Search

As a low-density, high-strength material with high energy release potential, Al/Ep cast metal braided tubes have a wide range of application prospects in the combatant shell, which is one of the most important means to realize the integrated destructive effect of kill and blast. In this paper, Al/Ep composites with mass ratios of 3:7, 4:6 and 5:5 were prepared, and the intrinsic model of Al/Ep was established by studying its quasi-static and dynamic mechanical properties. The Al/Ep cast three-dimensional braided metal skeletons were used to obtain the required cast braided tubes with different mass ratios, and the destruction behaviors of the tubes under axial and radial compressive loads were analyzed by a combination of experimental and numerical simulations. The results show that the addition of Al particles can significantly improve the elastic-plastic properties of Al/Ep composites, and the energy storage and absorption capacities are positively correlated with the ratio of the relative contents of Al powder. When the mass ratio of Al powder to epoxy resin is 5:5, the energy absorption of Al/Ep composites is 23.16 MJ/m3, which is optimal among similar specimens and much higher than that of pure epoxy resin materials (the energy absorption of epoxy resin is 9.63 MJ/m3). The strength of binary resin matrix composites is improved, and the intrinsic models of three kinds of different mass ratios of Al/Ep composites are obtained. The intrinsic models of various Al/Ep cast braided tubes with crushing force efficiency CFE, energy absorption capacity, and specific energy absorption SEA decreased with the ratio of mass occupied by the braided filaments.

Abstract Invasive pulmonary aspergillosis (IPA) in patients with diabetes mellitus has high incidence, especially in Type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) for IPA in patients with T2DM. A total of 66 patients with T2DM were included, including 21 IPA and 45 non-IPA patients, from January 2022 to December 2022. The demographic characteristics, comorbidities, laboratory test results, antibiotic treatment response, and 30-day mortality rate of patients were analyzed. The diagnostic accuracy of mNGS and conventional methods was compared, including sensitivity, specificity, positive predictive value and negative predictive value. The sensitivity and specificity of mNGS were 66.7% and 100.0%, respectively, which were significantly higher than those of fluorescence staining (42.1% and 100%), serum 1,3-β-D-glucan detection (38.1% and 90.9%), serum galactomannan detection (14.3% and 94.9%) and BALF galactomannan detection (47.3% and 70.7%). Although the sensitivity of BALF culture (75.0%) was higher than that of mNGS (66.7%), the turnover time of mNGS was significantly shorter than that of traditional culture (1.6 days vs. 5.0 days). The sensitivity of mNGS combined with BALF culture reached 100.0%. In addition, mNGS has a stronger ability to detect co-pathogens with IPA. 47.6% of T2DM patients with IPA were adjusted the initial antimicrobial therapy according to the mNGS results. This is the first study to focus on the diagnostic performance of mNGS in IPA infection in T2DM patients. MNGS can be used as a supplement to conventional methods for the diagnosis of IPA in patients with T2DM.

Abstract Tumor immune microenvironment (TIME) consists of intra-tumor immunological components and plays a significant role in tumor initiation, progression, metastasis, and response to therapy. Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the cancer treatment paradigm. Although CAR-T cell immunotherapy has emerged as a successful treatment for hematologic malignancies, it remains a conundrum for solid tumors. The heterogeneity of TIME is responsible for poor outcomes in CAR-T cell immunotherapy against solid tumors. The advancement of highly sophisticated technology enhances our exploration in TIME from a multi-omics perspective. In the era of machine learning, multi-omics studies could reveal the characteristics of TIME and its immune resistance mechanism. Therefore, the clinical efficacy of CAR-T cell immunotherapy in solid tumors could be further improved with strategies that target unfavorable conditions in TIME. Herein, this review seeks to investigate the factors influencing TIME formation and propose strategies for improving the effectiveness of CAR-T cell immunotherapy through a multi-omics perspective, with the ultimate goal of developing personalized therapeutic approaches.

Background Hepatocellular carcinoma (HCC) is a common malignant tumor with high morbidity and mortality. Alpha-fetoprotein (AFP) is the most widely used diagnostic serum biomarker, but it still has limited accuracy in detecting HCC, suggesting the necessity of seeking more ideal biomarkers with high sensitivity and specificity. Soluble growth stimulation gene 2 (sST2) form of growth stimulating expression gene 2 (ST2), is expressed in various organs and can bind competitively to interleukin 33 (IL-33). Whether sST2 can serve as a serum biomarker for HCC is largely unknown. Objective To investigate the value of sST2 as a serum diagnostic marker for HCC. Methods This study included 93 newly diagnosed HCC patients (HCC group), 90 chronic hepatitis B patients (CHB group), and 90 healthy individuals (HCs group). Spearman correlation analysis was used to explore the relationships between sST2 and the experimental indicators in HCC group. The receiver operating characteristic (ROC) curve evaluated the efficacy of sST2 alone or in combination with AFP in the diagnosis of HCC. Result The median level of sST2 was significantly higher in HCC group (24.00 [15.20-49.90] ng/mL) compared to CHB group (19.55 [15.23-24.95] ng/mL) and HCs group (7.65 [5.20-10.53] ng/mL). No significant correlations were found between sST2 and other clinical indicators in HCC group. The Area Under Curve (AUC) of ROC curve to distinguish HCC patients from healthy controls and CHB group was 0.861 (sensitivity 82.80%, specificity 72.10%) and 0.709 (sensitivity 80.60%, specificity 52.50%), respectively. When combined with AFP, the AUC increased to 0.963 (sensitivity 82.90%, specificity 94.20%), and 0.895 (sensitivity 72.0%, specificity 100%), respectively. Conclusions The serum level of sST2 increased in HCC and its diagnostic performance is comparable to that of AFP, supporting its potential as a promising biomarker for detection of HCC. The combined use of sST2 and AFP enhances diagnostic efficacy for HCC.

