Approaches for Enhancing Wastewater Treatment of Photocatalytic Fuel Cells: A Review.

Environmental pollution and energy crises have garnered global attention. The substantial discharge of organic waste into water bodies has led to profound environmental contamination. Photocatalytic fuel cells (PFCs) enabling the simultaneous removal of refractory contaminants and recovery of the chemical energy contained in organic pollutants provides a potential strategy to solve environmental issues and the energy crisis. This review will discuss the fundamentals, working principle, and configuration development of PFCs and photocatalytic microbial fuel cells (PMFCs). We particularly focus on the strategies for improving the wastewater treatment performance of PFCs/PMFCs in terms of coupled advanced oxidation processes, the rational design of high-efficiency electrodes, and the strengthening of the mass transfer process. The significant potential of PFCs/PMFCs in various fields is further discussed in detail. This review is intended to provide some guidance for the better implementation and widespread adoption of PFC wastewater treatment technologies.

Seeds Priming with Melatonin Improves Root Hydraulic Conductivity of Wheat Varieties under Drought, Salinity, and Combined Stress.

Drought and salinity stress reduce root hydraulic conductivity of plant seedlings, and melatonin application positively mitigates stress-induced damage. However, the underlying effect of melatonin priming on root hydraulic conductivity of seedlings under drought-salinity combined remains greatly unclear. In the current report, we investigated the influence of seeds of three wheat lines' 12 h priming with 100 µM of melatonin on root hydraulic conductivity (Lpr) and relevant physiological indicators of seedlings under PEG, NaCl, and PEG + NaCl combined stress. A previous study found that the combined PEG and NaCl stress remarkably reduced the Lpr of three wheat varieties, and its value could not be detected. Melatonin priming mitigated the adverse effects of combined PEG + NaCl stress on Lpr of H4399, Y1212, and X19 to 0.0071 mL·h-1·MPa-1, 0.2477 mL·h-1·MPa-1, and 0.4444 mL·h-1·MPa-1, respectively, by modulating translation levels of aquaporin genes and contributed root elongation and seedlings growth. The root length of H4399, Y1212, and X19 was increased by 129.07%, 141.64%, and 497.58%, respectively, after seeds pre-treatment with melatonin under PEG + NaCl combined stress. Melatonin -priming appreciably regulated antioxidant enzyme activities, reduced accumulation of osmotic regulators, decreased levels of malondialdehyde (MDA), and increased K+ content in stems and root of H4399, Y1212, and X19 under PEG + NaCl stress. The path investigation displayed that seeds primed with melatonin altered the modification of the path relationship between Lpr and leaf area under stress. The present study suggested that melatonin priming was a strategy as regards the enhancement of root hydraulic conductivity under PEG, NaCl, and PEG + NaCl stress, which efficiently enhanced wheat resistant to drought-salinity stress.

Severe flood modulates the sources and age of dissolved organic carbon in the Yangtze River Estuary.

Floods in global large rivers modulate the transport of dissolved organic carbon (DOC) and estuarine hydrological characteristics significantly. This study investigated the impact of a severe flood on the sources and age of DOC in the Yangtze River Estuary (YRE) in 2020. Comparing the flood period in 2020 to the non-flood period in 2017, we found that the flood enhanced the transport of young DOC to the East China Sea (ECS), resulting in significantly enriched Δ14C-DOC values. During the flood period, the proportion of modern terrestrial organic carbon (OC) was significantly higher compared to the non-flood period. Conversely, the proportion of pre-aged sediment OC was significantly lower during the flood period. The high turbidity associated with the flood facilitated rapid transformation and mineralization of sedimentary and fresh terrestrial OC, modifying the sources of DOC. The flux of modern terrestrial OC transported to the ECS during the flood period was 1.58 times higher than that of the non-flood period. These findings suggest that floods can modulate the sources and decrease the age of DOC, potentially leading to increased greenhouse gas emissions. Further research is needed to understand the long-term impacts of floods on DOC dynamics in global estuaries.

Machine Learning to Promote Efficient Screening of Low-Contact Electrode for 2D Semiconductor Transistor Under Limited Data.

