Rutin prevents EqHV-8 induced infection and oxidative stress via Nrf2/HO-1 signaling pathway.

Introduction: The Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway has been extensively studied for its role in regulating antioxidant and antiviral responses. The Equid herpesvirus type 8 (EqHV-8) poses a significant threat to the equine industry, primarily manifesting as respiratory disease, abortions, and neurological disorders in horses and donkeys. Oxidative stress is considered a key factor associated with pathogenesis of EqHV-8 infection. Unfortunately, there is currently a dearth of therapeutic interventions available for the effective control of EqHV-8. Rutin has been well documented for its antioxidant and antiviral potential. In current study we focused on the evaluation of Rutin as a potential therapeutic agent against EqHV-8 infection. Methods: For this purpose, we encompassed both in-vitro and in-vivo investigations to assess the effectiveness of Rutin in combatting EqHV-8 infection. Results and Discussion: The results obtained from in vitro experiments demonstrated that Rutin exerted a pronounced inhibitory effect on EqHV-8 at multiple stages of the viral life cycle. Through meticulous experimentation, we elucidated that Rutin's antiviral action against EqHV-8 is intricately linked to the Nrf2/HO-1 signaling pathway-mediated antioxidant response. Activation of this pathway by Rutin was found to significantly impede EqHV-8 replication, thereby diminishing the viral load. This mechanistic insight not only enhances our understanding of the antiviral potential of Rutin but also highlights the significance of antioxidant stress responses in combating EqHV-8 infection. To complement our in vitro findings, we conducted in vivo studies employing a mouse model. These experiments revealed that Rutin administration resulted in a substantial reduction in EqHV-8 infection within the lungs of the mice, underscoring the compound's therapeutic promise in vivo. Conclusion: In summation, our finding showed that Rutin holds promise as a novel and effective therapeutic agent for the prevention and control of EqHV-8 infections.

A 3D spheroid model of quadruple cell co-culture with improved liver functions for hepatotoxicity prediction.

Drug-induced liver injury (DILI) is one of the major concerns during drug development. Wide acceptance of the 3 R principles and the innovation of in-vitro techniques have introduced various novel model options, among which the three-dimensional (3D) cell spheroid cultures have shown a promising prospect in DILI prediction. The present study developed a 3D quadruple cell co-culture liver spheroid model for DILI prediction via self-assembly. Induction by phorbol 12-myristate 13-acetate at the concentration of 15.42 ng/mL for 48 hours with a following 24-hour rest period was used for THP-1 cell differentiation, resulting in credible macrophagic phenotypes. HepG2 cells, PUMC-HUVEC-T1 cells, THP-1-originated macrophages, and human hepatic stellate cells were selected as the components, which exhibited adaptability in the designated spheroid culture conditions. Following establishment, the characterization demonstrated the competence of the model in long-term stability reflected by the maintenance of morphology, viability, cellular integration, and cell-cell junctions for at least six days, as well as the reliable liver-specific functions including superior albumin and urea secretion, improved drug metabolic enzyme expression and CYP3A4 activity, and the expression of MRP2, BSEP, and P-GP accompanied by the bile acid efflux transport function. In the comparative testing using 22 DILI-positive and 5 DILI-negative compounds among the novel 3D co-culture model, 3D HepG2 spheroids, and 2D HepG2 monolayers, the 3D culture method significantly enhanced the model sensitivity to compound cytotoxicity compared to the 2D form. The novel co-culture liver spheroid model exhibited higher overall predictive power with margin of safety as the classifying tool. In addition, the non-parenchymal cell components could amplify the toxicity of isoniazid in the 3D model, suggesting their potential mediating role in immune-mediated toxicity. The proof-of-concept experiments demonstrated the capability of the model in replicating drug-induced lipid dysregulation, bile acid efflux inhibition, and α-SMA upregulation, which are the key features of liver steatosis and phospholipidosis, cholestasis, and fibrosis, respectively. Overall, the novel 3D quadruple cell co-culture spheroid model is a reliable and readily available option for DILI prediction.

Nanogalvanic Cells Release Highly Reactive Electrons in Tumors to Effectively Eliminate Tumors.

