Targeting SNRNP200-induced splicing dysregulation offers an immunotherapy opportunity for glycolytic triple-negative breast cancer.

Metabolic dysregulation is prominent in triple-negative breast cancer (TNBC), yet therapeutic strategies targeting cancer metabolism are limited. Here, utilizing multiomics data from our TNBC cohort (n = 465), we demonstrated widespread splicing deregulation and increased spliceosome abundance in the glycolytic TNBC subtype. We identified SNRNP200 as a crucial mediator of glucose-driven metabolic reprogramming. Mechanistically, glucose induces acetylation at SNRNP200 K1610, preventing its proteasomal degradation. Augmented SNRNP200 then facilitates splicing key metabolic enzyme-encoding genes (GAPDH, ALDOA, and GSS), leading to increased lactic acid and glutathione production. Targeting SNRNP200 with antisense oligonucleotide therapy impedes tumor metabolism and enhances the efficacy of anti-PD-1 therapy by activating intratumoral CD8+ T cells while suppressing regulatory T cells. Clinically, higher SNRNP200 levels indicate an inferior response to immunotherapy in glycolytic TNBCs. Overall, our study revealed the intricate interplay between RNA splicing and metabolic dysregulation, suggesting an innovative combination strategy for immunotherapy in glycolytic TNBCs.

Segmentation and Completion of Human Motion Sequence via Temporal Learning of Subspace Variety Model.

Subspace-based models have been extensively employed in unsupervised segmentation and completion of human motion sequence (HMS). However, existing approaches often neglect the incorporation of temporal priors embedded in HMS, resulting in suboptimal results. This paper presents a subspace variety model for HMS, along with an innovative Temporal Learning of Subspace Variety Model (TL-SVM) method for enhanced segmentation and completion in HMS. The key idea is to segment incomplete HMS into motion clusters and extracting the subspace features of each motion through the temporal learning of the subspace variety model. Subsequently, the HMS is completed based on the extracted subspace features. Thus, the main challenge is to learn the subspace variety model with temporal priors when confronted with missing entries. To tackle this, the paper develops a spatio-temporal assignment consistency (STAC) constraint for the subspace variety model, leveraging temporal priors embedded in HMS. In addition, a subspace clustering approach under the STAC constraint is proposed to learn the subspace variety model by extracting subspace features from HMS and segmenting HMS into motion clusters alternatively. The proposed subspace clustering model can also handle missing entries with theoretical guarantees. Furthermore, the missing entries of HMS are completed by minimizing the distance between each human motion frame and its corresponding subspace. Extensive experimental results, along with comparisons to state-of-the-art methods on four benchmark datasets, underscore the advantages of the proposed method.

Acid-mediated strategies designed for stretchable and durable polyacrylamide/sodium alginate dual-network hydrogels toward flexible capacitors and wearable sensors.

The utilization of acid as a synthesis assistant provides an effective means to regulate the structure of hydrogels, thereby simplifying the design and preparation process of multifunctional hydrogels. However, there remains a dearth of discourse concerning the utilization of this convenient acid-mediated strategy, which possesses the potential to directly govern molecular interactions within gel networks for rational structure and property design. Herein, we describe the preparation of flexible dual-network conductive hydrogels using polyacrylamide (PAM) and sodium alginate (SA) as substrates, driven by the strategy of acid-mediated (HCI, H2SO4, and H2C2O4) in detail for the first time. Especially, the structure-activity relationship of hydrogels was elucidated through a comparative analysis of molecular dynamics (MD) simulations and empirical properties, thereby enhancing the understanding of this field. Furthermore, extensive investigations have been conducted to explore the distinct impacts of acid ions and concentrations. The acid-mediated method exhibits superior versatility and operability compared to the filler modification method, thereby enabling a more convenient acquisition of conductive and robust hydrogels suitable for flexible capacitors and wearable sensors. Consequently, this study presents a straightforward, efficient, and cost-effective universal strategy for targeted functional hydrogel design.

Fabrication of cinnamon essential oil nanoemulsions with high antibacterial activities via microfluidization.

