Targeting HSP47 for cancer treatment.

Heat shock protein 47 (HSP47) serves as an endoplasmic reticulum residing collagen-specific chaperone and plays an important role in collagen biosynthesis and structural assembly. HSP47 is encoded by the SERPINH1 gene, which is located on chromosome 11q13.5, one of the most frequently amplified regions in human cancers. The expression of HSP47 is regulated by multiple cellular factors, including cytokines, transcription factors, microRNAs, and circular RNAs. HSP47 is frequently upregulated in a variety of cancers and plays an important role in tumor progression. HSP47 promotes tumor stemness, angiogenesis, growth, epithelial-mesenchymal transition, and metastatic capacity. HSP47 also regulates the efficacy of tumor therapies, such as chemotherapy, radiotherapy, and immunotherapy. Inhibition of HSP47 expression has antitumor effects, suggesting that targeting HSP47 is a feasible strategy for cancer treatment. In this review, we highlight the function and expression of regulatory mechanisms of HSP47 in cancer progression and point out the potential development of therapeutic strategies in targeting HSP47 in the future.

Catalytic Refining Lignin-derived Monomers: Seesaw Effect between Nanoparticle and Single-Atom Pt.

Pt automatically adsorbed on oxygen vacancy of TiO2 via an in-situ interfacial redox reaction, resulting in atomically dispersion of Pt on TiO2.In the upgrading of lignin-derived 4-propylguaiacol, single-atom catalyst (SAC) Pt/TiO2-H achieved a conversion of 96.9% and a demethoxylation selectivity of 93.3% under 3 MPa H2 at 250 °C for 3 h, markedly different from the performance of nanoparticle counterpart that gave deep deoxygenation selectivity over 99.0%. The high demethoxylation activity of SAC Pt/TiO2-H is mainly attributed to its weak hydrogen spillover capacity that suppressed the benzene ring hydrogenation and the deep deoxygenation. Additionally, SAC Pt/TiO2-H reduced the energy barrier of CAr-OCH3 bond cleavage and accordingly lowered the Gibbs free energy of the demethoxylation reaction. This facile method could fabricate single-atom Au, Pd, Ir, and Ru supported on TiO2-H, demonstrating the generality of this strategy for the establishment of a library of SACs. Moreover, SAC exhibited versatile capacity in demethoxylation of different lignin-derived monomers and high stability.This study showcases the superiority of atomically dispersed metal catalysts for selective demethoxylation reactions and proposes a renewable alternative to fossil-based 4-alkylphenols through upgrading of lignin-derived monomers.

Understanding asymmetric switching times in accumulation mode organic electrochemical transistors.

Understanding the factors underpinning device switching times is crucial for the implementation of organic electrochemical transistors in neuromorphic computing, bioelectronics and real-time sensing applications. Existing models of device operation cannot explain the experimental observations that turn-off times are generally much faster than turn-on times in accumulation mode organic electrochemical transistors. Here, using operando optical microscopy, we image the local doping level of the transistor channel and show that turn-on occurs in two stages-propagation of a doping front, followed by uniform doping-while turn-off occurs in one stage. We attribute the faster turn-off to a combination of engineering as well as physical and chemical factors including channel geometry, differences in doping and dedoping kinetics and the phenomena of carrier-density-dependent mobility. We show that ion transport limits the operation speed in our devices. Our study provides insights into the kinetics of organic electrochemical transistors and guidelines for engineering faster organic electrochemical transistors.

Selectively Modulating Componential Morphologies of Bulk Heterojunction Organic Solar Cells.

Achieving precise control over the nanoscale morphology of bulk heterojunction films presents a significant challenge for the conventional post-treatments employed in organic solar cells (OSCs). In this study, a near-infrared photon-assisted annealing (NPA) strategy is developed for fabricating high-performance OSCs under mild processing conditions. It is revealed a top NIR light illumination, together with the bottom heating, enables the selective tuning of the molecular arrangement and assembly of narrow bandgap acceptors in polymer networks to achieve optimal morphologies, as well as the acceptor-rich top surface of active layers. The derived OSCs exhibit a remarkable power conversion efficiency (PCE) of 19.25%, representing one of the highest PCEs for the reported binary OSCs so far. Moreover, via the NPA strategy, it has succeeded in accessing top-illuminated flexible OSCs using thermolabile polyethylene terephthalate from mineral water bottles, displaying excellent mechanical stabilities. Overall, this work will hold the potential to develop organic solar cells under mild processing with various substrates.

