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Background: Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly surgical patients. Structural MRI and arterial spin labelling (ASL) techniques found that the grey matter volume and cerebral perfusion in some specific brain areas are associated with the occurrence of POCD, but the results are inconsistent, and the predictive accuracy is low. We hypothesised that the combination of cortical grey matter volumetry and cerebral blood flow yield higher accuracy than either of the methods in discriminating the elderly individuals who are susceptible to POCD after abdominal surgery. Materials and Methods: Participants underwent neuropsychological testing before and after surgery. Postoperative cognitive dysfunction (POCD) was defined as a decrease in cognitive score of at least 20%. ASL-MRI and T1-weighted imaging were performed before surgery. We compared differences in cerebral blood flow (CBF) and cortical grey matter characteristics between POCD and non-POCD patients and generated receiver operating characteristic curves. Results: Out of 51 patients, 9 (17%) were diagnosed with POCD. CBF in the inferior frontal gyrus was lower in the POCD group compared to the non-POCD group (p < 0.001), and the volume of cortical grey matter in the anterior cingulate gyrus was higher in the POCD group (p < 0.001). The highest AUC value was 0.973. Conclusions: The combination of cortical grey matter volumetry and cerebral perfusion based on ASL-MRI has improved efficacy in the early warning of POCD to elderly abdominal surgical patients.

The impact of Mg on the solidification structure of hypereutectic Al–Si alloys with different Si contents (15 wt% and 18 wt%) was investigated. 3%Mg was added to Al–15Si alloy to modify the phases in the solidification structure for the improvement of mechanical properties, and T6 heat treatment was used to optimize the microstructure and precipitate strengthening phase. The solidification structure was observed by OM and TEM respectively, and the precipitation behavior of each phase was detected through DSC. The results show that the addition of Mg decreased the undercooling of the alloy melt, thus suppressing the precipitation of primary Si phase. Nanoscale β” precipitates were precipitated in the matrix after T6 heat treatment. This resulted in an increase of 54% and 165% in the UTS and EL of the alloy, reaching 252 MP and 15.1%, respectively. Primary Si crystals were present in two forms in Al–18Si–8Mg alloy: spinel twin and non-twin, while Mg2Si always maintained the faceted crystals during the growing process, where only (100) and (111) crystal planes were observed. XRD, SEM and EBSD have been used to prove that Mg2Si crystals with different morphologies could become the heterogeneous nuclei of two types of primary Si crystals. The process of nucleation and growth of primary Si with Mg2Si as the heterogeneous nuclei was experimentally analyzed and theoretically predicted.

Abstract Background Albendazole (ABZ) and atovaquone (ATO) achieve killing efficacy on Echinococcus granulosus (Egs) by inhibiting energy metabolism, but their utilization rate is low. This study aims to analyze the killing efficacy of ABZ-ATO loading nanoparticles (ABZ-ATO NPs) on Egs. Methods Physicochemical properties of NPs were evaluated by ultraviolet spectroscopy and nanoparticle size potentiometer. In vitro experiments exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on protoscolex activity, drug toxicity on liver cell LO2, ROS production, and energy metabolism indexes (lactic dehydrogenase, lactic acid, pyruvic acid, and ATP). In vivo of Egs-infected mouse model exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on vesicle growth and organ toxicity. Results Drug NPs are characterized by uniform particle size, stability, high drug loading, and − 21.6mV of zeta potential. ABZ or ATO NPs are more potent than free drugs in inhibiting protoscolex activity. The protoscolex-killing effect of ATO-ABZ NPs was stronger than that of free drugs. In vivo Egs-infected mice experiment showed that ATO-ABZ NPs reduced vesicle size and could protect various organs. The results of energy metabolism showed that ATO-ABZ NPs significantly increased the ROS level and pyruvic acid content, and decreased lactate dehydrogenase, lactic acid content, and ATP production in the larvae. In addition, ATO-ABZ NPs promoted a decrease in DHODH protein expression in protoscolexes. Conclusion ATO-ABZ NPs exhibits anti-CE in vitro and in vivo, possibly by inhibiting energy production and promoting pyruvic acid aggregation.

Context Epigallocatechin-3-gallate (EGCG), the predominant catechin in green tea, has shown the potential to combat various types of cancer cells through its ability to modulate multiple signaling pathways. However, its low bioavailability and rapid degradation hinder its clinical application.Objective This review explores the potential of nanoencapsulation to enhance the stability, bioavailability, and therapeutic efficacy of EGCG in cancer treatment.Methods We searched the PubMed database from 2019 to the present, using ‘epigallocatechin gallate’, ‘EGCG’, and ‘nanoparticles’ as search terms to identify pertinent literature. This review examines recent nano-engineering technology advancements that encapsulate EGCG within various nanocarriers. The focus was on evaluating the types of nanoparticles used, their synthesis methods, and the technologies applied to optimize drug delivery, diagnostic capabilities, and therapeutic outcomes.Results Nanoparticles improve the physicochemical stability and pharmacokinetics of EGCG, leading to enhanced therapeutic outcomes in cancer treatment. Nanoencapsulation allows for targeted drug delivery, controlled release, enhanced cellular uptake, and reduced premature degradation of EGCG. The studies highlighted include those where EGCG-loaded nanoparticles significantly inhibited tumor growth in various models, demonstrating enhanced penetration and efficacy through active targeting mechanisms.Conclusions Nanoencapsulation of EGCG represents a promising approach in oncology, offering multiple therapeutic benefits over its unencapsulated form. Although the results so far are promising, further research is necessary to fully optimize the design of these nanosystems to ensure their safety, efficacy, and clinical viability.

AbstractContext Podophyllotoxin (PPT) derivatives, used in cancer therapy, require development toward enhanced efficacy and reduced toxicity.Objective This study synthesizes PPT derivatives to assess their anticancer activities.Materials and methods Compounds E1-E16 antiproliferative activity was tested against four human cancer cell lines (H446, MCF-7, HeLa, A549) and two normal cell lines (L02, BEAS-2B) using the CCK-8 assay. The effects of compound E5 on A549 cell growth were evaluated through molecular docking, in vitro assays (flow cytometry, wound healing, Transwell, colony formation, Western blot), and in vivo tests in female BALB/c nude mice treated with E5 (2 and 4 mg/kg). E5 (4 mg/kg) significantly reduced xenograft tumor growth compared to the DMSO control group.Results Among the 16 PPT derivatives tested for cytotoxicity, E5 exhibited potent effects against A549 cells (IC50: 0.35 ± 0.13 µM) and exceeded the reference drugs PPT and etoposide to inhibit the growth of xenograft tumours. E5-induced cell cycle arrest in the S and G2/M phases accelerated tubulin depolymerization and triggered apoptosis and mitochondrial depolarization while regulating the expression of apoptosis-related proteins and effectively inhibited cell migration and invasion, suggesting a potential to limit metastasis. Molecular docking showed binding of E5 to tubulin at the colchicine site and to Akt, with a consequent down-regulation of PI3K/Akt pathway proteins.Discussion and conclusions This research lays the groundwork for advancing cancer treatment through developing and using PPT derivatives. The encouraging results associated with E5 call for extended research and clinical validation, leading to novel and more effective cancer therapies.