Abstract Background Pyroptosis has been demonstrated being closely associated with the inflammatory progression in chronic rhinosinusitis (CRS). However, platycodon D (PLD) has emerged as a key anti-inflammatory mediator in the inflammatory progression of various respiratory diseases. This study aims at investigating whether PLD could reduce inflammatory progression of CRS by inhibiting pyroptosis. Methods Nasal mucosal tissues from patients with CRS and the control group (simple nasal septal deviation) were analyzed for morphological difference using hematoxylin & eosin staining and for the expression of pyroptosis-related makers by immunofluorescence (IF). Human nasal epithelial cells (HNEpCs) were cultured and co-stimulated with lipopolysaccharide (LPS)/adenosine triphosphate (ATP) to construct an in vitro cellular model simulating CRS. After pretreatment with PLD, EthD-I staining, TUNEL staining, transmission electron microscopy (TEM), and GSDMD-NT detection were performed to evaluate pyroptosis markers. The NLRP3 inflammasome was detected by IF and western blotting (WB). Reactive oxygen species (ROS) were detected by H2DCFDA staining, and mitochondrial membrane potential was evaluated by JC-1 staining. Mitochondrial morphology and structure were observed using TEM. The Nrf2/HO-1 antioxidant signaling pathway was detected using WB. Results The nasal mucosa structure of patients with CRS exhibited significant damage, with a marked increase in the expression of pyroptosis-related proteins compared with the control group. LPS/ATP co-stimulation resulted in an increased expression of IL-18 and IL-1β in HNEpCs, causing significant damage to nuclear and cell membranes, GSDMD-NT accumulation around the cell membrane, and intracellular NLRP3 inflammasome activation. Furthermore, it led to increased ROS expression, significantly decreased mitochondrial membrane potential, and damaged mitochondrial structure. However, pretreatment with PLD significantly reversed the aforementioned trends and activated the Nrf2/HO-1 antioxidant signaling pathway. Conclusions The results of this study confirm that NLRP3-mediated pyroptosis plays a crucial role in the pathological process of nasal mucosal impairment in patients with CRS. PLD inhibits NLRP3-mediated pyroptosis, preventing inflammatory damage in HNEpCs of patients with CRS by activating the Nrf2/HO-1 antioxidant signaling pathway, which in turn reduces ROS production and ameliorates mitochondrial damage.

In order to study the dynamic and electrical coupling response characteristics of Metal Oxide Semiconductor Controlled Thyristor (MCT) high-voltage switch under the synergic action of mechanical load and high voltage, the separated Hopkinson pressure bar (SHPB) test system was used to simulate different impact load environments, and combined with the multi-layer high-voltage ceramic capacitor charging and discharging system, the instantaneous electrical signals of MCT high-voltage switch were collected. Combined with numerical simulation and theoretical analysis, the failure mode and stress wave propagation characteristics of MCT high voltage switch were determined. The mechanical and electrical coupling response characteristics and failure mechanism of MCT high voltage switch under dynamic load were revealed from macroscopic and microscopic levels. The results show that the damage modes of MCT high-voltage switches can be divided into non-functional damage, recoverable functional damage, non-recoverable damage and structural damage. Due to the gap between the metal gate and the oxide layer, the insulating oxide layer was charged. After placing for a period of time, the elastic deformation of the metal gate partially recovered and the accumulated charge disappeared, which induced the recoverable functional damage failure of the device. In addition, obvious cracks appeared on both sides of the monocrystalline silicon inside the MCT high-voltage switch, leading to unrecoverable damage of the device.

The new STF impregnated Kevlar fabric coated GFRP (glass fiber reinforced polymer) composite structure obtained by combining STF（shear thickening fluid） impregnated Kevlar fabric and GFRP can obtain strong energy absorption capacity with light weight compared with two separate structures, so it has strong impact resistance. In this paper, the experiments of STF impregnated Kevlar fabric, GFRP laminated plate and STF impregnated Kevlar fabric coating GFRP laminated structure were carried out, respectively. Based on reliable numerical simulation, the macroscopic damage and energy absorption characteristics of the same material in STF impregnated Kevlar fabric, GFRP laminated plate and STF impregnated Kevlar fabric coating GFRP laminated structure were analyzed. The results show that the GFRP laminate and the rear Kevlar fabric in the STF-impregnated Kevlar fabric coating GFRP laminate structure show a larger damage area than that of GFRP laminate and STF impregnated Kevlar fabric alone, and a larger deflection is generated during the process of impact. The increase of the number of layers of Kevlar fabric in the front and back of the laminate and the increase of the thickness of the laminate make the Kevlar fabric absorb more energy. If the energy absorption capacity of GFRP laminates is increased, the number of layers of the front Kevlar fabric can be reduced, the thickness of the laminates can be increased, and materials with greater strength can be added to the front ply of the laminates. However, increasing the thickness of GFRP laminates will reduce the lightweight requirements of laminated structures.

