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In this paper, the modular design is adopted to study the control strategy of photovoltaic system, energy storage system and flexible DC system, so as to achieve the design and control strategy research of the whole system of “photovoltaic + energy storage + DC + flexible DC”. This realizes the flexibility and diversity of networking. Due to space reasons, this article focuses on the detailed explanation of the photovoltaic energy storage system control strategy, including the maximum power tracking control strategy of photovoltaic power generation, photovoltaic power generation boost chopper circuit control strategy, photovoltaic power generation DC/AC converter control strategy, PCS device control strategy, PCS virtual impedance control algorithm, etc. Simulation experiments are carried out according to the specific case setting parameters. The simulation results prove that the proposed flexible DC system coordinated control strategy can ensure grid frequency stability and grid voltage stability, and improve the consumption capacity of distributed new energy.

Background and objective Rapid on-site evaluation (ROSE) is a technique used for simultaneous evaluation of biopsy specimens through rapid cytology staining. Diff-Quik (DQ) staining is the most commonly employed method for cytological rapid on-site evaluation (C-ROSE). However, the utilization of DQ staining for on-site cytological interpretation remains uncommon among pathologists in China, posing challenges to the implementation of C-ROSE. This study aims to assess the application of rapid hematoxylin-eosin (HE) staining and DQ staining for C-ROSE during percutaneous needle biopsy of peripheral lung cancer and evaluate the value of rapid HE staining in C-ROSE. Methods Computed tomography (CT)-guided lung biopsies were conducted on 300 patients diagnosed with peripheral lung cancer. The patients were randomly assigned to two groups for C-ROSE using either rapid HE staining or DQ staining, and subsequently the two methods were compared and evaluated. Results The concordance rate between C-ROSE and histopathological diagnosis was 96.7%. The median staining time for rapid HE staining was 160 s, while that for DQ staining was 120 s, representing a significant difference between the two groups (P0.05). Conclusion Both staining methods comply with C-ROSE criteria in the biopsy setting of peripheral lung cancer. Rapid HE staining is more aligned with domestic clinical requirements and holds potential for further promotion and adoption in C-ROSE.

Abstract Background Variated anti-cancer therapies are combined with immune checkpoint blockades (ICBs) for improving ICB therapeutic efficacy. Occurrence of tissue damage is common that triggers multiple inflammatory cytokine generation. Gastrointestinal organs are the commonly affected. We investigated the impact of acute colitis on tumor infiltration of antigen-specific CD8+ cytotoxic T lymphocytes (CTLs) for controlling tumor growth and responding to antibody against PD-1 (anti-PD-1). Methods Several tumor cell lines were inoculated into syngeneic mice subcutaneously or intra-hepatically. When tumor mass formed, activated CTLs were intravenously transferred into the tumor-bearing mice, that were given the drinking water containing 2% dextran sulfate sodium (DSS) for acute colitis induction. Tumor growth, infiltration of two exhausted CTL subsets, and the CTL interaction with tumor vascular endothelium were examined. Results Acute colitis dampened CTL-mediated antitumor effects, correlating with IL-17A elevation in the inflamed intestine. In the tumor bed, stem-like exhausted CTLs, which were defined as PD-1+Slamf6+Tim3−, expressed higher IL-17A receptor heterodimers and lower leukocyte function-associated antigen-1 (LFA-1) than terminally exhausted CTLs did, that were defined as PD-1+Slamf6−Tim3+. IL-17A stimulation reduced LFA-1 surface expression on stem-like exhausted CTLs and the counterpart ICAM-1 (intracellular adhesion molecule-1) on tumor vascular endothelium. IL-17A stimulation suppressed the extravasation across tumor vascular endothelium and self-renewal of stem-like, not the terminally exhausted CTLs. Administration of anti-IL-17A neutralizing antibody to the colitis mice restored the CTL tumor infiltration and enhanced anti-PD-1 treatment efficacy against tumors. In 33 hepatocellular carcinoma patients being treated with anti-PD-1 plus antibody against vascular endothelial growth factor, disease progression of 15 patients, that exhibited serum IL-17A increase 24 h post-therapy as compared to pre-therapy level, was poorer than that of 18 patients that exhibited serum IL-17A no-increase. Conclusions Abnormal generation of IL-17A mainly repressed tumor infiltration of stem-like exhausted CTLs. ICB-based immunotherapeutic efficacy could be upgraded with administration of anti-IL-17A, when treatment-related IL-17A elevation occurred due to tissue damage, such as acute colitis.

Abstract Background Tuberculosis (TB) is a chronic respiratory infection. Co-infection with human immunodeficiency virus (HIV) has been a significant obstacle to TB control. Insufficient attention has been given to TB/HIV, and more information is needed to address this issue. We conducted an observational study to investigate the epidemiological characteristics, treatment outcomes and its associated factors of HIV-positive TB patients in Southeast China. Methods An observational study was conducted based on data collected directly from China National TB Surveillance System during 2012–2021. Epidemiological characteristics, drug resistance and outcomes were described as frequency (n) and percentage (%). Risk factors for unsuccessful outcomes were determined using univariate (chi-squared) and multivariate logistic regression analysis. Results A total of 347 TB/HIV cases were included, and the proportion of HIV-positive cases among all TB cases increased significantly from 0.06% to 2012 to 0.40% in 2021. The majority of cases were males (86.5%), non-local household registers (139, 40.1%), farmers or workers (179, 51.6%), and aged 40–59 (142, 40.9%). Of 347 cases, 290 (83.6%) had pulmonary TB (PTB), 10 (2.9%) had extra pulmonary TB (EPTB) and 47(13.5%) had both PTB and EPTB. A total A total of 258 (74.4%) were HIV positive prior to TB diagnosis. 8.0% (4/50) of cases were resistant to rifampicin (RIF) and 274 patients (83.8%) had successful outcomes. Being non-local (AOR = 2.193, 95% CI = 1.196–4.022, P = 0.011) and diagnosed HIV infection after TB (AOR = 2.365, 95% CI = 1.263–4.430, P = 0.007) were independent risk factors for unsuccessful outcomes of anti-TB treatment. Conclusion During 2012–2021, the proportion of HIV-positive cases among all TB cases increased significantly in Southeast China. HIV-positive TB patients were significantly more likely to develop resistance to RIF and INH and unsuccessful anti-TB treatment. Non-local registration and becoming HIV positive after TB diagnosis were independent risk factors associated with unsuccessful outcomes.

With the continuous development of hydrogen storage systems, power-to-gas (P2G) and combined heat and power (CHP), the coupling between electricity–heat–hydrogen–gas has been promoted and energy conversion equipment has been transformed from an independent operation with low energy utilization efficiency to a joint operation with high efficiency. This study proposes a low-carbon optimization strategy for a multi-energy coupled IES containing hydrogen energy storage operating jointly with a two-stage P2G adjustable thermoelectric ratio CHP. Firstly, the hydrogen energy storage system is analyzed to enhance the wind power consumption ability of the system by dynamically absorbing and releasing energy at the right time through electricity–hydrogen coupling. Then, the two-stage P2G operation process is refined and combined with the CHP operation with an adjustable thermoelectric ratio to further improve the low-carbon and economic performance of the system. Finally, multiple scenarios are set up, and the comparative analysis shows that the addition of a hydrogen storage system can increase the wind power consumption capacity of the system by 4.6%; considering the adjustable thermoelectric ratio CHP and the two-stage P2G, the system emissions reduction can be 5.97% and 23.07%, respectively, and the total cost of operation can be reduced by 7.5% and 14.5%, respectively.

To further optimize the low-carbon economy of the integrated energy system (IES), this paper establishes a two-stage P2G hydrogen-coupled electricity–heat–hydrogen–gas IES with carbon capture (CCS). First, this paper refines the two stages of P2G and introduces a hydrogen fuel cell (HFC) with a hydrogen storage device to fully utilize the hydrogen energy in the first stage of power-to-gas (P2G). Then, the ladder carbon trading mechanism is considered and CCS is introduced to further reduce the system’s carbon emissions while coupling with P2G. Finally, the adjustable thermoelectric ratio characteristics of the combined heat and power unit (CHP) and HFC are considered to improve the energy utilization efficiency of the system and to reduce the system operating costs. This paper set up arithmetic examples to analyze from several perspectives, and the results show that the introduction of CCS can reduce carbon emissions by 41.83%. In the CCS-containing case, refining the P2G two-stage and coupling it with HFC and hydrogen storage can lead to a 30% reduction in carbon emissions and a 61% reduction in wind abandonment costs; consideration of CHP and HFC adjustable thermoelectric ratios can result in a 16% reduction in purchased energy costs.