Highly Efficient and Stable ITO-Free Organic Solar Cells Based on Squaraine N-Doped Quaternary Bulk Heterojunction.

Simultaneously achieving high efficiency and robust device stability remains a significant challenge for organic solar cells (OSCs). Solving this challenge is highly dependent on the film morphology of the bulk heterojunction (BHJ) photoactive blends; however, there is a lack of rational control strategy. Herein, it is shown that the molecular crystallinity and nanomorphology of nonfullerene-based BHJ can be effectively controlled by a squaraine-based doping strategy, leading to an increase in device efficiency from 17.26% to 18.5% when doping 2 wt% squaraine into the PBDB-TF:BTP-eC9:PC71 BM ternary BHJ. The efficiency is further improved to 19.11% (certified 19.06%) using an indium-tin-oxide-free column-patterned microcavity (CPM) architecture. Combined with interfacial modification, CPM quaternary OSC excitingly shows an extrapolated lifetime of ≈23 years based on accelerated aging test, with the mechanism behind enhanced stability well studied. Furthermore, a flexible OSC module with a high and stable efficiency of 15.2% and an overall area of 5 cm2 is successfully fabricated, exhibiting a high average output power for wearable electronics. This work demonstrates that OSCs with new design of BHJ and device architecture are highly promising to be practical relevance with excellent performance and stability.

TSPAN1 inhibits metastasis of nasopharyngeal carcinoma via suppressing NF-kB signaling.

Nasopharyngeal carcinoma (NPC) originates in the epithelial cells of the nasopharynx and is a common malignant tumor in southern China and Southeast Asia. Metastasis of NPC remains the main cause of death for NPC patients even though the tumor is sensitive to radiotherapy and chemotherapy. Here, we found that the transmembrane protein tetraspanin1 (TSPAN1) potently inhibited the in vitro migration and invasion, as well as, the in vivo metastasis of NPC cells via interacting with the IKBB protein. In addition, TSPAN1 was essential in preventing the overactivation of the NF-kB pathway in TSPAN1 overexpressing NPC cells. Furthermore, reduced TSPAN1 expression was associated with NPC metastasis and the poor prognosis of NPC patients. These results uncovered the suppressive role of TSPAN1 against NF-kB signaling in NPC cells for preventing NPC metastasis. Its therapeutic value warrants further investigation.

A dual-channel fluorescence probe for simultaneously visualizing cysteine and viscosity during drug-induced hepatotoxicity.

Cysteine (Cys), one of the important participants in protecting cells from oxidative stress, is closely associated with the occurrence and development of various diseases. Moreover, cell viscosity as a pivotal microenvironmental parameter has recently attracted increasing attention due to its dominant role in governing intracellular signal transduction and diffusion of reactive metabolites. Thus, simultaneous detection of Cys and viscosity is imperative for investigating their pathophysiological functions and cross-link. Herein we present a mitochondria-targetable dual-channel fluorescence probe ABDSP by grafting the acrylate modified pyridinium unit to dimethylaminobenzene. Whilst the probe is a seemingly simple, it could simultaneously discriminate Cys and viscosity in a fashion of distinguishable signals. Furthermore, the probe was successfully employed for visualizing mitochondrial Cys and viscosity, and probe into their cross-link during acetaminophen-induced hepatotoxicity.

Incorporation of Digital Modulation into Vital Sign Detection and Gesture Recognition Using Multimode Radar Systems.

The incorporation of digital modulation into radar systems poses various challenges in the field of radar design, but it also offers a potential solution to the shrinking availability of low-noise operating environments as the number of radar applications increases. Additionally, digital systems have reached a point where available components and technology can support higher speeds than ever before. These advancements present new avenues for radar design, in which digitally controlled phase-modulated continuous wave (PMCW) radar systems can look to support multiple collocated radar systems with low radar-radar interference. This paper proposes a reconfigurable PMCW radar for use in vital sign detection and gesture recognition while utilizing digital carrier modulation and compares the radar responses of various modulation schemes. Binary sequences are used to introduce phase modulation to the carrier wave by use of a field programable gate array (FPGA), allowing for flexibility in the modulation speed and binary sequence. Experimental results from the radar demonstrate the differences between CW and PMCW modes when measuring the respiration rate of a human subject and in gesture detection.

