Insolubility and aggregation of crystallins are common features in cataracts. CYP51 has been identified as a novel candidate gene for cataracts; however, its associated phenotypes remain unconfirmed. We investigated the role of FF-MAS, synthesized by CYP51, in αA-crystallin solubility and lens transparency. FF-MAS was administered to HLE-B3 cells expressing αA-crystallin (R116C) and to rats with selenite-induced cataracts. Lens transparency was assessed using slit-lamp photography. Congo red staining and transmission electron microscopy were used to analyze lens uniformity. Western blotting and immunofluorescence were employed to detect αA-crystallin aggregation. Additionally, we evaluated the effects of FF-MAS on apoptosis, antioxidant capacity, and protein homeostasis. In HLE-B3 cells, FF-MAS reduced αA-crystallin (R116C) aggregation. In rats with selenite-induced cataracts, FF-MAS increased αA-crystallin solubility, enhanced antioxidant capacity, reduced HSP90 levels, and protected α-tubulin and AQP-0, thereby improving lens uniformity and transparency. Inhibition of CYP51 by ketoconazole also led to cataract formation in rats and mice and increased apoptosis in HLE-B3 cells. Exogenous supplementation with FF-MAS inhibited these processes. FF-MAS plays a significant role in improving αA-crystallin solubility and lens transparency. Elevating FF-MAS levels may offer a novel approach to preventing and alleviating cataracts.

In this study, an innovative experiment for undergraduates was designed. Inspired by the efficient cellular entry mechanism of viruses, a virus-like nanophotothermal agent (AuNS@CuS) was constructed. This agent is composed of a gold nanostars (AuNS) core, which mimics viral surface protrusions, and a functional shell of in-situ-grown copper sulfide quantum dots (CuS QDs). Its morphology, physicochemical properties, and photothermal conversion performance were systematically studied. The experiment integrates material synthesis, characterization and performance testing. The operation is safe and controllable, and the results are intuitive and significant. It not only cultivates students' abilities in material preparation, performance characterization, and data analysis but also effectively fosters their understanding of nanotechnology, interdisciplinary application skills, and innovative practical capabilities. The experimental process deeply integrates artificial intelligence (AI) technology, including the use of AI for literature research and analysis, experimental feed prediction, and mechanism exploration and scheme optimization of growth anomalies. The results show that the AI-assisted preparation of the virus-like nanophotothermal agent AuNS@CuS endows it with excellent near-infrared (NIR) photothermal conversion performance, good photothermal stability, and efficient cell uptake capability due to its virus-like structure, providing a new strategy for tumor photothermal therapy. This experimental design provides an interdisciplinary scientific research practice platform for undergraduates, effectively cultivates students' interdisciplinary thinking and AI-enabled scientific research ability, and improves students' cognition and application ability of

The rapid development of wearable and deformable electronics has created an urgent need for energy storage devices that combine high mechanical adaptability, environmental sustainability, and robust electrochemical performance. Although flexible zinc-ion hybrid supercapacitors (ZHSs) offer high capacity and fast charge-discharge characteristics, their stretchability remains limited. Here, we address this challenge by employing direct laser writing (DLW) to in situ convert lignin into B/N/O/Zn heteroatom-doped lignin-derived porous laser-induced graphene (LPLIG) as the cathode on a zinc borate (ZB)-modified lignin/XNBR composite (THZLX). ZB significantly reduces lignin aggregation and forms multiple sacrificial bonds (hydrogen bonds, coordination bonds, and borate ester bonds) at the lignin-rubber interface. These sacrificial bonds constitute a dynamic thermally-responsive network, enhancing the mechanical strength of THZLX to similar to 18 MPa while maintaining a high elongation at break (597%). More importantly, they endow the THZLX substrate with high thermally-triggered healing efficiencies of 83.9 +/- 3% (strength) and 77.8 +/- 2% (elongation) after healing at 100 degrees C. In addition, synergistic B/N/O/Zn heteroatom doping improves the hydrophilicity and electrochemical activity of the LPLIG cathode. By integrating an electrodeposited zinc anode and a CMC-Alg dual-network organic solid-state gel electrolyte, we constructed a "dumbbell-shaped'' rubber-based ZHS that delivers an areal capacitance of 782.6 mF cm(-)(2) at 0.1 mA cm(-)(2) and retains 350 mF cm(-)(2) at 3 mA cm(-)(2). The device maintains 96.53% capacitance after 10,000 cycles. Furthermore, a kirigami-inspired "fishnet-like'' configuration enables stable operation under stretching. This work provides a scalable strategy for developing mechanically robust, stretchable, and sustainable ZHSs for next-generation flexible electronics.

