach empowered by hierarchical multi-scale segmentation for generating binary ecosystem change maps. This approach meticulously segments images into optimal sizes and leverages multidimensional features to adapt the Iteratively Reweighted Multivariate Alteration Detection (IRMAD) algorithm for GaoFen WFV data. We rigorously evaluated its performance in the Yellow River Source Region, a critical ecosystem conservation zone. The results unveil three key strengths: (1) the approach achieved excellent object-level change detection results, making it particularly suited for identifying changes in subtle features; (2) while simply increasing object features did not lead to a linear accuracy gain, optimized feature space construction effectively mitigated dimensionality issues; and (3) the scalability of our approach is underscored by its success in mapping the entire Yellow River Source Region, achieving an overall accuracy of 90.09% and F-score of 0.8844. Furthermore, our analysis reveals that from 2015 to 2022, changed ecosystems comprised approximately 1.42% of the total area, providing valuable insights into regional ecosystem dynamics.

Cardiomyocytes differentiated from human induced pluripotent stem cells (iPSCs) are valuable for the understanding/treatment of the deadly heart diseases and their drug screening. However, the very much needed homogeneous 3D cardiac differentiation of human iPSCs is still challenging. Here, it is discovered surprisingly that Rock inhibitor (RI), used ubiquitously to improve the survival/yield of human iPSCs, induces early gastrulation-like change to human iPSCs in 3D culture and may cause their heterogeneous differentiation into all the three germ layers (i.e., ectoderm, mesoderm, and endoderm) at the commonly used concentration (10 μM). This greatly compromises the capacity of human iPSCs for homogeneous 3D cardiac differentiation. By reducing the RI to 1 μM for 3D culture, the human iPSCs retain high pluripotency/quality in inner cell mass-like solid 3D spheroids. Consequently, the beating efficiency of 3D cardiac differentiation can be improved to more than 95 % in ~7 days (compared to less than ~50 % in 14 days for the 10 μM RI condition). Furthermore, the outset beating time (OBT) of all resultant cardiac spheroids (CSs) is synchronized within only 1 day and they form a synchronously beating 3D construct after 5-day culture in gelatin methacrylol (GelMA) hydrogel, showing high homogeneity (in terms of the OBT) in functional maturity of the CSs. Moreover, the resultant cardiomyocytes are of high quality with key functional ultrastructures and highly responsive to cardiac drugs. These discoveries may greatly facilitate the utilization of human iPSCs for understanding and treating heart diseases.

Bovine spongiform encephalopathy (BSE) is a fatal disease in cattle caused by misfolded prion proteins and linked to indel polymorphisms in the promoter and intron 1 of the PRNP gene. The aim of this study was to determine the allele, genotype, and haplotype frequencies of PRNP indel polymorphisms and to investigate the effect of PRNP gene expressions of 23 bp and 12 bp indels via polymerase chain reaction (PCR) in Zhongdian Yak (Bos-grunniens) (YK), Zhongdian Yellow cattle (Bos-taurus) (YC), and Zhongdian Yakow (Bos-primigenius taurus × Bos-grunniens) (PK). Resultant high allelic frequencies were found in 23− and 12+, while haplotype frequencies were very low in 23+/12 in YK, YC, and PK. PRNP expression was higher in the +−/−− diplotype of the PK and (mean ± SE) was 3.6578 ± 1.85964. Furthermore, two variable sites were investigated—a 23 bp indel polymorphism holding AP1 binding site and a 12 bp indel polymorphism holding SP1 binding site. Additionally, reporter gene assays revealed a link between two proposed transcription factors and lower expression levels of the +/+ allele compared with the −/− allele. The expression level of PRNP was shown to be dependent on two indel polymorphisms in the bovine PRNP promoter, which includes binding sites for RP58 and SP1 transcription factors. These findings raised the possibility that the PRNP genotype may contribute to the high variation in PRNP expression.

