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Abstract Diabetic kidney disease (DKD) is a prevalent microvascular complication of diabetes mellitus and a primary cause of end-stage renal disease (ESRD). Increasing studies suggest that immune cells are involved in regulating renal inflammation, which contributes to the progression of DKD. Compared with conventional methods, single-cell sequencing technology is more developed technique that has advantages in resolving cellular heterogeneity, parallel multi-omics studies, and discovering new cell types. ScRNA-seq helps researchers to analyze specifically gene expressions, signaling pathways, intercellular communication as well as their regulations in various immune cells of kidney biopsy and urine samples. It is still challenging to investigate the function of each cell type in the pathophysiology of kidney due to its complex and heterogeneous structure and function. Here, we discuss the application of single-cell transcriptomics in the field of DKD and highlight several recent studies that explore the important role of immune cells including macrophage, T cells, B cells etc. in DKD through scRNA-seq analyses. Through combing the researches of scRNA-seq on immune cells in DKD, this review provides novel perspectives on the pathogenesis and immune therapeutic strategy for DKD.

Abstract Background Coronary artery calcification (CAC) is a common risk factor of cardiovascular disease. Although triglyceride glucose (TYG) index and high-density lipoprotein cholesterol (HDL-c) are both associated with CAC, no study has evaluated the correlation between the TYG/HDL-c ratio and CAC. In the present study, we investigated the relationships between CAC and the TYG index and the TYG/HDL-c ratio. Methods A total of 9585 participants who underwent computed tomography (CT) screening for lung cancer from 2018 to 2020 were included in this cross-sectional study. Demographic data, laboratory test data and medical history data were collected from medical records. TYG = Ln[fasting glucose (mg/dL)×fasting TG (mg/dL/2]. The triglyceride glucose-HDL-c ratio was calculated as TYG/HDL-c. CAC was evaluated on chest CT images. Multivariate logistic regression analysis and restricted cubic splines were used to determine the relationships among the TYG index, TYG/HDL-c ratio and risk of CAC. The receiver operating characteristic (ROC) curve was used to evaluate the performance of the TYG index and TYG/HDL-c ratio in identifying CACs in individuals aged 60 years and above. Results CAC was detected in 2515 of 9585 participants (mean age 51.8 ± 15.5 years, 61.2% men). The prevalence of CAC was significantly greater in participants with a high TYG/HDL-c ratio (32.6% in the fourth quartile vs. 19.1% in the first quartile, p

Abstract Although observational clinical studies have established an association between Intestinal Diseases (IDS) and Anal Diseases (ADS), the causal relationship is still not fully understood due to the limitations of observational studies. Genome-wide association study (GWAS) statistical data for IDS and ADS were obtained from publicly available databases. To assess the causal effects of IDS on ADS, we conducted Mendelian randomization analysis. The inverse variance weighted method indicated that Inflammatory bowel disease (IBD) had a significant causal relationship with three kinds of ADS: Anorectal abscess (ARB), Haemorrhoidal disease (HEM), and Fissure and fistula of anal and rectal regions (FISSANAL). Crohn’s disease (CD) and Ulcerative colitis (UC) also showed significant causal effects with three ADS: ARB, HEM, and FISSANAL. Furthermore, a potential link between CD and BNA(Benign neoplasm of anus and anal canal), Irritable bowel syndrome (IBS) and HEM, Colorectal cancer (CRC) and BNA, and Celiac disease and MNA (Malignant neoplasm of anus and anal canal) was observed. This comprehensive MR analysis highlight the significant and increased risk of common Anal Diseases (ARB, FISSANAL, and HEM) in patients with IBD, CD, and UC. Additionally, potential positive causal associations emerged between IBS and HEM, CRC and BNA, as well as between celiac disease and MNA.

Lung cancer (LC) is considered to have the highest mortality rate around the world. Because there are no early diagnostic signs or efficient clinical alternatives, distal metastasis and increasing numbers of recurrences are a challenge in the clinical management of LC. Long non-coding RNAs (lncRNAs) have recently been recognized as a critical regulator involved in the progression and treatment response to LC. The Wnt/β-catenin pathway has been shown to influence LC occurrence and progress. Therefore, discovering connections between Wnt signaling pathway and lncRNAs may offer new therapeutic targets for improving LC treatment and management. In this review, the purpose of this article is to present possible therapeutic approaches by reviewing particular relationships, key processes, and molecules associated to the beginning and development of LC.

Excessive inflammation caused by bacterial infection is the primary cause of implant failure. Antibiotic treatment often fails to prevent peri-implant infection and may induce unexpected drug resistance. Herein, a non-antibiotic strategy based on the synergy of silver ion release and macrophage reprogramming is proposed for preventing infection and bacteria-induced inflammation suppression by the organic-inorganic hybridization of silver nanoparticle (AgNP) and quercetin (Que) into a polydopamine (PDA)-based coating on the 3D framework of porous titanium (SQPdFT). Once the planktonic bacteria (e.g., Escherichia coli, Staphylococcus aureus) reach the surface of SQPdFT, released Que disrupts the bacterial membrane. Then, AgNP can penetrate the invading bacterium and kill them, which further inhibits the biofilm formation. Simultaneously, released Que can regulate macrophage polarization homeostasis via the peroxisome proliferators-activated receptors gamma (PPARγ)-mediated nuclear factor kappa-B (NF-κB) pathway, thereby terminating excessive inflammatory responses. These advantages facilitate the adhesion and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), concomitantly suppressing osteoclast maturation, and eventually conferring superior mechanical stability to SQPdFT within the medullary cavity. In summary, owing to its excellent antibacterial effect, immune remodeling function, and pro-osteointegration ability, SQPdFT is a promising protective coating for titanium-based implants used in orthopedic replacement surgery.

Abstract Exposure to certain heavy metals has been demonstrated to be associated with a higher risk of preterm birth (PTB). However, studies focused on the effects of other metal mixtures were limited. A nested case‒control study enrolling 94 PTB cases and 282 controls was conducted. Metallic elements were detected in maternal plasma collected in the first trimester using inductively coupled plasma‒mass spectrometry. The effect of maternal exposure on the risk of PTB was investigated using logistic regression, least absolute shrinkage and selection operator, restricted cubic spline (RCS), quantile g computation (QGC) and Bayesian kernel machine regression (BKMR). Vanadium (V) and arsenic (As) were positively associated with PTB risk in the logistic model, and V remains positively associated in the multi‐exposure logistic model. QGC analysis determined V (69.42%) and nickel (Ni) (70.30%) as the maximum positive and negative contributors to the PTB risk, respectively. BKMR models further demonstrated a positive relationship between the exposure levels of the mixtures and PTB risk, and V was identified as the most important independent variable among the elements. RCS analysis showed an inverted U‐shape effect of V and gestational age, and plasma V more than 2.18 μg/L was considered a risk factor for shortened gestation length. Exposure to metallic elements mixtures consisting of V, As, cobalt, Ni, chromium and manganese in the first trimester was associated with an increased risk of PTB, and V was considered the most important factor in the mixtures in promoting the incidence of PTB.

The need to combine various metals in light-weight constructions requires the development of coatings that prevent galvanic corrosion. Layered double hydroxides (LDHs) can be an example of such coatings, which were previously successfully obtained in situ on individual materials. In addition, the possibility of LDH growth (including LDH growth in the presence of chelating agents) on the surface of plasma electrolytic oxidation (PEO)-coated metals was previously shown. This PEO ​+ ​LDH combination could improve both corrosion and mechanical characteristics of the system. The possibility of LDHs formation in situ on the surface of PEO-coated friction stir welded (FSW) magnesium-aluminum materials (AZ31/AA5754 system was selected as a model one) was demonstrated in the presence of 1,3-diamino-2-hydroxypropane-N,N,N’,N’-tetraacetic acid (DHPTA) as a chelating agent, which was selected based on analysis of respective metal-ligand compounds stability. LDHs growth was achieved under ambient pressure without addition of carbonates in the electrolyte. The effectiveness of the resulting coating is shown both for corrosion resistance and hardness.

