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[Introduction] With the rapid development of power electronic equipment and artificial intelligence and other high-tech, DC (Direct Current) system has been popularized and applied in substations. The grounding fault of the substation DC system has become an important factor affecting the safe and stable operation of the substation. [Method] Firstly, the DC system of the substation was introduced, and its components, typical types of DC ground faults and their adverse effects were analyzed. Then, the principle of five common DC ground fault finding strategies was emphasized. [Result] Based on their respective research status and application scenarios, the advantages and disadvantages of various finding strategy are compared and analyzed. [Conclusion] Combined with the existing problems and technical development trends, the future research directions of DC grounding fault detection at home and abroad are prospected from the perspectives of accurate fault location, complex fault identification, finding accuracy and the improvement of the endurance of portable insulation detection device.

Abstract Objective To observe and evaluate the effectiveness and safety of Esketamine or Sufentanil combined with Dexmedetomidine for sedation and analgesia in lung tumor percutaneous radiofrequency ablation (PRFA) to provide a clinical basis for the optimization of sedation and analgesia in lung tumor PRFA protocols outside the operating room. Methods In this trial, 44 patients aged 37 to 84 undergoing lung tumor PRFA were enrolled and assigned to Group E (n = 22, Esketamine 0.2 mg/kg) or Group S (n = 22,Sufentanil 0.1 μg/kg ). Dexmedetomidine was infused intravenously as a sedative in both groups. The modified observer’s assessment of alertness and sedation scale (MOAAS), physical movement pain scale, intraoperative vital signs, anesthesia recovery time, radiologist and patient satisfaction rates, incidence of respiratory depression, and incidence of postoperative nausea and vomiting were recorded. Results Although there was no significant difference in the physical movement pain scale, blood oxygen saturation or incidence of perioperative adverse events between the two groups during ablation, the MOAAS, mean arterial pressure (MAP) and heart rate (HR) were higher in Group E than in Group S. The anesthesia recovery time was shorter in Group E than in Group S, and radiologist satisfaction was better in Group E than in Group S, but there was no significant difference between the two groups in terms of patient satisfaction. Conclusion Esketamine or Sufentanil combined with Dexmedetomidine is safe for lung tumor PRFA. However, in elderly patients with multiple underlying diseases, low-dose Esketamine combined with Dexmedetomidine has fewer hemodynamic effects on patients, milder respiratory depression, shorter recovery time, and better radiologist satisfaction because of its better controllability of sedation depth. Trial registration Chinese Clinical Trial Registry (Registration number#ChiCTR ChiCTR21000500 21); Date of Registration: 16/08/2021

Abstract Introduction Endometrial cancer (EC) is the most common female reproductive system cancer in developed countries with growing incidence and associated mortality, which may be due to the growing prevalence of obesity. Metabolism reprogramming including glucose, amino acid, and lipid remodeling is a hallmark of tumors. Glutamine metabolism has been reported to participate in tumor proliferation and development. This study aimed to develop a glutamine metabolism‐related prognostic model for EC and explore potential targets for cancer treatment. Method Transcriptomic data and survival outcome of EC were retrieved from The Cancer Genome Atlas (TCGA). Differentially expressed genes related to glutamine metabolism were recognized and utilized to build a prognostic model by univariate and multivariate Cox regressions. The model was confirmed in the training, testing, and the entire cohort. A nomogram combing prognostic model and clinicopathologic features was established and tested. Moreover, we explored the effect of a key metabolic enzyme, PHGDH, on the biological behavior of EC cell lines and xenograft model. Results Five glutamine metabolism‐related genes, including PHGDH, OTC, ASRGL1, ASNS, and NR1H4, were involved in prognostic model construction. Kaplan–Meier curve suggested that patients recognized as high risk underwent inferior outcomes. The receiver operating characteristic (ROC) curve showed the model was sufficient to predict survival. Enrichment analysis recognized DNA replication and repair dysfunction in high‐risk patients whereas immune relevance analysis revealed low immune scores in the high‐risk group. Finally, a nomogram integrating the prognostic model and clinical factors was created and verified. Further, knockdown of PHGDH showed cell growth inhibition, increasing apoptosis, and reduced migration. Promisingly, NCT‐503, a PHGDH inhibitor, significantly repressed tumor growth in vivo (p = 0.0002). Conclusion Our work established and validated a glutamine metabolism‐related prognostic model that favorably evaluates the prognosis of EC patients. DNA replication and repair may be the crucial point that linked glutamine metabolism, amino acid metabolism, and EC progression. High‐risk patients stratified by the model may not be sufficient for immune therapy. PHGDH might be a crucial target that links serine metabolism, glutamine metabolism as well as EC progression.

Modular Multilevel Converter (MMC) is widely used in applications such as High Voltage Direct Current (HVDC) transmission, AC/DC power conversion centers, and large-scale power quality management in electrical grids due to its highly modular structure, strong redundancy and low harmonic content in AC output. The application of the traditional deadbeat predictive current control to MMC enhances the fast tracking ability of the output current, but it still has the problems of low output current accuracy and high dependence on bridge arm inductor. Based on this, this paper proposes an improved two-beat deadbeat synchronous predictive current control based on Newton interpolation method. By improving the two-beat deadbeat synchronous predictive current control strategy, the accuracy of the output current can be further improved and its fast tracking ability can be enhanced. Newton interpolation is introduced to improve the accuracy of the output current while reducing the dependence on the bridge arm inductor. The results show that the control strategy proposed in this paper reduces the output current THD by 2.88% compared with the two-beat deadbeat predictive current control, thus improving the accuracy; the bridge arm inductor value is reduced by 1.28%, thus reducing the dependence; and under the transient environment, the output current can be tracked to its predicted reference value 843 μs in advance, which enhances the fast tracking capability.

BackgroundGlioblastoma (GBM) is a highly malignant brain tumor, and immune cells play a crucial role in its initiation and progression. The immune system's cellular components, including various types of lymphocytes, macrophages, and dendritic cells, among others, engage in intricate interactions with GBM. However, the precise nature of these interactions remains to be conclusively determined.MethodIn this study, a comprehensive two-sample Mendelian Randomization (MR) analysis was conducted to elucidate the causal relationship between immune cell features and the incidence of GBM. Utilizing publicly available genetic data, we investigated the causal associations between 731 immune cell signatures and the risk of GBM. Subsequently, we conducted a reverse Mendelian randomization analysis to rule out reverse causation. Finally, it was concluded that there is a unidirectional causal relationship between three subtypes of immune cells and GBM. Comprehensive sensitivity analyses were employed to validate the results robustness, heterogeneity, and presence of horizontal pleiotropy. To enhance the accuracy of our results, we concurrently subjected them to Bayesian analysis.ResultsAfter conducting MR analyses, we identified 10 immune phenotypes that counteract glioblastoma, with the most protective being FSC-A on Natural Killer T cells (OR = 0.688, CI = 0.515–0.918, P = 0.011). Additionally, we found 11 immune cell subtypes that promote GBM incidence, including CD62L– HLA DR++ monocyte % monocyte (OR = 1.522, CI = 1.004–2.307, P = 0.048), CD4+CD8+ T cell % leukocyte (OR = 1.387, CI = 1.031–1.866, P = 0.031). Following the implementation of reverse MR analysis, where glioblastoma served as the exposure variable and the outcomes included 21 target immune cell subtypes, we discerned that only three cell subtypes (CD45 on CD33+ HLA DR+ CD14dim, CD33+ HLA DR+ Absolute Count, and IgD+ CD24+ B cell Absolute Count) exhibited a unidirectional causal association with glioblastoma.ConclusionOur study has genetically demonstrated the close relationship between immune cells and GBM, guiding future clinical research.