External stimuli triggering chemical reactions in cancer cells to generate highly reactive chemical species are very appealing for cancer therapy, in which external irradiation activating sensitizers to transfer energy or electrons to surrounding oxygen or other molecules is critical for generating cytotoxic reactive species. However, poor light penetration into tissue, low activity of sensitizers, and reliance on oxygen supply restrict the generation of cytotoxic chemical species in hypoxic tumors, which lowers the therapeutic efficacy. Here, this work presents galvanic cell nanomaterials that can directly release highly reactive electrons in tumors without external irradiation or photosensitizers. The released reactive electrons directly react with surrounding biomolecules such as proteins and DNA within tumors to destroy them or react with other surrounding (bio)molecules to yield cytotoxic chemical species to eliminate tumors independent of oxygen. Administering these nanogalvanic cells to mice results in almost complete remission of subcutaneous solid tumors and deep metastatic tumors. The results demonstrate that this strategy can further arouse an immune response even in a hypoxic environment. This method offers a promising approach to effectively eliminate tumors, similar to photodynamic therapy, but does not require oxygen or irradiation to activate photosensitizers.

Superhydrophobic, Highly Conductive, and Trilayered Fabric with Connected Carbon Nanotubes for Energy-Efficient Electrical Heating.

Current electrically heated fabrics provide heat in cold climates, suffer from abundant wasted radiant heat energy to the external environment, and are prone to damage by water. Thus, constructing energy-efficient and superhydrophobic conductive fabrics is in high demand. Therefore, we propose an effective and facile methodology to prepare a superhydrophobic, highly conductive, and trilayered fabric with a connected carbon nanotube (CNT) layer and a titanium dioxide (TiO2) nanoparticle heat-reflecting layer. We construct polyamide/fluorinated polyurethane (PA/FPU) nanofibrous membranes via first electrospinning, then performing blade-coating with the polyurethane (PU) solution with CNTs, and finally fabricating FPU/TiO2 nanoparticles via electrospraying. This strategy causes CNTs to be connected to form a conductive layer and enables TiO2 nanoparticles to be bound together to form a porous, heat-reflecting layer. As a consequence, the as-prepared membranes demonstrate high conductivity with an electrical conductivity of 63 S/m, exhibit rapid electric-heating capacity, and exhibit energy-efficient asymmetrical heating behavior, i.e., the heating temperature of the PA/FPU nanofibrous layer reaches more than 83 °C within 90 s at 24 V, while the heating temperature of the FPU/TiO2 layer only reaches 53 °C, as well as prominent superhydrophobicity with a water contact angle of 156°, indicating promising utility for the next generation of electrical heating textiles.

Terf2ip deficiency accelerates non-alcoholic steatohepatitis through regulating lipophagy and fatty acid oxidation via Sirt1/AMPK pathway.

BACKGROUND & AIMS: Our previous study has demonstrated that Telomeric repeat-binding factor 2-interacting protein 1(Terf2ip), played an important role in hepatic ischemia reperfusion injury. This study is aimed to explore the function and mechanism of Terf2ip in non-alcoholic steatohepatitis (NASH). METHODS: The expression of Terf2ip was detected in liver tissue samples obtained from patients diagnosed with NASH. Mice NASH models were constructed by fed with high-fat diet (HFD) or methionine/choline deficient diet (MCD) in Terf2ip knockout and wild type (WT) mice. To further investigate the role of Terf2ip in NASH, adeno-associated viruses (AAV)-Terf2ip was administrated to mice. RESULTS: We observed a significant down-regulation of Terf2ip levels in the livers of NASH patients and mice NASH models. Terf2ip deficiency was associated with an exacerbation of hepatic steatosis in mice under HFD or MCD. Additionally, Terf2ip deficiency impaired lipophagy and fatty acid oxidation (FAO) in NASH models. Mechanically, we discovered that Terf2ip bound to the promoter region of Sirt1 to regulate Sirt1/AMPK pathway activation. As a result, Terf2ip deficiency was shown to inhibit lipophagy through the AMPK pathway, while the activation of Sirt1 alleviated steatohepatitis in the livers of mice. Finally, re-expression of Terf2ip in hepatocyes alleviated liver steatosis, inflammation, and restored lipophagy. CONCLUSIONS: These results revealed that Terf2ip played a protective role in the progression of NASH through regulating lipophagy and FAO by binding to Sirt1 promoter. Our findings provided a potential therapeutic target for the treatment of NASH.