As an exemplary model for examining molecular mechanisms responsible for extreme phenotypic variations, plumage color has garnered significant interest. The Cygnus genus features two species, Cygnus olor and Cygnus atratus, that exhibit striking disparities in plumage color. However, the molecular foundation for this differentiation has remained elusive. Herein, we present two high-quality genomes for C. olor and C. atratus, procured using the Illumina and Nanopore technologies. The assembled genome of C. olor was 1.12 Gb in size with a contig N50 of 26.82 Mb, while its counterpart was 1.13 Gb in size with a contig N50 of 21.91 Mb. A comparative analysis unveiled three genes (TYR, SLC45A2, and SLC7A11) with structural variants in the melanogenic pathway. Notably, we also identified a novel gene, PWWP domain containing 2A (PWWP2A), that is related to plumage color, for the first time. Using targeted gene modification analysis, we demonstrated the potential genetic effect of the PWWP2A variant on pigment gene expression and melanin production. Finally, our findings offer insight into the intricate pattern of pigmentation and the role of polygenes in birds. Furthermore, these two high-quality genome references provide a comprehensive resource and perspective for comparative functional and genetic studies of evolution within the Cygnus genus.

UAVs can be deployed in many scenarios to provide various types of services via 6G edge communication. In these scenarios, it is necessary to obtain the position of the UAVs in a timely and accurate manner to avoid UAV collisions. In this paper, we consider improved passive localization algorithms aimed at reducing convergence time and adapting to extreme conditions. For the sake of reducing the complexity of signals and ensuring the reliability of receiving processes, we reconsidered the angle between arrival signals as the feature in positioning. Then, according to the characteristics of the positioning process, we draw on the cyclical process of the iterative greedy algorithm to construct the coding, destruction, and reorganization process to guide the movement of the UAV. Moreover, an improved Metropolis criterion is added to prevent falling into the local optimal solution. Finally, the proposed algorithm is verified in the simulation results. The results show that the algorithm can achieve precise positioning and excellent track planning within a small number of iterations, and it reduces the amount of information carried by the signal and convergence time compared with the traditional method.

Human induced pluripotent stem cells (hiPSCs) possess tremendous potential for tissue regeneration and banking hiPSCs by cryopreservation for their ready availability is crucial to their widespread use. However, contemporary methods for hiPSC cryopreservation are associated with both limited cell survival and high concentration of toxic cryoprotectants and/or serum. The latter may cause spontaneous differentiation and/or introduce xenogeneic factors, which may compromise the quality of hiPSCs. Here, sand from nature is discovered to be capable of seeding ice above −10 °C, which enables cryopreservation of hiPSCs with no serum, much-reduced cryoprotectant, and high cell survival. Furthermore, the cryopreserved hiPSCs retain high pluripotency and functions judged by their pluripotency marker expression, cell cycle analysis, and capability of differentiation into the three germ layers. This unique sand-mediated cryopreservation method may greatly facilitate the convenient and ready availability of high-quality hiPSCs and probably many other types of cells/tissues for the emerging cell-based translational medicine.

ObjectiveAtrial fibrillation (AF) is an important risk factor for stroke, but the currently used CHA2DS2-VASc score has significant limitations in predicting the risk of stroke. It is important to find new biomarkers to predict stroke risk in patients with AF or as a complement to the CHA2DS2-VASc score. Neutrophil-to-lymphocyte ratio (NLR) may be of potential value. This systematic review and meta-analysis evaluated the association between NLR and stroke risk.MethodsWe searched in electronic databases such as PubMed and EMBASE. The final included studies were analyzed by Stata 12.0 software. Subgroup analyses were used to explore sources of heterogeneity. Publication bias was assessed by Egger's test and Begg's test. Sensitivity analyses assessed the stability of outcomes.ResultsA total of 11 studies with a total of 35,221 patients were included. NLR levels are associated with stroke risk in patients with atrial fibrillation (WMD = 0.72, 95%CI = 0.43–1.01). There was a correlation between the occurrence of stroke and NLR level in AF patients (WMD = 1.96, 95%CI = 1.38–2.53). The incidence of stroke was significantly higher in patients with atrial fibrillation with NLR ≥3 than in those with NLR