Abstract Blue corona discharges are often generated in thunderclouds penetrating into the stratosphere and are the optical manifestation of narrow bipolar events (NBEs) observed in radio signals. While their production appears to depend on convection, the cause and nature of such discharges are not well known. Here we show the observations by a lightning detection array of unusual amounts of 982 NBEs during a tropical storm on the coastline of China. NBEs of negative polarity are predominantly observed at the cloud top reaching the stratosphere, and positive NBEs are primarily at lower altitudes. We find that the dominant polarity changes with the typical time of development of thunderstorm cells, suggesting that the polarity depends on the phase of the storm cells. Furthermore, we find that the lightning jump of negative NBEs is associated with above-anvil cirrus plumes of ice crystals and water vapor in the lower stratosphere. We propose that variations in updrafts induce changes in the altitude and charge concentrations of the cloud layers, which lead to the polarity transition. Our results have implications for studies of the chemical perturbations of greenhouse gas concentrations by corona discharges at the tropopause.

Abstract Objective To conduct a bibliometric analysis of the prospects and obstacles associated with dual- and multi-energy CT in thoracic disease, emphasizing its current standing, advantages, and areas requiring attention. Methods The Web of Science Core Collection was queried for relevant publications in dual- and multi-energy CT and thoracic applications without a limit on publication date or language. The Bibliometrix packages, VOSviewer, and CiteSpace were used for data analysis. Bibliometric techniques utilized were co-authorship analyses, trend topics, thematic map analyses, thematic evolution analyses, source’s production over time, corresponding author’s countries, and a treemap of authors’ keywords. Results A total of 1992 publications and 7200 authors from 313 different sources were examined in this study. The first available document was published in November 1982, and the most cited article was cited 1200 times. Siemens AG in Germany emerged as the most prominent author affiliation, with a total of 221 published articles. The most represented scientific journals were the “European Radiology” (181 articles, h-index = 46), followed by the “European Journal of Radiology” (148 articles, h-index = 34). Most of the papers were from Germany, the USA, or China. Both the keyword and topic analyses showed the history of dual- and multi-energy CT and the evolution of its application hotspots in the chest. Conclusion Our study illustrates the latest advances in dual- and multi-energy CT and its increasingly prominent applications in the chest, especially in lung parenchymal diseases and coronary artery diseases. Photon-counting CT and artificial intelligence will be the emerging hot technologies that continue to develop in the future. Critical relevance statement This study aims to provide valuable insights into energy-based imaging in chest disease, validating the clinical application of multi-energy CT together with photon-counting CT and effectively increasing utilization in clinical practice. Key Points Bibliometric analysis is fundamental to understanding the current and future state of dual- and multi-energy CT. Research trends and leading topics included coronary artery disease, pulmonary embolism, and radiation dose. All analyses indicate a growing interest in the use of energy-based imaging techniques for thoracic applications. Graphical Abstract

With the growing demand for weight reduction, the application of joint lightweight structural materials is increasing. Magnesium alloys feature low density, high specific strength and good formability, offering significant advantages for fuel efficiency and load capacity. Combined with Ti, a dissimilar Ti/Mg composite material provides great flexibility combining the properties of each material. However, because of the great differences in chemical and electrochemical properties between Mg and Ti, it is imperative to address the galvanic corrosion problem of such dissimilar Ti/Mg components. This work presents an investigation of the PEO processing of sintered Ti/Mg0.6Ca couples, aiming to improve the corrosion resistance of such dissimilar alloy combinations using a phosphate-aluminate electrolyte. The results show that uniform and continuous coatings can be formed on the dissimilar Ti/Mg0.6Ca couple. The coating mainly contains MgO and MgAl2O4 on the Mg0.6Ca side, and Al2TiO5 is the dominant phase on the Ti side. The work also took advantage of synchrotron X-ray computed tomography (CT) scanning to achieve 3D reconstruction of the coating morphology, which can be a fast method to assess the porosity and compactness of the coating and further predict the coating corrosion resistance. The coating effectively improved the corrosion resistance of the dissimilar Ti/Mg0.6Ca couple.

Abstract Background The cold tolerance of rice is closely related to its production and geographic distribution. The identification of cold tolerance-related genes is of important significance for developing cold-tolerant rice. Dongxiang wild rice (Oryza rufipogon Griff.) (DXWR) is well-adapted to the cold climate of northernmost-latitude habitats ever found in the world, and is one of the most valuable rice germplasms for cold tolerance improvement. Results Transcriptome analysis revealed genes differentially expressed between Xieqingzao B (XB; a cold sensitive variety) and 19H19 (derived from an interspecific cross between DXWR and XB) in the room temperature (RT), low temperature (LT), and recovery treatments. The results demonstrated that chloroplast genes might be involved in the regulation of cold tolerance in rice. A high-resolution SNP genetic map was constructed using 120 BC5F2 lines derived from a cross between 19H19 and XB based on the genotyping-by-sequencing (GBS) technique. Two quantitative trait loci (QTLs) for cold tolerance at the early seedling stage (CTS), qCTS12 and qCTS8, were detected. Moreover, a total of 112 candidate genes associated with cold tolerance were identified based on bulked segregant analysis sequencing (BSA-seq). These candidate genes were divided into eight functional categories, and the expression trend of candidate genes related to ‘oxidation-reduction process’ and ‘response to stress’ differed between XB and 19H19 in the RT, LT and recovery treatments. Among these candidate genes, the expression level of LOC_Os12g18729 in 19H19 (related to ‘response to stress’) decreased in the LT treatment but restored and enhanced during the recovery treatment whereas the expression level of LOC_Os12g18729 in XB declined during recovery treatment. Additionally, XB contained a 42-bp deletion in the third exon of LOC_Os12g18729, and the genotype of BC5F2 individuals with a survival percentage (SP) lower than 15% was consistent with that of XB. Weighted gene coexpression network analysis (WGCNA) and modular regulatory network learning with per gene information (MERLIN) algorithm revealed a gene interaction/coexpression network regulating cold tolerance in rice. In the network, differentially expressed genes (DEGs) related to ‘oxidation-reduction process’, ‘response to stress’ and ‘protein phosphorylation’ interacted with LOC_Os12g18729. Moreover, the knockout mutant of LOC_Os12g18729 decreased cold tolerance in early rice seedling stage signifcantly compared with that of wild type. Conclusions In general, study of the genetic basis of cold tolerance of rice is important for the development of cold-tolerant rice varieties. In the present study, QTL mapping, BSA-seq and RNA-seq were integrated to identify two CTS QTLs qCTS8 and qCTS12. Furthermore, qRT-PCR, genotype sequencing and knockout analysis indicated that LOC_Os12g18729 could be the candidate gene of qCTS12. These results are expected to further exploration of the genetic mechanism of CTS in rice and improve cold tolerance of cultivated rice by introducing the cold tolerant genes from DXWR through marker-assisted selection.