External corrosion poses a significant threat to the integrity and lifespan of buried pipelines. Accurate prediction of corrosion rates is important for the safe and efficient transportation of oil and natural gas. However, limited data availability often impacts the performance of conventional predictive models. This study proposes a novel composite modeling approach integrating kernel principal component analysis (KPCA), particle swarm optimization (PSO), and extreme learning machine (ELM). The key innovation lies in using KPCA for reducing the dimensionality of complex input data combined with PSO for optimizing the parameters of the ELM network. The model was rigorously trained on 12 different datasets and comprehensively evaluated using metrics such as the coefficient of determination (R2), standard deviation (SD), mean relative error (MRE), and root mean square error (RMSE). The results show that KPCA effectively extracted four primary components, accounting for 91.33% of the data variability. The KPCA-PSO-ELM composite model outperformed independent models with a higher accuracy, achieving an R2 of 99.59% and an RMSE of only 0.0029%. The model comprehensively considered various indicators under the conditions of limited data. The model significantly improved the prediction accuracy and provides a guarantee for the safety of oil and gas transport.

This study proposes a method for personalized daily hand exercise training to address the lack of personalization in rehabilitation training and its disconnect from daily life. This research aims to evaluate the impact of Happiness Memory Therapy on patients’ hand function through gamified daily life training. The methodology integrates Happiness Memory Therapy and Positive Mirror Theory to assist in life game design. Patient interviews and empathy are used to gather life experiences, interests, hobbies, and challenges, which are then incorporated into personalized rehabilitation training. The experimental process includes pre- and post-intervention tests to assess changes in subjective well-being (SWLS), happiness (SHS), positive and negative emotions (PANAS), psychological well-being (PWB), and hand function impairment (DASH). The results show that the intervention significantly enhances patients’ subjective well-being, happiness, positive emotions, and reduces negative emotions and hand function impairments. In conclusion, Happiness Memory Therapy and Positive Mirror Theory are effective in developing personalized daily hand exercise training methods and have a significant impact on improving the psychological health and quality of life of stroke patients, offering new ideas and methods for personalized rehabilitation training.

3-nitro-1,2,4-triazol-5-one (NTO) has been widely used as a kind of insensitive single-compound explosive owing to its excellent balance between safety and explosive energy. To reduce its possible acid corrosion and extend its application to insensitive ammunition, acid protection research on NTO-based explosives is significant. Traditionally, the acid protection effect was evaluated by metal corrosion, which is time-consuming and qualitative. An efficient and quantitative method is desirable for evaluating the acid protection effect and exploring novel protection materials. Herein, a polyimide of 4,4’-(hexafluoroisopropene)diphthalic anhydride (6FDA)/2,2-bis(trifluoromethyl)-4,4-diaminobiphenyl (TFMB) was synthesized by replacing the 4,4’-diaminodiphenyl ether (ODA) monomer with a TFMB monomer to act as an acid-protective coating material for NTO-based explosives. Compared with three other coating materials, polyvinylidene fluoride (PVDF), polyetherimide (PEI), and copolyimide (P84), the fluorinated polyimide exhibits the best acid protection effect. Moreover, a new method was constructed to obtain the pH time-dependent curve in order to evaluate efficiently the acid protection effect of the polymer materials. By the virtue of molecular dynamic simulation (Materials Studio 2023), the interfacial effects of the coating materials with NTO-based explosives were obtained. The study provides an interpretation of the acid protection effect on the molecular level, suggesting that the higher content of fluorine atoms is beneficial for stabilizing the active hydrogen atom of the NTO by forming intermolecular hydrogen bonds.

The aim of this study was to explore how the total flavonoids from Eucommia ulmoides leaves (EULs) regulate ischemia-induced nerve damage, as well as the protective effects mediated by oxidative stress. The cell survival rate was significantly improved compared to the ischemic group (p < 0.05) after treatment with the total flavonoids of EULs. The levels of reactive oxygen species (ROS), lactate dehydrogenase (LDH), and malondialdehyde (MDA) decreased, while catalase (CAT) and glutathione (GSH) increased, indicating that the total flavonoids of EULs can significantly alleviate neurological damage caused by ischemic stroke by inhibiting oxidative stress (p < 0.01). The mRNA expression level of VEGF increased (p < 0.01), which was consistent with the protein expression results. Meanwhile, the protein expression of ERK and CCND1 increased (p < 0.01), suggesting that the total flavonoids of EULs could protect PC12 cells from ischemic injury via VEGF-related pathways. MCAO rat models indicated that the total flavonoids of EULs could reduce brain ischemia–reperfusion injury. In conclusion, this study demonstrates the potential mechanisms of the total flavonoids of EULs in treating ischemic stroke and their potential therapeutic effects in reducing ischemic injury, which provides useful information for ischemic stroke drug discovery.

The high standard of communication quality in optical access networks makes forward error correction (FEC) schemes, such as LDPC, an integral part of the system. However, pipeline conflict arising from data dependencies is a common issue encountered in the hardware implementation of layered QC-LDPC decoders. This paper proposes an efficient layered decoding architecture to reduce pipeline conflicts without introducing stall cycles. It can solve some of the pipeline conflicts by flexibly reordering the processing order of inter-layer and intra-layer submatrices offline. In addition, the patch method, based on variable-to-check messages, allows for the delayed use of gains between layer iterations, which can further minimize the performance loss caused by the remaining pipeline conflicts. The experimental results on the LDPC code of the IEEE802.16 standard in the OFDM-PON system demonstrate that the proposed architecture has sensitivity improvements of 0.125 dBm and 0.375 dBm, respectively, compared with our previous work and the method described in the other work. The optimized architecture improves the reliability of the decoder and can also make a contribution to efficient PON systems.

With the rapid development of voltage source converter (VSC) and line commutated converter (LCC) technology and the relative concentration of power and load, the inverter station of the flexible DC system is fed into the same AC bus with the conventional DC rectifier station, and the high-voltage direct current (HVDC) parallel hybrid feed system is formed in structure. As the electrical distance between the converter stations is very close, when a fault occurs in the near area, the current on the AC wiring on the VSC side will fluctuate greatly, resulting in the misoperation of the AC wiring protection. For this reason, this paper proposes a fault identification method based on VSC/LCC hybrid multi-fed HVDC system, which discriminates the fault and outputs the protection signal according to the protection criterion, and logically judges the combination of the output protection signal to identify the fault type. The simulation results show that the method can identify all kinds of faults of hybrid multi-feed DC system and solve the problem of protection misoperation of the hybrid multi-feed DC system.

IntroductionThis research investigates the complex interplay of factors influencing teacher emotional exhaustion within the educational environment. It draws upon a diverse sample of 680 teachers from 15 primary educational institutions in various districts of Shanghai, China.MethodsThe study examines the interrelationships among teacher-student relationships, perceived autonomy, teaching motivation, and emotional exhaustion. It employs validated scales to measure these constructs and utilizes Structural Equation Modeling (SEM) for analysis.ResultsThe analyses using SEM reveal significant associations among the variables under study. The findings indicate robust correlations between positive teacher-student relationships, perceived autonomy, and higher teaching motivation. Concurrently, these factors exhibit a negative relationship with emotional exhaustion.DiscussionMediation analysis further unveils that teaching motivation plays a significant mediating role in the associations between teacher-student relationships, perceived autonomy, and emotional exhaustion. This emphasizes the intricate indirect effects of these constructs.ConclusionThe study underscores the multifaceted nature of these factors and their collective impact on teacher well-being within educational settings. The implications derived highlight the importance for educational institutions to prioritize interventions fostering positive teacher-student relationships, autonomy-supportive environments, and intrinsic motivation among educators. These interventions aim to alleviate emotional exhaustion and enhance teacher well-being.

BackgroundThe diagnosis of lung adenocarcinoma (LUAD) leptomeningeal metastasis (LM) remains a clinical challenge. Human epididymis protein 4 (HE4) functions as a novel tumor biomarker for cancers. This study aimed to assess the diagnostic value of cerebrospinal fluid (CSF) HE4, and combined with CEACAM6, for LUAD LM.MethodsThe CSF HE4 protein level was measured in two independent cohorts by electrochemiluminescence. Test cohort included 58 LUAD LM patients, 22 LUAD patients without LM (Wiot-LM), and 68 normal controls. Validation cohort enrolled 50 LUAD LM patients and 40 normal controls, in parallel with Wiot-LM patients without brain metastases (19 Wiot-LM/BrM patients) or with BrM (26 BrM patients). The CSF level of CEA, CA125, CA153, CA199, CA724, NSE and ProGRP of these samples was measured by electrochemiluminescence, whereas the CSF CEACAM6 level was detected by enzyme-linked immunosorbent assay (ELISA). In addition, the serum level of these biomarkers was detected by same method as CSF.ResultsThe level of HE4 or CEACAM6 in CSF samples from LUAD LM patients was significantly higher than those from normal controls and Wiot-LM patients. The HE4 or CEACAM6 level in CSF was higher than that in serum of LM patient. The CSF HE4 or CEACAM6 level for distinguished LM from Wiot-LM showed good performance by receiver-operating characteristic analysis. The better discriminative power for LM was achieved when HE4 was combined with CEACAM6. In addition, the CSF HE4 and CEACAM6 level showed little or no difference between Wiot-LM/BrM and BrM patients, the BrM would not significantly influence the HE4 or CEACAM6 level in CSF. The diagnostic power of CSF CA125, CA153, CA199, CA724, NSE and ProGRP for LUAD LM were not ideal.ConclusionThe combination with HE4 and CEACAM6 has the promising application for the diagnosis of LUAD LM.