Potential factors affecting the success rate of indirect pulp therapy in primary molars with deep caries: a retrospective study.

Indirect pulp therapy (IPT) is a common conservative treatment for deep dental caries. However, the potential risk factors for the prognosis of IPT have not been well studied. This study retrospectively investigated the success rate of IPT in treating primary molars with deep caries and the factors potentially affecting the two-year success rate. A total of 303 primary molars in 202 children (106 boys and 96 girls) were included in this study. These primary molars were identified as having deep caries by clinical and radiographic examinations and were treated with IPT. The factors potentially affecting the IPT success rate were analyzed after two years of follow-up. The results indicated that the two-year IPT success rate was 86% (262/303). The success rate of primary molars with and without stainless steel crowns was 96% (120/125) and 80% (142/178), respectively. Primary molars treated with stainless steel crowns showed a significantly lower risk of failure (hazard ratio (HR) = 0.18, 95% confidence interval (CI): (0.10, 0.34), p = 0.01). There were no significant differences in other factors, including gender (male vs. female), age (preschool vs. school age), cooperation level (Frankl 2 vs. 3 or 4 scales), arch type (maxillary vs. mandibular), tooth type (first vs. second primary molar), or pulp capping material (calcium hydroxide vs. glass ionomer cement). IPT is an effective, conservative treatment modality for primary molars with deep caries. Stainless steel crowns could significantly improve the IPT success rate.

WUSCHEL RELATED HOMEOBOX5 and 7 maintain callus development by promoting cell division in Arabidopsis.

In tissue culture, a high concentration of auxin in the callus induction medium (CIM) stimulates cell division and subsequent callus formation, which acquires root primordium-like characteristics necessary for cell pluripotency. In Arabidopsis, WUSCHEL-RELATED HOMEOBOX5 (WOX5) and its closest homolog WOX7, which are abundant in the middle cell layer of mature callus, play a crucial role in maintaining pluripotency by promoting auxin accumulation and enhancing cytokinin sensitivity. However, the mechanism by which WOX5/7 regulate callus formation remains unclear. In this study, we found that mutations in WOX5/7 resulted in a significant down-regulation of genes involved in the G2M and S phases during callus induction. Loss-of-function mutants of WOX5/7 exhibited reduced callus formation, which was correlated with decreased expression of CYCB1;1 compared to the wild-type. Furthermore, we provided evidence that WOX5 physically interacts with PHYTOCHROME A SIGNAL TRANSDUCTION1 (PAT1), which spatio-temporally co-expresses with WOX5 in early-induced callus, and up-regulates a subset of cycle-regulating genes targeted by PAT1. Collectively, our findings suggest a critical role for the WOX5-PAT1 protein complex in regulating cell cycle progression, thereby promoting the continuous growth capacity of pluripotent callus.

Enhanced Electron Delocalization Induced by Ferromagnetic Sulfur doped C 3 N 4 Triggers Selective H 2 O 2 Production.

For the 2D metal-free carbon catalysts, the atomic coplanar architecture enables a large number of pz orbitals to overlap laterally, thus forming π-electron delocalization, and the delocalization degree of the central atom dominates the catalytic activity. Herein, designing sulfur-doped defect-rich graphitic carbon nitride (S-Nv-C3N4) materials as a model, we propose a strategy to promote localized electron polarization by enhancing the ferromagnetism of ultra-thin 2D carbon nitride nanosheets. The introduction of sulfur (S) further promotes localized ferromagnetic coupling, thereby inducing long-range ferromagnetic ordering and accelerating the electron interface transport. Meanwhile, the hybridization of sulfur atoms breaks the symmetry and integrity of the unit structure, promotes electron enrichment and stimulating electron delocalization at the active site. This optimization enhances the *OOH desorption, providing a favorable kinetic pathway for the production of hydrogen peroxide (H2O2). Consequently, S-Nv-C3N4 exhibits high selectivity (>95%) and achieves a superb H2O2 production rate, approaching 4374.8 ppm during continuous electrolysis over 300-hour. According to theoretical calculation and in-situ spectroscopy, the ortho-S configuration can provide ferromagnetic perturbation in carbon active centers, leading to the electron delocalization, which optimizes the OOH* adsorption during the catalytic process.

