Dynamic Lock-And-Release Mechanism Enables Reduced ΔG at Low Temperatures for High-Performance Polyanionic Cathode in Sodium-Ion Batteries.

Low-temperature synthesis of polyanionic cathodes for sodium-ion batteries is highly desirable but often plagued by prolonged reaction times and suboptimal crystallinity. To address these challenges, a novel self-adaptive coordination field regulation (SACFR) strategy based on a dynamic lock-and-release (DLR) mechanism is introduced. Specifically, urea is used as a DLR carrier during synthesis, which dynamically "locks" and "releases" vanadium ions for controlled release, simultaneously "locking" H+ ions to enhance phosphate group release, thereby creating a self-adaptive coordination field that can intelligently respond to real-time demands of the reaction system. This dynamic coordination behavior contributes to both an improvement in reaction kinetics and a significant reduction in Gibbs free energy change (ΔG). As a result, the kinetic efficiency and thermodynamic spontaneity of the reaction are greatly enhanced, enabling the efficient synthesis of high-crystalline Na3V2O2(PO4)2F (NVOPF) at 90 °C within just 3 hours. The as-prepared NVOPF cathode exhibits exceptional rate performance and ultra-stable cycling stability across a broad temperature range. Furthermore, the successful kilogram-scale synthesis underscores the practical potential of the innovative strategy. This work pioneers the regulation of coordination field chemistry for polyanionic cathode synthesis, providing transformative insights into material design.

Chemical profiling and mechanisms of Agarikon pill in a rat model of cigarette smoke-induced chronic obstructive pulmonary disease.

Background and aim: Agarikon pill (AGKP), a traditional Chinese herbal formula, and has been used for chronic obstructive pulmonary disease (COPD) treatment clinically. However, the active components and exact pharmacological mechanisms are still unclear. We aimed to investigate the therapeutic effects and mechanisms of AGKP on COPD and identify the chemical constituents and active compounds. Experimental procedure: The chemical components of AGKP were identified by ultrahigh-performance liquid chromatography coupled with quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). Network pharmacology analysis was performed to uncover the potential mechanism of AGKP. The efficiencies and mechanisms of AGKP were further confirmed in COPD animal models. Results and conclusion: Ninety compounds from AGKP, such as flavonoids, triterpenoids, saponins, anthracenes, derivatives, phenyl propionic acid, and other organic acids, were identified in our study. AGKP improved lung function and pathological changes in COPD model rats. Additionally, inflammatory cell infiltration and proinflammatory cytokine levels were markedly reduced in COPD rats administered AGKP. Network pharmacology analysis showed that the inflammatory response is the crucial mechanism by which AGKP exerts therapeutic effects on COPD rats. WB and PCR data indicated that AGKP attenuated the inflammatory response in COPD model rats. AGKP reduces the pulmonary inflammatory response through the PI3K/AKT and MAPK TLR/NF-κB signaling pathways and exerts therapeutic effects via inhibition of inflammation and mucus hypersecretion on COPD model rats.

Efficient circularly polarized multiple resonance thermally activated delayed fluorescence from B,N-embedded hetero[8]helicene enantiomers.

Helicene-based circularly polarized multiple resonance thermally activated delayed fluorescence (CP-MR-TADF) materials are promising for ultra-high-definition and 3D displays, but most of them encounter potential problems such as easy racemization during the thermal deposition process, low luminous efficiency, and low luminescence dissymmetry factor (g lum), making the development of efficient circularly polarized organic light-emitting diodes (CP-OLEDs) a significant challenge. Here, we report a pair of CP-MR-TADF enantiomers with high-order B,N-embedded hetero[8]helicene, (P/M)-BN-TP-ICz, by fusing two MR chromophores, DtCzB and indolo[3,2,1-jk]carbazole (ICz). BN-TP-ICz exhibits green emission in toluene with a peak of 531 nm and a full-width at half-maximum (FWHM) of 36 nm. The optimized CP-OLEDs with enantiomers (P/M)-BN-TP-ICz exhibit green emission with peaks of 540 nm, FWHMs of 38 nm and Commission Internationale de L'Eclairage coordinates of (0.33, 0.65). Moreover, they showcase maximum external quantum efficiencies (EQEs) of 32.0%, with g ELs of +6.49 × 10-4 and -7.74 × 10-4 for devices based on (P)-BN-TP-ICz- and (M)-BN-TP-ICz, respectively.