ABSTRACTThe emergence and nosocomial spread of the multidrug-resistant Candida auris pose a severe public health threat. Most C. auris clinical isolates are fluconazole resistant. In this study, we conduct transposon-mediated screens to profile genes whose inactivation causes fluconazole resistance in C. auris. We discover that mutation of genes encoding the Ubr2/Mub1 ubiquitin-ligase complex results in high fluconazole resistance by stabilizing the transcription activator, Rpn4. Global transcriptomic analysis, quantitative PCR, and combinatorial gene deletion reveal that Rpn4 causes fluconazole resistance by upregulating four efflux pump genes, SNQ21, SNQ22, MDR1, and CDR1, increasing efflux activity of the cell. Rpn4 autoactivates its own expression by binding to a PACE element in its promoter, forming a positive autoregulatory loop. Rpn4 also promotes CDR1 expression by binding to a PACE element in the CDR1 promoter. Furthermore, using the published genome sequence data of 304 clinical isolates, we identified a UBR2 A316T mutation in isolates from clades I and III. Although complementation of the ubr2Δ mutant with the UBR2A316T allele resulted in increased susceptibility to fluconazole, the UBR2A316T mutant was still more resistant to fluconazole compared to wild type, suggesting that acquisition of the mutation is sufficient to confer an increase in fluconazole resistance. In conclusion, this study identifies Rpn4 as a critical transcription factor that regulates fluconazole resistance via the Rpn4-efflux pump axis in C. auris.IMPORTANCECandida auris is a recently emerged pathogenic fungus of grave concern globally due to its resistance to conventional antifungals. This study takes a whole-genome approach to explore how C. auris overcomes growth inhibition imposed by the common antifungal drug fluconazole. We focused on gene disruptions caused by a “jumping genetic element” called transposon, leading to fluconazole resistance. We identified mutations in two genes, each encoding a component of the Ubr2/Mub1 ubiquitin-ligase complex, which marks the transcription regulator Rpn4 for degradation. When either protein is absent, stable Rpn4 accumulates in the cell. We found that Rpn4 activates the expression of itself as well as the main drug efflux pump gene CDR1 by binding to a PACE element in the promoter. Furthermore, we identified an amino acid change in Ubr2 in many resistant clinical isolates, contributing to Rpn4 stabilization and increased fluconazole resistance.

ABSTRACTEvidence suggests that the type of nutrition fed to preterm infants influences their intestinal microbiome and immunity. However, few studies have conducted a longitudinal analysis of the microbiota of mother’s own milk (MOM) and the factors shaping its composition. Furthermore, the microbiota of pasteurized donor human milk (PDHM) and infant formula have not been extensively investigated. Here, we examine the microbiota of 238 MOM, 30 PDHM, and 73 formula samples from a cohort of 72 preterm infants using 16S rRNA sequencing. We find differences in the microbial diversity and composition between nutrition types. Additionally, we demonstrate that the microbiota of MOM exhibits temporal fluctuations and has associations with several maternal factors. Lastly, we identify three microbiota community clusters within MOM—termed lactotypes—that have distinct taxonomic compositions and maternal factors. Collectively, our findings lay the foundation for exploring the relationship between the microbiota of nutrition and preterm infant health outcomes.IMPORTANCEDespite a growing recognition that the type of nutrition received by preterm infants influences their intestinal microbiome and health outcomes, the microbiota of mother's own milk (MOM), pasteurized donor human milk (PDHM), and infant formula remain poorly characterized. In our study, we found that the structure of microbial communities, bacterial diversity, and relative abundances of specific genera were significantly different between MOM, PDHM, and formula. Additionally, our results suggest that the microbiota of MOM changes as a function of time and maternal factors. Lastly, we identified three lactotypes within MOM that have distinct microbial compositions and described the maternal factors associated with them. These findings set the stage for future research aimed at advancing our knowledge of the microbiota of preterm infant nutrition and the specific influence it may have on health outcomes.

Background Epidemiological characteristics of paediatric burn can help to protect children from burn injuries. Most of the previous studies have been conducted on small scale and single centre in China. This study analysed the epidemiological characteristics of paediatric burn using a large-scale and multicentre database from 23 children’s hospitals in China to increase child protection against burn injuries, improve the quality of care and reduce hospitalisation costs.Methods Excerpted information from medical records of 6741 paediatric burn cases was extracted from the Futang Research Center of Pediatric Development database from 2016 to 2019. The epidemiological characteristics of patients, including gender, age, cause of burn injuries, complication, the timing of hospitalisation (season and month) and hospitalisation length and cost, were collected.Results Male gender (63.23%), aged 1–2 years (69.95%), and hydrothermal scald (80.57%) were significantly dominant among cases. Furthermore, complications were significantly different among groups with different age of patients. Pneumonia was the most common complication (21%). Meanwhile, most paediatric burn occurred in spring (26.73%), and hospitalisation length and cost significantly depended on the cause of the burn injuries and surgical intervention.Conclusions This large-scale epidemiological study of paediatric burn in China revealed that boys aged 1–2 years with higher activity and lack of self-awareness are more likely to suffer from burn injuries by hydrothermal scald. In addition, complications, especially pneumonia, need attention and early prevention in paediatric burn.

IntroductionEstablishing a driving fatigue monitoring system is of utmost importance as severe fatigue may lead to unimaginable consequences. Fatigue detection methods based on physiological information have the advantages of reliable and accurate. Among various physiological signals, EEG signals are considered to be the most direct and promising ones. However, most traditional methods overlook the functional connectivity of the brain and fail to meet real-time requirements.MethodsTo this end, we propose a novel detection model called Attention-Based Multi-Semantic Dynamical Graph Convolutional Network (AMD-GCN). AMD-GCN consists of a channel attention mechanism based on average pooling and max pooling (AM-CAM), a multi-semantic dynamical graph convolution (MD-GC), and a spatial attention mechanism based on average pooling and max pooling (AM-SAM). AM-CAM allocates weights to the input features, helping the model focus on the important information relevant to fatigue detection. MD-GC can construct intrinsic topological graphs under multi-semantic patterns, allowing GCN to better capture the dependency between physically connected or non-physically connected nodes. AM-SAM can remove redundant spatial node information from the output of MD-GC, thereby reducing interference in fatigue detection. Moreover, we concatenate the DE features extracted from 5 frequency bands and 25 frequency bands as the input of AMD-GCN.ResultsFinally, we conduct experiments on the public dataset SEED-VIG, and the accuracy of AMD-GCN model reached 89.94%, surpassing existing algorithms.DiscussionThe findings indicate that our proposed strategy performs more effectively for EEG-based driving fatigue detection.

ObjectiveThis study aimed to identify risk factors for intracranial aneurysms (IAs) recurrence and establish a predictive model to aid evaluation.MethodsA total of 302 patients with 312 IAs undergoing coil embolization between September 2017 and October 2022 were divided into two groups based on digital subtraction angiography follow-up. Clinical characteristics, operation-related factors, and morphologies were measured. Cox proportional hazard regression was used to identify the risk factors. Hazard ratios (HRs) were used to score points, and a predictive model was established. The test cohorts consisted of 51 IAs. Receiver operating characteristic curves were generated to determine the cutoff values and area under the curves (AUCs). A Delong test was performed to compare the AUCs.ResultsDiameter maximum (D max) (p < 0.001, HR = 1.221), Raymond-Roy occlusion classification (RROC) II or III (p = 0.004, HR = 2.852), and ruptured status (p < 0.001, HR = 7.782) were independent risk factors for the recurrence of IAs. A predictive model was established: D max + 2 * RROC (II or III; yes = 1, no = 0) + 6 * ruptured status (yes = 1; no = 0). The AUC of the predictive model (0.818) was significantly higher than those of D max (0.704), RROC (II or III) (0.645), and rupture status (0.683), respectively (Delong test, p < 0.05). The cutoff values of the predictive model and D max were 9.75 points and 6.65 mm, respectively.ConclusionThe D max, RROC (II or III), and ruptured status could independently predict the recurrence of IAs after coil embolization. Our model could aid in practical evaluations.