BackgroundThis study represented the inaugural effort to develop predictive survival nomograms for metastatic soft tissue sarcoma (mSTS) patients in the era of immune checkpoint inhibitors.MethodFrom the Surveillance, Epidemiology, and End Results (SEER) program database, we extracted 3078 eligible patients with mSTS between 2016 and 2022. Kaplan-Meier survival analysis, univariate and multivariable Cox analyses, and univariate and multivariable logistic analyses were conducted. Subsequently, predictive nomograms were constructed. Clinical effectiveness was validated using the area under the curve (AUC), calibration curve, and decision curve analysis (DCA) methods.ResultsWe used the SEER database to include 3078 eligible patients with mSTS between 2016 and 2022. All the eligible patients were randomly allocated in a ratio of 6:4 and stratified into a training group (n = 1846) and a validation group (n = 1232). In the multivariate Cox analysis, age, race, marital status, pathological grade, histologic subtype, surgery, and chemotherapy were identified as independent prognostic factors. These factors were used to construct the nomogram to predict the 1-, 3-, and 5-year OS of mSTS patients. The C-index for the training cohort and the validation cohort was 0.722(95% confidence interval [CI]: 0.708–0.736), and 0.716(95% CI: 0.698–0.734), respectively. The calibration curves for 1-, 3-, and 5-year OS probability demonstrated excellent calibration between the predicted and the actual survival. The AUC values of the nomogram at 1-, 3-, and 5-year were 0.785, 0.767, and 0.757 in the training cohort, 0.773, 0.754, and 0.751 in the validation cohort, respectively. Furthermore, DCA indicated the favorable clinical utility of the nomogram in both cohorts. The risk stratification system was constructed using the established nomogram, which enhanced prediction accuracy, aided clinicians in identifying high-risk patients and informing treatment decisions.ConclusionThis study marked the inaugural effort in constructing predictive survival nomograms mSTS patients in the era of immune checkpoint inhibitors. The robustly constructed nomograms, alongside actual outcomes, offered valuable insights to inform follow-up management strategies.

ABSTRACTInfluenza virus is known to cause respiratory tract infections of varying severity in individuals of all ages. The EasyNAT Rapid Flu assay is a newly developed in vitro diagnostic test that employs cross-priming isothermal amplification (CPA) to detect and differentiate influenza A and B viruses in human nasopharyngeal (NP) swabs. The aim of this study is to determine the performance characteristics of the EasyNAT Rapid Flu assay for rapid detection of influenza virus. The limit of detection (LOD) and cross-reactivity of the EasyNAT Rapid Flu assay were assessed. The clinical performance of the assay was evaluated using NP swab samples that were tested with real-time reverse-transcription polymerase chain reaction (RT-PCR) and Xpert Xpress Flu/RSV assay. The LOD for the detection of influenza A and B using the EasyNAT Rapid Flu assay was found to be 500 copies/mL. Furthermore, the assay exhibited no cross-reactivity with other common respiratory viruses tested. For the 114 NP swab samples tested for influenza A using both the EasyNAT Rapid Flu assay and real-time RT-PCR, the two assays demonstrated a high level of agreement (κ = 0.963, P < 0.001), with a positive percentage agreement (PPA) of 97.7% and a negative percentage agreement (NPA) of 98.6%. Similarly, for the 43 NP swab samples tested for influenza A and B using both the EasyNAT Rapid Flu assay and Xpert Xpress Flu/RSV assay, the two assays showed a high level of agreement (κ = 0.933, P < 0.001), with the overall rate of agreement (ORA) of 97.7% for influenza A and 100% for influenza B. The EasyNAT Rapid Flu assay demonstrates excellent performance in the detection of influenza A, highlighted by its strong agreement with RT-PCR-based assays.IMPORTANCEThe newly developed EasyNAT Rapid Flu assay is an innovative cross-priming isothermal amplification-based method designed for detecting influenza A and B viruses at point-of-care settings. This study aims to thoroughly assess the analytical and clinical performance of the assay, offering valuable insights into its potential advantages and limitations. The findings of this research hold significant implications for clinical practice.

Epoxy/Al as a functional structural energetic composite material that can be used as an adhesive, energetic fragments and warhead shells due to its high energy density, low density, and high strength. It can release a large amount of chemical energy (about 21.36 kJ/g) through chemical reactions when subjected to high-speed impact and thermal stimulation. Whether used as a matrix or auxiliary component, it has enormous development potential. Therefore, it is particularly important to study the mechanical properties of Epoxy/Al energetic composite materials under different temperature environments and strain rates of loading. This article describes the preparation of Epoxy/Al specimens with a mass percentage of 70%–30% using vacuum curing after 24 h under 0.8 Bar and 50 °C. The mechanical properties of Epoxy/Al specimens under different loading conditions were characterized using a high and low temperature universal testing machine and a separate Hopkinson experimental system. The modulus prediction method of binary composite materials was improved by combining SEM (scanning electron microscopy) and microstructure, and an adaptive constitutive model was developed combined with the K Srinivas model and neural network model based on the Sherwood Frost empirical constitutive relationship. The results show that Epoxy/Al energetic composite material has a significant temperature effect. When the temperature exceeds 100 °C, Epoxy/Al energetic composite material will be a significant physical and chemical property transition (the specimen exhibits viscous fluid characteristics and gradually begins to slowly decompose). As the temperature decreases, the specimen gradually exhibits a certain degree of brittleness and strength is improved. Due to the deformation, displacement, and interfacial debonding of internal particles during the loading process, Epoxy/Al materials exhibit excellent impact energy absorption effects, with energy absorption reaching 15.30 MJ/m3 at room temperature, and unit mass cost much lower than popular CFRP (carbon fiber-reinforced polymer) materials (CFRP energy absorption cost is 0.268 J/g/£, while Epoxy/Al materials do not exceed 0.013 J/g/£). During the dynamic loading process, Epoxy/Al energetic composite materials exhibit a phenomenon of structural reconstruction and enhancement throughout the entire loading process. The maximum strength at room temperature can reach 240.70 MPa, which is superior to all existing energetic materials of the same type. By introducing interface effects and quantifying them in the Halpin Tsai model, the existing prediction method for the Young's modulus of binary particle added composite materials has been effectively improved, reducing the prediction error of the Young's modulus of Epoxy/Al energetic composite materials from 14.2% to 2.4%. The numerical simulation results indicate that the newly developed constitutive model has high accuracy and can better reflect the mechanical properties of Epoxy/Al materials. The development method of this constitutive model has a positive contribution to the development of composite materials.