Artificial light harvesting system of CM6@Zn-MOF nanosheets with highly enhanced photoelectric performance.

As donors for effective energy transfer, metal-organic frameworks (MOFs) have attracted the attention of many experts in the field of artificial light-harvesting materials. This study introduces a novel two-dimensional Zn-MOF, synthesized using flexible 1,3-phenyldiacetic acid (H2mpda) and rigid 1,3,5-tris(1-imidazolyl)benzene (tib) as organic ligands. Through atomic force microscopy (AFM), we have determined the monolayer thickness of this novel material to be 5 nm. Achieving two-dimensional Zn-MOF nanosheets with large BET surface area was made possible by employing ultrasonic stripping techniques. The fluorescence emission spectrum of Zn-MOF nanosheets overlaps with the UV-vis absorption spectrum of coumarin 6 (CM6), so they can be used as a donor and acceptor for fluorescence resonance energy transfer (FRET) to construct an artificial light-harvesting system (ALHS). Compared with single crystal Zn-MOF, CM6@Zn-MOF(2) has a larger BET surface area (41 m2/g), higher quantum yield (Φfl, 30.56 %), narrower energy gap (Eg, 2.87 eV), and the light-harvesting range extends to the visible green light area. Notably, CM6@Zn-MOF(2) demonstrates a robust photocurrent response, characterized by a photocurrent on/off ratio (Ilight/Idark) of 21, and a maximum photocurrent density that surpasses that of pure Zn-MOF (2.25:1). This study successfully designed a high-performance photoelectric conversion material CM6@Zn-MOF(2), which laid a certain theoretical foundation for new artificial optical acquisition systems and electrochemical material selection.

Modulating Charge-Transfer Excited States of Multiple Resonance Emitters via Intramolecular Covalent Bond Locking.

Advanced multiple resonance thermally activated delayed fluorescence (MR-TADF) emitters with high efficiency and color purity have emerged as a research focus in the development of ultra-high-definition displays. Herein, we disclose an approach to modulate the charge-transfer excited states of MR emitters via intramolecular covalent bond locking. This strategy can promote the evolution of strong intramolecular charge-transfer (ICT) states into weak ICT states, ultimately narrowing the full-width at half-maximum (FWHM) of emitters. To modulate the ICT intensity, two octagonal rings are introduced to yield molecule m-DCzDAz-BNCz. Compounds m-CzDAz-BNCz and m-DCzDAz-BNCz exhibit bright light-green and green fluorescence in toluene, with emission maxima of 504 and 513 nm, and FWHMs of 28 and 34 nm, respectively. Sensitized organic light-emitting diodes (OLEDs) employing emitters m-CzDAz-BNCz and m-DCzDAz-BNCz exhibit green emission with peaks of 508 and 520 nm, Commission Internationale de L'Eclairage (CIE) coordinates of (0.12, 0.65) and (0.19, 0.69), and maximum external quantum efficiencies (EQEs) of 30.2 % and 32.6 %, respectively.

From Lab to Application: Challenges and Opportunities in Achieving Fast Charging with Polyanionic Cathodes for Sodium-Ion Batteries.

Sodium-ion batteries (SIBs), recognized for balanced energy density and cost-effectiveness, are positioned as a promising complement to lithium-ion batteries (LIBs) and a substitute for lead-acid batteries, particularly in low-speed electric vehicles and large-scale energy storage. Despite their extensive potential, concerns about range anxiety due to lower energy density underscore the importance of fast-charging technologies, which drives the exploration of high-rate electrode materials. Polyanionic cathode materials are emerging as promising candidates in this regard. However, their intrinsic limitation in electronic conductivity poses challenges for synchronized electron and ion transport, hindering their suitability for fast-charging applications. This review provides a comprehensive analysis of sodium ion migration during charging/discharging, highlighting it as a critical rate-limiting step for fast charging. By delving into intrinsic dynamics, key factors that constrain fast-charging characteristics are identified and summarized. Innovative modification routes are then introduced, with a focus on shortening migration paths and increasing diffusion coefficients, providing detailed insights into feasible strategies. Moreover, the discussion extends beyond half cells to full cells, addressing challenges and opportunities in transitioning polyanionic materials from the laboratory to practical applications. This review aims to offer valuable insights into the development of high-rate polyanionic cathodes, acknowledging their pivotal role in advancing fast-charging SIBs.

