Recent progress in stimuli-responsive polymeric micelles for targeted delivery of functional nanoparticles.

Stimuli-responsive polymeric micelles have emerged as a revolutionary approach for enhancing the in vivo stability, biocompatibility, and targeted delivery of functional nanoparticles (FNPs) in biomedicine. This article comprehensively reviews the preparation methods of these polymer micelles, detailing the innovative strategies employed to introduce stimulus responsiveness and surface modifications essential for precise targeting. We delve into the breakthroughs in utilizing these micelles to selectively deliver various FNPs including magnetic nanoparticles, upconversion nanoparticles, gold nanoparticles, and quantum dots, highlighting their transformative impact in the biomedical realm. Concluding, we present an insight into the current research landscape, addressing the challenges at hand, and envisioning the future trajectory in this burgeoning domain. Join us as we navigate the exciting confluence of polymer science and nanotechnology in reshaping biomedical solutions.

M1-type polarized macrophage contributes to brain damage through CXCR3.2/CXCL11 pathways after RGNNV infection in grouper.

The vertebrate central nervous system (CNS) is the most complex system of the body. The CNS, especially the brain, is generally regarded as immune-privileged. However, the specialized immune strategies in the brain and how immune cells, specifically macrophages in the brain, respond to virus invasion remain poorly understood. Therefore, this study aimed to examine the potential immune response of macrophages in the brain of orange-spotted groupers (Epinephelus coioides) following red-spotted grouper nervous necrosis virus (RGNNV) infection. We observed that RGNNV induced macrophages to produce an inflammatory response in the brain of orange-spotted grouper, and the macrophages exhibited M1-type polarization after RGNNV infection. In addition, we found RGNNV-induced macrophage M1 polarization via the CXCR3.2- CXCL11 pathway. Furthermore, we observed that RGNNV triggered M1 polarization in macrophages, resulting in substantial proinflammatory cytokine production and subsequent damage to brain tissue. These findings reveal a unique mechanism for brain macrophage polarization, emphasizing their role in contributing to nervous tissue damage following viral infection in the CNS.

Jaceosidin attenuates the progression of hepatic fibrosis by inhibiting the VGLL3/HMGB1/TLR4 signaling pathway.

BACKGROUND: Jaceosidin (JA) is a natural flavone extracted from Artemisia that is used as a food and traditional medicinal herb. It has been reported to possess numerous biological activities. However, the regulatory mechanisms underlying amelioration of hepatic fibrosis remain unclear. HYPOTHESIS/PURPOSE: We hypothesized that jaceosidin acid (JA) modulates hepatic fibrosis and inflammation. METHODS: Thioacetamide (TAA) was used to establish an HF mouse model. In vitro, mouse primary hepatocytes and HSC-T6 cells were induced by TGF-ß, whereas mouse peritoneal macrophages received a treatment lipopolysaccharide (LPS)/ATP. RESULTS: JA decreased serum transaminase levels and improved hepatic histological pathology in TAA-treated mice stimulated by TAA. Moreover, the expression of pro-fibrogenic biomarkers associated with the activation of liver stellate cells was downregulated by JA. Likewise, JA down-regulated the expression of vestigial-like family member 3 (VGLL3), high mobility group protein B1 (HMGB1), toll-like receptors 4 (TLR4), and nucleotide-binding domain-(NOD-) like receptor protein 3 (NLRP3), thereby inhibiting the inflammatory response and inhibiting the release of mature-IL-1ß in TAA-stimulated mice. Additionally, JA suppressed HMGB1 release and NLRP3/ASC inflammasome activation in LPS/ATP-stimulated murine peritoneal macrophages. JA decreases the expression of pro-fibrogenic biomarkers related to liver stellate cell activation and inhibits inflammasome activation in mouse primary hepatocytes. It also down-regulated α-SMA and VGLL3 expressions and also suppressed inflammasome activation in HSC-T6 cells. VGLL3 and α-SMA expression levels were decreased in TGF-ß-stimulated HSC-T6 cells following Vgll3 knockdown. In addition, the expression levels of NLRP3 and cleaved-caspase-1 were decreased in Vgll3-silenced HSC-T6 cells. JA enhanced the inhibitory effects on Vgll3-silenced HSC-T6 cells. Finally, Vgll3 overexpression in HSC-T6 cells affected the expression levels of α-SMA, NLRP3, and cleaved-caspase-1. CONCLUSION: JA effectively modulates hepatic fibrosis by suppressing fibrogenesis and inflammation via the VGLL3/HMGB1/TLR4 axis. Therefore, JA may be a candidate therapeutic agent for the management of hepatic fibrosis. Understanding the mechanism of action of JA is a novel approach to hepatic fibrosis therapy.

