Gut Microbiome-Driven metabolites influence skin pigmentation in TYRP1 mutant Oujiang Color Common Carp.

The gut microbiome plays a key role in regulating the gut-skin axis, and host genetics partially influence this regulation. The study investigated the role of gut microbiota and host genetics in the gut-skin axis, focusing on the unusual "coffee-like" color phenotype observed in TYRP1 mutant Oujiang Color Common Carp. We employed comparative high-throughput omics data from wild-type and mutant fish to quantify the influence of both genetics and gut microbes on skin transcriptomic expression and blood metabolites. We found 525 differential metabolites (DMs) and 45 distinct gut microbial genera in TYRP1 mutant fish compared to wild type. Interaction and causal mediation analyses revealed a complex interplay. The TYRP1 mutation likely triggers an inflammatory pathway involving Acinetobacter bacteria, Leukotrience-C4 and Spermine. This inflammatory response appears to be counterbalanced by an anti-inflammatory cardiovascular genetic network. The net effect is the upregulation of COMT, PLG, C2, C3, F10, TDO2, MHC1, and SERPINF2, leading to unusual coffee-like coloration. This study highlights the intricate interplay between gut microbiota, host genetics, and metabolic pathways in shaping complex phenotypes.

A temperature-compensated CO2 detection system based on non-dispersive infrared spectral technology.

The concentration of carbon dioxide (CO2) is an important indicator for coal mine safety. Real-time monitoring of CO2 concentration is of great importance for taking actions in advance to avoid the occurrence of potential accidents. To address the issues of poor portability and high cost associated with existing coal mine CO2 detection equipment, this paper develops a miniaturized CO2 detection system based on non-dispersive infrared (NDIR) technology. This sensor integrates an infrared light source and a dual-channel pyroelectric detector into a reflective gas chamber, thereby achieving an extended optical path and higher system sensitivity within limited space. Meanwhile, the noise interference was greatly mitigated by using hardware and software filtering techniques. Based on principle analysis, the Lambert-Beer law was parametrically corrected, and then, a model relationship between the dual-channel voltage ratio and concentration was established. In addition, temperature compensation for zero and span values was introduced to improve the adaptability of the detection results to temperature changes. Testing results indicate that the developed detection system can realize CO2 measurement in the concentration range of 0 to 50 000 ppm within a temperature range of 0-40 °C, with a maximum detection error of less than 0.12% and a repeatability deviation of less than 1.04%. During a stability test for 12 h, the maximum concentration drift is 0.07%, indicating that the developed system meets the requirements for monitoring CO2 safety in coal mines.

Exosomes originating from neural stem cells undergoing necroptosis participate in cellular communication by inducing TSC2 upregulation of recipient cells following spinal cord injury.

ABSTRACT: We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury. While exosomes are recognized as playing a pivotal role in neural stem cells exocrine function, their precise function in spinal cord injury remains unclear. To investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury, we conducted single-cell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord injury. Subsequently, we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted exosomes. The results showed that necroptosis did not significantly impact the fundamental characteristics or number of exosomes. Transcriptome sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs, 104 long non-coding RNAs, 720 circular RNAs, and 14 microRNAs compared with the control group. Construction of a competing endogenous RNA network identified the following hub genes: tuberous sclerosis 2 (Tsc2), solute carrier family 16 member 3 (Slc16a3), and forkhead box protein P1 (Foxpl). Notably, a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord injury. TSC2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury zone. Furthermore, in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other cells. Further assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling pathways. In addition, Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling pathways. Collectively, these findings confirm that exosomes derived from neural stem cells undergoing necroptosis play an important role in cellular communication after spinal cord injury and induce TSC2 upregulation in recipient cells.

Stimuli-Responsive mRNA Vaccines to Induce Robust CD8+ T Cell Response via ROS-Mediated Innate Immunity Boosting.

