Bicontinuous RuO2 nanoreactors for acidic water oxidation.

Improving activity and stability of Ruthenium (Ru)-based catalysts in acidic environments is eager to replace more expensive Iridium (Ir)-based materials as practical anode catalyst for proton-exchange membrane water electrolyzers (PEMWEs). Here, a bicontinuous nanoreactor composed of multiscale defective RuO2 nanomonomers (MD-RuO2-BN) is conceived and confirmed by three-dimensional tomograph reconstruction technology. The unique bicontinuous nanoreactor structure provides abundant active sites and rapid mass transfer capability through a cavity confinement effect. Besides, existing vacancies and grain boundaries endow MD-RuO2-BN with generous low-coordination Ru atoms and weakened Ru-O interaction, inhibiting the oxidation of lattice oxygen and dissolution of high-valence Ru. Consequently, in acidic media, the electron- and micro-structure synchronously optimized MD-RuO2-BN achieves hyper water oxidation activity (196 mV @ 10 mA cm-2) and an ultralow degradation rate of 1.2 mV h-1. A homemade PEMWE using MD-RuO2-BN as anode also conveys high water splitting performance (1.64 V @ 1 A cm-2). Theoretical calculations and in-situ Raman spectra further unveil the electronic structure of MD-RuO2-BN and the mechanism of water oxidation processes, rationalizing the enhanced performance by the synergistic effect of multiscale defects and protected active Ru sites.

A novel nonparametric time-dependent precision-recall curve estimator for right-censored survival data.

In order to assess prognostic risk for individuals in precision health research, risk prediction models are increasingly used, in which statistical models are used to estimate the risk of future outcomes based on clinical and nonclinical characteristics. The predictive accuracy of a risk score must be assessed before it can be used in routine clinical decision making, where the receiver operator characteristic curves, precision-recall curves, and their corresponding area under the curves are commonly used metrics to evaluate the discriminatory ability of a continuous risk score. Among these the precision-recall curves have been shown to be more informative when dealing with unbalanced biomarker distribution between classes, which is common in rare event, even though except one, all existing methods are proposed for classic uncensored data. This paper is therefore to propose a novel nonparametric estimation approach for the time-dependent precision-recall curve and its associated area under the curve for right-censored data. A simulation is conducted to show the better finite sample property of the proposed estimator over the existing method and a real-world data from primary biliary cirrhosis trial is used to demonstrate the practical applicability of the proposed estimator.

[Scale Effects of Landscape Pattern on Impacts of River Water Quality： A Meta-analysis].

The landscape pattern determines water pollution source and sink processes and plays an important role in regulating river water quality. Due to scale effects, studies on the relationship between landscape pattern and river water quality showed variance at different scales. However, there is still a lack of integrated study on the scale effect of landscape pattern and river water quality dynamics. This study collected 4 041 data from results of previous publications to address the characteristics of landscape pattern and river water quality dynamics at different scales and to identify the key temporal and spatial scales as well as landscape pattern indices for regulating river water quality. The results indicated that, compared to precipitation events, base flow periods, and interannual scales, the high-flow period was the key temporal scale for linking landscape pattern on river water quality. Compared to the watershed scale, the landscape pattern of buffer zones had a greater impact on river water quality. The high-flow period-buffer zone scale was the key spatiotemporal coupling scale for linking landscape pattern and river water quality. Compared to croplands, water bodies, grasslands, and the overall landscape of the watershed, the landscape pattern of forests and urban areas had a greater impact on river water quality. Fragmentation degree was the most important landscape pattern factor regulating river water quality. In river water quality management, it is important to focus on the landscape configuration of buffer zones, increase forest area, reduce patch density of forests and water bodies, and decrease the aggregation degree of urban areas.

Benefit analysis of the auto-verification system of intelligent inspection for microorganisms.

