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ObjectiveThe objectives of this study were to integrate the Prognostic Nutritional Index, Controlling Nutritional Status, and Nutritional Risk Index, into a novel Nutrition-combined Prognostic Index (NCPI), and to develop and validate a nomogram to predict overall survival (OS) in patients with gastric cancer (GC).Materials and methodsData from 609 patients with GC, collected between January 1, 2017, and April 30, 2023, were retrospectively analyzed. Optimal cut-off values for nutritional parameters were determined using X-Tile software, and the Kaplan–Meier method applied for survival analysis. Univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses were conducted, and a nomogram for predicting OS in patients with GC constructed and validated.ResultsInferior nutritional status was strongly correlated with worse clinicopathologic features and prognosis of patients with GC. NCPI, body mass index, American Joint Committee on Cancer T stage, and lymph node ratio were identified as independent risk factors for OS. A nomogram including these factors predicted 1-, 3-, and 5-year OS, with training and validation set C-index values of 0.716 and 0.77, respectively. Calibration curves demonstrated that the predicted outcomes closely matched the actual results, and decision curve analysis highlighted the high practical value of the model.ConclusionThe novel nutritional marker, NCPI, is closely associated with the clinicopathologic features and OS of patients with GC. The practical value of the NCPI-based nomogram was demonstrated and a web-based calculator developed.

BackgroundPlatelets can dynamically regulate tumor development and progression. Nevertheless, research on the predictive value and specific roles of platelets in gastric cancer (GC) is limited. This research aims to establish a predictive platelets-related gene signature in GC with prognostic and therapeutic implications.MethodsWe downloaded the transcriptome data and clinical materials of GC patients (n=378) from The Cancer Genome Atlas (TCGA) database. Prognostic platelets-related genes screened by univariate Cox regression were included in Least Absolute Shrinkage and Selection Operator (LASSO) analysis to construct a risk model. Kaplan-Meier curves and receiver operating characteristic curves (ROCs) were performed in the TCGA cohort and three independent validation cohorts. A nomogram integrating the risk score and clinicopathological features was constructed. Functional enrichment and tumor microenvironment (TME) analyses were performed. Drug sensitivity prediction was conducted through The Cancer Therapeutics Response Portal (CTRP) database. Finally, the expression of ten signature genes was validated by quantitative real-time PCR (qRT-PCR).ResultsA ten-gene (SERPINE1, ANXA5, DGKQ, PTPN6, F5, DGKB, PCDH7, GNG11, APOA1, and TF) predictive risk model was finally constructed. Patients were categorized as high- or low-risk using median risk score as the threshold. The area under the ROC curve (AUC) values for the 1-, 2-, and 3-year overall survival (OS) in the training cohort were 0.670, 0.695, and 0.707, respectively. Survival analysis showed a better OS in low-risk patients in the training and validation cohorts. The AUCs of the nomogram for predicting 1-, 2-, and 3-year OS were 0.708, 0.763, and 0.742, respectively. TME analyses revealed a higher M2 macrophage infiltration and an immunosuppressive TME in the high-risk group. Furthermore, High-risk patients tended to be more sensitive to thalidomide, MK-0752, and BRD-K17060750.ConclusionThe novel platelets-related genes signature we identified could be used for prognosis and treatment prediction in GC.

ObjectiveVulvar carcinoma exhibits a robust correlation alongside HPV infection; however, the impact of HPV rank on the prognostic outcomes of radiation therapy within vulvar malignancies stays ambiguous. In the present study, we performed a comprehensive examination as well as meta-analysis to assess the influence of infection with HPV upon the long-term outlook as well as sensitivity of individuals with vulvar cancer undergoing radiation therapy.MethodsA meticulous examination of the existing research was conducted in accordance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A thorough search was conducted in the PubMed, Embase, Web of Science, as well as Cochrane Library databases, covering the entire available literature till April 1, 2023. The studies that met the inclusion criteria contained data about HPV infection and oncological outcomes in patients with vulvar cancer who received radiation therapy. This study was registered in PROSPERO (CRD42023417957).ResultsWe identified 12 retrospective studies meeting our inclusion criteria, which included a total of 3967 patients. Patients with HPV-associated vulvar cancer achieved a better overall survival rate after radiotherapy (HR=0.71, 95%CI: 0.54-0.93, P=0.01), and showed a significant improvement in disease-free survival (HR=0.75, 95%CI: 0.58-0.97, P=0.09) and progression-free survival (HR=0.31, 95%CI: 0.22-0.45, P,

BackgroundNonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder strongly linked to type 2 diabetes mellitus (T2DM). Understanding the predictive value of lipid parameters in identifying abnormal glucose metabolism in NAFLD patients is crucial for early intervention.MethodsThis study analyzed data from the National Health and Nutrition Examination Survey(NHANES) database (2017-2020) involving 1066 NAFLD patients. Participants were categorized into three groups: T2DM (n=414), prediabetes mellitus (pre-DM) (n=507), and normoglycemia (NG) (n=145). Traditional lipid parameters [triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)] and nontraditional lipid parameters [atherogenic index of plasma (AIP), residual cholesterol (RC), and non-high-density lipoprotein cholesterol (non-HDL-C)] were evaluated for their association with T2DM and pre-DM.ResultsElevated TG levels were significantly associated with an increased risk of T2DM and pre-DM, whereas high HDL-C demonstrated a protective effect. Among nontraditional lipid parameters, increased AIP and RC were most strongly associated with T2DM risk, while high non-HDL-C was best associated with the development of pre-DM. Stratified analyses revealed that these associations were stronger in younger, non-obese, smoking, and female NAFLD patients.ConclusionNontraditional lipid parameters, particularly AIP and RC, show superior predictive value over traditional lipid parameters in identifying abnormal glucose metabolism in NAFLD patients. Incorporating these novel biomarkers into clinical practice could enhance early detection and prevention strategies for T2DM and pre-DM in this high-risk population.

Niemann-Pick disease type C1 (NP-C1) is a rare and devastating recessive inherited lysosomal lipid and cholesterol storage disorder caused by mutations in the NPC1 or NPC2 gene. These two proteins bind to cholesterol and cooperate in endosomal cholesterol transport. Characteristic clinical manifestations of NP-C1 include hepatosplenomegaly, progressive neurodegeneration, and ataxia. While the rarity of NP-C1 presents a significant obstacle to progress, researchers have developed numerous potential therapeutic approaches over the past two decades to address this condition. Various methods have been proposed and continuously improved to slow the progression of NP-C1, although they are currently at an animal or clinical experimental stage. This overview of NP-C1 therapy will delve into different theoretical treatment strategies, such as small molecule therapies, cell-based approaches, and gene therapy, highlighting the complex therapeutic challenges associated with this disorder.

Most colon cancer patients are diagnosed at an advanced stage, with a grim prognosis. In clinical, various combination therapies have been employed to enhance the efficacy of colon cancer treatment. The essence of combined treatment is the judicious selection and combination of various treatment units. Phototherapy (PT), sonodynamic therapy (SDT), and chemotherapy are treatment modalities that rely on the active molecules to treat tumors, and have been demonstrated to synergistically enhance tumor treatment efficacy. However, the differences in the metabolism of active molecules and hypoxic microenvironment of tumors have limited the synergistic effects of the aforementioned methods. To address this significant issue, in this study, we utilized polydopamine (PDA) as the encapsulated material to form a rigid shell that contains the therapeutic molecules IR-780 and methotrexate (MTX) on the surface of perfluorohexane (PFH) microdroplets through self-assembling method to develop an SDT/chemotherapy/PT combined nanoparticles (SCP NPs). Transmission electron microscopy (TEM) revealed that the nanoparticles exhibited a hollow shell structure, with an average size of approximately 100 nm. SCP NPs have excellent stability and biocompatibility in both in vitro and in vivo. The absorption and emission spectrum of the loaded IR-780 did not exhibit any significant shift, and the photothermal temperature rose to 92°C. Their ultrasonic cavitation effect was good and their cell inhibitory effect of MTX was maintained. SCP NPs can achieve multi-modal triggered release through ultrasound, laser irradiation, and pH, ensuring a simultaneous accumulation of therapeutic molecules in the tumor area and effectively alleviating tumor hypoxia. Additionally, both the near-infrared fluorescence (NIF) signal and the ultrasonic cavitation signal of the nanoparticles can be utilized for tracking and monitoring treatment efficacy. Most notably, SCP NPs exhibited outstanding synergistic treatment effects at low intervention levels, resulting in a 67% cure rate of tumors. These results provide an experimental basis for developing the new clinical treatments for colon cancer.