Endometrial cancer (EC) is a common malignant tumor in women worldwide. Although early EC has a good prognosis, advanced endometrial cancer is still associated with the risk of drug resistance and recurrence. Cancer stem cells (CSCs), a category closely related to drug resistance and recurrence, are rarely studied at present. Here, we constructed a risk model containing ten stemness-related prognostic genes. Compared with patients in the low-risk group, patients in the high-risk group had a shorter overall survival time. The accuracy of this model was verified by ROC in the TCGA (AUC = 0.779) and Peking University People's Hospital (PKUPH, AUC = 0.864) cohorts. The risk score and stage were independent risk factors in the multivariate regression analysis, which was subsequently used to construct the nomogram and verified in the TCGA cohort. LGR5 was significantly correlated with overall survival and involvement in the Wnt signaling pathway. In addition, LGR5 was highly expressed in EC tissues and was related to age, stage, histological type, and menopause status in the TCGA database. Overexpression of LGR5 accelerated the proliferation rate of EC cells, which may be related to autophagy activation. Taken together, our study established a prognostic model based on transcription sequencing data from the TCGA database and verified it in the PKUPH cohort, which has prospective clinical implications for the prognostic evaluation of EC. We systematically studied the code gene LGR5 in EC, which may help clinicians make personalized prognostic assessments and effective clinical decisions for EC.

Pectin methylesterase (PME), a family of enzymes that catalyze the demethylation of pectin, influences seed germination. Phytohormone abscisic acid (ABA) inhibits seed germination. However, little is known about the function of PMEs in response to ABA-mediated seed germination. In this study, we found the role of PME31 in response to ABA-mediated inhibition of seed germination. The expression of PME31 is prominent in the embryo and is repressed by ABA treatment. Phenotype analysis showed that disruption of PME31 increases ABA-mediated inhibition of seed germination, whereas overexpression of PME31 attenuates this effect. Further study found that ABI5, an ABA signaling bZIP transcription factor, is identified as an upstream regulator of PME31. Genetic analysis showed that PME31 functions downstream of ABI5 in ABA-mediated seed germination. Detailed studies showed that ABI5 directly binds to the PME31 promoter and inhibits its expression. In the plants, PME31 expression is reduced by ABI5 in ABA-mediated seed germination. Taken together, PME31 is transcriptionally inhibited by ABI5 and negatively regulates ABA-mediated seed germination inhibition. These findings shed new light on the mechanisms of PMEs in response to ABA-mediated seed germination.

Abstract Background Lymph node metastasis (LNM) is an important factor affecting endometrial cancer (EC) prognosis. Current controversy exists as to how to accurately assess the risk of lymphatic metastasis. Metabolic syndrome has been considered a risk factor for endometrial cancer, yet its effect on LNM remains elusive. We developed a nomogram integrating metabolic syndrome indicators with other crucial variables to predict lymph node metastasis in endometrial cancer. Methods This study is based on patients diagnosed with EC in Peking University People’s Hospital between January 2004 and December 2020. A total of 1076 patients diagnosed with EC and who underwent staging surgery were divided into training and validation cohorts according to the ratio of 2:1. Univariate and multivariate logistic regression analyses were used to determine the significant predictive factors. Results The prediction nomogram included MSR, positive peritoneal cytology, lymph vascular space invasion, endometrioid histological type, tumor size > = 2 cm, myometrial invasion > = 50%, cervical stromal invasion, and tumor grade. In the training group, the area under the curve (AUC) of the nomogram and Mayo criteria were 0.85 (95% CI: 0.81–0.90) and 0.77 (95% CI: 0.77–0.83), respectively (P

Abstract Wilkes Land and Totten Glacier (TG) in East Antarctica (EA) have been losing ice mass significantly since 1989. There is a lack of knowledge of long-term mass balance in the region which hinders the estimation of its contribution to global sea level rise. Here we show that this acceleration trend in TG has occurred since the 1960s. We reconstruct ice flow velocity fields of 1963–1989 in TG from the first-generation satellite images of ARGON and Landsat-1&4, and build a five decade-long record of ice dynamics. We find a persistent long-term ice discharge rate of 68 ± 1 Gt/y and an acceleration of 0.17 ± 0.02 Gt/y2 from 1963 to 2018, making TG the greatest contributor to global sea level rise in EA. We attribute the long-term acceleration near grounding line from 1963 to 2018 to basal melting likely induced by warm modified Circumpolar Deep Water. The speed up in shelf front during 1973–1989 was caused by a large calving front retreat. As the current trend continues, intensified monitoring in the TG region is recommended in the next decades.

Abstract Background Ferroptosis, iron-dependent cell death, is an established mechanism for cancer suppression, particularly in hepatocellular carcinoma (HCC). Sorafenib (SOR), a frontline drug for the treatment of HCC, induces ferroptosis by inhibiting the Solute Carrier family 7 member 11 (SLC7A11), with inadequate ferroptosis notably contributing to SOR resistance in tumor cells. Methods To further verify the biological targets associated with ferroptosis in HCC, an analysis of the Cancer Genome Atlas (TCGA) database was performed to find a significant co-upregulation of SLC7A11 and transferrin receptor (TFRC), Herein, cell membrane-derived transferrin nanovesicles (TF NVs) coupled with Fe3+ and encapsulated SOR (SOR@TF-Fe3+ NVs) were established to synergistically promote ferroptosis, which promoted the iron transport metabolism by TFRC/TF-Fe3+ and enhanced SOR efficacy by inhibiting the SLC7A11. Results In vivo and in vitro experiments revealed that SOR@TF-Fe3+ NVs predominantly accumulate in the liver, and specifically targeted HCC cells overexpressing TFRC. Various tests demonstrated SOR@TF-Fe3+ NVs accelerated Fe3+ absorption and transformation in HCC cells. Importantly, SOR@TF-Fe3+ NVs were more effective in promoting the accumulation of lipid peroxides (LPO), inhibiting tumor proliferation, and prolonging survival rates in HCC mouse model than SOR and TF- Fe3+ NVs alone. Conclusions The present work provides a promising therapeutic strategy for the targeted treatment of HCC. Graphical abstract

Abstract Background Acute fibrinous and organizing pneumonia (AFOP) is a rare histological interstitial pneumonia pattern characterized by patches of “fibrin balls” distributed within the alveoli and organizing pneumonia. Currently, there is no consensus on the diagnosis and treatment of this disease. Methods We present the case of a 44‐year‐old male with AFOP secondary to Mycobacterium tuberculosis. We have further reviewed organizing pneumonia (OP) and AFOP caused by tuberculosis. Conclusion Tuberculosis secondary to OP or AFOP is rare and challenging to diagnose. We need to constantly adjust the treatment plan based on the patient's symptoms, test results, and response to treatment in order to arrive at an accurate diagnosis and maximize treatment efficacy.

Background Since the Internet dependence of the supply and demand sides of health popularization is increasing, eHealth literacy has become a primary skill that chronic disease patients need to master. Objective To analyze the current situation and existing problems of online health information usage habits and eHealth literacy in middle-aged and elderly residents, and discuss the relationship between online health information usage habits and eHealth literacy, providing a reference for improving the level of eHealth literacy and developing appropriate Internet-based health popularization services for these populations. Methods From June to September 2021, a questionnaire survey was conducted among 1 061 middle-aged and elderly residents in Shanghai communities selected by multistage sampling using the General Information Questionnaire and the Chinese version of the eHealth Literacy Scale (eHEALS-C) to understand their habits of using online health information and levels of eHealth literacy. Stepwise multiple linear regression was used to assess the association of habit of using online health information and other potential candidate factors with the level of eHealth literacy. Results Altogether, 1 019 cases (96.04%) who effectively responded to the survey were included for analysis. Following health care accounts〔411 cases (40.33%) 〕was a major channel used for seeking online health information, followed by the search functionality or engines〔336 cases (32.97%) 〕, while the health apps or mini programs〔254 cases (24.93%) 〕, and online health communities〔65 cases (6.38%) 〕were less used. The online health information was less sourced from medical institutions〔397 cases (38.96%) 〕and medical workers〔187 cases (18.35%) 〕. The average total score of the eHEALS-C for the respondents was (27.62±8.57). The respondents scored lower in item 2〔 (3.36±1.27) points〕and item 6〔 (3.38±1.23) points〕of the eHEALS-C, indicating that they had low awareness of applying online health information to health problems, and low perceived skills at evaluating the online health information. Multiple linear regression analysis showed that age, participation in both basic and commercial medical insurance, using at least two channels for seeking online health information, having at least two sources of online health information, the habit of forwarding and sharing online health information, participation in collective online learning, and having an attitude of acceptance towards online health information were influencing factors of the level of eHealth literacy. Conclusion The eHealth literacy of these middle-aged and elderly residents is at a medium level, which is affected by online health information usage habits and other factors. To help them make better use of online health information and to improve their eHealth literacy, it is suggested to spread integrated authoritative information and retrieval platforms among these populations, give priority to supervision and elderly-oriented transformation of online health information platforms, and mobilize community, family, health associations, and commercial medical insurance institutions to co-deliver health-promotion services targeting these people.