Abstract Background The triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), and triglyceride-density lipoprotein cholesterol ratio (TG/HDL-C) are substitute indicators for insulin resistance (IR). This study aimed to compare the predictive value of these indicators for 5-year mortality in critically ill patients with chronic heart failure (CHF). Methods Critically ill patients with CHF were identified from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) III and IV databases. The primary outcome was 5-year mortality. The relationship between the three indices and mortality risk was determined using multivariate Cox proportional hazards models, Kaplan–Meier (K‒M) analysis and restricted cubic splines analysis. A receiver operating characteristic (ROC) curve was generated to compare the ability of the three indices to predict mortality. Finally, whether the IR indices would further increase the predictive ability of the basic model including baseline variables with a significance level between survivors and non-survivors was evaluated by ROC curve. Results Altogether, 1329 patients with CHF were identified from the databases. Cox proportional hazards models indicated that the TyG index was independently associated with an elevated risk of 5-year mortality (hazard ratio [HR], 1.56; 95% confidence interval [CI] 1.29–1.9), while the TyG-BMI index and TG/HDL-C level were significantly associated with 5-year mortality, with an HR (95% CI) of 1.002 (1.000–1.003) and 1.01 (1.00–1.03), respectively. The K–M analysis revealed that the cumulative incidence of all-cause 5-year death increased with increasing quartiles of the TyG index, TyG-BMI index, or TG/HDL-C ratio. According to the ROC curve, the TyG index outperformed the TyG-BMI and TG/HDL-C ratio at predicting all-cause 5-year mortality (0.608 [0.571–0.645] vs. 0.558 [0.522–0.594] vs. 0.561 [0.524–0.598]). The effect of the TyG index on all-cause mortality was consistent across subgroups, with no significant interaction with randomized factors. Furthermore, adding the TyG index to the basic model for 5-year mortality improved its predictive ability (area under the curve, 0.762 for the basic model vs. 0.769 for the basic model + TyG index); however, the difference was not statistically significant. Conclusion As continuous variables, all three indices were significantly associated with 5-year mortality risk in critically ill patients with CHF. Although these IR indices did not improve the predictive power of the basic model in patients with CHF, the TyG index appears to be the most promising index (vs. TyG-BMI and TG/HDL-C ratio) for prevention and risk stratification in critically ill patients with CHF.

Abstract Background and purpose The persistent progression of pneumonia is a critical determinant of adverse outcomes in patients afflicted with COVID-19. This study aimed to predict personalized COVID-19 pneumonia progression between the duration of two weeks and 1 month after admission by integrating radiological and clinical features. Methods A retrospective analysis, approved by the Institutional Review Board, encompassed patients diagnosed with COVID-19 pneumonia between December 2022 and February 2023. The cohort was divided into training and validation groups in a 7:3 ratio. A trained multi-task U-Net network was deployed to segment COVID-19 pneumonia and lung regions in CT images, from which quantitative features were extracted. The eXtreme Gradient Boosting (XGBoost) algorithm was employed to construct a radiological model. A clinical model was constructed by LASSO method and stepwise regression analysis, followed by the subsequent construction of the combined model. Model performance was assessed using ROC and decision curve analysis (DCA), while Shapley’s Additive interpretation (SHAP) illustrated the importance of CT features. Results A total of 214 patients were recruited in our study. Four clinical characteristics and four CT features were identified as pivotal components for constructing the clinical and radiological models. The final four clinical characteristics were incorporated as well as the RS_radiological model to construct the combined prediction model. SHAP analysis revealed that CT score difference exerted the most significant influence on the predictive performance of the radiological model. The training group’s radiological, clinical, and combined models exhibited AUC values of 0.89, 0.72, and 0.92, respectively. Correspondingly, in the validation group, these values were observed to be 0.75, 0.72, and 0.81. The DCA curve showed that the combined model exhibited greater clinical utility than the clinical or radiological models. Conclusion Our novel combined model, fusing quantitative CT features with clinical characteristics, demonstrated effective prediction of COVID-19 pneumonia progression from 2 weeks to 1 month after admission. This comprehensive model can potentially serve as a valuable tool for clinicians to develop personalized treatment strategies and improve patient outcomes.

Abstract In this paper, an ultra-wideband stealth antenna with high gain on the basis of asymmetric transmission metasurface (ATMS) is proposed. ATMS can convert an incident y-polarised sphere wave into an x-polarised plane wave at the front side and controls the scattering of the incident y-polarised wave to the back side. Excitation of ATMS via a horn antenna, a low radar cross-section (RCS) and wideband antenna system is designed. Furthermore, through design of the meta-atoms and optimization of the macrosequencing, broadband RCS reduction is achieved. The experimental data indicated the reduction of the RCS of the antenna system by up to 10 dB and more than 20 dB in the frequency range of 10.1 GHz to 18 GHz (relative bandwidth is 56.2%) and 13.9 GHz to 18 GHz (relative bandwidth is 25.7%), respectively. In addition, a 3 dB gain relative bandwidth of 57.4% is achieved between 10 and 18 GHz, with a peak gain of 28.2 dB. It is noteworthy that the high gain and low scattering performance of the antenna are achieved in the same spectral range (10–18 GHz), and there is no interference between the scattering performance and radiation performance of the antenna, which could be controlled separately.

Abstract Aims The study aims to provide comprehensive evidence for the selection of agents in type 2 diabetes mellitus (T2DM) patients with cardiovascular risk and summarize the lasted evidence for the cardiovascular effects of sodium glucose cotransporter‐2 inhibitor (SGLT2i) in patients with heart failure (HF). Methods and results Several online databases were searched. All studies that explored the cardiovascular effects of SGLT2i or glucagon‐like peptide 1 receptor agonist (GLP1‐RA) were screened and reviewed. A total of 38 studies were included. Compared with GLP1‐RA, the use of SGLT2i significantly reduced the risk of cardiovascular death [risk ratio (RR) = 0.59; 95% confidence interval (CI), 0.44–0.58], hospitalization of heart failure (HHF) (RR = 0.77; 95% CI, 0.74–0.80), death from any cause (RR = 0.64; 95% CI, 0.60–0.68), and myocardial infarction (MI) (RR = 0.81; 95% CI, 0.76–0.87). However, SGLT2i significantly increased the risk of stroke (RR = 1.10; 95% CI, 1.04–1.17). Compared with the control group, SGLT2i treatment reduced the risk of cardiovascular death by 14% (RR = 0.86; 95% CI, 0.79–0.94), HHF by 25%, and death from any cause by 9% in patients with HF, regardless of diabetes status. Conclusions SGLT2i is associated with a lower risk of cardiovascular death, HHF, death from any cause, and MI in patients with T2DM compared with GLP1‐RA. In addition, SGLT2i brought more benefits with respect to the effects of cardiovascular death, HHF, and death from any cause in patients with HF, regardless of diabetes status.

Pericarpium Citri Reticulatae ‘Chachi’ (PCR-C), abundant in flavonoids, is traditionally believed to enhance its pharmacological effects with long-term storage. The efficacy of these flavonoids is closely related to their intestinal absorption, which is primarily affected by P-glycoprotein (P-gp). This study explored the interaction between flavonoid absorption and P-gp in PCR-C flavonoid extracts (PCR-CF) over different storage periods using a Caco-2 monolayer model and KB/MDR cells, respectively. The transported concentrations (TC) of key flavonoids-hesperidin, isosinensetin, nobiletin, and tangeretin-significantly varied with the storage duration of PCR-CF. Notably, nobiletin and tangeretin enhanced the TC of these flavonoids by inhibiting P-gp activity, thereby influencing intestinal absorption of PCR-CF with different storage time. These findings provide a scientific basis for the traditional belief that long-stored PCR-C possesses superior medicinal properties.

BackgroundDifficulty in achieving complete resection leads to a poor prognosis for retroperitoneal soft tissue sarcoma, hence emphasizing the significance of adjuvant treatment. The benefit of preoperative radiotherapy for retroperitoneal liposarcoma was initially demonstrated by the STRASS trial. However, the impact of intraoperative radiotherapy (IORT) on retroperitoneal liposarcoma remains unexplored.MethodPatients with retroperitoneal liposarcoma were identified in the Surveillance, Epidemiology, and End Results (SEER) database, treated between 2000 and 2019. Subsequently, a 1:1 propensity score-matched (PSM) analysis was conducted based on variables identified from a multivariate analysis. T-tests were used to assess differences in normally distributed continuous variables, while the rank-sum test was applied to variables that did not follow a normal distribution. The chi-squared test was utilized to evaluate differences in categorical variables. Ultimately, survival analysis was performed using SPSS to evaluate patient prognosis.ResultA total of 2129 patients with retroperitoneal liposarcoma were included in our study. Age, sex, histology, grading, chemotherapy, and tumor size as independent prognostic risk factors for these patients through multivariate Cox regression analysis. Subsequently, 66 patients were included in the survival analysis through PSM, with 33 patients receiving IORT. Finally, the survival analysis revealed that there was no difference in overall survival among patients with retroperitoneal liposarcoma, regardless of whether they received IORT or not (p= 0.711).ConclusionAs an exploratory study, our findings suggest that patients may not derive benefit from intraoperative radiotherapy. These observations are intended to lay the groundwork for future prospective clinical studies.