BackgroundCuproptosis is copper-induced cell death. Copper metabolism related genes (CMRGs) were demonstrated that used to assess the prognosis out of tumors. In the study, CMRGs were tested for their effect on TME cell infiltration in Ewing’s sarcoma (ES).MethodsThe GEO and ICGC databases provided the mRNA expression profiles and clinical features for downloading. In the GSE17674 dataset, 22prognostic-related copper metabolism related genes (PR-CMRGs) was identified by using univariate regression analysis. Subsequently, in order to compare the survival rates of groups with high and low expression of these PR-CMRGs,Kaplan-Meier analysis was implemented. Additionally, correlations among them were examined. The study employed functional enrichment analysis to investigate probable underlying pathways, while GSVA was applied to evaluate enriched pathways in the ES (Expression Set). Through an unsupervised clustering algorithm, samples were classified into two clusters, revealing significant differences in survival rates and levels of immune infiltration.ResultsUsing Lasso and step regression methods, five genes (TFRC, SORD, SLC11A2, FKBP4, and AANAT) were selected as risk signatures. According to the Kaplan-Meier survival analysis, the high-risk group had considerably lower survival rates than the low-risk group(p=6.013e-09). The area under the curve (AUC) values for the receiver operating characteristic (ROC) curve were 0.876, 0.883, and 0.979 for 1, 3, and 5 years, respectively. The risk model was further validated in additional datasets, namely GSE63155, GSE63156, and the ICGC datasets. To aid in outcome prediction, a nomogram was developed that incorporated risk levels and clinical features. This nomogram’s performance was effectively validated through calibration curves.Additionally, the study evaluated the variations in immune infiltration across different risk groups, as well as high-expression and low-expression groups. Importantly, several drugs were identified that displayed sensitivity, offering potential therapeutic options for ES.ConclusionThe findings above strongly indicate that CMRGs play crucial roles in predicting prognosis and immune status in ES.

Diagenetic physical simulation is a reliable means to study patterns of pore evolution and variations of physical properties, however, the current compaction model is mostly based on sandstone, and there is a lack of quantitative compaction and porosity reduction studies for more complex rock fabrics. In order to simulate the continuous change of intergranular porosity in the reservoir under compaction during the diagenesis of buried sedimentary strata, a self-designed diagenesis simulation experimental system was adopted. Using different modern sediment samples, the simulation experiment of mechanical compaction of glutenite was carried out. The experiment shows that during the process of mechanical compaction of glutenite, the change of porosity with depth is segmented, and there is a good logarithmic relationship between depth and porosity in the process of diagenetic compaction. The larger the grain size in the reservoir rock, the better the pore preservation capacity; When the sand particles fill the pores among gravel, stable secondary support structure formed by gravel and sand grades can effectively take over the bearing pressure, and when the sand-grade particle content is about 30%, the pressure-bearing capacity is the strongest; Intergranular heterobase filling is greater in samples with high heterobase content, high heterobasic content is not favourable to the preservation of primary pores. This study provides favorable experimental support for the preservation mechanism of deep clastic reservoir pores, and has important theoretical and practical significance for oil and gas exploration in the study area. The use of simulation experiment provides a useful idea for the evaluation and prediction of reservoirs and the search for favorable reservoir development zones in the future.

Neuropathic pain is a type of chronic pain caused by an injury or somatosensory nervous system disease. Drugs and exercise could effectively relieve neuropathic pain, but no treatment can completely stop neuropathic pain. The integration of exercise into neuropathic pain management has attracted considerable interest in recent years, and treadmill training is the most used among exercise therapies. Neuropathic pain can be effectively treated if its mechanism is clarified. In recent years, the association between neuroinflammation and neuropathic pain has been explored. Neuroinflammation can trigger proinflammatory cytokines, activate microglia, inhibit descending pain modulatory systems, and promote the overexpression of brain-derived neurotrophic factor, which lead to the generation of neuropathic pain and hypersensitivity. Treadmill exercise can alleviate neuropathic pain mainly by regulating neuroinflammation, including inhibiting the activity of pro-inflammatory factors and over activation of microglia in the dorsal horn, regulating the expression of mu opioid receptor expression in the rostral ventromedial medulla and levels of γ-aminobutyric acid to activate the descending pain modulatory system and the overexpression of brain-derived neurotrophic factor. This article reviews and summarizes research on the effect of treadmill exercise on neuropathic pain and its role in the regulation of neuroinflammation to explore its benefits for neuropathic pain treatment.

In this study, a Bayesian data assimilation method that fuses physics with motion sensor data is demonstrated to infer the dynamic states at points of interest on the bottomhole assembly (BHA) with proper uncertainty quantification. A 4.75 inch-LWD (Logging-while-drilling) tool has been used as a use case, where the dynamic states at the formation evaluation sensor can be predicted in real time with the measurements at the motion sensor as the required inputs. This was achieved with a developed transfer function that utilizes unscented Kalman filtering technique. The robustness of the transfer function was evaluated with synthetic data obtained from finite element analysis (FEA) simulations for various BHA configurations and drilling conditions. It was found that the prediction by the transfer function agrees favorably well with the true states of motion at the formation evaluation sensor. Specifically, using the developed transfer function can help reduce the relative errors for the motion trajectories at the formation evaluation sensor by a factor of 3, and can significantly enhance measurement quality risk classification. The developed transfer function method was further assessed with experimental roll test data, which is considered as close to drilling conditions. The prediction by the transfer function was found consistently close to the ground truth in the presence of backward whirl. The developed modeling method can potentially have broader impacts by enabling fit-for-basin virtual V&V (Verification and Validation) to accelerate LWD tool development, or enabling future drilling optimization.

Improving the nighttime vision of drivers is essential, given the growing advancements in urban transportation. In this study, polyurethane-based self-luminous pavement coatings (PSCs) were prepared by doping luminous powders (LPs) into the polyurethane materials. The superior optical properties and chemical stabilities of these coatings were ensured by synthesizing the polyurethane-based material. Then, the PSCs were evaluated for their comprehensive performances, such as luminescence, aging resistance, and abrasion resistance, using various characterization methods, including fluorescence spectral analysis, Fourier-transform infrared spectroscopy, fluorescence microscopy, and mechanical property testing. The results show that the 50-mesh LP has the optimal overall performance, with an initial luminescence that exceeds those of the 100 and 400 meshes. The initial brightness of the PSC is mainly influenced by the LP and increases with dosage. The lattice structure and luminescent properties of the luminescent material did not change after coating preparation. The peak excitation wavelength of 420 nm implies that the coating has the best excitation effect under UV light. The primer-marking coating effectively improves the abrasion resistance of the PSC, and the mass loss of the PSC with a coating thickness of 0.4 kg/m2 is 52.9% of that without the primer-marking coating, with the optimal coating thickness being 0.6 kg/m2. This research provides an innovative solution to improve nighttime roadway lighting, which provides useful support for the sustainable development of urban transportation infrastructures and construction of intelligent transportation systems.

BackgroundThe intimal hyperplasia (IH) and vascular remodelling that follows endovascular injury, for instance after post-angioplasty re-stenosis, results in downstream ischaemia and progressive end organ damage. Interferon gamma (IFNγ) is known to play a critical role in this process. In mouse models we have previously shown that fibrocytes expressing tissue factor (TF) are recruited early to the site of injury. Through thrombin generation and protease activated receptor-1 (PAR-1) activation, fibrocytes secrete angiopoietin-2, stimulate neointimal cell proliferation, inhibit apoptosis and induce CXCL-12 production, all of which contribute to the progressive IH that then develops. In this study we investigated the relationship between TF, angiopoietin-2 and IFNγ.Methods and resultsIH developing in carotid arteries of wild-type mice 4 weeks after endoluminal injury contained a significant proportion of IFNγ+ fibrocytes and macrophages, which we show, using a previously defined adoptive transfer model, were derived from circulating CD34+ cells. IH did not develop after injury in IFNγ-deficient mice, except after transplantation of WT bone marrow or adoptive transfer of WT CD34+ cells. In vitro, CD34+ cells isolated from post-injury mice did not express IFNγ, but this was induced when provided with FVIIa and FX, and enhanced when prothrombin was also provided: In both cases IFNγ secretion was TF-dependent and mediated mainly through protease activated PAR-1. IFNγ was predominantly expressed by fibrocytes. In vivo, all IFNγ+ neointimal cells in WT mice co-expressed angiopoietin-2, as did the small numbers of neointimal cells recruited in IFNγ-/- mice. Adoptively transferred WT CD34+ cells treated with either an anti-TIE-2 antibody, or with siRNA against angiopoetin-2 inhibited the expression of IFNγ and the development of IH.ConclusionTF-dependent angiopoietin-2 production by newly recruited fibrocytes, and to a lesser extent macrophages, switches on IFNγ expression, and this is necessary for the IH to develop. These novel findings enhance our understanding of the pathophysiology of IH and expose potential targets for therapeutic intervention.

