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Abstract Background Chronic infection by Helicobacter pylori strains expressing cytotoxin-associated gene A (CagA) are the strongest risk factor for gastric cancer. CagA can be classified into East Asian-type and Western-type (CagAE and CagAW), with CagAE being more closely associated with gastric cancer. This study aimed to investigate the impact of CagAE on intracellular signaling pathways to explain its high oncogenicity. Results Mutant H. pylori strains expressing either CagAE or CagAW were generated by transforming CagAE/W-expression plasmid into CagA-deleted G27 strain (G27ΔCagA). In human gastric epithelial cells (GES-1) infection, CagAE induced more severe cytopathic changes, including higher interleukin-8 (IL-8) secretion, reduced cell viability, more pronounced “hummingbird phenotype” alterations, and increased cell migration and invasion compared to CagAW. Transcriptome analysis revealed that CagAE had a stronger effect on the up-regulation of key intracellular processes, including tumor necrosis factor-ɑ (TNF-ɑ) signal pathway via nuclear factor kappa-B (NF-κB), inflammatory response, interferon-γ (IFN-γ) response, hypoxia, ultraviolet (UV) response, and Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) signaling. A significant upregulation of hypoxia-related genes was a notable feature of CagAE. GES-1 cells infected with CagAE exhibited more severe intracellular hypoxia and higher levels of reactive oxygen species (ROS) than those infected with CagAW. Inhibition of hypoxia-inducible factor-1α (HIF-1α), which blocks hypoxia signaling, mitigated CagAE-induced cell migration, emphasizing the role of hypoxia in mediating CagAE effects. Conclusions The study provides transcriptome evidence of CagA-associated intracellular regulation during H. pylori infection, demonstrating that CagAE exerts stronger effects on intracellular signaling than CagAW. These findings offer insights into the heightened carcinogenic potential of CagAE in H. pylori-induced gastric cancer.

Abstract Background To introduce a new flange technique (called the Z.S. fixation technique) for 8 − 0 polypropylene suture in scleral fixation of a one-piece intraocular lens (IOL) and evaluate its effectiveness and safety. Methods All surgeries were performed using two strategies. First, the Z.S. fixation technique was used to fix 8 − 0 polypropylene sutures to the sclera and the two haptics of a one-piece IOL, respectively. The one-piece IOL previously implanted in the anterior chamber was then relocated to the posterior chamber. Finally, the suture ends outside the sclera were cauterized into flanges and buried in the sclera. All effectiveness and safety data related to the Z.S. technique were recorded and compared. Results The Z.S. fixation technique was employed in 16 eyes of 13 patients, with a follow-up duration of at least 6 months. Postoperative uncorrected distance visual acuity (UDVA) was greatly improved in most of the operated eyes (11/16). The mean log MAR UDVA after surgery was significantly improved compared with that before surgery (0.93 ± 0.72 vs. 1.53 ± 0.73, P = 0.002). IOLs in the vast majority of operated eyes (15/16) remained stable during half-year follow-up. No severe intra-/post-operative complications were observed in any of the operated eyes. Conclusion The Z.S. fixation technique for 8 − 0 polypropylene suture in scleral fixation of one-piece IOL reduced surgical injuries and had ideal surgical effectiveness and safety.

In order to evaluate the working condition of swivel flange under high temperature and high pressure more accurately, based on the swivel flange in existing pressure level (300~900 lb), the structure and model of the 1 500 lb and 2 500 lb swivel flange were constructed, and the strength and stiffness of the model were checked. Meanwhile, the finite element static mechanical analysis was carried out by using ABAQUS software. The results show that the calculated stress of the swivel flange under each nominal diameter is less than the allowable stress, and the stiffness meets the requirements. The pressure grade and the flange dimension have certain influence on the stress distribution of the swivel flange, and there are two stress concentration areas in the 1 500 lb swivel flange, which are the high neck of the small end of the hub and the contact area between the gaskets and the flange; In addition to the above two stress concentration areas, the 2 500 lb swivel flange also has stress concentration at the edge of the hub's step. The maximum stress always occurs at the high neck of the small end of the hub, and the maximum stress is less than the allowable stress of the material, so the designed high-pound swivel flange meets the usage requirement. The results of the study further enrich the structural design cases of 2 500 lb swivel flange, and provide some reference for the structure design of high-pound swivel flange.

Growth factor receptor bound protein 7 (GRB7) is reportedly upregulated in human gastric cancer (GC), which is closely associated with tumor progression and prognosis. However, the mechanism underlying its dysregulation in GC remains poorly understood. In this study, we found that GRB7 overexpression was associated with Helicobacter pylori (H. pylori) infection. GC cells (AGS and MGC-803) infection assays revealed that this upregulation was mediated by the transcription factor STAT3, and activation of STAT3 by H. pylori promoted GRB7 expression in infected GC cells. Moreover, CagA, the key virulence factor of H. pylori, was found involved in STAT3-mediated GRB7 overexpression. The overexpressed GRB7 further promoted GC cell proliferation, migration, and invasion by activating ERK signaling. Mice infection was further used to investigate the action of GRB7. In H. pylori infection, GRB7 expression in mice gastric mucosa was elevated, and higher STAT3 and ERK activation were also detected. These results revealed GRB7-mediated pathogenesis in H. pylori infection, in which H. pylori activates STAT3, leading to increased GRB7 expression, then promotes activation of the ERK signal, and finally enhances malignant properties of infected cells. Our findings elucidate the role of GRB7 in H. pylori-induced gastric disorders, offering new prospects for the treatment and prevention of H. pylori-associated gastric carcinogenesis by targeting GRB7.

CagA is a significant oncogenic factor injected into host cells by Helicobacter pylori, which is divided into two subtypes: East Asian type (CagAE), characterized by the EPIYA-D motif, and western type (CagAW), harboring the EPIYA-C motif. CagAE has been reported to have higher carcinogenicity than CagAW, although the underlying reason is not fully understood. SHIP2 is an intracellular phosphatase that can be recruited by CagA to perturb the homeostasis of intracellular signaling pathways. In this study, we found that SHIP2 contributes to the higher oncogenicity of CagAE. Co-Immunoprecipitation and Pull-down assays showed that CagAE bind more SHIP2 than CagAW. Immunofluorescence staining showed that a higher amount of SHIP2 recruited by CagAE to the plasma membrane catalyzes the conversion of PI(3,4,5)P3 into PI(3,4)P2. This alteration causes higher activation of Akt signaling, which results in enhanced IL-8 secretion, migration, and invasion of the infected cells. SPR analysis showed that this stronger interaction between CagAE and SHIP2 stems from the higher affinity between the EPIYA-D motif of CagAE and the SH2 domain of SHIP2. Structural analysis revealed the crucial role of the Phe residue at the Y + 5 position in EPIYA-D. After mutating Phe of CagAE into Asp (the corresponding residue in the EPIYA-C motif) or Ala, the activation of downstream Akt signaling was reduced and the malignant transformation of infected cells was alleviated. These findings revealed that CagAE hijacks SHIP2 through its EPIYA-D motif to enhance its carcinogenicity, which provides a better understanding of the higher oncogenic risk of H. pylori CagAE.

With the development of the economy, more and more electronic manufacturing enterprises are emerging like mushrooms after rain. These enterprises, while developing, also face financial risks caused by various reasons. In order to provide early warning for financial risks of enterprises, improve the accuracy of identifying financial risks, avoid financial crises, and provide assistance for sustainable development decisions, this paper proposes a financial management model based on modified random forest. In order to improve the generalization ability of financial management models, pruning methods were adopted in the study to avoid overfitting. Synthetic minority oversampling technique is used to optimize the financial management model and reduce the calculation deviation of the model through its sampling ability. At the same time, the prediction index system is proposed to improve the analysis ability of the financial management model. The results show that the accuracy and recall rate of the improved algorithm based on random forest proposed in this study in identifying corporate financial distress are 98.03 % and 100 % respectively. The importance value of operating income and cash flow in enterprise indicators is 0.391, which is the most relevant indicator for enterprise financial forecasting. The results show that after the improvement of synthetic minority oversampling technique, the stochastic forest model can effectively improve the recognition and early warning ability of enterprises’ financial distress, and is conducive to maintaining good operating efficiency and sustainable operation of enterprises. Electronic manufacturing enterprises need to strengthen their attention to cash flow, improve their cash flow, and enhance their profitability. The financial management model designed by the research institute can provide technical and information support for financial early warning and sustainable development of electronic manufacturing enterprises.