Autoblinking is a widespread phenomenon and exhibits high level of intensity in some bacteria. In Deinococcus radiodurans (D. radiodurans), strong autoblinking was found to be indistinguishable from PAmCherry and greatly prevented single-molecule tracking of proteins of interest. Here we employed the bright photoswitchable fluorescent protein mMaple3 to label PprI, one essential DNA repair factor, and characterized systematically the fluorescence intensity and bleaching kinetics of both autoblinking and PprI-mMaple3 molecules within cells grown under three different conditions. Under minimal media, we can largely separate autoblinking from mMaple3 molecules and perform reliably single-molecule tracking of PprI in D. radiodurans, by means of applying signal-to-noise ratio and constraining the minimal length for linking the trajectories. We observed three states of PprI molecules, which bear different subcellular localizations and distinct functionalities. Our strategy provides a useful means to study the dynamics and distributions of proteins of interest in bacterial cells with high level of autoblinking.

Unsaturated fatty acids (UFAs) play a fundamental role in maintaining human health and serve as an important raw material for functional foods. However, UFAs are prone to oxidization during processing and storage, leading to deterioration. Microencapsulation of UFAs is an effective processing method to minimize oxidation and enhance its stability. In this paper, the physiological functions of UFAs and their applications in food, medicine, and other fields are summarized. The research progress of microencapsulation technology of UFAs is systematically reviewed, aiming to provide a theoretical basis and rationale for their applications in the food industry. Research has shown that the wall materials widely used were mainly proteins and carbohydrates, whereas their combination can overcome their disadvantages. Spray drying, freeze drying, molecular encapsulation, and coacervation method are most commonly used in the fabrication of microencapsulated UFAs. Using various wall materials and fabrication methods leads to very different encapsulation efficiency, which also greatly impacts the stability of UFAs during processing and storage. Hence, it is still necessary to select appropriate materials and methods according to the properties and functions of the food products. Microencapsulated UFAs exhibited slow-release properties and improved physiological functions. Therefore, it may have broad applications and excellent future development prospects in the food industry.

Abstract Accumulating evidence indicates that metabolic responses are deeply integrated into signal transduction, which provides novel opportunities for the metabolic control of various disorders. Recent studies suggest that itaconate, a highly concerned bioactive metabolite catalyzed by immune responsive gene 1 (IRG1), is profoundly involved in the regulation of apoptosis, but the underlying mechanisms have not been fully understood. In the present study, the molecular mechanisms responsible for the apoptosis-modulatory activities of IRG1/itaconate have been investigated in mice with lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced apoptotic liver injury. The results indicated that LPS/D-Gal exposure upregulated the level of IRG1 and itaconate. Deletion of IRG1 resulted in exacerbated hepatocytes apoptosis and liver injury. The phospho-antibody microarray analysis and immunoblot analysis indicated that IRG1 deletion enhanced the activation of AMP-activated protein kinase (AMPK)/c-jun-N-terminal kinase (JNK) pathway in LPS/D-Gal exposed mice. Mechanistically, IRG1 deficiency impaired the anti-oxidative nuclear factor erythroid-2 related factor 2 (Nrf2) signaling and then enhanced the activation of the redox-sensitive AMPK/JNK pathway that promotes hepatocytes apoptosis. Importantly, post-insult supplementation with 4-octyl itaconate (4-OI), a cell-permeable derivate of itaconate, resulted in beneficial outcomes in fulminant liver injury. Therefore, IRG1/itaconate might function as a negative regulator that controls AMPK-induced hepatocyte apoptosis in LPS/D-Gal-induced fulminant liver injury.

Abstract Wound healing is a common occurrence. However, delayed healing and aberrant scarring result in pathological wound healing. Accordingly, a scarless wound healing remains a significant clinical challenge. In this study, we constructed hyaluronic acid (HA)-modified and verteporfin (VP)-loaded polylactic acid (PLA) nanogels (HA/VP-PLA) to promote scarless wound healing by accelerating wound re-epithelialization and controlling scar formation. Owing to the unique structure of HA incorporating and coating in VP-loaded PLA nanoparticles, HA/VP-PLA could be topically applied on wound to achieve targeted delivery to fibroblasts. Then, HA/VP-PLA released HA and lactic acid (LA) to stimulate the proliferation and migration of fibroblasts, as well as VP to inhibit Yes-associated protein (YAP) expression and nuclear localization to suppress fibrosis. In vitro (skin fibroblasts) and in vivo (rat and rabbit models) experiments strongly suggested that HA/VP-PLA promoted scarless wound healing by accelerating wound re-epithelialization and controlling scar formation. Therefore, our work provides a feasible strategy for scarless wound healing, and the sophisticated HA/VP-PLA exhibit a great potential for clinical applications.

Abstract Background Cognitive impairment is the main factor in the poor prognosis of schizophrenia, but its mechanism remains unclear. The inferior parietal lobule (IPL) is related to various clinical symptoms and cognitive impairment in schizophrenia. We aimed to explore the relationship between IPL-related functions and cognitive impairment in schizophrenia. Methods 136 schizophrenia patients and 146 demographically matched healthy controls were enrolled for a cross-sectional study. High-spatial-resolution structural and resting-state functional images were acquired to demonstrate the alternations of brain structure and function. At the same time, the digit span and digit symbol coding tasks of the Chinese Wechsler Adult Intelligence Test Revised (WAIS-RC) were utilized in assessing the subjects’ cognitive function. Patients were divided into cognitive impairment and normal cognitive groups according to their cognitive score and then compared whether there were differences between the three groups in fractional amplitude of low-frequency fluctuation (fALFF). In addition, we did a correlation analysis between cognitive function and the fALFF for the left IPL of patients and healthy controls. Based on the Allen Human Brain Atlas, we obtained genes expressed in the left IPL, which were then intersected with the transcriptome-wide association study results and differentially expressed genes in schizophrenia. Results Grouping of patients by the backward digit span task and the digit symbol coding task showed differences in fALFF values between healthy controls and cognitive impairment patients (P 0.017). In addition, we found that diacylglycerol kinase ζ (DGKζ) is differentially expressed in the left IPL and associated with schizophrenia. Conclusion Our study demonstrates that the left IPL plays a vital role in cognitive impairment in schizophrenia. DGKζ may act as an essential regulator in the left IPL of schizophrenia patients with cognitive impairment.

Abstract Background Body fat composition is believed to be associated with the progression, medical response, and prognosis of inflammatory bowel disease (IBD). Hence, we conducted this study to explore if fat metrics were associated with the disease activity of severe IBD and the response to intravenous corticosteroids (IVCS). Methods We included 69 patients with ulcerative colitis (UC) and 72 patients with Crohn's disease (CD) who had previously received IVCS during hospitalization. We quantified individual fat distribution using abdominal computed tomography slices. The correlations between fat parameters and disease activity were available with Spearman correlation analysis. The prediction model was developed using independent risk factors derived from multivariable logistic regression analysis. Model discrimination was evaluated leveraging the receiver operating characteristic curve. 1000 bootstrap resamples internally validated the model's prediction performance. Results Notable differences in age, nutritional status, serum cytomegalovirus replication, stool condition, and extraintestinal involvement between UC and CD patients were observed. UC subjects who responded to IVCS had higher subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), and mesorectal adipose tissue index (MATI) than non-responders. IVCS-responding CD individuals had lower VATI and mesenteric fat index (MFI) than non-responders. CD patients with a prolonged disease duration had a decreased SATI and an elevated MFI. VATI and MATI were reduced as UC clinically progressed, while more prominent clinical activity in CD correlated with increased VATI, MATI, and MFI. A high SATI indicated that patients with UC were more prone to be IVCS responders. For patients with CD, levels of VATI and MFI were negatively associated with effective IVCS treatment. The established models showed a discriminative accuracy of 0.834 [95% confidence interval (CI) 0.740–0.928] in the UC cohort and 0.871 (95% CI 0.793–0.949) in the CD cohort. Repeated samples supported the reliability of the developed models (AUCUC = 0.836, 95% CI 0.735–0.919; AUCCD = 0.876, 95% CI 0.785–0.946). Conclusion Human fat indexes represent novel imaging biomarkers for identifying IBD patients who respond to IVCS, thus building accelerated therapy regimens and avoiding the adverse effects of ineffective IVCS.