Summary: Biologically derived redox-active motifs have great potential in energy storage due to their inherent functionality and availability from natural resources. In this protocol, we describe the synthesis and characterization of a class of bio-derived 4-electron-accepting carbonyl-N-methylpyridinium species for lithium-organic batteries. This protocol enables the synthesis of three small molecules and two conjugated polymers with carbonyl-N-methylpyridinium units in good quantities. We also detail the fabrication process and performance evaluation of the coin-cell-type lithium-organic batteries.For complete details on the use and execution of this protocol, please refer to Wang et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

This study was conducted to evaluate the influences of supplementing Ampelopsis grossedentata flavonoids (AGF) on the rumen bacterial microbiome, plasma physiology and biochemistry, and growth performance of goats. Twenty-four Nubian kids were randomly allocated to three dietary treatments: the control (CON, basal diet), the 1.0 g/kg AGF treatment (AGF), and the 12.5 mg/kg monensin treatment (MN). This trial consisted of 10 days for adaptation and 90 days for data and sample collection. The results reveal that Bacteroidetes, Firmicutes, and Proteobacteria are the dominant phyla in kids’ rumen. Compared with the CON group, the alpha diversity in the MN and AGF groups significantly increased (p < 0.01). Beta-diversity shows that rumen microbial composition is more similar in the MN and AGF groups. LEfSe analysis shows that Prevotella_1 in the AGF group were significantly higher than those in the MN and CON group. The high-density lipoprotein cholesterol and glucose levels in the AGF group were significantly higher than those in the CON group (p < 0.05), whereas the low-density lipoprotein cholesterol, glutamic-pyruvic transaminase, and alkaline phosphatase levels exhibited the opposite trend. The average daily gains in the AGF and MN groups significantly increased, while the feed-to-gain ratios were significantly decreased (p < 0.05). The results suggest that adding AGF to the diet improves microbial composition and has important implications for studying juvenile livestock growth and improving economic benefits.

BackgroundFemoral neck fracture (FNF) is a commonly encountered injury in orthopedic practice, and many studies have been conducted in this field. However, no bibliometric studies regarding the global research trend concerning FNF have been performed. This study aims to analyze the knowledge framework, research hotspots, and theme trends in the field of FNF research.MethodsThe scientific outputs related to FNF from 1994 to 2021 were retrieved from the Web of Science Core Collection. Three bibliometric tools were used for this study. The main analyses include publication and citation counts, contributions of countries, institutions, authors, funding agencies and journals, and clustering of keywords.ResultsIn total, 3,553 articles were identified. The annual publication counts of FNF showed an ascending tendency as a whole. The United States has the most prominent contributions, with the most number of publications and the highest H-index. Karolinska Institutet devoted the most in this domain. Professors Bhandari M, Schemitsch EH, Frihagen F, Parker MJ, and Rogmark C were the core authors in this field. The most productive journal was Injury International Journal of the Care of the Injured. Keywords were divided into four clusters: epidemiology and mortality, fracture prevention, internal-fixation and risk factors, and hip replacement. A trend of balanced and diversified development existed in these clusters. Keywords with the ongoing bursts, including “outcome,” “reoperation,” “complication,” “revision,” “displaced intracapsular,” “fracture,” and “adult,” are considered as the research hotspots in the future and deserve more attention.ConclusionsThe management of FNF in young patients is drawing more attention from orthopedic surgeons, and it is expected that these research topics may continue to be the research hotspots and focus in the near future.

As a new data acquisition technology, network telemetry has greatly enriched the diversity of data acquisition and expanded the range of traditional OAM data acquisition, whose goal is to realize real-time global network state visibility and traffic visibility.By combining with big data and AI technology, it can reduce human intervention and improve the operation and maintenance level of network automation.Firstly, the problems and challenges faced by the current IP network operation and maintenance were analyzed, and then it was elaborated that the network telemetry technology was the key enabler to realize the automatous network operation and maintenance.On this basis, the application of network telemetry technology in the IP network automatic operation and maintenance was investigated and discussed, and the reference and guidance for the automatic operation and maintenance of large-scale IP network were provided.