Fusarium pathogens and their mycotoxins are considered as the main threats to cereal production and food safety worldwide. However, due to the constant discovery of new Fusarium species especially along with mycotoxin production profile differentiation in certain species, efforts on their species composition, geographical distribution, and chemotype proportion are urgently required. In the Fusarium goolgardi species, two distinct trichothecene (TB) genotype populations have recently been identified. Previous studies have shown that the structural variance of TBs biosynthesized by the two genotypes is attributed to the Tri1 gene. Polymorphisms of Tri1 gene from type A TB-producers were investigated in different Fusarium species in the current study. According to these DNA sequence variations identified in Tri1 gene sequences, a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based diagnostic approach for the differentiation of T-2 and 4,15-diacetoxyscirpenol (DAS) genotypes in F. goolgardi was successfully developed. The PCR-RFLP assay will facilitate the studies on geographic distribution, frequency and other aspects of the two genotypes within F. goolgardi species.

Abstract Background The tumor-specific immune responses, essential for removing residual lesions and preventing tumor metastases, can be stimulated by tumor-associated antigens (TAAs) released following photothermal therapy (PTT). However, due to the immunosuppressed microenvironment of pancreatic ductal adenocarcinoma (PDAC), the TAAs released by PTT are difficult to induce an effective immune response. In this work, we prepared the mesoporous silica (mSiO2) coated black titanium dioxide (bTiO2) photothermal nanoparticles (NPs) for enhanced photothermal-immunotherapy toward PDAC, in which resiquimod (R848) was loaded and DOTA-Gd was conjugated. The NPs are specified as bTiO2@mSiO2@Gd/R848 and abbreviated to NPs/R848. R848 as a kind of Toll-like receptor 7/8 agonist can remodel the tumor microenvironment (TME) in PDAC and induce a strong immune response. Furthermore, DOTA-Gd serves as a magnetic resonance imaging (MRI) contrast agent to improve the T1-weighted MRI performance of the NPs. Results In vitro results of this study show that NPs/R848 could thermally ablate tumor cells and efficiently trigger dendritic cell (DC) maturation. The results of in vivo investigations demonstrate that the combined use of photothermal-immunotherapy exhibits a significant inhibitory effect on tumor growth. Besides, it promoted maturation of DCs and enhanced infiltration of CD8 + , CD4 + T cells to improve the TME in PDAC. Conclusions Our study anticipates that by encouraging the maturation of DCs, this strategy will improve the TME and enable the successful photothermal-immunotherapy of PDAC.

Abstract Due to the requirement for highly precise synchronous sampling and the substantial reliance on time difference calculations, the current partial discharge (PD) localization based on the time difference of arrival is only applicable in certain situations. As digital twin technology has advanced, it is possible to employ virtual models to support gas‐insulated switchgear (GIS) PD localization. To do this, we propose a meta‐learning (ML) network with the aid of digital twin for actual GIS PD localization. Firstly, a GIS digital twin model was established to acquire an auxiliary simulated sample library. Then, a temporal convolutional network is established to extract the discriminable features, effectively obtain the time dependence between features, and improve the accuracy of localization. Next, ML is adopted to quickly learn meta‐knowledge that can be applied across tasks, and the model's sensitivity to task changes is improved. Finally, the model is fine‐tuned through a limited number of samples from the target task, and high precise PD localization is achieved. The experimental results demonstrate that the ML has an average localization error of only 9.25 cm and a probability density rose to 93% within 20 cm, which is clearly superior to previous methods.

The prosperity of the nighttime economy is an important criterion for measuring urban development. Based on regression analysis of data from 330 prefecture-level cities in China, this study explores the potential link between urban lighting and urban innovation capacity. The results show that the relationship between nighttime light intensity and urban innovation capacity follows an inverted U-shaped curve. Moreover, urban nighttime light stability moderates the above relationship. In addition, the heterogeneity analysis indicates that low population density, weak economic foundation, and high administrative grade weaken the relationship between lighting intensity and urban innovation capacity. Finally, the mechanism analysis suggested that the inverted U-shaped relationship between urban lighting and innovation capacity may be caused by the encroachment of the service industry and the loss of urban attractiveness. By exploring the proxy effect of nighttime lighting on urban innovation, this study reveals the imbalance between extrinsic image and the intrinsic capacity of cities, which not only extends the research on urban construction and development but also provides guidance for local governments concerning how to achieve all-round coordination of cities.

The seed storage materials accumulate during seed development, and are essential for seed germination and seedling establishment. Here we employed two bi-parental populations of an F2:3 population developed from a cross of improved 220 (I220, small seeds with low starch) and PH4CV (large seeds with high starch), as well as recombinant-inbred lines (RILs) of X178 (high starch) and its improved introgression line I178 (low starch), to identify the genes that control seed storage materials. We identified a total of 12 QTLs for starch, protein and oil, which explained 3.44–10.79% of the phenotypic variances. Among them, qSTA2-1 identified in F2:3 and qSTA2-2 identified in the RILs partially overlapped at an interval of 7.314–9.554 Mb, and they explained 3.44–10.21% of the starch content variation, so they were selected for further study. Fine mapping of qSTA2-2 with the backcrossed populations of I220/PH4CV in each generation narrowed it down to a 199.7 kb interval that contains 14 open reading frames (ORFs). Transcriptomic analysis of developing seeds from the near-isogenic lines (NILs) of I220/PH4CV (BC5F2) showed that only 11 ORFs were expressed in 20 days after pollination (DAP) seeds. Five of them were upregulated and six of them were downregulated in NILI220, and the differentially expressed genes (DEGs) between NILI220 and NILPH4CV were enriched in starch metabolism, hormone signal transduction and glycosaminoglycan degradation. Of the eleven NILI220 differential expressed ORFs, ORF4 (Zm00001d002260) and ORF5 (Zm00001d002261) carry 75% protein sequence similarity, both encodes an glycolate oxidase, were the possible candidates of qSTA2-2. Further analysis and validation indicated that mutation of the qSTA2-2 locus resulted in the dysfunction of ABA accumulation, the embryo/endosperm ratio and the starch and hormone levels.

Abstract Background Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. Methods This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. Discussion This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. Trial registration ChiCTR1800017646.

Abstract Fully homomorphic encryption (FHE) has experienced significant development and continuous breakthroughs in theory, enabling its widespread application in various fields, like outsourcing computation and secure multi-party computing, in order to preserve privacy. Nonetheless, the application of FHE is constrained by its substantial computing overhead and storage cost. Researchers have proposed practical acceleration solutions to address these issues. This paper aims to provide a comprehensive survey for systematically comparing and analyzing the strengths and weaknesses of FHE acceleration schemes, which is currently lacking in the literature. The relevant researches conducted between 2019 and 2022 are investigated. We first provide a comprehensive summary of the latest research findings on accelerating FHE, aiming to offer valuable insights for researchers interested in FHE acceleration. Secondly, we classify existing acceleration schemes from algorithmic and hardware perspectives. We also propose evaluation metrics and conduct a detailed comparison of various methods. Finally, our study presents the future research directions of FHE acceleration, and also offers both guidance and support for practical application and theoretical research in this field.