Lymph node targeting strategy using a hydrogel sustained-release system to load effector memory T cells improves the anti-tumor efficacy of anti-PD-1.

Communication between tumors and lymph nodes carries substantial significance for antitumor immunotherapy. Remodeling the immune microenvironment of tumor-draining lymph nodes (TdLN) plays a key role in enhancing the anti-tumor ability of immunotherapy. In this study, we constructed a biomimetic artificial lymph node structure composed of F127 hydrogel loading effector memory T (TEM) cells and PD-1 inhibitors (aPD-1). The biomimetic lymph nodes facilitate the delivery of TEM cells and aPD-1 to the TdLN and the tumor immune microenvironment, thus realizing effective and sustained anti-tumor immunotherapy. Exploiting their unique gel-forming and degradation properties, the cold tumors were speedily transformed into hot tumors via TEM cell supplementation. Meanwhile, the efficacy of aPD-1 was markedly elevated compared with conventional drug delivery methods. Our finding suggested that the development of F127@TEM@aPD-1 holds promising potential as a future novel clinical drug delivery technique. STATEMENT OF SIGNIFICANCE: F127@TEM@aPD-1 show unique advantages in cancer treatment. When injected subcutaneously, F127@TEM@aPD-1 can continuously supplement TEM cells and aPD-1 to tumor draining lymph nodes (TdLN) and the tumor microenvironment, not only improving the efficacy of ICB therapy through slow release, but also exhibiting dual regulatory effects on the tumor and TdLN.

Synthesis of (Furyl)Methyl Disulfides via Tandem Reaction of Conjugated Ene-Yne-Ketones with Acetyl-Masked Disulfide Nucleophiles.

In this study, we outline a general method for the construction of various (furyl)methyl disulfides from acetyl-masked disulfide nucleophiles and ene-yne-ketones. This protocol is feathered by metal-free, simple experimental conditions, high efficiency, and scalable potential, which make it attractive and practical.

Combining genome-wide association study and transcriptome analysis to identify molecular markers and genetic basis of population-asynchronous ovarian development in Coilia nasus.

Coilia nasus, a migratory fish species found in the middle and lower reaches of the Yangtze River and along offshore areas of China, possesses considerable aquacultural and economic potential. However, the species faces challenges due to significant variation in the gonadal development rate among females, resulting in inconsistent ovarian maturation times at the population level, an extended reproductive period, and limitations on fish growth rate due to ovarian prematurity. In the present study, we combined genome-wide association study (GWAS) and comparative transcriptome analysis to investigate the potential single nucleotide polymorphisms (SNPs) and candidate genes associated with population-asynchronous ovarian development in C. nasus. Genotyping of the female population based on whole-genome resequencing yielded 2 120 695 high-quality SNPs, 39 of which were suggestively associated with ovarian development. Of note, a significant SNP peak on LG21 containing 30 suggestively associated SNPs was identified, with cpne5a determined as the causal gene of the peak. Therefore, single-marker and haplotype association analyses were performed on cpne5a, revealing four genetic markers ( P<0.05) and seven haplotypes (r 2>0.9) significantly associated with the phenotype. Comparative transcriptome analysis of precociously and normally maturing individuals screened out 29 and 426 overlapping differentially expressed genes in the brain and ovary, respectively, between individuals of different body sizes. Integrating the GWAS and transcriptome analysis results, this study identified genes and pathways related to hypothalamic-pituitary-gonadal axis hormone secretion, extracellular matrix, angiogenesis, and gap junctions involved in population-asynchronous ovarian development. The insights gained from this study provide a basis for a deeper understanding of the molecular mechanisms underlying ovarian development in fish and may facilitate the genetic breeding of C. nasus strains exhibiting population-synchronous ovarian development in the future.

