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Abstract Background Early, rapid, and accurate pathogen diagnosis can help clinicians select targeted treatment options, thus improving prognosis and reducing mortality rates of severe pneumonia. Metagenomic next-generation sequencing (mNGS) has a higher sensitivity and broader pathogen spectrum than traditional microbiological tests. However, the effects of mNGS-based antimicrobial treatment procedures on clinical outcomes and cost-effectiveness in patients with severe pneumonia have not been evaluated. Methods This is a regional, multi-center, open, prospective, randomized controlled trial to evaluate that whether the combination of mNGS and traditional testing methods could decrease 28-day call-cause mortality with moderate cost-effectiveness. A total of 192 patients with severe pneumonia will be recruited from four large tertiary hospitals in China. Bronchoalveolar lavage fluid will be obtained in all patients and randomly assigned to the study group (mNGS combined with traditional microbiological tests) or the control group (traditional microbiological tests only) in a 1:1 ratio. Individualized antimicrobial treatment and strategy will be selected according to the analysis results. The primary outcome is 28-day all-cause mortality. The secondary outcomes are ICU and hospital length of stay (LOS), ventilator-free days and ICU-free days, consistency between mNGS and traditional microbiological tests, detective rate of mNGS and traditional microbiological tests, turn-out time, time from group allocation to start of treatment, duration of vasopressor support, types and duration of anti-infective regimens, source of drug-resistant bacteria or fungi, and ICU cost. Discussion The clinical benefits of mNGS are potentially significant, but its limitations should also be considered. Trial registration ChineseClinicalTrialRegistry.org, ChiCTR2300076853. Registered on 22 October 2023.

During cancer metastasis, cancer cells will encounter various microenvironments with diverse physical characteristics. Changes in these physical characteristics such as tension, stiffness, viscosity, compression, and fluid shear can generate biomechanical cues that affect cancer cells, dynamically influencing numerous pathophysiological mechanisms. For example, a dense extracellular matrix drives cancer cells to reorganize their cytoskeleton structures, facilitating confined migration, while this dense and restricted space also acts as a physical barrier that potentially results in nuclear rupture. Identifying these pathophysiological processes and understanding their underlying mechanobiological mechanisms can aid in the development of more effective therapeutics targeted to cancer metastasis. In this review, we outline the advances of engineering microfluidic devices in vitro and their role in replicating tumor microenvironment to mimic in vivo settings. We highlight the potential cellular mechanisms that mediate their ability to adapt to different microenvironments. Meanwhile, we also discuss some important mechanical cues that still remain challenging to replicate in current microfluidic devices in future direction. While much remains to be explored about cancer mechanobiology, we believe the developments of microfluidic devices will reveal how these physical cues impact the behaviors of cancer cells. It will be crucial in the understanding of cancer metastasis, and potentially contributing to better drug development and cancer therapy.

Lung cancer remains one of the leading causes of cancer-related mortality worldwide necessitating the development of innovative therapeutic strategies. Chimeric antigen receptor (CAR) natural killer (NK) cell therapy represents a promising advancement in the field of oncology offering a novel approach to target and eliminate tumor cells with high specificity and reduced risk of immune-related adverse effects. This paper reviews the mechanism, potential targets, and recent advances in CAR-NK cell therapy for lung cancer, including the design and engineering of CAR-NK cells, preclinical studies, and the outcomes of early-phase clinical trials. We highlight the unique advantages of using NK cells, such as their innate ability to recognize and kill cancer cells and their reduced potential for inducing graft-versus-host disease (GvHD) and cytokine release syndrome (CRS) compared to CAR T-cell therapies. Results from recent studies demonstrate significant antitumor activity in lung cancer models with improved targeting and persistence of CAR-NK cells observed in vitro and in vivo. Finally, we discuss the challenges in optimizing CAR-NK cell therapies, including the potential resistance mechanisms. The paper concludes with an outlook on the future directions of CAR-NK cell research and its implications for lung cancer treatment emphasizing the importance of continued innovation and collaboration in the field.

Background Circular RNAs can serve as regulators influencing the development of pulmonary hypertension (PH). However, their function in pulmonary vascular intimal injury remains undefined. Thus, we aimed to identify specifically expressed circular RNAs in pulmonary microvascular endothelial cells (PMECs) under hypoxia and PH. Methods and Results Deep RNA sequencing and quantitative real‐time polymerase chain reaction revealed that circALMS1 (circular RNA Alstrom syndrome protein 1) was reduced in human PMECs under hypoxia (P

Summary: Brain metastases (BM) of lung adenocarcinoma (LUAD) are the most common intracranial malignancy leading to death. However, the cellular origins and drivers of BM from LUAD have not been clarified. Cellular composition was characterized by single-cell sequencing analysis of primary lung adenocarcinoma (pLUAD), BM and lymph node metastasis (LNM) samples in GSE131907. Our study briefly analyzed the tumor microenvironment (TME), focusing on the role of epithelial cells (ECs) in BM. We have discovered a population of brain metastasis-associated epithelial cells (BMAECs) expressing SPP1, SAA1, and CDKN2A, and it has been observed that this population is mainly composed of aneuploid cells from pLUAD, playing a crucial role in brain metastasis. Our study concluded that both LNM and BM in LUAD originated from pLUAD lesions, but there is currently insufficient evidence to prove a direct association between BM lesions and LNM lesions, which provides inspiration for further investigation of the TME in BM.

Background: To investigate the expression of high mobility group box B-1 (HMGB-1) in patients with colorectal cancer (CRC) and its association with clinicopathological features and prognosis in colorectal carcinoma by combining bioinformatics and clinical data analysis, and to clarify the role of HMGB-1. To examine whether HMGB-1 expression is related to the damage of the intestinal mucosal barrier, and then explore the potential HMGB-1-dependent mechanisms affecting the progression of CRC. Methods: CRC datasets of GSE12945, GSE17536, and GSE17537 from the public gene chip database were screened and downloaded. Clinical information and CRC tissue samples from patients with stage I-III CRC from the hospital were collected. Serum samples of patients were applied by enzyme-linked immunosorbent assay on HMGB-1, and were divided into high and low HMGB-1 expression, which was examined by 16S rDNA sequencing. Immunohistochemistry was performed to examine the relationship between the expression of HMGB-1 and tight junction protein, occludin, tumor necrosis factor-α, and interferon-γ. Results: Based on the Cutoff value of 10.24 ng/mL, the CRC patients were divided into high and low expression groups. In the HMGB-1H patient group, the TNM staging, overall survival, disease-free survival, recurrence, and metastasis were inferior to the HMGB-1L group. The results of 16S rDNA sequencing demonstrated that the Providencia genus was found to be enriched in the HMGB-1L group. Immunohistochemical results showed that HMGB-1 expression was negatively correlated with the expression of ZO-1 and occludin ( R = 0.035, R = 0.003, P

