Microfluidic Immunosensing Platform Based on a Rolling Circle Amplification-Assisted DNA Dendrimer Probe for Portable and Sensitive Detection of Allergen-Specific IgE.

The robust point-of-care platform for sensitive, multiplexed, and affordable detection of allergen-specific IgE (sIgE) is an urgent demand in component-resolved diagnostics. Here, we developed a microfluidic immunosensing platform based on a rolling circle amplification-assisted DNA dendrimer probe for sensitive detection of multiple sIgEs. The versatile multichannel microfluidic whole blood analytical device integrates cell filtration, recombinant antigen-modified magnetic enrichment, and DNA dendrimer probe-amplified signal transduction for portable on-chip analysis. Three sIgEs against common oyster allergens were simultaneously detected in blood samples by simple smartphone-based imaging without any pretreatment. The quantitative detection of multiple allergen-specific antibodies on the platform was achieved with limits of detection of less than 50 pg/mL, exhibiting superior sensitivity compared to most point-of-care testing. The detection results of 55 serum samples and 4 whole blood samples were 100% consistent with the ELISA results, confirming the accuracy and stability of our platform. Additionally, the reversible combination of hexahistidine6-tag and Ni-IMAC magbead was elegantly utilized on the immunosensing platform for desired reversibility. With the advantages of general applicability, high sensitivity, and reversibility, the DNA dendrimer-based microfluidic immunosensing platform provides great potential for the portable detection of immune proteins as a point-of-care platform in disease diagnostics and biological analysis.

Layer-by-layer assembly of quercetin-loaded zein/γPGA/low-molecular-weight chitosan/fucoidan nanosystem for targeting inflamed blood vessels.

Chitosan acts as a versatile carrier in polymeric nanoparticle (NP) for diverse drug administration routes. Delivery of antioxidants, such as quercetin (Qu) showcases potent antioxidant and anti-inflammatory properties for reduction of various cardiovascular diseases, but low water solubility limits uptake. To address this, we developed a novel layer-by-layer zein/gamma-polyglutamic acid (γPGA)/low-molecular-weight chitosan (LC)/fucoidan NP for encapsulating Qu and targeting inflamed vessel endothelial cells. We used zein (Z) and γPGA (r) to encapsulate Qu (Qu-Zr NP) exhibited notably higher encapsulation efficiency compared to zein alone. Qu-Zr NP coated with LC (Qu-ZrLC2 NP) shows a lower particle size (193.2 ± 2.9 nm), and a higher zeta potential value (35.2 ± 0.4 mV) by zeta potential and transmission electron microscopy analysis. After coating Qu-ZrLC2 NP with fucoidan, Qu-ZrLC2Fa NP presented particle size (225.16 ± 0.92 nm), zeta potential (-25.66 ± 0.51 mV) and maintained antioxidant activity. Further analysis revealed that Qu-ZrLC2Fa NP were targeted and taken up by HUVEC cells and EA.hy926 endothelial cells. Notably, we observed Qu-ZrLC2Fa NP targeting zebrafish vessels and isoproterenol-induced inflamed vessels of rat. Our layer-by-layer formulated zein/γPGA/LC/fucoidan NP show promise as a targeted delivery system for water-insoluble drugs. Qu-ZrLC2Fa NP exhibit potential as an anti-inflammatory therapeutic for blood vessels.

An EEG Dataset of Neural Signatures in a Competitive Two-Player Game Encouraging Deceptive Behavior.

Studying deception is vital for understanding decision-making and social dynamics. Recent EEG research has deepened insights into the brain mechanisms behind deception. Standard methods in this field often rely on memory, are vulnerable to countermeasures, yield false positives, and lack real-world relevance. Here, we present a comprehensive dataset from an EEG-monitored competitive, two-player card game designed to elicit authentic deception behavior. Our extensive dataset contains EEG data from 12 pairs (N = 24 participants with role switching), controlled for age, gender, and risk-taking, with detailed labels and annotations. The dataset combines standard event-related potential and microstate analyses with state-of-the-art decoding approaches of four scenarios: spontaneous/instructed truth-telling and lying. This demonstrates game-based methods' efficacy in studying deception and sets a benchmark for future research. Overall, our dataset represents a unique resource with applications in cognitive neuroscience and related fields for studying deception, competitive behavior, decision-making, inter-brain synchrony, and benchmarking of decoding frameworks in a difficult, high-level cognitive task.