The field of bone regeneration has witnessed significant advancements with the exploration and incorporation of marine biomaterials, offering promising avenues for orthopaedic and dental applications. Marine environments are a rich source of biological materials with unique properties conducive to bone healing and regeneration. Repurposing and reusing some waste by-products of marine products for bone regeneration not only contribute to environmental protection but also drives the development of the marine economy, thereby achieving sustainable development. Moreover, the lower production costs associated with the abundant availability and easy processing of marine biomaterials make bone regeneration therapies more accessible to a broader population, enhancing global health equity. By exploring the current research progressions on marine biomaterials and recounting their sources, properties, mechanisms of action, and applications in bone regeneration research, this review provides a comprehensive overview of the potential and challenges of marine biomaterials for future bone healing and regeneration applications.

Summary: Piezoelectric atomization is becoming mainstream in the field of inhalation therapy due to its significant advantages. With the rapid development of high-viscosity gene therapy drugs, the demand for piezoelectric atomization devices is increasing. However, conventional piezoelectric atomizers with a single-dimensional energy supply are unable to provide the energy required to atomize high-viscosity liquids. To address this problem, our team has designed a flow tube internal cavitation atomizer (FTICA). This study focuses on dissecting the atomization mechanism of FTICA. In contrast to the widely supported capillary wave hypothesis, our study provides evidence in favor of the cavitation hypothesis, proving that cavitation is the key to atomizing high-viscosity liquids with FTICA. In order to prove that the cavitation is the key to atomizing in the structure of FTICA, the performance of atomization is experimented after changing the cavitation conditions by heating and stirring of the liquids.

Abstract Objective Benzene, ethylbenzene, meta/para-xylene, and ortho-xylene, collectively referred to as benzene, ethylbenzene, and xylene (BEX), constitute the main components of volatile organic aromatic compounds (VOACs) and can have adverse effects on human health. The relationship between exposure to BEX and hearing loss (HL) in the adult U.S. population was aimed to be assessed. Methods Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) for the years 2003–2004, 2011–2012, and 2015–2016 were analyzed. This dataset included complete demographic characteristics, pure-tone audiometry measurements, and volatile organic compound detection data from the NHANES database. A weighted multivariate logistic regression model was employed to investigate the associations between blood BEX concentrations HL, low-frequency hearing loss (SFHL), and high-frequency hearing loss (HFHL). Results 2174 participants were included, with weighted prevalence rates of HL, SFHL, and HFHL being 46.81%, 25.23%, and 45.86%, respectively. Exposure to benzene, ethylbenzene, meta/para-xylene, and ortho-xylene, and cumulative BEX concentrations increased the risk of hearing loss (odds ratios [ORs] were 1.36, 1.22, 1.42, 1.23, and 1.31, respectively; all P

Abstract Background Leishmaniasis is mainly prevalent in tropical and subtropical developing countries, where chronic undernutrition often co-exists. Undernutrition is reported to promote the progression of leishmaniasis, but its immune mechanisms have not been fully elucidated. Methods To simulate chronic undernutrition of patients in epidemic areas and explore the immune mechanism of undernutrition promoting leishmaniasis, BALB/c mouse models with different nutritional imbalances were established, including undernutrition 75%, undernutrition 65% and obesity mouse models. After infection with Leishmania donovani in these model mice, we focused on evaluating the progress of leishmaniasis in the spleen and liver, the expression of important immunosuppressive and immunoactivation molecules, and changes of spleen transcriptome. The immune signaling pathways enriched by differentially expressed genes and hub genes were analyzed. Results The results showed that among the mouse infection models, undernutrition 75% + infection group had the highest parasite load in the spleen and liver at the 8th week post-infection, possibly due to the continuous increase of PD-1, PD-L1 and TCR. Spleen RNA-seq results suggested that some immune signaling pathways were downregulated in undernutrition 75% + infection group, including neutrophil extracellular trap formation, IL-17 signaling pathway, natural killer cell-mediated cytotoxicity, etc. Among them, neutrophil extracellular trap formation pathway had the largest number of downregulated genes. This also explained why undernutrition 75% + infection group had the highest parasite load. Through PPI network analysis, hub genes such as Lcn2, Ltf, Mpo, Dnaja1, Hspa1a, Hspa1b and Hsph1 were screened out and might play important roles in the process of undernutrition promoting leishmaniasis. Conclusions Undernutrition upregulated PD-1 and PD-L1 expression and downregulated immune signaling pathways in mice with visceral leishmaniasis. The signaling pathways and hub genes may serve as drug targets or intervention targets for the treatment of leishmaniasis patients with undernutrition. Graphical Abstract

Abstract Introduction ReCOV is a recombinant protein vaccine that aims to induce cross-neutralization against SARS-CoV-2 variants. The phase I and phase II studies were conducted in New Zealand and the Philippines, respectively, for ReCOV primary series. Methods Both studies were randomized, double-blind, placebo-controlled designed among COVID-19 vaccine-naïve healthy adults who received two doses of study vaccination with a 21-day interval. In phase I, 100 younger (15–55 years) and older (56–80 years) subjects were 4:1 randomized to receive ReCOV (20 µg or 40 µg) or placebo. In the phase II study, 347 subjects (≥ 18 years) were 2:1 randomized to receive 40 µg ReCOV or placebo. Subjects that received ReCOV were followed up for 6 months after the second dosing. The safety outcomes included solicited and unsolicited AEs, SAEs, and AESIs. The immunogenicity outcomes were live-virus neutralizing antibody (NAb) against prototype, while pseudovirus NAbs against several SARS-CoV-2 variants were included in phase II as well. Results No related SAE, AESI, or AE leading to early discontinuation were reported. The AE incidences were higher in ReCOV groups than placebo group in phase I while they were similar between study groups in phase II. The majority of solicited AEs were mild or moderate with median duration of 1.0–4.0 days. The common (≥ 10%) solicited AEs in phase I were injection site reactions, headache, pyrexia, fatigue, and myalgia, and common reported (≥ 5%) ones in phase II included injection site pain, headache, and pyrexia. Robust neutralizing activities against the prototype were observed in ReCOV groups, peaking at 14 days post the second dosing: in phase I, the GMTs for 20 μg and 40 μg ReCOV groups were 1643.2 IU/mL (95% CI 1188.5, 2271.9) and 1289.2 IU/mL (95% CI 868.3, 1914.1) in younger adults, and 1122.3 IU/mL (95% CI 722.6, 1743.1) and 680.3 IU/mL (95% CI 440.2, 1051.4) in older adults, respectively, while in the ReCOV group of phase II, the GMTs for subjects with seronegative and seropositive status at baseline were 3741.0 IU/mL (95% CI 3113.4, 4495.0) and 6138.3 IU/mL (95% CI 5255.1, 7169.9), respectively. In phase II, substantial levels of pseudovirus NAbs against SARS-CoV-2 variants were demonstrated; the peak GMTs for prototype, Omicron BA.2, and BA.4/5 were 8857, 4441, and 2644, and 15,667.3, 7334.3, and 4478.8 among seronegative and seropositive subjects, respectively. The neutralization persisted till 6 months post the second dosing, with only 2.5- to 5.2-fold declines for Omicron variants. Conclusions Two doses of 20 µg and 40 µg ReCOV are safe and immunogenic against SARS-CoV-2 prototype. The cross-neutralizing activities against Omicron variants support ReCOV advance to late-stage clinical trials. Trial Registration Phase I study, clinicaltrials.gov NCT04818801; phase II study, clinicaltrials.gov NCT05084989.