Abstract Background Unintentional injuries among children and adolescents are a major public health problem worldwide. These injuries not only have negative effects on children’s physiology and psychology, but also bring huge economic losses and social burdens to families and society. Unintentional injuries are the leading cause of disability and death among Chinese adolescents, and left-behind children (LBC) are more prone to experience unintentional injury. The purpose of this study was to evaluate the type and incidence of unintentional injury among Chinese children and adolescents and explore the influences of personal and environmental factors by comparing the differences between LBC and not left-behind children (NLBC). Methods This cross-sectional study was conducted in January and February 2019. Additionally, 2786 children and adolescents from 10 to 19 years old in Liaoning Province in China were collected in the form of self-filled questionnaires, including Unintentional Injury Investigation, Unintentional Injury Perception Questionnaire, Multidimensional Subhealth Questionnaire of Adolescent (MSQA), Negative life events, “My Class” questionnaire and Bullying/victim Questionnaire. Multiple logistic regression analysis was used to explore the factors associated with unintentional injury among children and adolescents. Binary logistic regression analysis was used to explore the factors affecting unintentional injuries between LBC and NLBC. Results The top three unintentional injuries were falling injuries (29.7%), sprains (27.2%) and burns and scalds (20.3%) in our study population. The incidence of unintentional injuries in LBC was higher than that in NLBC. Burn and scalds, cutting injury and animal bites in LBC were higher than those in NLBC. The results show that junior high school students (odds ratio (OR) = 1.296, CI = 1.066–1.574) were more likely to report multiple unintentional injuries than primary school students. Girls (OR = 1.252, CI = 1.042–1.504) had higher odds of reporting multiple unintentional injuries. The odds of multiple injuries in children and adolescents with low levels of unintentional injury perception were higher than those in children and adolescents with high levels of unintentional injury perception (OR = 1.321, C = 1.013–1.568). Children and adolescents with a higher levels of mental health symptoms (OR = 1.442, CI = 1.193–1.744) had higher odds of reporting multiple unintentional injuries. Compared with teenagers who had never experienced negative life events, teenagers who had experienced negative life events many times (OR = 2.724, CI = 2.121–3.499) were more likely to suffer unintentional injuries many times. Low-level discipline and order (OR = 1.277, CI = 1.036–1.574) had higher odds of reporting multiple unintentional injuries. In-school adolescents who were bullied were more likely to report being injured multiple times than their counterparts who were not bullied (OR = 2.340, CI = 1.925–2.845). Low levels of unintentional injury perception, experienced negative life events and bullying had greater impacts on LBC than on NLBC. Conclusion The survey found that the incidence of at least one unintentional injury was 64.8%. School level, sex, unintentional injury perception, subhealth, negative life events, discipline and order and bullying were associated with incidents of unintentional injury. Compared with NLBC, LBC had a higher incidence of unintentional injury, and special attention should be given to this group.

Evacuation simulation is an important method for studying and evaluating the safety of passenger evacuation, and the key lies in whether it can accurately predict personnel evacuation behavior in different environments. The existing models have good adaptability in building environments but have weaker adaptability to personnel evacuation in civil aircraft cabins with more obstacles and stronger hindrances. We target the narrow seat aisle environment on airplanes and use a BP neural network to establish a continuous displacement model for personnel evacuation. We compare the simulation accuracy of evacuation time with the social force model based on continuous displacement and further compare the similarity of personnel evacuation process behavior. The results show that both models were close to the experimental values in simulating evacuation time, while our BP neural network evacuation model based on experimental data was more accurate in predicting the personnel evacuation process, showing more realistic details such as the probability of conflicts and bottleneck evolution in the cross aisle.

In order to extend the basic theory of boundary value problems, the existence of solutions for a class of Hilfer fractional impulsive differential equations with finite impulsive points was studied. Firstly, the integral equation equivalent to the differential equation was obtained; Secondly, appropriate Banach spaces and norms were defined, and appropriate operators were constructed. When the nonlinear term satisfies different conditions, sufficient conditions for the existence of solutions of such boundary value problems were obtained by using Krasnoselskii fixed point theorem; Finally, two examples were used to illustrate the universality of the research results. It is shown that the solution of the boundary value problem of impulsive differential equations with Hilfer fractional derivative exists. By using the Krasnoselskii fixed-point theorem, the existence of solutions for impulsive differential equation boundary value problems with Hilfer fractional order can be effectively solved, which provides some reference for solving other types of impulsive fractional differential equation boundary value problems.

Abstract Background Attenuated live bacterial therapy and medical BSA materials have their own advantages in anti-cancer research, and their combination is expected to overcome some of the disadvantages of conventional anti-cancer therapeutics. Methods and objective Utilizing the high affinity between biotin and streptavidin, BSA modification on the surface of Escherichia coli (E. coli) was achieved. Then, the adhesion and targeting abilities of BSA modified E. coli was explored on different bladder cancer cells, and the underlying mechanism was also investigated. Results BSA modification on the surface of E. coli enhances its ability to adhere and target cancer cells, and we speculate that these characteristics are related to the expression of SPARC in different bladder cancer cell lines. Conclusion BSA and live bacteria have their own advantages in anti-cancer research. In this study, we found that E. coli surface-modified by BSA had stronger adhesion and targeting effects on bladder cancer cells with high expression of SPARC. These findings pave the way for the future studies exploring the combination of BSA combined with live bacteria for cancer therapy.

Highlights The skin-inspired multifunctional ultra-tough electronic skin with tunable mechanical properties was developed by a physically cross-linking salting-freezing-thawing method. The hydrogel integrates transparency (>60%), super toughness (up to 13.96 MJ m−3), good antibacterial properties (E. coli and S. aureus), UV protection (Filtration: 80%–90%), high electrical conductivity (4.72 S m−1), anti-swelling and recyclability. As a human–machine interface, it can be used for complex underwater activities, information encryption/decryption and finger joint rehabilitation training.

Abstract Assembly geometric error as a part of the machine tool system errors has a significant influence on the machining accuracy of the multi-axis machine tool. And it cannot be eliminated due to the error propagation of components in the assembly process, which is generally non-uniformly distributed in the whole working space. A comprehensive expression model for assembly geometric error is greatly helpful for machining quality control of machine tools to meet the demand for machining accuracy in practice. However, the expression ranges based on the standard quasi-static expression model for assembly geometric errors are far less than those needed in the whole working space of the multi-axis machine tool. To address this issue, a modeling methodology based on the Jacobian-Torsor model is proposed to describe the spatially distributed geometric errors. Firstly, an improved kinematic Jacobian-Torsor model is developed to describe the relative movements such as translation and rotation motion between assembly bodies, respectively. Furthermore, based on the proposed kinematic Jacobian-Torsor model, a spatial expression of geometric errors for the multi-axis machine tool is given. And simulation and experimental verification are taken with the investigation of the spatial distribution of geometric errors on five four-axis machine tools. The results validate the effectiveness of the proposed kinematic Jacobian-Torsor model in dealing with the spatial expression of assembly geometric errors.

Abstract With an increase in tunnel construction and retention, traditional waterproofing and drainage systems have been unable to meet the needs of tunnels in heavy rainfall areas, and disasters such as tunnel lining cracking, leakage, and even collapse, occur frequently. In order to ensure the safe operation and maintenance of tunnels, this paper analyses the characteristics of the traditional waterproofing and drainage system, and puts forward a new drainage structure through numerical simulation and indoor testing. This structure removes the circular drainage blind pipe and adds a convex shell drainage plate between the waterproof board and the secondary lining. The research shows that the new drainage system greatly decreases the water pressure in the easily blocked area of the drainage structure. With the special surface discharge model, the external water pressure of the lining far away from the blocked area can quickly fall back to the normal level. In addition, the drainage capacity of different waterproof and drainage boards is different. With an increase in support pressure, the drainage capacity decreases; the geotextile decreases the most, followed by the capillary drainage board and then the convex shell drainage board. At the same time, after the muddy water drainage test of the three materials, it is found that the convex shell type drainage plate has the best anti-sludge performance. The research in this paper provides a beneficial attempt for the design of waterproofing and drainage structure of a water-rich karst tunnel, and provides a guarantee for the safe operation and maintenance of the tunnel.