Springback error is a major obstacle in L-bending sheets via cold working. Although thermal processing can effectively reduce the springback phenomenon, it is challenging to heat the sheet globally due to the influence of working conditions. Therefore, this study applied local induction heating to reduce the springback of 45 steel sheets and investigated the effects of bending parameters on springback behavior. Initially, a thermodynamic coupling model and a static model were created utilizing the VOCE hardening model and the von Mises yield criterion in the ANSYS workbench 2022 R2 software. The springback behavior and stress distribution of the sheets were then investigated under different temperatures (room temperature and 800 °C) and bending angles (15°, 30°, 45°, 60°, 75°, and 90°). Simultaneously, the experiments were performed to investigate springback behavior and guarantee the accuracy of the model. The results indicate that the springback reached a minimum value at the 45° bending angle at room temperature while increasing with the increasing bending angle under 800 °C local heating. The springback under local heating can be decreased by 75.2% and the error of the bending angle can improve by 2–7° compared with samples processed in room temperature.

The magnetic shielding device, made of high-permeability soft magnetic material, is sensitive to external influences and requires a protective steel enclosure. A steel enclosure, being strongly ferrimagnetic, can alter the surrounding magnetic field distribution, thus impacting the shielding effectiveness. This study proposes a novel analytical approach to quantify this effect, which has not been previously researched. The method develops a simplified finite element simulation model based on the structural symmetry of the steel enclosure. By using this model, this study analyzes the impact of steel structures with varying heights, widths, and remanent magnetization values. The validity of the method is confirmed through experimental tests on steel buildings. The findings offer insights into the optimal placement of magnetic shielding systems and provide theoretical guidance for designing large-scale magnetic shielding devices.

BackgroundHyperlipidemia is common in primary membranous nephropathy (PMN) patients, and tubular atrophy (TA) is an unfavorable prognostic factor. However, the correlation between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and TA is controversial. Therefore, our study aimed to investigate the association between the TG/HDL-C ratio and TA in PMN patients.MethodsWe conducted a cross-sectional study and collected data from 363 PMN patients at Shenzhen Second People’s Hospital from January 2008 to April 2023. The primary objective was to evaluate the independent correlation between the TG/HDL-C ratio and TA using binary logistic regression model. We used a generalized additive model along with smooth curve fitting and multiple sensitivity analyses to explore the relationship between these variables. Additionally, subgroup analyses were conducted to delve deeper into the results.ResultsOf the 363 PMN patients, 75 had TA (20.66%). The study population had a mean age of 46.598 ± 14.462 years, with 217 (59.78%) being male. After adjusting for sex, age, BMI, hypertension, history of diabetes, smoking, alcohol consumption, UPRO, eGFR, HB, FPG, and ALB, we found that the TG/HDL-C ratio was an independent risk factor for TA in PMN patients (OR=1.29, 95% CI: 1.04, 1.61, P=0.0213). A non-linear correlation was observed between the TG/HDL-C ratio and TA, with an inflection point at 4.25. The odds ratios (OR) on the left and right sides of this inflection point were 1.56 (95% CI: 1.17, 2.07) and 0.25 (95% CI: 0.04, 1.54), respectively. Sensitivity analysis confirmed these results. Subgroup analysis showed a consistent association between the TG/HDL-C ratio and TA, implying that factors such as gender, BMI, age, UPRO, ALB, hypertension and severe nephrotic syndrome had negligible effects on the link between the TG/HDL-C ratio and TA.ConclusionOur study demonstrates a non-linear positive correlation between the TG/HDL-C ratio and the risk of TA in PMN patients, independent of other factors. Specifically, the association is more pronounced when the ratio falls below 4.25. Based on our findings, it would be advisable to decrease the TG/HDL-C ratio below the inflection point in PMN patients as part of treatment strategies.

The nucleation and growth of topologically close-packed (TCP) phases in Ni-based single crystal superalloys (SCs) are controlled by composition, temperature, time, interface structure and stress. The formation of TCP phases causes detrimental effects on the mechanical properties of SCs. Therefore, it is crucial to study the formation mechanism and control factors of TCP phases to develop new-generation Ni-based SCs. Different alloying elements influence the TCP phase nucleation by adjusting the chemical driving force. The interface structure determined by interface energy and strain energy mainly affects the growth mechanism and morphology of the TCP phase. Various temperature determines the driving force for TCP nucleation and diffusion rates of elements during TCP phase growth. Holding time is also crucial to the growth and evolution of TCP phases. Applied stress also has an impact on the precipitation of TCP phases. Evolution between different types of TCP phases depends on the temperature, composition and crystal structure of TCP phases. TCP phases damage the mechanical properties mainly by causing stress concentration and weak interface strength. The review aims to establish a link among TCP phase formation, alloy design and microstructure from the macroscopic view to the microscopic view, providing some perspectives for future research.

The disheveled-associated antagonist of β-catenin homolog 3 (DACT3) has been recognized as a tumor suppressor in various cancers. However, the function of DACT3 on glioma malignant progression along with potential molecular mechanisms is poorly clarified. This research aimed to investigate how DACT3 contributes to suppressing the progression of glioma. In our investigation, a pronounced decrease in DACT3 expression was observed in glioma tissues. Through the overexpression of DACT3, we noted a significant suppression in the proliferation, invasion, and migration of glioma cells, while concurrently observing an increase in cell adhesion. Our exploration into the molecular mechanisms revealed that DACT3 executes its tumor-suppressive role by impeding the expression of notch 1 intracellular domain (NICD) and translocating into the nucleus by downregulating the expression of β-catenin. Consequently, this process leads to the suppression of Notch1 signaling. To summarize, our findings reveal the function of DACT3 to inhibit glioma progression via the Notch1 signaling pathway in β-catenin dependent manner. This study stands as the pioneer in examining the role of DACT3 in glioma progression and comprehensively elucidating its molecular mechanisms in glioma development. Therefore, our results suggest that DACT3 holds promise as both a prognostic factor and a potential biomarker for guiding treatment strategies in glioma patients (Graphical Abstract).

Background: The cachexia index (CXI) has been proposed as a novel biomarker of cancer cachexia. We aimed to investigate the association between CXI and survival outcomes after stereotactic radiotherapy (SRT) in patients with non-small cell lung cancer (NSCLC) and brain metastases. Methods: Data from 145 patients with NSCLC, who underwent SRT for brain metastases between April 2016 and August 2020, were retrospectively analyzed. Cachexia index was calculated as skeletal muscle index (SMI) × serum albumin level/neutrophil-to-lymphocyte ratio, whereas SMI was calculated from computed tomography images captured at the L1 level. Kaplan-Meier curves and Cox proportional hazards models were used to assess progression-free survival (PFS) and overall survival (OS). The prognostic values of CXI and other cachexia biomarkers were assessed using receiver operating characteristic (ROC) curve analysis. Results: Lower pretreatment CXI (

Abstract In this letter, a novel single parity check‐aided minimum sum (SPC‐aided MS) algorithm is proposed. A cascaded compiled code scheme is used to approximate the adaptive belief propagation (ABP) algorithm for Reed–Solomon (RS) codes using the min sum (MS) algorithm. The computational complexity is greatly reduced compared with the previous algorithm. Simulation results show that the SPC‐aided MS algorithm can achieve coding gains of up to 1.1, 0.7, and 0.6 dB for RS (255,239) code compared with the conventional ABP, LRBP, and HD‐P‐ABP algorithms, respectively under the condition of FER=10−3.