Anthocyanins are important secondary metabolites in plants, which contribute to fruit color and nutritional value. Anthocyanins can be regulated by environmental factors such as light, low temperature, water conditions, and nutrition limitations. Nitrogen (N) is an essential macroelement for plant development, its deficiency as a kind of nutrition limitation often induces anthocyanin accumulation in many plants. However, there is a lack of reports regarding the effect of nitrogen deficiency on anthocyanin biosynthesis in pears. In this study, we found that N deficiency resulted in anthocyanin accumulation in pear callus and upregulated the expression of anthocyanin biosynthesis pathway structural genes (PyPAL, PyCHS, PyCHI, PyF3H, PyDFR, PyANS, and PyUFGT) and key regulatory factors (PyMYB10, PyMYB114, and PybHLH3). Through analysis of transcriptome data of treated pear callus and RT-qPCR assay, a differentially expressed gene PyNAC42 was identified as significantly induced by the N deficiency condition. Overexpression of PyNAC42 promoted anthocyanin accumulation in “Zaosu” pear peels. Additionally, dual luciferase assay and yeast one-hybrid assay demonstrated that PyNAC42 could not directly activate the expression of PyDFR, PyANS, and PyUFGT. Furthermore, yeast two-hybrid and pull-down assays confirmed that PyNAC42 interacted with PyMYB10 both in vivo and in vitro. Co-expression of PyNAC42 and PyMYB10 significantly enhanced anthocyanin accumulation in “Zaosu” pear peels. Dual luciferase assay showed that PyNAC42 significantly enhanced the activation of PyDFR, PyANS, and PyUFGT promoters by interacting with PyMYB10, which suggests that PyNAC42 can form the PyNAC42-PyMYB10 complex to regulate anthocyanin biosynthesis in pear. Thus, the molecular mechanism underlying anthocyanin biosynthesis induced by N deficiency is preliminarily elucidated. Our finding has expanded the regulatory network of anthocyanin biosynthesis and enhanced our understanding of the mechanisms underlying nutrient deficiency modulates anthocyanin biosynthesis in pear.

Ferroptosis, an iron-dependent lipid peroxidation-induced form of regulated cell death, shows great promise as a cancer therapy strategy. Despite the critical role of mitochondria in ferroptosis regulation, the underlying mechanisms remain elusive. This study reveals that the mitochondrial protein METTL17 governs mitochondrial function in colorectal cancer (CRC) cells through epigenetic modulation. Bioinformatic analysis establishes that METTL17 expression positively correlates with ferroptosis resistance in cancer cells and is up-regulated in CRC. Depletion of METTL17 sensitizes CRC cells to ferroptosis, impairs cell proliferation, migration, invasion, xenograft tumor growth, and AOM/DSS-induced CRC tumorigenesis. Furthermore, suppression of METTL17 disrupts mitochondrial function, energy metabolism, and enhances intracellular and mitochondrial lipid peroxidation and ROS levels during ferroptotic stress. Mechanistically, METTL17 inhibition significantly reduces mitochondrial RNA methylation, including m4C, m5C, m3C, m7G, and m6A, leading to impaired translation of mitochondrial protein-coding genes. Additionally, the interacting proteins associated with METTL17 are essential for mitochondrial gene expression, and their knockdown sensitizes CRC cells to ferroptosis and inhibits cell proliferation. Notably, combined targeting of METTL17 and ferroptosis in a therapeutic approach effectively suppresses CRC xenograft growth in vivo. This study uncovers the METTL17-mediated defense mechanism for cell survival and ferroptosis in mitochondria, highlighting METTL17 as a potential therapeutic target for CRC.

The secretions of the glandular trichomes of tobacco leaves and flowers contain abundant secondary metabolites of different compounds, such as cebradanes, labdanes, and saccharide esters. These secondary metabolites have shown interesting biological properties, such as antimicrobial, insecticidal, and antioxidant activity. In this study, 81 air/sun-cured tobacco germplasms were used as experimental materials. Quantitative and qualitative analyses of the glandular secretion components were conducted using ultra-performance liquid chromatography–quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF MS) and gas chromatography–mass spectrometry (GC-MS). The ethanol extracts of glandular trichomes from tobacco leaves and flowers were evaluated for antifungal activity against the fungus Botrytis cinerea using the mycelial growth rate method. Orthogonal Partial Least Squares (OPLS) analysis was then performed to determine the relationship between the trichome secretion components and their anti-fungal activity. The results showed significant differences among the antifungal activities of the tested ethanol extracts of tobacco glandular trichomes. The inhibition rates of the upper leaves and flower extracts against B. cinerea were significantly higher than those of the middle and lower leaves, and 59 germplasms (73.75% of the tested resources) showed antifungal rates higher than 50%, with four germplasms achieving a 95% antifungal rate at the same fresh weight concentration (10 mg/mL). The OPLS analysis revealed that the antifungal activity was primarily associated with alpha-cembratriene-diol (α-CBT-diol (Peak7)) and beta-cembratriene-diol (β-CBT-diol (Peak8)), followed by sucrose esters III (SE(III)) and cembratriene-diol oxide. These findings help identify excellent tobacco germplasms for the development and utilization of botanical pesticides against fungi and provide a theoretical reference for the multipurpose utilization of tobacco germplasms.

The composite films of metal and SiC have attracted much attention in the fields of microelectronics, heat conduction, and electromagnetic wave absorption because of their excellent properties. In this work, SiC/Cu3N composite films were prepared by magnetron sputtering technique, and the films were annealed at 500 °C to obtain microporous SiC/Cu composite films. The effects of different N2 flow ratios (r) on the structure and properties of the composite films were investigated. The results show that the Cu grain size in the microporous SiC/Cu composite films increases and decreases as r increases. When r = 1/4, the surface particles of the composite films are uniform in size, with uniform pores and stable structure. At the same time, the degree of graphitization in the film is relatively high. The composite films exhibit semiconductor properties with an optical band gap of 0.92 eV–1.29 eV. With the increase of r, the sp2C bond content in the films increases and then decreases, and the optical band gap shows a trend of reducing and then increasing. This study provides a new strategy for preparing microporous SiC/Cu composite films for applications in the field of optoelectronic devices and energy storage devices.

This study aimed to obtain a high yield and purity of Sargassum pallidum polyphenol extracts (SPPE) and study its enzyme activity. Fresh Sargassum pallidum seaweed was selected for optimization of ultrasound-assisted extraction (UAE) conditions and purification conditions using macroporous resin and Sephadex LH20 to obtain SPPE. The SPPE was characterized using UPLC-QTOF-MS/MS and α-amylase, α-glucosidase, tyrosinase, and AchE inhibitory activity were determined. The maximum extraction rate of SPPE was 7.56 mg GAE/g and the polyphenol purity reached 70.5% after macroporous resin and Sephadex LH-20 purification. A total of 50 compounds were identified by UPLC-QTOF-MS/MS. The IC50 values of SPPE were 334.9 μg/mL, 6.290 μg /mL, 0.834 mg /mL and 0.6538 mg /mL for α-amylase, α-glucosidase, tyrosinase and AchE, respectively. Molecular docking technology further revealed the effects of SPPE on the above enzymes. This study provided information on the potential hypoglycemic, whitening and anti-Alzheimer's disease biological activities of SPPE, which had guiding significance for the purification and development of other seaweed polyphenols.

As a clean fossil energy source, natural gas plays a crucial role in the global energy transition. Forecasting natural gas prices is an important area of research. This paper aims at developing a novel hybrid model that contributes to the prediction of natural gas prices. We develop a novel hybrid model that combines the “Decomposition Algorithm” (CEEMDAN), “Ensemble Algorithm” (Bagging), “Optimization Algorithm” (HHO), and “Forecasting model” (SVR). The hybrid model is used for monthly Henry Hub natural gas forecasting. To avoid the problem of data leakage caused by decomposing the whole time series, we propose a rolling decomposition algorithm. In addition, we analyzed the factors affecting Henry Hub natural gas prices for multivariate forecasting. Experimental results indicate that the proposed model is more effective than the traditional model at predicting natural gas prices.