Spin crossover (SCO) complexes hold immense potential for thermoelectric applications due to their temperature sensitivity. Herein, a kind of thermoelectric composite material based on SCO iron (II) complex [Fe(NH2trz)3] (BF4)2 and single-walled carbon nanotubes (SWCNT) has been fabricated for advanced temperature sensing applications. When the mass ratio of SCO to SWCNTs is 3:20 and the temperature is 300 K, the composite has an electrical conductivity of 2033.1 f 26.6 S cm- 1 and a power factor of 144.4 f 3.8 mu W m- 1 K-2. In contrast, pure SWCNTs only have an electrical conductivity of 1414.6 f 22.5 S cm- 1 and a power factor of 88.2 f 4.2 mu W m-1 K-2 at the same temperature. Moreover, the electrical conductivity of the composite changes more with temperature than that of pure SWCNTs when the temperature rises from 300 K to 400 K, which indicates that the composite is more sensitive to temperature. Therefore, a thermoelectric material with enhanced thermoelectric performance and temperature sensitivity has been successfully fabricated and has potential application in the field of temperature sensing.

Single-walled carbon nanotubes (SWCNTs) are considered highly promising flexible thermoelectric materials because of their excellent electrical transport properties, mechanical flexibility, and solution processability. However, their thermoelectric performance is still limited by the difficulty of simultaneously optimizing electrical conductivity and the Seebeck coefficient. In this work, semiconducting nonmetallic carbon- and metallic iron- doped exfoliated hexagonal boron nitride nano-sheets (BNNSs) have been firstly synthesized by hightemperature pyrolysis and microwave-assisted synthesis method, respectively. Then, the as-prepared C(Fe)doped BNNSs are incorporated into SWCNT networks to construct composite films with designed heterointerfaces for improved thermoelectric performance. The introduction of Fe-BNNSs and C-BNNSs creats abundant heterointerfaces, inducing an energy-filtering effect and increasing the Seebeck coefficient. Notably, CBNNS forms a conformal coating on SWCNTs, and C-BNNS enhances pi-pi interactions with SWCNTs, improving their dispersion and facilitating carrier transport. Meanwhile, the stable coated heterojunction synergistically boosts electrical conductivity and the Seebeck coefficient, further enhancing thermoelectric properties. In this system, carbon doping plays a dual role by simultaneously realizing band engineering of BNNSs and interfacial regulation within the SWCNT network, whereas iron doping mainly contributes through band structure modulation. As a result, the optimized C-BNNS/SWCNT composite film achieves a maximum power factor of 389.7 mu W m- 1 K- 2. In addition, the assembled thermoelectric device delivers a normalized power density of 1.9 & times; 10- 2 W m- 2 K- 2. Therefore, this work demonstrates that element-doped BNNSs serve as efficient nano-fillers to modulate charge transport behavior and interfacial properties in SWCNT films, which offers a feasible route toward highperformance carbon nanotube-based thermoelectric composites.