Cavitation can induce drastic disruption and significantly enhance heat transfer, especially in microchannels. However, due to the scale effect, the cavitation characteristics in micro-scale can be significantly different from those in conventional scale. A modified cavitation model according to the Rayleigh-Plesset bubble kinetic equation is formulated by including the effects of surface tension, and temperature difference between the local environment and the far-field environment. The impacts of latent heat of vaporization and condensation are introduced into the energy equation. The micro-scale cavitation model proposed in the paper is verified through comparison with experimental data. The influence of surface roughness on cavitation flow in microchannel with restrictor is then investigated. The results demonstrate that bottom surface roughness in microchannels significantly increases flow resistance, suppresses cavitation flow and causes high frequency pressure fluctuations.

BackgroundTotal knee arthroplasty (TKA) is currently the main treatment for end-stage knee disease. The number of cases of TKA in China increased from 53,880 in 2011 to 374,833 in 2019, representing a 5.9-fold increase. Moderate to severe pain often occurs after TKA, which seriously affects postoperative rehabilitation, patient satisfaction, and overall outcome. Multimodal analgesia is considered the ideal solution. Adequate postoperative analgesia can not only reduce pain, opioid consumption, and, consequently, opioid-related adverse events, but can also reduce the length of hospital stay and costs and improve rehabilitation and patient satisfaction. ObjectiveEffective multimodal pain management in the early postoperative period is essential for anesthesiologists. Additional studies have demonstrated that a low-dose intravenous infusion of ketamine can be administered as an adjuvant drug to alleviate acute postoperative pain. Therefore, we aim to appraise the efficacy and safety of intraoperative intravenous injection of S(+)-ketamine to relieve acute pain after TKA in older patients. MethodsThis is a protocol for a randomized, placebo-controlled trial. A total of 144 participants aged 65 years and older undergoing TKA will be randomly allocated into the S(+)-ketamine and placebo groups in a 1:1 ratio. S(+)-ketamine or the placebo will be intravenously administered at 0.3 mg/kg/h during the operation by anesthesiologists. Blinded evaluation by trained investigators will be completed at 2 hours, 24 hours, and 48 hours after surgery. The primary outcome measure will be the numeric rating scale score at rest and movement at 24 hours after surgery. The secondary outcomes will include the numeric rating scale scores at rest and movement at 2 hours and 48 hours after surgery, the number of patients who require additional analgesics during the first 48 hours after operation, the total consumption of opioids or nonsteroid anti-inflammatory drugs during the first 48 hours after operation, and adverse events at 2, 24, and 48 hours after operation. ResultsThe protocol was registered at Clinical Trials.gov on February 26, 2022. It was performed in accordance with the approved guidelines and regulations of the participating institutions. Recruitment began in April 2022. Data collection is expected to conclude in September 2024. Study completion is expected in December 2024. ConclusionsA randomized, controlled, clinical study was designed to observe the analgesic effect of intraoperative intravenous administration of a lower dose of S(+)-ketamine (0.3 mg/kg/h) in older patients after TKA surgery. The protocol will appraise the efficacy and safety of intraoperative intravenous injection of S(+)-ketamine to relieve acute pain after TKA in older patients who may benefit from the administration of S(+)-ketamine. Trial RegistrationClinicalTrials.gov NCT05289050; https://clinicaltrials.gov/ct2/show/NCT05289050 International Registered Report Identifier (IRRID)DERR1-10.2196/53063

The evaluation of seismic vulnerability of traditional brick-wood buildings is hindered by the presence of cracks in their walls. The purpose of this study is to explore the influence of wall cracks on the vulnerability of traditional brick-wood buildings, with a specific focus on Zhang Fang's former residence in Kaifeng City as a representative case. The dynamic characteristics of the structure are analyzed by ambient vibration test. The stress analysis under static loading and the vulnerability analysis under different seismic waves are carried out for the finite element method (FEM) models with and without cracks to evaluate the failure probability of structure under damage state. The results show that the dynamic response characteristics of the FEM model with cracks are closer to the results of ambient vibration test than that of the FEM model without cracks. From the time-history analysis results, the acceleration and displacement of the structure are mainly transmitted and diffused along the longitudinal direction under seismic waves. With the increase of seismic intensity, the structural acceleration amplification factor tends to increase and then decrease, and the inter-story drift angle tends to increase. Compared the vulnerability analysis results of models with cracks to that of models without cracks, the failure probabilities of FEM model with cracks under different seismic intensity are higher. Consequently, it is crucial to consider wall cracks in numerical simulations of traditional brick-wood buildings in order to ensure more accurate results for seismic vulnerability analysis.

Abstract Background Grade 4 glioma is the most aggressive and currently incurable brain tumor with a median survival of one year in adult patients. Elucidating novel transcriptomic and epigenetic contributors to the molecular heterogeneity underlying its aggressiveness may lead to improved clinical outcomes. Methods To identify grade 4 glioma -associated 5-hydroxymethylcytosine (5hmC) and transcriptomic features as well as their cross-talks, genome-wide 5hmC and transcriptomic profiles of tissue samples from 61 patients with grade 4 gliomas and 9 normal controls were obtained for differential and co-regulation/co-modification analyses. Prognostic models on overall survival based on transcriptomic features and the 5hmC modifications summarized over genic regions (promoters, gene bodies) and brain-derived histone marks were developed using machine learning algorithms. Results Despite global reduction, the majority of differential 5hmC features showed higher modification levels in grade 4 gliomas as compared to normal controls. In addition, the bi-directional correlations between 5hmC modifications over promoter regions or gene bodies and gene expression were greatly disturbed in grade 4 gliomas regardless of IDH1 mutation status. Phenotype-associated co-regulated 5hmC–5hmC modules and 5hmC–mRNA modules not only are enriched with different molecular pathways that are indicative of the pathogenesis of grade 4 gliomas, but also are of prognostic significance comparable to IDH1 mutation status. Lastly, the best-performing 5hmC model can predict patient survival at a much higher accuracy (c-index = 74%) when compared to conventional prognostic factor IDH1 (c-index = 57%), capturing the molecular characteristics of tumors that are independent of IDH1 mutation status and gene expression-based molecular subtypes. Conclusions The 5hmC-based prognostic model could offer a robust tool to predict survival in patients with grade 4 gliomas, potentially outperforming existing prognostic factors such as IDH1 mutations. The crosstalk between 5hmC and gene expression revealed another layer of complexity underlying the molecular heterogeneity in grade 4 gliomas, offering opportunities for identifying novel therapeutic targets.