Abstract The reversible oxidation-reduction homeostasis mechanism functions as a specific signal transduction system, eliciting related physiological responses. Disruptions to redox homeostasis can have negative consequences, including the potential for cancer development and progression, which are closely linked to a series of redox processes, such as adjustment of reactive oxygen species (ROS) levels and species, changes in antioxidant capacity, and differential effects of ROS on downstream cell fate and immune capacity. The tumor microenvironment (TME) exhibits a complex interplay between immunity and regulatory cell death, especially autophagy and apoptosis, which is crucially regulated by ROS. The present study aims to investigate the mechanism by which multi-source ROS affects apoptosis, autophagy, and the anti-tumor immune response in the TME and the mutual crosstalk between these three processes. Given the intricate role of ROS in controlling cell fate and immunity, we will further examine the relationship between traditional cancer therapy and ROS. It is worth noting that we will discuss some potential ROS-related treatment options for further future studies.

Circulating cfRNA in plasma has emerged as a fascinating area of research with potential applications in disease diagnosis, monitoring, and personalized medicine. Circulating RNA sequencing technology allows for the non-invasive collection of important information about the expression of target genes, eliminating the need for biopsies. This comprehensive review aims to provide a detailed overview of the current knowledge and advancements in the study of plasma cfRNA, focusing on its diverse landscape and biological functions, detection methods, its diagnostic and prognostic potential in various diseases, challenges, and future perspectives.

Background: Diabetes is common yet challenging chronic disease, that affects a wide range of people around the world. Complex cellular environments around diabetic wounds tend to damage the function of effector cells, including vascular endothelial cells (VECs), fibroblasts and epithelial cells. This study aims to analyze the differences between diabetic wounds and normal skin as well as whether adipose-derived stem cell (ADSC) exosome could promote healing of diabetic wound. Methods: Human diabetic wounds and normal skin were collected and stained with HE, Masson, CD31 and 8-hydroxy-2 deoxyguanosine immunohistochemical staining. RNA-seq data were collected for further bioinformatics analysis. ADSC exosomes were isolated and identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. The effect of ADSC exosomes on diabetic wound healing was assessed on full thickness wounds in mice. To further verify the regulative impact of ADSCs exosomes in high glucose treated fibroblasts, we isolated fibroblasts from normal skin tissue and measured the cell viability, apoptosis rate, proliferation and migration of fibroblasts. In addition, collagen formation and fibrosis-related molecules were also detected. To further disclose the mechanism of ADSC exosomes on the function of high glucose treated fibroblasts, we detected the expression of apoptosis related molecules including BCL2, Bax, and cleaved caspase-3. Results: Histological observation indicated that perilesional skin tissues from diabetic patients showed structural disorder, less collagen disposition and increased injury compared with normal skin. Bioinformatics analysis showed that the levels of inflammatory and collagen synthesis related molecules, as well as oxidative stress and apoptosis related molecules, were significantly changed. Furthermore, we found that ADSC exosomes could not only speed up diabetic wound healing, but could also improve healing quality. ADSC exosomes restored high glucose induced damage to cell viability, migration and proliferation activity, as well as fibrosis-related molecules such as SMA, collagen 1 and collagen 3. In addition, we verified that ADSC exosomes downregulated high glucose induced increased apoptosis rate in fibroblast and the protein expression of Bax as well as cleaved caspases 3. Conclusions: This study indicated that ADSC exosomes alleviated high glucose induced damage to fibroblasts and accelerate diabetic wound healing by inhibiting Bax/caspase 3.

The COVID-19 pandemic caused by SARS-CoV-2 has emerged as a major global public health concern. In November 2022, Guangzhou experienced a significant outbreak of Omicron. This study presents detailed epidemiological and laboratory data on Omicron infection in a general hospital in Guangzhou between December 1, 2022, and January 31, 2023. Out of the 55,296 individuals tested, 12,346 were found to be positive for Omicron. The highest prevalence of positive cases was observed in the 20 to 39 age group (24.6%), while the lowest was in children aged 0 to 9 years (1.42%). Females had a higher incidence of infection than males, accounting for 56.6% of cases. The peak time of Omicron infection varied across different populations. The viral load was higher in older adults and children infected with Omicron, indicating age-related differences. Spearman’s rank correlation analysis revealed positive correlations between Ct values and laboratory parameters in hospitalized patients with Omicron infection. These parameters included CRP (rs = 0.059, p = 0.009), PT (rs = 0.057, p = 0.009), INR (rs = 0.055, p = 0.013), AST (rs = 0.067, p = 0.002), LDH (rs = 0.078, p = 0.001), and BNP (rs = 0.063, p = 0.014). However, EO (Eosinophil, rs = −0.118, p

