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Fifteen poplar varieties were used in a field trial to investigate the phytoremediation efficiency, stress resistance, and wood property of poplar hybrid varieties with diverse genetic backgrounds under the composite pollution of heavy metals. The coefficient of variation and clone repeatability for growth traits and Cd concentration were large. The Cd accumulation of poplar varieties 107 and QHQ reached 1.9 and 1.7 mg, respectively, followed by QHB, Ti, 69, and Pa, in which Cd accumulation reached 1.3 mg. Most of the intra-specific hybrid varieties (69, QH1, SL4, T3, and ZL46) had low Cd concentrations and small biomass, resulting in weak Cd accumulation and low phytoremediation efficiency for Cd-polluted soil. By contrast, the inter-sectional and inter-specific hybrid varieties exhibited better growth performance and accumulated higher concentrations of heavy metals than the intra-specific hybrids. The bioconcentration factor and translocation factor of Hg, As, and Pb were less than 1, indicating that poplars have low phytoremediation efficiency for these heavy metals. The hybrids between section Aigeiros and Tacamahaca (QHQ and QHB) and the inter-specific hybrid 107 within section Aigeiros were more resistant to composite heavy metal stress than the other poplar varieties were partially because of their high levels of free proline that exceeded 93 μg·g−1 FW. According to the correlation analysis of the concentrations of the different heavy metals, the poplar roots absorbed different heavy metals in a cooperative manner, indicating that elite poplar varieties with superior capacity for accumulating diverse heavy metals can be bred feasibly. Compared with the intra-specific hybrid varieties, the inter-sectional (QHQ and QHB) and inter-specific (107) hybrid varieties had higher pollution remediation efficiency, larger biomass, higher cellulose content, and lower lignin content, which is beneficial for pulpwood. Therefore, breeding and extending inter-sectional (QHQ and QHB) and inter-specific hybrid varieties can improve the phytoremediation of composite pollution.

ABSTRACT: In the late growth stage of commercial Pekin ducks, a significant increase in feed intake and a decline in body weight gain have been observed, leading to impaired feed conversion efficiency. To address this issue, we investigated alterations in production performance, blood biochemical indices, ileum tissue architecture, and microbial community structure in Pekin ducks. The primary objective was to provide robust data supporting the improvement of meat duck production efficiency during the late growth stage (28–42-days-old). Forty 28-day-old Pekin ducks were randomly assigned to 8 replicates, with five ducks per replicate. The rearing period lasted 14 days, with feed and water provided ad libitum. Our findings indicated a significant increase in Pekin duck body and heart weights with advancing age (P < 0.05). Moreover, serum antioxidant enzyme and high-density lipoprotein concentrations significantly increased, whereas triglyceride levels decreased (P < 0.05). Notably, the height of the ileal villi was significantly reduced (P < 0.05). The microbial community structure of the ileum exhibited significant changes as ducks aged, accompanied by a substantial increase in microbial flora diversity, particularly with the formation of more tightly connected microbial network modules. Time-dependent enrichment was observed in microbial gene functions related to energy metabolism pathways. At the genus level, Sphingomonas and Subdoligranulum have emerged as crucial players in microbial differential functional pathways and network formation. These bacteria likely serve as the key driving factors in the dynamic microbial changes that occur in Pekin ducks over time. Overall, our findings suggest a potential decline in the absorption function of the small intestine and fat deposition performance of Pekin ducks during later growth stages, which may be attributed to the maturation and proliferation of the gut microbial community.

Abstract Catalpa bungei is a precious timber species distributed in North China where drought often occurs. To clarify adaptive responses of C. bungei to partial- and full- root-zone drought under the influence of nitrogen forms, a two-factor experiment was conducted in which well-watered (WW), partial root-zone drought in horizontal direction (H-PRD) and in vertical direction (V-PRD), and full root-zone drought (FRD) were combined with nitrate-nitrogen (NN) and ammonium-nitrogen (AN) treatments. C. bungei responded to FRD by sharply closing stomata, decreasing gas exchange rate and increasing leaf instantaneous water use efficiency (WUE i). Under FRD condition, the growth of seedlings was severely inhibited and the effect of N forms was covered up by the drastic drought effect. In comparison, stomata conductance and gas exchanges were moderately inhibited by PRDs. WUE i in V-PRD treatment was superior to H-PRD due to the active stomata regulation resulting from a higher ABA level and active transcription of genes in abscisic acid (ABA) signaling pathway under V-PRD. Under both PRDs and FRD, nitrate benefited antioxidant defense, stomata regulation and leaf WUE i. Under V-PRD, WUE i in nitrate treatment was superior to that in ammonium treatment due to active stomata regulation by signaling network of nitric oxide (NO), Ca2+ and ABA. Under FRD, WUE i was higher in nitrate treatment due to the favoring photosynthetic efficiency resulting from active NO signal and antioxidant defense. The interactive effect of water and N forms was significant on wood xylem development. Superoxide dismutase (SOD) and catalase (CAT) largely contributes to stress tolerance and xylem development.

Abstract Background The increasingly severe salinization of the aquatic environment has led to serious damage to the habitats of aquatic organisms. Benthic diatoms are commonly employed as indicator species for assessing water quality and serve as a reflection of the overall health of the aquatic ecosystem. Nitzschia palea is a common diatom found in freshwater, with high oil content, rapid reproductive rate, and it is a commonly dominant species in various rivers. Results The results showed that after 4 days (d) of saline-alkali stress, the cell density and chlorophyll a content of Nitzschia palea reached their maximum values. Therefore, we selected Nitzschia palea under 4 d stress for Tandem Mass Tag (TMT) quantitative proteomic analysis to explore the molecular adaptation mechanism of freshwater diatoms under saline-alkali stress. Totally, 854 proteins were enriched, of which 439 differentially expressed proteins were identified. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and subcellular fractionation analysis revealed that these proteins were mainly enriched in the photosynthesis pathway, citric acid cycle (TCA cycle), fatty acid synthesis, and glutathione cycle. Conclusions This study aims to reveal the physiological, biochemical and proteomic mechanisms of salt and alkali tolerance and molecular adaptation of Nitzschia palea under different saline-alkali concentrations. This study showed that Nitzschia palea is one candidate of the environmental friendly, renewable bioenergy microalgae. Meantime, Nitzschia palea reveals for the proteome of the freshwater and provides the basis, it became a model algal species for freshwater diatoms.

Abstract Acute lung injury (ALI) as well as its more severe form, acute respiratory distress syndrome (ARDS), frequently leads to an uncontrolled inflammatory response. N6-methyladenosine (m6A) modification was associated with the progression of several inflammatory diseases. However, the role of methyltransferase-like 14 (METTL14)-mediated m6A methylation in ALI/ARDS remains unclear. Here, we reported an increase in overall expression levels of m6A and METTL14 in circulating monocyte-derived macrophages recruited to the lung following ALI, which is correlated with the severity of lung injury. We further demonstrated the critical function of METTL14 in activating NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in vitro and in mouse models of ALI/ARDS, and validated NLRP3 as the downstream target of METTL14 by the m6A RNA immunoprecipitation (MeRIP) and RIP assays. Mechanistically, METTL14-methylated NLRP3 transcripts were subsequently recognized by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an m6A reader, which stabilized NLRP3 mRNA. Furthermore, we observed that IGF2BP2 knockdown diminished LPS-induced ALI in mice by downregulating NLRP3 expression. In summation, our study revealed that the molecular mechanism underlying the pathogenesis of ALI/ARDS involves METTL14-mediated activation of NLRP3 inflammasome in an IGF2BP2 dependent manner, thereby demonstrating the potential of METTL14 and IGF2BP2 as promising biomarkers and therapeutic targets for ALI/ARDS treatment.