The elimination of traditional thermal generators and the increase of renewable energy source access reduced the inertia of the power system, and thermostatically controlled loads have the potential to provide ancillary services to the power system. This paper introduces a decentralized control strategy for thermostatically controlled loads (TCLs), which focuses on assisting large-scale TCLs in providing frequency support to power systems while considering energy efficiency ratio and measurement error correction. Initially, the nonlinear relationship between heat flow and TCLs’ power is modeled using a polynomial relationship, and the coefficients are determined through a data-driven method to enhance accuracy in TCLs modeling and assess their regulation potential precisely. Subsequently, a decentralized control strategy tailored for power system frequency regulation is developed. To account for measurement errors in TCLs controllers, a measurement error back-correction method is proposed. Simulation examples demonstrate the effectiveness of the proposed control strategy in achieving accurate modeling and control of TCLs and reducing power system frequency fluctuations.

BackgroundTo investigate the knowledge, attitude, and practice (KAP) of atrial fibrillation (AF) among the general population in high-altitude areas.MethodologyA web-based cross-sectional study was conducted among the general population in high-altitude areas.ResultsA total of 786 valid questionnaires were enrolled, with a mean age of 34.75 ± 14.16 years. The mean score of knowledge, attitude and practice were 8.22 ± 6.50 (possible range: 0–10), 28.90 ± 5.63 (possible range: 8–40), 34.34 ± 6.44 (possible range: 9–45), respectively. The multivariate analysis showed that knowledge scores (OR = 1.108, 95% CI = 1.075–1.142, p

Virtual reality (VR) has become an important interactive visualization tool for various industrial processes including facility inspection and maintenance. The capability of a VR application to present users with realistic simulations of complex systems and immerse them in, for example, inaccessible remote environments is often essential for using VR in real-world industrial domains. While many VR solutions have already been developed to support virtual facility inspection, previous systems provide immersive visualizations only with limited realism, because the real-world conditions of facilities are often difficult to reconstruct with accurate meshes and point clouds or typically too time-consuming to be consistently updated in computer-aided design (CAD) software toolkits. In this work, we present Magic NeRF Lens, a VR framework that supports immersive photorealistic visualizations of complex industrial facilities leveraging the recent advancement of neural radiance fields (NeRF). We introduce a data fusion technique to merge a NeRF model with the polygonal representation of it’s corresponding CAD model, which optimizes VR NeRF rendering through magic-lens-style interactions while introducing a novel industrial visualization design that can support practical tasks such as facility maintenance planning and redesign. We systematically benchmarked the performance of our framework, investigated users’ perceptions of the magic-lens-style visualization design through a visual search experiment to derive design insights, and performed an empirical evaluation of our system through expert reviews. To support further research and development of customized VR NeRF applications, the source code of the toolkit was made openly available.

BackgroundThe status of the sentinel lymph nodes (SLNs) was an important prognostic factor in varies cancers. A one-step nucleic acid amplification (OSNA) assay, a molecular-based whole-node analysis method based on CK19 mRNA copy number, was developed to diagnose lymph node metastases. We aimed to evaluate the value of OSNA for the diagnosis of sentinel lymph node metastasis in CK19 positive cancers. CK19 mRNA and protein expression for pan-caner analysis were obtained from TCGA and the Human protein atlas database.MethodsTwo researchers independently searched the PubMed, Cochrane Library and Web of Science databases for qualified articles published before December 1, 2023. A meta-analysis was performed using MetaDisc and STATA. Risk bias and quality assessments of the included studies were evaluated, and a subgroup analysis was performed. Ten cancer types were found to be CK19 positively expressed and 7 of 10 had been reported to use OSNA for SLN detection.ResultsAfter literature review, there were 61 articles included in the meta-analysis, which consisted of 7115 patients with 18007 sentinel lymph nodes. The pooled sensitivity and specificity of OSNA were 0.87 and 0.95 in overall patients. Moreover, we found the background CK19 expression in normal tissue affected the diagnostic accuracy of OSNA. In breast cancer, we performed subgroup analysis. OSNA exhibited to be a stable method across different population groups and various medical centers. In addition, when 250 copies/μl was chosen as the cutoff point of CK19 mRNA, there were a relatively higher sensitivity and AUC in detecting SLN micro-metastasis than 5000 copies/μl.DiscussionOSNA can predict the occurrence of SLN metastasis accurately in CK19 positive cancers, especially in breast cancer, colorectal cancer, lung cancer, gastric cancer and endometrial cancer. Our study warrants future studies investigating the clinical application of OSNA in pancreatic, ovarian and bladder cancers.

This study investigated the population genetics and distribution patterns of Artemia populations from ten inland salt lakes in China. A total of 1,274,698 Artemia single nucleotide polymorphisms (SNPs) were identified. The results showed that these populations could be geographically and genetically divided into four distinct groups, and that the Tibetan populations were further divided into two subpopulations with a trend of decreasing genetic diversity from west to east. The Tibetan population had the highest genetic diversity, whereas the Shanxi population had the lowest. There was moderate genetic differentiation between the Tibetan populations and greater genetic differentiation between the Xinjiang and Shanxi populations. IBD (isolation by distance) suggested that geographical isolation contributes to genetic differentiation. In addition, there was some degree of gene flow among the ten populations, with A. sinica showing unidirectional gene flow in all populations in the eastern Nagri region. Species distribution modeling showed that mean annual temperature, temperature seasonality, and annual precipitation were the main environmental factors affecting the distribution of Artemia populations and suitable habitats for Tibetan populations will be further reduced in the future. It is necessary to strengthen the protection of germplasm resources and formulate scientific protocols for the sustainable development and utilization of Artemia resources.

BackgroundIn recent years, novel therapies targeting specific molecular pathways and immunotherapies have exhibited promising outcomes for treating human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Our work aimed to assess the effectiveness and safety of these emerging treatment regimens for this disease.Material and methodsWe systematically searched databases including PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials their inception to August 2023 to identify relevant randomized controlled trials (RCTs). The quality of eligible RCTs was evaluated with the Cochrane risk-of-bias tool, version 2 (RoB2). Investigated outcomes encompassed progression-free survival (PFS), overall survival (OS), disease-free survival (DFS), pathologic complete remission (pCR), and adverse events (AEs). They were expressed as hazard ratio (HR) with 95% conference intervals (CI) or risk ratio (RR) with 95% CI.ResultsOur analysis identified a total of 28 RCTs suitable for inclusion in the NMA. Regarding the PFS, all these treatment regimens exhibited comparable effectiveness. In terms of OS, Capecitabine+Trastuzumab, Lapatinib+Trastuzumab and Pyrotinib+Capecitabine exhibited better effect compared to other treatments. Regarding pCR and AEs, all these treatment regimens exhibited comparable effectiveness, especially Lapatinib+Trastuzumab and Pyrotinib+Capecitabine.ConclusionOur study highlights the prominent role of targeted therapies and immunotherapies in treating HER2-positive breast cancer. The efficacy of trastuzumab-containing regimens was superior to other treatment options, while maintaining a comparable safety profile. Based on these findings, trastuzumab-containing regimens emerge as a preferable and recommended choice in clinical practice for managing HER2-positive breast cancer.Systematic Review RegistrationPROSPERO, identifier CRD42023414348.