Federated learning (FL) is a framework which is used in distributed machine learning to obtain an optimal model from clients' local updates. As an efficient design in model convergence and data communication, cloud-edge-client hierarchical federated learning (HFL) attracts more attention than the typical cloud-client architecture. However, the HFL still poses threats to clients' sensitive data by analyzing the upload and download parameters. In this paper, to address information leakage effectively, we propose a novel privacy-preserving scheme based on the concept of differential privacy (DP), adding Gaussian noises to the shared parameters when uploading them to edge and cloud servers and broadcasting them to clients. Our algorithm can obtain global differential privacy with adjustable noises in the architecture. We evaluate the performance on image classification tasks. In our experiment on the Modified National Institute of Standards and Technology (MNIST) dataset, we get 91% model accuracy-layer HFL-DP, our design is more secure while as being accurate.

The southeastern Tibetan Plateau, which profoundly affects East Asia by helping to maintain the stability of climate systems, biological diversity and clean water, is one of the regions most vulnerable to water erosion, wind erosion, tillage erosion, freeze–thaw erosion and overgrazing under global climate changes and intensive human activities. Spatial variations in soil erosion in terraced farmland (TL), sloping farmland (SL) and grassland (GL) were determined by the 137Cs tracing method and compared with spatial variations in soil organic carbon (SOC) and total nitrogen (total N). The 137Cs concentration in the GL was higher in the 0–0.03 m soil layer than in the other soil layers due to weak migration and diffusion under low precipitation and temperature conditions, while the 137Cs concentration in the soil layer of the SL was generally uniform in the 0–0.18 m soil layer due to tillage-induced mixing. Low 137Cs inventories appeared at the summit and toe slope positions in the SL due to soil loss by tillage erosion and water erosion, respectively, while the highest 137Cs inventories appeared at the middle slope positions due to soil accumulation under relatively flat landform conditions. In the GL, the 137Cs data showed that higher soil erosion rates appeared at the summit due to freeze–thaw erosion and steep slope gradients and at the toe slope position due to wind erosion, gully erosion, freeze–thaw erosion and overgrazing. The 137Cs inventory generally increased from upper to lower slope positions within each terrace (except the lowest terrace). The 137Cs data along the terrace toposequence showed abrupt changes in soil erosion rates between the lower part of the upper terrace and the upper part of the immediate terrace over a short distance and net deposition on the lower and toe terraces. Hence, tillage erosion played an important role in the soil loss at the summit slope positions of each terrace, while water erosion dominantly transported soil from the upper terrace to the lower terrace and resulted in net soil deposition on the flat lower terrace. The SOC inventories showed similar spatial patterns to the 137Cs inventories in the SL, TL and GL, and significant correlations were found between the SOC and 137Cs inventories in these slope landscapes. The total N inventories showed similar spatial patterns to the inventories of 137Cs and SOC, and significant correlations were also found between the total N and 137Cs inventories in the SL, TL and GL. Therefore, 137Cs can successfully be used for tracing soil, SOC and total N dynamics within slope landscapes in the southeastern Tibetan Plateau.

Planar reconstruction detects planar segments and deduces their 3D planar parameters (normals and offsets) from the input image; this has significant potential in the fields of digital preservation of cultural heritage, architectural design, robot navigation, intelligent transportation, and security monitoring. Existing methods mainly employ multiple-view images with limited overlap for reconstruction but lack the utilization of the relative position and rotation information between the images. To fill this gap, this paper uses two views and their relative camera pose to reconstruct indoor scene planar surfaces. Firstly, we detect plane segments with their 3D planar parameters and appearance embedding features using PlaneRCNN. Then, we transform the plane segments into a global coordinate frame using the relative camera transformation and find matched planes using the assignment algorithm. Finally, matched planes are merged by tackling a nonlinear optimization problem with a trust-region reflective minimizer. An experiment on the Matterport3D dataset demonstrates that the proposed method achieves 40.67% average precision of plane reconstruction, which is an improvement of roughly 3% over Sparse Planes, and it improves the IPAA-80 metric by 10% to 65.7%. This study can provide methodological support for 3D sensing and scene reconstruction in sparse view contexts.

Anthocyanins play a crucial role in imparting red coloration to pear fruits. However, the specific number and expression patterns of each member within the anthocyanin biosynthesis-related gene families in pears require systematic exploration. In this study, based on the pear genome we identified 15 gene families involved in the anthocyanin biosynthesis pathway using the BLASTP and Hidden Markov Model search methods, comprising a total of 94 enzyme genes. Through phylogenetic analysis, conserved domains, motif, and gene structure analysis, these gene families were further categorized into eight distinct lineages. Subsequent collinearity analysis revealed that the expansion of anthocyanin synthesis-related gene families primarily originated from segmental duplications. Analysis of cis-element in the promoter regions of genes related to anthocyanin synthesis unveiled the presence of light-responsive elements and various hormone-responsive elements. This suggests that changes in light stimulation and hormone levels may influence anthocyanin synthesis. RNA-Seq and qRT-PCR analyses indicated differential expression of anthocyanin biosynthesis-related genes between the peel and flesh tissues. During the accumulation of anthocyanins in red-fleshed pears, upstream genes in the anthocyanin biosynthesis pathway such as PbrPAL2, PbrC4H2, PbrC4H3, Pbr4CL2, Pbr4CL17, PbrF3H5, and PbrF3H6 exhibited high expression levels, likely contributing significantly to the red coloration of pear flesh. In summary, we have identified the number of gene family members involved in pear anthocyanin biosynthesis and analyzed the expression patterns of the genes related to pear anthocyanin biosynthesis. These findings provide a solid foundation for further research on the regulatory mechanisms underlying pear anthocyanin biosynthesis and the breeding of red pear varieties.

ObjectiveThe Omicron BA.5.2 variant of SARS-CoV-2 has undergone several evolutionary adaptations, leading to multiple subvariants. Rapid and accurate characterization of these subvariants is essential for effective treatment, particularly in critically ill patients. This study leverages Next-Generation Sequencing (NGS) to elucidate the clinical and immunological features across different Omicron BA.5.2 subvariants.MethodsWe enrolled 28 patients infected with the Omicron variant, hospitalized in Zhangjiajie People’s Hospital, Hunan, China, between January 20, 2023, and March 31, 2023. Throat swabs were collected upon admission for NGS-based identification of Omicron subvariants. Clinical data, including qSOFA scores and key laboratory tests, were collated. A detailed analysis of lymphocyte subsets was conducted to ascertain the extent of immune cell damage and disease severity.ResultsPatients were infected with various Omicron subvariants, including BA.5.2.48, BA.5.2.49, BA.5.2.6, BF.7.14, DY.1, DY.2, DY.3, and DY.4. Despite having 43 identical mutation sites, each subvariant exhibited unique marker mutations. Critically ill patients demonstrated significant depletion in total lymphocyte count, T cells, CD4, CD8, B cells, and NK cells (P < 0.05). However, there were no significant differences in clinical and immunological markers across the subvariants.ConclusionThis study reveals that critically ill patients infected with different Omicron BA.5.2 subvariants experience similar levels of cellular immune dysfunction and inflammatory response. Four mutations - ORF1a:K3353R, ORF1a:L3667F, ORF1b:S997P, S:T883I showed correlation with immunological responses although this conclusion suffers from the small sample size. Our findings underscore the utility of NGS in the comprehensive assessment of infectious diseases, contributing to more effective clinical decision-making.