The transmembrane P-glycoprotein (P-gp) pumps are known to promote drug resistance by enhancing drug efflux. Here, the authors deliver P-gp inhibitor and a chemotherapeutic agent using tumor blood vessel-targeting nanoparticle, to overcome drug resistance.

BackgroundHip fractures are a common type of fracture in the elderly and are characterized by many complications and high mortality. Many topics concerning postoperative rehabilitation of hip fracture in elderly people still remain controversial, and the global research trend in this field has not yet been well studied. The aim of the present study was to illustrate the overall knowledge structure, development trends, and research hot spots of postoperative rehabilitation of hip fracture in elderly people.MethodsArticles and reviews regarding postoperative rehabilitation of hip fracture in elderly people from 2001 to 2021 were identified from the Web of Science database. An online bibliometric platform, CiteSpace, and VOSviewer software were used to generate visualization knowledge maps, including annual trends of publications, contributions of countries, institutions, authors, funding agencies, and journals, and clustering of keywords.ResultsA total of 1,724 publications were identified from Web of Science Core Collection (WoSCC). In the past 20 years, the number of published studies on the rehabilitation of hip fracture in the elderly has exhibited an overall upward trend. The USA was the leading contributor in this field, with the largest number of publications (354, 20.65%) and the most citations (13,786 times). The international cooperation map among relevant countries/regions indicated that the USA collaborated most closely with Canada and China. The University of Maryland and Professor Marcantonio were the most prolific institution and influential author, respectively. Injury: International Journal of the Care of the Injured was the most productive journal concerning the research of postoperative rehabilitation of hip fracture in elderly people. The keyword co-occurrence analysis identified six clusters: quality of life study, rehabilitation and outcomes study, cognitive impairment study, operative approaches study, mortality study, and osteoporosis study.ConclusionsThere will be an increasing number of publications on the research of postoperative rehabilitation of hip fracture in elderly people, and the United States will stay ahead in this field. Our findings could offer practical sources for scholars to understand the current status and trend of studies on rehabilitation of hip fracture in the elderly and provide references and suggestions for the development of related research in future.

Objective: To present an overview of different approaches and recent advances for long-term preservation of germ cells and gonadal tissues at ambient temperatures. Methods: Review of the existing literature. Results: Preserving viable spermatozoa, eggs, embryos, and gonadal tissues for the long term is critical in human fertility treatment and for the management of animal populations (livestock, biomedical models, and wild species). The need and number of banked germplasms are growing very fast in all disciplines, but current storage options at freezing temperatures are often constraining and not always sustainable. Recent research indicates that structures and functions of gametes or gonadal tissues can be preserved for the long term using different strategies based on dehydration and storage at supra-zero temperatures. However, more studies are needed in rehydration and reanimation of germplasms (including proper molecular and cellular evaluations). Conclusions: While a lot of research is still warranted to optimize drying and rehydration conditions for each sample type and each species, alternative preservation methods will change the paradigm in fertility preservation and biobanking. It will transform the way we maintain and manage precious biomaterials for the long term.

Abstract Background Fruit skin color play important role in commercial value of cucumber, which is mainly determined by the content and composition of chlorophyll and anthocyanins. Therefore, understanding the related genes and metabolomics involved in composition of fruit skin color is essential for cucumber quality and commodity value. Results The results showed that chlorophyll a, chlorophyll b and carotenoid content in fruit skin were higher in Lv (dark green skin) than Bai (light green skin) on fruit skin. Cytological observation showed more chloroplast existed in fruit skin cells of Lv. A total of 162 significantly different metabolites were found between the fruit skin of the two genotypes by metabolome analysis, including 40 flavones, 9 flavanones, 8 flavonols, 6 anthocyanins, and other compounds. Crucial anthocyanins and flavonols for fruit skin color, were detected significantly decreased in fruit skin of Bai compared with Lv. By RNA-seq assay, 4516 differentially expressed genes (DEGs) were identified between two cultivars. Further analyses suggested that low expression level of chlorophyll biosynthetic genes, such as chlM, por and NOL caused less chlorophylls or chloroplast in fruit skin of Bai. Meanwhile, a predicted regulatory network of anthocyanin biosynthesis was established to illustrate involving many DEGs, especially 4CL, CHS and UFGT. Conclusions This study uncovered significant differences between two cucumber genotypes with different fruit color using metabolome and RNA-seq analysis. We lay a foundation to understand molecular regulation mechanism on formation of cucumber skin color, by exploring valuable genes, which is helpful for cucumber breeding and improvement on fruit skin color.