ABSTRACTOxidative stress and neuronal dysfunction caused by intracerebral haemorrhage (ICH) can lead to secondary injury. The m6A modification has been implicated in the progression of ICH. This study aimed to investigate the role of the m6A reader YTHDC2 in ICH-induced secondary injury. ICH models were established in rats using autologous blood injection, and neuronal cell models were induced with Hemin. Experiments were conducted to overexpress YTH domain containing 2 (YTHDC2) and examine its effects on neuronal dysfunction, brain injury, and neuronal ferritinophagy. RIP-qPCR and METTL3 silencing were performed to investigate the regulation of YTHDC2 on nuclear receptor coactivator 4 (NCOA4). Finally, NCOA4 overexpression was used to validate the regulatory mechanism of YTHDC2 in ICH. The study found that YTHDC2 expression was significantly downregulated in the brain tissues of ICH rats. However, YTHDC2 overexpression improved neuronal dysfunction and reduced brain water content and neuronal death after ICH. Additionally, it reduced levels of ROS, NCOA4, PTGS2, and ATG5 in the brain tissues of ICH rats, while increasing levels of FTH and FTL. YTHDC2 overexpression also decreased levels of MDA and Fe2+ in the serum, while promoting GSH synthesis. In neuronal cells, YTHDC2 overexpression alleviated Hemin-induced injury, which was reversed by Erastin. Mechanistically, YTHDC2-mediated m6A modification destabilized NCOA4 mRNA, thereby reducing ferritinophagy and alleviating secondary injury after ICH. However, the effects of YTHDC2 were counteracted by NCOA4 overexpression. Overall, YTHDC2 plays a protective role in ICH-induced secondary injury by regulating NCOA4-mediated ferritinophagy.

Lychee, a key economic crop in southern China, has numerous similar-looking varieties. Classifying these can aid farmers in understanding each variety's growth and market demand, enhancing agricultural efficiency. However, existing classification techniques are subjective, complex, and costly. This paper proposes a lychee classification method using an improved ResNet-34 residual network for six common varieties. We enhance the CBAM attention mechanism by replacing the large receptive field in the SAM module with a smaller one. Attention mechanisms are added at key network stages, focusing on crucial image information. Transfer learning is employed to apply ImageNet-trained model weights to this task. Test set evaluations demonstrate that our improved ResNet-34 network surpasses the original, achieving a recognition accuracy of 95.8442%, a 5.58 percentage point improvement.

AimOur study aimed to assess the association between UCP2 gene 3’ untranslated region insertion/deletion (3’UTR I/D) and A55V (alanine/valine) polymorphisms and neural tube defects (NTDs) susceptibility.Materials and methodsAccording to pre-determined inclusion and exclusion criteria, the article search was conducted to search articles published before October 2023. Two authors independently screened the included articles and extracted their basic characteristics. After quality evaluation, the meta-analysis and trial sequential analysis (TSA) were conducted using RevMan 5.4, Stata/MP 17, and TSA 0.9.5.10 Beta. Subgroup analysis was conducted based on country and case group composition. Sensitivity analysis was conducted using a one-by-one exclusion method. Begg’s and Egger’s tests were used to evaluate publication bias.ResultsA total of seven articles were included. Overall meta-analysis revealed significant heterogeneity among the included studies for 3’UTR I/D polymorphism of the UCP2 gene. Significant statistical data indicated that those with the DD genotype and D allele had higher chances of NTD compared to those with the II genotype and the I allele, respectively. The combined result of II vs. ID was not statistically significant. A55V variation showed no statistical significance in the risk of NTD, despite the absence of significant heterogeneity across the included studies. Most of the heterogeneity was resolved after subgrouping, and a higher risk of the ID genotype was found than the II genotype for Chinese people. Genotyping NTD patients or their mothers was not a factor affecting the heterogeneity. Sensitivity analysis and publication bias analysis suggested that positive findings supported our results.ConclusionThe UCP2 gene 3’UTR I/D polymorphism increased the likelihood of developing NTDs in the Chinese population, with the D allele being the risk factor, which contributed to the understanding of the genetic basis of NTDs. TSA indicated that more high-quality original studies were needed in the future for further validation.

Abstract The emergence of various topological semimetal states presents a novel opportunity for enhancing the efficiency of thermoelectric transport. This study introduces a recipe to improve the thermoelectric (TE) performance in topological materials containing single‐pair Weyl points (SP WPs) fermions and phonons. The recipe focuses on two key factors contributing to the enhancement of TE performance: the increase in the density of states to achieve a high power factor, and the introduction of additional phonon scattering to reduce the lattice thermal conductivity. The proposed recipe is confirmed in a half‐metallic SP WPs material BaNiIO6 through first‐principles methods. An enhanced density of states arises near the energy of the SP WPs in BaNiIO6, leading to a peak power factor connected to the complex Fermi surface due to the degeneracy of Weyl pockets in energy. Furthermore, it is shown that the SP WPs phonons in BaNiIO6 possess a high scattering rate and can likely contribute to the low lattice thermal conductivity, especially when two crossing points in SP WPs do not degenerate in frequency. The new recipe can be used for discovering high‐performance thermoelectric materials in the future by utilizing the transport advantages of degenerate‐in‐energy SP WPs fermions and non‐degenerate‐in‐frequency SP WPs phonons.

Geopolymer is an emerging green cementitious material that can be used to stabilize dredged clay (DC) as construction materials. This paper presented an experimental study on the effects of desulfurized gypsum (DG) on the mechanical properties (e.g., stress-strain characteristics, unconfined compressive strength (UCS) and water stability) of stabilized DC with high initial water content using the ternary geopolymer based on fly ash (FA), ground granulated blast-furnace slag (GGBS) and DG. Moreover, microstructure tests were conducted to elucidate the mechanism of the mechanical enhancement of the stabilized DC. The results clearly demonstrated that DG exerted a significant influence on the mechanical properties of the stabilized DC. Notably, the incorporation of DG led to a transition from ductile to brittle behavior and a notable increase in the deformation modulus (E50). DG effectively enhances the unconfined compression strength (UCS) of stabilized DC with a high initial water content. The peak UCS for the stabilized DC sample with an initial water content of 2.0wL reached 1632.9 kPa with the mass ratio of DG to solid waste FA and GGBS (i.e., D/S) of 8%. Stabilized DC at the low D/S ratio exhibited excellent water stability, while the stabilized DC at the D/S ratio of 8% retained the highest strength after water immersion. The threshold of the D/S ratio is determined to be 8%. Microstructure characterization revealed that the strength enhancement of the stabilized DC primarily relies on the cementation effect of geopolymer gel and crystalline C-(A)-S-H, along with the filling effect of ettringite. However, a significant amount of ettringite can lead to an expansion in the DC volume and disrupt the weak cementation bonding, ultimately causing a deterioration in strength.

In this study, a UPLC-MS/MS method was developed for the rapid detection of 71 neuropsychotropic drugs in human serum for drug concentration monitoring and toxicity screening. The analytes were separated from the biological matrix by protein precipitation using a methanol-acetonitrile solvent mixture. The chromatographic separation was performed on a Kromasil ClassicShell C18 column (2.1*50 mm, 2.5 μ m) with gradient elution using acetonitrile-0.2 % acetic acid and 10 mM ammonium acetate as the mobile phases (flow rate 0.4 mL/min, column temperature 40 °C, injection volume 5 μL). An electrospray ion source in both positive and negative ion modes with multiple ion monitoring was used. The total run time was 6 min. All compounds were quantified using the isotope internal standard method. Totally, 71 drugs were detected within their linear ranges with correlation coefficients greater than 0.990. The intra- and inter-batch precision relative standard deviations (RSDs) for the low, medium, and high concentration points were less than 15 %, with an accuracy of 90%–110 %. All compounds except Moclobemide N-oxindole are stabilised within 7 days. The relative matrix effect results for each analyte were within ±20 % of the requirements. The method is validated according to Clinical and Laboratory Standards Institute guidelines, easy to use, and has a low cost.