Soy protein isolate-catechin complexes conjugated by pre-heating treatment for enhancing emulsifying properties: Molecular structures and binding mechanisms.

This study aimed to investigate the impact of different pre-heating temperatures (ranging from 40 °C to 80 °C) on the interactions between soy protein isolate (SPI) and catechin to effectively control catechin encapsulation efficiency and optimize the emulsifying properties of soy protein isolate. Results showed that optimal heat treatment at 70 °C improved catechin encapsulation efficiency up to 93.71 ±â€¯0.14 %, along with the highest solubility, enhanced emulsification activity index and improved thermal stability of the protein. Multiple spectroscopic techniques revealed that increasing pretreatment temperature (from 40 °C to 70 °C) altered the secondary structures of SPI, resulting in a more stable unfolded structure for the composite system with a significant increase in α-helical structures and a decrease in random coil and ß-sheet structures. Moreover, optimal heat treatment also leads to an augmentation of free sulfhydryl groups within complex as well as exposure of more internal chromophore amino acids on molecular surface. Size-exclusion high-performance liquid chromatography and SDS-PAGE analysis indicated that the band intensity of newly formed high-molecular-weight soluble macromolecules (>180 kDa) increased as the pre-heating temperature rose. Furthermore, fluorescence spectroscopy and molecular docking analysis suggest that hydrophobic and covalent interactions were involved in complex formation, which intensified with increasing temperature.

Bionic nanotheranostic for multimodal imaging-guided NIR-II-photothermal cancer therapy.

In photothermal therapy (PTT), the photothermal conversion of the second near-infrared (NIR-II) window allows deeper penetration and higher laser irradiance and is considered a promising therapeutic strategy for deep tissues. Since cancer remains a leading cause of deaths worldwide, despite the numerous treatment options, we aimed to develop an improved bionic nanotheranostic for combined imaging and photothermal cancer therapy. We combined a gold nanobipyramid (Au NBP) as a photothermal agent and MnO2 as a magnetic resonance enhancer to produce core/shell structures (Au@MnO2; AM) and modified their surfaces with homologous cancer cell plasma membranes (PM) to enable tumour targeting. The performance of the resulting Au@MnO2@PM (AMP) nanotheranostic was evaluated in vitro and in vivo. AMP exhibits photothermal properties under NIR-II laser irradiation and has multimodal in vitro imaging functions. AMP enables the computed tomography (CT), photothermal imaging (PTI), and magnetic resonance imaging (MRI) of tumours. In particular, AMP exhibited a remarkable PTT effect on cancer cells in vitro and inhibited tumour cell growth under 1064 nm laser irradiation in vivo, with no significant systemic toxicity. This study achieved tumour therapy guided by multimodal imaging, thereby demonstrating a novel strategy for the use of bionic gold nanoparticles for tumour PTT under NIR-II laser irradiation.

Polarized Ultrathin BN Induced Dynamic Electron Interactions for Enhancing Acidic Oxygen Evolution.

Developing ruthenium-based heterogeneous catalysts with an efficient and stable interface is essential for enhanced acidic oxygen evolution reaction (OER). Herein, we report a defect-rich ultrathin boron nitride nanosheet support with relatively independent electron donor and acceptor sites, which serves as an electron reservoir and receiving station for RuO2, realizing the rapid supply and reception of electrons. Through precisely controlling the reaction interface, a low OER overpotential of only 180 mV (at 10 mA cm-2) and long-term operational stability (350 h) are achieved, suggesting potential practical applications. In situ characterization and theoretical calculations have validated the existence of a localized electronic recycling between RuO2 and ultrathin BN nanosheets (BNNS). The electron-rich Ru sites accelerate the adsorption of water molecules and the dissociation of intermediates, while the interconnection between the O-terminal and B-terminal edge establishes electronic back-donation, effectively suppressing the over-oxidation of lattice oxygen. This study provides a new perspective for constructing a stable and highly active catalytic interface.