IP RAN need to adapt to the changes of 5G network architecture to meet the differentiated bearing requirements of eMBB,uRLLC and mMTC services defined by 5G.The network capabilities of “large bandwidth,low latency,flexible connection” are the basic requirements of IP RAN for 5G bearer.Firstly,the characteristics of 5G services and network architecture were analyzed,and the 5G-oriented IP RAN evolution scheme was proposed.Then,the key technologies of 5G-beared IP RAN were investigated and tested to provide support and suggestions for large-scale commercial deployment of 5G.

Glucose-dependent insulinotropic polypeptide (GIP) has pleiotropic actions on pancreatic endocrine function, adipose tissue lipid metabolism, and skeletal calcium metabolism. Recent data indicate a potential new role for GIP in the pathogenesis of cardiovascular disease. This review focuses on the emerging literature that highlights GIP’s role in inflammation—an established process in the initiation and progression of atherosclerosis. In vasculature tissue, GIP may reduce concentrations of circulating inflammatory cytokines, attenuate vascular endothelial inflammation, and directly limit atherosclerotic vascular damage. Important to recognize is that evidence exists to support both pro- and anti-inflammatory effects of GIP even within the same tissue/cell type. Therefore, future study designs must account for factors such as model heterogeneity, physiological relevance of doses/exposures, potential indirect effects on inflammatory pathways, and the glucose-dependent insulinotropic polypeptide receptor (GIPR) agonist form. Elucidating the specific effects of enhanced GIP signaling in vascular inflammation and atherosclerosis is crucial given the existing widespread use of DPP4 inhibitors and the emergence of dual-incretin receptor agonists for type 2 diabetes treatment.

Background Therapy with mesenchymal stem cells remains a promising but challenging approach to critical limb ischemia in diabetes because of the dismal cell survival. Methods and Results Critical limb ischemia in type 2 diabetes mouse model was used to explore the impact of diabetic limb ischemia on the survival of bone marrow mesenchymal stromal cells (bMSCs). Inhibition of intracellular reactive oxygen species was achieved with concomitant overexpression of superoxide dismutase (SOD)‐1 and glutathione peroxidase‐1 in the transplanted bMSCs, and extracellular reactive oxygen species was attenuated using SOD‐3 overexpression and N‐acetylcysteine treatment. In vivo optical fluorescence imaging and laser Doppler perfusion imaging were used to track cell retention and determine blood flow in diabetic ischemic limb, respectively. Survival of the transplanted bMSCs was significantly decreased in diabetic ischemic limb compared with the control. In vitro study indicated that advanced glycation end products, not high glucose, significantly decreased the proliferation of bMSCs and increased their apoptosis associated with increased reactive oxygen species production and selective reduction of SOD‐1 and SOD‐3. In vivo study demonstrated that concomitant overexpression of SOD‐1, SOD‐3, and glutathione peroxidase‐1, or host treatment with N‐acetylcysteine, significantly enhanced in vivo survival of transplanted bMSCs, and improved critical limb ischemia in diabetic mice. Combination of triple antioxidant enzyme overexpression in bMSCs with host N‐acetylcysteine treatment further improved bMSC survival with enhanced circulatory and functional recovery from diabetic critical limb ischemia. Conclusions Simultaneous suppression of reactive oxygen species from transplanted bMSCs and host tissue could additively enhance bMSC survival in diabetic ischemic limb with increased therapeutic efficacy in diabetes.