Breaking the poor permeability of immune checkpoint inhibitors (ICIs) caused by the stromal barrier and reversing the immunosuppressive microenvironment are significant challenges in pancreatic cancer immunotherapy. In this study, we synthesized core-shell Fe3O4@TiO2 nanoparticles to act as carriers for loading VISTA monoclonal antibodies to form Fe3O4@TiO2@VISTAmAb (FTV). The nanoparticles are designed to target the overexpressed ICIs VISTA in pancreatic cancer, aiming to improve magnetic resonance imaging-guided sonodynamic therapy (SDT)-facilitated immunotherapy. Laser confocal microscopy and flow cytometry results demonstrate that FTV nanoparticles are specifically recognized and phagocytosed by Panc-2 cells. In vivo experiments reveal that ultrasound-triggered TiO2 SDT can induce tumor immunogenic cell death (ICD) and recruit T-cell infiltration within the tumor microenvironment by releasing damage-associated molecular patterns (DAMPs). Furthermore, ultrasound loosens the dense fibrous stroma surrounding the pancreatic tumor and increases vascular density, facilitating immune therapeutic efficiency. In summary, our study demonstrates that FTV nanoparticles hold great promise for synergistic SDT and immunotherapy in pancreatic cancer.

The NF1 gene is related to neurofibromatosis type 1 (NF1), which is an autosomal dominant disorder associated with multisystem involvement and epilepsy susceptibility. A human induced pluripotent stem cell (iPSC) line was derived from a pediatric patient with NF1 and epilepsy, harboring a heterozygous NF1 gene mutation. The iPSC line exhibits high levels of pluripotency markers, maintains the NF1 gene mutation, and demonstrates the capacity to undergo differentiation potential in vitro into three germ layers. The iPSC line will serve as a valuable resource for investigating the underlying mechanisms and conducting drug screening related to NF1 and NF1-associated epilepsy.

BackgroundSepsis is commonly associated with a sudden impairment of brain function, thus leading to significant rates of illness and mortality. The objective of this research was to integrate microbiome and metabolome to reveal the mechanism of microbiota-hippocampus-metabolites axis dysfunction in a mouse model of sepsis.MethodsA mouse model of sepsis was established via cecal ligation and puncture. The potential associations between the composition of the gut microbiota and metabolites in the hippocampus of mice with sepsis were investigated by combining 16S ribosomal RNA gene sequencing and ultra-high-performance liquid chromatography tandem mass spectrometry.ResultsA total of 140 differential metabolites were identified in the hippocampal tissues of mice with sepsis when compared to those of control mice. These differential metabolites in mice with sepsis were not only associated with autophagy and serotonergic synapse, but also involved in the metabolism and synthesis of numerous amino acids. At the phylum level, the abundance of Bacteroidota was increased, while that of Firmicutes (Bacillota) was decreased in mice with sepsis. At the genus level, the abundance of Alistipes was increased, while that of Lachnospiraceae_NK4A136_group was decreased in mice with sepsis. The Firmicutes (Bacillota)/Bacteroidota (F/B) ratio was decreased in mice with sepsis when compared to that of control mice. Furthermore, the F/B ratio was positively correlated with 5′-methylthioadenosine, PC (18:3(9Z,12Z,15Z)/18:0) and curdione, and negatively correlated with indoxylsulfuric acid, corticosterone, kynurenine and ornithine.ConclusionAnalysis revealed a reduction in the F/B ratio in mice with sepsis, thus contributing to the disturbance of 5′-methylthioadenosine, curdione, PC (18:3(9Z,12Z,15Z)/18:0), corticosterone, ornithine, indoxylsulfuric acid and kynurenine; eventually, these changes led to hippocampus dysfunction. Our findings provide a new direction for the management of sepsis-induced hippocampus dysfunction.

Abstract Prostate cancer (PCa) is an extensive heterogeneous disease with a complex cellular ecosystem in the tumor microenvironment (TME). However, the manner in which heterogeneity is shaped by tumors and stromal cells, or vice versa, remains poorly understood. In this study, single‐cell RNA sequencing, spatial transcriptomics, and bulk ATAC‐sequence are integrated from a series of patients with PCa and healthy controls. A stemness subset of club cells marked with SOX9highARlow expression is identified, which is markedly enriched after neoadjuvant androgen‐deprivation therapy (ADT). Furthermore, a subset of CD8+CXCR6+ T cells that function as effector T cells is markedly reduced in patients with malignant PCa. For spatial transcriptome analysis, machine learning and computational intelligence are comprehensively utilized to identify the cellular diversity of prostate cancer cells and cell‐cell communication in situ. Macrophage and neutrophil state transitions along the trajectory of cancer progression are also examined. Finally, the immunosuppressive microenvironment in advanced PCa is found to be associated with the infiltration of regulatory T cells (Tregs), potentially induced by an FAP+ fibroblast subset. In summary, the cellular heterogeneity is delineated in the stage‐specific PCa microenvironment at single‐cell resolution, uncovering their reciprocal crosstalk with disease progression, which can be helpful in promoting PCa diagnosis and therapy.

Environmental issues associated with the aviation industry are getting more attention as air traffic increases. Stringent standards are imposed for fuel consumption and pollution emissions for next-generation aircraft. Superconducting electrical propulsion aircraft (SEPA) have been seen as an efficient way to achieve this goal. High-temperature superconducting (HTS) devices are extensively used in the power system to supply enormous energy. Power is distributed to the different loads via a DC distribution network. However, it will generate an inrush current over ten times higher than the rated current in short-circuit state, which is very harmful to the system. Therefore, it is essential to adopt an appropriate protection scheme. This paper discusses one protection scheme that combines DC vacuum circuit breakers (DC VCB) and resistive superconducting current limiters (RSFCL) for superconducting aircraft applications. Considering problems of cost and loss, the auxiliary capacitor is pre-charged by system voltage, and mechanical elements extinguish the arc. Furthermore, combined with RSFCL, the interrupting environment is fully improved. RSFCL limits fault current, and then the VCB breaks this limited current based on creating an artificial current zero (ACZ). The prospective rated power is 8MW, rated voltage and current are 4 kV and 1 kA, respectively. In this paper, we discuss and simulate switching devices that protect SEPA. The interrupting performance of the circuit breaker is analysed in the DC short-circuit fault that occurs on the transmission line. Finally, the residual energy consumption of different situations is calculated. A comparison is made between using RSFCL with metal oxide varistor (MOV) and just using MOV. The scheme with RSFCL shows a significant advantage in energy consumption.

The existing surface electromyography-based pattern recognition system (sEMG-PRS) exhibits limited generalizability in practical applications. In this paper, we propose a stacked weighted random forest (SWRF) algorithm to enhance the long-term usability and user adaptability of sEMG-PRS. First, the weighted random forest (WRF) is proposed to address the issue of imbalanced performance in standard random forests (RF) caused by randomness in sampling and feature selection. Then, the stacking is employed to further enhance the generalizability of WRF. Specifically, RF is utilized as the base learner, while WRF serves as the meta-leaning layer algorithm. The SWRF is evaluated against classical classification algorithms in both online experiments and offline datasets. The offline experiments indicate that the SWRF achieves an average classification accuracy of 89.06%, outperforming RF, WRF, long short-term memory (LSTM), and support vector machine (SVM). The online experiments indicate that SWRF outperforms the aforementioned algorithms regarding long-term usability and user adaptability. We believe that our method has significant potential for practical application in sEMG-PRS.