Slc43a2+ T cell metastasis from spleen to brain in RGNNV infected teleost.

The origin of T cells in the teleost's brain is unclear. While viewing the central nervous system (CNS) as immune privileged has been widely accepted, previous studies suggest that T cells residing in the thymus but not in the spleen of the teleost play an essential role in communicating with the peripheral organs. Here, we identified nine T cell subpopulations in the thymus and spleen of orange-spotted grouper (Epinephelus coioices) through single-cell RNA-sequencing analysis. After viral CNS infection with red-spotted grouper nervous necrosis virus (RGNNV), the number of slc43a2+ T cells synchronously increased in the spleen and brain. During the infection tests in asplenic zebrafish (tlx1▲ zebrafish model), no increase in the number of slc43a2+ T cells was observed in the brain. Single-cell transcriptomic analysis indicated that slc43a2+ T cells mature and functionally differentiate within the spleen and then migrate into the brain to trigger an immune response. This study suggests a novel route for T cell migration from the spleen to the brain during viral infection in fish.

Targeting the cGAS-STING Pathway Inhibits Peripheral T-cell Lymphoma Progression and Enhances the Chemotherapeutic Efficacy.

Peripheral T-cell lymphoma (PTCL) is a highly heterogeneous group of mature T-cell malignancies. The efficacy of current first-line treatment is dismal, and novel agents are urgently needed to improve patient outcomes. A close association between the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway and tumor promotion exists, revealing prospective therapeutic targets. This study, investigates the role of the cGAS-STING pathway and its underlying mechanisms in PTCL progression. Single-cell RNA sequencing showes that the cGAS-STING pathway is highly expressed and closely associated with PTCL proliferation. cGAS inhibition suppresses tumor growth and impaires DNA damage repair. Moreover, Cdc2-like kinase 1 (CLK1) is critical for residual tumor cell survival after treatment with cGAS inhibitors, and CLK1 suppression enhances sensitivity to cGAS inhibitors. Single-cell dynamic transcriptomic analysis indicates reduced proliferation-associated nascent RNAs as the underlying mechanism. In first-line therapy, chemotherapy-triggered DNA damage activates the cGAS-STING pathway, and cGAS inhibitors can synergize with chemotherapeutic agents to kill tumors. The cGAS-STING pathway is oncogenic in PTCL, whereas targeting cGAS suppresses tumor growth, and CLK1 may be a sensitivity indicator for cGAS inhibitors. These findings provide a theoretical foundation for optimizing therapeutic strategies for PTCL, especially in patients with relapsed/refractory disease.

3D Printed All-Natural Hydrogels: Flame-Retardant Materials Toward Attaining Green Sustainability.

Biomass-based hydrogel is a promising flame-retardant material and has a high potential for applications in transportation, aerospace, building and electrical engineering, and electronics. However, rapid vat photopolymerization (VP) 3D printing of biomass-based hydrogels, especially that of all-natural ones, is still rare. Herein, a new class of VP 3D-printed hydrogels with strong covalent networks, fabricating using fully biomass materials and a commercial liquid crystal display (LCD) printer assembled with low-intensity visible light is presented. Encouragingly, the highly ordered layer-by-layer packing structures provided by VP 3D printing technology endow these hydrogels with remarkable flame retardancy, exceptional temperature resistance, advantageous combustion behaviors, and favorable mechanical strength, in particular, giving them a better limit oxygen index (83.5%) than various biomass-based hydrogels. The proposed approach enables the green design as well as the precise and efficient preparation for flame-retardant materials, paving the way for the future flame-retardant materials toward attaining green sustainability.