Objective: This study aimed to identify common therapeutic targets for well-differentiated and dedifferentiated retroperitoneal liposarcoma. Methods: Patient clinical data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, and survival differences were analyzed using the log-rank test. Gene expression data were sourced from the Gene Expression Omnibus (GEO) dataset GSE159659, with differential gene expression analysis conducted through GEO2R. Protein-protein interaction networks were developed using STRING and Cytoscape to identify key hub genes. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed using R, and transcription factors associated with the hub genes were predicted with TRRUST. Results: Significant survival differences were found between patients with well-differentiated and dedifferentiated retroperitoneal liposarcoma. Ninety-six differentially expressed genes with similar expression patterns were identified in both types. A protein-protein interaction network highlighted 12 hub genes and 24 transcription factors. Enrichment analysis pointed to the importance of lipid localization, storage, cytokine signaling, and metal ion absorption in both liposarcoma subtypes. Four potential therapeutic drugs were successfully predicted. Conclusion: This study identifies common molecular targets in well-differentiated and dedifferentiated retroperitoneal liposarcoma, providing new avenues for mechanistic studies and potential therapeutic development.

ABSTRACT: Phytic acid (PA) is a natural antioxidant with various biological activities, providing protective effects in multiple animals. Ochratoxin A (OTA) is a mold toxin commonly found in feed, which induces multi-organ damage, with kidney being the target organ of its toxicity. This study investigates the protective effects of PA on OTA-induced renal damage and its potential mechanisms in chicks. The results demonstrates that PA treatment restores OTA-induced renal pathological injuries, reverses the diminished activities of antioxidant enzymes, reduces the accumulation of malondialdehyde, and normalizes the expression of pro-inflammatory cytokines, which confirms that PA can alleviate OTA-induced renal damage. Further investigations reveal that OTA-induced renal injury accompanied by an increase in tissue iron content and the transcription levels of ferroptosis-related genes (TFR, ACSL4, and HO-1), and a decrease in the levels of SLC7A11 and GPX4. PA treatment reverses all these effects, indicating that PA mitigates OTA-induced renal ferroptosis. Moreover, PA supplementation improves intestinal morphology and mucosal function, corrects OTA-induced changes in the intestinal microbiota. Besides, PA microbiota transplantation alleviates renal inflammation and oxidative stress caused by OTA. In conclusion, PA plays a protective role against renal damage through the regulation of ferroptosis and the intestinal microbiota, possibly providing novel insights into the control and prevention of OTA-related nephrotoxicity.

Parapristipoma trilineatum is an edible and economically important marine fish with high farming potential; however, this fish has not been widely investigated. To understand the germplasm resources of this marine fish, we investigated the range of P. trilineatum from Maizuru, Japan, to Hainan, China. Using the mitochondrial control region as a molecular marker, we analyzed the population structure, genetic diversity, and population history dynamics of P. trilineatum. The control region exhibited high haplotype diversity and nucleotide diversity of 0.996 and 0.016, respectively. The genetic differentiation coefficients indicated low differentiation between Japanese and other populations. Additionally, based on the results of SAMOVA, AMOVA, and genetic differentiation coefficients, P. trilineatum can be divided into two management units in fishery resources management: China and Japan. Populations with high genetic diversity are useful as genetic breeding materials. This study provides a basis for the selection and breeding of P. trilineatum.

Abstract Background Aldosterone plays important parts in development of cardio-metabolic diseases as end product of renin-angiotensin-aldosterone system. However, factors elevating circulating aldosterone are not clear, and lifestyle-related factors are suggested to be involved, whereas less studied. Therefore, we aimed to explore the association of lifestyle factors with plasma aldosterone concentration (PAC) in community population. Methods In this cross-sectional study, we recruited participants using multistage random sampling from Emin China in 2019, and collected data and fasting blood samples. The considered lifestyle factors included obesity parameters (neck circumference, abdominal circumference), alcohol consumption, blood pressure (BP), physical activity, sleep duration, sleep quality, mental state (depression and anxiety), fasting blood glucose (FBG), and lipid profiles (total cholesterol and triglyceride). PAC was measured using radioimmunoassay. We performed sex-stratified linear and logistic regressions to explore associated factors of PAC. Component analysis was further performed to identify the main factors affecting PAC. Results Twenty-seven thousand four hundred thirty-six participants with 47.1% men were included. Obesity parameters (neck circumference, abdominal circumference), glucose metabolism (FBG), psychological status (anxiety status in men and women, depression status in men), BP, liver function (in men), lipid metabolism (TC and TG in men), sleep parameters (sleep quality in women), and renal function (in women) are the main factors associated with elevated PAC. Conclusion lower physical activity, alcohol consumption, higher BP, fat accumulation, dyslipidemia, higher fasting blood glucose, and presence of depression and anxiety were the main factors associated with eleveated PAC.

Abstract Background The application of radiomics in thoracic lymph node metastasis (LNM) of lung adenocarcinoma is increasing, but diagnostic performance of radiomics from primary tumor to predict LNM has not been systematically reviewed. Therefore, this study sought to provide a general overview regarding the methodological quality and diagnostic performance of using radiomic approaches to predict the likelihood of LNM in lung adenocarcinoma. Methods Studies were gathered from literature databases such as PubMed, Embase, the Web of Science Core Collection, and the Cochrane library. The Radiomic Quality Score (RQS) and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) were both used to assess the quality of each study. The pooled sensitivity, specificity, and area under the curve (AUC) of the best radiomics models in the training and validation cohorts were calculated. Subgroup and meta-regression analyses were also conducted. Results Seventeen studies with 159 to 1202 patients each were enrolled between the years of 2018 to 2022, of which ten studies had sufficient data for the quantitative evaluation. The percentage of RQS was between 11.1% and 44.4% and most of the studies were considered to have a low risk of bias and few applicability concerns in QUADAS-2. Pyradiomics and logistic regression analysis were the most commonly used software and methods for radiomics feature extraction and selection, respectively. In addition, the best prediction models in seventeen studies were mainly based on radiomics features combined with non-radiomics features (semantic features and/or clinical features). The pooled sensitivity, specificity, and AUC of the training cohorts were 0.84 (95% confidence interval (CI) [0.73–0.91]), 0.88 (95% CI [0.81–0.93]), and 0.93(95% CI [0.90–0.95]), respectively. For the validation cohorts, the pooled sensitivity, specificity, and AUC were 0.89 (95% CI [0.82–0.94]), 0.86 (95% CI [0.74–0.93]) and 0.94 (95% CI [0.91–0.96]), respectively. Conclusions Radiomic features based on the primary tumor have the potential to predict preoperative LNM of lung adenocarcinoma. However, radiomics workflow needs to be standardized to better promote the applicability of radiomics. Trial registration CRD42022375712.