ObjectiveCoronary heart disease (CHD) is one of the major cardiovascular diseases, a common chronic disease in the elderly and a major cause of disability and death in the world. Currently, intensive care unit (ICU) patients have a high probability of concomitant coronary artery disease, and the mortality of this category of patients in the ICU is receiving increasing attention. Therefore, the aim of this study was to verify whether the composite inflammatory indicators are significantly associated with ICU mortality in ICU patients with CHD and to develop a simple personalized prediction model.Method7115 patients from the Multi-Parameter Intelligent Monitoring in Intensive Care Database IV were randomly assigned to the training cohort (n = 5692) and internal validation cohort (n = 1423), and 701 patients from the eICU Collaborative Research Database served as the external validation cohort. The association between various inflammatory indicators and ICU mortality was determined by multivariate Logistic regression analysis and Cox proportional hazards model. Subsequently, a novel predictive model for mortality in ICU patients with CHD was developed in the training cohort and performance was evaluated in the internal and external validation cohorts.ResultsVarious inflammatory indicators were demonstrated to be significantly associated with ICU mortality, 30-day ICU mortality, and 90-day ICU mortality in ICU patients with CHD by Logistic regression analysis and Cox proportional hazards model. The area under the curve of the novel predictive model for ICU mortality in ICU patients with CHD was 0.885 for the internal validation cohort and 0.726 for the external validation cohort. The calibration curve showed that the predicted probabilities of the model matched the actual observed probabilities. Furthermore, the decision curve analysis showed that the novel prediction model had a high net clinical benefit.ConclusionIn ICU patients with CHD, various inflammatory indicators were independent risk factors for ICU mortality. We constructed a novel predictive model of ICU mortality risk in ICU patients with CHD that had great potential to guide clinical decision-making.

Accurate ice flow velocity data are essential for studying the mass balance of the Antarctic ice sheet. However, there is a lack of ice velocity maps of 1960s–80s in basin-wide regions or the entire ice sheet. In this study, an enhanced hierarchical network densification approach is developed for basin-wide Antarctic velocity mapping using historical ARGON and Landsat images. The produced multiple historical velocity maps from 1963 to 1989 in the region of the Fimbul and Jelbart ice shelves, East Antarctica, achieved an accuracy better than 29 m a−1. They revealed that the ice flow velocity had no significant changes over the period. Combining the surface mass balance estimate with the ice discharge estimated from our historical velocity maps and recently published velocity maps, we estimated a positive mass balance of 8.6 ± 3.9 Gt a−1 in the study area from 1963 and 2015. Our results indicate that the region's positive mass balance, as estimated in recently published studies, has been maintained since the 1960s. It is also in concordance with the low level of mass balance from 1992 to 2017 in East Antarctica. This suggests that the study area has been stable since the 1960s.

Abstract Objective The objective of this study was to explore the clinical utility of the implementation of expanded carrier screening (ECS) in Chinese population of childbearing age. Materials and methods Based on capillary electrophoresis, a first-generation sequencing technology, a prospective screening study of carriers of 15 single-gene diseases was carried out in 327 subjects in Anhui Province, including 84 couples and 159 women of childbearing age, the disease carrier rate, types of screened pathogenic genes, and incidence of both partners carrying the same pathogenic genes were summarized and analyzed. Results In 320 people with normal phenotypes who underwent ECS for 15 genetic diseases and 7 spouses who underwent targeted gene sequencing, 65 carriers of at least one disease were detected, with a total carrier rate of 20.31% (65/320). Among the 65 carriers, 81.54% (53/65) carried one genetic variant, 16.92% (11/65) carried two genetic variants, and 1.54% (1/65) carried three genetic variants. In this study, the three diseases with the highest carrier rates were hereditary deafness (8.13%, 26/320), Wilson's disease (4.06%, 13/320), and phenylketonuria (3.13%, 10/320). One high-risk couple (1.19%, 1/84) was detected. Conclusions It has certain clinical application value to implement ECS in the population of childbearing age in China.

Abstract Exosomes, the cell-derived small extracellular vehicles, play a vital role in intracellular communication by reciprocally transporting DNA, RNA, bioactive protein, chains of glucose, and metabolites. With great potential to be developed as targeted drug carriers, cancer vaccines and noninvasive biomarkers for diagnosis, treatment response evaluation, prognosis prediction, exosomes show extensive advantages of relatively high drug loading capacity, adjustable therapeutic agents release, enhanced permeation and retention effect, striking biodegradability, excellent biocompatibility, low toxicity, etc. With the rapid progression of basic exosome research, exosome-based therapeutics are gaining increasing attention in recent years. Glioma, the standard primary central nervous system (CNS) tumor, is still up against significant challenges as current traditional therapies of surgery resection combined with radiotherapy and chemotherapy and numerous efforts into new drugs showed little clinical curative effect. The emerging immunotherapy strategy presents convincing results in many tumors and is driving researchers to exert its potential in glioma. As the crucial component of the glioma microenvironment, tumor-associated macrophages (TAMs) significantly contribute to the immunosuppressive microenvironment and strongly influence glioma progression via various signaling molecules, simultaneously providing new insight into therapeutic strategies. Exosomes would substantially assist the TAMs-centered treatment as drug delivery vehicles and liquid biopsy biomarkers. Here we review the current potential exosome-mediated immunotherapeutics targeting TAMs in glioma and conclude the recent investigation on the fundamental mechanisms of diversiform molecular signaling events by TAMs that promote glioma progression.

The difficulty of reducing the diameter of lutetium oxide (Lu2O3) continuous fibers below 50 μm not only limits the flexibility of the sample but also seriously affects their application and development in high-energy lasers. In this work, a Lu-containing precursor with high ceramic yield was used as raw material, fiberized into precursor fibers by dry spinning. The pressure-assisted water vapor pretreatment (PAWVT) method was creatively proposed, and the effect of pretreatment temperature on the ceramization behavior of the precursor fibers was studied. By regulating the decomposition behavior of organic components in the precursor, the problem of fiber pulverization during heat treatment was effectively solved, and the Lu2O3 continuous fibers with a diameter of 40 μm were obtained. Compared with the current reported results, the diameter was reduced by about 50%, successfully breaking through the diameter limitation of Lu2O3 continuous fibers. In addition, the tensile strength, elastic modulus, flexibility, and temperature resistance of Lu2O3 continuous fibers were researched for the first time. The tensile strength and elastic modulus of Lu2O3 continuous fibers were 373.23 MPa and 31.55 GPa, respectively. The as-obtained flexible Lu2O3 continuous fibers with a limit radius of curvature of 3.5–4.5 mm had a temperature resistance of not lower than 1300 ℃, which established a solid foundation for the expansion of their application form in the field of high-energy lasers.