A regular calligraphy script of each calligrapher has unique strokes, and a script’s authenticity can be identified by comparing them. Hence, this study introduces a method for identifying the authenticity of regular script calligraphy works based on the improved YOLOv7 algorithm. The proposed method evaluates the authenticity of calligraphy works by detecting and comparing the number of single-character features in each regular script calligraphy work. Specifically, first, we collected regular script calligraphy works from a well-known domestic calligrapher and divided each work into a single-character dataset. Then, we introduced the PConv module in FasterNet, the DyHead dynamic detection header network, and the MPDiou bounding box loss function to optimize the accuracy of the YOLOv7 algorithm. Thus, we constructed an improved algorithm named YOLOv7-PDM, which is used for regular script calligraphy identification. The proposed YOLOv7-PDM model was trained and tested using a prepared regular script single-character dataset. Through experimental results, we confirmed the practicality and feasibility of the proposed method and demonstrated that the YOLOv7-PDM algorithm model achieves 94.19% accuracy (mAP50) in detecting regular script font features, with a single-image detection time of 3.1 m and 31.67M parameters. The improved YOLOv7 algorithm model offers greater advantages in detection speed, accuracy, and model complexity compared to current mainstream detection algorithms. This demonstrates that the developed approach effectively extracts stroke features of regular script calligraphy and provides guidance for future studies on authenticity identification.

Abstract BiFeO3 is a rare single‐phase multiferroic which shows coupled ferroelectricity, ferroelasticity and antiferromagnetism at room temperature. Many fantastic properties of BiFeO3 are regulated by its domain structure. While (001) rhombohedral BiFeO3 thin films can possibly develop up‐to eight degenerate states of two‐variant 71° ferroelastic domain stripes, complete selective control of all possible switching paths between these states has not yet been achieved. Here, combining phase field simulations and scanning probe microscopy experiments, we demonstrated such a complete selective control. The tip bias and the built‐in field were shown to affect the volume fraction of the 71°, 109° and 180° switched domains in rhombohedral BiFeO3 thin films under single‐point loading. Meanwhile, tip scanning further broke the symmetry of the nucleated domains, leading to different switched domain patterns. We then grew BiFeO3 thin films with a specific two‐variant 71° ferroelastic domain state and showed that such a state could be deterministically switched into the other seven two‐variant domain states by collaborative controlling tip scanning and tip bias in scanning probe microscopy experiments. These results should deepen our current understanding on the domain switching kinetics in BiFeO3 thin films and indicate they are promising platforms for developing configurable electronic and spintronic devices.

Abstract Background Heat shock factor (HSF), a typical class of transcription factors in plants, has played an essential role in plant growth and developmental stages, signal transduction, and response to biotic and abiotic stresses. The HSF genes families has been identified and characterized in many species through leveraging whole genome sequencing (WGS). However, the identification and systematic analysis of HSF family genes in Rye is limited. Results In this study, 31 HSF genes were identified in Rye, which were unevenly distributed on seven chromosomes. Based on the homology of A. thaliana, we analyzed the number of conserved domains and gene structures of ScHSF genes that were classified into seven subfamilies. To better understand the developmental mechanisms of ScHSF family during evolution, we selected one monocotyledon (Arabidopsis thaliana) and five (Triticum aestivum L., Hordeum vulgare L., Oryza sativa L., Zea mays L., and Aegilops tauschii Coss.) specific representative dicotyledons associated with Rye for comparative homology mapping. The results showed that fragment replication events modulated the expansion of the ScHSF genes family. In addition, interactions between ScHSF proteins and promoters containing hormone- and stress-responsive cis-acting elements suggest that the regulation of ScHSF expression was complex. A total of 15 representative genes were targeted from seven subfamilies to characterize their gene expression responses in different tissues, fruit developmental stages, three hormones, and six different abiotic stresses. Conclusions This study demonstrated that ScHSF genes, especially ScHSF1 and ScHSF3, played a key role in Rye development and its response to various hormones and abiotic stresses. These results provided new insights into the evolution of HSF genes in Rye, which could help the success of molecular breeding in Rye.

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and severe side effect of first-line chemotherapeutic agents. The association between circular RNAs (circRNAs) and CIPN remains unclear. In this study, CIPN models were constructed with Taxol, while 134 differentially expressed circRNAs, 353 differentially expressed long non-coding RNAs, and 86 differentially expressed messenger RNAs (mRNAs) were identified utilizing RNA sequencing. CircRNA-targeted microRNAs (miRNAs) were predicted using miRanda, and miRNA-targeted mRNAs were predicted using TargetScan and miRDB. The intersection of sequencing and mRNA prediction results was selected to establish the circRNA–miRNA–mRNA networks, which include 15 circRNAs, 18 miRNAs, and 11 mRNAs. Functional enrichment pathway analyses and immune infiltration analyses revealed that differentially expressed mRNAs were enriched in the immune system, especially in T cells, monocytes, and macrophages. Cdh1, Satb2, Fas, P2ry2, and Zfhx2 were further identified as hub genes and validated by RT-qPCR, correlating with macrophages, plasmacytoid dendritic cells, and central memory CD4 T cells in CIPN. Additionally, we predicted the associated diseases, 36 potential transcription factors (TFs), and 30 putative drugs for hub genes using the DisGeNET, TRRUST, and DGIdb databases, respectively. Our results indicated the crucial role of circRNAs, and the immune microenvironment played in CIPN, providing novel insights for further research.

Sleep deprivation (SD) leads to impaired intestinal barrier function and intestinal flora disorder, especially a reduction in the abundance of the next generation of probiotic Faecalibacterium prausnitzii (F. prausnitzii). However, it remains largely unclear whether F. prausnitzii can ameliorate SD-induced intestinal barrier damage. A 72 h SD mouse model was used in this research, with or without the addition of F. prausnitzii. The findings indicated that pre-colonization with F. prausnitzii could protect against tissue damage from SD, enhance goblet cell count and MUC2 levels in the colon, boost tight-junction protein expression, decrease macrophage infiltration, suppress pro-inflammatory cytokine expression, and reduce apoptosis. We found that the presence of F. prausnitzii helped to balance the gut microbiota in SD mice by reducing harmful bacteria like Klebsiella and Staphylococcus, while increasing beneficial bacteria such as Akkermansia. Ion chromatography analysis revealed that F. prausnitzii pretreatment increased the fecal butyrate level in SD mice. Overall, these results suggested that incorporating F. prausnitzii could help reduce gut damage caused by SD, potentially by enhancing the intestinal barrier and balancing gut microflora. This provides a foundation for utilizing probiotics to protect against intestinal illnesses.

Sepsis is a life-threatening multiple organ dysfunction syndrome (MODS) caused by a microbial infection that leads to high morbidity and mortality worldwide. Sepsis-induced cardiomyopathy (SIC) and coagulopathy promote the progression of adverse outcomes in sepsis. Here, we reported that ACT001, a modified compound of parthenolide, improved the survival of sepsis mice. In this work, we used cecal ligation and puncture (CLP) model to induce SIC. Transthoracic echocardiography and HE staining assays were adopted to evaluate the influence of ACT001 on sepsis-induced cardiac dysfunction. Our results showed that ACT001 significantly improved heart function and reduced SIC. Coagulation accelerates organ damage in sepsis. We found that ACT001 decreased blood clotting in the FeCl3-induced carotid artery thrombosis experiment. ACT001 also reduced the production of neutrophil extracellular traps (NETs). RNA-sequencing of heart tissues revealed that ACT001 significantly downregulated the expression of pro-inflammatory cytokines and the JAK-STAT signaling pathway. These results were confirmed with real-time PCR and ELISA. In summary, we found ACT001 rescued mice from septic shock by protecting the cardiovascular system. This was partially mediated by inhibiting pro-inflammatory cytokine production and down-regulating the JAK-STAT signaling.