Fluoroscopically calibrated 3D-printed patient-specific instruments improve the accuracy of osteotomy during bone tumor resection adjacent to joints.

BACKGROUND: Inadequate surface matching, variation in the guide design, and soft tissue on the skeletal surface may make it difficult to accurately place the 3D-printed patient-specific instrument (PSI) exactly to the designated site, leading to decreased accuracy, or even errors. Consequently, we developed a novel 3D-printed PSI with fluoroscopy-guided positioning markers to enhance the accuracy of osteotomies in joint-preserving surgery. The current study was to compare whether the fluoroscopically calibrated PSI (FCPSI) can achieve better accuracy compared with freehand resection and conventional PSI (CPSI) resection. METHODS: Simulated joint-preserving surgery was conducted using nine synthetic left knee bone models. Osteotomies adjacent to the knee joint were designed to evaluate the accuracy at the epiphysis side. The experiment was divided into three groups: free-hand, conventional PSI (CPSI), and fluoroscopically Calibrated PSI (FCPSI). Post-resection CT scans were quantitatively analyzed. Analysis of variance (ANOVA) was used. RESULT: FCPSI improved the resection accuracy significantly. The mean location accuracy is 2.66 mm for FCPSI compared to 6.36 mm (P < 0.001) for freehand resection and 4.58 mm (P = 0.012) for CPSI. The mean average distance is 1.27 mm compared to 2.99 mm (p < 0.001) and 2.11 mm (p = 0.049). The mean absolute angle is 2.16° compared to 8.50° (p < 0.001) and 5.54° (p = 0.021). The mean depth angle is 1.41° compared to 8.10° (p < 0.001) and 5.32° (p = 0.012). However, there were no significant differences in the front angle compared to the freehand resection group (P = 0.055) and CPSI (P = 0.599) group. The location accuracy observed with FCPSI was maintained at 4 mm, while CPSI and freehand resection exhibited a maximum deviation of 8 mm. CONCLUSION: The fluoroscopically calibrated 3D-printed patient-specific instruments improve the accuracy of osteotomy during bone tumor resection adjacent to joint joints compared to conventional PSI and freehand resection. In conclusion, this novel 3D-printed PSI offers significant accuracy improvement in joint preserving surgery with a minimal increase in time and design costs.

Generally applicable circulating tumor cell enrichment and identification through a membrane glycoprotein-targeting strategy combining magnetic isolation and biological orthogonality labeling.

Although the importance of circulating tumor cells (CTCs) has been widely recognized, it is still a challenge to realize high-efficiency and accurate enrichment and identification of highly heterogeneous CTCs derived from various types of tumors in complex cancer processes. Currently, the most widely used methods follow the general idea of sequential immunoaffinitive capture and immunostaining to achieve the abovementioned goal. However, different organ/tissue origins as well as the inherent heterogeneity of CTCs would lead to the missed detection of certain CTC subtypes using such methods. Further, immunocytochemistry (ICC) immunostaining disrupts the physiological structure of cells, severely limiting the detection and application scenarios that require the participation of live cells. To address these limitations, we have developed a generally applicable strategy for the isolation and labeling of CTCs. This strategy focuses on targeting the universal characteristics of all tumor cells, specifically the abnormally expressed cell membrane glycoproteins, such as the transferrin receptor and sialic acid. Strategically, transferrin-functionalized magnetic beads (TMBs) were applied to enrich CTCs, and azide-based bioorthogonal chemistry was employed to label target CTCs. Accordingly, the membrane glycoprotein-targeting strategy achieved unbiased enrichment and labeling of broad-spectrum CTCs that were both epithelial and non-epithelial phenotypic populations with varied organ/tissue origins (MCF-7, HepG2, A549, Jurkat, and B16), with a capture efficiency of >95% and a detection limit as low as 5 cells per mL in artificial blood. In particular, our developed strategy displayed excellent specificity, and the CTCs under capture and fluorescence labelling remained with good viability and could be further cultivated and analyzed. Finally, the membrane glycoprotein-targeting strategy successfully detected and identified 33-223 CTCs from 1 mL patient blood samples.