Low-barrier and high-injection electrodes are crucial for high-performance (HP) 2D semiconductor devices. Conventional trial-and-error methodologies for electrode material screening are impractical because of their low efficiency and arbitrary specificity. Although machine learning has emerged as a promising alternative to tackle this problem, its practical application in semiconductor devices is hindered by its substantial data requirements. In this paper, a comprehensive scheme combining an autoencoding regularized adversarial neural network and a feature-adaptive variational active learning algorithm for screening low-contact electrode materials for 2D semiconductor transistors with limited data is proposed. The proposed scheme exhibits exceptional performance by training with only 15% of the total data points, where the mean square errors are 0.17 and 0.27 eV for the vertical and lateral Schottky barrier, respectively, and 2.88% for tunneling probability. Further, it exhibits an optimal predictive performance for 100 randomly sampled training datasets, reveals the underlying physical insight based on the identified features, and realizes continual improvement by employing detailed density-of-states descriptors. Finally, the empirical evaluations of the transport characteristics are conducted and verified by constructing MOSFET devices. These findings demonstrate the considerable potential of machine-learning techniques for screening high-efficiency electrode materials and constructing HP 2D semiconductor devices.

Systemic immune-inflammation index is associated with cardiac complications following acute ischemic stroke: A retrospective single-center study.

BACKGROUND: Stroke-induced heart syndrome is a feared complication of ischemic stroke, that is commonly encountered and has a strong association with unfavorable prognosis. More research is needed to explore underlying mechanisms and inform clinical decision making. This study aims to explore the relationship between the early systemic immune-inflammation (SII) index and the cardiac complications after acute ischemic stroke. METHODS: Consecutive patients with acute ischemic stroke were prospectively collected from January 2020 to August 2022 and retrospectively analyzed. We included subjects who presented within 24 hours after symptom onset and were free of detectable infections or cancer on admission. SII index [(neutrophils × platelets/ lymphocytes)/1000] was calculated from laboratory data at admission. RESULTS: A total of 121 patients were included in our study, of which 24 (19.8 %) developed cardiac complications within 14 days following acute ischemic stroke. The SII level was found higher in patients with stroke-heart syndrome (p<.001), which was an independent predictor of stroke-heart syndrome (adjusted odds ratio 5.089, p=.002). CONCLUSION: New-onset cardiovascular complications diagnosed following a stroke are very common and are associated with early SII index.

High-Performance Broadband Image Sensing Photodetector Based on MnTe/WS2 van der Waals Epitaxial Heterostructures.

Two-dimensional transition metal dichalcogenide (TMDC) heterostructure is receiving considerable attention due to its novel electronic, optoelectronic, and spintronic devices with design-oriented and functional features. However, direct design and synthesis of high-quality TMDC/MnTe heterostructures remain difficult, which severely impede further investigations of semiconductor/magnetic semiconductor devices. Herein, the synthesis of high-quality vertically stacked WS2/MnTe heterostructures is realized via a two-step chemical vapor deposition method. Raman, photoluminescence, and scanning transmission electron microscopy characterizations reveal the high-quality and atomically sharp interfaces of the WS2/MnTe heterostructure. WS2/MnTe-based van der Waals field effect transistors demonstrate high rectification behavior with rectification ratio up to 106, as well as a typical p-n electrical transport characteristic. Notably, the fabricated WS2/MnTe photodetector exhibits sensitive and broadband photoresponse ranging from UV to NIR with a maximum responsivity of 1.2 × 103 A/W, a high external quantum efficiency of 2.7 × 105%, and fast photoresponse time of ∼50 ms. Moreover, WS2/MnTe heterostructure photodetectors possess a broadband image sensing capability at room temperature, suggesting potential applications in next-generation high-performance and broadband image sensing photodetectors.

Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases.

Bovine respiratory disease (BRD) is a significant veterinary challenge, often exacerbated by pathogen resistance, hindering effective treatment. Traditional testing methods for primary pathogens - Mycoplasma bovis, Pasteurella multocida, and Mannheimia haemolytica - are notably time-consuming and lack the rapidity required for effective clinical decision-making. This study introduces a TaqMan MGB probe detection chip, utilizing fluorescent quantitative PCR, targeting key BRD pathogens and associated drug-resistant genes and sites. We developed 94 specific probes and primers, embedded into a detection chip, demonstrating notable specificity, repeatability, and sensitivity, reducing testing time to under 1 h. Additionally, we formulated probes to detect mutations in the quinolone resistance-determining region, associated with fluoroquinolone resistance in BRD pathogens. The chip exhibited robust sensitivity and specificity, enabling rapid detection of drug-resistant mutations in clinical samples. This methodology significantly expedites the diagnostic process for BRD and sensitive drug screening, presenting a practical advancement in the field.