The ratio of torque to copper loss can be increased by injecting third-harmonic current into five-phase permanent-magnetic synchronous motor (PMSM). Accurate flux linkage information is indispensable in the process of calculating third-harmonic current reference corresponding to the maximum torque/copper loss ratio. In harsh working environments, the flux linkage will deviate from the initial measured value, resulting in the deviation between the third-harmonic current and the maximum torque/copper working point. Therefore, a third-harmonic current injection control strategy of five-phase PMSM based on third-harmonic current reference online identification is proposed in this paper. The key of this strategy is to transform the steady-state voltage equations into an equation containing only voltages and currents. The transformed equation has a characteristic that it is equal to 0 when the motor operates at the maximum torque/copper loss ratio working point. Meanwhile, an observer is designed to estimate the third-harmonic current reference by using the characteristic. Finally, the observer is applied in third-harmonic current injection control of five-phase PMSM. Compared with previous methods, the proposed strategy is simple, no need of flux linkage information and not affected by the change of flux linkage. The experimental results demonstrate the robustness of the proposed strategy.

Accurate shrimp seed counting is an important task in the aquaculture and stocking shrimp seeds processes. At present, most shrimp seed counting tasks are still performed manually, which is not only time-consuming and laborious but also has low accuracy, and this counting method cannot realize modern aquaculture. Therefore, to promote the modernization of aquaculture, a portable shrimp seed counting system is proposed in this paper. The system is based on Shrimpseed_Net, a modified CSRNet convolutional neural network, and can achieve higher accuracy in shrimp seed counting. The algorithm has been successfully implemented on a smartphone, enabling automatic counting of shrimp seeds within seconds by simply taking a picture of the shrimp seeds or selecting an image from the photo album to upload to the internal algorithm. Experimental results show that after only 50 iterations, the average absolute error of the algorithm is reduced to 17.28, with an accuracy rate of 95.53%. The system can accurately count shrimp seeds in real scenarios within a short period. The shrimp seed counting system studied in this paper can be widely used in the aquaculture industry to promote its development and enable intelligent aquaculture practices.

Objective To explore the therapeutic effects of biofeedback in the treatment of faecal incontinence (FI) after surgery for anorectal malformation (ARM).Methods Clinical data were collected from paediatric patients for postoperative biofeedback due to FI caused by ARM between May 2017 and November 2021. The data included the duration of symptoms, the integrity of the anal sphincter, anorectal manometry parameters, and FI scores. These patients were divided into the low ARM group (group A) and the high ARM group (group B).Results A total of 45 paediatric patients were enrolled in the study. There were 28 cases in group A and 17 cases in group B. The differences in age, gender, and body weight were not statistically significant between the two groups (p > 0.05). The differences in the clinical indicators were also not statistically significant between the two groups at the time of the initial evaluation. The duration of symptoms was 2.21 ± 0.71 years and 4.14 ± 1.89 years in groups A and B. There were 16 cases with an intact anal sphincter in group A and only two cases with an intact anal sphincter in group B. This difference was statistically significant between the two groups (p

The influence of long-term thermal exposure on microstructure evolution and tensile behavior of a new wrought γ′-hardened Ni-base superalloy at different temperatures are investigated. The experimental superalloys are thermal exposure at 650 °C for different times up to 2300 h and tensile tests are performed in both heat treatment and thermal exposure conditions. The results show that some discontinuous carbides precipitate at the grain boundaries and spherical γ′ precipitates homogeneously disperse within the γ matrix after heat treatment. During thermal exposure, the γ′ precipitates remain spherical morphology, and the coarsening behavior of γ′ conforms to the LSW model. The tensile strength of the experimental superalloy after heat treatment generally shows a downward trend with the increase of tensile temperature while the elongation reaches a maximum at 650 °C. After thermal exposure, the tensile strength of the experimental superalloy has improved while the elongation slightly decreases.

The microstructural stability during thermal exposure at 900 °C of Ni-based single crystal superalloys with various Mo content was investigated. The coarsening of γ′ precipitates and formation of TCP (topologically close-packed) phases were discussed in detail. The LSW theory and TIDC theory were applied to study the coarsening behavior of γ′ particles, and both models fitted well with the experimental results. Increasing Mo content enhanced the partitioning behavior of alloying elements, thus increasing the lattice misfit and interfacial stress of γ′/γ phases. Additionally, Mo addition also decreased γ′ coarsening rate by retarding the diffusion process of elements. However, Mo addition significantly promoted the precipitation of TCP phases, consuming massive solution strengthener elements, such as Re, W and Mo. TCP precipitation may significantly limit the creep life at 900 °C.

Large yellow croaker (Larimichthys crocea) is a commercially important fish species worldwide, but high-density cultivation has led to serious diseases especially by Vibrio harveyi. Understanding the molecular response of large yellow croaker to V. harveyi infection is vital for the development of effective measures to combat the disease. In this study, RNA-Seq was performed on the spleen of uninfected and V. harveyi-infected large yellow croaker. A total of 7527 differentially expressed genes (DEGs) were identified, with 4413 up-regulated and 3114 down-regulated genes. Functional enrichment analysis revealed that several immune-related pathways were highlighted, including Toll-like receptors (TLRs) signaling pathway, apoptosis, p53 signaling pathway, and lysosome. In the TLRs signaling pathway, up-regulated genes included IL1b, bactericidal permeability-increasing protein, and IL12b, while down-expressed genes included tlr3 and irf3. The apoptosis pathway showed up-regulated genes such as casp6, bcl-2-like protein, and cytochrome c, and down-expressed genes such as granzyme B, sptan1, and FADD-Fas (tnfrsf6)-associated via death domain. These results suggest that V. harveyi infection induced inflammatory response and apoptotic cell death in the spleen of large yellow croaker. This study provides valuable insights into the molecular mechanisms underlying the immune response of large yellow croaker to V. harveyi infection

Volatile organic compounds (VOCs) play a significant role in influencing the flavor quality of cherry tomatoes (Solanum lycopersicum var. cerasiforme). The scarcity of systematic analysis of VOCs in cherry tomatoes can be attributed to the constraints imposed by detection technology and other contributing factors. In this study, the cherry tomato cultivar var. ‘Zheyingfen1’ was chosen due to its abundant fruit flavor. Two detection technology platforms, namely the commonly employed headspace solid-phase microextraction—gas chromatography–mass spectrometry (HS-SPME-GC-MS) and the most advanced headspace solid-phase microextraction—full two-dimensional gas chromatography–time-of-flight mass spectrometry (HS-SPME-GC×GC-TOFMS), were employed in the analysis. The VOCs of cherry tomato cultivar var. ‘Zheyingfen1’ fruits at red ripening stage were detected. A combined total of 1544 VOCs were detected using the two aforementioned techniques. Specifically, 663 VOCs were identified by through the HS-SPME-GC-MS method, 1026 VOCs were identified by through the HS-SPME-GC×GC-TOFMS, and 145 VOCs were identified by both techniques. The identification of β-ionone and (E)-2-nonenal as the principal VOCs was substantiated through the application of the relative odor activity value (rOAV) calculation and subsequent analysis. Based on the varying contribution rates of rOAV, the analysis of sensory flavor characteristics revealed that cherry tomato cultivar var. ‘Zheyingfen1’ predominantly exhibited green and fatty attributes, accompanied by elements of fresh and floral flavor characteristics. In conclusion, our study conducted a comprehensive comparison of the disparities between these two methodologies in detecting VOCs in cherry tomato fruits. Additionally, we systematically analyzed the VOC composition and sensory flavor attributes of the cherry tomato cultivar var. ‘Zheyingfen1’. This research serves as a significant point of reference for investigating the regulatory mechanisms underlying the development of volatile flavor quality in cherry tomatoes.