Customizable Organic Charge-Transfer Cocrystals for the Dual-Mode Optoelectronics in the NIR (II) Window.

Organic molecules have been regarded as ideal candidates for near-infrared (NIR) optoelectronic active materials due to their customizability and ease of large-scale production. However, constrained by the intricate molecular design and severe energy gap law, the realization of optoelectronic devices in the second near-infrared (NIR (II)) region with required narrow band gaps presents more challenges. Herein, we have originally proposed a cocrystal strategy that utilizes intermolecular charge-transfer interaction to drive the redshift of absorption and emission spectra of a series BFXTQ (X = 0, 1, 2, 4) cocrystals, resulting in the spectra located at NIR (II) window and reducing the optical bandgap to ∼0.98 eV. Significantly, these BFXTQ-based optoelectronic devices can exhibit dual-mode optoelectronic characteristics. An investigation of a series of BFXTQ-based photodetectors exhibits detectivity (D*) surpassing 1013 Jones at 375 to 1064 nm with a maximum of 1.76 × 1014 Jones at 1064 nm. Moreover, the radiative transition of CT excitons within the cocrystals triggers NIR emission over 1000 nm with a photoluminescence quantum yield (PLQY) of ∼4.6% as well as optical waveguide behavior with a low optical-loss coefficient of 0.0097 dB/µm at 950 nm. These results promote the advancement of an emerging cocrystal approach in micro/nanoscale NIR multifunctional optoelectronics.

Assessment of radiation in fishes derived from radiocesium in the port of Fukushima Daiichi nuclear power plant.

This study established specialized radiation dose models to evaluate the internal radiation doses derived from 137Cs and 134Cs in fishes in the port of the Fukushima Daiichi Nuclear Power Plant from 2012 to 2023. By August 2018, the activities of 134Cs and 137Cs in fishes decreased at the T1/2 of 176 d and 191 d, respectively. The corresponding mass concentrations were far lower than 1 mg/kg and the chemical toxicity can be negligible. Regarding radiotoxicity, 18,000 Bq/kgfresh weight of 134Cs and 137Cs in grouper Sebastes schlegelii produced 276 µGy/h of radiation dose, which was below the no-effect-dose-rate benchmarks (400 µGy/h). 740,000 Bq/kgfresh weight of 134Cs and 137Cs in greenling Hexagrammos otakii produced 12,600 µGy/h of radiation dose, which was much higher than 400 µGy/h, indicating the possibility of radiation effects. If a person eats these two reported fishes, the resulting committed effective doses for humans are 7.7 µSv and 6.31 mSv, respectively.

Assessment of the impact of Tianwan Nuclear Power Plant on the adjacent marine ecosystem.

Based on the monitoring data of 137Cs and 90Sr in Tian Bay in 2005-2023, the impacts of the operation of Tianwan Nuclear Power Plant on the marine ecosystem were assessed. The 137Cs and 90Sr activity concentrations in the seawater and sediment varied within the background ranges. The radiation dose rates derived from 137Cs and 90Sr for the marine organisms ranged from 2.4 × 10-5 to 2.2 × 10-4 nGy/h, it was far below the most conservative screening dose rate (10 µGy/h). The committed effective dose for humans was 0.070-0.094 µSv, 1/1500th of the world's mean annual effective dose (0.12 mSv) from ingesting food containing uranium and thorium series nuclides. Radiation risk assessment showed no radiation risk for the long-term discharge of nuclear wastes in the future. Overall, the long-term normal operation of TNPPs has almost no radiation impact on the adjacent marine ecosystem.

RAC1high NK cell-based immunotherapy in hepatocellular carcinoma via STAT3-NKG2D axis.