In recent years, the automatic machine for microbial identification and antibiotic susceptibility tests has been introduced into the microbiology laboratory of our hospital, but there are still many steps that need manual operation. The purpose of this study was to establish an auto-verification system for bacterial naming to improve the turnaround time (TAT) and reduce the burden on clinical laboratory technologists. After the basic interpretation of the gram staining results of microorganisms, the appearance of strain growth, etc., the 9 rules were formulated by the laboratory technologists specialized in microbiology for auto-verification of bacterial naming. The results showed that among 70,044 reports, the average pass rate of auto-verification was 68.2%, and the reason for the failure of auto-verification was further evaluated. It was found that the main causes reason the inconsistency between identification results and strain appearance rationality, the normal flora in the respiratory tract and urine that was identified, the identification limitation of the mass spectrometer, and so on. The average TAT for the preliminary report of bacterial naming was 35.2 h before, which was reduced to 31.9 h after auto-verification. In summary, after auto-verification, the laboratory could replace nearly 2/3 of manual verification and issuance of reports, reducing the daily workload of medical laboratory technologists by about 2 h. Moreover, the TAT on the preliminary identification report was reduced by 3.3 h on average, which could provide treatment evidence for clinicians in advance.

Host-Host Interactions Enhanced the Structural Rigidity in a 6-Fold Interpenetrated Diamondoid Metal-Organic Framework Exhibiting C2H2/C2H4 Separation.

Multi-interpenetrated metal-organic frameworks (MOFs) have exhibited excellent performance in selective adsorption due to the variable post-interspersed flexibility, but the design and control remain challenging. Herein, two anthracene-based ligands, 4,4'-(anthracene-9,10-diyl)dibenzoic acid (H2L1) and 9,10-di(pyridin-4-yl)anthracene (L2), are used to construct a new three-dimensional 6-fold interpenetrated MOF [Zn(L1)(L2)]n (NBU-X1), which exhibits multiple C-H···π interactions that enhance the structural rigidity, thereby entangling with a C2H2/C2H4 separation performance. In this material, the incorporation of abundant anthracene rings within the framework not only partitions and restricts the pore window size to a quasi-double pore but also stabilizes it through host-host interactions. The structural stability upon heating or guest displacement/removal has been investigated by single-crystal X-ray diffraction and in situ variable-temperature powder X-ray diffraction, in contrast to the extreme flexibility of most multi-interpenetrated MOFs. The performance of purifying C2H4 from C2H2/C2H4 mixtures has been proved by dynamic breakthrough tests.

FOXP4-AS1 promotes CD8+ T cell exhaustion and esophageal cancer immune escape through USP10-stabilized PD-L1.

Esophageal cancer (EC) is the 9th most frequently diagnosed malignancy globally with unfavorable prognosis. Immune escape is one of the principal factors leading to poor survival, however, the mechanism underlying immune escape remains largely uninvestigated. The xenograft mouse model and EC cell-CD8+ cytotoxic T lymphocytes (CTLs) co-culture system were established. Immunohistochemistry, qRT-PCR or western blot were employed to detect the levels of long non-coding RNA (lncRNA) FOXP4-AS1, PD-L1, USP10 and other molecules. The abundance of T cells, cytokine production and cell apoptosis were monitored by flow cytometry. The viability of CTLs was assessed by Trypan blue staining. The binding between FOXP4-AS1 and USP10 was validated by RNA pull-down assay, and the interaction between USP10 and PD-L1, as well as the ubiquitination of PD-L1, were detected by co-immunoprecipitation. The elevation of FOXP4-AS1 in EC was associated with decreased CTL abundance, and upregulated PD-L1 facilitated CTL apoptosis in EC. FOXP4-AS1 accelerated EC tumor growth by decreasing the abundance of tumor infiltrating CTLs in vivo. FOXP4-AS1 inhibited the viability of CTLs and facilitated the cytotoxicity and exhaustion of CTLs. In Kyse 450 cell-CTL co-culture system, FOXP4-AS1 suppressed the viability and abundance of CTLs, and inhibited EC cell apoptosis via PD-L1. Mechanistically, FOXP4-AS1 regulated the ubiquitination of PD-L1 through deubiquitinating enzyme USP10. FOXP4-AS1 promoted CTL exhaustion and EC immune escape through USP10-stabilized PD-L1. HIGHLIGHTS: PD-L1 facilitated CD8+ T cell apoptosis in EC. Upregulated FOXP4-AS1 promoted EC tumor growth by inhibiting the viability and facilitating the cytotoxicity and exhaustion of tumor infiltrating CD8+ T cells. FOXP4-AS1 suppressed the viability and abundance of CD8+ T cells through USP10-mediated deubiquitination of PD-L1.