The messenger RNA (mRNA) vaccines hold great significance in contagion prevention and cancer immunotherapy. However, safely and effectively harnessing innate immunity to stimulate robust and durable adaptive immune protection is crucial, yet challenging. In this study, we synthesized a library of stimuli-responsive bivalent ionizable lipids (srBiv iLPs) with smart molecular blocks responsive to esterase, H2O2, cytochrome P450, alkaline phosphatase, nitroreductase, or glutathione (GSH), aiming to leverage physiological cues to trigger fast lipid degradation, promote mRNA translation, and induce robust antitumor immunity via reactive oxygen species (ROS)-mediated boosting. After subcutaneous immunization, esterase-responsive vaccine (eBiv-mVac) was rapidly internalized and transported into the draining lymph nodes. It then underwent fast decaging and self-immolative degradation in esterase-rich antigen-presenting cells, releasing sufficient mRNA for antigen translation and massive reactive quinone methides to elevate ROS levels. This resulted in broad activation of innate immunity to boost T cell response, prompting a large number of primed antigen-specific CD8+ T cells to circulate and infiltrate into tumors (>1000-fold versus unvaccinated control), thereby orchestrating innate and adaptive immunity to control tumor growth. Moreover, by further combining our vaccination strategy with immune checkpoint blockade, we demonstrated a synergism that significantly amplified the magnitude and function of antigen-specific CD8+ T cells. This, in turn, caused potent systemic antitumor efficacy and prolonged survival with high complete response rate in xenograft and metastasis models. Overall, our generalized stimuli-responsive mRNA delivery platform promises a paradigm shift in the design of potent vaccines for cancer immunotherapy, as well as effective and precise carriers for gene editing, protein replacement, and cell engineering.

Dynamic Addressing Molecular Robot (DAMR): An Effective and Efficient Trial-and-Error Approach for the Analysis of Single Nucleotide Polymorphisms.

Accurate and efficient molecular recognition plays a crucial role in the fields of molecular detection and diagnostics. Conventional trial-and-error-based molecular recognition approaches have always been challenged in distinguishing minimal differences between targets and non-targets, such as single nucleotide polymorphisms (SNPs) of oligonucleotides. To address these challenges, here, a novel concept of dynamic addressing analysis is proposed. In this concept, by dissecting the regions of the target and creating a corresponding recognizer, it is possible to eliminate the inaccuracy and inefficiency of recognition. To achieve this concept, a Dynamic Addressing Molecular Robot (DAMR), a DNA-based dynamic addressing device is developed which is capable of dynamically locating targets. DAMR is designed to first bind to the conserved region of the target while addressing the specific region dynamically until accurate recognition is achieved. DAMR has provided an approach for analyzing low-resolution targets and has been used for analyzing SNP of miR-196a2 in both cell and serum samples, which has opened new avenues for effective and efficient molecular recognition.

Facilitation of coke gasification by coking wastewater and its degradation properties in thermochemical reactions.

The thermochemical reaction between coking wastewater and gasification-coke is a new way to achieve efficient and clean use of coal and solve the problem of coking wastewater treatment in the Gansu Longdong region. To further investigate the thermochemical reaction characteristics of coking wastewater and gasification-coke, this paper explores the effect of coking wastewater on syngas production from coke gasification at 1000 °C, the degradation effect of organic pollutants in coking wastewater, the thermochemical reactivity of gasification-coke, and the reasons why wastewater promotes coke gasification and wastewater degradation. The results showed that the thermochemical reaction of coking wastewater with gasification-coke not only facilitates the improvement of syngas yield and low-level calorific value but also improves the thermochemical reactivity of gasification-coke. Notably, phenol in coking wastewater plays a major role in promoting the gasification of gasification-coke. During the thermochemical reaction, the organic pollutants in the wastewater were effectively degraded, the degradation rate of CODCr reached more than 85%, and the degradation of organic pollutants reached more than 75%. Phenol water and coking wastewater can not only improve the dispersion of the ash phase on the surface of gasification-coke, effectively inhibiting the sintering and agglomeration of the ash phase in gasification-coke, but also change the type and number of organic functional groups in gasification-coke. Therefore, coking wastewater can promote the gasification of coke. The thermochemical reaction between coke wastewater and gasification-coke can simultaneously promote coke gasification and the degradation of coke wastewater and achieve the resourceful use of coke wastewater.

Glass Ceramic Fibers Containing PbS Quantum Dots for Fluorescent Temperature Sensing.