Durable Janus membrane with on-demand mode switching fabricated by femtosecond laser.

Despite their notable unidirectional water transport capabilities, Janus membranes are commonly challenged by the fragility of their chemical coatings and the clogging of open microchannels. Here, an on-demand mode-switching strategy is presented to consider the Janus functionality and mechanical durability separately and implement them by simply stretching and releasing the membrane. The stretching Janus mode facilitates unidirectional liquid flow through the hydrophilic micropores-microgrooves channels (PG channels) fabricated by femtosecond laser. The releasing protection mode is designed for the in-situ closure of the PG channels upon encountering external abrasion and impact. The protection mode imparts the Janus membrane robustness to reserve water unidirectional penetration under harsh conditions, such as 2000 cycles mechanical abrasion, 10 days exposure in air and other rigorous tests (sandpaper abrasion, finger rubbing, sand impact and tape peeling). The underlying mechanism of gridded grooves in protecting and enhancing water flow is unveiled. The Janus membrane serves as a fog collector to demonstrate its unwavering mechanical durability in harsh real-world conditions. The presented design strategy could open up new possibilities of Janus membrane in a multitude of applications ranging from multiphase separation devices to fog harvesting and wearable health-monitoring patches.

Rational design of a ratiometric fluorescent nanoprobe for real-time imaging of hydroxyl radical and its therapeutic evaluation of diabetes.

Hydroxyl radical (•OH), one of the most reactive and deleterious substances in organisms, belongs to a class of reactive oxygen species (ROS), and it has been verified to play an essential role in numerous pathophysiological scenarios. However, due to its extremely high reactivity and short lifetime, the development of a reliable and robust method for tracking endogenous •OH remains an ongoing challenge. In this work, we presented the first ratiometric fluorescent nanoprobe NanoDCQ-3 for •OH sensing based on oxidative C-H abstraction of dihydroquinoline to quinoline. The study mainly focused on how to modulate the electronic effects to achieve an ideal ratiometric detection of •OH, as well as solving the inherent problem of hydrophilicity of the probe, so that it was more conducive to monitoring •OH in living organisms. The screened-out probe NanoDCQ-3 exhibited an exceptional ratiometric sensing capability, better biocompatibility, good cellular uptake, and appropriate in vivo retention, which has been reliably used for detecting exogenous •OH concentration fluctuation in living cells and zebrafish models. More importantly, NanoDCQ-3 facilitated visualization of •OH and evaluation of drug treatment efficacy in diabetic mice. These findings afforded a promising strategy for designing ratiometric fluorescent probes for •OH. NanoDCQ-3 emerged as a valuable tool for the detection of •OH in vivo and held potential for drug screening for inflammation-related diseases.

Severity of fatty liver is highly correlated with the risk of hypertension and diabetes: a cross-sectional and longitudinal cohort study.

BACKGROUND AND AIMS: Fatty liver disease (FLD) is associated with several metabolic derangements. We conducted a retrospective cross-sectional and longitudinal study to evaluate the role of FL severity in the risk of new-onset and co-existing hypertension (HTN) and diabetes mellitus (DM). METHODS: The cross-sectional cohort consisted of 41,888 adults who received health checkups in a tertiary hospital of Taiwan from 1999 to 2013. Of them, 34,865 without HTN and/or DM at baseline and within 1 year after enrollment were included as a longitudinal cohort (mean, 6.45 years for HTN; 6.75 years for DM). FL severity based on the degree of hepatic steatosis was assessed by ultrasound sonography. RESULTS: In cross-sectional cohort, 22,852 (54.6%) subjects had FL (18,203 [43.46%] mild FL and 4,649 [11.10%] moderate/severe FL); 13.5% (n = 5668) had HTN; and 3.4% (n = 1411) had DM. Moderate/severe FL and mild FL had significantly higher risks of existing HTN (adjusted odds ratio/95% confidence interval [CI] 1.59/1.43-1.77 and 1.22/1.13-1.32, respectively). In longitudinal cohort, 3,209 and 822 subjects developed new-onset HTN and DM, respectively (annual incidence, 14.3 and 3.5 per 1000 person-years; 10-year cumulative incidence, 14.35% and 3.89%, respectively). Moderate/severe and mild FL had significantly higher risks of new-onset HTN (adjusted hazard ratio [aHR]/CI 1.54/1.34-1.77 and 1.26/1.16-1.37, respectively) and DM (aHR/CI 5.88/4.44-7.81 and 3.22/2.56-4.07, respectively). Resolved FL during follow-up decreased the risk of HTN and/or DM. CONCLUSIONS: Patients with FL are at high risk of prevalent and incident HTN and/or DM. The risk increases with the severity of FL.