Abstract With the development of a distributed generation, direct current (DC) load and energy‐storage equipment, voltage‐source‐converter‐based medium‐voltage DC systems (VSC‐MVDC) have attracted more attention due to its low power consumption, high reliability, independent power control and so on. However, VSC‐MVDC has the problem of DC fault isolation, which requires the fast‐acting DC circuit‐breakers to isolate faulty lines and ensure low cost. This problem can be solved by coordinating resistive type superconducting‐fault‐current‐limiter (R‐SFCL) and integrated‐gate‐commutated‐thyristor (IGCT) based hybrid circuit breaker. Based on this, IGCT based superconducting DC circuit breaker (SDCCB) is proposed and analysed. Combining R‐SFCL with IGCT could realise large current limiting and interruption and ensure low cost. In addition, the IGCT based hybrid DC circuit breaker (IGCT‐HDCCB) is compared with the traditional insulated gate bipolar transistor (IGBT) based hybrid DC circuit breaker (IGBT‐HDCCB) to evaluate which circuit breaker is more suitable for VSC‐MVDC. The results show that, coordination based on R‐SFCL and SDCCB, the fault current is successfully limited from 17.6 to 2.1 kA, and then interrupted within 3.8 ms. In addition, IGCT‐HDCCB overcomes the disadvantage that IGCT has less interrupting capacity than IGBT, retains the advantage of low cost of IGCT and is more suitable for MVDC system.

Abstract The objective of this paper is to determine the transient characteristics and sites of the pre‐breakdown (pre‐BD) in the spark conditioning under power frequency voltage (PFV) in vacuum. A multi‐angle optical path system was designed and made the determination of the pre‐BD sites in spark conditioning possible, through one camera at two viewing angles. The experimental results indicate that, in the spark conditioning under PFV, the pre‐BDs continuously occurred at a random moment. Within several half‐waves, the number of the pre‐BDs could reach dozens of times, which was the key for the treatment of the electrode surface in conditioning. Under the application of PFV, the single pre‐BD occurred at a random moment, in which it would last for several microseconds and the peak value of the current would reach several amperes. Moreover, the pre‐BD sites randomly distributed in the surface of the electrode and almost covered the whole surface of the electrode. The pre‐BDs took place independently in both time and space, in which there should be no effect between each other of two sequential pre‐BDs. To sum up, the transient characteristics and the sites of the pre‐BDs determined in this paper could reveal the physical mechanism of the pre‐BD on the treatment of electrode surface in the conditioning process, which is quite significant to improve the BD voltage of vacuum interrupter.

Abstract Background Jaundice occurs in some pancreatic disease. However, its occurrences and role in pancreatic neuroendocrine neoplasms (PNENs) has not been well studied. In this study we showed the association between jaundice and the risk of high grade and poorly differentiated PNENs. Methods Ninety-three patients with head-neck PNENs were included. Poorly differentiated pancreatic neuroendocrine neoplasms were defined by a ki67 index > 55.0%. Logistic regression was used to show the association between demographic information, clinical signs and symptoms and the risk of poorly differentiated tumors. A nomogram model was developed to predict poorly differentiated tumor. Results Eight of 93 PNEN patients (8.6%) had jaundice. The age and ki67 index in patients with jaundice were significantly higher than those patients without jaundice. All jaundice occurred in patients with grade 3 PNENs. Mutivariable regression analysis showed that age (odds ratio(OR) = 1.10, 95% confidence interval (CI):1.02–1.19), tumor size (OR = 1.42, 95%CI:1.01-2.00) and jaundice (OR = 14.98, 95%CI: 1.22-184.09) were associated with the risk of poorly differentiated PNENs. The age and size combination showed a good performance in predicting poorly differentiated PNENs (area under the curve (AUC) = 0.81, 95% CI: 0.71–0.90). The addition of jaundice further improved the age- and size-based model (AUC = 0.86, 95% CI: 0.78–0.91). A nomogram was developed based on age, tumor size and jaundice. Conclusion Our data showed that jaundice was associated with the risk of high grade PNENs and poorly differentiated PNENs.

Abstract Pathogenic Escherichia coli is one of the most common causes of diarrhea diseases and its characteristic component of the outer membrane-lipopolysaccharide (LPS) is a major inducer of sepsis. Few drugs have been proven to kill bacteria and simultaneously neutralize LPS toxicity. Here, the chimeric peptides-R7, A7 and G7 were generated by connecting LBP14 (LPS-targeting domain) with L7 (killing domain) via different linkers to improve antibacterial and anti-inflammatory activities. Compared to parent LBP14-RKRR and L7, the antibacterial activity of R7 with a cleavable “RKRR” linker and the “LBP14-RKRR + L7” cocktail against Escherichia coli, Salmonella typhimurium and Staphylococcus aureus was increased by 2 ~ 4-fold. Both A7 and G7 with non-cleavable linkers almost lost antibacterial activity. The ability of R7 to neutralize LPS was markedly higher than that of LBP14-RKRR and L7. In vivo, R7 could be cleaved by furin in a time-dependent manner, and release L7 and LBP14-RKRR in serum. In vivo, R7 can enhance mouse survival more effectively than L7 and alleviate lung injuries by selective inhibition of the NF-κB signaling pathways and promoting higher IAP activity. It suggests that R7 may be promising dual-function candidates as antibacterial and anti-endotoxin agents.

Abstract Backgrounds This study aimed to compare whether Calcium phosphate cement (CPC) promotes the stability of osteoporotic lumbar pedicle screw by enhancer-injecters with different number of holes. Methods Through a self-designed bone cement injection device, the pedicle screw canal was strengthened with calcium phosphate bone cement, and divided into 4-hole group, 6-hole group, 8-hole group, straight pore group and the control group. The screw was inserted into the mechanical test module, the Maximum insertion torque and Maximum axial pull-out strength were recorded, and the distribution of calcium phosphate bone cement was analyzed by CT and X-ray. The data results were analyzed using SPSS19.0 statistical software package. Results The distribution of bone cement in different reinforcement groups was different and showed regularity. The bone cement in the 4-hole group was roughly located in the head 1/3 of the screw, the 6-hole group was located in the middle 1/3 of the screw, and the 8-hole group was located in the caudal 1/3 of the screw. Compared with the control group, the maximum axial pull-out force of screws in the lateral hole and full screw tunnel reinforcement group was significantly increased. There was no significant difference between the 4-hole, 6-hole and straight pore groups. There was no difference in the screw-in torque between the reinforcement groups, and they all increased significantly compared with the control group, and the difference was statistically significant. After the screw was pulled out, the interface between the bone cement and the polyurethane material was fractured, and a tight package was formed with the screw. Conclusions Enhancer syringes with different hole numbers combined with CPC bone cement injection can significantly increase the maximum screw pull-out force. The 8-hole group has a smaller pull-out force and is relatively prone to leakage of reinforcing material, which lacks safety in use. The local reinforcement of 4-hole and 6-hole sheath can play a similar role to that of total nail tunnel reinforcement.