Glass ceramics (GCs) containing PbS quantum dots (QDs) are prepared for temperature sensing. Broadband emissions are detected in the GCs when PbS QDs are precipitated from the glasses, and emissions centers are modulated from 1250 nm to 1960 nm via heat treatments. The emission centers of GCs exhibit blue-shifts when environment temperatures increase from room temperature to 210 °C. Importantly, the shift values of emission centers increase linearly with the test temperature, which is beneficial for applications in temperature sensing. A temperature sensor based on PbS QDs GC is heat-treated at 500 °C for 10 h, possesses the highest sensitivity of 0.378 nm/°C, and exhibits excellent stability and repeatability at high temperatures (up to 210 °C). Moreover, GC fibers are fabricated by using the GCs as the fiber core. The sensitivity of the temperature-sensing sensor of the GC fibers is also demonstrated and the sensitivity is as high as 0.558 nm/°C. The designed PbS QDs GCs provide a significant materials base for the manufacturing of fluorescent temperature sensors and the GC fibers offer significant opportunities for temperature detection in complex, integrated and compact devices.

Effects of Five Dietary Carbohydrate Sources on Growth, Glucose Metabolism, Antioxidant Capacity and Immunity of Largemouth Bass (Micropterus salmoides).

This study investigated the effects of glucose (GLU), tapioca starch (TS), gelatinized tapioca starch (GTS), potato starch (PS) and gelatinized potato starch (GPS) on growth and physiological responses in juvenile largemouth bass Micropterus salmoides. After 8 weeks, fish fed with starch diets had better weight gain and growth rates. Counts of red blood cells and monocytes were increased in the PS and GPS groups, compared to GLU group. Contents of serum triglyceride and total cholesterol were markedly elevated in the TS, PS and GPS groups. There were lower levels of serum glucose, insulin and cholecystokinin, and higher agouti-related peptide contents in the PS group compared to GLU group. PS and GPS could enhance glycolysis and TCA cycle by increasing their enzyme activities and transcriptional levels. Additionally, starch sources markedly heightened mRNA levels of key genes involved in the respiratory electron transport chain. Additionally, elevated mRNA levels of key antioxidant genes were shown in the TS and GTS groups. Moreover, TS and PS could promote immunity by upregulating transcriptional levels of the complement system, lysozyme and hepcidin. Taken together, starch exhibited better growth via increasing glycolysis and TCA cycle compared with GLU, and PS could improve antioxidant and immune capacities in largemouth bass.

High Starch Induces Hematological Variations, Metabolic Changes, Oxidative Stress, Inflammatory Responses, and Histopathological Lesions in Largemouth Bass (Micropterus salmoides).

This study evaluated effects of high starch (20%) on hematological variations, glucose and lipid metabolism, antioxidant ability, inflammatory responses, and histopathological lesions in largemouth bass. Results showed hepatic crude lipid and triacylglycerol (TAG) contents were notably increased in fish fed high starch. High starch could increase counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils and serum contents of TAG, TBA, BUN, and LEP (p < 0.05). There were increasing trends in levels of GLUT2, glycolysis, gluconeogenesis, and LDH in fish fed high starch through the AKT/PI3K signal pathway. Meanwhile, high starch not only triggered TAG and cholesterol synthesis, but mediated cholesterol accumulation by reducing ABCG5, ABCG8, and NPC1L1. Significant increases in lipid droplets and vacuolization were also shown in hepatocytes of D3-D7 groups fed high starch. In addition, high starch could decrease levels of mitochondrial Trx2, TrxR2, and Prx3, while increasing ROS contents. Moreover, high starch could notably increase amounts of inflammatory factors (IL-1ß, TNF-α, etc.) by activating NLRP3 inflammasome key molecules (GSDME, caspase 1, etc.). In conclusion, high starch could not only induce metabolic disorders via gluconeogenesis and accumulation of glycogen, TAG, and cholesterol, but could disturb redox homeostasis and cause inflammatory responses by activating the NLRP3 inflammasome in largemouth bass.

Orthogonal retrieval algorithm of atmospheric temperature profiles from pure rotational Raman lidar signals.