Abstract This article presents a closed‐form synthesis method for wideband bandpass filters with suppressed harmonics, where stepped‐impedance resonators (SIRs), scaled lines, and vertically installed planar (VIP) structures are introduced to improve the in‐band and out‐of‐band performances. By combining SIRs and scaled lines, the rejection level of the filter is greatly improved and a more compact size is achieved. And the VIP structures help to bring wide passband as well as suppressed harmonics. Then, a 3rd‐order filter is designed to verify the validity of the proposed method and topology. The simulated and measured results demonstrate that the proposed design has a wide passband (FBW = 52.9%), low insertion loss (

Abstract The long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) plays an oncogenic role in multiple cancers due to its high expression. However, the expression and associated regulatory mechanisms of PVT1 in cutaneous squamous cell carcinoma (cSCC) remain unclear. Our results revealed that PVT1 was highly upregulated in cSCC tissues and cSCC cell lines. To determine the functional role of PVT1 in cSCC, we constructed a stable knockdown cell model of PVT1 in the A431 and COLO16 cell lines using a lentiviral approach. Xenograft tumor experiments of nude mice in vivo, and colony formation, CCK-8, and EdU assays in vitro demonstrated that knockdown of PVT1 could widely suppress cell proliferation in vivo and in vitro. In addition, PVT1 knockdown induced cell cycle arrest and promoted apoptosis, as detected by flow cytometry analysis. Wound healing and transwell assays revealed that PVT1 knockdown significantly inhibited the migration and invasion of CSCC cell lines. To gain insight into the tumorigenic mechanism and explore the potential target molecules of PVT1, we employed label-free quantitative proteomic analysis. The GO, KEGG enrichment, and protein–protein interaction (PPI) networks suggested that 4E-binding protein 1 (4EBP1) is the possible downstream target effector of PVT1, which was validated by western blot analysis. PVT1 silencing markedly decreased 4EBP1 protein expression levels and directly bound 4EBP1 in the cytoplasm of cSCC cells. 4EBP1 overexpression counteracted the effects of PVT1 knockdown on tumorigenesis in cSCC cells, including cell proliferation, apoptosis, migration, and invasion. Our findings provide strong evidence that PVT1 is an oncogene which plays a role in tumorigenesis of cSCC, that PVT1 may interact with 4EBP1 in the cytoplasm as an underlying mechanism in cSCC carcinogenesis, and that PVT1 combined with 4EBP1 may serve as a potential new therapeutic target for cSCC.

Abstract Background The TIFY family is a plant-specific gene family and plays an important role in plant growth and development. But few reports have been reported on the phylogenetic analysis and gene expression profiling of TIFY family genes in birch (Betula platyphylla). Results In this study, we characterized TIFY family and identified 12 TIFY genes and using phylogeny and chromosome mapping analysis in birch. TIFY family members were divided into JAZ, ZML, PPD and TIFY subfamilies. Phylogenetic analysis revealed that 12 TIFY genes were clustered into six evolutionary branches. The chromosome distribution showed that 12 TIFY genes were unevenly distributed on 5 chromosomes. Some TIFY family members were derived from gene duplication in birch. We found that six JAZ genes from JAZ subfamily played essential roles in response to Methyl jasmonate (MeJA), the JAZ genes were correlated with COI1 under MeJA. Co-expression and GO enrichment analysis further revealed that JAZ genes were related to hormone. JAZ proteins involved in the ABA and SA pathways. Subcellular localization experiments confirmed that the JAZ proteins were localized in the nucleus. Yeast two-hybrid assay showed that the JAZ proteins may form homologous or heterodimers to regulate hormones. Conclusion Our results provided novel insights into biological function of TIFY family and JAZ subfamily in birch. It provides the theoretical reference for in-depth analysis of plant hormone and molecular breeding design for resistance.

Abstract Background Psoriasis is a chronic inflammatory dermatosis with an unclear pathogenesis. Mast cells (MCs) can serve as a bridge between innate and adaptive immunity and are involved in the regulation of the inflammatory state and immune homeostasis in diseases. MCs constitutively express interleukin-33 receptor T1/ST2 (IL-33R). IL-33 is a potent MCs activator that is actively secreted by keratinocytes in psoriasis. However, the regulatory role of MCs in psoriasis remains uncertain. Therefore, we hypothesised that IL-33 could promote MC activation to regulate psoriasis development. Methods We performed experiments on wild-type (WT) and MC-deficient (Kit Wsh/Wsh) mice, established psoriasis-like mouse models using imiquimod (IMQ), and performed RNA sequencing and transcriptomic analysis of skin lesions. Exogenous administration was performed using recombinant IL-33. Validation and evaluation were performed using PSI scoring, immunofluorescence, immunohistochemistry, and qPCR. Results We observed an upregulation in the number and activation of MCs in patients with psoriasis and in IMQ-induced psoriasis-like dermatitis. Deficiency of MCs ameliorates IMQ-induced psoriatic dermatitis at an early stage. IL-33 is increased and co-localized with MCs in the dermis of psoriasis-like lesions using immunofluorescence. Compared to WT mice, IMQ-induced KitWsh/Wsh mice demonstrated a delayed response to exogenous IL-33. Conclusions MCs are activated by IL-33 in the early stages of psoriasis and exacerbate psoriasis-associated skin inflammation. The regulation of MC homeostasis may be a potential therapeutic strategy for psoriasis. Video Abstract

Seismic landslides can seriously aggravate the losses of earthquake disasters. Therefore, it is of great significance to assessment the distribution of earthquake induced landslides for emergency relief. In this paper, based on the 30 m resolution DEM and regional geologic data with a scale of 1∶500 000, emergency rapid assessment of earthquake induced landslides is carried out using the Newmark cumulative displacement model for the 5 September 2022 Luding MS6.8 earthquake, China. The results show that the earthquake induced landslides are relatively serious in this earthquake. The high hazard zones of the coseismic landslides are about 45 km2, which is mainly distributed on the two banks of the nearly east-west tributaries on the west bank of the Dadu River and the west of the Xianshuihe fault, especially along the Yanzigou, Mozigou, Hailuogou, Feishuigou gullies and the Wandong, Shiyue, Tianwan rivers, posing a great threat to the lives of residents and tourists. The rivers and roads in these tributaries are at high risk of being blocked by landslides. The Lengqi, Xinglong, Moxi and Detuo towns in Luding County and Tianwan, Caoke, Xinmin, Xianfeng, Xieluo and Wajiao towns in Shimian County are at high risk of landslides. The S434 Provincial Road and S211 Provincial Road along the Dadu River near the epicenter are more likely to be blocked by landslides. The predicted earthquake landslide hazard in the Gongga Snow Mountain area is medium, but it is necessary to pay attention to the risks of long range and high position landslide disaster (chain), such as ice avalanche and rock avalanche. Comparison between the distribution of induced landslides in zones with intensity VIII and IX obtained from post-earthquake emergency investigation and remote sensing interpretation shows that the obtained displacements can well reflect the macro distribution of coseismic landslides along the tributaries on the west bank of the Dadu River, but cannot be exerted effectively around the edge of the Moxi platform and the banks of the main stream of Dadu River, which can be enhanced through the improvement of large scale of geologic maps and high quality topography data. The results can provide reference for valuable timely reference information on post-earthquake reconstruction planning and long-time activity of post-earthquake geohazard and risk recognition of landslide disaster chains.

Abstract Background and aims Diagnosis of leptomeningeal metastasis (LM) is challenging. In our previous study, CEACAM6 mRNA was found to be highly expressed in the circulating tumor cells of cerebrospinal fluid (CSF) from patients with lung adenocarcinoma with LM (LUAD‐LM). The aim of this study was to identify whether CEACAM6 could be used as a biomarker for LUAD‐LM. Materials and methods The level of CEACAM6 was determined by enzyme‐linked immunosorbent assay (ELISA) in CSF from 40 LUAD‐LM and 44 normal controls, and additional serum samples from 138 LUAD patients, including 12 LUAD‐LM patients, and 30 healthy controls. Carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21‐1) and neuron‐specific enolase (NSE) levels in the CSF and sera were detected by chemiluminescent immunoassay. Receiver operating characteristic curve was plotted to evaluate the diagnostic performance for LUAD‐LM. Results CSF CEACAM6 level was higher in LUAD‐LM than that in normal controls. In serum, LUAD patients had a higher level of CAECAM6 than healthy controls, and LM patients had the highest level among them. Serum CEACAM6 had a higher AUC than CEA in differentiating LM from non‐LM in LUAD patients (0.95 vs. 0.64, p

Abstract Electromagnetic pulse (EMP), a unique type of electromagnetic radiation, may induce diverse neuropsychiatric disorders, such as irritability, hyperkinesis, retardation of learning and memory. However, the underlying mechanism of EMP exposure on neuronal injury has not been elucidated. Here, we aimed to delineate the regulatory expression networks based on high-throughput sequencing data to explore the possible molecular mechanisms related to EMP-induced delirium-like neuropsychiatric disorder in rats. It’s shown that EMP exposure induced anxiety, cognitive decline and short-term memory impairment. The expression profiles of the long noncoding RNAs (lncRNAs) and mRNAs, along with their biological function and regulatory network, were explored in rats after EMP exposure. We identified 41 differentially expressed lncRNAs (DELs) and 266 differentially expressed mRNAs (DEMs) between EMP and sham groups. Sixty-one co-expression relationships between 18 DELs and 56 DEMs were mostly associated with synapse- and metabolic-related pathways. We predicted 51 DEL-miRNA pairs and 290 miRNA-mRNA pairs using the miRanda database to constructed a DEL-miRNA-DEM network. LncRNA AABR07042999.1 and mRNA Tph2, Slc6a4, Dbh and Th were upregulated, and the contents of serotonin, dopamine and norepinephrine were increased in both PFC and HIP after EMP exposure. The current study provided a better understanding of the ceRNA network, which might reveal the pathological mechanism and provide more treatment options for the EMP-induced neurobehavioral disorder.