LGP2 is a RIG-I-like receptor (RLR) known to bind and recognize the intermediate double-stranded RNA (dsRNA) during virus infection and to induce type-I interferon (IFN)-related antiviral innate immune responses. Here, we find that LGP2 inhibits Zika virus (ZIKV) and tick-borne encephalitis virus (TBEV) replication independent of IFN induction. Co-immunoprecipitation (Co-IP) and confocal immunofluorescence data suggest that LGP2 likely colocalizes with the replication complex (RC) of ZIKV by interacting with viral RNA-dependent RNA polymerase (RdRP) NS5. We further verify that the regulatory domain (RD) of LGP2 directly interacts with RdRP of NS5 by biolayer interferometry assay. Data from in vitro RdRP assays indicate that LGP2 may inhibit polymerase activities of NS5 at pre-elongation but not elongation stages, while an RNA-binding-defective LGP2 mutant can still inhibit RdRP activities and virus replication. Taken together, our work suggests that LGP2 can inhibit flavivirus replication through direct interaction with NS5 protein and downregulates its polymerase pre-elongation activities, demonstrating a distinct role of LGP2 beyond its function in innate immune responses.

Frequent processes of mutual transfer and transformation generally take place between the material flow, the energy flow, and the information flow in complex engineering systems, and complex coupling relationships exist between the different flows. Abnormal coupling of flows will cause flow problems, which can easily lead to the failure of the system functions. To address these problems, in this study, the starting point has been taken as the change in the attributes and types of the study flow, the attributes of the flows have been categorized, and a flow transfer and transformation model, oriented to the flow problem analysis has been proposed. Secondly, based on the analysis of the effect of the attribute changes of flows in complex engineering systems on the generation of flow problems, an innovatively introduced information processing mathematical tool, the polychromatic sets theory, has been used to explore and determine the flow problems existing in complex engineering systems. Further, depending on the different manifestations of flow problems, three solution strategies have been proposed. Finally, the process model of the flow problem judgment and a solution strategy for complex engineering systems has been constructed. The feasibility of the process model has been verified by considering the engineering case of the tubular feeding machine (TFM) system of a large-scale integrated marine resource survey ship.

Aerated stirring pretreatment to achieve effective flotation separation of chalcopyrite and pyrrhotite has been studied in this paper. It is mainly investigated the relationship between the dosing sequence, mixing time and aeration rate and the recovery rate of chalcopyrite. The results of the study show that the effect of adding chemicals before aerated stirring is better than that of adding chemicals after aerated stirring; the increase of aeration rate helps to increase the recovery rate of chalcopyrite, and the recovery rate changes gentle after the rate reaches 2 m3/h ; the recovery rate of chalcopyrite increases with the increase of stirring time within 0~35 min of stirring, and the recovery rate reaches highest at 35 min and then tends to be gentle. The possible reason for the analysis of the above phenomenon is that the oxidation of pyrrhotite consumes the oxygen in the pulp, resulting in insufficient oxygen in the pulp to participate in the adsorption process of xanthate on chalcopyrite surface. After the slurry is filled with air, the oxygen in the air participates in the surface oxidation of pyrrhotite, thereby ensuring that there is enough oxygen in the slurry to participate in the adsorption process of xanthate on the surface of chalcopyrite, thereby increasing the chalcopyrite’s recovery rate.

The University of Hawai’i at Mānoa’s Uehiro Academy for Philosophy and Ethics in Education (UHM Uehiro Academy) prepares, supports and sustains philosophy for children Hawai‘i (p4cHI) educators, researchers, and students in Hawai‘i and beyond. This paper documents the impact of the Uehiro Academy’s philosophy outreach program at Kailua High School (KHS), a public secondary school on the Hawaiian Island of O’ahu. It describes the twenty year partnership between the University and KHS, which built a foundation for p4cHI to become integrated across the curriculum and within the school culture. To better understand the overall impact of the UHM Uehiro Academy philosophy outreach program on KHS, researchers asked, ‘How has the UHM Uehiro Academy philosophy outreach program impacted the school culture at KHS?’ Qualitative methods were applied to design and conduct a research study, which included interviewing 68 members of the KHS community. Data analysis revealed four main themes: (1) a schoolwide learner-centred pedagogy, (2) a place for learning more than just academics, (3) a community of diverse and connected individuals, (4) a commitment to professional growth for the purpose of a better world. The paper ends with conclusions, implications of the findings, and the researchers reflecting on the findings, including the benefits and challenges of university philosophy outreach programs in the secondary school setting.

The Array for Real-time Geostrophic Oceanography (Argo) program provides valuable data for maritime research and rescue operations. This paper is based on Argo historical and satellite observations, and inverted sea surface and submarine drift trajectories. A neural network method was developed to predict the position of Argo buoys, improving target tracking and emergency support capabilities. Based on a deep learning framework using a Simple Recurrent Unit (SRU), a new Time–Space Feature Fusion Method based on an Attention Mechanism (TSFFAM) model was constructed. The TSFFAM mechanism can predict the target trajectory more accurately, avoiding the disadvantages of traditional Long Short-Term Memory (LSTM) models, which are time consuming and difficult to train. The TSFFAM model is able to better capture multi-scale ocean factors, leading to more accurate and efficient buoy trajectory predictions. In addition, it aims to shed light on the mechanism of the joint multi-element and multi-scale effects of laminar and surface currents on multi-scale ocean factors, thereby deepening our understanding of the multi-element and multi-scale interactions in different spatio-temporal regimes of the ocean. Experimental verification was conducted in the Pacific Ocean using buoy trajectory data, and the experimental results showed that the buoy trajectory prediction models proposed in this paper can achieve high prediction accuracy, with the TSFFAM model improving the accuracy rate by approximately 20%. This research holds significant practical value for the field of maritime studies, precise rescue operations, and efficient target tracking.

Piezoelectric pumps play an important role in modern medical technology. To improve the flow rate of valveless piezoelectric pumps with flow tube structures and promote the miniaturization and integration of their designs, a cardioid flow tube valveless piezoelectric pump (CFTVPP) is proposed in this study. The symmetric dual-bend tube design of CFTVPP holds great potential in applications such as fluid mixing and heat dissipation systems. The structure and working principle of the CFTVPP are analyzed, and flow resistance and velocity equations are established. Furthermore, the flow characteristics of the cardioid flow tube (CFT) are investigated through computational fluid dynamics, and the output performance of valveless piezoelectric pumps with different bend radii is studied. Experimental results demonstrate that CFTVPP exhibits the pumping effect, with a maximum vibration amplitude of 182.5 μm (at 22 Hz, 100 V) and a maximum output flow rate of 5.69 mL/min (at 25 Hz, 100 V). The results indicate that a smaller bend radius of the converging bend leads to a higher output flow rate, while the performance of valveless piezoelectric pumps with different diverging bends shows insignificant differences. The CFTVPP offers advantages such as a high output flow rate, low cost, small size for easy integration, and ease of manufacturing.

Abstract Traditional atomization devices always exhibit many drawbacks, such as non-uniform atomization particle sizes, instability of transient atomization quantity and uncontrollability of precise energy, which seriously restrict further practical application of atomization inhalation therapy. The formation and separation process of droplets belongs to a microphenomenon of atomization. The investigation of the droplet formation and separation process will be favorable for understanding the atomization mechanism. In present work, the Conservative Level Set Method (CLSM) is successfully applied on the simulation of the formation and separation of droplets in a medical piezoelectric atomization device induced by intra-hole fluctuation. The intra-hole fluctuation mechanism is systematically explored and analyzed, and also the expression of the volume change in the micro cone hole is built and evaluated. Both the control equation and simulation model of droplet formation and separation process have been well established by meshing the simulation model, and thereby the process of droplet formation and separation is simulated. The corresponding results demonstrate that the breaking time of droplets is decreased with the inlet velocity and liquid temperature rising, while enhanced with the liquid concentration increasing. Meanwhile, the volume of droplet is decreased with the inlet velocity and liquid concentration increasing, but increased with the liquid temperature rising. The velocity of droplet is enhanced with the inlet velocity and liquid temperature rising, and reduced with the increase of liquid concentration. When the large side diameter of micro-cone hole is set as 79 μm, the breaking time of the droplet reaches a minimum value of 38.7 μs, whereas the volume and the velocity of droplet reach a maximum value of 79.8 pL and 4.46 m/s, respectively. This study provides theoretical guidance for the design of medical piezoelectric atomization devices and contributes to the promotion of inhalation therapy in practical use.