Aimed at the stability of calibration coefficients in a general non-orthogonal retrieval algorithm (NRA) of pure rotational Raman lidars (PRRLs), an orthogonal retrieval algorithm (ORA) of atmospheric temperature profiles based on the orthogonal basis function is proposed. This algorithm eliminates the correlation between the calibration coefficients in the NRA to reduce the influence of the number of calibration points and the selection scheme on the calibration coefficients. In this paper, the stabilities of calibration coefficients in the NRA and ORA are compared and analyzed, and the data analysis for atmospheric temperature profiles with a time resolution of minute-level are given, based on the developed Cloud Precipitation Potential Evaluation (CPPV) lidar data and the parallel radiosonde temperature data. The analysis results show that coefficients of variation (CVs) of ORA calibration coefficients are one order of magnitude smaller than those of NRA coefficients. The mean deviation of the ORA retrieval results is roughly reduced by 16.1% compared with the NRA, and the root-mean-square deviation is roughly reduced by 15.0% compared with the NRA. Therefore, the temperature retrieval performance of the ORA is better than that of the NRA.

Effects of Five Lipid Sources on Growth, Hematological Parameters, Immunity and Muscle Quality in Juvenile Largemouth Bass (Micropterus salmoides).

This study investigated the effects of fish oil (FO), soybean oil (SO), rapeseed oil (RO), peanut oil (PO) and lard oil (LO) on growth, immunity and muscle quality in juvenile largemouth bass. After 8 weeks, the results showed that FO and RO could increase weight gain and serum alkaline phosphatase and apelin values compared with LO (p < 0.05). Except lower crude lipid contents, higher amounts of n-3 polyunsaturated fatty acids (15.83% and 14.64%) were present in the dorsal muscle of the FO and RO groups. Meanwhile, FO and RO could heighten mRNA levels of immune defense molecules (lysozyme, hepcidin, and transforming growth factor ß1) compared with PO (p < 0.05). While SO could increase potential inflammatory risk via rising counts of white blood cells, platelets, neutrophils and monocytes, and mRNA levels of interleukins (IL-1ß, IL-8, IL-12 and IL-15), FO and RO could improve hardness, chewiness and springiness through increasing amounts of hydroxyproline, collagen and lysyl oxidase, and mRNA levels of collagen 1α2 and prolyl hydroxylase in the fish dorsal muscle. Moreover, FO and RO could improve firmness through increasing glycogen and glycogen synthase 1 levels when compared with LO (p < 0.05). Therefore, these results could provide dietary lipid source references during the feeding process of adult largemouth bass.

Dual-responsive 3D DNA nanomachines cascaded hybridization chain reactions for novel self-powered flexible microRNA-detecting platform.

The microRNA-21 is closely related to chromatin remodeling and epigenetic regulation. In this work, an efficient double-response 3D DNA nanomachine (DRDN) was assembled by co-immobilizing two different lengths of hairpin DNA on the surface of gold nanoparticles (AuNPs) to capture microRNA-21 (miRNA-21), recycle miRNA-21, and trigger hybridization chain reactions (HCR). This work reports the fabrication of a laser-scribed graphene (LSG) electrode with excellent flexibility and electrical conductivity by laser-scribing commercial polyimide films (PI). The as-proposed self-powered biosensing platform presents significantly increased instantaneous current to in real-time monitor miRNA-21 by a capacitor. The biosensing platform exhibited highly sensitive detection of miRNA-21 with a detection limit of 0.142 fM in the range of 0.5 fM to 1 × 104 fM, and demonstrated high efficiency in the analysis of the tumor markers.

Effects of selenoprotein extracts from Cardamine hupingshanensis on growth, selenium metabolism, antioxidant capacity, immunity and intestinal health in largemouth bass Micropterus salmoides.