IntroductionIt is well-known that different populations and animals, even experimental animals with the same rearing conditions, differ in their susceptibility to obesity. The disparity in gut microbiota could potentially account for the variation in susceptibility to obesity. However, the precise impact of gut microbiota on gut metabolites and its subsequent influence on susceptibility to obesity remains uncertain.MethodsIn this study, we established obesity-prone (OP) and obesity-resistant (OR) mouse models by High Fat Diet (HFD). Fecal contents of cecum were examined using 16S rDNA sequencing and untargeted metabolomics. Correlation analysis and MIMOSA2 analysis were used to explore the association between gut microbiota and intestinal metabolites.ResultsAfter a HFD, gut microbiota and gut metabolic profiles were significantly different between OP and OR mice. Gut microbiota after a HFD may lead to changes in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), a variety of branched fatty acid esters of hydroxy fatty acids (FAHFAs) and a variety of phospholipids to promote obesity. The bacteria g_Akkermansia (Greengene ID: 175696) may contribute to the difference in obesity susceptibility through the synthesis of glycerophosphoryl diester phosphodiesterase (glpQ) to promote choline production and the synthesis of valyl-tRNA synthetase (VARS) which promotes L-Valine degradation. In addition, gut microbiota may affect obesity and obesity susceptibility through histidine metabolism, linoleic acid metabolism and protein digestion and absorption pathways.

Crack detection is a crucial task for the structural health diagnosis of buildings. The current widely used manual inspection methods have inherent limitations and safety hazards, while traditional digital image processing methods require manual feature extraction and also have substantial limitations. In this paper, we propose a crack recognition method based on pyramid features and memory mechanisms that leverages a U-shaped network, long short-term memory mechanisms, and a pyramid feature design to address the recognition accuracy, robustness, and universality issues with deep learning-based crack detection methods in recent years. Experiments were conducted on four publicly available datasets and one private dataset. Compared with the commonly used FCN8s, SegNet, UNet, and DeepLabv3+ models and other related studies using the same evaluation criteria and datasets, our proposed model shows better overall performance in terms of all metrics evaluated.

To fairly use demand response to regulate customer load , support the economic and environmental protection, and assess the quantity and quality of the synergistic growth of the integrated energy system, a multi-objective optimum scheduling model and a solution method considering exergy efficiency and demand response are presented. To begin with, a mathematical model of each energy gadget is created. The electricity–gas load demand response model is then built using the price elasticity matrix, while the cooling load demand response model is built taking into account the user’s comfort temperature. On this basis, a multi-objective optimal dispatching model is developed with the optimization goals of minimizing system operation costs, reducing carbon emissions, and increasing exergy efficiency. Finally, the model is solved using NSGA-II to produce the Pareto optimal frontier solution set in various situations, and the VIKOR decision procedure is utilized to identify the complete best dispatching solution. The simulation results suggest that the proposed model can match the system’s scheduling needs in terms of numerous objectives such as economy, environmental protection, and exergy efficiency while also assuring user’s comfort.

Background: The Fangji Dihuang formulation (FJDHF) is a widely recognized Traditional Chinese Medicine (TCM) formula that consists of five plant drugs: Stephaniae Tetrandrae Radix, Cinnamomi Ramulus, Rehmanniae Radix, Saposhnikoviae Radix, and Glycyrrhiza Urensis Fisch. This formulation has been known to exhibit clinical therapeutic effects in the treatment of inflammatory skin diseases. However, there is a lack of pharmacological research on its anti-atopic dermatitis (AD) activity.Methods: To investigate the potential anti-AD activity of FJDHF, DNCB was used to induce AD-like skin inflammation in the back of mice. Following successful modeling, the mice were administered FJDHF orally. The extent of the inflammatory skin lesions was recorded at day 4, 7, 14 and 28. UHPLC-Q-Exactive Orbitrap MS was used to identify and match the compounds present in FJDHF with ITCM, TCMIP and TCMSID. In silico predictions of potential target proteins of the identified compounds were obtained from SwishTargetPrediction, ITCM and TargetNet databases. AD-related genes were identified from GSE32924 data set, and FJDHF anti-AD hub genes were identified by MCODE algorithm. ClueGo enrichment analysis was employed to identify the core pathway of FJDHF’s anti-AD effect. To further investigate the anti-AD effect of FJDHF, single-cell RNA sequencing data set (GSE148196) from AD patients was analyzed to determine the target cells and signaling pathways of FJDHF in AD. Finally, rt-PCR, flow cytometry, and mouse back skin RNA sequencing were utilized to validate our findings.Results: FJDHF was found to be effective in improving the degree of the AD-like lesions in the mice. Network pharmacological analysis revealed the core pathway of FJDHF to be the IL-17 signaling pathway, which is interactively associated with cytokines. Single-cell RNA sequencing analysis suggested that FJDHF may play an anti-AD role by influencing dendritic cells. Flow cytometry and rt-PCR results showed that FJDHF can reduce the influence of AD sample of IL-4, IFN-γ and the expression of IL-17. The RNA sequencing of mouse back skin also confirmed our conclusion.Conclusion: FJDHF may inhibit DNCB-induced AD-like skin inflammation in mice by inhibiting the IL-17 signaling pathway. Thus, FJDHF can be considered as a potential therapeutic agent for AD.

AimsThis research sought to assess the perceived levels of participation and autonomy in senior patients who had received total hip arthroplasty (THA) or total knee arthroplasty (TKA) in Hangzhou, China. Furthermore, the study aimed to identify the factors linked to these outcomes.Study designThis investigation will utilize a cross-sectional study design to assess perceived participation and autonomy among older adults total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients. The research was conducted in Hangzhou, China, at a tertiary hospital.MethodsConvenient sampling was utilized to select 139 patients who underwent THA or TKA between March 2022 and March 2023 and met the inclusion criteria at a tertiary hospital in Hangzhou. The Impact on Participation and Autonomy Questionnaire, Hip/Knee Injury and Osteoarthritis Outcome Score (HOOS/KOOS), 5-Item Geriatric Depression Scale, Multidimensional Scale of Perceived Social Support, and Elders Health Empowerment Scale were used to assess perceived participation, hip/knee-related symptoms and functional restrictions, depression symptoms, social support, and health empowerment.ResultsThe mean score for perceived participation and autonomy was 22.554 (SD: 13.042). The mean scores for participation in indoor autonomy, outdoor autonomy, family roles, and social relations were 0.654 (SD: 0.608), 1.324 (SD: 0.792), 1.053 (SD: 0.657), and 0.664 (SD: 0.542), respectively. Negative correlations were observed between perceived participation/autonomy scores and HOOS/KOOS, social support, and health empowerment scores. Conversely, a positive correlation was found between perceived participation/autonomy scores and depression scores. The detrimental effect of HOOS/KOOS, social support, and health empowerment scores on perceived participation and autonomy was notable, while the impact of depressive symptoms was comparatively minor.ConclusionOlder Chinese patients, at first six months post THA/TKA surgery, reported higher levels of perceived participation compared to individuals with other conditions, such as stroke patients. Functional limitations resulting from hip/knee-related symptoms, as well as social support and health empowerment, emerged as significant influencing factors for perceived participation and autonomy. This research enhances our comprehension of the elements influencing perceived participation among older adults individuals who have undergone THA/TKA procedures.

Plants produce a wide range of bioactive peptides as part of their innate defense mechanisms. With the explosive growth of plant-derived peptides, verifying the therapeutic function using traditional experimental methods are resources and time consuming. Therefore, it is necessary to predict the therapeutic function of plant-derived peptides more effectively and accurately with reduced waste of resources and thus expedite the development of plant peptides. We herein developed a repository of plant peptides predicted to have multiple therapeutic functions, named as MFPPDB (multi-functional plant peptide database). MFPPDB including 1,482,409 single or multiple functional plant origin therapeutic peptides derived from 121 fundamental plant species. The functional categories of these therapeutic peptides include 41 different features such as anti-bacterial, anti-fungal, anti-HIV, anti-viral, and anti-cancer. The detailed physicochemical information of these peptides was presented in functional search and physicochemical property search module, which can help users easily access the peptide information by the plant peptide species, ID, and functions, or by their peptide ID, isoelectric point, peptide sequence, and molecular weight through web-friendly interface. We further matched the predicted peptides to nine state-of-the-art curated functional peptide databases and found that at least 293,408 of the peptides possess functional potentials. Overall, MFPPDB integrated a massive number of plant peptides have single or multiple therapeutic functions, which will facilitate the comprehensive research in plant peptidomics. MFPPDB can be freely accessed through http://124.223.195.214:9188/mfppdb/index.