m6A-Modified circTET2 Interacting with HNRNPC Regulates Fatty Acid Oxidation to Promote the Proliferation of Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is a hematological malignancy with high metabolic heterogeneity. N6-methyladenosine (m6A) modification plays an important role in metabolism through regulating circular RNAs (circRNAs). However, the underlying mechanism is not yet fully understood in CLL. Herein, an m6A scoring system and an m6A-related circRNA prognostic signature are established, and circTET2 as a potential prognostic biomarker for CLL is identified. The level of m6A modification is found to affect the transport of circTET2 out of the nucleus. By interacting with the RNA-binding protein (RBP) heterogeneous nuclear ribonucleoprotein C (HNRNPC), circTET2 regulates the stability of CPT1A and participates in the lipid metabolism and proliferation of CLL cells through mTORC1 signaling pathway. The mTOR inhibitor dactolisib and FAO inhibitor perhexiline exert a synergistic effect on CLL cells. In addition, the biogenesis of circTET2 can be affected by the splicing process and the RBPs RBMX and YTHDC1. CP028, a splicing inhibitor, modulates the expression of circTET2 and shows pronounced inhibitory effects. In summary, circTET2 plays an important role in the modulation of lipid metabolism and cell proliferation in CLL. This study demonstrates the clinical value of circTET2 as a prognostic indicator as well as provides novel insights in targeting treatment for CLL.

Treatment strategies and survival outcomes of primary mediastinal large B-cell lymphoma.

OBJECTIVES: Primary mediastinal large B-cel l lymphoma (PMBCL) is a rare subtype of B-cell lymphoma that is not yet fully understood. This population-based study aimed to assess the latest survival and treatment strategies for patients with PMBCL. METHODS: The study used the dataset from the Surveillance, Epidemiology, and End Results Program registry to retrospectively analyze adult patients diagnosed with PMBCL between 2001 and 2018. The primary outcome measures included overall survival (OS) and disease-specific survival (DSS). RESULTS: Among the 814 identified cases, the study revealed a 5-year OS rate of 86.7% and a 5-year DSS rate of 88.2% after a median follow-up of 54 months. Cox regression analysis indicated that age over 60 years, pre-2010 diagnosis, non-White ethnicity, advanced stage, and absence of chemotherapy significantly reduced both OS and DSS. It also found that chemotherapy has remained the primary therapeutic protocol for PMBCL over the last 20 years, whereas the utilization of surgery and radiation declined significantly. Patients diagnosed with PMBCL between 2010 and 2018 had a significantly reduced mortality risk (∼50%) compared to those diagnosed between 2001 and 2009. Notably, in the era of rituximab's widespread usage, recipients of radiotherapy exhibited a poorer OS rate than non-recipients. CONCLUSION: Survival outcomes for patients with PMBCL have significantly improved in the current era, possibly due to the evolving treatment paradigm. The value of radiotherapy in PMBCL is still debated and requires further prospective evaluation.

The Explanation of Photopic Luminous Efficiency Curve by Using Both of the Cones' Optical Fiber Coupling Effects and the Absorption of L Cones.

In this paper, we build four-part cone models to explore the coupling effect of seven cone fiber couplers. Moreover, this is the first study of the coupling effect of four layers of biological couplers in animals and other biological lives. We simulate the four layers cone couplers by using the beam propagation method, and we assume the input beam is located at the outer fiber of the central cone. Our simulation results showed that there are two wavelength regions (short and long wavelength regions) with the strongest coupling, where the most power of input optical powers of the central cones will transfer to the six surrounding cones after transmitting through the four layers of cone couplers. However, within a wavelength region of ±75 nm near to the peak wavelengths, located in the yellow-green wavelength range, the splitting ratios at the output of the outer segment of the central cone are always greater than the sum of the splitting ratios of the six surrounding cones. These cone couplers may play an important role in color preprocessing (e.g., doing opponent color processing partially). The cone fiber coupler effect and light absorption of cones are considered separately in our models. By taking account of both the cone fiber coupling effect and absorption of outer segment of L cone, we find the multiplication of the relative optical power of cone couplers, the spectral sensitivity data of the L cone, and a normalized coefficient that matches with the photopic luminous efficiency of the human eye well. This is the attempt to use both the cone fiber coupling effect and the absorption of L cones to explain the photopic luminous efficiency. The splitting ratios of the central cones are greater than 80% at peak wavelengths located in the yellow-green wavelength range, and this can help to explain why the human eye is more sensitive to green light.

CircRIC8B regulates the lipid metabolism of chronic lymphocytic leukemia through miR199b-5p/LPL axis.