Phthalate metabolites and sex steroid hormones in relation to obesity in US adults: NHANES 2013-2016.

Background: Obesity and metabolic syndrome pose significant health challenges in the United States (US), with connections to disruptions in sex hormone regulation. The increasing prevalence of obesity and metabolic syndrome might be associated with exposure to phthalates (PAEs). Further exploration of the impact of PAEs on obesity is crucial, particularly from a sex hormone perspective. Methods: A total of 7780 adult participants in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016 were included in the study. Principal component analysis (PCA) coupled with multinomial logistic regression was employed to elucidate the association between urinary PAEs metabolite concentrations and the likelihood of obesity. Weighted quartiles sum (WQS) regression was utilized to consolidate the impact of mixed PAEs exposure on sex hormone levels (total testosterone (TT), estradiol and sex hormone-binding globulin (SHBG)). We also delved into machine learning models to accurately discern obesity status and identify the key variables contributing most to these models. Results: Principal Component 1 (PC1), characterized by mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) as major contributors, exhibited a negative association with obesity. Conversely, PC2, with monocarboxyononyl phthalate (MCNP), monocarboxyoctyl phthalate (MCOP), and mono(3-carboxypropyl) phthalate (MCPP) as major contributors, showed a positive association with obesity. Mixed exposure to PAEs was associated with decreased TT levels and increased estradiol and SHBG. During the exploration of the interrelations among obesity, sex hormones, and PAEs, models based on Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) algorithms demonstrated the best classification efficacy. In both models, sex hormones exhibited the highest variable importance, and certain phthalate metabolites made significant contributions to the model's performance. Conclusions: Individuals with obesity exhibit lower levels of TT and SHBG, accompanied by elevated estradiol levels. Exposure to PAEs disrupts sex hormone levels, contributing to an increased risk of obesity in US adults. In the exploration of the interrelationships among these three factors, the RF and XGBoost algorithm models demonstrated superior performance, with sex hormones displaying higher variable importance.

[Nitrate Pollution Characteristics and Its Quantitative Source Identification of Major River Systems in China].

Accurate source identification/apportionment is essential for optimizing water NO3--N pollution control strategies. This study conducted a meta-analysis based on data from 167 rivers across China from 2000 to 2022 to analyze the spatial and temporal variation patterns of nitrate pollution in seven major river systems and to quantitatively identify the source composition of riverine nitrate. The average ρ（NO3--N） in the seven major river systems was （4.54±3.99） mg·L-1， with 9.6% of river ρ（NO3--N） exceeding 10 mg·L-1. The riverine ρ（NO3--N） in eastern China were higher than that in western China， and the highest concentration was observed in the Haihe River system. Additionally， tributaries experienced more serious NO3--N pollution than that in the main stream. The ρ（NO3--N） in most river systems in the dry season was higher than that in the wet season， except in the Yellow River system. There was significant nitrification in the Pearl River system， the middle and lower reaches of the Yellow River system， the middle reaches of the Liaohe River system， the Songhua River system， and the Haihe River system， whereas there was significant denitrification in the Yangtze River system， the Huaihe River system， and the lower reaches of the Pearl River system. Based on the dual stable isotopes-based MixSIAR model， the major NO3--N source was sewage/manure （ > 50%） in the Yangtze River system， Haihe River system， Liaohe River system， and Southeast River system. Soil nitrogen was the main NO3--N source in the Songhua River system （56.4%）， and the contribution of fertilizer nitrogen， soil nitrogen， and sewage/manure to NO3--N pollution in the Pearl River system， Huai River system， and Yellow River system was 20%-40%. The contribution rate of sewage/manure to NO3--N in the tributaries was higher than that in the main stream， whereas the contribution rate of soil nitrogen to NO3--N in the main stream was higher than that in the tributaries. The contribution rate of soil nitrogen， fertilizer nitrogen， and atmospheric deposition nitrogen to nitrate nitrogen in the wet season was higher than that in the dry season， whereas the contribution rate of sewage/manure to NO3--N pollution in the dry season was higher than that in the wet season. Therefore， point source pollution such as domestic and production sewage discharge should be controlled in the Haihe River system， the Yangtze River system， the Liaohe River system， the tributaries and the downstream main stream areas of Yellow River system， and the downstream area of the Pearl River system， whereas non-point source pollution caused by the loss of fertilizer and soil nitrogen should be controlled in the Huaihe River system， the Songhua River system， the middle reaches of the main stream area of the Yellow River system， and the middle and upper reaches of the Pearl River system. The results can provide a scientific basis for the effective control of nitrate pollution in the river systems in China.