Expression of concern: A hypoxia-dissociable siRNA nanoplatform for synergistically enhanced chemo-radiotherapy of glioblastoma.

Expression of concern for 'A hypoxia-dissociable siRNA nanoplatform for synergistically enhanced chemo-radiotherapy of glioblastoma' by Yandong Xie, et al., Biomater. Sci., 2022, 10, 6791-6803, https://doi.org/10.1039/D2BM01145J.

Dual-channel hypergraph convolutional network for predicting herb-disease associations.

Herbs applicability in disease treatment has been verified through experiences over thousands of years. The understanding of herb-disease associations (HDAs) is yet far from complete due to the complicated mechanism inherent in multi-target and multi-component (MTMC) botanical therapeutics. Most of the existing prediction models fail to incorporate the MTMC mechanism. To overcome this problem, we propose a novel dual-channel hypergraph convolutional network, namely HGHDA, for HDA prediction. Technically, HGHDA first adopts an autoencoder to project components and target protein onto a low-dimensional latent space so as to obtain their embeddings by preserving similarity characteristics in their original feature spaces. To model the high-order relations between herbs and their components, we design a channel in HGHDA to encode a hypergraph that describes the high-order patterns of herb-component relations via hypergraph convolution. The other channel in HGHDA is also established in the same way to model the high-order relations between diseases and target proteins. The embeddings of drugs and diseases are then aggregated through our dual-channel network to obtain the prediction results with a scoring function. To evaluate the performance of HGHDA, a series of extensive experiments have been conducted on two benchmark datasets, and the results demonstrate the superiority of HGHDA over the state-of-the-art algorithms proposed for HDA prediction. Besides, our case study on Chuan Xiong and Astragalus membranaceus is a strong indicator to verify the effectiveness of HGHDA, as seven and eight out of the top 10 diseases predicted by HGHDA for Chuan-Xiong and Astragalus-membranaceus, respectively, have been reported in literature.

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.

Zn-coordination polymers for fluorescence sensing various contaminants in water.

Luminescent coordination polymers (LCPs) have garnered significant attention from researchers as promising materials for detecting contaminants. In this paper, three new LCPs ([Zn(tib)(opda)]n⋅H2O (1), [Zn3(tib)2(mpda)3]n⋅5H2O (2), [Zn (tib)(ppda)]n⋅H2O (3)) with different structures (LCP 1-3: 1D, 2D, 1D) using phenylenediacetic acid isomers and 1,3,5-tris (1-imidazolyl) benzene (tib) are synthesized. The specific surface areas (BET) of LCP 1-3 are 4 m2/g, 19 m2/g, and 13 m2/g respectively. LCP 1-3 exhibit excellent fluorescence properties and can serve as fluorescent probe for the detection of inorganic contaminants and organic contaminants. Due to the large BET of LCP 2, the detection limits for trace analytes surpass those of LCP 1 and 3. The detection limits of LCP 2 for Fe3+, nitrobenzene (NB), chloramphenicol (CAP), and pyrimethanil (PTH) are 8.3 nM, 0.016 µM, 0.19 µM, and 0.032 µM, respectively, and the fluorescence quenching rates are 98.6 %, 98.8 %, 92.3 %, and 98.8 %, respectively. These values outperform most reported in the literature. The quantum yields of LCP 1-3 are 11.84 %, 25.22 %, 22.00 % respectively. Real sample testing of LCP 1-3 reveals favorable performance, where spiked recoveries of LCP 2 for the detection of pyrimethanil in grape skins ranged from 99.62 % to 119.3 % with a relative standard deviation (RSD) of 0.627 % to 4.56 % (n = 3). The fluorescence quenching mechanism was attributed to a combination of photoelectron transfer (PET), resonance energy transfer (RET), and competitive absorption (CA). This study advances the application of LCPs in luminescence sensing and contributes to the expansion of novel materials for detecting environmental pollutants.

Rspo2 exacerbates rheumatoid arthritis by targeting aggressive phenotype of fibroblast-like synoviocytes and disrupting chondrocyte homeostasis via Wnt/ß-catenin pathway.