Abstract Background Sleep loss is a serious global health concern. Consequences include memory deficits and gastrointestinal dysfunction. Our previous research showed that melatonin can effectively improve cognitive impairment and intestinal microbiota disturbances caused by sleep deprivation (SD). The present study further explored the mechanism by which exogenous melatonin prevents SD-induced cognitive impairments. Here, we established fecal microbiota transplantation, Aeromonas colonization and LPS or butyrate supplementation tests to evaluate the role of the intestinal microbiota and its metabolites in melatonin in alleviating SD-induced memory impairment. Results Transplantation of the SD-gut microbiota into normal mice induced microglia overactivation and neuronal apoptosis in the hippocampus, cognitive decline, and colonic microbiota disorder, manifesting as increased levels of Aeromonas and LPS and decreased levels of Lachnospiraceae_NK4A136 and butyrate. All these events were reversed with the transplantation of SD + melatonin-gut microbiota. Colonization with Aeromonas and the addition of LPS produced an inflammatory response in the hippocampus and spatial memory impairment in mice. These changes were reversed by supplementation with melatonin, accompanied by decreased levels of Aeromonas and LPS. Butyrate administration to sleep-deprived mice restored inflammatory responses and memory impairment. In vitro, LPS supplementation caused an inflammatory response in BV2 cells, which was improved by butyrate supplementation. This ameliorative effect of butyrate was blocked by pretreatment with MCT1 inhibitor and HDAC3 agonist but was mimicked by TLR4 and p-P65 antagonists. Conclusions Gut microbes and their metabolites mediate the ameliorative effects of melatonin on SD-induced cognitive impairment. A feasible mechanism is that melatonin downregulates the levels of Aeromonas and constituent LPS and upregulates the levels of Lachnospiraceae_NK4A136 and butyrate in the colon. These changes lessen the inflammatory response and neuronal apoptosis in the hippocampus through crosstalk between the TLR4/NF-κB and MCT1/ HDAC3 signaling pathways. Video Abstract

This paper presents an innovative approach to tackle Bayesian inverse problems using physics-informed invertible neural networks (PI-INN). Serving as a neural operator model, PI-INN employs an invertible neural network (INN) to elucidate the relationship between the parameter field and the solution function in latent variable spaces. Specifically, the INN decomposes the latent variable of the parameter field into two distinct components: the expansion coefficients that represent the solution to the forward problem, and the noise that captures the inherent uncertainty associated with the inverse problem. Through precise estimation of the forward mapping and preservation of statistical independence between expansion coefficients and latent noise, PI-INN offers an accurate and efficient generative model for resolving Bayesian inverse problems, even in the absence of labeled data. For a given solution function, PI-INN can provide tractable and accurate estimates of the posterior distribution of the underlying parameter field. Moreover, capitalizing on the INN’s characteristics, we propose a novel independent loss function to effectively ensure the independence of the INN’s decomposition results. The efficacy and precision of the proposed PI-INN are demonstrated through a series of numerical experiments.

IntroductionThe emergence of multidrug-resistant (MDR) Acinetobacter baumannii prompts clinicians to consider treating these infections with polymyxin combination.MethodsMetabolomic analysis was applied to investigate the synergistic effects of polymyxin-B, amikacin and sulbactam combination therapy against MDR A. baumannii harboring OXA-23 and other drug resistant genes. The drug concentrations tested were based on their clinical breakpoints: polymyxin-B (2 mg/L), amikacin (16 mg/L), polymyxin-B/amikacin (2/16 mg/L), and polymyxin-B/amikacin/sulbactam (2/16/4 mg/L).ResultsThe triple antibiotic combination significantly disrupted levels of metabolites involved in cell outer membrane structure including fatty acids, glycerophospholipids, nucleotides, amino acids and peptides as early as 15 min after administration. Amikacin and polymyxin-B alone perturbed a large number of metabolites at 15 min and 1 h, respectively, but the changes in metabolites were short-lived lasting for less than 4 h. In contrast, the combination treatment disrupted a large amount of metabolites beyond 4 h. Compared to the double-combination, the addition of sulbactam to polymyxin-B/amikacin combination produce a greater disorder in A. baumannii metabolome that further confer susceptibility of bacteria to the antibiotics.ConclusionThe metabolomic analysis identified mechanisms responsible for the synergistic activities of polymyxin-B/amikacin/sulbactam against MDR A. baumannii.

Calligraphy works have high artistic value, but there is the rampant problem of forgery. Indeed, the authentication of traditional calligraphy heavily relies on calligraphers’ subjective judgment. Therefore, spurred by the recent development of neural networks, this paper proposes a method for authenticating calligraphy works based on an improved EfficientNet network. Specifically, the developed method utilizes the character box algorithm to efficiently extract individual calligraphy characters, which are then augmented and used as the training set for the model. The training process employs CBAM and Self-Attention modules to enhance the attention mechanism of the EfficientNet network. The trained network model is used to judge the calligraphy works’ similarity; tested on authentic works, imitated works, and works from other calligraphers; and compared with other networks. The experimental results demonstrate that the proposed method effectively achieves the authentication of calligraphy works, and the improved CBAM-EfficientNet network and SA-EfficientNet network achieve better authentication performance.

Subway vehicle roofs must be inspected when entering and exiting the depot to ensure safe subway vehicle operations. This paper presents an improved method for detecting foreign objects on subway vehicle roofs based on the YOLOv7 algorithm. First, we capture images of foreign objects using a line-scan camera at the depot entrance and exit, creating a dataset of foreign roof objects. Subsequently, we address the shortcomings of the YOLOv7 algorithm by introducing the Ghost module, an improved weighted bidirectional feature pyramid network (WBiFPN), and the Wise intersection over union (WIoU) bounding-box regression loss function. These enhancements are incorporated to build the subway vehicle roof foreign object detection model based on the improved YOLOv7, which we refer to as YOLOv7-GBW. The experimental results demonstrate the practicality and usability of the proposed method. The analysis of the experimental results indicates that the YOLOv7-GBW algorithm achieves a detection accuracy of 90.29% at a speed of 54.3 frames per second (fps) with a parameter count of 15.51 million. The improved YOLOv7 model outperforms mainstream detection algorithms in terms of detection accuracy, speed, and parameter count. This finding confirms that the proposed method meets the requirements for detecting foreign objects on subway vehicle roofs.

Protein disulfide isomerase (PDI) is a member of the thioredoxin (Trx) superfamily with important functions in cellular stability, ion uptake, and cellular differentiation. While PDI has been extensively studied in humans and animals, its role in fungi remains relatively unknown. In this study, the biological functions of FgEps1, a disulfide bond isomerase in the fungal pathogen Fusarium graminearum, were investigated. It was found that FgEps1 mutation affected nutritional growth, asexual and sexual reproduction, and stress tolerance. Additionally, its deletion resulted in reduced pathogenicity and impaired DON toxin biosynthesis. The involvement of FgEps1 in host infection was also confirmed, as its expression was detected during the infection period. Further investigation using a yeast signal peptide secretion system and transient expression in Nicotiana benthamiana showed that FgEps1 suppressed the immune response of plants and promoted infection. These findings suggest that virulence factor FgEps1 plays a crucial role in growth, development, virulence, secondary metabolism, and host infection in F. graminearum.