LncRNA MIR22HG/microRNA-9-3p/IGF1 in nonalcoholic steatohepatitis, the ceRNA network increases fibrosis by inhibiting autophagy and promoting pyroptosis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is known to progress due to the impact of long non-coding RNAs (lncRNAs), which have been linked to autophagy, pyroptosis, and fibrosis in NASH cells. However, the exact mechanisms underpinning these processes remain unclear. This study focuses on the role of lncRNA MIR22HG (MIR22HG) in NASH. METHODS: The expression of differentially expressed lncRNA was analyzed by RNA sequencing. Mouse models of NASH induced by MCD and HFD were validated. The expression of MIR22HG in HFD and MCD mouse liver tissue samples, FFA cells constructed with HepG2 and Huh7, and human liver tissue samples were detected by QRT-PCR. In addition, We used RNA immunoprecipitation, luciferase reporting, miRNA transfection, plasmid construction, immunofluorescence, Western blot, qRT-PCR, ELISA, and hybridization techniques to elucidate the relationship between MIR22HG, microRNA-9-3p (miR-9-3p), and IGF1. In addition, the mechanism of MIR22HG and PTEN/AKT was explored by Western blot analysis. RESULTS: RNA-seq found that 3751 mRNAs and 23 lncRNAs were differentially expressed, which constituted a lncRNA-miRNA-mRNA regulatory network. Studies demonstrated the downregulation of MIR22HG in HFD and MCD mouse liver tissue samples (p = 1.00E-04 and p = 4.6E-03). Our results showed that overexpression of MIR22HG promoted autophagy and inhibited pyroptosis and fibrosis through the miR-9-3p/IGF1 pathway, thus slowing the occurrence and development of NASH. Further, we observed a low expression of MIR22HG and IGF1, but a high expression of miR-9-3p in NASH patients, a finding in alignment with our in vivo and in vitro results. CONCLUSION: Using MIR22HG as a biomarker and therapeutic target for NASH patients, we found that it plays a pivotal role in detecting autophagy, pyroptosis, and fibrosis through the ceRNA pathway.

One-Year Follow-Up Study on Assessing the Range of Segmental Motion and Clinical Outcomes Following Cervical Disc Arthroplasty for Treatment of Severe Cervical Disc Degeneration.

BACKGROUND: Though previous studies have documented various clinical outcomes after cervical arthroplasty for degenerative cervical disc disease, none of them reported the impact of cervical arthroplasty on severe cervical disc degeneration (CDD). METHODS: This retrospective cohort study included severe 40 CDD (C3-C7) patients who underwent single-level cervical arthroplasty using ProDisc-C between January 2017 and December 2019. After surgical intervention, the range of motion (ROM) was determined, whereas clinical outcomes were measured in terms of the Visual Analogue Scale (VAS) and Neck Disability Index (NDI) to evaluate neck pain and disability, respectively. RESULTS: Compared to the mean preoperative ROM (6.57 ± 4.85°), the cervical dynamic ROM was increased 3 months after cervical arthroplasty, and the increment was maintained for at least 1 year. The increased ROM is attributed to the extension and not flexion components. The mean preoperative ROM of 6.57 ± 4.85° significantly increased to 11.67 ± 4.98° (P = 0.0005), 10.05 ± 5.18° (P = 0.0426) and 10.46 ± 4.73° (P = 0.0247) after 3 months, 6 months and 1 year, respectively. The extension ROM also revealed a similar trend. VAS for neck and arm decreased from 7.4 and 6.6 to 1.4 and 1.2, respectively. Consistently, the preoperative mean Neck Disability Index (NDI) score of 27.6 decreased to 14.6. We recorded a case of device subsidence, but without extrusion. CONCLUSIONS: Cervical arthroplasty can improve clinical outcomes and restore ROM in severe CDD patients.