Lead halide perovskite quantum dots (PQDs) exhibit outstanding optical properties, including high photoluminescence quantum yield, narrow emission bandwidth, and tunable emission wavelengths. However, structural instability and susceptibility to degradation in aqueous environments significantly limit their applicability in biological imaging systems. Therefore, the development of PQD-based imaging platforms with excellent optical performance and enhanced aqueous stability remains a critical challenge. Herein, a water-dispersible nanocomposite nanoimaging platform CsPbBr3-Fe3O4@SA@DSPE-mPEG (CPB-Fe@SA@DSPE) was successfully synthesized by employing stearic acid (SA) as a hydrophobic shell and amphiphilic molecule DSPE-mPEG as a hydrophilic layer, enabling dual-modal fluorescence and magnetic resonance imaging (MRI) for tumor diagnostics. This platform demonstrates remarkable water dispersibility and stability, retaining 42.8% of its initial fluorescence intensity after 37 days in an aqueous medium. In addition, it exhibits superparamagnetic behavior with a saturation magnetization of 0.96 emu/g. In vitro experiments further confirmed its dual-mode imaging capability in tumor models, underscoring its potential in precision diagnostics. Therefore, this study provides a promising strategy to overcome the intrinsic limitation of PQDs in biomedical imaging and broadens the scope of PQD-based applications.

Doxorubicin (DOX) is an anthracycline chemotherapeutic drug used for tumour treatment. Due to DOX-induced cardiotoxicity (DIC), its clinical application has been widely limited. Multiple studies have shown that ferroptosis is involved in the pathogenesis of DIC and that arachidonate 5-lipoxygenase (Alox5) plays an important role in the occurrence and development of ferroptosis. The aim of this study was to provide evidence that silencing Alox5 alleviated DIC by affecting ferroptosis and identify mechanisms. Acute models of DIC were established in wild-type (WT) C57BL/6 and Alox5-deficient (Alox5 KO) mice and neonatal rat ventricular myocytes (NRVMs). Alox5 was upregulated in vivo and in vitro during DIC. Subsequently, we overexpressed the Alox5 gene in adult mice using a recombinant adenovirus expression vector (rAAV9). Compared with that in WT mice, overexpressing Alox5 accelerated DOX-induced myocardial injury and cardiac dysfunction. This finding was also confirmed in vitro. In contrast, silencing the Alox5 gene protected against myocardial injury in the DIC model and reduced ferroptosis and inflammation, and this effect was confirmed in vitro. In addition, transcriptomics and GO enrichment analysis of adult mouse cardiomyocytes showed that Alox5 could ameliorate DIC by inhibiting ferroptosis and inflammation. Moreover, P53 was identified as a target of Alox5. Subsequently, in vivo and in vitro experiments showed that silencing Alox5 could alleviate ferroptosis and inflammation. Further in vivo and in vitro experiments demonstrated that dexrazoxane (DXZ) could ameliorate DIC caused by Alox5 overexpression by alleviating ferroptosis. Mechanistically, silencing Alox5 could reduce reactive oxygen species (ROS) production through the P53/SLC7A11 pathway. Furthermore, P53 inhibitors significantly inhibited the adverse effects of Alox5 overexpression on DIC. The final experiment showed that pharmacological inhibition of Alox5 could prevent DIC in vivo and in vitro. Our study showed that the downregulation of Alox5 alleviated myocardial damage associated with DIC via the P53/SLC7A11 pathway. Therefore, inhibiting Alox5 might be a potential strategy for the treatment of DIC.

Tumor immune checkpoint therapy (ICT) aims to block immune escape signals between tumor and immune cells. However, low delivery efficiency of immune checkpoint inhibitors (ICIs), narrow single-target approach, and reduced responsiveness notably hinder clinical development of ICT. Here, we developed a nanoliposome-bacteria hybrid system that acts as an antibody (Ab) factory, enabling precise tumor targeting and macrophage activation in hypoxic environments. We reprogrammed attenuated Escherichia coli MG1655 to synthesize CD47 antibodies (aCD47) in response to hypoxic tumor microenvironments while surface conjugating with redox-responsive macrophage colony-stimulating factor-loaded liposomes. This system leverages bacterial tropism to enhance macrophage infiltration and polarization. The low oxygen levels trigger in situ aCD47 expression, blocking the "do not eat me" signal and boosting macrophage antitumor activity. In addition, macrophage antigen presentation activates CD8+CD3+ T cells, amplifying systemic antitumor immunity. Analysis of the gut microbiome shows reduced pathogenicity and improved intestinal tolerance with increased probiotics.