Exploring the roles of non-coding RNAs in liver regeneration.

Liver regeneration (LR) is a complex process encompassing three distinct phases: priming, proliferation phase and restoration, all influenced by various regulatory factors. After liver damage or partial resection, the liver tissue demonstrates remarkable restorative capacity, driven by cellular proliferation and repair mechanisms. The essential roles of non-coding RNAs (ncRNAs), predominantly microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNA (circRNA), in regulating LR have been vastly studied. Additionally, the impact of ncRNAs on LR and their abnormal expression profiles during this process have been extensively documented. Mechanistic investigations have revealed that ncRNAs interact with genes involved in proliferation to regulate hepatocyte proliferation, apoptosis and differentiation, along with liver progenitor cell proliferation and migration. Given the significant role of ncRNAs in LR, an in-depth exploration of their involvement in the liver's self-repair capacity can reveal promising therapeutic strategies for LR and liver-related diseases. Moreover, understanding the unique regenerative potential of the adult liver and the mechanisms and regulatory factors of ncRNAs in LR are crucial for improving current treatment strategies and exploring new therapeutic approaches for various liver-related diseases. This review provides a brief overview of the LR process and the ncRNA expression profiles during this process. Furthermore, we also elaborate on the specific molecular mechanisms through which multiple key ncRNAs regulate the LR process. Finally, based on the expression characteristics of ncRNAs and their interactions with proliferation-associated genes, we explore their potential clinical application, such as developing predictive indicators reflecting liver regenerative activity and manipulating LR processes for therapeutic purposes.

Phenotypic comparison and the potential antitumor function of immortalized bone marrow-derived macrophages (iBMDMs).

Introduction: Macrophages are an important component of innate immunity and involved in the immune regulation of multiple diseases. The functional diversity and plasticity make macrophages to exhibit different polarization phenotypes after different stimuli. During tumor progression, the M2-like polarized tumor-associated macrophages (TAMs) promote tumor progression by assisting immune escape, facilitating tumor cell metastasis, and switching tumor angiogenesis. Our previous studies demonstrated that functional remodeling of TAMs through engineered-modifying or gene-editing provides the potential immunotherapy for tumor. However, lack of proliferation capacity and maintained immune memory of infused macrophages restricts the application of macrophage-based therapeutic strategies in the repressive tumor immune microenvironment (TIME). Although J2 retrovirus infection enabled immortalization of bone marrow-derived macrophages (iBMDMs) and facilitated the mechanisms exploration and application, little is known about the phenotypic and functional differences among multi kinds of macrophages. Methods: HE staining was used to detect the biosafety of iBMDMs, and real-time quantitative PCR, immunofluorescence staining, and ELISA were used to detect the polarization response and expression of chemokines in iBMDMs. Flow cytometry, scratch assay, real-time quantitative PCR, and crystal violet staining were used to analyze its phagocytic function, as well as its impact on tumor cell migration, proliferation, and apoptosis. Not only that, the inhibitory effect of iBMDMs on tumor growth was detected through subcutaneous tumor loading, while the tumor tissue was paraffin sectioned and flow cytometry was used to detect its impact on the tumor microenvironment. Results: In this study, we demonstrated iBMDMs exhibited the features of rapid proliferation and long-term survival. We also compared iBMDMs with RAW264.7 cell line and mouse primary BMDMs with in vitro and in vivo experiments, indicating that the iBMDMs could undergo the same polarization response as normal macrophages with no obvious cellular morphology changes after polarization. What's more, iBMDMs owned stronger phagocytosis and pro-apoptosis functions on tumor cells. In addition, M1-polarized iBMDMs could maintain the anti-tumor phenotypes and domesticated the recruited macrophages of receptor mice, which further improved the TIME and repressed tumor growth. Discussion: iBMDMs can serve as a good object for the function and mechanism study of macrophages and the optional source of macrophage immunotherapy.

Dissecting the chiral recognition of TLR4/MD2 with Neoseptin-3 enantiomers by molecular dynamics simulations.