Ulinastatin inhibits the metastasis of nasopharyngeal carcinoma by involving uPA/uPAR signaling.

Distant metastasis is the primary reason for treatment failure in patients with nasopharyngeal carcinoma (NPC). In this study, we investigated the effect of ulinastatin (UTI) on NPC metastasis and its underlying mechanism. Highly-metastatic NPC cell lines S18 and 58F were treated with UTI and the effect on cell proliferation, migration, and invasion were determined by MTS and Transwell assays. S18 cells with luciferase-expressing (S18-1C3) were injected into the left hind footpad of nude mice to establish a model of spontaneous metastasis from the footpad to popliteal lymph node (LN). The luciferase messenger RNA (mRNA) was measured by quantitative polymerase chain reaction (qPCR), and the metastasis inhibition rate was calculated. Key molecular members of the UTI-related uPA, uPAR, and JAT/STAT3 signaling pathways were detected by qPCR and immunoblotting. UTI suppressed the migration and infiltration of S18 and 5-8F cells and suppressed the metastasis of S18 cells in vivo without affecting cell proliferation. uPAR expression decreased from 24 to 48 h after UTI treatment. The antimetastatic effect of UTI is partly due to the suppression of uPA and uPAR. UTI partially suppresses NPC metastasis by downregulating the expression of uPA and uPAR.

Robust and Sustainable Indium Anode Leading to Efficient and Stable Organic Solar Cells.

The fast degradation of the charge-extraction interface at indium tin oxide (ITO) poses a significant obstacle to achieving long-term stability for organic solar cells (OSCs). Herein, a sustainable approach for recycling non-sustainable indium to construct efficient and stable OSCs and scale-up modules is developed. It is revealed that the recovered indium chloride (InCl3 ) from indium oxide waste can be applied as an effective hole-selective interfacial layer for the ITO electrode (noted as InCl3 -ITO anode) through simple aqueous fabrication, facilitating not only energy level alignment to photoactive blends but also mitigating parasitic absorption and charge recombination losses of the corresponding OSCs. As a result, OSCs and modules consisting of InCl3 -ITO anodes achieve remarkable power conversion efficiencies (PCEs) of 18.92% and 15.20% (active area of 18.73 cm2 ), respectively. More importantly, the InCl3 -ITO anode can significantly extend the thermal stability of derived OSCs, with an extrapolated T80 lifetime of ≈10 000 h.

Cleavable-Branched Polymer-Modified Liposomes Reduce Accelerated Blood Clearance and Enhance Photothermal Therapy.

In recent years, cationic liposomes have been successfully used as delivery platforms for mRNA vaccines. Poly(ethylene glycol) (PEG)-lipid derivatives are widely used to enhance the stability and reduce the toxicity of cationic liposomes. However, these derivatives are often immunogenic, triggering the rise of anti-PEG antibodies. Understanding the role and impact of PEG-lipid derivatives on PEGylated cationic liposomes is key to solving the PEG dilemma. In this study, we designed linear, branched, and cleavable-branched cationic liposomes modified with PEG-lipid derivatives and investigated the effect of the liposome-induced accelerated blood clearance (ABC) phenomenon on photothermal therapy. Our study indicated that the linear PEG-lipid derivatives mediated the effect of photothermal therapy by stimulating splenic marginal zone (MZ) B cells to secrete anti-PEG antibodies and increasing the level of IgM expression in the follicular region of the spleen. However, the cleavable-branched and branched PEG-lipid derivatives did not activate the complement system and avoided the ABC phenomenon by inducing noticeably lower levels of anti-PEG antibodies. The cleavable-branched PEGylated cationic liposomes improved the effect of photothermal therapy by reversing the charge on the liposome surface. This detailed study of PEG-lipid derivatives contributes to the further development and clinical application of PEGylated cationic liposomes.

Imidazo[1,2-a]pyridine derivatives synthesis from lignin ß-O-4 segments via a one-pot multicomponent reaction.