Introduction: Metagenomic next-generation sequencing (mNGS) has emerged as a powerful tool for rapid pathogen identification in clinical practice. However, the parameters used to interpret mNGS data, such as read count, genus rank, and coverage, lack explicit performance evaluation. In this study, the developed indicators as well as novel parameters were assessed for their performance in bacterium detection.Methods: We developed several relevant parameters, including 10M normalized reads, double-discard reads, Genus Rank Ratio, King Genus Rank Ratio, Genus Rank Ratio*Genus Rank, and King Genus Rank Ratio*Genus Rank. These parameters, together with frequently used read indicators including raw reads, reads per million mapped reads (RPM), transcript per kilobase per million mapped reads (TPM), Genus Rank, and coverage were analyzed for their diagnostic efficiency in bronchoalveolar lavage fluid (BALF), a common source for detecting eight bacterium pathogens: Acinetobacter baumannii, Klebsiella pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus, Hemophilus influenzae, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Aspergillus fumigatus.Results: The results demonstrated that these indicators exhibited good diagnostic efficacy for the eight pathogens. The AUC values of all indicators were almost greater than 0.9, and the corresponding sensitivity and specificity values were almost greater than 0.8, excepted coverage. The negative predictive value of all indicators was greater than 0.9. The results showed that the use of double-discarded reads, Genus Rank Ratio*Genus Rank, and King Genus Rank Ratio*Genus Rank exhibited better diagnostic efficiency than that of raw reads, RPM, TPM, and in Genus Rank. These parameters can serve as a reference for interpreting mNGS data of BALF. Moreover, precision filters integrating our novel parameters were built to detect the eight bacterium pathogens in BALF samples through machine learning.Summary: In this study, we developed a set of novel parameters for pathogen identification in clinical mNGS based on reads and ranking. These parameters were found to be more effective in diagnosing pathogens than traditional approaches. The findings provide valuable insights for improving the interpretation of mNGS reports in clinical settings, specifically in BALF analysis.

Abstract Background Mycoplasma hominis is one of the main opportunistic pathogenic mycoplasmas in humans which has a major impact on patients with bloodstream infections. Because it is difficult to detect or isolate, rapid and accurate diagnosis using improved methods is essential and still challenging for patients with bloodstream infection. Case presentation In this case, we reported the application of next -generation sequencing for the diagnosis of bloodstream infection caused by Mycoplasma hominis in a patient with Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. After 9 days of combined treatment with levofloxacin, polymyxin B and meropenem, the patient’s condition was gradually controlled and he was discharged without further complications. During the three-month outpatient follow-up, no recurrence of symptoms or clinical signs was reported. Conclusions This successful application of next generation sequencing assisted the rapid diagnosis of Mycoplasma hominis bloodstream infection, provided a new perspective in the clinical approach and highlighted the potential of this technique in rapid etiological diagnosis.

Abstract Cell-in-cell structures (CICs) refer to a type of unique structure with one or more cells within another one, whose biological outcomes are poorly understood. The present study aims to investigate the effects of CICs formation on tumor progression. Using genetically marked hepatocellular cancer cell lines, we explored the possibility that tumor cells might acquire genetic information and malignant phenotypes from parental cells undergoing CICs formation. The present study showed that the derivatives, isolated from CICs formed between two subpopulations by flow cytometry sorting, were found to inherit aggressive features from the parental cells, manifested with increased abilities in both proliferation and invasiveness. Consistently, the CICs clones expressed a lower level of E-cadherin and a higher level of Vimentin, ZEB-1, Fibronectin, MMP9, MMP2 and Snail as compared with the parental cells, indicating epithelial-mesenchymal transition. Remarkably, the new derivatives exhibited significantly enhanced tumorigenicity in the xenograft mouse models. Moreover, whole exome sequencing analysis identified a group of potential genes which were involved in CIC-mediated genetic transfer. These results are consistent with a role of genetic transfer by CICs formation in genomic instability and malignancy of tumor cells, which suggest that the formation of CICs may promote genetic transfer and gain of malignancy during tumor progression.

To study the influence of inclusions on the fracture evolution and mechanical properties of mortar structures, a series of uniaxial compression tests for mortar samples containing cylinder inclusions of varying mechanical properties were conducted. The digital image correlation (DIC) technique was employed for the analysis of deformation characteristics. In addition, failure modes for each sample were determined using self-documenting code. The result shows that inclusions filled in holes significantly influence the mechanical properties and failure characteristics of mortar structures as they can change the stress distribution and cracking process. Cracks are typically initiated at the boundaries of the inclusions but will only extend into the inclusion if it is less robust than the surrounding matrix. Sample strength increases significantly with an increase in sample strength when the inclusion’s strength does not surpass that of the surrounding material. Once the inclusion’s strength exceeds that of the surrounding matrix, the strength of the specimen remains relatively unchanged.

In recent years, the semi-glutinous japonica rice variety has been extensively utilized in Jiangsu Province to greatly increase rice quality. Nevertheless, the increasing occurrence of seed variation presented a major threat to rice quality. Enhancing the quality of rice grains has emerged as a critical factor in guaranteeing consumer acceptance. Throughout this investigation, five lines (VJ1, VJ2, VJ3, VJ4, and VJ5) selected from the Nanjing9108 population in Liyang were used as research materials, and original cultivars of Nanjing9108 (CKJ1) provided by the original breeder were utilized as control materials to compare rice quality and differential metabolites. VJ4 and VJ3 demonstrated a significant reduction in milled rice rate and head milled rice rate when contrasted to CKJ1. Compared with CKJ1, the amylose content of the five strains was significantly increased. Only VJ3 amplified the 106 bp target band, and its 2-AP content was 0 ng/g. Most metabolites are mainly enriched in cutin, suberine, wax biosynthesis, histidine, and tryptophan metabolism. The primary metabolites throughout the metabolic pathway involve lipids and lipid-like molecules (mono palmitin, alpha-eleostearic, and palmitic acid) and amino acid metabolites (L-glutamate, L-tryptophan, and L-serine). The identification of these key metabolites helps in the discovery of prospective biomarkers for screening seed variation throughout seed production.