In this paper, the formation process, morphology, and electrochemical performance of PEO coatings on AM50 magnesium alloy prepared in low concentration phosphate, aluminate, and phosphate-aluminate electrolytes were systematically studied. The results show that the coatings prepared from the phosphate electrolytes have a higher thickness and better corrosion resistance properties compared to the other electrolytes. The coatings prepared from low concentration phosphate-aluminate mixed electrolytes have slightly thinner thickness, a similar coating structure and an order of magnitude lower value of electrochemical impedance compared with phosphate electrolyte coatings. The Coatings prepared from low concentration aluminate electrolytes have the lowest thickness and the worst corrosion resistance properties which gets close to corrosion behavior of the bare AM50 under the same test conditions. Considering application, coatings prepared from single low concentration phosphate electrolytes and low concentration phosphate-aluminate electrolytes have greater potential than single low concentration aluminate coatings. However, reducing the electrolyte concentrations of coating forming ions too much has negative influence on the coating growth rate.

Abstract Single-walled carbon nanotubes (SWCNTs)-based thermoelectric materials, valued for their flexibility, lightweight, and cost-effectiveness, show promise for wearable thermoelectric devices. However, their thermoelectric performance requires significant enhancement for practical applications. To achieve this goal, in this work, we introduce rational “triple treatments” to improve the overall performance of flexible SWCNT-based films, achieving a high power factor of 20.29 µW cm−1 K−2 at room temperature. Ultrasonic dispersion enhances the conductivity, NaBH4 treatment reduces defects and enhances the Seebeck coefficient, and cold pressing significantly densifies the SWCNT films while preserving the high Seebeck coefficient. Also, bending tests confirm structural stability and exceptional flexibility, and a six-legged flexible device demonstrates a maximum power density of 2996 μW cm−2 at a 40 K temperature difference, showing great application potential. This advancement positions SWCNT films as promising flexible thermoelectric materials, providing insights into high-performance carbon-based thermoelectrics.

Abstract There are important ways to solve the ecological risk problems of regional water resources and soil resources, and to promote the benign development of soil and water resources, involving scientific evaluation of the ecological risk of soil and water resources in Hefei metropolitan area, clarifying the intrinsic evolution law of ecological risk and identifying the characteristics of spatial and temporal variations. Based on the conceptual model of “ST-QS-RR”, the evaluation indicator system is constructed, the CRITIC method is used to assign weights, and the TOPSIS method, kernel density method, markov chain and resistance model are used to measure and analyse the spatial and temporal characteristics of ecological risk of soil and water resources, and to explore the main factors that cause ecological risk of soil and water resources. The results of the study show that: (1) Hefei metropolitan area and its cities show a steady decline and the characteristics of “high in the north and low in the south, high in the west and low in the east”. (2) Most of the subsystems in the Hefei metropolitan area and the cities show a decreasing trend, with its resistance factors mainly concentrated in the QS system. (3) There is club convergence in Hefei metropolitan area. When the type of adjacent domain is higher, the change of risk type is more sensitive.

Abstract The DC‐side stability of the grid‐tied converter under different control modes is fully investigated using electrical torque analysis. The small‐signal model of a single converter connected to an ideal DC bus under various control modes is formulated. Accordingly, the damping and synchronising coefficient contributed by the DC network and controllers of grid‐tied converter are separately accessed using the electrical torque analysis method and the stabilising conditions of the grid‐tied converter operating under different control modes are further derived. The system stability mainly corresponds with DC network dynamics under constant active power control mode. On the contrary, the grid‐tied converter under constant DC‐link voltage control mode has no stability problem. Generally, elevating the DC‐link capacitance or decreasing the droop gain can greatly improve the stability margin reserve of the VSC‐HVDC links. In addition, the control gains of the classical PQ controller are proven to have limited impacts on DC‐side system stability. Finally, the results of numerical simulation prove the validity of the proposed stability analysis method and the stable boundary for the grid‐tied converter with different control modes.

The nervous system possesses bidirectional, sophisticated and delicate communications with the immune system. These neuroimmune interactions play a vitally important role in the initiation and development of many disorders, especially neurodegenerative diseases. Although scientific advancements have made tremendous progress in this field during the last few years, neuroimmune communications are still far from being elucidated. By organizing recent research, in this review, we discuss the local and intersystem neuroimmune interactions and their roles in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Unveiling these will help us gain a better understanding of the process of interplay inside the body and how the organism maintains homeostasis. It will also facilitate a view of the diseases from a holistic, pluralistic and interconnected perspective, thus providing a basis of developing novel and effective methods to diagnose, intervene and treat diseases.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV). Predicting the incidence of this disease in advance is crucial for policymakers to develop prevention and control strategies. In this study, we utilized historical incidence data of SFTS (2013–2020) in Shandong Province, China to establish three univariate prediction models based on two time-series forecasting algorithms Autoregressive Integrated Moving Average (ARIMA) and Prophet, as well as a special type of recurrent neural network Long Short-Term Memory (LSTM) algorithm. We then evaluated and compared the performance of these models. All three models demonstrated good predictive capabilities for SFTS cases, with the predicted results closely aligning with the actual cases. Among the models, the LSTM model exhibited the best fitting and prediction performance. It achieved the lowest values for mean absolute error (MAE), mean square error (MSE), and root mean square error (RMSE). The number of SFTS cases in the subsequent 5 years in this area were also generated using this model. The LSTM model, being simple and practical, provides valuable information and data for assessing the potential risk of SFTS in advance. This information is crucial for the development of early warning systems and the formulation of effective prevention and control measures for SFTS.

Hepatitis E virus (HEV) is an important cause of acute hepatitis, however, is highly neglected and largely underreported. This study aimed to describe the detailed epidemiology of hepatitis E (HE) through a 10-year surveillance. A community-based active hepatitis surveillance was conducted between November 2007 and October 2017 in 11 townships of Dongtai City in China, involving 355,673 residents. Serum samples were obtained from patients presenting with hepatitis symptoms for more than 3 days. Serum alanine aminotransferase (ALT) levels greater than 2.5 times the upper limit of normal (ULN) were considered acute hepatitis. Samples were subsequently tested for IgG and IgM anti-HEV antibodies, HEV RNA, and hepatitis B surface antigen (HBsAg). The data indicated the incidence of HE fluctuated downward from 2007 to 2017, with an average annual age-standardized incidence of 17.50 per 100,000, exceeding the 10.26 per 100,000 in the National Notifiable Disease Report System (NNDRS). The incidence was notably higher among males (20.95 per 100,000) and individuals aged 50–69 years (37.47 per 100,000). Genotype 4 (HEV-4) was the predominantly circulating genotype during the study period. Furthermore, the study revealed the incidence of hepatitis with HEV and hepatitis B virus (HBV) co-infection was 4.99 per 100,000. The active surveillance system identified a higher incidence of HE compared to NNDRS, with a decreased prevalence over a 10-year period. While efforts are still needed to prevent HE in high-risk populations, including individuals with hepatitis B and the elderly.

ABSTRACTHepatic immunity is one of the driving forces for the development of nonalcoholic steatohepatitis (NASH), and targeting gut microbiota is believed to affect the hepatic immune constitution. Here, we aimed to investigate the hepatic immunological state in NASH, with a specific emphasis on natural killer (NK) cells. In addition, we aimed to identify the contributing species that target hepatic immunity to provide new directions and support the feasibility of immunotherapy for NASH. A possible NASH population was determined by combination of long-term severe fatty liver, metabolic disorders and increased serum CK18 to detect serum immune factors and gut microbiota. NASH was induced in mice fed a high-fat diet to verify the prophylactic effect of the functional species on the immunopathology and development of NASH. Hepatic immunologic state was examined, and the effector functions of NK cells were detected. Hepatic transcriptome, proteomic, and fecal metagenome were performed. We observed a statistical increase in serum IL-10 (p

ABSTRACTTo assess the pattern of multiple human papillomavirus infection to predict the type replacement postvaccination. A total of 7372 women aged 18–45y from a phase III trial of an Escherichia coli-produced HPV-16/18 vaccine were analyzed at enrollment visit before vaccination. Hierarchical multilevel logistic regression was used to evaluate HPV vaccine type and nonvaccine-type interactions with age as a covariate. Binary logistic regression was construed to compare multiple infections with single infections to explore the impact of multiple-type infections on the risk of cervical disease. Multiple HPV infections were observed in 25.2% of HPV-positive women and multiple infections were higher than expected by chance. Statistically significant negative associations were observed between HPV16 and 52, HPV18 and HPV51/52/58, HPV31 and HPV39/51/52/53/54/58, HPV33 and HPV52/58, HPV58 and HPV52, HPV6 and HPV 39/51/52/53/54/56/58. Multiple HPV infections increased the risk of CIN2+ and HSIL+, with the ORs of 2.27(95%CI: 1.41, 3.64) and 2.26 (95%CI: 1.29, 3.95) for multiple oncogenic HPV infection separately. However, no significant evidence for the type-type interactions on risk of CIN2+ or HSIL+. There is possibility of type replacement between several pairs of vaccine and nonvaccine HPV type. Multiple HPV infection increased the risk of cervical disease, but coinfection HPV types seem to follow independent disease processes. Continued post-vaccination surveillance for HPV 51/52/58 types and HPV 39/51 types separately was essential after the first and second generation of HPV vaccination implementation in China.