This study aimed to assess the impact of dietary selenoprotein extracts from Cardamine hupingshanensis (SePCH) on the growth, hematological parameters, selenium metabolism, immune responses, antioxidant capacities, inflammatory reactions and intestinal barrier functions in juvenile largemouth bass (Micropterus salmoides). The base diet was supplemented with four different concentrations of SePCH: 0.00, 0.30, 0.60 and 1.20 g/Kg (actual selenium contents: 0.37, 0.59, 0.84 and 1.30 mg/kg). These concentrations were used to formulate four isonitrogenous and isoenergetic diets for juvenile largemouth bass during a 60-day culture period. Adequate dietary SePCH (0.60 and 1.20 g/Kg) significantly increased weight gain and daily growth rate compared to the control groups (0.00 g/Kg). Furthermore, 0.60 and 1.20 g/Kg SePCH significantly enhanced amounts of white blood cells, red blood cells, platelets, lymphocytes and monocytes, and levels of hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin in the hemocytes. In addition, 0.60 and 1.20 g/Kg SePCH increased the mRNA expression levels of selenocysteine lyase, selenophosphate synthase 1, 15 kDa selenoprotein, selenoprotein T2, selenoprotein H, selenoprotein P and selenoprotein K in the fish liver and intestine compared to the controls. Adequate SePCH not only significantly elevated the activities of antioxidant enzymes (Total superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase), the levels of total antioxidant capacity and glutathione, while increased mRNA transcription levels of NF-E2-related factor 2, Cu/Zn-superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase. However, adequate SePCH significantly decreased levels of malondialdehyde and H2O2 and the mRNA expression levels of kelch-like ECH-associated protein 1a and kelch-like ECH-associated protein 1b in the fish liver and intestine compared to the controls. Meanwhile, adequate SePCH markedly enhanced the levels of immune factors (alkaline phosphatase, acid phosphatase, lysozyme, complement component 3, complement component 4 and immunoglobulin M) and innate immune-related genes (lysozyme, hepcidin, liver-expressed antimicrobial peptide 2, complement component 3 and complement component 4) in the fish liver and intestine compared to the controls. Adequate SePCH reduced the levels of pro-inflammatory cytokines (tumour necrosis factor-α, interleukin 8, interleukin 1ß and interferon γ), while increasing transforming growth factor ß1 levels at both transcriptional and protein levels in the liver and intestine. The mRNA expression levels of mitogen-activated protein kinase 13 (MAPK 13), MAPK14 and nuclear factor kappa B p65 were significantly reduced in the liver and intestine of fish fed with 0.60 and 1.20 g/Kg SePCH compared to the controls. Histological sections also demonstrated that 0.60 and 1.20 g/Kg SePCH significantly increased intestinal villus height and villus width compared to the controls. Furthermore, the mRNA expression levels of tight junction proteins (zonula occludens-1, zonula occludens-3, Claudin-1, Claudin-3, Claudin-5, Claudin-11, Claudin-23 and Claudin-34) and Mucin-17 were significantly upregulated in the intestinal epithelial cells of 0.60 and 1.20 g/Kg SePCH groups compared to the controls. In conclusion, these results found that 0.60 and 1.20 g/Kg dietary SePCH can not only improve growth, hematological parameters, selenium metabolism, antioxidant capacities, enhance immune responses and intestinal functions, but also alleviate inflammatory responses. This information can serve as a useful reference for formulating feeds for largemouth bass.

Coordination Environment Engineering of Metal Centers in Coordination Polymers for Selective Carbon Dioxide Electroreduction toward Multicarbon Products.

Electrocatalytic carbon dioxide reduction reaction (CO2RR) toward value-added chemicals/fuels has offered a sustainable strategy to achieve a carbon-neutral energy cycle. However, it remains a great challenge to controllably and precisely regulate the coordination environment of active sites in catalysts for efficient generation of targeted products, especially the multicarbon (C2+) products. Herein we report the coordination environment engineering of metal centers in coordination polymers for efficient electroreduction of CO2 to C2+ products under neutral conditions. Significantly, the Cu coordination polymer with Cu-N2S2 coordination configuration (Cu-N-S) demonstrates superior Faradaic efficiencies of 61.2% and 82.2% for ethylene and C2+ products, respectively, compared to the selective formic acid generation on an analogous polymer with the Cu-I2S2 coordination mode (Cu-I-S). In situ studies reveal the balanced formation of atop and bridge *CO intermediates on Cu-N-S, promoting C-C coupling for C2+ production. Theoretical calculations suggest that coordination environment engineering can induce electronic modulations in Cu active sites, where the d-band center of Cu is upshifted in Cu-N-S with stronger selectivity to the C2+ products. Consequently, Cu-N-S displays a stronger reaction trend toward the generation of C2+ products, while Cu-I-S favors the formation of formic acid due to the suppression of C-C couplings for C2+ pathways with large energy barriers.