ObjectiveTo study the effect of physical exercise on non-suicidal self-injury in adolescents and to verify the chain mediating role of perceived social support and self-concept. Methods: A survey study was conducted on 1,426 adolescents in Chengdu, Sichuan Province. A chain mediation model was used to verify whether perceived social support and self-concept played a mediating role.ResultsPhysical exercise was significantly negatively associated with non-suicidal self-injury in adolescents (β = −0.53, p

Pregnancy predisposes to arrhythmias in females due to physiological changes in the cardiovascular system, enhanced activity of the sympathetic nervous system (SNS), and changes in the endocrine system, regardless of whether there exist cardiovascular diseases before the pregnancy. Tachyarrhythmias may present for the first time or worsen persistently during pregnancy, potentially leading to maternal heart failure and sudden death, as well as some adverse fetal outcomes such as growth restriction, distress, premature birth, and stillbirth. Radiofrequency ablation (RFA) is one of the most important therapeutic methods for tachyarrhythmias. According to the 2019 European Society of Cardiology (ESC) guidelines, RFA in pregnant women should preferably be performed without x-rays. Since the 2000s, 3D mapping technique has rapidly developed, laying the foundation for cardiac electrophysiology examination free from x-rays. Ventricular arrhythmia originating from the left coronary cusp (LCC) is not common in clinic. RFA is challenging in the treatment of this type of disease due to the anatomical feature that the opening of the left main coronary artery is localized in the LCC.

Chronic stress is suspected to be a causal factor of female subfertility; however, the underlying mechanisms remain unclear. Here, we found that chronic stress inhibited the cyclic adenosine 3′,5′-monophosphate (cAMP) signaling pathway, leading to ovarian reserve decline in mice. A chronic stress model was constructed using restraint stress for 8 weeks. An elongated estrous cycle and a significant increase in the number of atretic follicles were observed in the stress group. We identified a significant increase in meiotic arrest failure (MAF) in oocytes in the stress group, characterized by condensed metaphase chromosomes, assembled spindles, or polar bodies in the oocytes. Whole-mount ovarian reserve estimation at the single-oocyte level using the CUBIC method (clear, unobstructed brain/body imaging cocktails and computational analysis) revealed a significant decrease in quiescent oocytes from 2,261/ovary in the control group to 1,373/ovary in the stress group. The number of growing oocytes also significantly decreased from 220/ovary in the control group to 150/ovary in the stress group. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis of the meiotic arrest maintenance pathways revealed significant downregulation of Gpr3, Nppc, and Npr2 in the stress group. These results indicate that blocking cAMP production contributes to MAF and a decline in ovarian reserve. Overall, we present new insights into the mechanisms underlying chronic-stress-induced oocyte loss and potential targets for ovarian reserve preservation.

BackgroundAccumulating evidence has suggested that glycometabolism plays an important role in the pathogenesis of tumorigenesis. However, few studies have investigated the prognostic values of glycometabolic genes in patients with osteosarcoma (OS). This study aimed to recognize and establish a glycometabolic gene signature to forecast the prognosis, and provide therapeutic options for patients with OS.MethodsUnivariate and multivariate Cox regression, LASSO Cox regression, overall survival analysis, receiver operating characteristic curve, and nomogram were adopted to develop the glycometabolic gene signature, and further evaluate the prognostic values of this signature. Functional analyses including Gene Ontology (GO), kyoto encyclopedia of genes and genomes analyses (KEGG), gene set enrichment analysis, single-sample gene set enrichment analysis (ssGSEA), and competing endogenous RNA (ceRNA) network, were used to explore the molecular mechanisms of OS and the correlation between immune infiltration and gene signature. Moreover, these prognostic genes were further validated by immunohistochemical staining.ResultsA total of four genes including PRKACB, SEPHS2, GPX7, and PFKFB3 were identified for constructing a glycometabolic gene signature which had a favorable performance in predicting the prognosis of patients with OS. Univariate and multivariate Cox regression analyses revealed that the risk score was an independent prognostic factor. Functional analyses indicated that multiple immune associated biological processes and pathways were enriched in the low-risk group, while 26 immunocytes were down-regulated in the high-risk group. The patients in high-risk group showed elevated sensitivity to doxorubicin. Furthermore, these prognostic genes could directly or indirectly interact with other 50 genes. A ceRNA regulatory network based on these prognostic genes was also constructed. The results of immunohistochemical staining showed that SEPHS2, GPX7, and PFKFB3 were differentially expressed between OS tissues and adjacent normal tissues.ConclusionThe preset study constructed and validated a novel glycometabolic gene signature which could predict the prognosis of patients with OS, identify the degree of immune infiltration in tumor microenvironment, and provide guidance for the selection of chemotherapeutic drugs. These findings may shed new light on the investigation of molecular mechanisms and comprehensive treatments for OS.

COVID-19-associated acute kidney injury (COVID-19 AKI) is an independent risk factor for in-hospital mortality and has the potential to progress to chronic kidney disease. Prunella vulgaris L., a traditional Chinese herb that has been used for the treatment of a variety of kidney diseases for centuries, could have the potential to treat this complication. In this study, we studied the potential protective role of Prunella vulgaris in COVID-19 AKI and explored its specific mechanisms applied by network pharmacology and bioinformatics methods. The combination of the protein-protein interaction network and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment -target gene network revealed eight key target genes (VEGFA, ICAM1, IL6, CXCL8, IL1B, CCL2, IL10 and RELA). Molecular docking showed that all these eight gene-encoded proteins could be effectively bound to three major active compounds (quercetin, luteolin and kaempferol), thus becoming potential therapeutic targets. Molecular dynamics simulation also supports the binding stability of RELA-encoded protein with quercetin and luteolin. Together, our data suggest that IL6, VEGFA, and RELA could be the potential drug targets by inhibiting the NF-κB signaling pathway. Our in silico studies shed new insights into P. vulgaris and its ingredients, e.g., quercetin, as potential botanical drugs against COVID-19 AKI, and warrant further studies on efficacy and mechanisms.

Introduction: Polarization-sensitive optical coherence tomography (PS-OCT) is a functional extension of standard OCT. PS-OCT systems can be generally categorized into two categories based on the number of input polarization states on the sample: multi-input polarization state (multi-IPS) and single IPS. In addition, each category includes two configurations: fiber-based system and bulk optics-based system. However, there are complex and time-consuming steps to calibrate the polarization states of light among the reference, the sample, and detection arms for fiber-based system. And it is not compact and robust enough for bulk optics-based system.Methods: In the modified SD PS-OCT system with structural symmetry in both arms of the reference and sample, there are no bulk polarization optical elements in both arms of the reference and the sample. A circularly polarized light was used to incident on sample, and Stokes vector of backscattered light was employed to characterize the birefringence of biological tissues based on the quaternion approach, which directly establishes the relationship between Stokes vectors of backscattered light and Jones matrix of the sample.Results and discussion: The new algorithm provides the analytic solution of retardance and fast-axis orientation. To evaluate the performance of the developed system, an eighth-wave plate is used. Then, the polarization properties of the myocardial tissue in vivo are quantitatively reconstructed based on the quaternion approach. The results demonstrated that the proposed method has an advantage over Jones formalism based on a single input state and two polarization input states. In the future, the modified SD PS-OCT could be improved as a common path SD PS-OCT for clinical applications.

Kawasaki disease (KD) is a childhood vasculitis disease that is difficult to diagnose, and there is an urgent need for the identification of accurate and specific biomarkers. Here, we aimed to investigate metabolic alterations in patients with KD to determine novel diagnostic and prognostic biomarkers for KD. To this end, we performed untargeted metabolomics and found that several metabolic pathways were significantly enriched, including amino acid, lipid, and tryptophan metabolism, the latter of which we focused on particularly. Tryptophan-targeted metabolomics was conducted to explore the role of tryptophan metabolism in KD. The results showed that Trp and indole acetic acid (IAA) levels markedly decreased, and that l-kynurenine (Kyn) and kynurenic acid (Kyna) levels were considerably higher in patients with KD than in healthy controls. Changes in Trp, IAA, Kyn, and Kyna levels in a KD coronary arteritis mouse model were consistent with those in patients with KD. We further analyzed public single-cell RNA sequencing data of patients with KD and revealed that their peripheral blood mononuclear cells showed Aryl hydrocarbon receptor expression that was remarkably higher than that of healthy children. These results suggest that the Trp metabolic pathway is significantly altered in KD and that metabolic indicators may serve as novel diagnostic and therapeutic biomarkers for KD.