Investigation on the Combustion Characteristics and Environmental Effects of Hydrogen-doped Natural Gas for Domestic Water Heaters.

The addition of hydrogen to natural gas is an effective approach to broaden the range of applications for hydrogen and address the issue of global warming. However, the inclusion of hydrogen alters the combustion properties of natural gas. The paper established a simplified mechanism consisting of 19 components and a 67-step reaction for hydrogen-doped natural gas combustion. With this simplified mechanism, the effects of hydrogen doping and the utilization of porous media combustion techniques on the combustion characteristics of natural gas were investigated numerically. The results suggested that the utilization of porous media combustion technology is beneficial for achieving the complete combustion of hydrogen-doped natural gas and reducing pollutant emissions. Additionally, the total gas cost and environmental impact of domestic gas water heaters with hydrogen-doping natural gas were estimated. The findings show that the use of 20% hydrogen-doped natural gas contributes to a decrement in fuel costs and reduced emissions of CO by 25.4%, NOX by 53.9%, and CO2 by 6.78%.

Mn(II) Optimized Sono/Chemodynamic Effect of Porphyrin-Metal-Organic Framework Nanosheets for MRI-Guided Colon Cancer Therapy and Metastasis Suppression.

Sonodynamic therapy (SDT) offers a remarkable non-invasive ultrasound (US) treatment by activating sonosensitizer and generating reactive oxygen species (ROS) to inhibit tumor growth. The development of multifunctional, biocompatible, and highly effective sonosensitizers remains a current priority for SDT. Herein, the first report that Mn(II) ions chelated Gd-TCPP (GMT) nanosheets (NSs) are synthesized via a simple reflux method and encapsulated with pluronic F-127 to form novel sonosensitizers (GMTF). The GMTF NSs produce a high yield of ROS under US irradiation due to the decreased highest occupied molecular orbital-lowest unoccupied molecular orbital gap energy (2.7-1.28 eV). Moreover, Mn(II) ions endow GMTF with a fascinating Fenton-like activity to produce hydroxyl radicals in support of chemodynamic therapy (CDT). It is also effectively used in magnetic resonance imaging (MRI) with high relaxation rate (r 1 : 4.401 mM-1  s-1 ) to track the accumulation of NSs in tumors. In vivo results indicate that the SDT and CDT in combination with programmed cell death protein 1 antibody (anti-PD-1) show effective metastasis prevention effects, and 70% of the mice in the GMTF + US + anti-PD-1 group survived for 60 days. In conclusion, this study develops a sonosensitizer with promising potential for utilizing both MRI-guided SDT and CDT strategies.

Live Imaging of 3D Hanging Drop Arrays through Manipulation of Light-Responsive Pyroelectric Slippery Surface and Chip Adhesion.

Three-dimensional (3D) hanging drop cell culture is widely used in organoid culture because of its lack of selection pressure and rapid cell aggregation. However, current hanging drop technology has limitations, such as a dependence on complex microfluidic transport channels or specific capillary force templates for drop formation, which leads to unchangeable drop features. These methods also hinder live imaging because of space and complexity constraints. Here, we have developed a hanging drop construction method and created a flexible 3D hanging drop construction platform composed of a manipulation module and an adhesion module. Their harmonious operation allows for the easy construction of hanging drops of varying sizes, types, and patterns. Our platform produces a cell hanging drop chip with small sizes and clear fields of view, thereby making it compatible with live imaging. This platform has great potential for personalized medicine, cancer and drug discovery, tissue engineering, and stem cell research.