The high volatility and hydrophobicity of cinnamon essential oils (CiEO) limited their practical application. To enhance their stability and antibacterial activity, nanoemulsions encapsulating CiEO were prepared using hydroxypropyl-ß-cyclodextrin/lauroyl arginate (HPCD/LAE) inclusion complexes through high-pressure microfluidization (HPM). Effects of HPM parameters on the stability and antibacterial properties of nanoemulsion were investigated. Results revealed that increased processing pressure and cycle numbers were associated with reduced droplet size and greater homogeneity in CiEO distribution. Storage and thermal stability were optimized at 100 MPa and seven cycles. Moreover, the nanoemulsions showed strong synergistic antibacterial against E. coli (19.79 mm) and S. aureus (23.61 mm) compared with LAE (11.52 mm and 12.82 mm, respectively) and CiEO alone (13.26 mm and 17.68 mm, respectively). This study provided new information for constructing CiEO nanoemulsion, which is suitable for use in the food industry.

Case report: Virtual reality-based arm and leg cycling combined with transcutaneous electrical spinal cord stimulation for early treatment of a cervical spinal cord injured patient.

Spinal cord injury is a condition affecting the central nervous system, causing different levels of dysfunction below the point of nerve damage. A 50-year-old woman suffered a neck injury as a result of a car accident. After undergoing posterior cervical C3-C6 internal fixation with titanium plates on one side and C7 lamina decompression, the patient, who had been diagnosed with C3-C7 cervical disk herniation and spinal stenosis causing persistent compression of the spinal cord, was transferred to the rehabilitation department. After implementing the combined therapy of Virtual Reality-based arm and leg cycling along with transcutaneous electrical stimulation of the spinal cord, the patients experienced a notable enhancement in both sensory and motor abilities as per the ASIA scores. The patient's anxiety and depression were reduced as measured by the Hamilton Anxiety and Hamilton Depression Tests. As evaluated by the SCIM-III, the patient's self-reliance and capacity to carry out everyday tasks showed ongoing enhancement, leading to the restoration of their functionality. Hence, the use of Virtual Reality-based arm and leg cycling along with transcutaneous electrical spinal cord stimulation has potential to positively impact function in patients with spinal cord injury. However, as this is a case report, the small number of patients and the fact that the intervention was initiated early after the injury, we were unable to separate the recovery due to the intervention from the natural recovery that is known to occur in the initial weeks and months after SCI. Therefore, further randomized controlled trials with a large sample size is necessary.

MnFe Prussian Blue Analogue Open Cages for Sodium-Ion Batteries: Simultaneous Evolution of Structure, Morphology, and Energy Storage Properties.

Prussian blue analogues (PBAs) exhibiting hollow morphologies have garnered considerable attention owing to their remarkable electrochemical properties. In this study, a one-pot strategy is proposed for the synthesis of MnFe PBA open cages. The materials are subsequently employed as cathode electrode in sodium-ion batteries (SIBs). The simultaneous evolution of structure, morphology, and performance during the synthesis process is investigated. The findings reveal substantial structural modifications as the reaction time is prolonged. The manganese content in the samples diminishes considerably, while the potassium content experiences an increase. This compositional variation is accompanied by a significant change in the spin state of the transition metal ions. These structural transformations trigger the occurrence of the Kirkendall effect and Oswald ripening, culminating in a profound alteration of the morphology of MnFe PBA. Moreover, the shifts in spin states give rise to distinct changes in their charge-discharge profiles and redox potentials. Furthermore, an exploration of the formation conditions of the samples and their variations before and after cycling is conducted. This study offers valuable insights into the intricate relationship between the structure, morphology, and electrochemical performance of MnFe PBA, paving the way for further optimizations in this promising class of materials for energy storage applications.

WITHDRAWN: Supinoxin blocks Small Cell Lung Cancer Progression by Inhibiting Mitochondrial Respiration through the RNA Helicase DDX5.

The authors have requested that this preprint be removed from Research Square.

Akkermansia muciniphila: a potential candidate for ameliorating metabolic diseases.