Human–wildlife conflicts are becoming increasingly common worldwide and are a challenge to biodiversity management. Compared with compensatory management, which often focuses on solving emergency conflicts, mitigation management allows decision-makers to better understand where the damage is distributed, how the species are distributed and when the species conduct their activity. Here, we integrated data collected from 90 districts/counties’ damage surveys and 1271 camera traps to understand the damage status, abundance, density and activity rhythms of wild boar (Sus scrofa) in Zhejiang, Eastern China, from January 2019 to August 2023. We found that (1) wild boar–human conflicts were mainly distributed in the northwest and southwest mountainous regions of Zhejiang Province; (2) the total abundance of wild boar was 115,156 ± 24,072 individuals, indicating a growing trend over the past decade and a higher density in the western and southern regions; (3) wild boar exhibited different activity patterns across different damage regions, and the periods around 7:00, 11:00 and 16:00 represented activity peaks for wild boar in seriously damaged regions. The damage distribution, density, distribution and activity rhythms provide specific priority regions and activity intensity peaks for conflict mitigation. We believe that these findings based on the damage, distribution and activity could provide a scientific basis for mitigation management at the county level and enrich the framework of human–wildlife conflict mitigation.

Abstract Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.

Magnetic pulse welding (MPW) is performed to join Al/Ta dissimilar metals possessing no mutual solubility. Using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS), the Al/Ta interface has been characterized in detail. The results show that the inhomogeneity of the MPW process resulting in the formation of different types of interfaces at the interface, namely, transition zone, irregular interface and flat interface. The co-existence of nanocrystalline/amorphous bi-phase interface and continuous intermetallic compound (IMC) at the same cooling rate proves that high strain is the main cause of interfacial amorphous. Nanoscale crystallization of amorphous is the result of the limited time and energy input at the interface. This finding challenges the general view on magnetic pulse welding of dissimilar metals. The results can be used in the development of new joints for the metals possessing no mutual solubility.

Induction motors are important equipment in industrial production processes. To solve the problem of characteristic harmonics overlapping when there is deterioration in different parts of the induction motor and diagnose the deterioration degree of internal components such as bearings, stator winding insulation, and air gap balance, a diagnostic method based on kernel principal component analysis (KPCA) and radial basis function neural network (RBF) is proposed. Firstly, through the experimental analysis, it is found that the 2nd, 3rd, 4th, and 5th order characteristic frequency harmonics in the current can reflect the deterioration of the motor. Secondly, KPCA is used to determine the correlation degrees between characteristic frequency harmonic contents and the deterioration of the corresponding parts of the motor. Finally, the products of characteristic frequency harmonic contents and corresponding correlation degrees are taken as the input vectors of radial basis neural network, and the deterioration degrees are taken as the output vectors to diagnose the deterioration of the motor. Through the diagnostic analysis of the experimental unit and the comparison of the actual deterioration degree of the motor after disassembly, it is proved that the proposed method can accurately diagnose the deterioration of the motor. By the proposed method, the correlation between motor deterioration and characteristic frequency harmonics has been identified, and the degree of deterioration of each part of the motor has been quantified. It can monitor the degree of motor deterioration in real-time, grasp the trend of motor deterioration, and detect early signs of motor deterioration.

Abstract Cancer cells in secondary tumors are found to form metastases more efficiently as compared to their primary tumor counterparts. This is partially due to the unfavorable microenvironments encountered by metastasizing cancer cells that result in the survival of a more metastatic phenotype from the original population. However, the role of deleterious mechanical stresses in this change of metastatic potential is unclear. Here, by forcing cancer cells to flow through small capillary‐sized constrictions, it is demonstrated that mechanical deformation can select a tumor cell subpopulation that exhibits resilience to mechanical squeezing‐induced cell death. Transcriptomic profiling reveals up‐regulated proliferation and DNA damage response pathways in this subpopulation, which are further translated into a more proliferative and chemotherapy‐resistant phenotype. These results highlight a potential link between the microenvironmental physical stresses and the enhanced malignancy of metastasizing cancer cells which may be utilized as a therapeutic strategy in preventing the metastatic spread of cancer cells.

Bone healing is associated with many orthopedic conditions, including fractures and osteonecrosis, arthritis, metabolic bone disease, tumors and periprosthetic particle-associated osteolysis. How to effectively promote bone healing has become a keen topic for researchers. The role of macrophages and bone marrow mesenchymal stem cells (BMSCs) in bone healing has gradually come to light with the development of the concept of osteoimmunity. Their interaction regulates the balance between inflammation and regeneration, and when the inflammatory response is over-excited, attenuated, or disturbed, it results in the failure of bone healing. Therefore, an in-depth understanding of the function of macrophages and bone marrow mesenchymal stem cells in bone regeneration and the relationship between the two could provide new directions to promote bone healing. This paper reviews the role of macrophages and bone marrow mesenchymal stem cells in bone healing and the mechanism and significance of their interaction. Several new therapeutic ideas for regulating the inflammatory response in bone healing by targeting macrophages and bone marrow mesenchymal stem cells crosstalk are also discussed.

Alpha decontamination of waste zircaloy cladding hull was studied using electrochemical dissolution with divalent silver. It was investigated that the electrochemical dissolution process of non-radioactive zircaloy cladding hull, it was found that the zircaloy cladding hull was insoluble in divalent silver and nitric acid solution, probably because the surface layer of the zircaloy cladding hull oxidized to zirconium oxide by the divalent silver in the divalent silver and nitric acid system, which inhibited the dissolution of the zircaloy cladding hull. The electrochemical dissolving process of waste zircaloy cladding hull was established, and the alpha decontamination test of waste zircaloy cladding hull shear section was carried out. The residual specific alpha activity of the waste zircaloy cladding hull is 2.0×105 Bq/kg after electrochemical dissolution. The source items of waste zircaloy cladding hull were analyzed. 241Am and 238Pu are the main nuclides contributing to the specific alpha activity of the waste zircaloy cladding hull.