Colored rice is richer in nutrients and contains more nutrients and bioactive substances than ordinary white rice. Moderate consumption of black (purple) rice has a variety of physiological effects, such as antioxidant effects, blood lipid regulation, and blood sugar control. Therefore, we utilized nontargeted metabolomics, quantitative assays for flavonoid and phenolic compounds, and physiological and biochemical data to explore the correlations between metabolites and the development of antioxidant characteristics in pigmented rice seeds. The findings indicated that, among Yangjinnuo 818 (YJN818), Hongnuo (HN), Yangchannuo 1 hao (YCN1H), and Yangzi 6 hao (YZ6H), YZ6H exhibited the highest PAL activity, which was 2.13, 3.08, and 3.25 times greater than those of YJN818, HN, and YCN1H, respectively. YZ6H likewise exhibited the highest flavonoid content, which was 3.8, 7.06, and 35.54 times greater than those of YJN818, HN, and YCN1H, respectively. YZ6H also had the highest total antioxidant capacity, which was 2.42, 3.76, and 3.77 times greater than those of YJN818, HN, and YCN1H, respectively. Thus, purple rice grains have stronger antioxidant properties than other colored rice grains. Receiver operating characteristic (ROC) curve analysis revealed that trans-3,3′,4′,5,5′,7-hexahydroxyflavanone, phorizin, and trilobatin in the YZ6H, HN, and YCN1H comparison groups all had area under the curve (AUC) values of 1. Phlorizin, trans-3,3′,4′,5,5′,7-hexahydroxyflavanone, and trilobatin were recognized as indices of antioxidant capability in colored rice in this research. This research adds to the understanding of antioxidant compounds in pigmented rice, which can increase the nutritional value of rice and promote the overall well-being of individuals. This type of information is of immense importance in maintaining a balanced and healthy diet.

To understand differences in the quality of different conventional japonica rice varieties and variations in metabolites related to rice quality, the quality of three conventional japonica varieties was determined, and the metabolites of the milled rice were investigated using nontargeted metabolomics technology. The results showed that the taste value (TV) of Yangda 4Hao (YD4) was significantly higher than that of Yangda 3Hao (YD3) and Huaidao 5Hao (HD5). The protein content (PC) of HD5 was significantly higher than that of YD3 and YD4. PC was significantly negatively correlated with TV. Ninety-one differential metabolites (59 increased and 32 decreased) were identified between YD3 and HD5. A total of 144 differential metabolites (96 upregulated and 48 downregulated) were identified between YD4 and HD5. A total of 114 differential metabolites (40 increased and 74 decreased) were identified between YD3 and YD4. The metabolites with a high correlation to rice quality were mostly involved in the amino acid metabolism pathway. Amino acid metabolites play an important role in the formation of rice quality. The key metabolites in the synthesis and regulation of metabolic pathways are sucrose, levan, and amylose, which are carbohydrates, and L-glutamine, L-aspartic acid, and L-asparagine, which are amino acid metabolites. It can be seen from this study that the metabolites of sucrose, levan, amylose, L-glutamine, L-aspartic acid, and L-asparagine may be the key metabolites in the quality formation of high-quality rice varieties.

Abstract Objective The aim of this study was to evaluate the effectiveness of metagenomic next-generation sequencing (mNGS) for the diagnosis of Pneumocystis jirovecii Pneumonia (PCP) in critically pediatric patients. Methods Seventeen critically pediatric patients with PCP and sixty patients diagnosed with non-PCP pneumonia who were admitted in pediatric intensive care unit between June 2018 and July 2021 were enrolled. Conventional methods and mNGS for detecting Pneumocystis jirovecii (P. jirovecii) were compared. The patients’ demographics, comorbidities, laboratory test results, antibiotic treatment response and 30 day mortality were analyzed. Result The mNGS showed a satisfying diagnostic performance with a sensitivity of 100% in detecting P. jirovecii compared with Gomori methenamine silver staining (5.9%), serum (1,3)-β-D-glucan (86.7%) and and LDH (55.6%). The diagnostic specificity of mNGS for PCP was higher than that of serum BDG (56.7%) and LDH (71.4%). In PCP group, over one thirds’ cases had mixed infections. Compared with survivors, non-survivors had higher stringently mapped read numbers (SMRNs) in bronchoalveolar lavage fluid (BALF) sample (P

Nasal osteoblastoma (OB) is a rare and locally aggressive osteogenic tumor that has rarely been reported, and there is a lack of effective evidence data for its diagnosis and treatment. In this study, we report a 31-year-old female patient who presented with nasal congestion and associated progressive painless swelling of the left maxillofacial region. A preoperative computed tomography (CT) examination of the paranasal sinuses was performed, and based on the imaging presentation, the surgeon was unable to differentiate between OB, osteoid osteoma (OO), fibrous dysplasia of bone (FDB) and osteoblastic fibroma (OF). After excluding contraindications to surgery, the patient underwent nasal endoscopic excision of the left nasal mass, which was found to be gravel-like and difficult to remove cleanly during the operation. The mass was brittle and bled easily, resulting in inadequate exposure of the operative field, prolonged operation time, and substantial intraoperative blood loss. This indicates that definite preoperative diagnosis (biopsy of deeper parts of the mass is recommended) and appropriate preoperative preparations (e.g., preoperative angiography and embolization, adequate blood preparation) are very important. The intraoperative frozen and postoperative pathological results clearly identified the tumor as OB. No local recurrence of the tumor was observed at the 11-month postoperative follow-up.