Metabolic diseases are comprehensive disease based on obesity. Numerous cumulative studies have shown a certain correlation between the fluctuating abundance of Akkermansia muciniphila and the occurrence of metabolic diseases. A. muciniphila, a potential probiotic candidate colonized in the human intestinal mucus layer, and its derivatives have various physiological functions, including treating metabolic disorders and maintaining human health. This review systematically explicates the abundance change rules of A. muciniphila in metabolic diseases. It also details the high efficacy and specific molecules mechanism of A. muciniphila and its derivatives in treating obesity, type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease.

Evaluation of the aroma and taste contributions of star anise (I. Verum hook. f.) in braised duck leg via flavor omics combined with multivariate statistics.

To promote the rationalized and standardized application of star anise in braised poultry products, the effects of different concentrations of star anise (0 %, 0.1 %, 0.2 %, 0.3 %, and 0.4 %) on the aroma and taste compounds intensities of braised duck legs from the perspective of flavor were evaluated by using flavor omics approach combined with multivariate statistics. The volatile flavor results showed that there were 17 key aroma compounds with odor activity values (OAVs) > 1, including aldehydes, alcohols, ketones, furans, hydrocarbons, and ethers. Most of the aroma compounds related to lipid oxidation were significantly inhibited when the concentration of star anise reached 0.2 %, especially inhibited the concentrations of the unpleasant off-odorants containing hexanal, heptanal, 1-octen-3-ol, and 2-pentyl-furan by 30.27 %, 15.08 %, 30.30 %, and 41.63 %, respectively. And the flavor intensities of these compounds were negatively correlated with the concentration of star anise. Additionally, star anise gave braised duck legs characteristic aroma such as floral and herbal notes. The taste results revealed that the maximum umami value (4.36 g MSG/100 g) of braised duck legs was observed when the concentration of star anise reached 0.2 %. Six flavor markers were obtained via PLS-DA model, and the flavors of braised duck legs with different concentrations of star anise were distinguished. This study provided a vital theoretical basis for the rational application and flavor control of star anise in braised poultry products.

Vaccination of Poultry Against Influenza.

The complexity of influenza A virus (IAV) infections in avian hosts leads to equally complex scenarios for the vaccination of poultry. Vaccination against avian influenza strains can be used to prevent infections from sources with a single strain of IAV. It has been used as a part of outbreak control strategies as well as a way to maintain production for both low and high pathogenicity outbreaks. Unlike other viral pathogens of birds, avian influenza vaccination when used against highly pathogenic avian influenza virus, is tied to international trade and thus is not freely available for use without specific permission.

Vacunación de aves comerciales contra la influenza aviar. La complejidad de las infecciones por el virus de la influenza A en las aves hospedadoras conduce a escenarios igualmente complejos para la vacunación en la avicultura. La vacunación contra cepas de influenza aviar se puede utilizar para prevenir infecciones provenientes de fuentes con una sola cepa del virus de influenza. Se ha utilizado como parte de las estrategias de control de brotes, así como como una forma de mantener la producción tanto en brotes de baja como de alta patogenicidad. A diferencia de otros patógenos virales de las aves, la vacunación contra la influenza aviar, cuando se usa contra el virus de la influenza aviar altamente patógeno, está vinculada al comercio internacional y por lo tanto, no está disponible para su uso sin un permiso específico.

Heterostructured grafting of NiFe-layered double hydroxide@TiO2 for boosting photoelectrochemical cathodic protection.

Accelerating the oxidation process at photoanode-electrolyte interfaces can prolong the lifetime of photoexcited electrons and improve the efficiency of photoelectrochemical cathodic protection (PECCP) systems without relying on hole scavengers. However, the systematic design of precisely structured heterostructures for efficient photoanodes remains challenging. Here we meticulously engineered a type-II heterostructure featuring precise spatial organization, wherein NiFe-layered double hydroxide nanosheets (NiFe-LDH NSs) were assembled onto annealed TiO2 nanorod arrays (ATNAs), demonstrating their effectiveness in achieving efficient PECCP. The interfacial electronic coupling and appropriate energy alignment between the NiFe-LDH NSs and ATNAs allowed rapid hole extraction from the ATNAs to the NiFe-LDH NSs. Furthermore, the uniform distribution of the NiFe-LDH NSs on top of ATNAs drastically reduced the overpotential of oxygen evolution reactions (OER) from 370 to 200 mV and Tafel slope from 162 to 56 mV dec-1, leading to significantly improved cathodic protection of 304 stainless steel (SS) under extended illumination and interesting post-illumination protection. In addition, with the increase of testing cycles, the as-prepared NiFe-LDH NSs@ATNAs demonstrated a progressively enhanced cathodic protection potential from 0.15 to 0.13 V vs. RHE over 50 cycles. These findings provide important guidelines for the design of future high-efficiency green metal protection through rational photoanode design.