ABSTRACT: Lactoferrin is an iron-binding glycoprotein of the transferrin family that is found in most bodily fluids of mammals and has a variety of biological and beneficial functions, with great importance in health enhancement as a supplement for humans and other animals. More than 300 t of lactoferrin were produced in 2021, and this number is expected to grow yearly by 10% to 12%, to over 580 t in 2030. With new and important functions of lactoferrin being revealed and studied, focus on its industrial production and application is increasing accordingly. However, lactoferrin is mainly sourced from cheese whey or skim milk by cation-exchange column chromatography, which is a costly and low-quality method. A potential solution for lactoferrin global supply chain construction is proposed in this article as a complement to traditional routes of purification from whey or skim milk. The large-scale production of lactoferrin, mainly by recombinant yeast, mammal, and grain systems, as well as the market niche and product design, are discussed.

Wound infections caused by Staphylococcus aureus often result in localized suppurative lesions that severely impede the healing process, so it is urgent to develop a dress with efficient antimicrobial and pro-healing functions. In this study, the bifunctional injectable hydrogel lactoferrin (Lf)/NZ2114/lithium magnesium silicate hydrogel (LMSH) was first successfully prepared through the electrostatic interaction method. The physical, biological, and efficacy properties are systematically analyzed with good shear-thinning capacity and biocompatibility. More importantly, it inhibits infection and promotes wound healing in a mouse wound infection model after 14 d treatment, and the bactericidal rate and healing rate were over 99.92% and nearly 100%, respectively. Meanwhile, the massive reduction of inflammatory cells, restoration of tissue structure, and angiogenesis in mice showed the anti-inflammatory and pro-healing properties of the hydrogel. The healed wounds showed thickening with more hair follicles and glands, suggesting that the hydrogel Lf/NZ2114/LMSH (Three in One) could be a better dressing candidate for the treatment of S. aureus-induced wound infections.

Plant seedling morphogenesis is considerably related to photosynthesis, pigment synthesis, and circadian periodicity during seedling development. We identified and cloned a maize zebra or crossbanding leaves mutant wk3735, which produces pale white kernels and was identified and plays a role in the equilibrium of the Redox state the in/out of ETC by active oxygen scavenging. Interestingly, it produces the zebra leaves during the production of the first seven leaves, which is apparently different from the mutation of homologs AtPTOX in Arabidopsis. It is intriguing to investigate how and why yellow crossbands (zebra leaf phenotype) emerge on leaves. As expected, chlorophyll concentration and photosynthetic efficiency both significantly declined in the yellow sector of wk3735 leaves. Meanwhile, we observed the circadian expression pattern of ZmPTOX1, which was further validated by protein interaction assays of the circadian clock protein TIM1 and ZmPTOX1. The transcriptome data of yellow (muW) and green (muG) sectors of knock-out lines and normal leaves of overexpression lines (OE) at the 5th-leaf seedling stage were analyzed. Zebra leaf etiolated sections exhibit a marked defect in the expression of genes involved in the circadian rhythm and rhythmic stress (light and cold stress) responses than green sections. According to the analysis of co-DEGs of muW vs. OE and muG vs. OE, terms linked to cell repair function were upregulated while those linked to environmental adaptability and stress response were downregulated due to the mutation of ZmPTOX1. Further gene expression level analyses of reactive oxygen species (ROS) scavenging enzymes and detection of ROS deposition indicated that ZmPTOX1 played an essential role in plant stress resistance and ROS homeostasis. The pleiotropic roles of ZmPTOX1 in plant ROS homeostasis maintenance, stress response, and circadian rhythm character may collectively explain the phenotype of zebra leaves during wk3735 seedling development.

With the increasing demand for the resilient capacity of transformers in high-proportion renewable energy grids, the overload capacity of transformers and the thermal conductivity of winding insulation materials have been put forward as important requirements. In response to these requirements, a novel ceramic high temperature tolerance insulation winding is proposed in this paper and is applied in a ceramic insulated winding transformer. A combination of simulation and experimentation is used to analyze the thermal-flow characteristics of this transformer. The temperature and flow field distribution characteristics of transformers with both winding insulation methods (ceramic and Nomex paper) are compared. The internal mechanism of reflux near the iron core and high voltage winding under forced air cooling is clarified. A superior outside cooling condition is obtained. A prototype ceramic insulated winding transformer is developed and tested to verify the accuracy of the simulation model. The results show that the hotspot temperature of the ceramic insulated winding transformer under natural cooling is 10.7% lower than that of the Nomex paper insulated winding transformer. With forced air cooling of 2, 3, 4, 5, and 6 m/s applied at the bottom, the hotspot temperature of the ceramic insulated winding transformer is 11.4%, 10.5%, 9.7%, 14.0%, and 17.8% lower than that of the Nomex paper insulation winding transformer, respectively. Under forced air cooling, a reflux phenomenon is observed in both transformers in the vicinity of the iron core and high voltage winding due to the formation of adverse pressure gradient region and wall viscous force blocking. The strength of the reflux is affected by the magnitude of the forced air cooling flow velocity and the construction of the transformer. The optimal range of the external cooling flow velocity for the ceramic insulated winding transformer is 3–4 m/s. The errors between the simulated temperature and the measured temperature at the nine monitoring points of the prototype are all less than 5%, which verifies the effectiveness of the simulation model. The experimental and theoretical basis for the design and application of resilient capacity dry type transformers is provided by this research.

Background: Cervicocerebral CT angiography (CTA) using the bolus tracking technique has been widely used for the assessment of cerebrovascular diseases. Regions of interest (ROI) can be placed in the descending aorta, ascending aorta, and the aortic arch. However, no study has compared the arteries and veins display when when the region of interest (ROI) is placed at different sites. In this study, we showed the impact of ROI positions on the image quality of cervicocerebral CTA. Methods: Two hundred and seventy patients who underwent cervicocerebral CTA with bolus tracking technique were randomly divided into three groups based on the position of the ROI placement: ascending aorta (Group 1, n = 90), aortic arch (Group 2, n = 90), and descending aorta (Group 3, n = 90). The scanning parameters and contrast agent injection protocols were consistent across all groups. Three observers independently assessed the objective image quality, while two observers jointly assessed the subjective image quality using a grade scale: poor (grade 1), average (grade 2), good (grade 3), and excellent (grade 4). The differences in intravascular CT values, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), AVCR (arterial venous contrast ratio), and subjective image quality scores were compared among the three groups. Results: The CT values of the intracranial veins (superior sagittal sinus, ethmoid sinus and great cerebral vein) in group 1 were significantly lower than those in group 3 (p

Objectives: The Knee Injury and Osteoarthritis Outcome Score (KOOS) has been utilized to evaluate short- and long-term outcomes in individuals following knee injuries, such as those with anterior cruciate ligament reconstruction and knee osteoarthritis, but has not yet been applied to individuals undergoing total knee arthroplasty (TKA) in China. The aim of this study was to assess the psychometric properties of the Simplified Chinese version of the KOOS in Chinese individuals undergoing TKA. Methods: This study distributed 170 questionnaires, and assessed the KOOS of the participants, along with requiring them to complete the Short Form 36 (SF-36) survey. There were 35 participants completed a test-retest reliability survey with a 24-h interval, 129 participants completed a pre - surgery survey, and 119 individuals completed a post - surgery survey 6 weeks after the surgery. The following tests were conducted: Cronbach's alpha (α) to assess internal consistency, intraclass correlation coefficient (ICC) to evaluate test-retest reliability, Spearman's correlation coefficient (ρ) to examine construct validity, effect size (ES) to detect measure responsiveness, minimal detectable change (MDC) to assess measurement errors. Floor and ceiling effects (