Toll-like receptor 4 (TLR4) is a pivotal innate immune recognition receptor that regulates intricate signaling pathways within the immune system. Neoseptin-3 (Neo-3), a recently identified small-molecule agonist for mouse TLR4/MD2, exhibits chiral recognition properties. Specifically, the L-enantiomer of Neo-3 (L-Neo-3) effectively activates the TLR4 signaling pathway, while D-Neo-3 fails to induce TLR4 activation. However, the underlying mechanism by which TLR4 enantioselectively recognizes Neo-3 enantiomers remains poorly understood. In this study, in silico simulations were performed to investigate the mechanism of chiral recognition of Neo-3 enantiomers by TLR4/MD2. Two L-Neo-3 molecules stably resided within the cavity of MD2 as a dimer, and the L-Neo-3 binding stabilized the (TLR4/MD2)2 dimerization state. However, the strong electrostatic repulsion between the hydrogen atoms on the chiral carbon of D-Neo-3 molecules caused the relative positions of two D-Neo-3 molecules to continuously shift during the simulation process, thus preventing the formation of D-Neo-3 dimer as well as their stable interactions with the surrounding residues in (TLR4/MD2)2. Considering that L-Neo-3 could not sustain a stable dimeric state in the bulk aqueous environment, it is unlikely that L-Neo-3 entered the cavity of MD2 as a dimeric unit. Umbrella sampling simulations revealed that the second L-Neo-3 molecule entering the cavity of MD2 exhibited a lower binding energy (-25.75 kcal mol-1) than that of the first L-Neo-3 molecule (-14.31 kcal mol-1). These results imply that two L-Neo-3 molecules enter the cavity of MD2 sequentially, with the binding of the first L-Neo-3 molecule facilitating the entry of the second one. This study dissects the binding process of Neo-3 enantiomers, offering a comprehensive understanding of the atomic-level mechanism underlying TLR4's chiral recognition of Neo-3 molecules.

Ferroelectric Bi2O2Te-Based Plasmonic Biosensor for Ultrasensitive Biomolecular Detection.

Ultrasensitive detection of biomarkers, particularly proteins, and microRNA, is critical for disease early diagnosis. Although surface plasmon resonance biosensors offer label-free, real-time detection, it is challenging to detect biomolecules at low concentrations that only induce a minor mass or refractive index change on the analyte molecules. Here an ultrasensitive plasmonic biosensor strategy is reported by utilizing the ferroelectric properties of Bi2O2Te as a sensitive-layer material. The polarization alteration of ferroelectric Bi2O2Te produces a significant plasmonic biosensing response, enabling the detection of charged biomolecules even at ultralow concentrations. An extraordinary ultralow detection limit of 1 fm is achieved for protein molecules and an unprecedented 0.1 fm for miRNA molecules, demonstrating exceptional specificity. The finding opens a promising avenue for the integration of 2D ferroelectric materials into plasmonic biosensors, with potential applications spanning a wide range.

Mechanical quenching phenomenon in diamond.

The structure of dislocation cores, the fundamental knowledge on crystal plasticity, remains largely unexplored in covalent crystals. Here, we conducted atomically resolved characterizations of dislocation core structures in a plastically deformed diamond anvil cell tip that was unloaded from an exceptionally high pressure of 360 GPa. Our observations unveiled a series of nonequilibrium dislocation cores that deviate from the commonly accepted "five-seven-membered ring" dislocation core model found in FCC-structured covalent crystals. The nonequilibrium dislocation cores were generated through a process known as "mechanical quenching," analogous to the quenching process where a high-energy state is rapidly frozen. The density functional theory-based molecular dynamic simulations reveal that the phenomenon of mechanical quenching in diamond arises from the challenging relaxation of the nonequilibrium configuration, necessitating a large critical strain of 25% that is difficult to maintain. Further electronic-scale analysis suggested that such large critical strain is spent on the excitation of valance electrons for bond breaking and rebonding during relaxation. These findings establish a foundation for the plasticity theory of covalent materials and provide insights into the design of electrical and luminescent properties in diamond, which are intimately linked to the dislocation core structure.

Ambient Air Pollution and Vision Disorder: A Systematic Review and Meta-Analysis.