High-intensity interval training induces lactylation of fatty acid synthase to inhibit lipid synthesis.

BACKGROUND: The aim of study was to observe the effect of increased lactate levels during high-intensity interval training (HIIT) on protein lactylation, identify the target protein, and investigate the regulatory effect of lactylation on the function of the protein. METHODS: C57B/L6 mice were divided into 3 groups: the control group, HIIT group, and dichloroacetate injection + HIIT group (DCA + HIIT). The HIIT and DCA + HIIT groups underwent 8 weeks of HIIT treatment, and the DCA + HIIT group was injected DCA before HIIT treatment. The expression of lipid metabolism-related genes was determined. Protein lactylation in subcutaneous adipose tissue was identified and analyzed using 4D label-free lactylation quantitative proteomics and bioinformatics analyses. The fatty acid synthase (FASN) lactylation and activity was determined. RESULTS: HIIT had a significant effect on fat loss; this effect was weakened when lactate production was inhibited. HIIT significantly upregulated the protein lactylation while lactate inhibition downregulated in iWAT. FASN had the most modification sites. Lactate treatment increased FASN lactylation levels, inhibited FASN activity, and reduced palmitate and triglyceride synthesis in 3T3-L1 cells. CONCLUSIONS: This investigation revealed that lactate produced by HIIT increased protein pan-lactylation levels in iWAT. FASN lactylation inhibited de novo lipogenesis, which may be an important mechanism in HIIT-induced fat loss.

Sensitive detection of heavy metal stress in aquatic plants by dissolved oxygen-quenched fluorescence/materials movement-induced beam deflection method.

Sensitive detection of heavy metal (HM) stress in aquatic plants by dissolved oxygen (DO)-quenched fluorescence/materials movement-induced beam deflection method is demonstrated. Egeria densa Planchon and Cu2+ were used as a model aquatic plant and HM ion, respectively. Reproducibility and experimental errors of the method were first investigated in a control culture solution only containing 10-6 M Ru (II) complex (Tris (2,2'-bipyridyl) ruthenium (II) chloride) without addition of any fertilizer and Cu2+. Changes of DO concentration (∆DO) and deflection (∆DE) during the monitoring periods were used as parameters to quantitatively evaluate the experimental errors and detection limits. Averages or means ([Formula: see text], [Formula: see text]) and standard deviations (σ∆DO, σ∆DE) of ∆DO and ∆DE in seven control experiments with different aquatic plants sheets during both the respiration and photosynthesis processes were obtained. Next, DO and deflection at the middle vicinities of the aquatic plant were monitored during 2 h of both respiration and photosynthesis in presence of 10-10 ~ 10-6 M Cu2+. Experimental results showed that the aquatic plant began to suffer from the HM stress in some extent in presence of 10-9 M Cu2+. When the concentration of Cu2+ was higher than 10-8 M, changing trends of both DO and deflection with time were not reversed during the respiration and photosynthesis, implying that the materials movements in the physiological activities had been altered greatly. It is demonstrated that the method could sensitively detect the HM stress in the aquatic plants given by nM HM ions in culture solution without addition of a fertilizer. Furthermore, detection limits of the method were quantitatively discussed by considering [Formula: see text] σ∆DO and [Formula: see text] σ∆DE as the minimum detectable changes of DO and deflection caused by the HM stress, respectively.

High-Intensity Interval Training Induces Protein Lactylation in Different Tissues of Mice with Specificity and Time Dependence.