Cuttage is a widely used technique for plant propagation, whose success relies on the refilling for water transport recovery. However, requirements for refilling characterization studies, including large penetration depth, fast temporal resolution and high spatial resolution, cannot be reached simultaneously via conventional imaging techniques. So far, the dynamic process of water refilling along the vessels at the initial stage of cuttage, as well as its characteristics, remains unclear. Hereby, we developed a move contrast X-ray microtomography method which achieves 3D dynamic non-destructive imaging of water refilling at the initial stage of willow branch cuttage, without the aid of any contrast agent. Experimental results indicate three primary refilling modalities in vessels: 1) the osmosis type, mainly manifested by the osmosis of tissue through the vessel wall into the cavity; 2) the linear type, revealed as the tissue permeates to a certain extent where the liquid column in the vessels is completely formed; and 3) an osmosis-linear mixed type refilling as an intermediate state. Further analysis also exhibits a “temporal-spatial relay” mode of refilling between adjacent vessels. Since the vessel length is quite limited, the cavitation and the relay refilling mode of vessels can be an important way to achieve long-distance water transport.

Background: As a novel non-apoptotic cell death, ferroptosis has been reported to play a crucial role in acute kidney injury (AKI), especially cisplatin-induced AKI. Valproic acid (VPA), an inhibitor of histone deacetylase (HDAC) 1 and 2, is used as an antiepileptic drug. Consistent with our data, a few studies have demonstrated that VPA protects against kidney injury in several models, but the detailed mechanism remains unclear.Results: In this study, we found that VPA prevents against cisplatin-induced renal injury via regulating glutathione peroxidase 4 (GPX4) and inhibiting ferroptosis. Our results mainly indicated that ferroptosis presented in tubular epithelial cells of AKI humans and cisplatin-induced AKI mice. VPA or ferrostatin-1 (ferroptosis inhibitor, Fer-1) reduced cisplatin-induced AKI functionally and pathologically, which was characterized by reduced serum creatinine, blood urea nitrogen, and tissue damage in mice. Meanwhile, VPA or Fer-1 treatment in both in vivo and in vitro models, decreased cell death, lipid peroxidation, and expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), reversing downregulation of GPX4. In addition, our study in vitro indicated that GPX4 inhibition by siRNA significantly weakened the protective effect of VPA after cisplatin treatment.Conclusion: Ferroptosis plays an essential role in cisplatin-induced AKI and inhibiting ferroptosis through VPA to protect against renal injury is a viable treatment in cisplatin-induced AKI.

Heart failure with preserved ejection fraction (HFpEF) is characterized by a complex, heterogeneous spectrum of pathologic features combined with average left ventricular volume and diastolic dysfunction. HFpEF is a significant public health problem associated with high morbidity and mortality rates. Currently, effective treatments for HFpEF represent the greatest unmet need in cardiovascular medicine. A lack of an efficient preclinical model has hampered the development of new devices and medications for HFpEF. Because large animal models have similar physiologic traits as humans and appropriate organ sizes, they are the best option for limiting practical constraints. HFpEF is a highly integrated, multiorgan, systemic disorder requiring a multipronged investigative approach. Here, we review the large animal models of HFpEF reported to date and describe the methods that have been used to create HFpEF, including surgery-induced pressure overloading, medicine-induced pressure overloading, and diet-induced metabolic syndrome. In addition, for the first time to our knowledge, we use two established clinical HFpEF algorithms (HFA-PEFF and H2FPEF scores) to evaluate the currently available large animal models. We also discuss new technologies, such as continuous remote pressure monitors and inflatable aortic cuffs, as well as how the models could be improved. Based on current progress and our own experience, we believe an efficient large animal model of HFpEF should simultaneously encompass multiple pathophysiologic factors, along with multiorgan dysfunction. This could be fully evaluated through available methods (imaging, blood work). Although many models have been studied, only a few studies completely meet clinical score standards. Therefore, it is critical to address the deficiencies of each model and incorporate novel techniques to establish a more reliable model, which will help facilitate the understanding of HFpEF mechanisms and the development of a treatment.

Objective: To understand the temporal trends of cancer incidence and mortality in women in Guangzhou during the past 11 years and provide clues for future research.Methods: Data were obtained from the Guangzhou Cancer and Death Registry. Average annual percentage changes (AAPCs) in age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were obtained by joinpoint regression. The age-period-cohort (APC) model was generated to quantify the effects of age, period, and cohort.Results: The ASIRs for cervical (AAPC = −4.3%) and ovarian (AAPC = −3.2%) cancers showed a downward trend during 2010–2020, and that for uterine cancer showed an upward trend. The ASMRs of breast (APC = 5.0%) and cervical (APC = 8.8%) cancers increased. The APC model highlights different age, period, and birth cohort effects depending on the cancer site.Conclusion: The ASIRs for cervical and ovarian cancers among women in Guangzhou showed a decreasing trend during the period. The APC model showed mortality for 4 cancers increased with age. Incidence and mortality decreased with increasing birth cohort. Annual reproductive cancer screening is recommended for women of appropriate age to reduce the disease burden.

ObjectivesLung cancer has been widely characterized through radiomics and artificial intelligence (AI). This review aims to summarize the published studies of AI based on positron emission tomography/computed tomography (PET/CT) radiomics in non-small-cell lung cancer (NSCLC).Materials and methodsA comprehensive search of literature published between 2012 and 2022 was conducted on the PubMed database. There were no language or publication status restrictions on the search. About 127 articles in the search results were screened and gradually excluded according to the exclusion criteria. Finally, this review included 39 articles for analysis.ResultsClassification is conducted according to purposes and several studies were identified at each stage of disease:1) Cancer detection (n=8), 2) histology and stage of cancer (n=11), 3) metastases (n=6), 4) genotype (n=6), 5) treatment outcome and survival (n=8). There is a wide range of heterogeneity among studies due to differences in patient sources, evaluation criteria and workflow of radiomics. On the whole, most models show diagnostic performance comparable to or even better than experts, and the common problems are repeatability and clinical transformability.ConclusionAI-based PET/CT Radiomics play potential roles in NSCLC clinical management. However, there is still a long way to go before being translated into clinical application. Large-scale, multi-center, prospective research is the direction of future efforts, while we need to face the risk of repeatability of radiomics features and the limitation of access to large databases.

Targeted delivery of antitumor drugs has been recognized as a promising therapeutic modality to improve treatment efficacy, reduce the toxic side effects and inhibit tumor recurrence. In this study, based on the high biocompatibility, large specific surface area, and easy surface modification of small-sized hollow mesoporous silica nanoparticles β-cyclodextrin (β-CD)-benzimidazole (BM) supramolecular nanovalve, together with bone-targeted alendronate sodium (ALN) were constructed on the surface of small-sized HMSNs. The drug loading capacity and efficiency of apatinib (Apa) in HMSNs/BM-Apa-CD-PEG-ALN (HACA) were 65% and 25%, respectively. More importantly, HACA nanoparticles can release the antitumor drug Apa efficiently compared with non-targeted HMSNs nanoparticles in the acidic microenvironment of the tumor. In vitro studies showed that HACA nanoparticles exhibited the most potent cytotoxicity in osteosarcoma cells (143B cells) and significantly reduced cell proliferation, migration and invasion. Therefore, the drug-efficient release of antitumor effect of HACA nanoparticles is a promising way to treat osteosarcoma.

IntroductionIn China, alfalfa (Medicago sativa L.) is often grown on marginal land with poor soil fertility and suboptimal climate conditions. Soil salt stress is one of the most limiting factors for alfalfa yield and quality, through its inhibition of nitrogen (N) uptake and N fixation.MethodsTo understand if N supply could improve alfalfa yield and quality through increasing N uptake in salt-affected soils, a hydroponic experiment and a soil experiment were conducted. Alfalfa growth and N fixation were evaluated in response to different salt levels and N supply levels.Results and discussionThe results showed that salt stress not only significantly decreased alfalfa biomass, by 43%–86%, and N content, by 58%–91%, but also reduced N fixation ability and N derived from the atmosphere (%Ndfa) through the inhibition of nodule formation and N fixation efficiency when the salt level was above 100 mmol Na2SO4 L–1. Salt stress also decreased alfalfa crude protein by 31%–37%. However, N supply significantly improved shoot dry weight by 40%–45%, root dry weight by 23%–29%, and shoot N content by 10%–28% for alfalfa grown in salt-affected soil. The N supply was also beneficial for the %Ndfa and N fixation for alfalfa with salt stress, and the increase reached 47% and 60%, respectively. Nitrogen supply offset the negative effects on alfalfa growth and N fixation caused by salt stress, in part through improving plant N nutrition status. Our results suggest that optimal N fertilizer application is essential to alleviate the loss of growth and N fixation in alfalfa in salt-affected soils.