Cucumber (Cucumis sativus L.) is an important vegetable crop, which is thermophilic not heat resistant. High-temperature stress always results in sterility at reproductive stage. In the present study, we evaluate the male flower developmental changes under normal (CK) and heat stress (HS) condition. After HS, the activities of peroxidase (POD) and superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) were increased. In addition, the pollen fertility was significantly decreased; and abnormal tapetum and microspore were observed by paraffin section. Transcriptome analysis results presented that total of 5828 differentially expressed genes (DEGs) were identified after HS. Among these DEGs, 20 DEGs were found at four stages, including DNA binding transcription factor, glycosyltransferase, and wound-responsive family protein. The gene ontology term of carbohydrate metabolic process was significantly enriched in all anther stages, and many saccharides and starch synthase-related genes, such as invertase, sucrose synthase, and starch branching enzyme, were significantly different expressed in HS compared with CK. Furthermore, co-expression network analysis showed a module (midnightblue) strongly consistent with HS, and two hub genes (CsaV3_6G004180 and CsaV3_5G034860) were found with a high degree of connectivity to other genes. Our results provide comprehensive understandings on male flower development in cucumber under HS.

Cucurbits fruits have diverse shapes and sizes, but their genomes evolution and genetic basis of diversity are unclear. Here, the authors show that the wax gourd genome has the most ancestral karyotype among cucurbits and identify candidate genes which contribute to large fruit size by comparative and population genomics analyses.

Abstract Background Chrysosplenetin is an O-methylated flavonol compound isolated from the plant Chamomilla recutita and Laggera pterodonta. The aim of our research is to evaluate the function of Chrysosplenetin on osteogenesis of human-derived bone marrow stromal cells (hBMSCs) and inhibition of estrogen deficiency-induced osteoporosis via the Wnt/β-catenin signaling pathway. Method hBMSCs are cultured and treated by Chrysosplenetin in the absence or presence of Wnt inhibitor dickkopf-related protein 1 (DKK1) or bone morphogenetic protein 2 (BMP2) antagonist Noggin. RT-qPCR is taken to identify the genetic expression of target genes of Wnt/β-catenin pathway and osteoblast-specific markers. The situation of β-catenin is measured by western blot and immunofluorescence staining. An ovariectomized (OVX) mouse model is set up to detect the bone loss suppression by injecting Chrysosplenetin. Micro-CT and histological assay are performed to evaluate the protection of bone matrix and osteoblast number. Serum markers related with osteogenesis are detected by ELISA. Results In the present study, it is found that Chrysosplenetin time-dependently promoted proliferation and osteoblastogenesis of hBMSCs reaching its maximal effects at a concentration of 10 μM. The expressions of target genes of Wnt/β-catenin pathway and osteoblast-specific marker genes are enhanced by Chrysosplenetin treatment. Furthermore, the phosphorylation of β-catenin is decreased, and nuclear translocation of β-catenin is promoted by Chrysosplenetin. Osteogenesis effects mentioned above are founded to be blocked by DKK1 or BMP2 antagonist Noggin. In vivo study reveals that Chrysosplenetin prevents estrogen deficiency-induced bone loss in OVX mice detected by Micro-CT, histological analysis, and ELISA. Conclusions Our study demonstrates that Chrysosplenetin improves osteoblastogenesis of hBMSCs and osteogenesis in estrogen deficiency-induced bone loss by regulating Wnt/β-catenin pathway.