Adoptive cell therapy (ACT) has been demonstrated to be one of the most promising cancer immunotherapy strategies due to its active antitumor capabilities in vivo. Engineering T cells to overexpress chimeric antigen receptors (CARs), for example, has shown potent efficacy in the therapy of some hematologic malignancies. However, the efficacy of chimeric antigen receptor T cell (CAR-T) therapy against solid tumors is still limited due to the immunosuppressive tumor microenvironment (TME) of solid tumors, difficulty in infiltrating tumor sites, lack of tumor-specific antigens, antigen escape, and severe side effects. In contrast, macrophages expressing CARs (CAR-macrophages) have emerged as another promising candidate in immunotherapy, particularly for solid tumors. Now at its nascent stage (with only one clinical trial progressing), CAR-macrophage still shows inspiring potential advantages over CAR-T in treating solid tumors, including more abundant antitumor mechanisms and better infiltration into tumors. In this review, we discuss the relationships and differences between CAR-T and CAR-macrophage therapies in terms of their CAR structures, antitumor mechanisms, challenges faced in treating solid tumors, and insights gleaned from clinical trials and practice for solid tumors. We especially highlight the potential advantages of CAR-macrophage therapy over CAR-T for solid tumors. Understanding these relationships and differences provides new insight into possible optimization strategies of both these two therapies in solid tumor treatment

Background: Due to the poor prognosis and rising occurrence, there is a crucial need to improve the diagnosis of Primary Central Nervous System Lymphoma (PCNSL), which is a rare type of non-Hodgkin’s lymphoma. This study utilized targeted metabolomics of cerebrospinal fluid (CSF) to identify biomarker panels for the improved diagnosis or differential diagnosis of primary central nervous system lymphoma (PCNSL).Methods: In this study, a cohort of 68 individuals, including patients with primary central nervous system lymphoma (PCNSL), non-malignant disease controls, and patients with other brain tumors, was recruited. Their cerebrospinal fluid samples were analyzed using the Ultra-high performance liquid chromatography - tandem mass spectrometer (UHPLC-MS/MS) technique for targeted metabolomics analysis. Multivariate statistical analysis and logistic regression modeling were employed to identify biomarkers for both diagnosis (Dx) and differential diagnosis (Diff) purposes. The Dx and Diff models were further validated using a separate cohort of 34 subjects through logistic regression modeling.Results: A targeted analysis of 45 metabolites was conducted using UHPLC-MS/MS on cerebrospinal fluid (CSF) samples from a cohort of 68 individuals, including PCNSL patients, non-malignant disease controls, and patients with other brain tumors. Five metabolic features were identified as biomarkers for PCNSL diagnosis, while nine metabolic features were found to be biomarkers for differential diagnosis. Logistic regression modeling was employed to validate the Dx and Diff models using an independent cohort of 34 subjects. The logistic model demonstrated excellent performance, with an AUC of 0.83 for PCNSL vs. non-malignant disease controls and 0.86 for PCNSL vs. other brain tumor patients.Conclusion: Our study has successfully developed two logistic regression models utilizing metabolic markers in cerebrospinal fluid (CSF) for the diagnosis and differential diagnosis of PCNSL. These models provide valuable insights and hold promise for the future development of a non-invasive and reliable diagnostic tool for PCNSL.

Background Postmenopausal osteoporosis and osteoporosis-related fractures are world-wide serious public health problem. Recent studies demonstrated that inhibiting caveolin-1 leads to osteoclastogenesis suppression and protection against OVX-induced osteoporosis. This study aimed to explore the mechanism of caveolin-1 mediating bone loss and the potential therapeutic target. Methods Thirty C57BL/6 female mice were allocated randomly into three groups: sham or bilateral ovariectomy (OVX) surgeries were performed for mice and subsequently daidzein or vehicle was administrated to animals (control, OVX + vehicle and OVX + daidzein). After 8-week administration, femurs were harvested for Micro-CT scan, histological staining including H&E, immunohistochemistry, immunofluorescence, TRAP. Bone marrow endothelial cells (BMECs) were cultured and treated with inhibitors of caveolin-1 (daidzein) or EGFR (erlotinib) and then scratch wound healing and ki67 assays were performed. In addition, cells were harvested for western blot and PCR analysis. Results Micro-CT showed inhibiting caveolin-1with daidzein alleviated OVX-induced osteoporosis and osteogenesis suppression. Further investigations revealed H-type vessels in cancellous bone were decreased in OVX-induced mice, which can be alleviated by daidzein. It was subsequently proved that daidzein improved migration and proliferation of BMECs hence improved H-type vessels formation through inhibiting caveolin-1, which suppressed EGFR/AKT/PI3K signaling in BMECs. Conclusions This study demonstrated that daidzein alleviates OVX-induced osteoporosis by promoting H-type vessels formation in cancellous bone, which then promotes bone formation. Activating EGFR/AKT/PI3K signaling could be the critical reason.

This paper analyzes an accident of abnormal increase of pole bus differential current and pole differential current of a converter station caused by line fault of a ±800 kV extra high-voltage direct current transmission project. After a lightning strike caused a short circuit and grounding of the DC line, the sudden voltage change protection of the DC line was triggered and the DC full voltage restart was successful. The pole bus differential current and pole differential current of the converter station have reached the protection set but have not reached the protection delay set; therefore, the differential protection has not acted. This paper first introduces the configuration principles of pole differential protection, pole bus differential protection, and line voltage sudden change protection for extra-high voltage converter stations. Second, the operation of the DC protection under this fault was analyzed in detail, and the reasons for the occurrence of pole bus differential current and pole differential current were also analyzed in this paper. Then, the range of equipment that caused the abnormal increase in differential current was identified. Finally, the lightning strike model was built on the real-time digital system, and the fault was simulated and replicated. It was determined that the abnormal increase in differential current was caused by the discharge of the pole bus surge arrester caused by the second lightning strike on the DC line.

Bone marrow stromal cells (BMSCs) have emerged as a potential therapy for sepsis, yet the underlying mechanisms remain unclear. In this study, we investigated the effects of BMSCs on serum inflammatory cytokines in a rat model of lipopolysaccharide (LPS)-induced sepsis. Sepsis was induced by intravenous injection of LPS, followed by transplantation of BMSCs. We monitored survival rates for 72 h and evaluated organ functions, histopathological changes, and cytokines expression. Sepsis rats showed decreased levels of white blood cells, platelets, lymphocyte ratio, and oxygen partial pressure, along with increased levels of neutrophil ratio, carbon dioxide partial pressure, lactic acid, alanine aminotransferase, and aspartate aminotransferase. Histologically, lung, intestine, and liver tissues exhibited congestion, edema, and infiltration of inflammatory cells. However, after BMSCs treatment, there was improvement in organ functions, histopathological injuries, and survival rates. Protein microarray analysis revealed significant changes in the expression of 12 out of 34 inflammatory cytokines. These findings were confirmed by enzyme-linked immunosorbent assay. Pro-inflammatory factors, such as interleukin-1β (IL-1β), IL-1α, tumor necrosis factor-α (TNF-α), tissue inhibitor of metal protease 1 (TIMP-1), matrix metalloproteinase 8 (MMP-8), Leptin, and L-selectin were upregulated in sepsis, whereas anti-inflammatory and growth factors, including IL-4, β-nerve growth factor (β-NGF), ciliary neurotrophic factor (CNTF), interferon γ (IFN-γ), and Activin A were downregulated. BMSCs transplantation led to a decrease in pro-inflammatory cytokines and an increase in anti-inflammatory and growth factors. We summarized relevant molecular signaling pathways that resulted from cytokines in BMSCs for treating sepsis. Our results illustrated that BMSCs could promote tissue repair and improve organ functions and survival rates in sepsis through modulating cytokine networks.