In this study, the extraction process and immune activity of polysaccharide from Anemarrhena asphodeloides Bunge were studied, in order to provide a theoretical basis for its development and utilization. Crude polysaccharide was obtained by complex enzyme method from Anemarrhena asphodeloides Bunge. On the basis of orthogonal experiment to determine compound enzyme ratio, the extraction conditions of Anemarrhena asphodeloides Bunge polysaccharide by enzyme complex were optimized by using response surface methodology and mono-factor experiments, and the optimum technological conditions were obtained. Four polysaccharide components, APSE-0, APSE-1, APSE-2 and APSE-3, were isolated and purified by DEAE-52 cellulose chromatography column. The effects of the polysaccharide fractions on the proliferation of RAW264.7 cells were determined by MTT assay, and the release capacity of nitrogen monoxide NO was determined by the Griess kit. The results showed that compound enzyme ratio was papain 16000 U/g, cellulose 1200 U/g, and pectinase 1600 U/g. The optimum extraction conditions were hydrolysis time of 2 h, liquid-solid of 15:1 (mL/g), temperature of enzymatic hydrolysis of 52 ℃. Under these conditions the extraction yield was (10.58%±0.03%). The results of in vitro immunoassay proved that four polysaccharides could significantly promote the proliferation of RAW246.7 cells, and APSE-0, APSE-2 and APSE-3 significantly induced NO production, among which APSE-2 showed the strongest immunoregulatory activity. APSE-2 could be explored as a potential source for immunomodulatory agents of the functional foods or dietary complementary for people with compromised immune system.

BackgroundPrior research has shown inconclusive findings regarding the relationship between blood pressure variability (BPV) in acute ischemic stroke (AIS) and functional outcomes. Most research has examined the connection between short-term BPV during the early 24–72 h after the occurrence of ischemic stroke and functional prognosis. We sought to determine the relationship between daily BPV at 7 days of commencement and functional outcomes during the 3 months following AIS.MethodsAltogether, 633 patients with AIS admitted within 72 h of commencement were enrolled. AIS was defined as the time from the onset of symptoms to 7 days. Throughout this period, blood pressure (BP) was recorded twice daily (casual BP cuffs). The daily BPV, with standard deviation (SD) and coefficient of variation (CV), was calculated and matched to the functional results. The adverse outcome was characterized as a modified Rankin scale (mRS)≥3, which comprised the recurrence of stroke, clinical intracranial bleeding, and death.ResultsIn total, 633 participants were included, and the incidence of adverse outcomes was 14.06% (89/633). There was a significant positive correlation between daily BPV and adverse outcomes but not between mean BP and risk. Smooth curve fitting revealed a U-shaped connection between the mean BP and adverse clinical outcomes. Multivariable logistic regression analysis showed an independent correlation between daily BPV and an adverse outcome in the top vs. bottom quartile of systolic BPV (odds ratio [OR] = 2.4, 95% confidence interval [CI]: 1.17–4.96, P = 0.018 for SD; OR = 2.4, 95% CI: 1.17–4.93, P = 0.017 for CV) during a 3-month follow-up period. Identical results have been reported for diastolic BPV.ConclusionIrrespective of BP level, elevated daily systolic BPV and diastolic BPV in AIS were associated with an increased risk of adverse outcomes within 3 months. We also discovered a U-shaped association between the mean BP and adverse clinical outcomes. These findings suggested that BPV should be a risk factor for adverse outcomes after ischemic stroke, which provided new insight into BP management strategy.

Abstract Background Hemangioblastoma is an indolent mesenchymal tumor most frequently occurring in the central nervous system (CNS), but can also arise extraneuraxially, as part of Von Hippel-Lindau (VHL) disease or in sporadic tumors. Extraneuraxial hemangioblastomas occur outside the central nervous system. It includes tumors arising from the nervous paraneuraxial structures and visceral organs. Sporadic hemangioblastoma of the kidney, a rare subset of extraneuraxial hemangioblastomas, is an under-recognized renal neoplasm. There have been only 25 cases described to date in the English language literature. We report herein one additional sporadic tumor in a patient without VHL disease. Case presentation A 61 year old male presenting with gross hematuria was found to have a 3.5 cm renal mass at the lateral mid to lower pole of the left kidney on computed tomography urogram. The patient underwent a partial nephrectomy for the mass. Pathological examination showed a well-circumscribed non-encapsulated tumor composed of sheets of large polygonal cells traversed by a rich vascular network. The tumor cells showed clear to eosinophilic cytoplasm and overall bland nuclei. The diagnosis of hemangioblastoma was confirmed by positive immunostaining for alpha-inhibin, S100, neuron-specific enolase, and PAX8. No significant gene mutations, including VHL gene and copy number changes were detected in the tumor using next generation sequencing supporting the diagnosis of sporadic renal hemangioblastoma. Conclusion Sporadic renal hemangioblastoma is a rare subset of extraneuraxial hemangioblastomas. We report one such tumor in a patient without clinical or molecular evidence of VHL disease. The literature was reviewed to better understand the clinical, radiological, pathological, and molecular features of this neoplasm. The majority of renal hemangioblastomas showed positive immunostaining for PAX8, which supports the idea that the immunoprofiles of extraneuraxial hemangioblastomas can vary depending on sites of origin. Diagnosis of renal hemangioblastoma is challenging because of its rarity and overlapping microscopic and immunophenotypic features with other renal tumors, including clear cell renal cell carcinoma. In some cases, molecular or genetic studies may be necessary to obtain an accurate diagnosis. Since renal hemangioblastoma is clinically benign, recognition of this pathological entity is important to avoid unnecessary over-treatment.

ImportanceThe number of infections and deaths caused by the global epidemic of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) invasion is steadily increasing daily. In the early stages of outbreak, approximately 15%–20% of patients with coronavirus disease 2019 (COVID-19) inevitably developed severe and critically ill forms of the disease, especially elderly patients and those with several or serious comorbidities. These more severe forms of disease mainly manifest as dyspnea, reduced blood oxygen saturation, severe pneumonia, acute respiratory distress syndrome (ARDS), thus requiring prolonged advanced respiratory support, including high-flow nasal cannula (HFNC), non-invasive mechanical ventilation (NIMV), and invasive mechanical ventilation (IMV).ObjectiveThis study aimed to propose a safer and more practical tracheotomy in invasive mechanical ventilated patients with COVID-19.DesignThis is a single center quality improvement study.ParticipantsTracheotomy is a necessary and important step in airway management for COVID-19 patients with prolonged endotracheal intubation, IMV, failed extubation, and ventilator dependence. Standardized third-level protection measures and bulky personal protective equipment (PPE) may hugely impede the implementation of tracheotomy, especially when determining the optimal pre-surgical positioning for COVID-19 patients with ambiguous surface position, obesity, short neck or limited neck extension, due to vision impairment, reduced tactile sensation and motility associated with PPE. Consequently, the aim of this study was to propose a safer and more practical tracheotomy, namely percutaneous dilated tracheotomy (PDT) with delayed endotracheal intubation withdrawal under the guidance of bedside ultrasonography without the conventional use of flexible fiberoptic bronchoscopy (FFB), which can accurately determine the optimal pre-surgical positioning, as well as avoid intraoperative damage of the posterior tracheal wall and prevent the occurrence of tracheoesophageal fistula (TEF).