Dual-targeting nanotheranostics for MRI-guided enhanced chemodynamic therapy of hepatoma via regulating the tumor microenvironment.

Chemodynamic therapy (CDT), as a reactive oxygen species (ROS)-based therapeutic modality, has attracted much attention in recent years. However, the insufficient therapeutic effect of CDT is due to the antioxidant system in the tumor microenvironment, such as high levels of glutathione (GSH). In this study, we developed a biological/physical dual-targeting nanotheranostic agent (relaxation rate, r1: 6.3 mM-1 s-1 and r2: 13.11 mM-1 s-1) for enhanced CDT of SMCC-7721 tumors. This nanotheranostic agent is composed of a homologous tumor cell membrane (TCM), magnetic ferric oxide, and manganese oxide and is denoted as FM@TCM nanoparticles (NPs). A favorable effect of in vitro CDT on SMCC-7721 cells (IC50: 20 µg mL-1) is demonstrated, attributed to the Fenton reaction and oxidative stress resulting from the reduction of the GSH level. In vivo T1/T2 magnetic resonance imaging (MRI) confirms that the tumor accumulation of FM@TCM NPs is promoted by concurrent bioactive targeting of the homologous TCM and physico-magnetic targeting of tumor tissues with an external magnetic field. Impressive chemodynamic therapeutic effects on SMCC-7721 tumors are demonstrated through the catalysis of endogenous hydrogen peroxide and depletion of GSH to generate high levels of ROS. Dual-targeting FM@TCM NPs inhibit SMCC-7721 tumor growth (∼90.9%) in vivo without any biotoxicity. This nanotheranostic agent has great potential for use in MRI-guided CDT.

Resolving phylogenetic relationships and taxonomic revision in the Pseudogastromyzon (Cypriniformes, Gastromyzonidae) genus: molecular and morphological evidence for a new genus, Labigastromyzon.

The Pseudogastromyzon genus, consisting of species predominantly distributed throughout southeastern China, has garnered increasing market attention in recent years due to its ornamental appeal. However, the overlapping diagnostic attributes render the commonly accepted criteria for interspecific identification unreliable, leaving the phylogenetic relationships among Pseudogastromyzon species unexplored. In the present study, we undertake molecular phylogenetic and morphological examinations of the Pseudogastromyzon genus. Our phylogenetic analysis of mitochondrial genes distinctly segregated Pseudogastromyzon species into two clades: the Pseudogastromyzon clade and the Labigastromyzon clade. A subsequent morphological assessment revealed that the primary dermal ridge (specifically, the second ridge) within the labial adhesive apparatus serves as an effective and precise interspecific diagnostic characteristic. Moreover, the distributional ranges of Pseudogastromyzon and Labigastromyzon are markedly distinct, exhibiting only a narrow area of overlap. Considering the morphological heterogeneity of the labial adhesive apparatus and the substantial division within the molecular phylogeny, we advocate for the elevation of the Labigastromyzon subgenus to the status of a separate genus. Consequently, we have ascertained the validity of the Pseudogastromyzon and Labigastromyzon species, yielding a total of six valid species. To facilitate future research, we present comprehensive descriptions of the redefined species and introduce novel identification keys.

Molecular classification of hormone receptor-positive HER2-negative breast cancer.

Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer is the most prevalent type of breast cancer, in which endocrine therapy resistance and distant relapse remain unmet challenges. Accurate molecular classification is urgently required for guiding precision treatment. We established a large-scale multi-omics cohort of 579 patients with HR+/HER2- breast cancer and identified the following four molecular subtypes: canonical luminal, immunogenic, proliferative and receptor tyrosine kinase (RTK)-driven. Tumors of these four subtypes showed distinct biological and clinical features, suggesting subtype-specific therapeutic strategies. The RTK-driven subtype was characterized by the activation of the RTK pathways and associated with poor outcomes. The immunogenic subtype had enriched immune cells and could benefit from immune checkpoint therapy. In addition, we developed convolutional neural network models to discriminate these subtypes based on digital pathology for potential clinical translation. The molecular classification provides insights into molecular heterogeneity and highlights the potential for precision treatment of HR+/HER2- breast cancer.