BACKGROUND: The aggressive phenotype of fibroblast-like synoviocytes (FLS) has been identified as a contributing factor to the exacerbation of rheumatoid arthritis (RA) through the promotion of synovitis and cartilage damage. Regrettably, there is currently no effective therapeutic intervention available to address this issue. Recent research has shed light on the crucial regulatory role of R-spondin-2 (Rspo2) in cellular proliferation, cartilage degradation, and tumorigenesis. However, the specific impact of Rspo2 on RA remains poorly understood. We aim to investigate the function and mechanism of Rspo2 in regulating the aggressive phenotype of FLS and maintaining chondrocyte homeostasis in the context of RA. METHODS: The expression of Rspo2 in knee joint synovium and cartilage were detected in RA mice with antigen-induced arthritis (AIA) and RA patients. Recombinant mouse Rspo2 (rmRspo2), Rspo2 neutralizing antibody (Rspo2-NAb), and recombinant mouse DKK1 (rmDKK1, a potent inhibitor of Wnt signaling pathway) were used to explore the role and mechanism of Rspo2 in the progression of RA, specifically in relation to the aggressive phenotype of FLS and chondrocyte homeostasis, both in vivo and in vitro. RESULTS: We indicated that Rspo2 expression was upregulated both in synovium and articular cartilage as RA progressed in RA mice and RA patients. Increased Rspo2 upregulated the expression of leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), as the ligand for Rspo2, and ß-catenin in FLS and chondrocytes. Subsequent investigations revealed that intra-articular administration of rmRspo2 caused striking progressive synovitis and articular cartilage destruction to exacerbate RA progress in mice. Conversely, neutralization of Rspo2 or inhibition of the Wnt/ß-catenin pathway effectively alleviated experimental RA development. Moreover, Rspo2 facilitated FLS aggressive phenotype and disrupted chondrocyte homeostasis primarily through activating Wnt/ß-catenin pathway, which were effectively alleviated by Rspo2-NAb or rmDKK1. CONCLUSIONS: Our data confirmed a critical role of Rspo2 in enhancing the aggressive phenotype of FLS and disrupting chondrocyte homeostasis through the Wnt/ß-catenin pathway in the context of RA. Furthermore, the results indicated that intra-articular administration of Rspo2 neutralizing antibody or recombinant DKK1 might represent a promising therapeutic strategy for the treatment of RA.

Optimization of preparation method of hepatoprotective active components from Coreopsis tinctoria Nutt. and its action mechanism in vivo.

Capitula of Coreopsis tinctoria are widely used as a flower tea with great health benefits due to rich content of flavonoids and phenolic acids. The hepatoprotective effect of C. tinctoria and its bioactive basis have seldom been investigated until now. In the present study, capitula of C. tinctoria were extracted with a method optimized by response surface methodology (RSM) and BoxBehnken design (BBD) and further purified by macroporous resin HPD-300 to obtain a fraction (CE) enriched with flavonoids and phenolic acids. The contents of the four most abundant compounds, isookanin-7-O-ß-d-glucoside (1), quercetigetin-7-O-ß-d-glucoside (2), okanin (3), and marein (4), were determined by HPLC as 9.98, 5.21, 41.78 and 1.85 mg/g, respectively. Seventy-four compounds including fifity-five flavonoids, fifteen organic acids (twelve of them were phenolic compounds), and three coumarins were tentatively identified in CE by LC-HRMS/MS. In vivo hepatoprotective effect and potential mechanism of CE were studied with a high-fat diet-induced NASH mouse model. CE administration decreased the amount of weight gain, hepatic lipid, and sequentially improved dyslipidemia, inflammation, oxidative stress, and IR in HFD-fed mice. Molecular data revealed that CE inhibited hepatic inflammation by reducing NFκB/iNOS/COX-2/NLRP3/MAPK in the liver tissues and ameliorated oxidative stress by activating the Nrf2/HO-1 pathway. Modulation of inflammation and oxidative stress with CE may represent a promising target for the treatment of NAFLD and provide insight into the mechanism by which CE protects against obesity.

TCFL5 knockdown sensitizes DLBCL to doxorubicin treatment via regulation of GPX4.