BackgroundThe purpose of this study was to evaluate the role of differentiation-related genes (DRGs) in tumor-associated macrophages (TAMs) in non-small cell lung cancer (NSCLC).MethodsSingle cell RNA-seq (scRNA-seq) data from GEO and bulk RNA-seq data from TCGA were analyzed to identify DRGs using trajectory method. Functional gene analysis was carried out by GO/KEGG enrichment analysis. The mRNA and protein expression in human tissue were analyzed by HPA and GEPIA databases. To investigate the prognostic value of these genes, three risk score (RS) models in different pathological types of NSCLC were generated and predicted NSCLC prognosis in datasets from TCGA, UCSC and GEO databases.Results1,738 DRGs were identified through trajectory analysis. GO/KEGG analysis showed that these genes were predominantly related to myeloid leukocyte activation and leukocyte migration. 13 DRGs (C1QB, CCL4, CD14, CD84, FGL2, MS4A6A, NLRP3, PLEK, RNASE6, SAMSN1, SPN, TMEM176B, ZEB2) related to prognosis were obtained through univariate Cox analysis and Lasso regression. C1QB, CD84, FGL2, MS4A6A, NLRP3, PLEK, SAMSN1, SPN, and ZEB2 were downregulated in NSCLC compared to non-cancer tissue. The mRNA of 13 genes were significantly expressed in pulmonary macrophages with strong cell specificity. Meanwhile, immunohistochemical staining showed that C1QB, CCL4, SPN, CD14, NLRP3, SAMSN1, MS4A6A, TMEM176B were expressed in different degrees in lung cancer tissues. ZEB2 (HR=1.4, P

BackgroundAcute respiratory distress syndrome (ARDS) is the most common cause of organ failure in acute pancreatitis (AP) patients, which associated with high mortality. Specific changes in the gut microbiota have been shown to influence progression of acute pancreatitis. We aimed to determine whether early alterations in the gut microbiota is related to and could predict ARDS occurrence in AP patients.MethodsIn this study, we performed 16S rRNA sequencing analysis in 65 AP patients and 20 healthy volunteers. The AP patients were further divided into two groups: 26 AP-ARDS patients and 39 AP-nonARDS patients based on ARDS occurrence during hospitalization.ResultsOur results showed that the AP-ARDS patients exhibited specific changes in gut microbiota composition and function as compared to subjects of AP-nonARDS group. Higher abundances of Proteobacteria phylum, Enterobacteriaceae family, Escherichia-Shigella genus, and Klebsiella pneumoniae, but lower abundances of Bifidobacterium genus were found in AP-ARDS group compared with AP-nonARDS groups. Random forest modelling analysis revealed that the Escherichia-shigella genus was effective to distinguish AP-ARDS from AP-nonARDS, which could predict ARDS occurrence in AP patients.ConclusionsOur study revealed that alterations of gut microbiota in AP patients on admission were associated with ARDS occurrence after hospitalization, indicating a potential predictive and pathogenic role of gut microbiota in the development of ARDS in AP patients.

Brain tumor-initiating cells (BTICs) and tumor cell plasticity promote glioblastoma (GBM) progression. Here, we demonstrate that clemastine, an over-the-counter drug for treating hay fever and allergy symptoms, effectively attenuated the stemness and suppressed the propagation of primary BTIC cultures bearing PDGFRA amplification. These effects on BTICs were accompanied by altered gene expression profiling indicative of their more differentiated states, resonating with the activity of clemastine in promoting the differentiation of normal oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes. Functional assays for pharmacological targets of clemastine revealed that the Emopamil Binding Protein (EBP), an enzyme in the cholesterol biosynthesis pathway, is essential for BTIC propagation and a target that mediates the suppressive effects of clemastine. Finally, we showed that a neural stem cell-derived mouse glioma model displaying predominantly proneural features was similarly susceptible to clemastine treatment. Collectively, these results identify pathways essential for maintaining the stemness and progenitor features of GBMs, uncover BTIC dependency on EBP, and suggest that non-oncology, low-toxicity drugs with OPC differentiation-promoting activity can be repurposed to target GBM stemness and aid in their treatment.

Abstract An electret-based mechanical antenna (EBMA), which can transmit extremely low frequency (ELF) electromagnetic signals, has the advantages of miniaturization and high transmitting efficiency, with great potential applications in air, underwater, and underground communications. To improve the charge density of the electret, which is a key factor in determining the radiation performance of an EBMA, this work proposes a fluorinated ethylene propylene/terpolymer of tetrafluoroethylene, hexafluoropropylene and vinylidene fluoride (FEP/THV) unipolar electret exhibiting negative polarity, reaching a total charge density up to −0.46 mC/m2 for each layer of electret. Long transmission distances can be achieved in sea water, soil, and air using a 3-layer-FEP/THV-based EBMA with a compact volume of 5 × 10−4 m3. As an application demonstration, binary ASCII-coded ELF information of “BUAA” is successfully transmitted with a power consumption

Hydroxyurea(HU) is a reducing and complexing agent that can be used in the PUREX process. Zr is an important fission product in the spent fuel and main element of concern in the nuclear fuel reprocessing. The decontamination of zirconium in the route of plutonium and uranium can be lowered by the complexation of hydroxyurea in the PUREX process. The complexation of Zr(Ⅳ) with hydroxyurea in the nitric acid system was investigated in this work. Under the condition of 0.3 mol/L HNO3, the complex ratio of Zr(Ⅳ) with HU is 1∶8 obtained by Job’s method. Combining with the half-integer method, the apparent stability constants of Zr(Ⅳ) with hydroxyurea are calculated as following: lg K1≈1.59, lg K2≈1.75, lg K3≈1.88, lg K4≈1.98, lg K5≈2.09, lg K6≈2.27, lg K7≈2.51, lg K8≈3.01. Under 1.0 mol/L HNO3, the complex ratio of Zr(Ⅳ) with hydroxyurea is 1∶4, and the apparent stability constants of Zr(Ⅳ) with hydroxyurea are lg K1≈2.33, lg K2≈2.51, lg K3≈2.78, lg K4≈3.31. Under 3.0 mol/L HNO3, the complex ratio of Zr(Ⅳ) with hydroxyurea is 1∶2, and the apparent stability constants of Zr(Ⅳ) with hydroxyurea are lg K1≈2.69 and lg K2≈2.79.

In this paper, the half-reaction time of the reaction between hydrazine and its derivatives with nitrous acid is measured using spectrophotometry and stopped-flow injection device. Using Gaussian09 and HyperChem, hydrazine and its derivatives have been structurally optimized and some quantization parameters are calculated. Combining the half-reaction time and the quantization parameters, and using statistical regression analysis, QSAR model of the reaction between hydrazine and its derivatives with nitrous acid is established. The results show that total energy of molecules is the most important influencing factor in the reaction, and the half-reaction time increases with total energy of the molecule except for allyl hydrazine, the reaction rate decreases with the increase of total energy of the molecule.