The Efficacy of Anthropometric Indicators in Predicting Non-Alcoholic Fatty Liver Disease Using FibroScan® CAP Values among the Taiwanese Population.

The controlled attenuation parameter (CAP) measurement obtained from FibroScan® is a low-risk method of assessing fatty liver. This study investigated the association between the FibroScan® CAP values and nine anthropometric indicators, including the abdominal volume index (AVI), body fat percentage (BFP), body mass index (BMI), conicity index (CI), ponderal index (PI), relative fat mass (RFM), waist circumference (WC), waist-hip ratio (WHR), and waist-to-height ratio (WHtR), and risk of non-alcoholic fatty liver disease (fatty liver). We analyzed the medical records of adult patients who had FibroScan® CAP results. CAP values <238 dB/m were coded as 0 (non- fatty liver) and ≥238 dB/m as 1 (fatty liver). An individual is considered to have class 1 obesity when their body mass index (BMI) ranges from 30 kg/m2 to 34.9 kg/m2. Class 2 obesity is defined by a BMI ranging from 35 kg/m2 to 39.9 kg/m2, while class 3 obesity is designated by a BMI of 40 kg/m2 or higher. Out of 1763 subjects, 908 (51.5%) had fatty liver. The BMI, WHtR, and PI were found to be more strongly correlated with the CAP by the cluster dendrogram with correlation coefficients of 0.58, 0.54, and 0.54, respectively (all p < 0.0001). We found that 28.3% of the individuals without obesity had fatty liver, and 28.2% of the individuals with obesity did not have fatty liver. The BMI, CI, and PI were significant predictors of fatty liver. The BMI, PI, and WHtR demonstrated better predictive ability, indicated by AUC values of 0.72, 0.68, and 0.68, respectively, a finding that was echoed in our cluster group analysis that showed interconnected clustering with the CAP. Therefore, of the nine anthropometric indicators we studied, the BMI, CI, PI, and WHtR were found to be more effective in predicting the CAP score, i.e., fatty liver.

SPDEF enhances cancer stem cell-like properties and tumorigenesis through directly promoting GALNT7 transcription in luminal breast cancer.

BACKGROUND: Luminal breast cancer (BC) is the predominant subtype of breast cancer with a sustained risk of late recurrence and death. Understanding the molecular mechanisms for the oncogenesis of luminal BC would improve the prognosis for this large subset of patients. SPDEF was reported to be dysregulated in breast cancers. However, the biological functions and underlying molecular mechanism of SPDEF in luminal BC remains largely unknown. The aim of the present study was to elucidate the potential roles of SPDEF underlying subtype-specific functions in BC, especially in luminal subtypes. METHODS: The expressions and clinicopathological characteristics of SPDEF in luminal BC patients were evaluated bioinformatically. In vitro and in vivo assays were performed to investigate the oncogenic function and stemness maintenance of SPDEF in luminal BC. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were conducted to determine the transcription regulation of GALNT7 by SPDEF. GALNT7 levels in serum from luminal BC patients were further detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: SPDEF is markedly upregulated in luminal BC and positively associated with tumor progression and poor prognosis. Furthermore, we confirmed that SPDEF enhanced the proliferation, migration, invasion and stemness of luminal BC cells in vitro as well the tumorigenicity in vivo. Mechanistically, we demonstrated the stimulative effect of SPDEF on the progression and stemness of luminal BC, which is mediated by its directly transcriptional target GALNT7. Clinically, we verified that the GALNT7 can be used as a noninvasive diagnostic marker. Noteworthy, the combined detection of serum GALNT7 and traditional tumor markers can enhance diagnostic accuracy thus is of vital importance in the early diagnosis of luminal BC. CONCLUSIONS: Our study reveals a novel mechanism by which SPDEF transcriptionally activates GALNT7 via directly binding to its promoter to promote cell proliferation, motility and stemness, and led to luminal BC tumorigenesis and poor prognosis.