BACKGROUND: Resistance to chemo-drug is a major cause of bad outcome in diffuse large B-cell lymphoma (DLBCL). It was reported that TCFL5 may be related to chemoresistance in childhood acute lymphoblastic leukemia. However, it is still unclear whether TCFL5 is involved in DLBCL drug-resistance. METHODS: To explore the underlying mechanism of doxorubicin resistance, recombinant lentivirus was applied to control expression of TCFL5 in DLBCL cells. CCK-8 assay was perfomed to investigate the influence of doxorubicin on proliferation of TCFL5-overexpressed or sh-TCFL5 DLBCL cells. Correlation between TCFL5 and GPX4 was analyzed with bioinformatic methods, which was further confirmed by qPCR and western blot. TCFL5 overexpression conferred doxorubicin resistance via regulating GPX4 and was verified by TUNEL assay and western blot in vitro and mice model in vivo. RESULTS: TCFL5 was enriched in DLBCL cells and conferred doxorubicin resistance through binding to GPX4. Inhibition of TCFL5 enhanced the sensitivity of DLBCL cells to doxorubicin. GPX4 knockdown reversed doxorubicin resistance in TCFL5-overexpressed DLBCL cells. CONCLUSION: DLBCL cells overexpress TCFL5 that promotes chemoresistance by regulating GPX4. Targeting TCFL5 may provide a prospective therapeutic strategy for doxorubicin-resistant DLBCL.

Organic Phase-Change Memory Transistor Based on an Organic Semiconductor with Reversible Molecular Conformation Transition.

Phase-change semiconductor is one of the best candidates for designing nonvolatile memory, but it has never been realized in organic semiconductors until now. Here, a phase-changeable and high-mobility organic semiconductor (3,6-DATT) is first synthesized. Benefiting from the introduction of electrostatic hydrogen bond (S···H), the molecular conformation of 3,6-DATT crystals can be reversibly modulated by the electric field and ultraviolet irradiation. Through experimental and theoretical verification, the tiny difference in molecular conformation leads to crystalline polymorphisms and dramatically distinct charge transport properties, based on which a high-performance organic phase-change memory transistor (OPCMT) is constructed. The OPCMT exhibits a quick programming/erasing rate (about 3 s), long retention time (more than 2 h), and large memory window (i.e., large threshold voltage shift over 30 V). This work presents a new molecule design concept for organic semiconductors with reversible molecular conformation transition and opens a novel avenue for memory devices and other functional applications.

Effects of traditional artiri La Li formulation on experimental models of vitiligo and mechanisms of melanogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Artiri La Li Honey Pill (ALLHP) is a traditional medicinal formula that is widely used in Xinjiang, China, for the treatment of vitiligo. Since the cause of vitiligo has not been determined, no satisfactory treatment is available. Clinical interventions include pharmacological treatment with psoralen, usually in conjunction with ultraviolet A (UVA) radiation, but toxic side effects limit this application. Studies on the activity and mechanisms of ALLHP are scarce. AIM OF THE STUDY: To verify the therapeutic effect of ALLHP on vitiligo and determine its effectiveness as a theoretical and experimental basis for the development of innovative drugs with independent intellectual property rights and the effective use of local resources. MATERIALS AND METHODS: The experimental animal model of vitiligo was established by chemical decoloring. Rats were treated with gradient doses of ALLHP. The therapeutic effect was judged by gross observation. The contents of TYR, MAO, AchE and MDA in serum and skin tissue, the number of hair follicles containing melanin in skin tissue, the distribution of epidermal melanin, and the weight index of immune organs were detected, and the therapeutic effect of ALLHP on vitiligo was evaluated. In addition, certain monomer components in ALLHP were used to intervene in the zebrafish juvenile melanin suppression model, and the melanin-activating activities of some monomer components in ALLHP were screened by counting the melanin area ratio. RESULTS: ALLHP increased the number of melanin-containing hair follicles and the epidermal melanin content in the skin of experimental vitiligo animals, repaired the skin cell morphology to a certain extent, increased the content of TYR in serum and skin, and reduced the content of MDA, AchE and MAO. Carvone, Luteolin, Psoralen and Psoraleae phenol and Bakuchiol could increase the melanin area of experimental melanin inhibition in zebrafish. CONCLUSION: According to the results of this study, ALLHP can increase the number of melanin-containing hair follicles and the epidermal melanin content in the skin of vitiligo animals and restore skin cell morphology to a certain extent by reducing oxidative stress in epidermal tissue. A wide range of active ingredients may promote melanogenesis with ALLHP.