Background: Growing competition in tight job market and academic excellence as a social norm in Asian culture have made Chinese college students burdened with immense academic stress. Objectives: This study aimed to explore the associations between academic stress and depression, and the mediating roles of negative affect and sleep quality, as well as the moderating role of social support in the relationship between negative affect and sleep quality. Methodology: A convenience sample of 221 male and 479 female college students aged between 17 and 25 completed questionnaires on academic stress, depression, negative affect, sleep quality and social support. Results: Results indicated that academic stress could not only directly affect depression (b = 0.31, p

BackgroundRNA methylation is closely involved in immune regulation, but its role in sepsis remains unknown. Here, we aim to investigate the role of RNA methylation-associated genes (RMGs) in classifying and diagnosing of sepsis.MethodsFive types of RMGs (m1A, m5C, m6Am, m7G and Ψ) were used to identify sepsis subgroups based on gene expression profile data obtained from the GEO database (GSE57065, GSE65682, and GSE95233). Unsupervised clustering analysis was used to identify distinct RNA modification subtypes. The CIBERSORT, WGCNA, GO and KEGG analysis were performed to explore immune infiltration pattern and biological function of each cluster. RF, SVM, XGB, and GLM algorithm were applied to identify the diagnostic RMGs in sepsis. Finally, the expression levels of the five key RMGs were verified by collecting PBMCs from septic patients using qRT-PCR, and their diagnostic efficacy for sepsis was verified in combination with clinical data using ROC analysis.ResultsSepsis was divided into three subtypes (cluster 1 to 3). Cluster 1 highly expressed NSUN7 and TRMT6, with the characteristic of neutrophil activation and upregulation of MAPK signaling pathways. Cluster 2 highly expressed NSUN3, and was featured by the regulation of mRNA stability and amino acid metabolism. NSUN5 and NSUN6 were upregulated in cluster 3 which was involved in ribonucleoprotein complex biogenesis and carbohydrate metabolism pathways. In addition, we identified that five RMGs (NSUN7, NOP2, PUS1, PUS3 and FTO) could function as biomarkers for clinic diagnose of sepsis. For validation, we determined that the relative expressions of NSUN7, NOP2, PUS1 and PUS3 were upregulated, while FTO was downregulated in septic patients. The area under the ROC curve (AUC) of NSUN7, NOP2, PUS1, PUS3 and FTO was 0.828, 0.707, 0.846, 0.834 and 0.976, respectively.ConclusionsOur study uncovered that dysregulation of RNA methylation genes (m1A, m5C, m6Am, m7G and Ψ) was closely involved in the pathogenesis of sepsis, providing new insights into the classification of sepsis endotypes. We also revealed that five hub RMGs could function as novel diagnostic biomarkers and potential targets for treatment.

ABSTRACT Systemic lupus erythematosus (SLE), characterized by persistent inflammation, is a complex autoimmune disorder that affects all organs, challenging clinical treatment. Dysbiosis of gut microbiota promotes autoimmune disorders that damage extraintestinal organs. Modulating the gut microbiome is proposed as a promising approach for fine-running parts of the immune system, relieving systematic inflammation in multiple diseases. This study demonstrated that the administration of Akkermansia muciniphila and Lactobacillus plantarum contributed to an anti-inflammatory environment by decreasing IL-6 and IL-17 and increasing IL-10 levels in the circulation. The treatment of A. muciniphila and L. plantarum restored the intestinal barrier integrity to a different extent. In addition, both strains reduced the deposit of IgG in the kidney and improved renal function significantly. Further studies revealed distinct remodeling roles of A. muciniphila and L. plantarum administration on the gut microbiome. This work demonstrated essential mechanisms of how A. muciniphila and L. plantarum remodel gut microbiota and regulate the immune responses in the SLE mice model. IMPORTANCE Several pieces of research have demonstrated that certain probiotic strains contribute to regulating excessive inflammation and restoring tolerances in the SLE animal model. More animal trials combined with clinical studies are urgently needed to further elucidate the mechanisms for the effect of specific probiotic bacteria in preventing SLE symptoms and developing novel therapeutic targets. In this study, we explored the role of A. muciniphila and L. plantarum in ameliorating the SLE disease activity. Both A. muciniphila and L. plantarum treatment relieved the systemic inflammation and improved renal function in the SLE mouse model. We demonstrated that A. muciniphila and L. plantarum contributed to an anti-inflammatory environment by regulating cytokine levels in the circulation, restoring the intestinal barrier integrity, and remodeling the gut microbiome, however, to a different extent.

PurposeThe purpose of this study was to investigate the quantitative retinal vascular morphological characteristics of Retinopathy of Prematurity (ROP) and Familial Exudative Vitreoretinopathy (FEVR) in the newborn by the application of a deep learning network with artificial intelligence.MethodsStandard 130-degree fundus photographs centered on the optic disc were taken in the newborns. The deep learning network provided segmentation of the retinal vessels and the optic disc (OD). Based on the vessel segmentation, the vascular morphological characteristics, including avascular area, vessel angle, vessel density, fractal dimension (FD), and tortuosity, were automatically evaluated.Results201 eyes of FEVR, 289 eyes of ROP, and 195 eyes of healthy individuals were included in this study. The deep learning system of blood vessel segmentation had a sensitivity of 72% and a specificity of 99%. The vessel angle in the FEVR group was significantly smaller than that in the normal group and ROP group (37.43 ± 5.43 vs. 39.40 ± 5.61, 39.50 ± 5.58, P = 0.001,

Background: Some blood groups, such as S and s blood groups in the MNS blood group system, and Kidd and CTL2 blood group systems, can cause severe fetal and newborn alloimmune disorders. Non-invasive prenatal testing (NIPT) to predict fetal blood groups and knowledge of local blood group gene frequency are both important for pregnancy management decisions. Droplet digital PCR (ddPCR) has high specificity and sensitivity in detecting fetal single nucleotide variation. Objectives: The objective is to predict fetal Ss, Kidd, and CTL2 blood groups using multiplex ddPCR. The gene frequencies of three blood groups were detected by ddPCR in northwest China. Design: This is a prospective study. Methods: Cell-free fetal DNA isolated from 26 healthy single pregnant women at different gestational stages was tested with QX200 Droplet Digital PCR. Results were compared with fetal genotypes. DNA samples purified from 20 blood pools containing a total of 1000 donors in northwest China were subjected to ddPCR to detect the gene frequency of three blood groups. Results: Ss, Kidd, and CTL2 blood groups of 26 pregnant fetuses were accurately detected by multiplex ddPCR. The multiplex ddPCR results were consistent with the Sanger sequencing results of 26 fetal blood samples after birth. The gene frequencies of the three blood groups detected by ddPCR were 9.30% for S, 90.70% for s, 48.43% for Jk a , 51.57% for Jk b , 66.57% for HNA-3A, and 33.43% for HNA-3B. Conclusions: It is reliable to predict fetal Ss, Kidd, and CTL2 blood groups by multiplex ddPCR. Meanwhile, we designed a simple and efficient method for inferring the gene frequency of three blood groups based on ddPCR.

Background: Essential trace elements (ETEs) are essential nutrients for keeping the nervous system functioning. Associations between ETEs and cognitive function are still inconclusive and limited. Objectives: We aimed to investigate the individual and joint associations between ETEs and cognitive function among older adults. Methods: A population (N = 2181) at an average age≥ 65 from Yiwu cohort in China was available for this study. Whole blood chromium (Cr), selenium (Se), manganese (Mn), and copper (Cu) concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), consisting of five specific cognitive domains: orientation, registry, attention and calculation, recall, and language and praxis. Linear regression, restricted cubic spline (RCS) analysis, and Bayesian kernel machine regression (BKMR) were used to analyze the individual and joint associations between ETEs and cognitive function. Results: The association between Cr and MMSE score presented an inverted-U shape (Q3 versus Q1: β = 0.774, 95 % CI: 0.297, 1.250; Q4 versus Q1: β = 0.481, 95 % CI: 0.006, 0.956); and Cr was especially associated with the registry, recall, and language and praxis. Per IQR (36.32 μg/L) increase of Se was positively associated with the MMSE score (β = 0.497, 95 % CI: 0.277, 0.717) and all five cognitive domains. The BKMR showed that the dose-response association between Se and cognitive function increased initially and then decreased with increasing Se concentration when fixed the other ETEs in median. ETEs mixture was positively associated with cognitive function, and Se (posterior inclusion probabilities, PIPs = 0.915) was the most important contributor within the ETEs mixture. Conclusions: The nonlinear association between Cr and cognitive function suggested further exploration of an appropriate concentration range for ETEs. A positive association between mixed ETEs and cognitive function is a reminder that their joint association should be considered. Further prospective studies or intervention studies are warranted to validate our findings in the future.