Purpose: To quantify the impact of image noise on CT-based lung ventilation biomarkers calculated using Jacobian determinant techniques.Methods: Five mechanically ventilated swine were imaged on a multi-row CT scanner with acquisition parameters of 120 kVp and 0.6 mm slice thickness in static and 4-dimensional CT (4DCT) modes with respective pitches of 1 and 0.09. A range of tube current time product (mAs) values were used to vary image dose. On two dates, subjects received two 4DCTs: one with 10 mAs/rotation (low-dose, high-noise) and one with CT simulation standard of care 100 mAs/rotation (high-dose, low-noise). Additionally, 10 intermediate noise level breath-hold (BHCT) scans were acquired with inspiratory and expiratory lung volumes. Images were reconstructed with and without iterative reconstruction (IR) using 1 mm slice thickness. The Jacobian determinant of an estimated transformation from a B-spline deformable image registration was used to create CT-ventilation biomarkers estimating lung tissue expansion. 24 CT-ventilation maps were generated per subject per scan date: four 4DCT ventilation maps (two noise levels each with and without IR) and 20 BHCT ventilation maps (10 noise levels each with and without IR). Biomarkers derived from reduced dose scans were registered to the reference full dose scan for comparison. Evaluation metrics were gamma pass rate (Γ) with 2 mm distance-to-agreement and 6% intensity criterion, voxel-wise Spearman correlation (ρ) and Jacobian ratio coefficient of variation (CoVJR).Results: Comparing biomarkers derived from low (CTDIvol = 6.07 mGy) and high (CTDIvol = 60.7 mGy) dose 4DCT scans, mean Γ, ρ and CoVJR values were 93% ± 3%, 0.88 ± 0.03 and 0.04 ± 0.009, respectively. With IR applied, those values were 93% ± 4%, 0.90 ± 0.04 and 0.03 ± 0.003. Similarly, comparisons between BHCT-based biomarkers with variable dose (CTDIvol = 1.35–7.95 mGy) had mean Γ, ρ and CoVJR of 93% ± 4%, 0.97 ± 0.02 and 0.03 ± 0.006 without IR and 93% ± 4%, 0.97 ± 0.03 and 0.03 ± 0.007 with IR. Applying IR did not significantly change any metrics (p>0.05).Discussion: This work demonstrated that CT-ventilation, calculated using the Jacobian determinant of an estimated transformation from a B-spline deformable image registration, is invariant to Hounsfield Unit (HU) variation caused by image noise. This advantageous finding may be leveraged clinically with potential applications including dose reduction and/or acquiring repeated low-dose acquisitions for improved ventilation characterization.

Background: Clear cell renal cell carcinoma (ccRCC), which is the most prevalent type of renal cell carcinoma, has a high mortality rate. Lipid metabolism reprogramming is a hallmark of ccRCC progression, but its specific mechanism remains unclear. Here, the relationship between dysregulated lipid metabolism genes (LMGs) and ccRCC progression was investigated.Methods: The ccRCC transcriptome data and patients’ clinical traits were obtained from several databases. A list of LMGs was selected, differentially expressed gene screening performed to detect differential LMGs, survival analysis performed, a prognostic model established, and immune landscape evaluated using the CIBERSORT algorithm. Gene Set Variation Analysis and Gene set enrichment analysis were conducted to explore the mechanism by which LMGs affect ccRCC progression. Single-cell RNA-sequencing data were obtained from relevant datasets. Immunohistochemistry and RT-PCR were used to validate the expression of prognostic LMGs.Results: Seventy-one differential LMGs were identified between ccRCC and control samples, and a novel risk score model established comprising 11 LMGs (ABCB4, DPEP1, IL4I1, ENO2, PLD4, CEL, HSD11B2, ACADSB, ELOVL2, LPA, and PIK3R6); this risk model could predict ccRCC survival. The high-risk group had worse prognoses and higher immune pathway activation and cancer development.Conclusion: Our results showed that this prognostic model can affect ccRCC progression.

RationaleIgE plays an important pathologic role in most, if not all, allergic conditions. We previously showed that ASHMI (anti-asthma herbal medicine intervention) suppressed IgE production in murine models of asthma and in asthma subjects. However, the active compounds in ASHMI responsible for the IgE suppression are still unknown.ObjectiveWe sought to identify the compound(s) in ASHMI that are responsible for IgE inhibition as well as investigate the mechanisms by which the identified compound(s) decreases IgE production.MethodsThe compounds in Sophorae Flavescentis were separated using Column chromatography and preparative-HPLC. The separated compounds were identified using LC-MS and 1H-NMR. U266 cells, an IgE-producing plasma cell line, were cultured with various concentrations of identified compounds. The levels of IgE production by the U266 cell were measured by ELISA. Trypan blue exclusion was used to determine the cell viability. The gene expression of XBP-1 and IgE-heavy chain was determined by RT-PCR.ResultsA single compound identified as formononetin was isolated from Sophorae Flavescentis. Formononetin significantly and dose dependently decreased the IgE production in U266 cells across a concentration range of 2–20 µg/ml (p

Introduction: Cytochrome P450 (CYP) 3A4 is a major drug metabolizing enzyme for corticosteroids (CS). Epimedium has been used for asthma and variety of inflammatory conditions with or without CS. It is unknown whether epimedium has an effect on CYP 3A4 and how it interacts with CS. We sought to determine the effects of epimedium on CYP3A4 and whether it affects the anti-inflammatory function of CS and identify the active compound responsible for this effect.Methods: The effect of epimedium on CYP3A4 activity was evaluated using the Vivid CYP high-throughput screening kit. CYP3A4 mRNA expression was determined in human hepatocyte carcinoma (HepG2) cells with or without epimedium, dexamethasone, rifampin, and ketoconazole. TNF-α levels were determined following co-culture of epimedium with dexamethasone in a murine macrophage cell line (Raw 264.7). Active compound (s) derived from epimedium were tested on IL-8 and TNF-α production with or without corticosteroid, on CYP3A4 function and binding affinity.Results: Epimedium inhibited CYP3A4 activity in a dose-dependent manner. Dexamethasone enhanced the expression of CYP3A4 mRNA, while epimedium inhibited the expression of CYP3A4 mRNA and further suppressed dexamethasone enhancement of CYP3A4 mRNA expression in HepG2 cells (p < 0.05). Epimedium and dexamethasone synergistically suppressed TNF-α production by RAW cells (p < 0.001). Eleven epimedium compounds were screened by TCMSP. Among the compounds identified and tested only kaempferol significantly inhibited IL-8 production in a dose dependent manner without any cell cytotoxicity (p < 0.01). Kaempferol in combination with dexamethasone showed complete elimination of TNF-α production (p < 0.001). Furthermore, kaempferol showed a dose dependent inhibition of CYP3A4 activity. Computer docking analysis showed that kaempferol significantly inhibited the catalytic activity of CYP3A4 with a binding affinity of −44.73kJ/mol.Discussion: Inhibition of CYP3A4 function by epimedium and its active compound kaempferol leads to enhancement of CS anti-inflammatory effect.

In order to investigate the carbon sequestration potential of biochar on soil, citrus orchard soils with a forest age of 5 years was taken as the research object, citrus peel biochar (OBC) and magnesium-modified citrus peel biochar (OBC-mg) were selected as additive materials, and organic carbon mineralization experiments were carried out in citrus orchard soil. OBC and OBC-Mg were applied to citrus orchard soils at four application rates (0, 1, 2, and 4%), and incubated at a constant temperature for 100 days. Compared with CK, the cumulative mineralization of soil organic carbon decreased by 5.11% with 1% OBC and 2.14% with 1% OBC-Mg. The application of OBC and OBC-Mg significantly increased the content of soil organic carbon fraction, while the content of soil organic carbon fraction was higher in OBC-Mg treated soil than in OBC treated soil. Meanwhile, the cumulative mineralization of soil organic carbon was significantly and positively correlated with the activities of soil catalase, urease and sucrase. The enzyme activities increased with the cumulative mineralization of organic carbon, and the enzyme activities of the OBC-Mg treated soil were significantly higher than those of the OBC treated soil. The results indicated that the OBC-Mg treatment inhibited the organic carbon mineralization in citrus orchard soils and was more favorable to the increase of soil organic carbon fraction. The Mg-modified approach improved the carbon sequestration potential of biochar for citrus orchard soils and provided favorable support for the theory of soil carbon sink in orchards.