Comparison of the cachexia index based on hand-grip strength (H-CXI) with the original CXI for the prediction of cancer cachexia and prognosis in patients who underwent radical colectomy for colorectal cancer.

Background and aims: The cachexia index (CXI) is a novel biomarker for estimating cancer cachexia. The cachexia index based on hand-grip strength (H-CXI) has been recently developed as a simple proxy for CXI. The present study aims to compare both the H-CXI and CXI for the prediction of cancer cachexia and postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. Methods: Patients who underwent radical operations for colorectal cancer were included in this study. Cancer cachexia was diagnosed according to the international consensus outlined by Fearon et al. The cachexia index (CXI) was calculated as [skeletal muscle index (SMI) × serum albumin/neutrophil-to-lymphocyte ratio (NLR)]. The H-CXI was calculated as [hand-grip strength (HGS)/height2 × serum albumin/NLR]. The SMI was measured based on the preoperative CT images at the third lumbar vertebra (L3) level. HGS was measured before surgery. Results: From July 2014 to May 2021, a total of 1,411 patients were included in the present study, of whom 361 (25.6%) were identified as having cancer cachexia. Patients with cachexia had a lower CXI (p < 0.001) and lower H-CXI (p < 0.001) than those without cachexia. A low CXI but not low H-CXI independently predicted cancer cachexia in the multivariate analysis (OR 1.448, p = 0.024). Both a low CXI (HR 1.476, p < 0.001 for OS; HR 1.611, p < 0.001 for DFS) and low H-CXI (HR 1.369, p = 0.007 for OS; HR 1.642, p < 0.001 for DFS) were independent predictors for overall survival (OS) and disease-free survival (DFS) after adjusting for the same covariates. A low H-CXI but not low CXI was an independent risk factor for postoperative complications (OR 1.337, p = 0.044). No significant association was found between cancer cachexia and postoperative complications. Conclusion: The CXI and H-CXI exhibited better prognostic value than cancer cachexia for the prediction of postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. The H-CXI was a superior index over the CXI in predicting short-term clinical outcomes, whereas the CXI demonstrated a closer correlation with Fearon's criteria for cancer cachexia. Ideal tools for the assessment of cancer cachexia should incorporate not only weight loss but also muscle mass, physical function, and inflammatory state.

Selective activation of MoS2 grain boundaries for enhanced electrochemical activity.

Molybdenum disulfide (MoS2) has emerged as a promising material for catalysis and sustainable energy conversion. However, the inertness of its basal plane to electrochemical reactions poses challenges to the utilization of wafer-scale MoS2 in electrocatalysis. To overcome this limitation, we present a technique that enhances the catalytic activity of continuous MoS2 by preferentially activating its buried grain boundaries (GBs). Through mild UV irradiation, a significant enhancement in GB activity was observed that approaches the values for MoS2 edges, as confirmed by a site-selective photo-deposition technique and micro-electrochemical hydrogen evolution reaction (HER) measurements. Combined spectroscopic characterization and ab-initio simulation demonstrates substitutional oxygen functionalization at the grain boundaries to be the origin of this selective catalytic enhancement by an order of magnitude. Our approach not only improves the density of active sites in MoS2 catalytic processes but yields a new photocatalytic conversion process. By exploiting the difference in electronic structure between activated GBs and the basal plane, homo-compositional junctions were realized that improve the photocatalytic synthesis of hydrogen by 47% and achieve performances beyond the capabilities of other catalytic sites.

The m6A modification-mediated positive feedback between glycolytic lncRNA SLC2A1-DT and c-Myc promotes tumorigenesis of hepatocellular carcinoma.