The effects of air pollution on physical health are well recognized, with many studies revealing air pollution's effects on vision disorder, yet no relationship has been established. Therefore, a meta-analysis was carried out in this study to investigate the connection between vision disorder and ambient particles (diameter ≤ 2.5 µm (PM2.5), diameter ≤ 10 µm (PM10)) and gaseous pollutants (nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), Ozone (O3)). Twelve relevant studies published by 26 February 2024 were identified in three databases. A pooled odds ratios (ORs) of 95% confidence intervals (CIs) were obtained using random-effects meta-analysis models. Meta-analysis results revealed that for every 10 µg/m3 increase in PM2.5 and NO2 exposure, a substantially higher incidence of vision disorder was observed (OR = 1.10; 95% CI: 1.01, 1.19; OR = 1.08, 95% CI: 1.00, 1.16). No significant correlation existed between exposure to PM10, SO2 and CO and vision disorder. However, O3 exposure was negatively associated with vision disorder. In addition, subgroup analyses revealed that PM2.5 exposure was significantly correlated with the risk of glaucoma and age-related macular degeneration and that children and adolescents were more susceptible to NO2 and PM2.5 than adults. Overall, exposure to air pollutants, especially PM2.5 and NO2, may increase the incidence of vision disorder.

Assessing the temporal within-day glycemic variability during hospitalization in patients with type 2 diabetes patients using continuous glucose monitoring: a retrospective observational study.

AIMS: Frequent and extensive within-day glycemic variability (GV) in blood glucose levels may increase the risk of hypoglycemia and long-term mortality in hospitalized patients with diabetes. We aimed to assess the amplitude and frequency of within-day GV in inpatients with type 2 diabetes and to explore the factors influencing within-day GV. METHODS: We conducted a single-center, retrospective observational study by analyzing hospital records and 10-day real-time continuous glucose monitoring data. Within-day GV was assessed using the coefficient of variation (%CV). The primary outcome was the amplitude and frequency of within-day GV. The frequency of within-day GV was assessed by the consecutive days (CD) of maintaining within the target %CV range after first reaching it (CD after first reaching the target) and the maximum consecutive days of maintaining within the target %CV range (Max-CD). The target %CV range was less than 24.4%. We evaluated the factors influencing within-day GV using COX regression and Poisson regression models. RESULTS: A total of 1050 cases were analyzed, of whom 86.57% reduced the amplitude of within-day GV before the sixth day of hospitalization. Of the 1050 hospitalized patients, 66.57% stayed within the target %CV range for less than two days after first reaching the target and 69.71% experienced a Max-CD of fewer than four days. Reducing the average postprandial glucose excursion (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.77-0.85; incidence rate ratios [IRR]: 0.72, 95% CI: 0.69-0.74) and the use of α-glucosidase inhibitors (IRR: 1.1, 95% CI: 1.01-1.18) and glucagon-like peptide-1 agonist (IRR: 1.30, 95% CI: 1.02-1.65) contributed to reducing the amplitude and decreasing the frequency of within-day GV. However, the use of insulin (HR: 0.64, 95% CI: 0.55-0.75; IRR: 0.86, 95% CI: 0.79-0.93) and glinide (HR: 0.47, 95% CI: 0.31-0.73; IRR: 0.84, 95% CI: 0.73-0.97) may lead to an increased frequency of within-day GV. CONCLUSIONS: An increasing frequency of within-day GV was observed during the hospitalization in patients with type 2 diabetes, despite the effective reduction in the amplitude of within-day GV. Using medications designed to lower postprandial blood glucose could contribute to minimize the risk of frequent within-day GV.

M1 macrophage-related gene model for NSCLC immunotherapy response prediction.

Patients diagnosed with non-small cell lung cancer (NSCLC) have a limited lifespan and exhibit poor immunotherapy outcomes. M1 macrophages have been found to be essential for antitumor immunity. This study aims to develop an immunotherapy response evaluation model for NSCLC patients based on transcription. RNA sequencing profiles of 254 advanced-stage NSCLC patients treated with immunotherapy are downloaded from the POPLAR and OAK projects. Immune cell infiltration in NSCLC patients is examined, and thereafter, different coexpressed genes are identified. Next, the impact of M1 macrophage-related genes on the prognosis of NSCLC patients is investigated. Six M1 macrophage coexpressed genes, namely, NKX2-1, CD8A , SFTA3, IL2RB, IDO1, and CXCL9, exhibit a strong association with the prognosis of NSCLC and serve as effective predictors for immunotherapy response. A response model is constructed using a Cox regression model and Lasso Cox regression analysis. The M1 genes are validated in our TD-FOREKNOW NSCLC clinical trial by RT-qPCR. The response model shows excellent immunotherapy response prediction and prognosis evaluation value in advanced-stage NSCLC. This model can effectively predict advanced NSCLC prognosis and aid in identifying patients who could benefit from customized immunotherapy as well as sensitive drugs.