Coal worker's pneumoconiosis (CWP) is a common occupational disease that coal miners are highly susceptible due to long-term exposure to coal dust particles (CDP). CWP can induce the accumulation of immune cells surrounding the bronchioles and alveoli in the lungs, resulting in pulmonary fibrosis and compromised immune function. Using single-cell RNA sequencing (scRNA-Seq), our previous studies disclose that CDP exposure triggers heterogeneity of transcriptional profiles in mouse pneumoconiosis, while Vitamin D3 (VitD3) supplementation reduces CDP-induced cytotoxicity; however, the mechanism by which how VitD3 regulates immune status in coal pneumoconiosis remains unclear. In this study, we elucidated the heterogeneity of pulmonary lymphocytes in mice exposed to CDP and demonstrated the therapeutic efficacy of VitD3 using scRNA-Seq dataset. The validation of key lymphocyte markers and their functional molecules was performed using immunofluorescence. The results demonstrated that VitD3 increased the number of naive T cells by modulating CD4 + T cell differentiation and decreased the number of Treg cells in CDP-exposed mice, thereby enhancing the cytotoxic activity of CD8 + effector T cells. These effects markedly alleviated lung fibrosis and symptoms. Taken together, the mechanism by which VitD3 regulates the functions of lymphocytes in CWP provides a new perspective for further research on the prevention and treatment of CWP.

Although several pentatricopeptide repeat (PPR) proteins are involved in post-transcriptional processing of mitochondrial RNA, it is unclear which specific protein is involved in the RNA editing of ccmC in maize (Zea mays). Here we report the identification of the maize empty pericarp 601 (emp601) mutant and the map-based cloning of the Emp601 gene, which encodes an E2-type PPR protein that is targeted to mitochondria. A single-nucleotide deletion in the emp601 mutant caused a frameshift and introduced a premature stop codon into the predicted EMP601. This mutation was associated with reduced accumulation of mitochondrial complex III as well as with inhibition of growth and differentiation of basal endosperm transfer layer cells, leading to final degeneration of the embryo and endosperm. We determine that loss of EMP601 function prevents the C-to-U RNA editing of the mitochondrial transcript ccmC at position 358. EMP601 binds to the ccmC transcript and directly interacts with Multiple organellar RNA editing factor 8 and may be a component of the plant mitochondrial editosome. We conclude that EMP601 functions in RNA editing of mitochondrial ccmC transcripts and influences mitochondrial function and seed development.

Abstract In recent years, deep learning‐based fault diagnosis technology for high‐voltage circuit breakers (HVCB) has advanced significantly, but the working environment of HVCBs is complex, resulting in unsatisfactory fault diagnosis results of HVCBs in noisy environment and existing deep learning methods are difficult to solve this problem. This paper proposes a multi‐channel convolutional neural network combines dense residual structure and attention mechanism to achieve high‐precision and high‐robust diagnosis of HVCBs in noisy backgrounds. A dense residual network is introduced into the convolutional neural network to prevent feature loss during network propagation to preserve the difference information between the network layers as much as possible, Simultaneously, a channel attention mechanism is introduced to adaptively adjust the weights of different convolution channels. The model can extract multi‐scale features from the original signal and fully exploit the intrinsic relationship between the vibration signal and the HVCB's operating state. The experimental results show that the diagnostic method can still meet the requirements of fault diagnosis in the presence of noise, with an average diagnostic accuracy rate of 85.92% when the signal‐to‐noise ratio is −4. The model outperforms the traditional single‐channel model in terms of diagnostic accuracy and stability.

Abstract Muscular fatty infiltration is a common and troublesome pathology after rotator cuff tears (RCT), which mainly derives from fibro-adipogenic progenitors (FAPs). Compared to the RCT, fatty infiltration is not so severe in Achilles tendon tears (ATT). The knowledge of why fatty infiltration is more likely to occur after RCT is limited. In this study, more severe fatty infiltration was verified in supraspinatus than gastrocnemius muscles after tendon injury. Additionally, we revealed higher adipogenic differentiation ability of RCT-FAPs in vitro. Activation of Akt significantly stimulated GSK-3β/β-catenin signaling and thus decreased PPARγ expression and adipogenesis of RCT-FAPs, while the inhibition effect was attenuated by β-catenin inhibitor. Furthermore, Wnt signaling activator BML-284 limited adipogenesis of RCT-FAPs, alleviated muscular fatty infiltration, and improved parameters in gait analysis and treadmill test for RCT model. In conclusion, our study demonstrated that suppressed Akt/GSK-3β/β-catenin signaling increased PPARγ expression and thus contributed to excessive adipogenesis in RCT-FAPs. Modulation of Akt/GSK-3β/β-catenin signaling ameliorated excessive fatty infiltration of rotator cuff muscles and improved shoulder function after RCT.

Abstract Endogenous retroviruses (ERVs) record past retroviral infections, providing molecular archives for interrogating the evolution of retroviruses and retrovirus-host interaction. However, the vast majority of ERVs are not active anymore due to various disruptive mutations, and ongoing retroviral invasion of vertebrate genomes has been rarely documented. Here we analyze genomics data from 2004 vertebrates for mining invading ERVs (ERVi). We find that at least 412 ERVi elements representing 217 viral operational taxonomic units are invading the genomes of 123 vertebrates, 18 of which have been assessed to be threatened species. Our results reveal an unexpected prevalence of ongoing retroviral invasion in vertebrates and expand the diversity of retroviruses recently circulating in the wild. We characterize the pattern and nature of ERVi in the historical and biogeographical context of their hosts, for instance, the generation of model organisms, sympatric speciation, and domestication. We suspect that these ERVi are relevant to conservation of threatened species, zoonoses in the wild, and emerging infectious diseases in humans.

The dissemination of carbapenem-resistant Gram-negative bacilli (CRGNB) is a global public health issue. CRGNB isolates are usually extensively drug-resistant or pandrug-resistant, resulting in limited antimicrobial treatment options and high mortality. A multidisciplinary guideline development group covering clinical infectious diseases, clinical microbiology, clinical pharmacology, infection control, and guideline methodology experts jointly developed the present clinical practice guidelines based on best available scientific evidence to address the clinical issues regarding laboratory testing, antimicrobial therapy, and prevention of CRGNB infections. This guideline focuses on carbapenem-resistant Enterobacteriales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Sixteen clinical questions were proposed from the perspective of current clinical practice and translated into research questions using PICO (population, intervention, comparator, and outcomes) format to collect and synthesize relevant evidence to inform corresponding recommendations. The grading of recommendations, assessment, development and evaluation (GRADE) approach was used to evaluate the quality of evidence, benefit and risk profile of corresponding interventions and formulate recommendations or suggestions. Evidence extracted from systematic reviews and randomized controlled trials (RCTs) was considered preferentially for treatment-related clinical questions. Observational studies, non-controlled studies, and expert opinions were considered as supplementary evidence in the absence of RCTs. The strength of recommendations was classified as strong or conditional (weak). The evidence informing recommendations derives from studies worldwide, while the implementation suggestions combined the Chinese experience. The target audience of this guideline is clinician and related professionals involved in management of infectious diseases.