The silicon carbide (SiC) inverter brings great advantages to the motor drive systems of new energy vehicles; however, severe challenges to the bearings also happen. The high dc bus voltage and switching frequency of SiC inverter can increase the discharge frequency and energy when the bearing grease film collapses. As a result, the bearing suffers severe electric corrosion, and the service life of the motor drive system can be shortened. In this paper, the characteristics of common-mode voltage and bearing voltage are analyzed, firstly under space vector pulse width modulation (SVPWM). After that, the common-mode equivalent circuit model of the motor drive system is established. The frequency characteristics of bearing voltage are revealed, and the safe working area is determined. Then, the frequency characteristics of bearing voltage and current are verified based on IGBT and SiC inverters in experiments. After that, by designing a common-mode filter, the bearing voltage and current are significantly attenuated. Furthermore, the active zero state PWM (AZSPWM) is adopted to reduce the common-mode voltage from the inverter. At the same time, combined with the common-mode filter, the bearing voltage and current are further reduced. The experimental results show that the switching frequency has a decisive effect on the amplitude of bearing voltage and current. The bearing voltage can be attenuated to around half of the reference bearing voltage by using the common-mode filter and AZSPWM strategy, respectively. The combination of the common-mode filter and AZSPWM strategy can reduce the bearing voltage to around one-fourth of the reference bearing voltage, which can effectively reduce the breakdown time and discharge energy of the grease oil film.

Adenocarcinoma is the most prevalent histological subtype of colorectal cancer (CRC), with mucinous colorectal adenocarcinoma (MCA) being a unique form. Although the mucinous subtype is known to elicit a worse response to chemotherapy and immunotherapy than the nonmucinous subtype, its pathogenesis remains poorly understood. Neurogenic locus notch homolog protein 3 (NOTCH3), a member of the NOTCH subfamilies, is highly expressed in CRC. In the past three decades, many studies have been performed evaluating the biological role of NOTCH3 in CRC. However, the precise activities of NOTCH3 in MCA, as well as the mechanisms involved in its transcriptional control, are yet to be elucidated. Our finding showed that the critical transcriptional regulatory factor transcription activator BRG1 (SMARCA4) directly binds to the intracellular domain of NOTCH3 to control transcriptional regulation. Moreover, RNA‐sequencing results indicated a common targeting effect on the transcriptional activity of mucin‐5AC (MUC5AC) and mucin‐2 (MUC2) in CRC cells by NOTCH3 and SMARCA4. Furthermore, NOTCH3 was found to control the expressions of MUC5AC and MUC2 in a SMARCA4‐dependent manner. MUC5AC and MUC2, which encode two secreted mucins, are located on chromosome 11p15.5, and are linked to the development of MCA. This finding suggests that the interaction between NOTCH3 and SMARCA4 may be involved in MCA differentiation by jointly targeting MUC5AC and MUC2. Patients with MCA are often treated in accordance with CRC guidelines. Determining the relationship between NOTCH3 and SMARCA4 by demonstrating their interactions in the pathophysiology of MCA could provide novel therapeutic targets and help identify potential prognostic markers for MCA.

Although antibiotics are one of the most significant factors contributing to the propagation of antibiotic resistance genes (ARGs), studies on the dose-response relationship at sub-lethal concentrations of antibiotics remain scarce, despite their importance for assessing the risks of antibiotics in the environment. In this study, we constructed a series of microcosms to investigate the propagation of intracellular (iARGs) and extracellular (eARGs) ARGs in both water and biofilms when exposed to antibiotics at various concentrations (1–100 μg/L) and frequencies. Results showed that eARGs were more abundant than iARGs in water, while iARGs were the dominant ARGs form in biofilms. eARGs showed differentiated dose-response relationships from iARGs. The abundance of iARGs increased with the concentration of antibiotics as enhanced selective pressure overcame the metabolic burden of antibiotic-resistant bacteria carrying ARGs. However, the abundance of eARGs decreased with increasing antibiotic concentrations because less ARGs were secreted from bacterial hosts at higher concentrations (100 μg/L). Furthermore, combined exposure to two antibiotics (tetracycline & imipenem) showed a synergistic effect on the propagation of iARGs, but an antagonistic effect on the propagation of eARGs compared to exposure to a single antibiotic. When exposed to antibiotic at a fixed total dose, one-time dosing (1 time/10 d) favored the propagation of iARGs, while fractional dosing (5 times /10 d) favored the propagation of eARGs. This study sheds light on the propagation of antibiotic resistance in the environment and can help in assessing the risks associated with the use of antibiotics.

ObjectiveThis study aimed to explore the relationship between the plasma metabolites of adolescent obesity and hypertension and whether metabolite alterations had a mediating effort between adolescent obesity and hypertension.MethodsWe applied untargeted ultra-performance liquid chromatography–mass spectrometry (UPLC-MS) to detect the plasma metabolomic profiles of 105 adolescents. All participants were selected randomly based on a previous cross-sectional study. An orthogonal partial least squares- discriminant analysis (OPLS-DA), followed by univariate statistics and enrichment analysis, was used to identify differential metabolites. Using logistic regression for variable selection, an obesity-related metabolite score (OMS, OMS=∑k=1nβnmetabolite n) was constructed from the metabolites identified, and hypertension risk was estimated.ResultsIn our study, based on P< 0.05, variable importance in projection (VIP) > 1.0, and impact value > 0.1, we identified a total of 12 differential metabolites. Significantly altered metabolic pathways were the sphingolipid metabolism, purine metabolism, pyrimidine metabolism, phospholipid metabolism, steroid hormone biosynthesis, tryptophan, tyrosine, and phenylalanine biosynthesis. The logistic regression selection resulted in a four-metabolite score (thymidine, sphingomyelin (SM) d40:1, 4-hydroxyestradiol, and L-lysinamide), which was positively associated with hypertension risk (odds ratio: 7.79; 95% confidence interval: 2.13, 28.47; for the quintile 4 compared with quartile 1 of OMS) after multivariable adjustment.ConclusionsThe OMS constructed from four differential metabolites was used to predict the risk of hypertension in adolescents. These findings could provide sensitive biomarkers for the early recognition of hypertension in adolescents with obesity.

BackgroundThe study aims to explore the relationship between obesity and serum uric acid in adolescents by combining body mass index and waist height ratio.Methods475 adolescents in our study were classified as normal weight without central obesity (NW), normal weight but central obesity (NWCO), overweight or obesity without central obesity (OB) and overweight or obesity with central obesity (OBCO). Odds ratios (OR) and 95% confidence intervals (CI) for hyperuricemia were calculated using a logistic regression model. The dose-response association between obesity indicators and serum uric acid were explored by restricted cubic spline model.ResultsThe highest serum uric acid level and the OR for hyperuricemia were found in the OBCO group, regardless of sex. After controlling for waist height ratio, the risk of hyperuricemia increased with increasing body mass index in boys and girls. The restricted cubic spline model showed that boys had higher ORs for hyperuricemia at the 25th and 75th percentiles of body mass index than for waist height ratio and girls had a higher OR for hyperuricemia than waist height ratio at the 25th percentile of body mass index.ConclusionsHyperuricemia in adolescence was not only associated with the overweight or obesity in BMI, but with the combination of overweight or obesity in BMI and central obesity in WHtR. However, in boys and girls, the increased risk of hyperuricemia associated with elevated body mass index was significantly better than that of waist height ratio.

Genome-wide association studies have revealed that the regulation of gene expression bridges genetic variants and complex phenotypes. Profiling of the bulk transcriptome coupled with linkage analysis (expression quantitative trait locus (eQTL) mapping) has advanced our understanding of the relationship between genetic variants and gene regulation in the context of complex phenotypes. However, bulk transcriptomics has inherited limitations as the regulation of gene expression tends to be cell-type-specific. The advent of single-cell RNA-seq technology now enables the identification of the cell-type-specific regulation of gene expression through a single-cell eQTL (sc-eQTL). In this review, we first provide an overview of sc-eQTL studies, including data processing and the mapping procedure of the sc-eQTL. We then discuss the benefits and limitations of sc-eQTL analyses. Finally, we present an overview of the current and future applications of sc-eQTL discoveries.