ContextPersons living with HIV (PLWH) commonly experience mental health symptoms. However, little is known about the core mental health symptoms and their relationships.ObjectiveThis study aimed to evaluate the prevalence of various mental health symptoms and to explore their relationships in symptom networks among PLWH.MethodsFrom April to July 2022, we recruited 518 participants through convenience sampling in Beijing, China, for this cross-sectional study. Forty mental health symptoms, including six dimensions (somatization symptoms, negative affect, cognitive function, interpersonal communication, cognitive processes, and social adaptation), were assessed through paper-based or online questionnaires. Network analysis was performed in Python 3.6.0 to explore the core mental health symptoms and describe the relationships among symptoms and clusters.ResultsOf the 40 mental health symptoms, the most common symptoms were fatigue (71.2%), trouble remembering things (65.6%), and uncertainty about the future (64.0%). In the single symptom network, sadness was the most central symptom across the three centrality indices (rS = 0.59, rC = 0.61, rB = 0.06), followed by feeling discouraged about the future (rS = 0.51, rC = 0.57, rB = 0.04) and feelings of worthlessness (rS = 0.54, rC = 0.53, rB = 0.05). In the symptom cluster network, negative affect was the most central symptom cluster across the three centrality indices (rS = 1, rC = 1, rB = 0.43).ConclusionOur study provides a new perspective on the role of each mental health symptom among PLWH. To alleviate the mental health symptoms of PLWH to the greatest extent possible and comprehensively improve their mental health, we suggest that psychological professionals pay more attention to pessimistic mood and cognitive processes in PLWH. Interventions that apply positive psychology skills and cognitive behavioral therapy may be necessary components for the mental health care of PLWH.

Identifying effective biomarkers in osteosarcoma (OS) is important for predicting prognosis. We investigated the prognostic value of ferroptosis-related genes (FRGs) in OS. Transcriptome and clinical data were obtained from The Cancer Genome Atlas and Gene Expression Omnibus. FRGs were obtained from the ferroptosis database. Univariate COX regression and LASSO regression screening were performed and an FRG-based prognostic model was constructed, which was validated using the Gene Expression Omnibus cohort. The predictive power of the model was assessed via a subgroup analysis. A nomogram was constructed using clinical markers with independent prognostic significance and risk score results. The CIBERSORT algorithm was used to detect the correlation between prognostic genes and 22 tumor-infiltrating lymphocytes. The expression of prognostic genes in erastin-treated OS cell lines was verified via real-time PCR. Six prognostic FRGs (ACSL5, ATF4, CBS, CDO1, SCD, and SLC3A2) were obtained and used to construct the risk prognosis model. Subjects were divided into high- and low-risk groups. Prognosis was worse in the high-risk group, and the model had satisfactory prediction performance for patients younger than 18 years, males, females, and those with non-metastatic disease. Univariate COX regression analysis showed that metastasis and risk score were independent risk factors for patients with OS. Nomogram was built on independent prognostic factors with superior predictive power and patient benefit. There was a significant correlation between prognostic genes and tumor immunity. Six prognostic genes were differentially expressed in ferroptosis inducer-treated OS cell lines. The identified prognostic genes can regulate tumor growth and progression by affecting the tumor microenvironment.

BackgroundWhile the tumor microenvironment (TME) affects immune checkpoint blockade (ICB) efficacy, ICB also reshapes the characteristics of TME. Thus far, studies have focused on the TME evolution during neoadjuvant or adjuvant ICB therapy in gastric cancer (GC). However, the interaction between TME characteristics and neoadjuvant immunotherapy plus chemotherapy remains to be elucidated.MethodsWe performed single-cell RNA sequencing on ten GC specimens pre- and post-neoadjuvant camrelizumab plus mFOLFOX6 to determine the impact of the TME on the efficacy of the combination therapy and the remodeling of TME by the therapy.ResultsA high baseline interferon gamma (IFN-γ) signature in CD8+ T cells predicts better responses to the combination therapy. We also observed that the IFN-γ signature significantly decreased in multiple cell types, and the exhausted signature of CD8+ T cells was significantly suppressed during the neoadjuvant therapy.ConclusionsOur data reveal interactions between the TME and neoadjuvant immunotherapy plus chemotherapy in GC. Importantly, it also highlights the signature of CD8+ T cells in predicting response to the combination therapy in GC.

Transient receptor potential vanilloid type 4 (TRPV4) can function as an oncogene or tumor suppressor depending on the tumor types. However, little is known regarding the effect of TRPV4 in nasopharyngeal carcinoma (NPC), a highly prevalent malignancy in Southern China and Southeast Asia. We found that TRPV4 mRNA and protein levels were significantly upregulated in NPC tissues. In addition, activation of TRPV4 in NPC cell lines using GSK1016790A (100 nM) induced a Ca2+ influx, whereas pharmacological inhibition or gene knockdown of TRPV4 reduced the proliferation rates of NPC cells. TRPV4 knockdown also decreased the growth of tumor xenografts in vivo. Mechanistically, TRPV4-mediated tumorigenesis is dependent on the activation of Ca2+/calcineurin/calcineurin-nuclear factor of activated T cell 4 (NFAT4) signaling. Furthermore, NFAT4 protein level was overexpressed in NPC tissues and correlated positively with TRPV4. Taken together, TRPV4 promotes the malignant potential of NPC cells by activating NFAT4 signaling. Our findings highlight TRPV4-NFAT4 axis as a potential therapeutic target in NPC.

IntroductionSARS-CoV-2 has ravaged the world and undergone multiple mutations during the course of the COVID-19 pandemic. On 7 April 2022, an epidemic caused by SARS-CoV-2 Omicron (BA.2) variant broke out in Guangzhou, China, one of the largest transportation and logistical hubs of the country.MethodsTo fast curtained the Omicron epidemic, based on the routine surveillance on the risk population of SARS-CoV-2 infection, we identify key places of the epidemic and implement enhanced control measures against Omicron.ResultsTransmission characteristics of the Omicron variant were analyzed for 273 confirmed cases, and key places involved in this epidemic were fully presented. The median incubation time and the generation time were 3 days, and the reproduction number Rt was sharply increased with a peak of 4.20 within 2 days. We tried an all-out effort to tackle the epidemic in key places, and the proportion of confirmed cases increased from 61.17% at Stage 2 to 88.89% at Stage 4. Through delimited risk area management, 99 cases were found, and the cases were isolated in advance for 2.61 ± 2.76 days in a lockdown zone, 0.44 ± 1.08 days in a controlled zone, and 0.27 ± 0.62 days in a precautionary zone. People assigned with yellow code accounted for 30.32% (84/277) of confirmed COVID-19 cases, and 83.33% of them were detected positive over 3 days since code assignment. For the districts outside the epicenter, the implementation duration of NPIs was much shorter compared with the Delta epidemic last year.ConclusionBy blocking out transmission risks and adjusting measures to local epidemic conditions through the all-out effort to tackle the epidemic in key places, by delimiting risk area management, and by conducting health code management of the at-risk population, the Omicron epidemic could be contained quickly.

ObjectiveGPHB5 has been found to be associated with glucose and lipid metabolism in animal studies. However, the association of GPHB5 with IR and metabolic disorders remains unknown, and there is a lack of research in humans. Our aim in this study was to investigate the relationship between circulating GPHB5 and metabolic disorders in humans.MethodsBioinformatics analysis was performed to understand the relationship between GPHB5 and metabolic disorders. GPHB5 mRNA expression in mice and rats was determined using RT-qPCR. Circulating GPHB5 concentrations were measured with an ELISA kit. EHC and OGTT were performed in humans.ResultsBioinformatics analysis shows that GPHB5 is associated with metabolic disorders and PCOS. GPHB5 mRNA expression levels in the metabolic-related tissues of HFD-fed mice, db/db and ob/ob mice, and PCOS rats were significantly higher than those of WT mice or rats. In human studies, we find that circulating GPHB5 levels were significantly higher in women with IR and PCOS. GPHB5 levels were positively correlated with age, BMI, WHR, BP, FBG, 2 h-BG, FIns, 2 h-Ins, TC, LDL-C, HbA1c, and FFA, but negatively correlated with adiponectin. Furthermore, GPHB5 was positively correlated with DHEAS and FAI, while negatively correlated with SHBG, FSH, SHBG and FSH. The increased GPHB5 concentration was related to IR and PCOS. After the treatment of metformin, GLP-1RA (Lira), and TZDs, circulating GPHB5 levels were decreased.ConclusionsOur results reveal that circulating GPHB5 could be a biomarker and potential therapeutic target for IR and PCOS in women.