Protein lysine lactylation (Kla) is a novel protein acylation reported in recent years, which plays an important role in the development of several diseases with pathologically elevated lactate levels, such as tumors. The concentration of lactate as a donor is directly related to the Kla level. High-intensity interval training (HIIT) is a workout pattern that has positive effects in many metabolic diseases, but the mechanisms by which HIIT promotes health are not yet clear. Lactate is the main metabolite of HIIT, and it is unknown as to whether high lactate during HIIT can induce changes in Kla levels, as well as whether Kla levels differ in different tissues and how time-dependent Kla levels are. In this study, we observed the specificity and time-dependent effects of a single HIIT on the regulation of Kla in mouse tissues. In addition, we aimed to select tissues with high Kla specificity and obvious time dependence for lactylation quantitative omics and analyze the possible biological targets of HIIT-induced Kla regulation. A single HIIT induces Kla in tissues with high lactate uptake and metabolism, such as iWAT, BAT, soleus muscle and liver proteins, and Kla levels peak at 24 h after HIIT and return to steady state at 72 h. Kla proteins in iWAT may affect pathways related to glycolipid metabolism and are highly associated with de novo synthesis. It is speculated that the changes in energy expenditure, lipolytic effects and metabolic characteristics during the recovery period after HIIT may be related to the regulation of Kla in iWAT.

Hepatocyte-targeted delivery using oleanolic acid-loaded liposomes for enhanced hepatocellular carcinoma therapy.

Drug-loaded liposomes have been shown to be effective in the treatment of hepatocellular carcinoma (HCC). However, the systemic non-specific distribution of drug-loaded liposomes in tumor patients is a critical therapeutic challenge. To address this issue, we developed galactosylated chitosan-modified liposomes (GC@Lipo) that could selectively bind to the asialoglycoprotein receptor (ASGPR), which is highly expressed on the membrane surface of HCC cells. Our study demonstrated that the GC@Lipo significantly enhanced the anti-tumor efficacy of oleanolic acid (OA) by enabling targeted drug delivery to hepatocytes. Remarkably, treatment with OA-loaded GC@Lipo inhibited the migration and proliferation of mouse Hepa1-6 cells by upregulating E-cadherin expression and downregulating N-cadherin, vimentin, and AXL expressions, compared to a free OA solution and OA-loaded liposomes. Furthermore, using an axillary tumor xenograft mouse model, we observed that OA-loaded GC@Lipo led to a significant reduction in tumor progression, accompanied by concentrated enrichment in hepatocytes. These findings strongly support the clinical translation of ASGPR-targeted liposomes for the treatment of HCC.

Applications, challenges and prospects of bionic nose in rapid perception of volatile organic compounds of food.

Bionic nose, a technology that mimics the human olfactory system, has been widely used to assess food quality due to their high sensitivity, low cost, portability and simplicity. This review briefly describes that bionic noses with multiple transduction mechanisms are developed based on gas molecules' physical properties: electrical conductivity, visible optical absorption, and mass sensing. To enhance their superior sensing performance and meet the growing demand for applications, a range of strategies have been developed, such as peripheral substitutions, molecular backbones, and ligand metals that can finely tune the properties of sensitive materials. In addition, challenges and prospects coexist are covered. Cross-selective receptors of bionic nose will help and guide the selection of the best array for a particular application scenario. It provides an odour-based monitoring tool for rapid, reliable and online assessment of food safety and quality.

Fully nondestructive analysis of capsaicinoids electrochemistry data with deep neural network enables portable system.

Electrochemical methods have been extensively applied for the detection of chemical information from food or other analytes. However, existing electrochemical methods are limited to focusing solely on the absorption peaks and disregard much of the hidden chemical fingerprint information. Consequently, electrochemical sensors are constrained by their ability to detect samples containing multiple source-material mixtures with overlapping constituents. We hypothesized that the target substances can be effectively identified and detected using differential sensor data combined with artificial intelligence (AI). In this study, we developed a novel signal array composed of five metal electrodes and used a convolutional neural network (CNN) model for feature extraction to detect capsaicinoids in stews. Our results indicate that the proposed method achieved satisfactory predictions with a root mean square error (RMSE) of 5.407 in independent brine samples. This provides a promising strategy and practical approach for the nondestructive analysis of multidimensional electrochemical data of mixed analytes.