Sodium ion insertion plays a critical role in developing robust sodium-ion technologies (batteries and hybrid supercapacitors). Diffusion coefficient values of sodium (DNa+) in tin phosphide between 0.1 V and 2.0 V vs. Na/Na+ are systematically determined by galvanostatic intermittent titration technique (GITT), electrochemical impedance spectroscopy (EIS), and potentiostatic intermittent titration technique (PITT). These values range between 4.55 × 10−12 cm2 s−1 and 1.94 × 10−8 cm2 s−1 and depend on the insertion/de-insertion current and the thickness of the electrode materials. Additionally, DNa+ values differ between the first and second cation insertion because of the solid electrolyte interface (SEI) formation. DNa+ vs. insertion potential alters non-linearly in a “W” form due to the strong interactions of Na+ with tin phosphide particles. The results reveal that GITT is a more appropriate electrochemical technique than PITT and EIS for evaluating DNa+ in tin phosphide.

Piezoelectric atomization has been applied in the field of respiratory medicine delivery and chemistry. However, the wider application of this technique is limited by the viscosity of the liquid. High-viscosity liquid atomization has great potential for applications in aerospace, medicine, solid-state batteries and engines, but the actual development of atomization is behind expectations. In this study, instead of the traditional model of single-dimensional vibration as a power supply, we propose a novel atomization mechanism that uses two coupled vibrations to induce micro-amplitude elliptical motion of the particles on the surface of the liquid carrier, which produces a similar effect as localized traveling waves to push the liquid forward and induce cavitation to achieve atomization. To achieve this, a flow tube internal cavitation atomizer (FTICA) consisting of a vibration source, a connecting block and a liquid carrier is designed. The prototype can atomize liquids with dynamic viscosities up to 175 cP at room temperature with a driving frequency of 507 kHz and a voltage of 85 V. The maximum atomization rate in the experiment is 56.35 mg/min, and the average atomized particle diameter is 10 µm. Vibration models for the three parts of the proposed FTICA are established, and the vibration characteristics and atomization mechanism of the prototype were verified using the vibration displacement measurement experiment and the spectroscopic experiment. This study offers new possibilities for transpulmonary inhalation therapy, engine fuel supply, solid-state battery processing and other areas where high-viscosity microparticle atomization is needed.

At present, most isomer scheduling models in DHR systems only considered second-order isomerism and lack dynamics.In order to solve these problems, a dynamic scheduling algorithm was proposed, which combined heterogeneity and dynamics by determining a scheduling scheme with maximum scheduling value.The value was obtained by combining high-order heterogeneity and historical information.The experimental results show that the proposed algorithm has better defense capabilities than other scheduling algorithms, and its strategy can achieve a balance of dynamics and security.

Lithium-ion batteries have rapidly become the most widely used energy storage devices in mobile electronic equipment, electric vehicles, power grid energy storage devices and other applications. Due to their outstanding stability and high conductivity, carbon materials are among the most preferred anode materials for lithium-ion batteries. In this study, mesophase pitch-based graphite fibers (GFs) were successfully prepared through melt-spinning, thermo-oxidative stabilization, carbonization and graphitization and used as anode materials. The radial fiber structure can lower the activation energy and minimize the distance of the Li+ diffusion, while the highly conductive cross-linked network within the fibers benefits the speed up charge transmission. Thus, the as-synthesized graphite fibers demonstrate superior rate capability and cycle stability. GFs exhibit a capacity retention rate of 97.94% and reversible capacity of 327.8 mA h g−1 after 100 cycles at 0.1 C, which is higher than that of natural graphite anode materials (85.66% and 289.7 mA h g−1, respectively). Moreover, the as-synthesized graphite fibers deliver a capacity retention of 64.7% at a high rate of 5 C, which is considerably higher than that of natural graphite (19.7%).

To explore the multipurpose utilization of tobacco germplasm resources, 80 representative air/sun-cured tobacco germplasms were used as experimental materials to determine the composition and content of the diterpenoids of glandular trichome secretions using ultra-performance liquid chromatography (UPLC). Correlation analysis, cluster analysis, and principal component analysis (PCA) were used to comprehensively evaluate 80 air/sun-cured tobacco germplasms. The results are as follows: (1) 11 chromatographic peaks (Peak1–Peak11) were detected by UPLC, and the coefficient of variation of their contents ranged from 26.3 to 143%. (2) Correlation analysis showed that alpha-cembratriene-diol (α-CBT-diol) and beta-cembratriene-diol (β-CBT-diol) had the highest correlation coefficients (0.97), showing a significantly negative correlation with cis-abienol and a significantly positive correlation with the other diterpenoids. (3) PCA showed that the cumulative contribution rate of the three principal components was 75.70%, and the diterpenoid-rich germplasms were ranked in the following order: X40 (Maiduo) > X48 (Jianpingpiaoba) > X58 (Mianzhu) > X54 (Shifangpipaliu) > X63 (Xuejia5) > X41 (Tangpeng) > X29 (OLOR) > X73 (Criollo) > X44 (Tiebanqing) > X70 (Nicaragua Changxin). The diterpenoid content of X36 was the lowest. These results provide excellent germplasm for the extraction and exploitation of the diterpenoids and for genetic studies of their metabolism.

In order to realize the optimization of autonomous navigation of mobile robot under the condition of partial environmental knowledge known. An improved Q-learning reinforcement learning algorithm based on prior knowledge is proposed to solve the problem of slow convergence and low learning efficiency in mobile robot path planning. Prior knowledge is used to initialize the Q-value, so as to guide the agent to move toward the target direction with a greater probability from the early stage of the algorithm, eliminating a large number of invalid iterations. The greedy factor ε is dynamically adjusted based on the number of times the agent successfully reaches the target position, so as to better balance exploration and exploitation and accelerate convergence. Simulation results show that the improved Q-learning algorithm has a faster convergence rate and higher learning efficiency than the traditional algorithm. The improved algorithm has practical significance for improving the efficiency of autonomous navigation of mobile robots.

Extensive peritoneal spread and capacity for distant metastasis account for the majority of mortality from epithelial ovarian cancer (EOC). Accumulating evidence shows that interleukin-6 (IL-6) promotes tumor invasion and migration in EOC, although the molecular mechanisms remain to be fully elucidated. Meanwhile, the hypoxic microenvironment has been recognized to cause metastasis by triggering epithelial–mesenchymal transition (EMT) in several types of cancers. Here, we studied the synergy between IL-6 and hypoxia in inducing EMT in two EOC cell lines, A2780 cells and SKOV3 cells. Exogenous recombination of IL-6 and autocrine production of IL-6 regulated by plasmids both induced EMT phenotype in EOC cells characterized by downregulated E-cadherin as well as upregulated expression of vimentin and EMT-related transcription factors. The combined effects of IL-6 and hypoxia were more significant than those of either one treatment on EMT. Suppression of hypoxia-inducible factor-1α (HIF-1α) before IL-6 treatment inhibited the EMT phenotype and invasion ability of EOC cells, indicating that HIF-1α occupies a key position in the regulatory pathway of EMT associated with IL-6. EMT score was found positively correlated with mRNA levels of IL-6, signal transducer and activator of transcription 3 (STAT3), and HIF-1α, respectively, in 489 ovarian samples from The Cancer Genome Atlas dataset. Next, blockade of the abovementioned molecules by chemical inhibitors reversed the alteration in the protein levels of EMT markers induced by either exogenous or endogenous IL-6. These findings indicate a positive feedback loop between IL-6 and HIF-1α, and induce and maintain EMT phenotype through STAT3 signaling, which might provide a novel rationale for prognostic prediction and therapeutic targets in EOC.