Abstract Background Rectal mucosal melanoma (RMM) is a rare and highly aggressive disease with a poor prognosis. Due to the rarity of RMM, there are few studies focusing on its genetic mechanism. This retrospective study aimed to analyze the genetic spectrum and prognosis of RMM in China and lay a foundation for targeted therapy. Methods 36 patients with primary RMM from Peking University Cancer Hospital were enrolled in this study. The Next-generation sequencing (NGS) data of the tumor samples were fitted into the TruSight™ Oncology 500 (TSO500) Docker pipeline to detect genomic variants. Then, the univariate and multivariate Cox hazard analysis were performed to evaluate the correlations of the variants with the overall survival (OS), along with Kaplan-Meier and log-rank test to determine their significance. Results BRAF mutations, NRG1 deletions and mitotic index were significant prognostic factors in the univariate analysis. In multivariable analysis of the OS-related prognostic factors in primary RMM patients, it revealed 2 significant alterations: BRAF mutations [HR 7.732 (95%CI: 1.735–34.456), P = 0.007] and NRG1 deletions [HR 14.976 (95%CI: 2.305–97.300), P = 0.005]. Conclusions This is the first study to show genetic alterations exclusively to Chinese patients with RMM. We confirmed genetic alterations of RMM differ from cutaneous melanoma (CM). Our study indicates that BRAF and NRG1 were correlated with a poor prognostic of RMM and may be potential therapeutic targets for RMM treatment.

The relation between enhanced superconductivity in monolayer FeSe grown on SrTiO3 and the large nematicity in multilayer FeSe on SrTiO3 remains not well understood. Here, the authors observe a long-range smectic phase in bilayer FeSe films but vanishes in monolayer FeSe, providing a new instability to help enhance the superconductivity.

Resource-based cities, which emerge due to the large-scale industrialization of China, mainly rely on local natural resources for industrial layout and economic development. However, resources have been gradually exhausted due to overuse, resulting in a series of negative impacts on the environment and resources. In order to realize long-term sustainable development and avoid falling into the “resource curse,” measures such as industrial structure adjustment and technological upgrading to promote the transformation of these cities ought to be implemented. Taking Benxi, one of the most typical mineral resource-based cities in China, as an example, this study discusses the economic and environmental performance and existing problems in the local transformation process, comparing it with successful transformation patterns of global mineral resource-based cities. On this basis, a series of policy suggestions together with possible ways toward sustainable development are put forward and summarized.

Peptide iron chelate is widely regarded as one of the best iron supplements for relieving iron deficiency. In this study, a new type of walnut peptide iron (WP-Fe) chelate was prepared using low molecular weight walnut peptides (WP) as raw materials. Under the conditions of this study, the chelation rate and iron content of the WP-Fe chelate were 71.87 ± 1.60% and 113.11 ± 2.52 mg/g, respectively. Fourier transform infrared spectroscopy (FTIR), zeta potential, amino acid composition, and other structural analysis showed that WP-Fe is formed by the combination of carboxyl, amino and carbonyl with Fe2+. The WP-Fe chelate exhibits a honeycomb-like bulk structure different from that of WP. In addition, we predicted and established the binding model of ferrous ion and WP by molecular docking technology. After chelation, the free radical scavenging ability of the WP-Fe chelate was significantly higher than that of the WP. Overall, the WP-Fe chelate has high iron-binding capacity and antioxidant activity. We believe that peptides from different sources also have better iron binding capacity, and peptide iron chelates are expected to become a promising source of iron supplement and antioxidant activities.

Context: Analysis of diagnostic information in pathology reports for the purposes of clinical or translational research and quality assessment/control often requires manual data extraction, which can be laborious, time-consuming, and subject to mistakes. Objective: We sought to develop, employ, and evaluate a simple, dictionary- and rule-based natural language processing (NLP) algorithm for generating searchable information on various types of parameters from diverse surgical pathology reports. Design: Data were exported from the pathology laboratory information system (LIS) into extensible markup language (XML) documents, which were parsed by NLP-based Python code into desired data points and delivered to Excel spreadsheets. Accuracy and efficiency were compared to a manual data extraction method with concordance measured by Cohen’s κ coefficient and corresponding P values. Results: The automated method was highly concordant (90%–100%, P

The aim of this study was to investigate the extraction of antibacterial substances from Galla chinensis (ASGC) that act against the aquatic pathogen Vibrio harveyi, to identify the chemical composition and explore the mechanism of action. The optimal extraction process was as follows: anhydrous methanol, liquid/material ratio (mL/g) 26:1, extraction temperature 98 °C and extraction time 157 min. The diameter of the inhibition zones (21.31 ± 0.51 mm) under the optimal conditions agreed with the predicted value by experimental rechecking. The yield of ASGC was 39.39% ± 0.69%, and two compounds including gallic acid (GA) and penta-O-galloyl-β-d-glucose (5GG) were identified in ASGC. The minimal inhibitory concentration (MIC) values of ASGC and GA were 0.50 and 0.25 mg/mL, respectively. Meanwhile, 5GG and other chemical constituents did not exert antibacterial activities against V. harveyi (MICs > 1 mg/mL). Further investigation of the mechanisms of action of ASGC and GA against V. harveyi revealed their strong destructive effects on the growth of bacterial cells, the integrity and permeability of the cell membrane, and morphological alterations. The report provides a favorable prospect of GA as a potential control agent against V. harveyi in aquaculture.

Benign tumors of the temporal bone are extremely rare, with an incidence of 1 in 200,000 individuals. The authors report a case of an 8-year-old girl with facial nerve schwannoma (FNS) involving the mastoid portion of her facial nerve. She initially presented with exam findings of postauricular swelling and tenderness mimicking acute infectious mastoiditis. During mastoidectomy, intraoperative frozen pathology revealed spindle cells consistent with FNS, and surgery was aborted. This is the first report of FNS mimicking acute infectious mastoiditis. Presenting symptoms are reviewed, along with radiographic, laboratory, and intraoperative features.

Objectives: Memory decline caused by insufficient sleep is a critical public health issues and currently lacks effective treatments. This study objective was to explore alleviative effect of melatonin on sleep deprivation (SD)-induced deficiencies in learning and memory.Materials and Methods: A continuous 72 h SD mouse model, with or without melatonin or Fer-1 supplementation were established. The changes of cognitive function, iron homeostasis, lipid peroxidation and intracellular signal pathways in mice were detected by Morris water maze, antioxidant assay, immunohistochemistry, western blot, RT-PCR and Prussian blue staining. In vitro, we treated HT-22 cells with ferroptosis inducer (Erastin) to further explore the specific mechanism of melatonin in ferroptosis.Results: Mice subjected to SD had significantly elevated latency and path length to reach hidden platform, as well as a decrease in number of entries and time spent in the target zone when the hidden platform was removed (p < 0.05). Nevertheless, supplementation with ferroptosis inhibitor (Fer-1) mitigated the memory impairment associated with SD. Further evaluation revealed an up-regulation of intracellular iron accumulation, transferrin receptor 1 and divalent metal transporter 1 expression and ROS and MDA production, and a down-regulation of ferroportin and antioxidant enzyme (GPX4 and SOD) expression in SD mice. SD decreased expression of MT2 receptor rather than of MT1, and inhibited ERK/Nrf2 signaling activation in the hippocampus (p < 0.05). In contrast, the aforementioned SD-inductions were reversed by supplementation using 20 and 40 mg/kg melatonin in SD mice. In vitro, melatonin pretreatment reversed Erastin-induced ferroptosis, abnormalities in iron transporter protein and antioxidant enzyme expression and suppression of ERK/Nrf2 signaling in HT-22 cells, however this protective effect of melatonin was blocked by MT2-, ERK- and Nrf2-specific antagonists (p < 0.05).Conclusion: Our finding suggested SD may induce ferroptosis, in turn leading to cognitive deficits. Melatonin alleviated memory loss and hippocampal ferroptosis caused by acute SD through binding to the MT2 receptor to activate ERK/Nrf2 signaling.