The relativistic effects on nonstationary Karpman–Washimi ponderomotive magnetization are investigated in relativistic electron plasmas. The magnetization Mp and radiation power P̄ are obtained as functions of the relativistic parameter α, scaled wave frequency ω̄, and wave number k̄. It is shown that the ponderomotive force is more likely to induce a low-frequency and small-scale magnetic field. In addition, the results indicate that the magnetization and radiation power are suppressed by the relativistic effects in the ultrarelativistic case but enhanced in the moderately and weakly relativistic cases, especially in the moderately relativistic regime.

Summary: The mechanical antenna (MA) is a new type of low-frequency (LF) transmitting antenna that generates an alternating electromagnetic (EM) signal through the mechanical movement of electric charges or magnetic dipoles, which is an interdisciplinary field including not only antennas but also electromagnetics, materials science, and dynamics. This principle of signaling makes it possible to break the constraints on physical dimensions decided by the wavelength of the traditional antenna so as to achieve LF communications with a smaller size and to provide a novel solution for long-range, underwater, and underground communications, navigation over the horizon, and geological exploring. Therefore, MA has become a research hotspot in the field of LF communications in recent 5 years, and this work proposed a survey on this topic of MA applied for LF transmitting. Firstly, we briefly review traditional low-frequency transmitting antennas and summarize the defect; then we introduce research progress of different implementation schemes for MA, comparing the signaling performance, advantages, and disadvantages of each scheme. Furthermore, we discuss the experiment setup, results, and related technology for MA including signal modulation methods. Finally, we explore prospects for future research about MA. This work presents a comprehensive and critical survey of small LF transmitters based on MA to help the readers to understand and identify the background, status, and challenges of research in this field.

Abstract Neoantigens derived from mutant proteins in tumour cells could elicit potent personalized anti‐tumour immunity. Nevertheless, the layout of vaccine vehicle and synthesis of neoantigen are pivotal for stimulating robust response. The power of synthetic biology enables genetic programming bacteria to produce therapeutic agents under contol of the gene circuits. Herein, we genetically engineered bacteria to synthesize fusion neoantigens, and prepared bacteria derived vesicles (BDVs) presenting the neoantigens (BDVs‐Neo) as personalized therapeutic vaccine to drive systemic antitumour response. BDVs‐Neo and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) were inoculated subcutaneously within hydrogel (Gel), whereas sustaining release of BDVs‐Lipopolysaccharide (LPS) and GM‐CSF recruited the dendritic cells (DCs). Virtually, Gel‐BDVs‐Neo combined with the programmed cell death protein 1 (PD‐1) antibody intensively enhanced proliferation and activation of tumour‐infiltrated T cells, as well as memory T cell clone expansion. Consequently, BDVs‐Neo combining with checkpoint blockade therapy effectively prevented tumour relapse and metastasis.

Wood-cement composites have the advantages of high flexural strength, toughness, and impact resistance. However, the components such as hemicellulose and lignin in the wood chips can inhibit cement hydration, and thus the interface bonding between wood chips and cement matrix is poor. In order to address these issues, alkali cooking (mass concentration is 2–8%) and silane coupling agent (mass concentration is 1–5%) were used in this study to modify wood chips, and the resulting compressive and flexural strengths of wood-cement composites prepared from different kinds of modified wood chips were evaluated. Further, the XRD, SEM, and FT -IR tests were carried out to characterize the modified wood chips and explore the mechanism of modified wood chips incorporated composites. The results showed that the alkali cooking agent could effectively remove amorphous components, such as hemicellulose and lignin, from wood chips, improve crystallinity and relative cellulose content, and increase the surface roughness of wood chips. The silane coupling agent could chemically bond with wood chips to improve the interfacial properties between wood chips and cement matrix. The flexural strength of the composites prepared with wood chips treated with 3% silane coupling agent and 4% alkali cooking agent was increased, which was 11.9% higher than that of the composites prepared from wood chips treated only with 4% alkali cooking agent, while it was 27.1% and 31.6% higher than the composites prepared with untreated wood chips and mortar without wood chips, respectively. Alkali cooking modification and silane coupling agent treatment of wood chips can effectively improve the mechanical properties of composite materials.

Abstract Background This study aims to establish a predictive model on the basis of 18F-FDG PET/CT for diagnosing the nature of pleural effusion (PE) in patients with lung adenocarcinoma. Methods Lung adenocarcinoma patients with PE who underwent 18F-FDG PET/CT were collected and divided into training and test cohorts. PET/CT parameters and clinical information in the training cohort were collected to estimate the independent predictive factors of malignant pleural effusion (MPE) and to establish a predictive model. This model was then applied to the test cohort to evaluate the diagnostic efficacy. Results A total of 413 lung adenocarcinoma patients with PE were enrolled in this study, including 245 patients with MPE and 168 patients with benign PE (BPE). The patients were divided into training (289 patients) and test (124 patients) cohorts. CEA, SUVmax of tumor and attachment to the pleura, obstructive atelectasis or pneumonia, SUVmax of pleura, and SUVmax of PE were identified as independent significant factors of MPE and were used to construct a predictive model, which was graphically represented as a nomogram. This predictive model showed good discrimination with the area under the curve (AUC) of 0.970 (95% CI 0.954–0.986) and good calibration. Application of the nomogram in the test cohort still gave good discrimination with AUC of 0.979 (95% CI 0.961–0.998) and good calibration. Decision curve analysis demonstrated that this nomogram was clinically useful. Conclusions Our predictive model based on 18F-FDG PET/CT showed good diagnostic performance for PE, which was helpful to differentiate MPE from BPE in patients with lung adenocarcinoma.

Abstract Background Mounting evidence in the cancer literature suggests that microRNAs (miRNAs) influence the progression of human cancer cells by targeting protein-coding genes. How insulin-like growth factor 1(IGF1) and miR-186-3p contribute to the development of cervical cancer (CC) remains unclear. This study examined the regulatory roles of miR-186-3p and IGF1 in CC development. Methods Gene expression levels were determined by qRT-PCR. Proliferation, migration, and apoptosis of CC and normal cells were determined by MTT, Transwell, and caspase-3 activity assays, respectively. Dual-luciferase reporter activity and RNA pull-down assays were performed to identify the target gene of miR-186-3p. Results IGF1 was the target of miR-186-3p. The expression of miR-186-3p inhibited cell proliferation and migration abilities of CC cell lines, but induced the apoptosis rate of CC cells. IGF1 could restore the inhibitory effects of miR-186-3p on the proliferation, migration, and apoptosis abilities of CC cells. Experimental results revealed that miR-186-3p could inhibit IGF1 expression, thereby reducing the viability of CC cells. Conclusions The data suggest that targeting of IGF1 by miR-186-3p could be crucial in regulating the progression of CC.