Background: Sepsis is a fatal disease with a high rate of morbidity and mortality, during which acute lung injury is the earliest and most serious complication. Injury of pulmonary microvascular endothelial cells (PMVECs) induced by excessive inflammation plays an important role in sepsis acute lung injury. This study is meant to explore the protective effect and mechanism of ADSCs exosomes on excessive inflammation PMVECs injury. Results: We successfully isolated ADSCs exosomes, the characteristic of which were confirmed. ADSCs exosomes reduced excessive inflammatory response induced ROS accumulation and cell injury in PMVECs. Besides, ADSCs exosomes inhibited excessive inflammatory response induced ferroptosis while upregulated expression of GPX4 in PMVECs. And further GPX4 inhibition experiments revealed that ADSCs exosomes alleviated inflammatory response induced ferroptosis via upregulating GPX4. Meanwhile, ADSCs exosomes could increase the expression and nucleus translocation of Nrf2, while decrease the expression of Keap1. miRNA analysis and further inhibition experiments verified that specific delivery of miR-125b-5p by ADSCs exosomes inhibited Keap1 and alleviated ferroptosis. In CLP induced sepsis model, ADSCs exosomes could relieve the lung tissue injury and reduced the death rate. Besides, ADSCs exosomes alleviated oxidative stress injury and ferroptosis of lung tissue, while remarkably increase expression of Nrf2 and GPX4. Conclusion: Collectively, we illustrated a novel potentially therapeutic mechanism that miR-125b-5p in ADSCs exosomes could alleviate the inflammation induced PMVECs ferroptosis in sepsis induced acute lung injury via regulating Keap1/Nrf2/GPX4 expression, hence improve the acute lung injury in sepsis.

Abstract Background The α-synuclein released by neurons activates microglia, which then engulfs α-synuclein for degradation via autophagy. Reactive microglia are a major pathological feature of Parkinson’s disease (PD), although the exact role of microglia in the pathogenesis of PD remains unclear. Transient receptor potential vanilloid type 1 (TRPV1) channels are nonselective cation channel protein that have been proposed as neuroprotective targets in neurodegenerative diseases. Methods Using metabolic profiling, microglia energy metabolism was measured including oxidative phosphorylation and aerobic glycolysis. The mRFP-GFP-tagged LC3 reporter was introduced to characterize the role of TRPV1 in microglial autophagy. α-synuclein preformed fibril (PFF) TRPV1 flox/flox ; Cx3cr1Cre mouse model of sporadic PD were employed to study the capacity of TRPV1 activation to attenuate neurodegeneration process. Results We found that acute exposure to PFF caused microglial activation as a result of metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis via the AKT–mTOR–HIF-1α pathway. Activated microglia eventually reached a state of chronic PFF-tolerance, accompanied by broad defects in energy metabolism. We showed that metabolic boosting by treatment with the TRPV1 agonist capsaicin rescued metabolic impairments in PFF-tolerant microglia and also defects in mitophagy caused by disruption of the AKT–mTOR–HIF-1α pathway. Capsaicin attenuated phosphorylation of α-synuclein in primary neurons by boosting phagocytosis in PFF-tolerant microglia in vitro. Finally, we found that behavioral deficits and loss of dopaminergic neurons were accelerated in the PFF TRPV1 flox/flox ; Cx3cr1Cre mouse model of sporadic PD. We identified defects in energy metabolism, mitophagy and phagocytosis of PFF in microglia from the substantia nigra pars compacta of TRPV1 flox/flox ; Cx3cr1Cre mice. Conclusion The findings suggest that modulating microglial metabolism might be a new therapeutic strategy for PD.

BackgroundColorectal cancer (CRC) is one of the most prevalent gastrointestinal cancers. Evidence for the importance of inflammation and immunology in the development and progression of CRC is growing steadily. The purpose of this study was to determine the clinical importance of Lactic Dehydrogenase (LDH) to Albumin (ALB) Ratio (LAR) and immune-inflammation biomarkers (IIBs) in patients with CRC.MethodsThis study enrolled 382 CRC patients. The LAR was determined as the serum LDH(U/l) to ALB(g/l) ratio. We compared the levels of LAR and IIBs in different TNM stages and tumor differentiation. The relationship between LAR and IIBs and overall survival (OS) of CRC was determined by Cox regression models. A prognostic nomogram was created using the results of the multivariate analysis and the effectiveness of the nomogram was assessed using the ROC, calibration, and decision curves. We evaluated the relationship between LAR and IIBs and clinical features of CRC.ResultsThe levels of LAR, SII, NLR and PLR in TNM IV stage group (LAR:5.92 (5.23–8.24); SII: 1040.02 (499.51–1683.54); NLR: 2.87 (2.07–5.3); PLR:187.08 (125.31–276.63)) were significantly higher than those in other groups. LAR and NLR showed no significant difference in different tumor differentiation groups, while SII and PLR in undifferentiated groups (SII:543.72 (372.63–1110.20); PLR: 147.06 (106.04–203.92)) were significantly higher than those in well and moderate groups (SII: 474.29 (323.75–716.01); PLR: 126.28 (104.31–167.88)). LAR (HR = 1.317, 95% CI = 1.019–1.454), TNM stage (HR = 2.895, 95% CI = 1.838–4.559), age (HR = 1.766, 95% CI = 1.069–2.922) and lymphocytes (HR = 0.663, 95% CI = 0.456–0.963) were predictors of OS. IIBs, including SII, NLR, and PLR are independent of OS. The LAR-based nomogram AUCs of 1-year, 3-year and 5-year survival probabilities in the training cohort were 0.86, 0.72, and 0.71, respectively, and the AUCs of the validation cohort were 0.85, 0.71, and 0.69 respectively. The LAR-based nomogram's ROC curves and calibration curves demonstrated higher OS discriminative performance. The decision curves demonstrated greater net benefit in the survival prediction.ConclusionPreoperative LAR is a potential prognostic marker in CRC patients, while SII, NLR, and PLR are independent of OS. LAR was associated with tumor stage in CRC patients, but not with tumor differentiation.