Immune cell infiltration occurs in the tumor microenvironment (TME) and influences cancer progression through interaction with tumor cells. Runt-related transcription factors (RUNXs), RUNX1-3, are the master regulators of development and differentiation and are all important to the development of immune cells. However, the role of RUNXs in the immune cells of TME remains unclear. In this study, we first used online related databases and related LGG data from TCGA and CGGA to conduct bioinformatics analysis, which confirmed that RUNXs were significantly and positively correlated with immune infiltration in multiple tumors, especially in low-grade glioma (LGG) and there was the highest correlation between RUNXs and the progress and prognosis of LGG. Furthermore, the functional enrichment analysis revealed that RUNXs might be involved in the inflammatory and immune responses of the biological processes, and RUNXs were tightly associated with the multiple immune checkpoint molecules. Subsequent results confirmed that RUNX1, as an independent prognostic factor for LGG, may target interferon-gamma receptor 2 (IFNGR2) to regulate glioma cell proliferation, invasion, and migration. Besides, we also found that the expression levels of RUNX1 and IFNGR2 were significantly reduced, and their correlation was enhanced in the IDH-mutant subtype. Patients with a high expression of RUNX1 and/or IFNGR2 (HH/H) in the IDH-mutant subtype showed poorer prognosis and significantly increased infiltration of M2 macrophages. This finding implied the possible key role of RUNX1 in the differentiation of IDH mutant subtypes as well as in the formation of tumor microenvironment (TME) infiltration signatures by monitoring IFNGR2.

This paper shows that given 0 < p < 3 and a complex Borel measure µ on the unit disk 𝔻 the inhomogeneous Cauchy-Riemann ̄∂-equation

Abstract Angiostatin, an endogenous angiogenesis inhibitor generated by the proteolytic cleavage of plasminogen, was recently reported to contribute to the development of Alzheimer’s disease (AD). However, whether there are pathological changes in angiostatin levels in individuals with AD dementia is unclear, and whether plasma angiostatin has a relationship with major AD pathological processes and cognitive impairment remains unknown. To examine plasma angiostatin levels in patients with AD dementia and investigate the associations of angiostatin with blood and cerebrospinal fluid (CSF) AD biomarkers, we conducted a cross-sectional study including 35 cognitively normal control (CN) subjects and 59 PiB-PET-positive AD dementia patients. We found that plasma angiostatin levels were decreased in AD dementia patients compared to CN subjects. Plasma angiostatin levels were negatively correlated with plasma Aβ42 and Aβ40 levels in AD dementia patients and positively correlated with CSF total tau (t-tau) levels and t-tau/Aβ42 in AD dementia patients with APOE-ε4. In addition, plasma angiostatin levels had the potential to distinguish AD from CN. These findings suggest a link between angiostatin and AD pathogenesis and imply that angiostatin might be a potential diagnostic biomarker for AD.

Abstract A therapeutic option for advanced non‐small‐cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitor (TKI) resistance is a clinical challenge. The clinical outcomes of pembrolizumab in those patients is inconclusive. Cytokine release syndrome (CRS) is a rarely reported immune‐related adverse event in the field of immune checkpoint inhibitors therapy, raising challenges given the paucity of data with such presentations. We present the unique case of a 67‐year‐old female with advanced EGFR‐mutated NSCLC who successfully responded to pembrolizumab after EGFR‐TKI resistance. However, the patient developed CRS after pembrolizumab initiation and presented with fever, rash, hypotension, hypoxemia, tachycardia, and multiple organ dysfunction. Blood tests showed elevated levels of peripheral CD8+ T cells, C‐reactive protein, and tumor necrosis factor‐α. The symptoms rapidly improved after corticosteroid initiation. Based on the present case, we propose that pembrolizumab might be a potential salvage therapy for patients with advanced EGFR‐mutated NSCLC after EGFR‐TKI resistance; CRS would be a sign of the antitumor effect of PD‐1 inhibitors in those patients. However, CRS can be a fatal adverse effect and clinicians must remain vigilant for the rare toxicities to make prompt diagnosis and treatment.

This study aims to explore the impact of dual learning on preschool teachers' thriving at work and creative performance, and whether preschool teachers' thriving at work acts as a mediating factor in the relationship between dual learning and teachers' creative work. The participants were preschool teachers from Taiwan. Convenience sampling was used, resulting in a sample size of 388 people. The study results found that preschool teachers' dual learning, which includes both exploitative and exploratory learning, can improve the novelty and usefulness of their work and creativity. Furthermore, the study found that preschool teachers' thriving at work mediates the relationship between dual learning and creativity. This study also discovered that dual learning should combine and complement both exploitative and exploratory learning to achieve balance and the most significant effect. Therefore, it is essential to first help preschool teachers engage in both exploitative and exploratory learning. Schools and kindergartens can also provide relevant courses to help teachers combine these two learning methods. By integrating and complementing their advantages and disadvantages, a balance in learning can be achieved, thereby promoting teachers' creativity in their work.

Black Carbon (BC), the second-largest contributor to global warming, has detrimental effects on human health and the environment. However, the accurate quantification of BC poses a significant challenge, impeding the comprehensive assessment of its impacts. Therefore, this paper aims to critically review three quantitative methods for measuring BC: Thermal Optical Analysis (TOA), the Optical Method, and Laser-Induced Incandescence (LII). The determination principles, available commercial instruments, sources of deviation, and correction approaches associated with these techniques are systematically discussed. By synthesizing and comparing the quantitative results reported in previous studies, this paper aims to elucidate the underlying relationships and fundamental disparities among Elemental Carbon (EC), Equivalent Black Carbon (eBC), and Refractory Black Carbon (rBC). Finally, based on the current advancements in BC quantification, recommendations are proposed to guide future research directions.

Sucrose, the primary carbon transport mode and vital carbohydrate for higher plants, significantly impacts plant growth, development, yield, and quality formation. Its metabolism involves three key steps: synthesis, transport, and degradation. Two genome triplication events have occurred in Solanaceae, which have resulted in massive gene loss. In this study, a total of 48 and 65 genes from seven sucrose metabolism gene families in Vitis vinifera and Solanum lycopersicum were identified, respectively. The number of members comprising the different gene families varied widely. And there were significant variations in the pattern of gene duplication and loss in the tomato following two WGD events. Tandem duplication is a major factor in the expansion of the SWEET and Acid INV gene families. All the genes are irregularly distributed on the chromosomes, with the majority of the genes showing collinearity with the grape, particularly the CIN family. And the seven gene families were subjected to a purifying selection. The expression patterns of the different gene families exhibited notable variations. This study presents basic information about the sucrose metabolism genes in the tomato and grape, and paves the way for further investigations into the impact of SCT events on the phylogeny, gene retention duplication, and function of sucrose metabolism gene families in the tomato or Solanaceae, and the adaptive evolution of the tomato.

Singapore grouper iridovirus (SGIV) is a virus with high fatality rate in the grouper culture industry. The outbreak of SGIV is often accompanied by a large number of grouper deaths, which has a great impact on the economy. Therefore, it is of great significance to find effective drugs against SGIV. It has been reported that edaravone is a broad-spectrum antiviral drug, most widely used clinically in recent years, but no report has been found exploring the effect of edaravone on SGIV infections. In this study, we evaluated the antiviral effect of edaravone against SGIV, and the anti-SGIV mechanism of edaravone was also explored. It was found that the safe concentration of edaravone on grouper spleen (GS) cells was 50 µg/mL, and it possessed antiviral activity against SGIV infection in a dose-dependent manner. Furthermore, edaravone could significantly disrupt SGIV particles and interference with SGIV binding to host cells, as well as SGIV replication in host cells. However, edaravone was not effective during the SGIV invasion into host cells. This study was the first time that it was determined that edaravone could exert antiviral effects in response to SGIV infection by directly interfering with the processes of SGIV infecting cells, aiming to provide a theoretical basis for the control of grouper virus disease.