Abstract Background The molecular pathogenesis of endometrial cancer is not completely understood. CypB upregulated in many cancers, however, its role in endometrial carcinoma has not been studied. Here, we determine the effect of CypB on the growth of endometrial cancer. Methods In this study, we examined the expression of CypB in endometrial cancer tissues using immunohistochemistry. CypB silenced in HEC-1-B cell line by shRNA. CCK-8, colony formation assays, wound healing assays, and transwell analysis were performed to assess its effect on tumor cell proliferation and metastasis. Furthermore, microarray analysis was carried out to compare the global mRNA expression profile between the HEC-1-B and CypB-silenced HEC-1-B cells. Gene ontology and KEGG pathway enrichment analysis were performed to determine the potential function of differentially expressed genes related to CypB. Results We found that CypB was upregulated in endometrial cancer, inhibit CypB expression could significantly suppress cell proliferation, metastasis, and migration. We identified 1536 differentially expressed genes related to CypB (onefold change, p

Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with a high recurrence rate and a low 5-year survival rate. Tumor-associated macrophages (TAMs) are important immune cells in the tumor microenvironment, which play an important role in the progression of many tumors. This article reviews the origin, and the role of TAMs in the invasion, metastasis, angiogenesis and immunosuppression of OSCC. Therapeutic strategies targeting TAMs are also discussed in hopes of providing new ideas for the treatment of OSCC.

Objectives: We aimed to identify whether ensemble learning can improve the performance of the epidermal growth factor receptor (EGFR) mutation status predicting model.Methods: We retrospectively collected 168 patients with non–small cell lung cancer (NSCLC), who underwent both computed tomography (CT) examination and EGFR test. Using the radiomics features extracted from the CT images, an ensemble model was established with four individual classifiers: logistic regression (LR), support vector machine (SVM), random forest (RF), and extreme gradient boosting (XGBoost). The synthetic minority oversampling technique (SMOTE) was also used to decrease the influence of data imbalance. The performances of the predicting model were evaluated using the area under the curve (AUC).Results: Based on the 26 radiomics features after feature selection, the SVM performed best (AUCs of 0.8634 and 0.7885 on the training and test sets, respectively) among four individual classifiers. The ensemble model of RF, XGBoost, and LR achieved the best performance (AUCs of 0.8465 and 0.8654 on the training and test sets, respectively).Conclusion: Ensemble learning can improve the model performance in predicting the EGFR mutation status of patients with NSCLC, showing potential value in clinical practice.

Non-canonical secretion pathways, collectively known as unconventional protein secretion (UPS), are alternative secretory mechanisms usually associated with stress-inducing conditions. UPS allows proteins that lack a signal peptide to be secreted, avoiding the conventional endoplasmic reticulum-Golgi complex secretory pathway. Molecules that generally rely on the canonical pathway to be secreted may also use the Golgi bypass, one of the unconventional routes, to reach the extracellular space. UPS studies have been increasingly growing in the literature, including its implication in the biology of several diseases. Intercellular communication between brain tumor cells and the tumor microenvironment is orchestrated by various molecules, including canonical and non-canonical secreted proteins that modulate tumor growth, proliferation, and invasion. Adult brain tumors such as gliomas, which are aggressive and fatal cancers with a dismal prognosis, could exploit UPS mechanisms to communicate with their microenvironment. Herein, we provide functional insights into the UPS machinery in the context of tumor biology, with a particular focus on the secreted proteins by alternative routes as key regulators in the maintenance of brain tumors.

Polysaccharides are important biological macromolecules in all organisms, and have recently been studied as therapeutic agents for ulcerative colitis (UC). However, the effects of Pinus yunnanensis pollen polysaccharides on ulcerative colitis remains unknown. In this study, dextran sodium sulfate (DSS) was used to induce the UC model to investigate the effects of Pinus yunnanensis pollen polysaccharides (PPM60) and sulfated polysaccharides (SPPM60) on UC. We evaluated the improvement of polysaccharides on UC by analyzing the levels of intestinal cytokines, serum metabolites and metabolic pathways, intestinal flora species diversity, and beneficial and harmful bacteria. The results show that purified PPM60 and its sulfated form SPPM60 effectively alleviated the disease progression of weight loss, colon shortening and intestinal injury in UC mice. On the intestinal immunity level, PPM60 and SPPM60 increased the levels of anti-inflammatory cytokines (IL-2, IL-10, and IL-13) and decreased the levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α). On the serum metabolism level, PPM60 and SPPM60 mainly regulated the abnormal serum metabolism of UC mice by regulating the energy-related and lipid-related metabolism pathways, respectively. On the intestinal flora level, PPM60 and SPPM60 reduced the abundance of harmful bacteria (such as Akkermansia and Aerococcus) and induced the abundance of beneficial bacteria (such as lactobacillus). In summary, this study is the first to evaluate the effects of PPM60 and SPPM60 on UC from the joint perspectives of intestinal immunity, serum metabolomics, and intestinal flora, which may provide an experimental basis for plant polysaccharides as an adjuvant clinical treatment of UC.

Abstract Despite N6-methyladenosine (m6A) is functionally important in various biological processes, its role and the underlying regulatory mechanism in the liver remain largely unexplored. In the present study, we showed that fat mass and obesity-associated protein (FTO, an m6A demethylase) was involved in mitochondrial function during hepatic ischemia–reperfusion injury (HIRI). We found that the expression of m6A demethylase FTO was decreased during HIRI. In contrast, the level of m6A methylated RNA was enhanced. Adeno-associated virus-mediated liver-specific overexpression of FTO (AAV8-TBG-FTO) ameliorated the HIRI, repressed the elevated level of m6A methylated RNA, and alleviated liver oxidative stress and mitochondrial fragmentation in vivo and in vitro. Moreover, dynamin-related protein 1 (Drp1) was a downstream target of FTO in the progression of HIRI. FTO contributed to the hepatic protective effect via demethylating the mRNA of Drp1 and impairing the Drp1-mediated mitochondrial fragmentation. Collectively, our findings demonstrated the functional importance of FTO-dependent hepatic m6A methylation during HIRI and provided valuable insights into the therapeutic mechanisms of FTO.