Micro(nano)plastics in the Human Body: Sources, Occurrences, Fates, and Health Risks.

The increasing global attention on micro(nano)plastics (MNPs) is a result of their ubiquity in the water, air, soil, and biosphere, exposing humans to MNPs on a daily basis and threatening human health. However, crucial data on MNPs in the human body, including the sources, occurrences, behaviors, and health risks, are limited, which greatly impedes any systematic assessment of their impact on the human body. To further understand the effects of MNPs on the human body, we must identify existing knowledge gaps that need to be immediately addressed and provide potential solutions to these issues. Herein, we examined the current literature on the sources, occurrences, and behaviors of MNPs in the human body as well as their potential health risks. Furthermore, we identified key knowledge gaps that must be resolved to comprehensively assess the effects of MNPs on human health. Additionally, we addressed that the complexity of MNPs and the lack of efficient analytical methods are the main barriers impeding current investigations on MNPs in the human body, necessitating the development of a standard and unified analytical method. Finally, we highlighted the need for interdisciplinary studies from environmental, biological, medical, chemical, computer, and material scientists to fill these knowledge gaps and drive further research. Considering the inevitability and daily occurrence of human exposure to MNPs, more studies are urgently required to enhance our understanding of their potential negative effects on human health.

Identification and Characterization of PrognosticMacrophage Subpopulations for HumanEsophagealCarcinoma.

AIMS: The aim of the present study was to investigate the relationship between the cellular ecosystem and the progression of esophageal carcinoma (ESCA) based on the evolution of macrophages and to analyze the potential of using macrophages as a new therapeutic approach in ESCA treatment. BACKGROUND: Macrophage-based immunotherapy could be used for treating ESCA patients, but its clinical application is limited by the intra-tumor heterogeneity of macrophages. OBJECTIVE: The objective of this study was to analyze the diversity, differentiation trajectory, and intercellular communication of macrophages in ESCA and its prognostic significance. METHODS: Single-cell RNA sequencing (scRNA-seq) data in the GSE154763 dataset were downloaded from Gene Expression Omnibus (GEO) to identify cell clusters and annotate cell types using the Seurat R package. The scRNA-seq profiles of macrophages were extracted, and cluster analysis was performed to identify macrophage subsets. The differentiation trajectories of macrophage subgroups were visualized employing Monocle2. Finally, ligand-receptor pairs and communication intensity among the classified subgroups were analyzed using CellChat. RESULTS: A total of 8 cell types were identified between ESCA tissues and paracancer tissues. The most abundant macrophages in ESCA tissues were further divided into 5 cell clusters. Compared with the normal tissues, the proportion of HSPA6+ macrophages in ESCA tissues increased the most, and the number of ligand-receptor pairs that mediated the communication of HSPA6+ macrophages with mast cells and monocytes also increased significantly. More importantly, a high proportion of HSPA6+ macrophages was inversely correlated with the survival outcomes for ESCA patients. CONCLUSIONS: This study analyzed the diversity, distribution and differentiation trajectory of macrophages in ESCA tissues at single-cell level and classified a prognostic macrophage subtype (HSPA6+ macrophages) of ESCA, providing a theoretical basis for macrophage-targeted therapy in ESCA.

Elevated of NDUFA4L2 expression in colon adenocarcinoma is correlated with an unfavorable prognosis and increased immune cell infiltration.