The catalytic conversion of lignin into N-containing chemicals is of great significance for the realization of value-added biorefinery concept. In this article, a one-pot strategy was designed for the transformation of lignin ß-O-4 model compounds to imidazo[1,2-a]pyridines in yields up to 95% using 2-aminopyridine as a nitrogen source. This transformation involves highly coupled cleavage of C-O bonds, sp3C-H bond oxidative activation, and intramolecular dehydrative coupling reaction to construction of N-heterobicyclic ring. With this protocol, a wide range of functionalized imidazo[1,2-a]pyridines sharing the same structure skeleton as those commercial drug molecules, such as Zolimidine, Alpidem, Saripidem, etc., were synthesized from different lignin ß-O-4 model compounds and one ß-O-4 polymer, emphasizing the application feasibility of lignin derivatives in N-heterobicyclic pharmaceutical synthesis.

Correlated with better prognosis, CSTA inhibits metastasis of nasopharyngeal carcinoma cells via suppressing AKT signaling through promoting METTL3 degradation.

BACKGROUND: Metastasis is one of the main obstacles impeding the survival of nasopharyngeal carcinoma (NPC) patients, with the molecular mechanism underlying NPC metastasis still unclear. RESULTS: In this study, Cystatin A (CSTA) was found downregulated in NPC tissues with metastasis compared with those without metastasis. Shorter overall survival and distant metastasis-free survival were found in NPC patients with lower CSTA expression. Using functional assays, we found that CSTA prevented both the in vitro motility of NPC cells and their ability to metastasize in vivo. Transcriptome sequencing and western blot analysis revealed that CSTA inhibited the phosphorylation of AKT. Moreover, activating AKT using AKT agonist SG79 rescued the motility of CSTA-overexpressing NPC cells, whereas, treatment with AKT inhibitor MK2206 inhibited the motility of CSTA-knockdown NPC cells. Mechanically, immunoprecipitation coupled mass spectrometry found that CSTA interacted with the N6-adenosine-methyltransferase subunit METTL3 and promoted its ubiquitin-proteasome-mediated degradation following the upregulation of NKX3-1 and LHPP, which are negative regulators of AKT. Furthermore, knock-down of NKX3-1 and LHPP enhanced the motility of CSTA-overexpressing NPC cells. CONCLUSIONS: The inhibitory effect of CSTA upon NPC metastasis mainly depended on suppressing AKT signaling by the upregulation of NKX3-1 and LHPP expression resulting from the binding between CSTA and METLL3. Our study suggests that the CSTA-METLL3-NKX3-1/LHPP-AKT axis could be of therapeutic value for inhibiting NPC metastasis.

Sialic acid-mediated photochemotherapy enhances infiltration of CD8+ T cells from tumor-draining lymph nodes into tumors of immunosenescent mice.

Immunoscenescence plays a key role in the initiation and development of tumors. Furthermore, immunoscenescence also impacts drug delivery and cancer therapeutic efficacy. To reduce the impact of immunosenescence on anti-tumor therapy, this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid (SA)-modified liposomes into the tumor, kill tumor cells via SA-mediated photochemotherapy, enhance infiltration of neutrophils into the tumor, induce immunogenic death of tumor cells with chemotherapy, enhance infiltration of CD8+ T cells into the tumor-draining lymph nodes and tumors of immunosenescent mice, and achieve SA-mediated photochemotherapy. We found that CD8+ T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2- and 8-month-old mice; 16-month-old mice exhibited immunosenescence. The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice, and tumors recurred after scabbing. SA-mediated photochemotherapy enhanced tumor infiltration by CD8+ T cells and neutrophils, induced crusting and regression of tumors in 8-month-old mice, inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion.

Multifunctional Hybrid Interfacial Layers for High-Performance Inverted Perovskite Solar Cells.

Challenges remain hindering the performance and stability of inverted perovskite solar cells (PSCs), particularly for the nonstable interface between lead halide perovskite and charge extraction metal oxide layer. Herein, a simple yet scalable interfacial strategy to facilitate the assemble of high-performance inverted PSCs and scale-up modules is reported. The hybrid interfacial layer containing self-assembly triphenylamine and conjugated poly(arylamine) simultaneously improves the chemical stability, charge extraction, and energy level alignment of hole-selective interface, meanwhile promoting perovskite crystallization. Consequently, the correspondent inverted PSCs and modules achieve remarkable power conversion efficiencies (PCEs) of 24.5% and 20.7% (aperture area of 19.4 cm2 ), respectively. The PSCs maintain over 80% of its initial efficiency under one-sun equivalent illumination of 1200 h. This strategy is also effective to perovskite with various bandgaps, demonstrating the highest PCE of 19.6% for the 1.76-eV bandgap PSCs. Overall, this work provides a simple yet scalable interfacial strategy for obtaining state-of-the-art inverted PSCs and modules.