Glycolysis exerts a key role in the metabolic reprogramming of cancer. Specific long non-coding RNAs (lncRNAs) have been identified to exhibit oncogenic glycolysis regulation. Nevertheless, the precise mechanisms by which glycolysis-related lncRNAs control hepatocellular carcinoma (HCC) are still unknown. We profiled and analyzed glycolysis-associated lncRNA signatures using HCC specimens from The Cancer Genome Atlas (TCGA) dataset. Considerable upregulation of the glycolysis-related lncRNA SLC2A1-DT was noted in HCC tissues; this upregulation was strongly linked with advanced tumor stage and poor prognosis. Cell culture and animal-related studies indicated that knockdown or overexpression of SLC2A1-DT obviously restrained or promoted glycolysis, propagation, and metastasis in HCC cells. Mechanistically, SLC2A1-DT enhanced the interaction of protein between ß-catenin and YWHAZ, suppressing the binding between ß-catenin and ß-TrCP, an E3 ubiquitin ligase. Thereby, SLC2A1-DT impeded the ß-TrCP-dependent ubiquitination and ß-catenin degradation. The upregulated ß-catenin activated the transcription of c-Myc, which then increased the transcription of glycolytic genes including SLC2A1, LDHA, and HK2. Additionally, we revealed that c-Myc transcriptionally induced the expression of methyltransferase 3 (METTL3), which increased N6-methyladenosine (m6A) modification and stability of SLC2A1-DT in a YTHDF1 dependent manner. Collectively, we show that the lncRNA SLC2A1-DT promotes glycolysis and HCC tumorigenesis by a m6A modification-mediated positive feedback mechanism with glycolytic regulator c-Myc and suggested as an innovative treatment option and indicator for HCC.

Secretory IgA reduced the ergosterol contents of Candida albicans to repress its hyphal growth and virulence.

Candida albicans, one of the most prevalent conditional pathogenic fungi, can cause local superficial infections and lethal systemic infections, especially in the immunocompromised population. Secretory immunoglobulin A (sIgA) is an important immune protein regulating the pathogenicity of C. albicans. However, the actions and mechanisms that sIgA exerts directly against C. albicans are still unclear. Here, we investigated that sIgA directs against C. albicans hyphal growth and virulence to oral epithelial cells. Our results indicated that sIgA significantly inhibited C. albicans hyphal growth, adhesion, and damage to oral epithelial cells compared with IgG. According to the transcriptome and RT-PCR analysis, sIgA significantly affected the ergosterol biosynthesis pathway. Furthermore, sIgA significantly reduced the ergosterol levels, while the addition of exogenous ergosterol restored C. albicans hyphal growth and adhesion to oral epithelial cells, indicating that sIgA suppressed the growth of hyphae and the pathogenicity of C. albicans by reducing its ergosterol levels. By employing the key genes mutants (erg11Δ/Δ, erg3Δ/Δ, and erg3Δ/Δ erg11Δ/Δ) from the ergosterol pathway, sIgA lost the hyphal inhibition on these mutants, while sIgA also reduced the inhibitory effects of erg11Δ/Δ and erg3Δ/Δ and lost the inhibition of erg3Δ/Δ erg11Δ/Δ on the adhesion to oral epithelial cells, further proving the hyphal repression of sIgA through the ergosterol pathway. We demonstrated for the first time that sIgA inhibited C. albicans hyphal development and virulence by affecting ergosterol biosynthesis and suggest that ergosterol is a crucial regulator of C. albicans-host cell interactions. KEY POINTS: • sIgA repressed C. albicans hyphal growth • sIgA inhibited C. albicans virulence to host cells • sIgA affected C. albicans hyphae and virulence by reducing its ergosterol levels.

FGF1ΔHBS ameliorates retinal inflammation via suppressing TSPO signal in a type 2 diabetes mouse model.