Selenium yeast improve growth, serum biochemical indices, metabolic ability, antioxidant capacity and immunity in black carp Mylopharyngodnpiceus.

This experiment was conducted to investigate the impacts of dietary selenium yeast (SeY) on the growth performance, fish body composition, metabolic ability, antioxidant capability, immunity and inflammatory responses in juvenile black carp (Mylopharyngodn piceus). The base diet was supplemented with 0.00, 0.30 and 0.60 g/kg SeY (0.04, 0.59 and 1.15 mg/kg of selenium) to form three isonitrogenous and isoenergetic diets for juvenile black carp with a 60-day. Adequate dietary SeY (0.30 and 0.60 g/kg) could significantly increase the weight gain (WG), special growth rate (SGR) compared to the SeY deficient groups (0.00 g/kg) (P < 0.05). Meanwhile, 0.30 and 0.60 g/kg SeY elevated the mRNA levels of selenoprotein T2 (SEPT2), selenoprotein H (SEPH), selenoprotein S (SEPS) and selenoprotein M (SEPM) in the liver and intestine compared with the SeY deficient groups (P < 0.05). Adequate dietary SeY could promote glucose catabolism and utilization through activating glucose transport (GLUT2), glycolysis (GCK, HK, PFK, PK, PDH), tricarboxylic acid cycle (ICDH and MDH), glycogen synthesis (LG, GCS and GBE) and IRS/PI3K/AKT signal pathway molecules (IRS2b, PI3Kc and AKT1) compared with the SeY deficient groups (P < 0.05). Similarly, adequate dietary SeY could improve lipid transport and triglycerides (TG) synthesis through increasing transcription amounts of CD36, GK, DGAT, ACC and FAS in the fish liver compared with the SeY deficient groups (P < 0.05). In addition, adequate SeY could markedly elevate activities of antioxidant enzymes (T-SOD, CAT, GR, GPX) and contents of T-AOC and GSH, while increased transcription amounts of Nrf2, Cu/Zn-SOD, CAT, and GPX in fish liver and intestine (P < 0.05). However, adequate SeY notably decreased contents of MDA, and the mRNA transcription levels of Keap1 in the intestine compared with the SeY deficient groups (P < 0.05). Adequate SeY markedly increased amounts or levels of the immune factors (ALP, ACP, LZM, C3, C4 and IgM) and the transcription levels of innate immune-related functional genes in the liver and intestine (LZM, C3 and C9) compared to the SeY deficient groups (P < 0.05). Moreover, adequate SeY could notably reduce levels of IL-8, IL-1ß, and IFN-γ and elevate TGF-1ß levels in fish intestine (P < 0.05). The transcription levels of MAPK13, MAPK14 and NF-κB p65 were notably reduced in fish intestine treated with 0.30 and 0.60 g/kg SeY (P < 0.05). In conclusion, these results suggested that 0.30 and 0.60 g/kg SeY could not only improve growth performance, increase Se, glucose and lipid metabolic abilities, enhance antioxidant capabilities and immune responses, but also alleviate inflammation, thereby supplying useful reference for producing artificial feeds in black carp.

Tunable Multivalent Aptamer-Based DNA Nanostructures To Regulate Multiheteroreceptor-Mediated Tumor Recognition.

Precise mapping and regulation of cell surface receptors hold immense significance in disease treatment, such as cancer, infection, and neurodisorders, but also face enormous challenges. In this study, we designed a series of adjustable multivalent aptamer-based DNA nanostructures to precisely control their interaction with receptors in tumor cells. By profiling surface receptors on 12 cell lines using 10 different aptamers, we generated a heatmap that accurately distinguished between various tumor types based on multiple markers. We then incorporated these aptamers onto DNA origami structures to regulate receptor recognition, with patch-like structures demonstrating a tendency to be trapped on the cell surface and with tube-like structures showing a preference for internalization. Through precise control of aptamer species, valence, and geometric patterns, we found that multiheteroreceptor-mediated recognition not only favored the specific binding of nanostructures to tumor cells but also greatly enhanced intracellular uptake by promoting clathrin-dependent endocytosis. Specifically, we achieved over 5-fold uptake in different tumor cells versus normal cells using tube-like structures modified with different diheteroaptamer pairs, facilitating targeted drug delivery. Moreover, patch-like structures with triheteroaptamers guided specific interactions between macrophages and tumor cells, leading to effective immune clearance. This programmable multivalent system allows for the precise regulation of cell recognition using multiple parameters, demonstrating great potential for personalized tumor treatment.