In recent years, China has proposed the goal of peaking carbon dioxide emissions by 2030 and achieving carbon neutrality by 2060, which will significantly alter its existing coal-based energy mix. Since coal is China’s primary source of energy and the largest contributor to carbon emissions, coal reduction is an important measure toward carbon neutrality. In order to guarantee the stable development of economy and society in the process of coal reduction, the path and cost of coal reduction need to be studied in depth. Based on coal use in China, this paper examines and measures the stages and costs of coal reduction. It also gives a definition for coal reduction costs for the first time, including economic cost, environment and ecology cost, and health cost, as well as proposes a framework for analyzing the “full cost, full process, and full scenario”. We measure the cost in combination with the KAYA formula, and take into account the time value of the cost. Based on the above measurement framework, we calculate the unit coal reduction cost and estimate the coal reduction cost between CNY 454.38 and 827.1 billion.

Fungalysin metallopeptidase (M36), a hydrolase, catalyzes the hydrolysis of alanine, glycine, etc. Normally, it is considered to play an important role in the progress of fungal infection. However, the function of fungalysin metallopeptidase (M36) in Fusarium graminearum has not been reported. In this study, we explored the biological functions of FgFly1, a fungalysin metallopeptidase (M36) of F. graminearum. We found that ΔFgFly1 did not affect the ability to produce DON toxin, although it inhibited spore germination during asexual reproduction and reduction in pathogenicity compared with PH-1. Therefore, we speculated that FgFly1 affects the pathogenicity of F.graminearum by affecting pathways related to wheat disease resistance. Target protein TaCAMTA (calmodulin-binding transcription activator) was selected by a yeast two-hybrid (Y2H) system. Then, the interaction between FgFly1 and TaCAMTA was verified by bimolecular fluorescent complimentary (BiFC) and luciferase complementation assay (LCA). Furthermore, compared with wild-type Arabidopsis thaliana, the morbidity level of ΔAtCAMTA was increased after infection with F.graminearum, and the expression level of NPR1 was significantly reduced. Based on the above results, we concluded that FgFly1 regulated F. graminearum pathogenicity by interacting with host cell CAMTA protein.

Next-generation sequencing (NGS) has drastically enhanced human cancer research, but diverse sequencing strategies, complicated open-source software, and the identification of massive numbers of mutations have limited the clinical application of NGS. Here, we first presented GPyFlow, a lightweight tool that flexibly customizes, executes, and shares workflows. We then introduced DIVIS, a customizable pipeline based on GPyFlow that integrates read preprocessing, alignment, variant detection, and annotation of whole-genome sequencing, whole-exome sequencing, and gene-panel sequencing. By default, DIVIS screens variants from multiple callers and generates a standard variant-detection format list containing caller evidence for each sample, which is compatible with advanced analyses. Lastly, DIVIS generates a statistical report, including command lines, parameters, quality-control indicators, and mutation summary. DIVIS substantially facilitates complex cancer genome sequencing analyses by means of a single powerful and easy-to-use command. The DIVIS code is freely available at https://github.com/niu-lab/DIVIS, and the docker image can be downloaded from https://hub.docker.com/repository/docker/sunshinerain/divis.

With the increasing incidence of colorectal cancer (CRC) and continued difficulty in treating it using immunotherapy, there is an urgent need to identify an effective immune-related biomarker associated with the survival and prognosis of patients with this disease. DNA methylation plays an essential role in maintaining cellular function, and changes in methylation patterns may contribute to the development of autoimmunity, aging, and cancer. In this study, we aimed to identify a novel immune-related methylated signature to aid in predicting the prognosis of patients with CRC. We investigated DNA methylation patterns in patients with stage II/III CRC using datasets from The cancer genome atlas (TCGA). Overall, 182 patients were randomly divided into training (n = 127) and test groups (n = 55). In the training group, five immune-related methylated CG sites (cg11621464, cg13565656, cg18976437, cg20505223, and cg20528583) were identified, and CG site-based risk scores were calculated using univariate Cox proportional hazards regression in patients with stage II/III CRC. Multivariate Cox regression analysis indicated that methylated signature was independent of other clinical parameters. The Kaplan–Meier analysis results showed that CG site-based risk scores could significantly help distinguish between high- and low-risk patients in both the training (P = 0.000296) and test groups (P = 0.022). The area under the receiver operating characteristic curve in the training and test groups were estimated to be 0.771 and 0.724, respectively, for prognosis prediction. Finally, stratified analysis results suggested the remarkable prognostic value of CG site-based risk scores in CRC subtypes. We identified five methylated CG sites that could be used as an efficient overall survival (OS)-related biomarker for stage II/III CRC patients.

BACKGROUND: Hypertension-induced renal damage is a serious and complex condition that has not been effectively treated by conventional blood pressure-lowering drugs. Tengdan capsule (TDC) is a China FDA-approved compound herbal medicine for treating hypertension; however, its chemical basis and pharmacological efficacy have not been fully investigated in a preclinical setting.METHODS: High-performance liquid chromatography (HPLC) was used to identify and quantify the major chemical components of TDC extracted from ultrapure water. Adult spontaneously hypertensive rats (SHR) and age/sex-matched Wistar Kyoto normotensive rats (WKY) were both treated with TDC, losartan, or saline for one month, and their blood pressure (BP) was monitored at the same time by tail-cuff BP system. Biochemical indexes such as urine creatinine (CRE) and blood urea nitrogen (BUN) were determined. Kidney tissue sections were examined with (H&E), and Masson staining to evaluate the pathological effect of TDC on SHR’s kidneys. After TDC treatment, the differentially expressed proteins in the kidneys of SHR were identified by the TMT-based quantitative proteomics analysis, which may provide the targets and possible mechanisms of TDC action. In addition, Western blot analysis, RT-qPCR, and ELISA assays were carried out to further verify the proteomics findings. Finally, two different models involving in vitro renal injuries were established using human kidney HEK293 cells; and the molecular mechanism of TDC kidney protection was demonstrated.RESULTS: Seven chemical compounds, namely Notoginsenoside R1, Ginsenoside RG1, Ginsenoside Re, Ginsenoside Rb1, Sodium Danshensu, Protocatechualdehyde, and Salvianolic acid B, were identified and quantified from the water-soluble extracts of TDC by HPLC. In vivo study using rats showed that TDC effectively reduced BP, BUN, and CRE levels and attenuated renal fibrosis in SHR, and ameliorated damage to the kidneys. Proteomics and subsequent bioinformatics analyses indicated that periostin-mediated inflammatory response and TGFβ/Smad signaling pathway proteins were closely related to the therapeutic effect of TDC in rat kidneys. Western blot analysis and RT-qPCR showed that TDC markedly downregulated the mRNA and protein expression of periostin in renal tissues compared to the untreated SHR. In addition, TGF-β and COL1A1 mRNA levels also decreased in SHR renal tissues following TDC treatment. In vitro studies showed that low to medium doses of TDC down-regulated the expression of periostin in the injury model of HEK293 cell. In addition, medium to high doses of TDC significantly inhibited collagen deposition in TGFβ1-induced HEK293 cell fibrosis.CONCLUSIONS: Major components from the compound herbal medicine Tengdan Capsule are identified and quantified. TDC effectively lowers blood pressure and protects against renal damage caused by hypertension in SHR. Mechanistically, TDC blocks periostin by regulating the TGF-β/Smad signaling pathway in the kidney, both in vivo and in vitro. Preventing periostin-mediated renal fibrosis and inflammation might be a promising strategy for treating a hypertensive renal injury.