Nanocarriers have been extensively utilized to improve the stability of photothermal agents in vivo, enhance delivery efficiency, and reduce drug side effects. However, challenges, such as the low safety of carrier materials, insufficient loading of therapeutic agents, and complex preparation procedures, still persist. In this study, the photothermal agent IR780 was encapsulated in network TA-Fe3+ (TF) which was self-assembled by tannic acid (TA) and Fe3+ to synthesize an acid-responsive multifunctional nanophotothermal agent TF@IR780 (TR). In the slightly acidic tumor microenvironment (TME), network shell TF is degraded, and the internal photothermal agent IR780 is exposed. On the one hand, the TF network can improve the solubility and stability of photothermal agent IR780 in vivo and significantly increase the uptake efficiency in tumor cells. On the other hand, Fe3+ exhibits magnetic resonance imaging (MRI) functionality, which combined with the fluorescence imaging of IR780 endows TR with multimodal imaging capabilities. In addition, TR is easy to release photosensitizers through acid response in the low pH environment of TME, and achieves precise damage to mitochondria through mitochondrial anchoring and light regulation. This overcomes the drawbacks of traditional tumor treatment methods, such as poor specificity, and demonstrates efficient and controllable antitumor activity.

Optimizing carrier concentration and transport has been demonstrated to be a practical strategy to improve the thermoelectric efficacy of single-walled carbon nanotube (SWCNT)-based composite films, which have potential application in self-powered wearable electronics. In this study, nonmetallic heteroatoms (boron, sulfur, and phosphorus) are selected to dope g-C3N4 to adjust the energy band structure for fabricating g-C3N4/SWCNT with high thermoelectric performance. Heteroatom doping of g-C3N4 improves the energy band structure and mobility of g-C3N4, which promotes the carrier transport between g-C3N4 and SWCNT and optimizes the carrier mobility and concentration of the composite, substantially improving both the Seebeck coefficient (S) and the electrical conductivity (sigma) of g-C3N4/SWCNT. The results show that boron doped g-C3N4/SWCNT exhibits the maximum room temperature power factor (PF) of 198.4 mu W m- 1 K- 2 alongside a Seebeck coefficient of 31.4 mu V K- 1 among the prepared nonmetallic heteroatom doped g-C3N4/SWCNT composite films. Furthermore, under a temperature difference of 60 K, the flexible thermoelectric device made of the composite film produces a high output power of 5.7 mu W and a large open-circuit voltage of 50.3 mV. Thus, this study presents an innovative method for improving the efficacy of composite thermoelectric materials utilizing SWCNT and inorganic materials, demonstrating potential applications in flexible electronics.

Nanomaterials offer enhanced stability and functionality for photothermal agents; however, their efficacy is often limited by suboptimal cellular internalization and photothermal conversion efficiency. To address these challenges, we designed a multicomponent inorganic-organic hybrid photothermal agent that integrates a virus-mimicking morphology and stimuli-responsive components. Gold nanostars (GNS) were functionalized with a pH-responsive epigallocatechin gallate (EGCG) polyphenol network, followed by in situ growth of CuS, yielding star-shaped GEC nanoassemblies with a rough surface. This biomimetic design leverages (i) the plasmonic photothermal properties of the GNS core, (ii) the acid-triggered disassembly of the EGCG network (mimicking viral protein shells), and (iii) the in situ synthesized CuS layer exhibiting a virus-mimetic rough surface and targeting capability, which enhances near-infrared light absorption and promotes endocytosis by the target cells. The synergistic integration of GNS and CuS significantly enhanced the photothermal conversion efficiency. Under tumor acidic conditions, the EGCG network disintegrated, leading to the shedding of the CuS shell and a reduction in overall size, which facilitated deep tissue penetration. Structural characterization confirmed the hierarchical architecture and pH-responsive size transition. Compared to unmodified GNS, the cellular uptake of GEC by 4T1 cells was approximately 4.5-fold higher, attributable to its virus-like rough surface, acid-responsive disintegration, and targeting ability. This work demonstrates a rational biomimetic strategy for engineering stimuli-responsive inorganic-organic hybrids with optimized photothermal performance through biomimetic component engineering.