A Novel Furocoumarin Derivative, 5-((diethylamino)me-13 thyl)-3-phenyl-7H-furo [3,2-g] chromen-7-one Upregulates Melanin Synthesis via the Activation of cAMP/PKA and MAPKs Signal Pathway: In Vitro and In Vivo Study.

Psoralen, a major furocoumarin component of the Fructus Psoralen (FP), in combination with ultraviolet radiation, cures abnormal pigmentation disorder. In a previous study, we synthesized a series of linear furocoumarins with different substituents, out of which 5-((diethylamino)methyl)-3-phenyl-7H-furo [3,2-g] chromen-7-one (encoded as 5D3PC) showed better pigmenting effect than others in B16 cells. In this study, we examined the mechanism underlying the melanogenic effect of 5D3PC both in vivo and in vitro. To examine the pigmentation effect, the B16 and human melanocyte cell lines, PIG1 and PIG3V melanocytes were incubated with 5D3PC. In animal experiments, C57BL/6 mice received 5% hydroquinone and were administrated with 5D3PC for 30 days. 5D3PC upregulated the melanin synthesis and tyrosinase in B16 cell, PIG1 and PIG3V. The expression level of tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2), microphthalmia-associated transcription factor (MITF), cyclic adenosine monophosphate (cAMP), phosphorylation of cAMP-responsive element binding protein (p-CREB), phosphorylation of p38 mitogen-activated protein kinase (MAPK), c- phosphorylation of Jun N-terminal kinase (p-JNK) was significantly higher in 5D3PC-treated B16 cells. The oral administration of 5D3PC attenuated the depigmentation of the C57BL/6 vitiligo mice model by increasing the numbers of melanin-containing hair follicles, melanogenic protein, and melanogenesis-relative genes expression in skin tissues.

A hypoxia-dissociable siRNA nanoplatform for synergistically enhanced chemo-radiotherapy of glioblastoma.

Glioblastoma (GBM), as the most aggressive adult brain tumor, seriously threatened people's lives with a low survival time. Standard postoperative treatment, chemotherapy combined with radiotherapy (RT), was the major therapeutic strategy for GBM. However, this therapeutic efficacy was hindered by chemoradiotherapy resistance of GBM. Herein, to sensitize temozolomide (TMZ)-based chemotherapy and RT, a hypoxia-radiosensitive nanoparticle for co-delivering TMZ and siMGMT (RDPP(Met)/TMZ/siMGMT) was synthesized in this study. Our nanoparticle could effectively release the encapsulated alkylating agent (TMZ) and small interfering O6-methylguanine-DNA-methyltransferase RNA (siMGMT) in the hypoxic GBM. DNA-damage repair was effectively inhibited by down-regulating MGMT expression and activating cell apoptosis, which obviously enhanced the sensitivity of TMZ as well as RT. In vitro and in vivo experiments showed that RDPP(Met)/TMZ/siMGMT could efficiently penetrate the blood-brain barrier (BBB), accurately target GBM cells and effectively inhibit GBM proliferation. Compared with traditional TMZ combined with RT, RDPP(Met)/TMZ/siMGMT remarkably improved the survival time of orthotopic GBM-bearing mice, which demonstrated that our nanoplatform was an efficient combinatorial GBM therapy.

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.

Regulating Crystal Packing by Terminal tert-Butylation for Enhanced Solid-State Emission and Efficacious Charge Transport in an Anthracene-Based Molecular Crystal.

Organic semiconductors with combinative high carrier mobility and efficient solid-state emission are full of challenges but urgently pursued for developing new emerging optoelectronics. Herein, by delicately regulating the crystal packing of an anthracene-based molecular crystal via terminal tert-butylation, we developed a superior high mobility emissive molecule, 2,6-di(6-tert-butylnaphthyl)anthracene (TBU-DNA). The unique "slipped herringbone" packing motif of TBU-DNA enables its appropriate exciton-exciton coupling and electron-phonon coupling, thus resulting in remarkably high solid-state emission (photoluminescence quantum yield, ΦF ≈74.9 %) and efficacious charge transport (carrier mobility, µ=5.0 cm2 V-1 s-1 ). Furthermore, OLETs based on TBU-DNA show an external quantum efficiency (EQE) of 1.8 %, which is among the highest EQE values for single component OLETs reported till now. This work presents a crystal engineering strategy via exquisite molecular design to realize high mobility emissive organic semiconductors.

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.