Cooperatively designed aptamer-PROTACs for spatioselective degradation of nucleocytoplasmic shuttling protein for enhanced combinational therapy.

Nucleocytoplasmic shuttling proteins (NSPs) have emerged as a promising class of therapeutic targets for many diseases. However, most NSPs-based therapies largely rely on small-molecule inhibitors with limited efficacy and off-target effects. Inspired by proteolysis targeting chimera (PROTAC) technology, we report a new archetype of PROTAC (PS-ApTCs) by introducing a phosphorothioate-modified aptamer to a CRBN ligand, realizing tumor-targeting and spatioselective degradation of NSPs with improved efficacy. Using nucleolin as a model, we demonstrate that PS-ApTCs is capable of effectively degrading nucleolin in the target cell membrane and cytoplasm but not in the nucleus, through the disruption of nucleocytoplasmic shuttling. Moreover, PS-ApTCs exhibits superior antiproliferation, pro-apoptotic, and cell cycle arrest potencies. Importantly, we demonstrate that a combination of PS-ApTCs-mediated nucleolin degradation with aptamer-drug conjugate-based chemotherapy enables a synergistic effect on tumor inhibition. Collectively, PS-ApTCs could expand the PROTAC toolbox to more targets in subcellular localization and accelerate the discovery of new combinational therapeutic approaches.

Novel Ultralow-Potential Electrochemiluminescence Aptasensor for the Highly Sensitive Detection of Zearalenone Using a Resonance Energy Transfer System.

An ultralow-potential electrochemiluminescence (ECL) aptasensor has been designed for zearalenone (ZEN) assay based on a resonance energy transfer (RET) system with SnS2 QDs/g-C3N4 as a novel luminophore and CuO/NH2-UiO-66 as a dual-quencher. SnS2 QDs were loaded onto g-C3N4 nanosheets and enhanced the ECL luminescence via strong synergistic effects under an ultralow potential. The UV-vis absorption spectrum of CuO/NH2-UiO-66 exhibits considerable overlap with the ECL emission spectrum of SnS2 QDs/g-C3N4, an important consideration for the RET process. In order to stimulate RET, the ZEN aptamer and complementary DNA are introduced for conjugation between the donor and the acceptor. With the binding interaction between ZEN by its aptamer, CuO/NH2-UiO-66 is removed from the electrode surface, resulting in the inhibition of the RET system and an increase in the ECL signal. Under optimal conditions, the as-prepared aptasensor quantified ZEN from 0.5 µg·mL-1 to 0.1 fg·mL-1 with a low limit of detection of 0.085 fg·mL-1, and it exhibited good stability, excellent specificity, high reproducibility, and desirable practicality. The sensing strategy provides a method for mycotoxins assay to monitor food safety.

Acylhydrazone functionalized naphthalene-based self-assembled supramolecular gels for efficient fluorescence detection of Fe3.

A new gel factor (named N) has been successfully designed and synthesized, which contains the conventional fluorophore naphthalene with the acylhydrazone bond as the self-assembly site. It can be self-assembled into stable organogels (named ON) in dimethyl sulfoxide (DMSO) and water mixed medium (V : V = 4 : 1) with a critical gel temperature and concentration (55 °C and 10 mg mL-1). Interestingly, under 365 nm UV light, the ON exhibits bright yellow Aggregation Induced Emission (AIE). The supramolecular organogel ON shows a fluorescent "OFF" response to the metal ions Fe3+, and the state of the gel ON remains constant before and after detection. Notably, the minimum detection limits (LODs) of the gel ON for Fe3+ are as low as 1.30 × 10-7 M. The binding mechanism of supramolecular organogels (ON) to ions has been investigated through a series of characterizations. Meanwhile, the organogel sensor ON can also be used as an ion-responsive membrane for the detection of Fe3+ in the aqueous phase.