Iron is one of the necessary trace elements for plant growth and the human body. The ‘hidden hunger’ phenomenon in the human body caused by an imbalance of iron in soil is increasingly prominent. Addressing this issue and optimizing soil through regulatory measures to improve the absorption and utilization of iron by crops has become an urgent priority in agricultural development. This study carries out pot experiments to observe the growth process of Triticum aestivum L. under various soil iron environments. Combined with previous research results, the transport mechanism of iron in the soil—Triticum aestivum L. system was systematically explored. The results indicate that during the jointing and maturity stages of Triticum aestivum L., iron was preferentially enriched in the underground parts; at the maturity stage, the iron content in various organs of Triticum aestivum L. shows a trend of increase followed by a decrease with the soil iron content varying in the following sequence: deficient, moderately deficient, medium, moderately adequate, and adequate. The iron-deficient stress environment causes an increase in the effectiveness of rhizosphere iron, resulting in a higher level of iron in the plant stems, leaves, and seeds. Conversely, when the soil iron content is medium or adequate, the effectiveness of rhizosphere iron decreases, leading to a reduction in the iron content in each part of the plant. A concentration gradient of 7.2 mg/kg in the experimental setup is found to be the most favorable to the enrichment of iron in the shoots of Triticum aestivum L. plants. The findings of this experiment provide guidance for the fertilization strategy to mitigate iron deficiency symptoms in plants under similar acidic-alkaline conditions of soil, as well as a systematic mechanism reference and basis for studying the soil-plant-human health relationship.

Cell dielectric property measurement holds significant potential for application in cell detection and diagnosis due to its label-free and noninvasive nature. In this study, we developed a biosensor designed to measure the permittivity of liquid samples, particularly cell suspensions at the nanoliter scale, utilizing microwave and millimeter wave coplanar waveguides in conjunction with a microchannel. This biosensor facilitates the measurement of scattering parameters within a frequency domain ranging from 1 GHz to 110 GHz. The obtained scattering parameters are then converted into dielectric constants using specific algorithms. A cell capture structure within the microchannel ensures that cell suspensions remain stable within the measurement zone. The feasibility of this biosensor was confirmed by comparison with a commercial Keysight probe. We measured the dielectric constants of three different cell suspensions (HepG2, A549, MCF-7) using our biosensor. We also counted the number of cells captured in multiple measurements for each cell type and compared the corresponding changes in permittivity. The results indicated that the real part of the permittivity of HepG2 cells is 0.2–0.8 lower than that of the other two cell types. The difference between A549 and MCF-7 was relatively minor, only 0.2–0.4. The fluctuations in the dielectric spectrum caused by changes in cell numbers during measurements were smaller than the differences observed between different cell types. Thus, the sensor is suitable for measuring cell suspensions and can be utilized for label-free, noninvasive studies in identifying biological cell suspensions.

Background: To improve the clinical evaluation of the prognosis of papillary renal cell carcinoma (PRCC), we screened a model to predict the survival of patients with mutations in related genes. Methods: We downloaded RNA sequencing information from all patients with PRCC in TCGA. We first analyzed the differences in genes and the enrichment of these differences. Then, by selecting mutant genes, constructing a protein-protein interaction network, least absolute shrinkage and selection operator regression, and multivariable Cox regression, a prognosis model was constructed. Additionally, the model was validated using external data sets. We analyzed the immune infiltration of PRCC and the correlation between the model and popular targets. Finally, we performed tissue microarray analysis and immunohistochemistry to verify the expression levels of the three genes. Results: We constructed a three-gene (never in mitosis gene A-related kinase 2 [NEK2], centromere protein A [CENPA], and GINS complex subunit 2 [GINS2]) model. The verification results indicated that the model had a good prediction effect. We also developed a visual nomogram. Enrichment analysis revealed the major pathways involved in muscle system processes. Immunoassays showed that the expression level of CENPA was positively correlated with PD-1 and CTLA4 expression levels. Immunohistochemical and tissue microarray results showed that these three genes were highly expressed in PRCC, which was consistent with the predicted results in the database. Conclusion: We constructed and verified a three-gene model to predict the patient survival. The results show that the model has a good prediction effect.

Abstract Background Intradialytic hypotension (IDH) is frequently accompanied by symptoms of nausea, dizziness, fatigue, muscle spasm, and arrhythmia, which can adversely impact the daily lives of patients who undergo hemodialysis and may lead to decreased quality of life (QoL). This study employed the KDQOL™-36 scale to evaluate the impact of frequent IDH, based on the definition determined by predialysis blood pressure (BP) and nadir systolic blood pressure (SBP) thresholds, on the QoL of patients. Methods This is a single center retrospective cohort study involving 160 hemodialysis patients. We enrolled adult patients with uremia who received routine hemodialysis (4 h/time, 3 times/week) from October 1, 2019, to September 30, 2021. Frequent IDH was defined as an absolute nadir SBP

Abstract Background Cardiovascular disease has become the leading cause of death worldwide, but there is a lack of data on whether cardiovascular health (CVH) is associated with elderly mortality in China. We investigated the relationship between the ideal CVH score of Chinese elderly and the all-cause mortality. Methods The Beijing Elderly Comprehensive Health Cohort Study included a total of 4,499 participants aged 60 years and above. The CVH metric was calculated at baseline and had a score ranging from 0 to 12. The relationship of CVH metrics with all-cause mortality was investigated using Cox proportional hazard regression analysis. The robustness of results was tested using subgroup and sensitivity analysis. Results The median CVH score among participants was 8.00 (2.00), with only 8.0% scoring 11–12 points. 667 deaths were observed during an average follow-up time of 8.2 years. Participants with a CVH score of 11–12 had a decreased risk of all-cause mortality when compared to those with a CVH score of 0–4(HR = 0.584, 95% CI: 0.373–0.913). Participants had a 7.5% lower risk of all-cause death with each unit higher CVH score (HR = 0.925, 95%CI: 0.885–0.967) with a linearly decreasing trend (P nonlinear = 0.575). The relationships were greater in younger elderly people and stroke patients (P interaction = 0.011 and 0.037. respectively). The consistency of significant trends in sensitivity analysis shows the robustness of association (P trend

In order to analyze the cooling effect of the internal cooling oil gallery on the piston, the temperature field and stress-strain distribution law of the oscillating cooling piston under thermal load, mechanical load and thermo-mechanical coupling were studied. The VOF(volume of fluid) multiphase flow model and dynamic mesh technology were used to simulate the oscillatory heat transfer process of the oil in the internal cooling oil gallery of the piston, and the heat transfer coefficient of oscillating cooling oil gallery was obtained. The data were mapped to the solid surface of the piston. The piston was loaded with thermal load, mechanical load and thermo-mechanical coupling load, respectively, to analyze the temperature field changes of the piston before and after using oscillating cooling oil gallery, and the distribution laws of thermal stress, mechanical stress and coupling stress of the piston before and after using oscillating cooling oil gallery were compared and analyzed. The results show that the temperature in each region of the piston decreases to different degrees after oscillating cooling, with the highest temperature of the piston decreasing by 75%; The maximum stress of the piston under the thermo-mechanical coupling action is less than the sum of the results of the two separate effects; After oscillating cooling, the thermal stress and coupling stress of the piston also decrease in some degrees. The stress distribution law of piston before and after cooling in the internal cooling gallery is obtained, which provides some theoretical reference for the optimization design of the internal cooling oil gallery of the piston.