OBJECTIVE: Circular RNAs (circRNAs) play a critical role in the modulation of tumor metabolism. However, the expression patterns and metabolic function of circRNAs in chronic lymphocytic leukemia (CLL) remain largely unknown. This study aimed to elucidate the role of circRNAs in the lipid metabolism of CLL. METHODS: The expression and metabolic patterns of circRNAs in a cohort of 53 patients with CLL were investigated using whole transcriptome sequencing. Cell viability, liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis, lipid analysis, Nile red staining as well as triglyceride (TG) assay were used to evaluate the biological function of circRIC8B in CLL. The regulatory mechanisms of circRIC8B/miR-199b-5p/lipoprotein lipase (LPL) axis were explored by luciferase assay, RNA immunoprecipitation (RIP), qRT-PCR, and fluorescence in situ hybridization (FISH). CCK-8 and flow cytometry were used to verify the inhibition role of cholesterol absorption inhibitor, ezetimibe, in CLL cells. RESULTS: Increased circRIC8B expression was positively correlated with advanced progression and poor prognosis. Knockdown of circRIC8B significantly suppressed the proliferation and lipid accumulation of CLL cells. In contrast, the upregulation of circRIC8B exerted opposite effects. Mechanistically, circRIC8B acted as a sponge of miR-199b-5p and prevented it from decreasing the level of LPL mRNA, and this promotes lipid metabolism alteration and facilitates the progression of CLL. What's more, ezetimibe suppressed the expression of LPL mRNA and inhibited the growth of CLL cells. CONCLUSIONS: In this study, the expressional and metabolic patterns of circRNAs in CLL was illustrated for the 1st time. Our findings revealed that circRIC8B regulates the lipid metabolism abnormalities in and development of CLL through the miR-199b-5p/LPL axis. CircRIC8B may serve as a promising prognostic marker and therapeutic target, which enhances the sensitivity to ezetimibe in CLL.

Exploring the significance of PAK1 through chromosome conformation signatures in ibrutinib-resistant chronic lymphocytic leukaemia.

Ibrutinib exerts promising anticancer effects in chronic lymphocytic leukaemia (CLL). However, acquired resistance occurs during treatment, necessitating the exploration of underlying mechanisms. Although three-dimensional genome organization has been identified as a major player in the development and progression of cancer, including drug resistance, little is known regarding its role in CLL. Therefore, we investigated the molecular mechanisms underlying ibrutinib resistance through multi-omics analysis, including high-throughput chromosome conformation capture (Hi-C) technology. We demonstrated that the therapeutic response to ibrutinib is associated with the expression of p21-activated kinase 1 (PAK1). PAK1, which was up-regulated in CLL and associated with patients' survival, was involved in cell proliferation, glycolysis and oxidative phosphorylation. Furthermore, the PAK1 inhibitor IPA-3 exerted an anti-tumour effect and its combination with ibrutinib exhibited a synergistic effect in ibrutinib-sensitive and -resistant cells. These findings suggest the oncogenic role of PAK1 in CLL progression and drug resistance, highlighting PAK1 as a potential diagnostic marker and therapeutic target in CLL including ibrutinib-resistant CLL.

Thermochromic VO2-SiO2composite coating from ammonium citrato-oxovanadate(IV).

Vanadium dioxide (VO2) coating plays an important role in energy saving and environmental protection due to its unique reversible phase transition. To solve the daylighting issue of VO2coating, a VO2(M)-silicon dioxide (SiO2) composite coating is fabricated from ammonium citrato-oxovanadate(IV) by a SiO2-assisted coating method. The VO2(M)-SiO2composite coating possesses excellent thermochromic properties that have produced varying results, i.e. 49.2% of visible transmittance, 52.3% of transmittance reduction at 2000 nm wavelength, 12% of solar energy modulation (ΔTsol) and a phase transition temperature of 56.0 °C. Our findings may pave the way to extending the large-scale application of smart windows based on thermochromic VO2.

Fluorescent Brighteners as Visible LED-Light Sensitive Photoinitiators for Free Radical Photopolymerizations.

The photochemical and electrochemical investigations of commercially available, safe, and cheap fluorescent brighteners, namely, triazinylstilbene (commercial name: fluorescent brightener 28) and 2,5-bis(5-tert-butyl-benzoxazol-2-yl)thiophene, as well as their original use as photoinitiators of polymerization upon light emitting diode (LED) irradiation are reported. Remarkably, their excellent near-UV-visible absorption properties combined with outstanding fluorescent properties allow them to act as high-performance photoinitiators when used in combination with diaryliodonium salt. These two-component photoinitiating systems can be employed for free radical polymerizations of acrylate. In addition, this brightener-initiated photopolymerization is able to overcome oxygen inhibition even upon irradiation with low LED light intensity. The underlying photochemical mechanisms are investigated by electron-spin resonance-spin trapping, fluorescence, cyclic voltammetry, and steady-state photolysis techniques.