The active ingredients in lingonberry leaves and their beneficial properties to the human body have been well confirmed. In order to improve the stability and antioxidant activity of the active ingredients in lingonberry leaves, the response surface optimization method was used to prepare an oil-in-water nanoemulsion of polyphenol extract from lingonberry leaves. The active components in the extract were analyzed by ultra-performance liquid chromatography with triple quadrupole mass spectrometry (UPLC-TQ-MS), and bioactive compounds such as apigenin, sorbitol, and hesperidin were mainly found. Nanoemulsion droplets of 120 nm in diameter were prepared using ultrasonic emulsification. The optimal nanoemulsion formulation was determined through rigorous testing, and it was determined to be 10% (w/w) lingonberry extract and 20% (w/w) medium chain triglyceride (MCT). Additionally, a surfactant mixture was used, which combined soy protein isolate (SPI) and whey protein isolate (WPI) at 4% (w/w). The preparation method utilized ultrasonic emulsification, applying an ultrasonic power of 360 W for a duration of 300 s. The antioxidant activity (DPPH inhibition rate, ABTS inhibition rate and total reducing power) of the lingonberry nanoemulsion was significantly higher than that of the lingonberry polyphenol (LBP) extract. The nanoemulsion prepared using the optimal formulation had an entrapping efficiency of 73.25% ± 0.73% and a diameter of 114.52 ± 0.015 nm, with a satisfactory particle size of nanoscale and a PDI of 0.119 ± 0.065, demonstrating good stability of the emulsion.

Objectives This network meta-analysis aimed to compare the efficacy and safety of intravenous (IV) hydralazine, oral nifedipine, and IV labetalol with different dosage regimens in the treatment of severe hypertension during pregnancy. Methods A comprehensive literature search was performed on PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) exploring the effects of hydralazine, nifedipine, and labetalol in the treatment of severe hypertension during pregnancy. Results A total of 21 RCTs with 2183 patients comparing 7 regimens (oral nifedipine 50,60,90 mg; hydralazine 15,25 mg; and labetalol 220,300 mg) were identified. Compared with IV labetalol 300 mg, nifedipine 50,60, and 90 mg significantly improved the successful treatment rate of severe hypertension during pregnancy, nifedipine 50 and 90 mg and IV hydralazine 25 mg required significantly fewer doses to achieve target blood pressure (BP), and nifedipine 50 mg took significantly shorter time to achieve target BP. Subgroup analysis showed that only nifedipine 50 mg tablets, not capsules, required a significantly shorter time and fewer doses to achieve target BP than IV labetalol 300 mg. Moreover, nifedipine 60,90 mg showed superior effectiveness than IV hydralazine 15,25 mg in the successful treatment rate of severe hypertension during pregnancy. SUCRA analysis suggested that nifedipine 50,60,90 mg as the better regimens with the lower rates of overall ADR and neonatal complications. Conclusion These findings demonstrated the superiority of oral nifedipine 50,60,90 mg, especially oral nifedipine 50 mg tablets, in the treatment of severe hypertension during pregnancy than IV labetalol 300 mg, while oral nifedipine 60,90 mg also showed superiority in the successful treatment rate of severe hypertension during pregnancy than IV hydralazine 15,25 mg. However, the limitations of the underlying data indicate that future large-scale and rigorous RCTs are needed to confirm such findings.

Abstract Background Temozolomide is applied as the standard chemotherapy agent in patients with glioblastoma (GBM) after surgery. However, the benefit of this treatment for patients is limited by the invasive growth of gliomas and drug resistance. There are indications from fundamental experimental and retrospective studies that levetiracetam has the potential to improve the survival rate of patients with GBM. However, it has yet to be determined whether the combination of temozolomide and levetiracetam is more effective than standard temozolomide chemotherapy. Therefore, we designed a randomized clinical trial to investigate the therapeutic effect of the new combined regime for treating GBM. Methods/design This is a double-blind and randomized clinical trial conducted in a single center. One hundred forty-two patients will be recruited and screened for the inclusion and exclusion criteria. Then, eligible participants will be randomly assigned to an experimental group or a control group in a 1:1 ratio. Based on the administration of radiation therapy (RT), participants in the experimental group will be prescribed levetiracetam plus temozolomide chemotherapy for 34 weeks while participants in the control group will receive placebo tablets plus temozolomide for the same duration. A 3-year follow-up will be conducted on all patients after intervention. Accordingly, the primary outcome will be progression-free survival (PFS). The secondary endpoints include overall survival (OS), the Karnofsky Performance Status (KPS), the objective response rate (ORR), and adverse event incidence. Discussion It is expected that the results of this trial will provide high-level evidence regarding the clinical benefits of levetiracetam and temozolomide combined in the treatment of GBM. Trial registration Chinese Clinical Trial Registry, ChiCTR2100049941 . Registered on 14 August 2021

Skin microbiota play an important role in skin barrier function and are associated with host health. The study of the skin microbiota is beneficial for managing disease with skin microbiota. Bullfrog (Rana catesbeiana) is an important cultured animal. Bacterial diseases like red leg syndrome (RLS) often occur in bullfrog cultured and cause huge economic losses around the world. However, the appearance of RLS is unknown. Here we compare the skin microbiota of RLS bullfrog and healthy bullfrog by 16 S rRNA microbiome profiles. The bacterial community diversity of bullfrog skin was significantly different between RLS and healthy group. Proteobacteria, Bacteroidota, Firmicutes were the most abundant phyla in bullfrog skin. Compared with healthy bullfrogs, RLS bullfrogs had high abundance of Acinetobacter, Chryseobacterium, Elizabethkingia, Flavobacterium and Streptococcus in skin microbiota, but the relative abundance of Cetobacterium, Bacteroides and Shewanella was overrepresented in the RLS bullfrog. The Tax4Fun function prediction showed that the relative abundance of genes associated with Nucleotide metabolism, Translation, Nucleotide metabolism, Translation, Glycan biosynthesis and metabolism exhibited was significantly higher in RLS bullfrogs. The results suggested that the RLS significantly changed the composition and predictive function of the skin bacterial community in cultured bullfrogs. This study is the first to report on the relationship between skin microbiota and red leg syndrome of bullfrog, which can expand our understanding of bacterial communities in bullfrog farming from the perspective of microbial ecology and help prevent and manage RLS in bullfrog farming.

ObjectiveTo test the feasibility and reliability of intracranial electrophysiological recordings in an acute status epilepticus model on laboratory swine.MethodIntrahippocampal injection of kainic acid (KA) was performed on 17 male Bama pigs (Sus scrofa domestica) weighing between 25 and 35 kg. Two stereoelectroencephalography (SEEG) electrodes with a total of 16 channels were implanted bilaterally along the sensorimotor cortex to the hippocampus. Brain electrical activity was recorded 2 h daily for 9–28 days. Three KA dosages were tested to evaluate the quantities capable of evoking status epilepticus. Local field potentials (LFPs) were recorded and compared before and after the KA injection. We quantified the epileptic patterns, including the interictal spikes, seizures, and high-frequency oscillations (HFOs), up to 4 weeks after the KA injection. Test–retest reliability using intraclass correlation coefficients (ICCs) were performed on interictal HFO rates to evaluate the recording stability of this model.ResultsThe KA dosage test suggested that a 10 μl (1.0 μg/μl) intrahippocampal injection could successfully evoke status epilepticus lasting from 4 to 12 h. At this dosage, eight pigs (50% of total) had prolonged epileptic events (tonic-chronic seizures + interictal spikes n = 5, interictal spikes alone n = 3) in the later 4 weeks of the video-SEEG recording period. Four pigs (25% of total) had no epileptic activities, and another four (25%) had lost the cap or did not complete the experiments. Animals that showed epileptiform events were grouped as E + (n = 8) and the four animals showing no signs of epileptic events were grouped as E– (n = 4). A total of 46 electrophysiological seizures were captured in the 4-week post-KA period from 4 E + animals, with the earliest onset on day 9. The seizure durations ranged from 12 to 45 s. A significant increase of hippocampal HFOs rate (num/min) was observed in the E+ group during the post-KA period (weeks 1, 2,4, p