Ginsenoside compound K (CK) is the main metabolite of protopanaxadiol-type ginsenosides and has been demonstrated to exert neuroprotective and cognition-enhancing effects. The effects of CK on cognitive function in vascular dementia (VD) has not been elucidated. Therefore, the present study aims to elucidate the effects of CK on memory function as well as its potential mechanism in VD rats. Sprague–Dawley rats were subjected to Chronic Cerebral Hypoperfusion (CCH) by permanent bilateral common carotid artery occlusion (2VO). CCH induced neuronal damage and aggravated the aggregation of Amyloid-β1-42 peptides (Aβ1-42), which plays a critical role in the neurotoxicity and cognitive impairment. CK treatment attenuated CCH-induced Aβ1-42 deposition and ameliorated cognition impairment. Furthermore, CK enhanced the activity of the pSer9-Glycogen synthase kinase 3β (pSer9-GSK3β) and the insulin degrading enzyme (IDE), which mainly involved the production and clearance of Aβ1-42. Moreover, CK treatment enhanced the activity of protein kinase B (PKB/Akt), a key kinase in phosphatidylinositol 3 kinase (PI3K)/Akt pathway that can regulate the activity of GSK-3β and IDE. In short, our findings provide the first evidence that CK might attenuate cognitive deficits and Aβ1-42 deposition in the hippocampus via enhancing the expression of pSer9-GSK-3β and IDE. Keywords: Ginsenoside compound K, Vascular dementia, Aβ1-42, GSK-3β, IDE

In order to improve land-use efficiency and solve traffic congestion, in recent years, many cities in China have focused on developing urban underground space resources and urban rail transit projects. However, there are various hidden risks for the sustainable development of the ecological environment and water resources. In this paper, a comprehensive investigation and analysis of spring water resources are carried out using the example of the karst area of Jinan, which is known as ‘spring city’. The engineering geological and hydrogeological conditions in Jinan are introduced in detail, and the geological causes of springs are analyzed. In addition, the causes of spring flow attenuation are revealed based on the investigation of the flow dynamics of spring water. Based on the current situation of traffic congestion in Jinan, the necessity and development statuses of rail transit construction are analyzed. Then, according to the different stratigraphic structure, limestone roof depth and karst water head depth, the Jinan spring area is divided into three research regions including the shallow limestone area, concentrated spring water area and deep limestone area. The spring protection problems faced by each region during the construction of urban railways are systematically described. In addition, the countermeasures and suggestions for spring protection are presented. This study aims to reduce the impact of urban rail transit construction on Jinan spring water so as to protect the Jinan spring. It also provides the water resources protection experience for urban rail transit construction in similar karst areas.

Paraneoplastic autoimmune multiorgan syndrome is a complex and deadly disease. We retrospectively reviewed the clinical features and risk factors for paraneoplastic autoimmune multiorgan syndrome in 145 Chinese patients. The most common neoplasm was Castleman disease (56%), and patients with Castleman disease tended to be younger (≤ 42 years old: 83% vs. 29%) and to have a greater proportions of lichen planus-like lesions (47% vs. 27%) and bronchiolitis obliterans (49% vs. 29%), compared to other neoplasm-associated patients. Among all 145 patients in the study, the survival rates were 84% at 1 year, 65% at 3 years, and 54% at 5 years. Kaplan-Meier curve analysis revealed that mortality was associated with older age (> 42 years), neoplasm type, labial lesions, and larger skin lesion area (> 17.5% of the body surface area). However, only older age and larger skin lesion area were independent factors associated with mortality in multivariate analysis. We suggest that patients with Castleman disease and paraneoplastic autoimmune multiorgan syndrome have many unique characteristics and the underlying risk factors for death require further exploration.

MicroRNAs (miRNAs) control the proliferation of thymic epithelial cells (TECs) for thymic involution. Previous studies have shown that expression levels of miR-152-3p were significantly increased in the thymus and TECs during the involution of the mouse thymus. However, the possible function and potential molecular mechanism of miR-152-3p remains unclear. This study identified that the overexpression of miR-152-3p can inhibit, while the inhibition of miR-152-3p can promote, the proliferation of murine medullary thymic epithelial cell line 1 (MTEC1) cells. Moreover, miR-152-3p expression was quantitatively analyzed to negatively regulate Smad2, and the Smad2 gene was found to be a direct target of miR-152-3p, using the luciferase reporter assay. Importantly, silencing Smad2 was found to block the G1 phase of cells and inhibit the cell cycle, which was consistent with the overexpression of miR-152-3p. Furthermore, co-transfection studies of siRNA–Smad2 (siSmad2) and the miR-152-3p mimic further established that miR-152-3p inhibited the proliferation of MTEC1 cells by targeting Smad2 and reducing the expression of Smad2. Taken together, this study proved miR-152-3p to be an important molecule that regulates the proliferation of TECs and therefore provides a new reference for delaying thymus involution and thymus regeneration.

Post-stroke neural damage is a serious health concern which does not yet have an effective treatment. We have shown previously that Shuxuening injection (SXNI), a Ginkgo biloba extract-based natural medicine, protects brain after an acute ischemic stroke, but its efficacy for post-stroke recovery is not known. This study was to investigate whether SXNI can improve the prognosis of stroke at a subacute phase. Mice with cerebral ischemia-reperfusion injury (CIRI) were established by middle cerebral artery occlusion (MCAO), and drugs or saline were injected by the tail vein every 12 h after reperfusion. The therapeutic effect of SXNI was evaluated by survival rate, modified neurologic severity scores (mNSS), open-field test, locomotive gait patterns, cerebral infarction volume, brain edema and histopathological changes. Subsequently, a combined method of RNA-seq and Ingenuity® Pathway Analysis (IPA) was performed to identify key targets and pathways of SXNI facilitating the prognosis of stroke in mouse brain. The results of the transcriptome analysis were verified by real time reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), western blot (WB) and immunohistochemistry (IHC). The experimental results showed that in the new subacute stroke model, SXNI markedly improves the survival rate, neurological and motor functions and histopathological changes, and significantly reduces cerebral infarction and edema volume. RNA-seq analysis of subacute stroke mice with or without SXNI (3 mL/kg) indicated 963 differentially expressed genes (DEGs) with a fold change ≥ 1.5 and a P-value ≤ 0.01. IPA analysis of DEGs showed that granulocyte adhesion and diapedesis ranked first in the pathway ranking, and the most critical gene regulated by SXNI was G-csf. Simultaneously, RT-PCR, ELISA, WB and IHC results demonstrated that SXNI not only obviously reduced the mRNA expression levels of key genes G-csf, Sele and Mac-1 in this pathway, but also significantly decreased the protein expression levels of G-CSF in serum and E-selectin and MAC-1 in brain tissues. In summary, our research suggested that SXNI can exert a remarkable neurofunctional therapeutic effect on stroke mice via down-regulating G-CSF to inhibit granulocyte adhesion and diapedesis. This study provides experimental evidence that SXNI may fulfill the need for stroke medicine targeting specifically at the recovery stage.