Abstract Background and purpose Osteoporosis is characterized by excessive bone resorption due to enhanced osteoclast activation. Stimulation of nuclear factor of activated T cells 1 (NFATc1) and accumulation of reactive oxygen species (ROS) are important mechanisms underlying osteoclastogenesis. Robinin (Rob) is a flavonoid glycoside that has shown anti‐inflammatory and antioxidative effects in previous studies, but little is known about its effects on bone homeostasis. The purpose of our research was to investigate whether Rob could prevent bone resorption in ovariectomized (OVX) mice by suppressing osteoclast production through its underlying mechanisms. Methods The docking pose of Rob and RANKL was identified by protein‐ligand molecular docking. Rob was added to bone marrow macrophages (BMMs) stimulated by nuclear factor‐κB (NF‐κB) ligand (RANKL). The effects of Rob on osteoclastic activity were evaluated by positive tartrate resistant acid phosphatase (TRAcP) staining kit and hydroxyapatite resorption assay. RANKL‐induced ROS generation in osteoclasts was detected by H2DCFDA and MitoSox Red staining. The classic molecular cascades triggered by RANKL, such as NF‐κB, ROS, calcium oscillations, and NFATc1‐mediated signaling pathways, were investigated using Fluo4 staining, western blot, and quantitative real‐time polymerase chain reaction. In addition, an OVX mouse model mimicking estrogen‐deficient osteoporosis was created to evaluate the therapeutic effects of Rob in vivo. Results Computational docking results showed that Rob could bind specifically to RANKL's predicted binding sites. In vitro, Rob inhibited RANKL‐mediated osteoclastogenesis dose‐dependently without obvious cytotoxicity at low concentrations. We also found that Rob attenuated RANKL‐induced mitochondrial ROS production or enhanced activities of ROS‐scavenging enzymes, and ultimately reduced intracellular ROS levels. Rob abrogated the RANKL‐induced mitogen‐activated protein kinase (MAPK) and NF‐κB signaling pathways, and subsequently blocked NFATc1 signaling and TRAcP expression. In addition, Rob inhibited osteoclast proliferation by downregulating the expression of osteoclast target genes (Acp5, Cathepsin K, Atp6v0d2, Nfact1, c‐Fos, and Mmp9) and reducing Ca2+ oscillations. Our in vivo results showed that Rob reduced bone resorption in OVX animal model by repressing osteoclast activity and function. Conclusions Rob inhibits the activation of osteoclasts by targeting RANKL and is therefore a potential osteoporosis drug.

Abstract Cancer stem cells (CSCs) are rare cancer cells that are postulated to be responsible for cancer relapse and metastasis. However, CSCs are difficult to isolate and poorly understood. Here, a bioinspired approach for label‐free isolation and culture of CSCs, by microencapsulating one cancer cell in the nanoliter‐scale hydrogel core of each prehatching embryo‐like core–shell microcapsule, is reported. Only a small percentage of the individually microencapsulated cancer cells can proliferate into a cell colony. Gene and protein expression analyses indicate high stemness of the cells in the colonies. Importantly, the colony cells are capable of cross‐tissue multilineage (e.g., endothelial, cardiac, neural, and osteogenic) differentiation, which is not observed for “CSCs” isolated using other contemporary approaches. Further studies demonstrate the colony cells are highly tumorigenic, metastatic, and drug resistant. These data show the colony cells obtained with the bioinspired one‐cell‐culture approach are truly CSCs. Significantly, multiple pathways are identified to upregulate in the CSCs and enrichment of genes related to the pathways is correlated with significantly decreased survival of breast cancer patients. Collectively, this study may provide a valuable method for isolating and culturing CSCs, to facilitate the understanding of cancer biology and etiology and the development of effective CSC‐targeted cancer therapies.

Mitochondria are critical subcellular organelles that produce most of the adenosine triphosphate (ATP) as the energy source for most eukaryotic cells. Moreover, recent findings show that mitochondria are not only the “powerhouse” inside cells, but also excellent targets for inducing cell death via apoptosis that is mitochondria-centered. For several decades, cancer nanotherapeutics have been designed to specifically target mitochondria with several targeting moieties, and cause mitochondrial dysfunction via photodynamic, photothermal, or/and chemo therapies. These strategies have been shown to augment the killing of cancer cells in a tumor while reducing damage to its surrounding healthy tissues. Furthermore, mitochondria-targeting nanotechnologies have been demonstrated to be highly efficacious compared to non-mitochondria-targeting platforms both in vitro and in vivo for cancer therapies. Moreover, mitochondria-targeting nanotechnologies have been intelligently designed and tailored to the hypoxic and slightly acidic tumor microenvironment for improved cancer therapies. Collectively, mitochondria-targeting may be a promising strategy for the engineering of nanoparticles for drug delivery to combat cancer.