Background: Liposarcoma is a malignant tumor that originates from adipose tissue and can occur in any part of the body. There is currently no clear conclusion on whether there are significant differences in prognosis between liposarcoma at different anatomical locations, especially retroperitoneal liposarcoma (RLPS) and non retroperitoneal liposarcoma (NRLPS). The aim of this study is to reveal whether there are differences in prognosis between these two locations of liposarcoma, and further explore the fundamental reasons behind these differences. Methods: We conducted an in-depth investigation into the factors affecting the prognosis of patients with liposarcoma by analyzing the data from the Surveillance, Epidemiology, and End Results Program (SEER) database. Then, we used propensity score matching (PSM) to balance these prognostic factors for comparative analysis of survival between RLPS and NRLPS. In addition, by analyzing transcriptome and whole exome data from TCGA and the Japan Genotypic Phenotype Archive (JGA), we identified genes with significant expression differences and explored changes in the immune microenvironment. Result: Through analysis of RLPS and NRLPS patients in the SEER database, we observed significant prognostic differences between the two groups, with RLPS exhibiting worse prognosis (p

IntroductionThis research seeks to investigate how early rehabilitation nursing, guided by Orem’s self-care theory, affects cognitive function, neurological function, and daily living skills in individuals who have suffered a traumatic brain injury (TBI).MethodsA study was conducted with 108 patients with traumatic brain injury who were hospitalized at our facility from January 2021 to March 2023. Based on their admission dates, the participants were separated into a control group (n = 56) and an observation group (n = 52). The control group received standard nursing care, while the observation group received a combination of conventional treatment and nursing interventions based on Orem’s self-care model. The research assessed alterations in the ability to perform daily tasks (Activities of Daily Living, ADL), neurological health (National Institutes of Health Stroke Scale, NIHSS; Glasgow Coma Scale, GCS), and cognitive abilities (Montreal Cognitive Assessment Scale, MoCA; Mini-Mental State Examination, MMSE) in both sets of participants prior to and following 4 and 8 weeks of nursing assistance.ResultsFollowing the intervention, the group being observed showed notably increased ADL scores at 4 weeks (p

PurposeThis study aims to evaluate the utility of radiomic features from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in distinguishing HER2-low from HER2-zero breast cancer.Patients and methodsWe retrospectively analyzed 118 MRI cases, including 78 HER2-low and 40 HER2-zero patients confirmed by immunohistochemistry or fluorescence in situ hybridization. From each DCE-MRI case, 960 radiomic features were extracted. These features were screened and reduced using intraclass correlation coefficient, Mann-Whitney U test, and least absolute shrinkage to establish rad-scores. Logistic regression (LR) assessed the model’s effectiveness in distinguishing HER2-low from HER2-zero. A clinicopathological MRI characteristic model was constructed using univariate and multivariate analysis, and a nomogram was developed combining rad-scores with significant MRI characteristics. Model performance was evaluated using the receiver operating characteristic (ROC) curve, and clinical benefit was assessed with decision curve analysis.ResultsThe radiomics model, clinical model, and nomogram successfully distinguished between HER2-low and HER2-zero. The radiomics model showed excellent performance, with area under the curve (AUC) values of 0.875 in the training set and 0.845 in the test set, outperforming the clinical model (AUC = 0.691 and 0.672, respectively). HER2 status correlated with increased rad-score and Time Intensity Curve (TIC). The nomogram outperformed both models, with AUC, sensitivity, and specificity values of 0.892, 79.6%, and 82.8% in the training set, and 0.886, 83.3%, and 90.9% in the test set.ConclusionsThe DCE-MRI-based nomogram shows promising potential in differentiating HER2-low from HER2-zero status in breast cancer patients.

Intrahepatic cholestasis of pregnancy (ICP) poses significant risks to maternal and neonatal health. Our study at Jiangxi Provincial Maternal and Child Health Hospital analyzed clinical and biochemical markers in singleton pregnancies diagnosed with ICP from October 2016 to December 2022. This research, supported by a systematic review and meta-analysis of existing studies, highlights the increasing incidence of ICP and its association with elevated levels of total bile acids, transaminases, and bilirubin. Our findings indicate a marked increase in the risk of preterm birth, cesarean delivery, and neonatal asphyxia as the severity of ICP escalates. This underscores the need for vigilant monitoring and management of affected pregnancies. By confirming the relationship between biochemical marker abnormalities and adverse pregnancy outcomes, our study advocates for enhanced clinical strategies and paves the way for future research aimed at improving prevention, diagnosis, and treatment methods for ICP.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is spreading rapidly in Asia. The pathway of SFTS virus shedding from patient and specific use of personal protective equipments (PPEs) against viral transmission have rarely been reported. The study was to determine SFTS virus (SFTSV) shedding pattern from the respiratory, digestive and urinary tract to outside in patients. Methods: Patients were divided into mild and severe groups in three sentinel hospitals for SFTS in Anhui province from April 2020 to October 2022. SFTSV level from blood, throat swabs, fecal/anal swabs, urine and bedside environment swabs of SFTS patients were detected by qRT-PCR. Specific PPEs were applied in healthcare workers contacting with the patients who had oropharyngeal virus shedding and hemorrhagic signs. Results: A total of 189 SFTSV-confirmed patients were included in the study, 54 patients died (case fatality rate, 28.57 %). Positive SFTSV in throat swabs (T-SFTSV), fecal/anal swabs (F-SFTSV) and urine (U-SFTSV) were detected in 121 (64.02 %), 91 (48.15 %) and 65 (34.4 %) severely ill patients, respectively. The levels of T-SFTSV, F-SFTSV and U-SFTSV were positively correlated with the load of SFTSV in blood. We firstly revealed that SFTSV positive rate of throat swabs were correlated with occurrence of pneumonia and case fatality rate of patients (P

Summary: Timely adjustments of antibiotic and corticosteroid treatments are vital for patients with diffuse parenchymal lung diseases (DPLDs). In this study, 41 DPLD patients with negative metagenomic next-generation sequencing (mNGS) results who were responsive to corticosteroids were enrolled. Among these patients, about 26.8% suffered from drug-induced DPLD, while 9.8% presented autoimmune-related DPLD. Following the report of the negative mNGS results, in 34 patients with complete antibiotics administration profiles, 79.4% (27/34) patients discontinued antibiotics after receiving negative mNGS results. Moreover, 70.7% (29/41) patients began or increased the administration of corticosteroid upon receipt of negative mNGS results. In the microbiota analysis, Staphylococcus and Stenotrophomonas showed higher detection rates in patients with oxygenation index (OI) below 300, while Escherichia and Stenotrophomonas had higher abundance in patients with pleural effusion. In summary, our findings demonstrated the clinical significance of mNGS in assisting the antibiotic and corticosteroid treatment adjustments in corticosteroid-responsive DPLD. Lung microbiota may imply the severity of the disease.