CO2 + O2in situ leaching has been extensively applied in uranium recovery in sandstone-type uranium deposits of China. The geochemical processes impact and constrain the leaching reaction and leaching solution migration; thus, it is necessary to study the CO2 + O2–water–rock geochemical reaction process and its influence on the physical properties of uranium-bearing reservoirs. In this work, a CO2 + O2–water–rock geochemical reaction simulation experiment was carried out, and the mineralogical and multiscale pore characteristics of typical samples before and after this simulation experiment were compared by X-ray diffraction and high-pressure mercury intrusion porosimetry (HPMIP). The results show that the CO2 + O2–water–rock geochemical reaction has complicated effects on the mineral compositions due to the various reaction modes and types. After the CO2 + O2–water–rock geochemical reaction, the femic minerals decrease and the clay minerals in the coarse sandstone, medium sandstone, fine sandstone, and siltstone increase, while the femic minerals and clay minerals in sandy mudstone show a contrary changing trend. The CO2 + O2–water–rock geochemical reaction decreases the total pore volume of uranium-bearing reservoirs and then promotes pore transformation from small scale to large scale. The fractal dimensions of macropores are decreased, and the fractal dimensions of mesopores, transition pores, and micropores are increased. The effects of felsic mineral and carbonate dissolution, secondary mineral precipitate, clay mineral swelling, and mineral particle migration are simultaneously present in the CO2 + O2in situ leaching process, which exhibit the positive transformation and the negative transformation for the uranium-bearing reservoirs. The mineral dissolution may improve reservoir permeability to a certain degree, while the siltation effect will gradually reveal with the extension of CO2 + O2in situ leaching. This research will provide a deep understanding of the physical property response of uranium-bearing reservoirs during CO2 + O2in situ leaching and indicate the direction for the efficient recovery of uranium resources.

Most of the blockchain-based identity authentication systems are based on public blockchain, which are still essentially traditional centralized identity management and verification methods, making it difficult to meet the needs of trusted access and fine-grained access control in microgrids.Therefore, based on the FISCO BCOS consortium blockchain technology, a distributed identity authentication system supporting multi-center was designed.A DID-based identity management protocol to achieve autonomous control of user identity in a practical scenarios was designed.Distributed trusted access technology for end nodes in microgrids was studied, and privacy-protecting credentials based on zero-knowledge proof were designed.This scheme meets the requirements of trustworthy and verifiable user identity in different privacy security scenarios, and achieves autonomous control of entity identity, fine-grained access control and trusted data exchange.The usability and effectiveness of the proposed algorithm are demonstrated through system experiments and performance analysis.

Abstract Oral inhalation of aerosolized drugs has be widely applied in healing the affected body organs including lesions of the throat and lungs and it is more efficient than those conventional therapies, such as intravenous drip, intramuscular injection and external topical administration in the aspects of the dosage reduction and side effects of drugs. Nevertheless, the traditional atomization devices always exhibit many drawbacks. For example, non-uniformed atomization particle distribution, the instability of transient atomization quantity and difficulties in precise energy control would seriously restrict an extensive use of atomization inhalation therapy. In this study, the principle of intra-hole fluctuation phenomenon occurred in the hole is fully explained, and the produced volume change is also estimated. Additionally, the mathematical expression of the atomization rate of the atomizing device is well established. The mechanism of the micro-pump is further clarified, and the influence of the vibration characteristics of the atomizing film on the atomization behavior is analyzed theoretically. The curves of sweep frequency against the velocity and amplitude of the piezoelectric vibrator are obtained by the Doppler laser vibrometer, and the corresponding mode shapes of the resonance point are achieved. The influence of vibration characteristics on atomization rate, atomization height and atomization particle size are also verified by experiments, respectively. Both the experimental results and theoretical calculation are expected to provide a guidance for the design of this kind of atomization device in the future.

Tobacco black shank caused by Phytophthora nicotianae is a devastating disease that causes huge losses to tobacco production across the world. Investigating the regulatory mechanism of tobacco resistance to P. nicotianae is of great importance for tobacco resistance breeding. The jasmonate (JA) signaling pathway plays a pivotal role in modulating plant pathogen resistance, but the mechanism underlying JA-mediated tobacco resistance to P. nicotianae remains largely unclear. This work explored the P. nicotianae responses of common tobacco cultivar TN90 using plants with RNAi-mediated silencing of NtCOI1 (encoding the perception protein of JA signal), and identified genes involved in this process by comparative transcriptome analyses. Interestingly, the majority of the differentially expressed bHLH transcription factor genes, whose homologs are correlated with JA-signaling, encode AtBPE-like regulators and were up-regulated in NtCOI1-RI plants, implying a negative role in regulating tobacco response to P. nicotianae. A subsequent study on NtbHLH49, a member of this group, showed that it’s negatively regulated by JA treatment or P. nicotianae infection, and its protein was localized to the nucleus. Furthermore, overexpression of NtbHLH49 decreased tobacco resistance to P. nicotianae, while knockdown of its expression increased the resistance. Manipulation of NtbHLH49 expression also altered the expression of a set of pathogen resistance genes. This study identified a set of genes correlated with JA-mediated tobacco response to P. nicotianae, and revealed the function of AtBPE-like regulator NtbHLH49 in regulating tobacco resistance to this pathogen, providing insights into the JA-mediated tobacco responses to P. nicotianae.

Introduction To deliver specific antigens in tumor immunotherapy, tumor cell lysates are commonly used to sensitize dendritic cells (DCs). However, the lysates possess low immunogenicity and contain many types of non-tumor-related antigens, which may induce autoimmune diseases. Tumor antigen peptides can provide high specificity but are expensive and their short half-lives limit their clinical application. Methods In this study, we used adenovirus to transfer the carbonic anhydrase IX (CA9) gene into DCs to generate specificity to renal cell carcinoma (RCC) which is the most common space-occupying lesion in humans. Inhibition of antigen presentation attenuators (iAPA) technology was also used to enhance the DC delivery capacity. Finally, DCs were co-cultured with cytotoxic T-lymphocytes (CTLs) and the anti-tumor effects were evaluated. Results The results showed that the CA9-DC-CTLs possessed a high specificity to CA9-positive cells and showed stronger anti-tumor activity than GFP-DC-CTLs both in vitro and in vivo. Discussion These findings may suggest a novel treatment option for RCC.

Toxoplasma gondii is an opportunistic pathogenic protozoan that can infect almost all kinds of warm-blooded animals, including humans. T. gondii can evade the host's immune response, a process known as immune evasion. Our main objective was to evaluate the role played by Sirtuin1 (SIRT1) [one of the sirtuins (SIRTs) that are a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases (HDACs)] in the T. gondii infection of RAW264.7 macrophages. In this study, we evaluated and observed alterations in the activity, expression, and localization of SIRT1 and assessed its involvement in the CD154/IFN-γ (CD40 ligand/interferon gamma) killing pathway and in autophagy during T. gondii infection. The inhibition of SIRT1 in host cells effectively reduced the number of intracellular tachyzoites, and the mechanism behind this effect might be the upregulation of IRGM1 [murine ortholog of IRGM (immunity-related GTPase family M)] and the initiation of autophagy. To the best of our knowledge, our study is the first to prove that T. gondii infection upregulates SIRT1 in RAW264.7 cells and that the inhibition of SIRT1 reduces the number of intracellular tachyzoites. Moreover, the upregulation of IRGM1 and the activation of autophagy may contribute to the intracellular inhibition of T. gondii caused by SIRT1 inhibition.

BackgroundImmunotherapy has been widely used to treat Colorectal cancer but has also observe some immune-related adverse effects. With proper treatment, most irAE can be solved and the effect of immunotherapy will not be affected by temporary immunosuppression. However, there are few reports about corneal irAE, and the current understanding of irAE is incomplete. Here we report a metastatic colorectal cancer case of immune-related keratitis caused by nivolumab and to explore the occurrence of immune-related keratitis.Case descriptionHere we report the case of a 49-year-old man with mCRC who had no previous ocular disease but developed immune-related ulcerative keratitis after treatment with nivolumab. We summarize a large amount of literature to discuss the mechanism of immune-related keratitis. In addition, we conclude a method that may be used to detect the occurrence of immune keratitis, by monitoring MMPs and maspin in patients treated with nivolumab. We believe immune-related keratitis may be a rare complication of nivolumab in the treatment of mCRC. The effect of simple anti-infective therapy and repair-promoting drugs was not obvious, but the effect of glucocorticoid combined with autologous serum was significant.ConclusionThe mechanism of immune-related keratitis is that nivolumab destroys the immune microenvironment and ACAID, and affects corneal healing. Patients who use nivolumab can prevent immune keratitis by testing MMPs and maspin. The occurrence of immune keratitis may be a good indicator of the efficacy of ICI, and further study can be done in the follow-up.