Translocator protein (18 kDa) (TSPO) plays an important role in retinal neuroinflammation in the early stage of diabetic retinopathy (DR). Studies have found that a FGF1 variant (FGF1ΔHBS) with reduced proliferative potency exerts excellent anti-inflammatory effects and potential therapeutic value for diabetic complications. In this study, intravitreal injection of FGF1ΔHBS was administrated every week for one month in db/db mice, which are genetically predisposed to develop type 2 diabetes mellitus and early retinopathy. Changes in retinal function and structure in the animal models were detected by electrophysiology (ERG) and optical tomography coherence (OCT). TSPO expression and retinal inflammation were analyzed by immunofluorescence, Western blot and real-time qPCR. In the retina of T2D (db/db) mice, FGF1 was significantly down-regulated while FGFR1 was up-regulated (both p < 0.05). TSPO and retinal inflammatory factors were all up-regulated. TSPO and FGFR1 were mainly co-stained in the inner retina. After FGF1ΔHBS treatment, ERG showed that the total amplitude of dark-adapted b-wave and oscillating potentials (Ops) was significantly improved, and OCT showed that the thickness of the retina around the optical nerve head was significantly preserved in T2D mice (all p < 0.05). The TSPO signal was significantly suppressed by FGF1ΔHBS. The activation of NF-κB p65 and the expression of inflammatory factors such as TNF-α, IL-1ß, IL-6, COX-2, MIP-1α, and iNOS were all significantly down-regulated (all p < 0.05). Collectively, our current data demonstrated that intravitreal FGF1ΔHBS treatment can effectively inhibit retinal inflammation via suppressing TSPO signal and to preserve retinal function and structure in a T2D mouse model.

Fully Spiking Actor Network With Intralayer Connections for Reinforcement Learning.

With the help of special neuromorphic hardware, spiking neural networks (SNNs) are expected to realize artificial intelligence (AI) with less energy consumption. It provides a promising energy-efficient way for realistic control tasks by combining SNNs with deep reinforcement learning (DRL). In this article, we focus on the task where the agent needs to learn multidimensional deterministic policies to control, which is very common in real scenarios. Recently, the surrogate gradient method has been utilized for training multilayer SNNs, which allows SNNs to achieve comparable performance with the corresponding deep networks in this task. Most existing spike-based reinforcement learning (RL) methods take the firing rate as the output of SNNs, and convert it to represent continuous action space (i.e., the deterministic policy) through a fully connected (FC) layer. However, the decimal characteristic of the firing rate brings the floating-point matrix operations to the FC layer, making the whole SNN unable to deploy on the neuromorphic hardware directly. To develop a fully spiking actor network (SAN) without any floating-point matrix operations, we draw inspiration from the nonspiking interneurons found in insects and employ the membrane voltage of the nonspiking neurons to represent the action. Before the nonspiking neurons, multiple population neurons are introduced to decode different dimensions of actions. Since each population is used to decode a dimension of action, we argue that the neurons in each population should be connected in time domain and space domain. Hence, the intralayer connections are used in output populations to enhance the representation capacity. This mechanism exists extensively in animals and has been demonstrated effectively. Finally, we propose a fully SAN with intralayer connections (ILC-SAN). Extensive experimental results demonstrate that the proposed method outperforms the state-of-the-art performance on continuous control tasks from OpenAI gym. Moreover, we estimate the theoretical energy consumption when deploying ILC-SAN on neuromorphic chips to illustrate its high energy efficiency.

Tenascin-C as a potential biomarker and therapeutic target for esophageal squamous cell carcinoma.

PURPOSE: To establish a prognostic model of esophageal squamous cell carcinoma (ESCC) patients based on tenascin-C (TNC) expression level and clinicopathological characteristics, and to explore the therapeutic potential of TNC inhibition. METHODS: The expression of TNC was detected using immunohistochemistry (IHC) in 326 ESCC specimens and 50 normal esophageal tissues. Prognostic factors were determined by Cox regression analyses and were incorporated to establish the nomogram. The effects of TNC knockdown on ESCC cells were assessed in vitro and in vivo. Transcriptome sequencing (RNA-seq) and gene set enrichment analysis (GSEA) were performed to reveal signaling pathways regulated by TNC knockdown. The therapeutic significance of TNC knockdown combined with small-molecule inhibitors on cell proliferation was examined. RESULTS: TNC protein was highly expressed in 48.77 % of ESCC tissues compared to only 2 % in normal esophageal epithelia (p < 0.001). The established nomogram model, based on TNC expression, pT stage, and lymph node metastasis, showed good performance on prognosis evaluation. More importantly, the reduction of TNC expression inhibited tumor cell proliferation and xenograft growth, and mainly down-regulated signaling pathways involved in tumor growth, hypoxia signaling transduction, metabolism, infection, etc. Knockdown of TNC enhanced the inhibitory effect of inhibitors targeting ErbB, PI3K-Akt, Ras and MAPK signaling pathways. CONCLUSION: The established nomogram may be a promising model for survival prediction in ESCC. Reducing TNC expression enhanced the sensitivity of ESCC cells to inhibitors of Epidermal Growth Factor Receptor (EGFR) and downstream signaling pathways, providing a novel combination therapy strategy.