Background Periodontal tissue regeneration is the ultimate goal of periodontitis treatment. Exosomes are nanoscale vesicles secreted by cells that participate in and regulate the physiological activities between cells. However, the relationship between inflammatory macrophage-derived exosomes and osteoblast differentiation in periodontitis has not been thoroughly reported. Here, we attempt to explore the role of inflammatory macrophage-derived exosomes in crosstalk with osteoblasts. Methods Porphyromonas gingivalis lipopolysaccharide was used to stimulate macrophages and inflate their inflammatory cellular state. Exosomes were extracted from inflammatory macrophages using supercentrifugation, and their characteristics were detected by transmission electron microscopy, particle size analysis, and Western blotting. Exosome uptake bybone marrow mesenchymal stem cells (BMSCs) was observed by fluorescence microscopy. The effects of exosomes on the BMSC inflammatory response and on osteogenic differentiation were detected by quantitative polymerase chain reaction and Western blot analysis. Alkaline phosphatase activity was tested for verification. Results We successfully extracted and identified inflammatory macrophage-derived exosomes and observed that BMSCs successfully took up exosomes. Inflammatory macrophage-derived exosomes upregulated the expression levels of the inflammatory factors interleukin-6 and tumour necrosis factor-alpha in BMSCs and mediated inflammatory stimulation. Additionally, they inhibited the transcription levels of the osteogenic genes alkaline phosphatase, type I collagen, and Runt-related transcription factor 2 as well as the alkaline phosphatase activity, while the use of the exosome inhibitor GW4869 attenuated this effect. Conclusion Our study shows that macrophages in periodontitis can mediate inflammatory stimulation and inhibit the osteogenic differentiation of bone marrow mesenchymal stem cells through the exosome pathway. Interference with exosome secretion is likely to be a promising method for bone tissue regeneration in inflammatory states.

ObjectivesTo establish a multi-classification model for precisely predicting the invasiveness (pre-invasive adenocarcinoma, PIA; minimally invasive adenocarcinoma, MIA; invasive adenocarcinoma, IAC) of lung adenocarcinoma manifesting as pure ground-glass nodules (pGGNs).MethodsBy the inclusion and exclusion criteria, this retrospective study enrolled 346 patients (female, 297, and male, 49; age, 55.79 ± 10.53 (24-83)) presenting as pGGNs from 1292 consecutive patients with pathologically confirmed lung adenocarcinoma. A total of 27 clinical were collected and 1409 radiomics features were extracted by PyRadiomics package on python. After feature selection with L2,1-norm minimization, logistic regression (LR), extra w(ET) and gradient boosting decision tree (GBDT) were used to construct the three-classification model. Then, an ensemble model of the three algorithms based on model ensemble strategy was established to further improve the classification performance.ResultsAfter feature selection, a hybrid of 166 features consisting of 1 clinical (short-axis diameter, ranked 27th) and 165 radiomics (4 shape, 71 intensity and 90 texture) features were selected. The three most important features are wavelet-HLL_firstorder_Minimum, wavelet-HLL_ngtdm_Busyness and square_firstorder_Kurtosis. The hybrid-ensemble model based on hybrid clinical-radiomics features and the ensemble strategy showed more accurate predictive performance than other models (hybrid-LR, hybrid-ET, hybrid-GBDT, clinical-ensemble and radiomics-ensemble). On the training set and test set, the model can obtain the accuracy values of 0.918 ± 0.022 and 0.841, and its F1-scores respectively were 0.917 ± 0.024 and 0.824.ConclusionThe multi-classification of invasive pGGNs can be precisely predicted by our proposed hybrid-ensemble model to assist patients in the early diagnosis of lung adenocarcinoma and prognosis.

Context Re-yan-ning mixture (RYNM) is a new national drug approved by China's State Food and Drug Administration for the treatment of colds, simple pneumonia and acute bronchitis. Objective To determine the mechanism of action of RYNM in the treatment of bacterial pneumonia. Materials and methods Using the network pharmacology approach, the multiple components, component candidate targets and multiple therapeutic targets of RYNM were screened and functionally enriched. Also, we established a rat Streptococcus pneumonia model to verify the results of network pharmacology enrichment analysis. Forty male SPF Sprague Dawley rats were divided into four groups of 10 rats: control (normal saline), model (normal saline), levofloxacin-intervened and RYNM-intervened groups. IL-10, NOS2, COX-1, IL-6, TNF-α and NF-κB in serum and BALF were detected by ELISA. Western blot detected IL-17, IL-6, TNF-α, COX-2 and Bcl-2. Results The network pharmacology approach successfully identified 48 bioactive components in RYNM, and 65 potential targets and 138 signal pathways involved in the treatment of Streptococcus pneumonia with RYNM. The in vivo experiments indicated that model group has visible inflammation and lesions while RYNM and levofloxacin groups have not. The RYNM exhibited its therapeutic effects on Streptococcus pneumonia mainly via the regulation of cell proliferation and survival through the IL-6/IL-10/IL-17, Bax/Bcl-2, COX-1/COX-2, NF-κB and TNF-α signalling pathways. Discussion and conclusions The present study demonstrated the protective effects of RYNM on Streptococcus pneumonia, providing a potential mechanism for the treatment of bacterial pneumonia with RYNM.

The shipbuilding industry is an important basis for China’s strategy of becoming a marine power. Promoting the innovative development of the shipbuilding industry is important means for China to build a marine power. Based on the analysis of the mechanism of the innovation ecosystem of shipbuilding enterprises, this paper studies the level of the coordinated development of the coupling between the internal innovation and the external environment of shipbuilding enterprises, quantitatively measures the overall coupling coordination degree of the innovation ecosystem of shipbuilding enterprises, and analyzes the coordinated development of the innovation coupling of various shipbuilding enterprises. The innovation and development of shipbuilding enterprises not only depend on their own innovation investment, but also have an important relationship with the external environment of the enterprises, and then give relevant enlightenment from the enterprise itself and the government.

During last two decades, transition-metal catalyzed asymmetric reactions under continuous flow system have attracted a widespread attention. With its prominent advantages including higher safety and efficiency, precise control, better heat/mass transfer, easier scale-up and better sustainability, it has impressed both the academia and related industries. However, comparing with the prosperous development of transition-metal catalyzed asymmetric reactions in batch, utilization of this type of chemistry under continuous flow is still at an early stage. To inspire more potential industrial application and further studies of this chemistry in flow, this review summarized the recent advances of transition-metal catalyzed asymmetric reactions under continuous flow. Moreover, we further discussed the encountered challenges including reactor engineering, catalyst design, catalyst deactivation, pressure drop, clogging, side reactions etc., as well as their corresponding solutions and achievements in this mini-review.