Rad50 is a member of the double strand break repair epistasis group of proteins that play important roles in regulating DNA damage checkpoint signaling, telomere maintenance, homologous recombination and non-homologous end-joining in eukaryotes. However, the function of Rad50 in fungal plant pathogens remains unknown. In this study, we report the functional investigation of FgRad50 in the wheat head blight pathogen Fusarium graminearum. FgRad50 is an ortholog of Saccharomyces cerevisiae Rad50 that could restore the sensitivity of the yeast Rad50 mutant to DNA damage agents. The FgRad50 deletion mutant (ΔFgRad50) exhibited defective vegetative growth, asexual/sexual development and virulence, as well as disrupted deoxynivalenol biosynthesis. Moreover, deletion of FgRad50 resulted in hypersensitivity to DNA damage agents. Unexpectedly, FgRad50 plays a key role in responses to cell wall-damaging agents by negatively regulating phosphorylation of FgMgv1, a MAP kinase in the cell wall integrity (CWI) pathway. Taken together, these results suggest that FgRad50 plays critical roles in fungal development, virulence and secondary metabolism in F. graminearum, as well as CWI and the DNA damage response.

Abstract Staphylococcus aureus can cause different types of diseases from mild skin infections to life-threatening sepsis worldwide. Owing to the emergence and transmission of multidrug-resistant strains, developing an impactful immunotherapy especially vaccine control approach against S. aureus infections is increasingly encouraged and supported. S. aureus manganese transport protein C (MntC), which is a highly-conserved cell surface protein, can elicit protective immunity against S. aureus and Staphylococcus epidermidis. In this study, we evaluated the humoral immune response and CD4+ T cell-mediated immune responses in a mouse peritonitis model. The results showed that MntC-specific antibodies conferred an essential protection for mice to reduce invasion of S. aureus, which was corroborated via the opsonophagocytic killing assay and passive immunization experiment in mice, and moreover MntC-induced Th17 played a remarkable part in preventing S. aureus infection since the MntC-induced protective immunity decreased after neutralization of IL-17 by antibody in vivo and the Th17 adoptive transferred-mice could partly resist S. aureus challenge. In conclusion, we considered that the MntC-specific antibodies and MntC-specific Th17 cells play cooperative roles in the prevention of S. aureus infection.

Ferroptosis is a newly recognized type of cell death that is different from traditional forms of cell death, such as apoptosis, autophagy, and necrosis. It is caused by the accumulation of intracellular iron, promoting lipid peroxidation and leading to cell death. Iron is essential as a redox metal in several physiological functions. The brain is one of the organs known to be affected by iron homeostatic balance disruption. An increased concentration of iron in the central nervous system has been associated with oxidative stress, lipid peroxidation of proteins, and cell death. The hippocampus is an important brain region for learning, memory, and emotional responses, and is also a sensitive part of the brain to the dysfunctional homeostasis of transition metals. Damage of hippocampal structure and function are intimately involved in the pathogenic mechanisms underlying neurodegenerative diseases. Currently, ferroptosis is playing an increasingly important role in treatment areas of central nervous system diseases. Thus, we provide an overview of ferroptosis regulatory mechanisms, such as lipid metabolism, glutathione metabolism, and iron metabolism in this review. We also highlight the role of ferroptosis in hippocampal-related diseases and investigate a theoretical basis for further research on the role of ferroptosis in nervous system disease treatment.

Rolling technology based on arc-shaped rollers is a novel method for rapid manufacturing of 3D curved parts. The method uses a pair of arc-shaped rollers (a convex roller and a concave roller) as forming tools, forming an unevenly distributed roll gap. The sheet metal has both transverse bending and longitudinal uneven extension during rolling, so that surface parts with double curvature are processed. The curvature of the formed surface part can be changed by changing the rolling reduction. Changing the vertical distance between the rollers will cause the overall change of the roll gap height, which will inevitably have a great impact on the forming effect of formed 3D curved parts. In this paper, a finite element model and experiment with different rolling reductions was designed; the influence of rolling reduction on the bending deformation and shape accuracy of formed 3D curved parts was studied. The results show that, with the slight increase of rolling reduction (from 0.04 to 0.12 mm), the longitudinal bending deformation of the formed 3D curved part increases significantly, but its transversal bending is almost not affected. When the maximum rolling reduction is 0.04 and 0.06 mm (the corresponding minimum rolling reduction is less than or equal to zero), the shape accuracy of the formed 3D curved parts is not good enough; when the maximum rolling reduction is greater than 0.06 mm (the corresponding minimum rolling reduction is greater than zero), the shape accuracy of the formed 3D curved parts is significantly better. This indicates that, for the rolling of 3D curved parts based on arc-shaped rollers, ensuring that the minimum rolling reduction is greater than zero is the key to ensuring good shape accuracy of the formed 3D curved parts.

We present an agent-based model of manipulating prices in financial markets through spoofing: submitting spurious orders to mislead traders who learn from the order book. Our model captures a complex market environment for a single security, whose common value is given by a dynamic fundamental time series. Agents trade through a limit-order book, based on their private values and noisy observations of the fundamental. We consider background agents following two types of trading strategies: the non-spoofable zero intelligence (ZI) that ignores the order book and the manipulable heuristic belief learning (HBL) that exploits the order book to predict price outcomes. We conduct empirical game-theoretic analysis upon simulated agent payoffs across parametrically different environments and measure the effect of spoofing on market performance in approximate strategic equilibria. We demonstrate that HBL traders can benefit price discovery and social welfare, but their existence in equilibrium renders a market vulnerable to manipulation: simple spoofing strategies can effectively mislead traders, distort prices and reduce total surplus. Based on this model, we propose to mitigate spoofing from two aspects: (1) mechanism design to disincentivize manipulation; and (2) trading strategy variations to improve the robustness of learning from market information. We evaluate the proposed approaches, taking into account potential strategic responses of agents, and characterize the conditions under which these approaches may deter manipulation and benefit market welfare. Our model provides a way to quantify the effect of spoofing on trading behavior and market efficiency, and thus it can help to evaluate the effectiveness of various market designs and trading strategies in mitigating an important form of market manipulation.

Recent research shows recurrent neural network-Transducer (RNN-T) architecture has become a mainstream approach for streaming speech recognition. In this work, we investigate the VGG2 network as the input layer to the RNN-T in streaming speech recognition. Specifically, before the input feature is passed to the RNN-T, we introduce a gated-VGG2 block, which uses the first two layers of the VGG16 to extract contextual information in the time domain, and then use a SEnet-style gating mechanism to control what information in the channel domain is to be propagated to RNN-T. The results show that the RNN-T model with the proposed gated-VGG2 block brings significant performance improvement when compared to the existing RNN-T model, and it has a lower latency and character error rate than the Transformer-based model.

Background and objective Malignant pleural effusion (MPE) is due tumor which arises from the mesothelium or metastases from tumor origniating other sites. Generally, the prognosis of MPE is poor, in the premise of reducing the pain of patients, as soon as possible make clear the property of pleural effusion and cause of the disesease, rightly and quickly, providing effective information for subsequent treatment. Methods The cell block of 103 patients by using natural sedimentation or plasma coagulation method combined with HE staining and immunohistochemical staining method maked clear diagnosis and compared with other methods. Results 90 patients were diagnosed by cell block section from 103 patients who had MPE (diagnostic rate 87.4%); 32 cases were diagnosed by cell block section only, 74 cases pointed out that the pathological type , 23 cases even pointed out the primary lesions; 71 cases examined other invasive methods at the same time, the diagnostic rate was 87.3% and 81.7%; the detection rate of cell block section and cytological smear in detecting malignant tumor cells was 86.7%and 44.0% respectively. Conclusion Cell block can not only increase the diagnosis, in contrast to cytological smear, and own the same diagnostic rate compared with other invasive methods, but also can confirm pathological type and primary lesion; especially, for other invasive methods, cell block method is a preferable complementary method, and that cell block method maybe the only way for some patients.