Performance of diagnostic tests based on continuous bivariate markers.

In medical diagnostic research, it is customary to collect multiple continuous biomarker measures to improve the accuracy of diagnostic tests. A prevalent practice is to combine the measurements of these biomarkers into one single composite score. However, incorporating those biomarker measurements into a single score depends on the combination of methods and may lose vital information needed to make an effective and accurate decision. Furthermore, a diagnostic cut-off is required for such a combined score, and it is difficult to interpret in actual clinical practice. The paper extends the classical biomarkers' accuracy and predictive values from univariate to bivariate markers. Also, we will develop a novel pseudo-measures system to maximize the vital information from multiple biomarkers. We specified these pseudo-and-or classifiers for the true positive rate, true negative rate, false-positive rate, and false-negative rate. We used them to redefine classical measures such as the Youden index, diagnostics odds ratio, likelihood ratios, and predictive values. We provide optimal cut-off point selection based on the modified Youden index with numerical illustrations and real data analysis for this paper's newly developed pseudo measures.

Predicting Severity in Hypertriglyceridemia-Induced Acute Pancreatitis: The Role of Neutrophils, Calcium, and Apolipoproteins.

BACKGROUND Hypertriglyceridemia-induced acute pancreatitis (HTG-AP), representing 10% of all acute pancreatitis cases, is characterized by younger onset age and more severe progression, often leading to higher ICU admission rates. This condition poses a significant challenge due to its rapid progression and the potential for severe complications, including multiple organ failure. HTG-AP is distinct from other forms of pancreatitis, such as those caused by cholelithiasis or alcohol, in terms of clinical presentation and outcomes. It's essential to identify early markers that can predict the severity of HTG-AP to improve patient management and outcomes. MATERIAL AND METHODS This study divided 127 HTG-AP patients into mild acute pancreatitis (MAP, n=71) and moderate-to-severe acute pancreatitis (MSAP/SAP, n=56) groups. Blood biological indicators within the first 24 hours of admission were analyzed. Risk factors for HTG-AP progression were determined using binary logistic regression and ROC curves. RESULTS Elevated levels of HCT, NLR, TBI, DBI, AST, Cre, and AMS were noted in the MSAP/SAP group, with lower levels of LYM, Na⁺, Ca²âº, ApoA, and ApoB compared to the MAP group (p<0.05). NEUT%, Ca²âº, ApoA, and ApoB were significantly linked with HTG-AP severity. Their combined ROC analysis yielded an area of 0.81, with a sensitivity of 61.8% and specificity of 90%. CONCLUSIONS NEUT%, Ca²âº, ApoA, and ApoB are significant risk factors for progressing to MSAP/SAP in HTG-AP. Their combined assessment provides a reliable predictive measure for early intervention in patients at risk of severe progression.

Symmetry-Broken Ru Nanoparticles with Parasitic Ru-Co Dual-Single Atoms Overcome the Volmer Step of Alkaline Hydrogen Oxidation.

Efficient dual-single-atom catalysts are crucial for enhancing atomic efficiency and promoting the commercialization of fuel cells, but addressing the sluggish kinetics of hydrogen oxidation reaction (HOR) in alkaline media and the facile dual-single-atom site generation remains formidable challenges. Here, we break the local symmetry of ultra-small ruthenium (Ru) nanoparticles by embedding cobalt (Co) single atoms, which results in the release of Ru single atoms from Ru nanoparticles on reduced graphene oxide (Co1 Ru1,n /rGO). In situ operando spectroscopy and theoretical calculations reveal that the oxygen-affine Co atom disrupts the symmetry of ultra-small Ru nanoparticles, resulting in parasitic Ru and Co dual-single-atom within Ru nanoparticles. The interaction between Ru single atoms and nanoparticles forms effective active centers. The parasitism of Co atoms modulates the adsorption of OH intermediates on Ru active sites, accelerating HOR kinetics through faster formation of *H2 O. As anticipated, Co1 Ru1,n /rGO exhibits ultrahigh mass activity (7.68 A mgRu -1 ) at 50 mV and exchange current density (0.68 mA cm-2 ), which are 6 and 7 times higher than those of Ru/rGO, respectively. Notably, it also displays exceptional durability surpassing that of commercial Pt catalysts. This investigation provides valuable insights into hybrid multi-single-atom and metal nanoparticle catalysis.