Ether-based electrolytes enable the application of nitrogen and sulfur co-doped 3D graphene frameworks as anodes in high-performance sodium-ion batteries.

The development of graphitic carbon materials as anodes of sodium-ion batteries (SIBs) is greatly restricted by their inherent low specific capacity. Herein, nitrogen and sulfur co-doped 3D graphene frameworks (NSGFs) were successfully synthesized via a simple and facile one-step hydrothermal method and exhibited high Na storage capacity in ether-based electrolytes. A systematic comparison was made between NSGFs, undoped graphene frameworks (GFs) and nitrogen-doped graphene frameworks (NGFs). It is demonstrated that the high specific capacity of NSGFs can be attributed to the free diffusion of Na ions within the graphene layer and reversible reaction between -C-Sx-C- covalent chains and Na ions thanks to the large interplanar distance and the dominant -C-Sx-C- covalent chains in NSGFs. NSGF anodes, therefore, exhibit a high initial coulombic efficiency (ICE) (92.8%) and a remarkable specific capacity of 834.0 mA h g-1 at 0.1 A g-1. Kinetic analysis verified that the synergetic effect of N/S co-doping not only largely enhanced the Na ion diffusion rate but also reduced the electrochemical impedance of NSGFs. Postmortem techniques, such as SEM, ex situ XPS, HTEM and ex situ Raman spectroscopy, all demonstrated the extremely physicochemically stable structure of the 3D graphene matrix and ultrathin inorganic-rich solid electrolyte interphase (SEI) films formed on the surface of NSGFs. Yet it is worth noting that the Na storage performance and mechanism are exclusive to ether-based electrolytes and would be inhibited in their carbonate ester-based counterparts. In addition, the corrosion of copper foils under the synergetic effect of S atoms and ether-based electrolytes was reported for the first time. Interestingly, by-products derived from this corrosion could provide additional Na storage capacity. This work sheds light on the mechanism of improving the electrochemical performance of carbon-based anodes by heteroatom doping in SIBs and provides a new insight for designing high-performance anodes of SIBs.

Effect of nano-TiO2 particle size on the bonding performance and film-forming properties of starch-based wood adhesives.

The effect of nano-TiO2 particle size on the properties of starch-based wood adhesives was studied in this work. Our findings indicate that a smaller size of nano-TiO2 particles corresponds with a larger specific surface area and more hydroxyl sites on the particle surface that interact with latex molecules, forming a more compact network structure. Therefore, the bonding performance and water resistance of the adhesive were enhanced. In addition, rheology results showed that the adhesive behaves as a pseudoplastic fluid. Small-angle X-ray scattering and energy dispersive spectroscopy confirmed the good compatibility and dispersion of nano-TiO2 in the adhesive films. Diffusing wave spectroscopy and scanning electron microscopy showed that smaller TiO2 particles were more favorable for the formation of smoother and denser films. These results are of great significance for improving the structure and properties of starch-based wood adhesives and preparing high-performance environmentally friendly biobased adhesives.

Ionic COF Composite Membranes for Selective Perfluoroalkyl Substances Separation.

High-performance membranes are critical to membrane separation technology. In recent years, 2D covalent organic frameworks (2D COFs) have attracted extensive attention in the field of membrane separation due to their high porosity, ordered channels, and fine-tuned pore sizes, which are considered as excellent candidate to solve the trade-off between membrane selectivity and permeability. Herein, two kinds of ionic 2D COFs with different charge properties (termed as iCOFs) are integrated into polyacrylonitrile (PAN) substrates to form two composite membranes (PAN@iCOFs) with excellent selective perfluoroalkyl substances (PFASs) separation performance with high solvent permeability and good mechanical properties. The as-prepared PAN@iCOFs composite membranes can selectively reject more than 99.0% of positively and negatively charged PFASs in wastewater while maintaining good stability and recyclability.