Background: Colon adenocarcinoma (COAD) is a prevalent malignancy worldwide, yet, its underlying pathogenesis and genetic characteristics are still unclear. Previous studies have suggested that NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) may affect tumor progression across various cancers. However, this effect on COAD has rarely been reported. Thus, this study investigated NDUFA4L2's prognostic and diagnostic relevance and explored its potential connection with immune cell infiltration in COAD. Methods: To achieve this, RNA sequencing data from Cancer Genome Atlas (TCGA) was analyzed to assess NDUFA4L2's prognostic value in COAD, and factors relevant to the prognosis of COAD, including NDUFA4L2, were scrutinized using Kaplan-Meier analyses as well as univariate and multivariate Cox regression. A nomogram model was created to project prognosis based on the results of multivariate Cox analysis. Furthermore, gene set enrichment analysis (GSEA) was employed to pinpoint key NDUFA4L2-related pathways, and single-sample GSEA (ssGSEA) on TCGA data was employed to investigate the connections of NDUFA4L2 with cancer immune infiltrations. Results: Our findings revealed significant associations of high NDUFA4L2 expression with poor overall survival, progression-free interval, and disease-specific survival of COAD patients. GSEA indicated close links of NDUFA4L2 with several signaling pathways implicated in tumorigenesis, including extracellular matrix receptor interaction, the intestinal immune network for immunoglobulin A production, natural killer (NK) cell-mediated cytotoxicity, pathways in cancer, cell adhesion molecules, mitogen-activated protein kinase signaling pathway, Hedgehog signaling pathway, transforming growth factor beta signaling pathway, and chemokine signaling pathway. Additionally, ssGSEA identified a positive link between increased NDUFA4L2 expression and higher infiltration degree of various immune cells, such as immature dendritic cells, macrophages, NK cells and dendritic cells. Conclusions: Collectively, our findings demonstrate the association of increased NDUFA4L2 expression with adverse prognosis and heightened immune cell infiltration in COAD patients.

Deficiency of ASGR1 Alleviates Diet-Induced Systemic Insulin Resistance via Improved Hepatic Insulin Sensitivity.

Background: Insulin resistance (IR) is the key pathological basis of many metabolic disorders. Lack of asialoglycoprotein receptor 1 (ASGR1) decreased the serum lipid levels and reduced the risk of coronary artery disease. However, whether ASGR1 also participates in the regulatory network of insulin sensitivity and glucose metabolism remains unknown. Methods: The constructed ASGR1 knockout mice and ASGR1-/- HepG2 cell lines were used to establish the animal model of metabolic syndrome and the IR cell model by high-fat diet (HFD) or drug induction, respectively. Then we evaluated the glucose metabolism and insulin signaling in vivo and in vitro. Results: ASGR1 deficiency ameliorated systemic IR in mice fed with HFD, evidenced by improved insulin intolerance, serum insulin, and homeostasis model assessment of IR index, mainly contributed from increased insulin signaling in the liver, but not in muscle or adipose tissues. Meanwhile, the insulin signal transduction was significantly enhanced in ASGR1-/- HepG2 cells. By transcriptome analyses and comparison, those differentially expressed genes between ASGR1 null and wild type were enriched in the insulin signal pathway, particularly in phosphoinositide 3-kinase-AKT signaling. Notably, ASGR1 deficiency significantly reduced hepatic gluconeogenesis and glycogenolysis. Conclusion: The ASGR1 deficiency was consequentially linked with improved hepatic insulin sensitivity under metabolic stress, hepatic IR was the core factor of systemic IR, and overcoming hepatic IR significantly relieved the systemic IR. It suggests that ASGR1 is a potential intervention target for improving systemic IR in metabolic disorders.

SERS-electrochemical dual-mode detection of microRNA on same interface assisted by exonuclease III signal transformation.

Dual-mode sensing has attracted more attentions which provide more accurate and reliable approach of cancer-related biomarkers. Herein, we developed a novel SERS/electrochemical dual-mode biosensor for miRNA 21 detection based on Exo III-assisted signal transformation. Firstly, the Au NPs were deposited on electrode as SERS substrate and Mn3O4/S4(DNA signal strand) was modified on Au NPs/S5 by the DNA strands S5-S4 pairing principle as hydrogen peroxide catalyst, leading to an obviously high DPV electrical signal without Raman signal. Subsequently, the presence of miRNA 21 will activate the Mn3O4/S4 to be decomposed under exonuclease III-assisted process, then the S3' chains modified with Raman molecular Cy3(Cy3-S3') is continuously connected to the Au NPs/S5 by DNA stands S5-S3' pairing principle, leading to the Raman signal response and DPV signal reduction. The biosensor shows good linear calibration curves of both SERS and electrochemical sensing modes with the detection limit of 3.98 × 10-3 nM and 6.89 × 10-5 nM, respectively. This work finds an ingenious mode for dual detection of microRNA on a same interface, which opens a new strategy for SERS and electrochemical analysis.