Inflammatory recruitment of healthy hematopoietic stem and progenitor cells in the acute myeloid leukemia niche.

Inflammation in the bone marrow (BM) microenvironment is a constitutive component of leukemogenesis in acute myeloid leukemia (AML). Current evidence suggests that both leukemic blasts and stroma secrete proinflammatory factors that actively suppress the function of healthy hematopoietic stem and progenitor cells (HSPCs). HSPCs are also cellular components of the innate immune system, and we reasoned that they may actively propagate the inflammation in the leukemic niche. In two separate congenic models of AML we confirm by evaluation of the BM plasma secretome and HSPC-selective single-cell RNA sequencing (scRNA-Seq) that multipotent progenitors and long-lived stem cells adopt inflammatory gene expression programs, even at low leukemic infiltration of the BM. In particular, we observe interferon gamma (IFN-γ) pathway activation, along with secretion of its chemokine target, CXCL10. We show that AML-derived nanometer-sized extracellular vesicles (EVAML) are sufficient to trigger this inflammatory HSPC response, both in vitro and in vivo. Altogether, our studies indicate that HSPCs are an unrecognized component of the inflammatory adaptation of the BM by leukemic cells. The pro-inflammatory conversion and long-lived presence of HSPCs in the BM along with their regenerative re-expansion during remission may impact clonal selection and disease evolution.

Naringin-induced M2 macrophage polarization facilitates osteogenesis of BMSCs and improves cranial bone defect healing in rat.

Osteoimmunology has uncovered the critical role of the immune microenvironment in the bone healing process, with macrophages playing a central part in generating immune responses via chemokine production. Naringin, a flavanone glycoside extracted from various plants, has been shown to promote osteoblast differentiation, thereby enhancing bone formation and mitigating osteoporosis progression. Current research on the osteogenic mechanism primarily focuses on the direct impact of naringin on mesenchymal stem cells, while its indirect immunoregulatory effects remain elusive. In this study, we investigated the bone defect-enhancing effects of varying naringin concentrations in vivo using a cranial bone defect model in Sprague-Dawley rats. We assessed the osteoimmune modulation capacity of naringin by exposing lipopolysaccharide (LPS)-induced RAW 264.7 macrophages to different doses of naringin. To further elucidate the underlying osteogenic enhancement mechanism, Bone Marrow Stromal Cells (BMSCs) derived from mice were treated with conditioned media from naringin-treated macrophages. Our findings indicated that naringin promotes M2 phenotype polarization in macrophages, as evidenced by the downregulation of pro-inflammatory cytokines Inducible Nitric Oxide Synthase (iNOS), interleukin (IL)-1ß, and Tumor Necrosis Factor (TNF)-α, and the upregulation of anti-inflammatory cytokine Transforming growth factor (TGF)-ß. Transcriptome analysis revealed that differentially expressed genes were significantly enriched in osteoblast differentiation and anti-inflammatory response pathways in naringin-pretreated macrophages, with the cytokines signaling pathway being upregulated. The conditioned media from naringin-treated macrophages stimulated the expression of osteogenic-related genes Alkaline phosphatase (Alp), osteocalcin (Ocn), osteopontin (Opn), and Runt-related transcription factor (Runx) 2, as well as protein expression in BMSCs. In conclusion, naringin alleviates macrophage inflammation by promoting M2 phenotype polarization, which in turn enhances the osteogenic differentiation of BMSCs, contributing to its bone healing effects in vivo. These results suggest that naringin holds significant potential for improving bone defect healing through osteoimmune modulation.