IntroductionGadoxetic acid–enhanced magnetic resonance imaging (MRI) contributes to evaluating the prognosis of small hepatocellular carcinoma (sHCC) following treatment. We have investigated the potential role of gadoxetic acid–enhanced MRI based on LI-RADS (Liver Imaging Reporting and Data System) v2018 imaging features in the prognosis prediction of patients with sHCC treated with radiofrequency ablation (RFA) as the first-line treatment and formulated a predictive nomogram.MethodsA total of 204 patients with sHCC who all received RFA as the first-line therapy were enrolled. All patients had undergone gadoxetic acid–enhanced MRI examinations before RFA. Uni- and multivariable analyses for RFS were assessing using a Cox proportional hazards model. A novel nomogram was further constructed for predicting RFS. The clinical capacity of the model was validated according to calibration curves, the concordance index (C-index), and decision curve analyses.ResultsAlpha fetoprotein (AFP) > 100 ng/ml (HR, 2.006; 95% CI, 1.111–3.621; P = 0.021), rim arterial phase hyperenhancement (APHE) (HR, 2.751; 95% CI, 1.511–5.011; P = 0.001), and targetoid restriction on diffusion-weighted imaging (DWI) (HR, 3.289; 95% CI, 1.832–5.906; P < 0.001) were considered as the independent risk features for recurrence in patients with sHCC treated with RFA. The calibration curves and C-indexes (C-index values of 0.758 and 0.807) showed the superior predictive performance of the integrated nomogram in both the training and validation groups.DiscussionThe gadoxetic acid–enhanced MRI features based on LI-RADS v2018, including rim APHE, targetoid restriction on DWI, and the AFP level, are the independent risk factors of recurrence in patients with sHCC treated with RFA as the first-line therapy. The predictive clinical-radiological nomogram model was constructed for clinicians to develop individualized treatment and surveillance strategies.

Abstract Alzheimer’s disease (AD) is marked by neurofibrillary tangles and senile plaques composed of amyloid β (Aβ) peptides. However, specific contributions of different cell types to Aβ deposition remain unknown. Non-coding microRNAs (miRNA) play important roles in AD by regulating translation of major associated proteins, such as Aβ precursor protein (APP) and β-site APP-cleaving enzyme (BACE1), two key proteins associated with Aβ biogenesis. MiRNAs typically silence protein expression via binding specific sites in mRNAs’ 3′-untranslated regions (3′-UTR). MiRNAs regulate protein levels in a cell-type specific manner; however, mechanisms of the variation of miRNA activity remain unknown. We report that miR-298 treatment reduced native APP and BACE1 protein levels in an astrocytic but not in a neuron-like cell line. From miR-298’s effects on APP-3′-UTR activity and native protein levels, we infer that differences in APP 3′-UTR length could explain differential miR-298 activity. Such varied or truncated, but natural, 3′-UTR specific to a given cell type provides an opportunity to regulate native protein levels by particular miRNA. Thus, miRNA’s effect tailoring to a specific cell type, bypassing another undesired cell type with a truncated 3′-UTR would potentially advance clinically-relevant translational research.

Cooking can lead to varying degrees of nutrient loss in purple rice. For this investigation, two varieties of purple rice (YZN1 and YZ6) were chosen as the focal points to explore the metabolites associated with rice nutrition post cooking using nontargeted and targeted metabolomics techniques. The results showed that after cooking the two purple rice varieties, the contents of the flavonoids; OPC; TP; total antioxidant capacity; and K, Na, Fe, Mn, Zn, Cu, Ca, and Mg significantly decreased. Compared with YZN1U (YZN1 uncooked), the amino acid and mineral element contents in YZN1C (YZN1 cooked) decreased to varying degrees. After cooking YZ6, the contents of seven amino acids significantly decreased. Following the preparation of purple rice, the metabolites primarily engaged in the pathways of flavonoid synthesis and flavone and flavonol synthesis. Flavonoids, total antioxidant capacity, mineral elements, and amino acids showed a strong correlation with delphinidin and luteolin. The ROC analysis demonstrated that the value of the area under the curve for delphinidin and luteolin was 1 when comparing YZ6C (YZ6 cooked) and YZ6U (YZ6 uncooked), as well as YZN1C and YZN1U. Delphinidin and luteolin can be used as potential biomarkers of nutrient loss after cooking purple rice. This study holds significant implications for the balanced nutrition and healthy development of human dietary grains.

Abstract Background Golgi phosphoprotein 3 (GOLPH3) has been frequently reported as an oncoprotein in a variety of tumors. However, its role in the cancer-associated intercellular signaling communication has not yet been explored. This study aimed at exploring whether GOLPH3 regulates angiogenesis and sorafenib resistance via exosomal mechanisms in hepatocellular carcinoma (HCC). Methods In vivo assays were performed to elucidate the function of GOLPH3 in HCC. Exosomes of HCC cells were isolated by differential centrifugation, and then measured and quantified using nanoparticle tracking analysis (NTA), BCA assay, western blot (WB), and transmission electron microscopy (TEM). Differentially expressed miRNAs in exosome were analyzed and verified through small RNA sequencing (sRNA-seq) and reverse-transcription polymerase chain reaction (RT-PCR). In addition, a series of in vitro assays were performed to determine the function of exosomes and miR-494-3p in HCC. The candidate target gene of miR-494-3p was identified by bioinformatics prediction and dual-luciferase reporter assay. Results Downregulation of GOLPH3 expression could suppress angiogenesis and enhance sorafenib sensitivity in HCC. Exosomes derived from GOLPH3 overexpression HCC cells promoted the angiogenesis ability of HUVECs and induced sorafenib resistance in HCC cells. A total of 13 differentially expressed miRNAs between negative control and GOLPH3 knockdown group were found in exosomes. However, GOLPH3 was only associated with miR-494-3p expression level in exosomes derived from HCC cells without affecting total cellular miR-494-3p content. Results confirmed that exosomal miR-494-3p promotes angiogenesis of HUVECs and sorafenib resistance in HCC cells through directly targeting PTEN. Conclusions HCC cells with high expression levels of GOLPH3 could promote angiogenesis and sorafenib resistance by enhancing exosomal miR-494-3p secretion to recipient HUVECs and HCC cells, respectively.