The 17q23 amplicon containing the WIP1 oncogene is frequently amplified in HER2+ breast cancer. Here they find MIR21 to be present in WIP1-containing amplicons, and report nanoparticle based co-delivery of WIP1 and miR-21 inhibitors to be effective in trastuzumab-resistant HER2+ breast cancer.

Heterozygous loss of chromosome 17p is a common genomic event in castration-resistant prostate cancers (CRPC). Here, the authors use CRISPR-based screen to identify RBX1 as a target gene for CRPC with 17p loss and targeting RBX1 sensitizes CRPC to the treatment of α-amanitin antibody conjugates.

In the age of big data, services in the pervasive edge environment are expected to offer end-users better Quality-of-Experience (QoE) than that in a normal edge environment. However, the combined impact of the storage, delivery, and sensors used in various types of edge devices in this environment is producing volumes of high-dimensional big data that are increasingly pervasive and redundant. Therefore, enhancing the QoE has become a major challenge in high-dimensional big data in the pervasive edge computing environment. In this paper, to achieve high QoE, we propose a QoE model for evaluating the qualities of services in the pervasive edge computing environment. The QoE is related to the accuracy of high-dimensional big data and the transmission rate of this accurate data. To realize high accuracy of high-dimensional big data and the transmission of accurate data through out the pervasive edge computing environment, in this study we focused on the following two aspects. First, we formulate the issue as a high-dimensional big data management problem and test different transmission rates to acquire the best QoE. Then, with respect to accuracy, we propose a Tensor-Fast Convolutional Neural Network (TF-CNN) algorithm based on deep learning, which is suitable for high-dimensional big data analysis in the pervasive edge computing environment. Our simulation results reveal that our proposed algorithm can achieve high QoE performance.

Multidrug resistance is a major challenge in cancer therapy. Here, the authors develop a mitochondria-targeting nanoparticle system that inhibits adenosine triphosphate transporter activity via reactive oxygen species generation and can thus be used to target multidrug-resistant cancer.

The alternating current potential drop technique has been widely used to measure subsurface cracks in metal structures. However, the application of the technique to random cracks has, to date, been limited. By using a multidirectional alternating current potential drop technique, the angle between crack and exciting electrode wire changes from 0° – 90° to 67.5° – 90°, which considerably expanded the ranges of detection. Simulation and experiment results showed that this technique can accurately measure the depth of random cracks.

MicroRNAs (miRNAs) are endogenous single-stranded non-coding small RNAs of 20–24 nucleotides and play important roles in many plant biological and metabolic processes. Wax gourd is an important vegetable of Cucurbitacea family, with great economic and medicinal value. Although miRNAs have been extensively studied in model plant species, less is known in wax gourd (Benincasa hispida). In this study, in order to identify miRNAs in wax groud, five independent small RNA libraries were constructed using leaf, root, stem, flower, and fruit of B227. Based on high-throughput Illumina deep sequencing. In total, 422 known and 409 novel miRNAs were identified from five libraries. Comparative analysis revealed that many miRNAs were differentially expressed among different tissues, indicating tissue-specific expression of some miRNAs. qRT-PCR verified the reliability of small RNA sequencing results. Furthermore, miRNAs with similar expression patterns among five tissues were clustered into the same profile, among which many miRNAs were found with relatively high expression in the fruit of wax gourd. MiR164-x had the highest expression in fruit than in other tissues and many NAC transcription factors were predicted as its target genes. We propose that miR164 might regulate fruit development by forming miR164-NAC module in wax gourd. Taken together, this study provides the first global miRNAs profiling of wax gourd, and lays the foundation for understanding the regulatory roles of miRNAs in the growth and development processes of wax gourd.