Growth differentiation factor-15 (GDF-15), a member of the transforming growth factor (TGF-β) superfamily, and is expressed and secreted in response to inflammation, oxidative stress and hypoxia. It has been shown in several studies to be a predictor of heart failure. However, the only kits available on the market are ELISA kits, which are costly and error-prone and are not conducive for clinical use. Here, we developed a chemiluminescence kit which optimized the reaction conditions and the reaction time was reduced to 10 min. We further proved that it can be used to measure GDF-15 in serum or plasma accurately and fastly, and provide additional information for the diagnosis of heart failure disease. Methodological comparison and clinical study verified this method is a reliable, economical and highly automated blood test method. • All necessary steps and the reagents needed are provided. • Reliability of the chemiluminescence immunoassay was verified by analyzing serum GDF-15 levels from different groups. • GDF-15 can provide clinicians with reliable prediction and disease assessment of heart failure.

Abstract Replication fork reversal, a critical protective mechanism against replication stress in higher eukaryotic cells, is orchestrated via a series of coordinated enzymatic reactions. The Bloom syndrome gene product, BLM, a member of the highly conserved RecQ helicase family, is implicated in this process, yet its precise regulation and role remain poorly understood. In this study, we demonstrate that the GCFC domain-containing protein TFIP11 forms a complex with the BLM helicase. TFIP11 exhibits a preference for binding to DNA substrates that mimic the structure generated at stalled replication forks. Loss of either TFIP11 or BLM leads to the accumulation of the other protein at stalled forks. This abnormal accumulation, in turn, impairs RAD51-mediated fork reversal and slowing, sensitizes cells to replication stress-inducing agents, and enhances chromosomal instability. These findings reveal a previously unidentified regulatory mechanism that modulates the activities of BLM and RAD51 at stalled forks, thereby impacting genome integrity.

Thousands of long-distance mobile mRNAs were identified from different grafting systems, based on high-throughput sequencing technology. Moreover, the long-distance delivery of RNAs was proved to involve multiple mechanisms. Here, we analyzed the homology, motif, and tRNA-like structure (TLS) of long-distance mobile mRNAs identified by RNA-seq as well as the RNA-binding protein (RBP) in nine grafting combinations including Arabidopsis thaliana, Vitis vinifera, Cucumis sativus, Citrullus lanatus, Nicotiana benthamiana, Malus domestica, Pyrus spp., Glycine max and Phaseolus vulgaris. Although several mRNAs were found to be shared in herbaceous, woody, and related species, the vast majority of long-distance mobile mRNAs were species-specific. Four non-specific movement-related motifs were identified, while the TLS was not necessary for mRNA long distance mobility. In addition, we found that RBPs were conserved among herbaceous and woody plants as well as related species. This paper reports a further in-depth analysis of the endogenous mechanisms by which the species-specific transportable mRNAs were selected by bioinformatics, in order to provide insights for future research on long-distance mobile mRNAs.

Abstract Hypoxic-ischemic brain damage (HIBD) is a leading cause of neonatal death and neurological dysfunction. Neuroinflammation is identified as one of the crucial pathological mechanisms after HIBD, and natural killer group 2 member D (NKG2D) is reported to be implicated in the pathogenesis of immunoinflammatory diseases. However, the role of NKG2D in neonatal HIBD is seldomly investigated. In this study, a neonatal mice model of HIBD was induced, and the role of the NKG2D in neuroinflammation and brain injury was explored by intracerebroventricular injection of lentivirus to knockdown NKG2D in neonatal mice with HIBD. The results showed that a significant increase in NKG2D protein level in the brain of neonatal mice with HIBD. The NKG2D knockdown in the brain significantly alleviated cerebral infarction, neurobehavioral deficits, and neuronal loss in neuronal HIBD. Moreover, the neuroprotective effect of NKG2D knockdown was associated with inhibition of the activation of microglia and astrocytes, expression of NKG2D ligands (NKG2DLs) and DAP10, and the nuclear translocation of NF-κB p65. Our findings reveal NKG2D knockdown may exert anti-inflammatory and neuroprotective effects in the neonatal mice with HIBD through downregulation of NKG2D/NKG2DLs/DAP10/NF-κB pathway. These results suggest that NKG2D may be a potential target for the treatment of neonatal HIBD.

Abstract Background Tumor immunotherapy is a new treatment breakthrough for retroperitoneal liposarcoma (RPLS), which is highly invasive and has few effective treatment options other than tumor resection. However, the heterogeneity of the tumor immune microenvironment (TIME) leads to missed clinical diagnosis and inappropriate treatment. Therefore, it is crucial to evaluate whether the TIME of a certain part of the tumor reliably represents the whole tumor, particularly for very large tumors, such as RPLS. Methods We conducted a prospective study to evaluate the TIME in different regions of dedifferentiated RPLS (DDRPLS) by detecting the expressions of markers such as CD4+, CD8+, Foxp3+, CD20+, CD68+, LAMP3+, PD-1+ tumor-infiltrating lymphocytes (TILs), and PD-L1 in tumors and corresponding paratumor tissues via immunohistochemistry and RNA sequencing. Results In DDRPLS, very few TILs were observed. Differentially expressed genes were significantly enriched in cell part and cell functions, as well as the metabolic pathway and PI3K-Akt signaling pathway. In addition, for most tumors (70–80%), the TIME was similar in different tumor regions. Conclusions For most tumors (70–80%), the TIME in any region of the tumor reliably represents the whole tumor. DDRPLS may regulate cell functions by modulating the metabolic and PI3K-Akt signaling pathways to promote its malignant behavior.

Abstract First-line chemoimmunotherapy (with or without bevacizumab) has improved outcomes in advanced non-small cell lung cancer (NSCLC). Here, this open-label, multi-cohort phase II study (NCT05329025) was done to investigate the safety and efficacy of QL1706 (a single bifunctional MabPair product against PD-1 and CTLA-4) and chemotherapy with or without bevacizumab in this population. Patients were enrolled into five different cohorts based on genotype (cohorts 1-4, epidermal growth factor receptor [EGFR] wild-type; cohort 5, EGFR-mutant and progressed on EGFR-tyrosine kinase inhibitors [TKIs]). Between June 11, 2021 and December 29, 2021, 91 patients were enrolled. Most frequent treatment-related adverse events (TRAEs) included decreased appetite (60 [65.9%]), anemia (60 [65.9%]), infusion-related reactions (48 [52.7%]), and pruritus (44 [48.4%]). Grade ≥ 3 TRAEs occurred in 30 (33.0%) patients. Twenty-seven (45%) patients with wild-type EGFR achieved partial response (PR) (objective response rate [ORR] = 45%) and had a median progression-free survival (mPFS) of 6.8 months (95% CI: 5.2-9.7). For 31 patients harboring mutated EGFR, 17 (54.8%) achieved PR (ORR = 54.8%), with an mPFS of 8.5 months (95% CI: 5.72-not evaluable). Overall, QL1706 plus chemotherapy, regardless of having bevacizumab, was generally tolerable and had promising antitumor activity for EGFR wild-type advanced NSCLC in first-line setting. Moreover, QL1706 plus chemotherapy and bevacizumab showed favorable antitumor activity for patients who had EGFR mutated NSCLC but failed in TKI therapy, demonstrating a potential for treating this population.