BackgroundWith approval of anti-PD-1/PD-L1, metastatic non-small cell lung cancer (NSCLC) has entered the era of immunotherapy. Since immune-related adverse events (irAEs) occur commonly in patients receiving anti-PD-1/PD-L1, the landscape of death causes may have changed in metastatic NSCLC. We aim to compare patterns of death causes in metastatic NSCLC between the pre-immunotherapy and immunotherapy era to identify the consequent landscape transition of death causes.MethodsIn this cohort study, 298,485 patients with metastatic NSCLC diagnosed between 2000 and 2018 were identified from the Surveillance, Epidemiology, and End Results Program. Unsupervised clustering with Bayesian inference method was performed for all patients’ death causes, which separated them into two death patterns: the pre-immunotherapy era group and the immunotherapy era group. Relative risk (RR) of each death cause between two groups was estimated using Poisson regression. Reduced death risk as survival time was calculated with locally weighted scatterplot smooth (Lowess) regression.ResultsTwo patterns of death causes were identified by unsupervised clustering for all patients. Thus, we separated them into two groups, the immunotherapy era (2015-2017, N=40,172) and the pre-immunotherapy era (2000-2011, N=166,321), in consideration of obscure availability to immunotherapy for patients diagnosed in 2012-2014, when the follow-up cutoff was set as three years. Although all-cause death risk had reduced (29.2%, 13.7% and 27.8% for death risks of lung cancer, non-cancer and other cancers), non-cancer deaths in the immunotherapy era (N=2,100, 5.2%; RR=1.155, 95%CI: 1.101-1.211, P

The shelf life of fresh-cut fruits and vegetables is affected by microbial growth, enzymatic browning, and loss of flavor. Although ultrasound (US) treatment is often used in the preservation of fresh-cut fruits and vegetables, it has limited antibacterial and preservative effects. Here, we used cactus polysaccharides (CP) to enhance the preservative effect of ultrasound treatment and extended the shelf life of fresh-cut potatoes. The results showed that combined treatment (CP + US) exerted better antimicrobial and anti-browning effects than individual treatments (either US or CP alone). In addition, CP + US has no adverse effect on texture and quality properties, as well as reduced the mobility of internal water. Combination treatment not only significantly decreased the activities of polyphenol oxidase and peroxidase (P

Tobacco contains a large amount of bioactive ingredients which can be used as source of feed. The objective of this study was to evaluate the effects of dietary addition of low-nicotine tobacco (LNT) on the growth performance, blood status, cecum microbiota and metabolite composition of meat rabbits. A total of 80 Kangda meat rabbits of similar weight were assigned randomly as four groups, and three of them were supplemented with 5%, 10%, and 20% LNT, respectively, with the other one fed with basal diet as control group. Each experiment group with 20 rabbits was raised in a single cage. The experiments lasted for 40 days with a predictive period of 7 days. The results revealed that LNT supplementation had no significant effect on the growth performance, but increased the half carcass weight compared with control group. Dietary supplemention of LNT decreased the triglycerides and cholesterol content in rabbit serum, and significantly increased the plasma concentration of lymphocytes (LYM), monocytes, eosinophils, hemoglobin HGB and red blood cells. In addition, LNT supplementation significantly changed the microbial diversity and richness, and metagenomic analysis showed that LNT supplementation significantly increased Eubacterium_siraeum_group, Alistipes, Monoglobus and Marvinbryantia at genus level. Moreover, LC–MS data analysis identified a total of 308 metabolites that markedly differed after LNT addition, with 190 significantly upregulated metabolites and 118 significantly downregulated metabolites. Furthermore, the correlation analysis showed that there was a significant correlation between the microbial difference and the rabbit growth performance. Overall, these findings provide theoretical basis and data support for the application of LNT in rabbits.

The rise of modern cryptographic protocols such as Zero-Knowledge proofs and secure Multi-party Computation has led to an increased demand for a new class of symmetric primitives. Unlike traditional platforms such as servers, microcontrollers, and desktop computers, these primitives are designed to be implemented in arithmetical circuits. In terms of security evaluation, arithmetization-oriented primitives are more complex compared to traditional symmetric cryptographic primitives. The arithmetization-oriented permutation Grendel employs the Legendre Symbol to increase the growth of algebraic degrees in its nonlinear layer. To analyze the security of Grendel thoroughly, it is crucial to investigate its resilience against algebraic attacks. This paper presents a preimage attack on the sponge hash function instantiated with the complete rounds of the Grendel permutation, employing algebraic methods. A technique is introduced that enables the elimination of two complete rounds of substitution permutation networks (SPN) in the sponge hash function without significant additional cost. This method can be combined with univariate root-finding techniques and Gröbner basis attacks to break the number of rounds claimed by the designers. By employing this strategy, our attack achieves a gain of two additional rounds compared to the previous state-of-the-art attack. With no compromise to its security margin, this approach deepens our understanding of the design and analysis of such cryptographic primitives.

Tick-borne pathogens have become emerging global health threats in humans and animals. The objective of the present study was to investigate Anaplasma, Ehrlichia, Babesia , and Borrelia in ticks in southern China. Ticks were collected from animals and identified to the species level. Tick-borne Anaplasma , Ehrlichia , Babesia , and Borrelia were tested by PCR assays, and analyzed by sequencing and phylogenetics. We collected 747 ticks, including Rhipicephalus microplus (n=225) and R. sanguineus (n=522), from pet dogs in Guangdong Province of southern China. Using PCR and phylogenetic analysis we showed that these ticks carried Anaplasma platys , Ehrlichia canis , Borrelia miyamotoi , Babesia vogeli , and an unclassified Ehrlichia species in Rhipicephalus ticks. Of these pathogens, B. miyamotoi was first found in southern China. A. platys , E. canis , and B. miyamotoi were zoonotic pathogens that infected both R. microplus and R. sanguineus , whereas Ba. vogeli only infected R. sanguineus , with a prevalence of 0.3%-1.5%. The results of this study showed diversity and complexity of tick-borne pathogens in Guangdong Province of southern China, implying the importance of tick-borne pathogen surveillance and control.

In plants, the timely degeneration of tapetal cells is essential for providing nutrients and other substances to support pollen development. Rapid alkalinization factors (RALFs) are small, cysteine-rich peptides known to be involved in various aspects of plant development and growth, as well as defense against biotic and abiotic stresses. However, the functions of most of them remain unknown, while no RALF has been reported to involve tapetum degeneration. In this study, we demonstrated that a novel cysteine-rich peptide, EaF82, isolated from shy-flowering ‘Golden Pothos’ (Epipremnum aureum) plants, is a RALF-like peptide and displays alkalinizing activity. Its heterologous expression in Arabidopsis delayed tapetum degeneration and reduced pollen production and seed yields. RNAseq, RT-qPCR, and biochemical analyses showed that overexpression of EaF82 downregulated a group of genes involved in pH changes, cell wall modifications, tapetum degeneration, and pollen maturation, as well as seven endogenous Arabidopsis RALF genes, and decreased proteasome activity and ATP levels. Yeast two-hybrid screening identified AKIN10, a subunit of energy-sensing SnRK1 kinase, as its interacting partner. Our study reveals a possible regulatory role for RALF peptide in tapetum degeneration and suggests that EaF82 action may be mediated through AKIN10 leading to the alteration of transcriptome and energy metabolism, thereby causing ATP deficiency and impairing pollen development.