Unsymmetrically Chlorinated Non-Fused Electron Acceptor Leads to High-Efficiency and Stable Organic Solar Cells.

Searching the cost-effective organic semiconductors is strongly needed in order to facilitate the practice of organic solar cells (OSCs), yet to be fulfilled. Herein, we have succeeded in developing two non-fused ring electron acceptors (NFREAs), leading to the highest efficiency of 16.2 % for the NFREA derived OSCs. These OSCs exhibit the superior operational stabilities under one sun equivalent illumination without ultraviolet (UV) filtration. It is revealed that the modulation of halogen substituents on aromatic side chains, as the new structural tool to tune the intermolecular interaction and optoelectronic properties of acceptors, not only promotes the interlocked tic-tac-toe frame of three-dimensional stacks in solid, but also improves charge dynamics of acceptors to enable high-performance and stable OSCs.

Particle Size Inversion Constrained by L∞ Norm for Dynamic Light Scattering.

Particle size inversion of dynamic light scattering (DLS) is a typically ill-posed problem. Regularization is an effective method to solve the problem. The regularization involves imposing constraints on the fitted autocorrelation function data by adding a norm. The classical regularization inversion for DLS data is constrained by the L2 norm. In the optimization equation, the norm determines the smoothness and stability of the inversion result, affecting the inversion accuracy. In this paper, the Lp norm regularization model is constructed. When p is 1, 2, 10, 50, 100, 1000, and ∞, respectively, the influence of their norm models on the inversion results of data with different noise levels is studied. The results prove that overall, the inversion distribution errors show a downward trend with the increase of p. When p is larger than 10, there is no significant difference in distribution error. Compared with L2, L∞ can provide better performance for unimodal particles with strong noise, although this does not occur in weak noise cases. Meanwhile, L∞ has lower sensitivity to noise and better peak resolution, and its inverse particle size distribution is closer to the true distribution for bimodal particles. Thus, L∞ is more suitable for the inversion of DLS data.

Successive Cleavage and Reconstruction of Lignin ß-O-4 Models and Polymer to Access Quinoxalines.

The construction of N-heterocyclic compounds from lignin remains a great challenge due to the complex lignin structure and the involvement of multiple steps, including the cleavage of lignin C-O linkages and the formation of heterocyclic aromatic rings. Herein, the first example of KOH mediated sustainable synthesis of quinoxaline derivatives from lignin ß-O-4 model compounds in a one-pot fashion under transition-metal-free conditions has been achieved. Mechanistic studies suggested that this transformation includes highly coupled cascade steps of cleavage of C-O bonds, dehydrative condensation, sp3 C-H bond oxidative activation, and intramolecular dehydrative coupling reaction. With this protocol, a wide range of functionalized quinoxalines, including an important drug compound AG1295, were synthesized from lignin ß-O-4 model compounds and ß-O-4 polymer, showcasing the application potential of lignin in pharmaceutical synthesis.

Structural materials with afterglow room temperature phosphorescence activated by lignin oxidation.

Sustainable afterglow room temperature phosphorescence (RTP) materials, especially afterglow RTP structural materials, are crucial but remain difficult to achieve. Here, an oxidation strategy is developed to convert lignin to afterglow materials with a lifetime of ~ 408 ms. Specifically, lignin is oxidized to give aromatic chromophores and fatty acids using H2O2. The aromatic chromophores are locked by a fatty acid-based matrix by hydrogen bonds, triggering enhanced spin orbit coupling and long afterglow emission. More interestingly, motivated by this discovery, an auto fabrication line is built to convert wood (natural structural materials) to wood with afterglow RTP emission (RTP wood) via in situ oxidation of naturally-occurring lignin located in the wood cell walls to oxidized lignin (OL). The as-prepared RTP wood exhibits great potential for the construction of sustainable afterglow furniture. With this research we provide a new strategy to promote the sustainability of afterglow RTP materials and structural materials.