Road information plays an increasingly important role in applications, such as map updating, urban planning, and intelligent supervision. However, roads in remote sensing images may be shaded by trees and buildings or interfered with by farmland. These intrinsic image features can cause road extraction results to suffer from breakage and misidentification problems. To address these problems, this article improves on D-LinkNet and proposes a dual codec structure network, namely RUW-Net. Specifically, we use ReSidual U-blocks instead of ordinary residual blocks to extract more global contextual information during the encoding stage. Moreover, we propose a decoder-encoder combination (DEC) module to build a dual codec structure. The DEC module links the decoder of the first U-block and the encoder of the following U-block to narrow the semantic gap in the encoding and decoding process. The RUW-Net model can extract more multiscale contextual features and effectively use them to enhance the semantic information of road entities. Therefore, the RUW-Net model can obtain more accurate extraction results. We conducted a series of experiments on public datasets, such as DeepGlobe, including comparative, robustness, and ablation experiments. The results show that the proposed model alleviates the road extraction breakage and misidentification problems. Compared with other representative methods, the RUW-Net performs better in terms of completeness and accuracy of road extraction results; overall, its extraction results are also the best. The RUW-Net model provides a new idea for road extraction from remote sensing images.

Lubrication and heat transfer control are two significant functions of mold fluxes. In order to coordinate the contradiction between lubrication and heat transfer, the effects of BaO and Li2O on basic characteristics of CaO-SiO2 based mold fluxes were studied by hemispherical melting temperature instrument, rotating cylinder method, X-ray diffractometer (XRD) in present study. The results show that the melting temperature and viscosity at 1300°C all represent a downward trend with BaO and Li2O enhancement at different basicity, and the break temperature decrease with BaO addition while decrease and then increase with Li2O addition, which illustrates that Li2O content should be no more than 0.8 wt% for the purpose of lubrication. Meanwhile, to ensure a sufficient thickness of the liquid slag film and avoid discontinuity of the liquid slag film, the BaO content is better to be 10 wt% with low melting temperature and viscosity. The main crystalline phase in the mold fluxes is cuspidine (3CaO·2SiO2·CaF2), and the crystallization ratio rises sharply when basicity increased to 1.65. For better deal with the contradiction of lubrication and heat transfer, the mold fluxes composition w(BaO) = 10 wt%, w(Li2O) = 0.8 wt%, R ≥1.65 is reasonable, which has a profound impact on high crystallization and lubricity mold fluxes.

Abstract Aims In-depth studies on plant ion uptake and plant growth-promoting rhizobacteria (PGPR) at the molecular level will help to further reveal the effects of PGPR on plants and their interaction mechanisms under salt stress. Methods Cotton was inoculated with a PGPR-Enterobacter cloacae Rs-35, and the ion uptake capacity, membrane transporter protein activity, and expression of key genes were determined under salt stress. Changes in the endogenous hormone content of cotton were also determined. Further, the genome-wide metabolic pathway annotation of E. cloacae Rs-35 and its differential enrichment pathway analysis of multi-omics under salinity environments were performed. Results In a pot experiment of saline-alkali soil, E. cloacae Rs-35-treated cotton significantly increased its uptake of K+ and Ca2+ and decreased uptake of Na+, elevated the activity of the H+-ATPase, and increased the sensitivity of the Na+/H+ reverse transporter protein on the vesicle membrane. Meanwhile, inoculation with E. cloacae Rs-35 could promote cotton to maintain the indole-3-acetic acid (IAA) content under salt stress. Genome-wide annotation showed that E. cloacae Rs-35 was respectively annotated to 31, 38, and 130 related genes in osmotic stress, phytohormone and organic acid metabolism, and ion uptake metabolic pathway. Multi-omics differences analysis showed that E. cloacae Rs-35 were enriched to tryptophan metabolism, multiple amino acid biosynthesis, carbon and glucose synthesis, and oxidative phosphorylation metabolic pathways at the transcriptome, proteome, and metabolome. Conclusion E. cloacae Rs-35 can promote cotton balance cell ion concentration, stabilize intracellular IAA changes, stimulate induction of systemic tolerance, and promote the growth of cotton plants under salt stress.

Abstract Background Significant lower genital tract (LGT) dysbiosis and an associated lower rate of clinical pregnancy after in vitro fertilization–frozen embryo transfer (IVF-FET) among polycystic ovary syndrome (PCOS) patients have been previously reported by our group. We aimed to assess whether transvaginal Lactobacillus supplementation can reverse LGT dysbiosis and further improve perinatal outcomes in PCOS patients after IVF-FET. Methods/design This is a protocol for a multicenter, open-label, randomized controlled trial in China. Women diagnosed with PCOS who are undergoing IVF-FET treatment will be recruited. Allocation to the intervention/control arms at a ratio of 1:1 will be executed by an electronic randomization system. Participants in the intervention arm will receive the live Lactobacillus capsule vaginally for 10 consecutive days before embryo transfer, while those in the control arm will receive standard individualized care. The primary outcomes will be the clinical pregnancy rate, implantation rate, and live birth rate. 16S rRNA sequencing and liquid chromatography–mass spectrometry will be conducted to evaluate the LGT microbiome and systemic metabonomics before and after the intervention. A sample of 260 participants will provide 95% power to detect a 20% increase in the rate of clinical pregnancy (α = 0.025, one-tailed test, 15% dropout rate). A total of 300 participants will be recruited. Discussion This is the first large and multicenter randomized controlled trial aimed at assessing the efficacy of transvaginal Lactobacillus supplementation on restoring the LGT microbiome and improving perinatal outcomes in PCOS patients after IVF-FET. This pragmatic trial is promising for increasing the rates of clinical pregnancy and live birth in PCOS patients after IVF-FET. Ethics and dissemination Ethical review approval was obtained from the Medical Research Ethics Committees of the International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University (15 October 2020, GKLW 2020-29). To maximize dissemination, these findings will be reported in open access publications in journals with high impact, and oral and poster conference presentations will be performed. Trial registration ChiCTR ChiCTR2000036460. Registered on 13 September 2020, https://www.chictr.org.cn/showproj.html?proj=59549 .

Autophagy leads to cellular tolerance of the therapeutic pressure of chemotherapeutic drugs, resulting in treatment resistance. Therefore, the effective monitoring of the autophagy status of tumors in vivo and the regulating of the autophagy level are crucial for improving the efficacy of chemotherapy. In this work, we grafted nitroxide radicals onto the surface of iron oxide nanoparticles (Fe3O4 NPs) using dendrimer polymers, yielding Fe3O4-NO· NPs that are responsive to reactive oxygen species (ROS) and possess enhanced T1 and T2 signal capabilities in a magnetic resonance imaging (MRI) measurement. The ROS in tumor cells generated by autophagy quenches the nitroxide radicals, thereby weakening the T1 signal. In contrast, Fe3O4 NPs are unaffected by intracellular ROS, leading to a stable T2 signal. By comparing the intensity ratio of T1 to T2 in Fe3O4-NO· NPs, we can evaluate the in vivo autophagy status within tumors in real time. It also revealed that Fe3O4-NO· NPs loaded with doxorubicin (Dox) and combining the autophagy inhibitor exhibited high antitumor activity in cells and tumor-bearing mice. This system, which combines real-time monitoring of tumor cell autophagy with the delivery of chemotherapeutic drugs, provides an innovative and effective strategy for tumor treatment with potential clinical application prospects.

We have studied the parameters of preliminary breakdown (PB) pulses in 395 normal and 319 inverted intracloud (IC) flashes observed in Gifu, Japan, and Ningxia, China, respectively, by using a low-frequency mapping system called fast antenna lightning mapping array (FALMA). These parameters are extracted from the first half of the PB pulses. It is found that compared to normal IC flashes, inverted IC flashes exhibited PB pulses with slower rise times (6.8 vs. 3.1 μs), wider half-peak widths (3.8 vs. 2.5 μs), longer zero-crossing times (26.2 vs. 14 μs), and extended fall times (4 vs. 3.2 μs). We further demonstrated that such discrepancies between normal and inverted IC flashes should not be caused by subjective factors, like noise threshold setting, or objective factors, like signal propagation distance. Based on this analysis, finally, we inferred that the discrepancies should be a reflection of the PB channel properties of normal and inverted IC flashes.