Natural killer (NK) cells exert an indispensable role in innate immune responses against cancer progression, however NK cell dysfunction has been rarely reported in hepatocellular carcinoma (HCC). This study sought to uncover the immunoregulatory mechanisms of tumor-infiltrating NK cells in HCC. A consensus NK cell-based signature (NKS) was constructed using integrative machine learning algorithms based on multi-omics data of HCC patients. HCC tumors had lower numbers of infiltrating NK cells than para-tumor normal liver tissues. Based on the NK cell-associated genes, the NKS was built for HCC prognostic prediction and clinical utilities. Drug targets and novel compounds were then identified for high-NKS groups. RAC1 was confirmed as the hub gene in the NKS genes. RAC1 was upregulated in HCC tumors and positively correlated with shorter survival time. RAC1 overexpression in NK-92 cells facilitated the cancer-killing capacity by the anticancer cytotoxic effectors and the upregulated NKG2D. The survival time of PDX-bearing mice was also prolonged upon NK-92RAC1 cells. Mechanistically, RAC1 interacted with STAT3 and facilitated its activation, thereby enabling its binding to the promoter region of NKG2D and functioning as a transcriptional regulator in NK-92 via molecular docking, Co-IP assay, CHIP and luciferase experiments. Collectively, our study describes a novel function of RAC1 in potentiating NK cell-mediated cytotoxicity against HCC, highlighting the clinical utilities of NKS score and RAC1high NK cell subset in HCC immunotherapy.

DNA-functionalized cryogel based colorimetric biosensor for sensitive on-site detection of aflatoxin B1 in food samples.

Hydrogel biosensors present numerous advantages in food safety analysis owing to their remarkable biocompatibility, cargo-loading capabilities and optical properties. However, the current drawbacks (slow target responsiveness and poor mechanical strength) restricted their further utilization at on-site detection of targets. To address these challenges, a DNA-functionalized cryogel with hierarchical pore structures is constructed to improve the reaction rate and the robustness of hydrogel biosensor. During cryogel preparation, ice crystals serve as templates, shaping interconnected hierarchical microporous structures to enhance mass transfer for faster responses. Meanwhile, in the non-freezing zone, concentrated monomers create a dense cross-linked network, strengthening cryogel matrix strength. Accordingly, a colorimetric biosensor based on DNA cryogel has been developed as a proof of concept for rapid detection of aflatoxin B1 (AFB1) in food samples, and an excellent analytical performance was obtained under the optimized conditions with a low detection limit (1 nM), broad detection range (5-100 nM), satisfactory accuracy and precision (recoveries, 81.2-112.6 %; CV, 2.75-5.53 %). Furthermore, by integrating with a smartphone sensing platform, a portable device was created for rapid on-site measurement of target within 45 min, which provided some insight for hydrogel biosensors design.

A synergistically antimicrobial and antioxidant hyaluronic acid hydrogel for infected wounds.

Bacterial infections during wound healing impede the healing process and trigger local or systemic inflammatory reactions. Consequently, there is an urgent need to develop a new material with antimicrobial and antioxidant properties to promote infected wound healing. A synergistically antimicrobial and antioxidant hyaluronic acid hydrogel (HMn) is prepared by employing MnO2 nanosheets into 4ARM-PEG5000-SH crosslinked methacrylated hyaluronic acid (HAMA) network. The coordination between sulfhydryl groups of 4ARM-PEG5000-SH and MnO2 nanosheets ensures entrapment of the nanosheets within the hydrogel, while the interaction between 4ARM-PEG5000-SH and HAMA results in facile gelation through thiol-ene click reaction. MnO2 nanosheets exhibit strong photothermal properties and reactive oxygen species (ROS) scavenging abilities, while hyaluronic acid promotes wound healing. When subjected to near-infrared (NIR) irradiation, the HMn achieves a bactericidal rate of 95.24 % for Staphylococcus aureus and nearly 100 % for Escherichia coli. In animal experiments, treatment with the HMn under NIR irradiation results in the best wound healing outcomes. Both in vitro and vivo biocompatible assays demonstrate that the HMn has rarely cell cytotoxicity and tissue damage. The HMn is easy to prepare and has good biocompatibility as well as efficient antibacterial and antioxidant properties, providing a novel method for the treatment of infected wounds.