Aiming at the problem that the Global Navigation Satellite System (GNSS) is confronted with great challenges in terms of continuity, integrity and usability due to the complex electromagnetic environment, an improved signal detecting algorithm of weak interference based on polarization-sensitive array was proposed. Through the joint-processing in space domain, frequency domain and polarization domain of the real-time data received from antenna elements and the descending processing of eigenvalues in each frequency bin, the weak signals in strong interference environment could be accurately separated and identified by the distribution curve of eigenvalues in the whole frequency domain. The results show that the power consumption and computational complexity were reduced greatly through the improved minimum description length (MDL) criterion based on multistage wiener filter, as the step of eigen-decomposition was omitted. Simulation results also demonstrate the efficiency and accuracy of the proposed method. The improved algorithm can be applied to different antenna arrays, keeps highly effective detecting probability even with amplitude and phase errors, and has high engineering practice value.

Abstract Background Toxic stress (TS), minority race and their interaction are evaluated as determinants of change in quality of life (QOL) over 8 years follow-up in a nationally representative sample of United States (US) adults (≥50 years old) with heart disease (HD) and/or type-2 diabetes (T2DM) diagnosed by 2006 as part of the Health and Retirement Study (HRS). Methods Recent and life-course stress plus experiences of lifetime discrimination were measured every 2 years using the stressful life experiences questionnaire. QOL was assessed by participant self-rated health (SRH) and operationally defined as improved, unchanged or declined in current year versus two years prior. Repeated measures multinomial logistic regressionusing generalized estimating equations (GEEs) was implemented to estimate race-, TS and their interaction- related odds of worse SRH from2006–2014. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with adjustment for time, age, sex and socio-economic status. Results Three thousand nine hundred four adults with HD/T2DM, mean age 71.1 ± 9.3 years old, 80.9, 14.7 and 4.4% that respectively self-identified as Caucasian, African-American and Other race, were included. Over the eight-year follow-up, the odds of worse SRH for African-American and Other race were respectively 1.46 (95% CI: 1.25–1.70) and 1.43 (95% CI, 1.10–1.86) times higher relative to Caucasians. Relative to older Americans that reported ≥2 lifetime discrimination events, the odds of poor SRH was respectively 33% (OR = 0.67, 95%CI: 0.50–0.89) and 17% (OR = 0.83, 95%CI: 0.59–1.17) lower for those that reported none vs one lifetime discrimination experience. Furthermore, the relationship of life-course stress to SRH decline over 8 years varied by race (time*stress*race, p = 0.1173). Specifically, increasing life-course stress predicted worse QOL among Caucasians (p = 0.0063) and among African-American (p = 0.0820) but not among Other race (p = 0.9943). Conclusion Toxic stress and minority race are social determinants of deterioration in QOL among older Americans with chronic diseases (HD/T2DM). The types and prevalence of toxic stressors varied by race/ethnicity. Policy interventions to address root causes of TS while targeted at proximate drivers of TS by race/ethnicity represent a viable strategy for mitigating racial disparities in overall wellbeing and improving QOL in all aging Americans regardless of race.

Abstract Background Immunotherapy targeting programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) has shown promising results in non-small cell lung cancer (NSCLC) patients. Exploring PD-L1 expression could help to select NSCLC candidates for immunotherapy. Fluorine-18 fluorodeoxyglucose (FDG) PET/CT could provide phenotypic information on malignant tumors. Thus, this study investigated PD-L1 expression correlation with metabolic parameters of FDG PET/CT and clinicopathological characteristics in NSCLC. Methods FDG PET/CT metabolic parameters including maximum standard uptake (SUVmax), metabolic tumor volume and total lesion glycolysis of primary lesion (MTV-P, TLG-P), and combination of primary lesion and metastases (MTV-C, TLG-C) were compared with PD-L1-positive expression in patients with NSCLC. Moreover, clinicopathological characteristics, including age, gender, smoking history, serum tumor markers, tumor location, size, TNM stage, and genetic mutation were also reviewed. Results All 374 patients (215 men; 159 women; age 63 ± 9 years) included 283 adenocarcinomas (ACs) and 91 squamous cell carcinomas (SCCs). PD-L1 expression was positive in 27.8% (104/374) cases. SUVmax, TLG-P, and TLG-C of PD-L1 positivity were significantly higher than PD-L1 negativity. Moreover, PD-L1 expression was obviously correlated with man, smoking, and central NSCLC. If ACs and SCCs were separately analyzed, PD-L1 positivity in ACs and SCCs was 21.6% (61/283) and 47.5% (43/91), respectively, and only SUVmax was obviously associated with PD-L1 expression. Furthermore, multivariate analysis revealed that only SUVmax was an independent predictor of PD-L1 positive expression in overall NSCLC, AC, and SCC. Using a SUVmax cut-off value of 12.5, PD-L1 status of NSCLC was predicted by FDG PET/CT with sensitivity, specificity, and accuracy of 65.4%, 86.7%, and 80.7%, respectively. Conclusions PD-L1 expression of NSCLC was related to SUVmax, TLG, man, smoking, and central location. However, only SUVmax was an independent predictor of PD-L1 positivity, which could help to explore the existence of immune checkpoints.

Fipronil and its metabolites (fipronil sulfone, fipronil sulfide and fipronil desulfinyl) adversely affect the environment and human health. Targeted metabolomics and lipidomics based on ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to analyse the alterations of glycerophospholipids and amino acids after exposure to fipronil and its metabolites at dosages of 0.5, 12.5 and 50 μM for 72 h and to evaluate their different toxic effects. Results showed that fipronil sulfone and fipronil desulfinyl are more toxic than their parent compound, with fipronil desulfinyl as the most toxic and fipronil sulfide as the least toxic. Fipronil and its metabolites affected the metabolism of PC18:1/16:0, PI18:0/20:4, arginine, leucine and tyrosine and the “phenylalanine, tyrosine and tryptophan biosynthesis” pathway, indicating their possible inducing role in cellular macromolecule damage, nerve signal transmission disturbance and energy metabolism disruption caused by oxidative stress. Importantly, fipronil sulfone and fipronil desulfinyl more strongly influenced lipid and amino acid metabolism, mainly reflected in the number of changed glycerophospholipids and differential metabolites associated with oxidative stress, including PS18:0/20:4, glutamate, phenylalanine and histidine for fipronil sulfone and PS18:0/20:4, glutamate, phenylalanine, serine and aspartic acid for fipronil desulfinyl. Therefore, the higher toxicity of fipronil desulfinyl and fipronil sulfone may be also related to oxidative stress. This study provides implications for risk assessment and toxic mechanism research on fipronil and its metabolites.