Photothermal therapy (PTT) is an effective cancer treatment method. Due to its easy focusing and tunability of the irradiation light, direct and accurate local treatment can be performed in a noninvasive manner by PTT. This treatment strategy requires the use of photothermal agents to convert light energy into heat energy, thereby achieving local heating and triggering biochemical processes to kill tumor cells. As a key factor in PTT, the photothermal conversion ability of photothermal agents directly determines the efficacy of PTT. In addition, photothermal agents generally have photothermal imaging (PTI) and photoacoustic imaging (PAI) functions, which can not only guide the optimization of irradiation conditions but also achieve the integration of disease diagnosis. If the photothermal agents have function of fluorescence imaging (FLI) or fluorescence enhancement, they can not only further improve the accuracy in disease diagnosis but also accurately determine the tumor location through multimodal imaging for corresponding treatment. In this paper, we summarize recent advances in photothermal agents with FLI or fluorescence enhancement functions for PTT and tumor diagnosis. According to the different recognition sites, the application of specific targeting photothermal agents is introduced. Finally, limitations and challenges of photothermal agents with fluorescence imaging/enhancement in the field of PTT and tumor diagnosis are prospected.

Mitochondria-targeting photothermal therapy could significantly enhance the tumor cell killing effect. However, since therapeutic reagents need to overcome a series of physiological obstacles to arrive at mitochondria accurately, precise mitochondria-targeting photothermal therapy still faces great challenges. In this study, we developed a self-delivery nanoplatform that specifically targeted the mitochondria of tumor cells for precise photothermal therapy. Photothermal agent IR780 was encapsulated by amphiphilic apoptotic peptide KLA with mitochondria-targeting ability to form nanomicelle KI by self-assembly through hydrophilic and hydrophobic interactions. Subsequently, negatively charged tumor-targeting polymer HA was coated on the surface of KI through electrostatic interactions, to obtain tumor mitochondria-targeting self-delivery nanoplatform HKI. Through CD44 receptor-mediated recognition, HKI was internalizated by tumor cells and then disassembled in an acidic environment with hyaluronidase in endosomes, resulting in the release of apoptotic peptide KLA and photothermal agent IR780 with mitochondria anchoring capacity, which achieved precise mitochondria guidance and destruction. This tumor mitochondria-targeting self-delivery nanoplatform was able to effectively deliver photothermal agents and apoptotic peptides to tumor cell mitochondria, resulting in precise destruction to mitochondria and enhancing tumor cell inhibition at the subcellular organelle level.

Cuproptosis is an emerging mode of programmed cell death for tumor suppression but sometimes gets resisted by tumor cells resist under specific mechanisms. Inhibiting copper transporter ATPase (ATP7A) was found to disrupt copper ion homeostasis, thereby enhancing the effect of cuproptosis and eventually inhibiting tumor invasion and metastasis. In this study, we develop a multifunctional nanoplatfrom based on Cu9S8 (CAPSH), designed to enhance cuproptosis in tumor cells by specifically targeting ATP7A interference, while combining thermodynamic therapy with immune effects. The release of copper ions from CAPSH and the copper homeostasis interference by siRNA cooperatively increases the concentration of copper ions in tumor cells, which induces effectively cuproptosis and activates immune responses for suppressing development and metastasis of tumor. This nanoplatform simultaneously regulates cuproptosis from both principles of onset and development, facilitating the application of cuproptosis in tumor therapy. Cuproptosis is an emerging mode of programmed cell death for tumor suppression but limited by the copper ion regulatory mechanisms in most tumor cells. Here, this group develops a Cu9S8-based nanoplatform for breast cancer-targeting and cuproptosis-induction via ATP7A interference, thereby eliciting thermodynamic cancer therapy.

Efficient charge separation and transfer in photocatalytic systems continuously enable better water splitting for clean H-2 evolution. Herein, a feasible in situ growth hydrothermal strategy by coupling an ultrathin Ti3C2 (TC) MXene nanosheet electron acceptor with a Mn0.5Cd0.5S (MCS) nanoparticle donor is introduced to construct a multifunctional donor-acceptor MCS/TC photocatalyst with a strong Schottky junction toward green and sustainable photocatalytic H(2 )production. The strong Schottky junction realizes a rapid carrier directional separation and transportation. The ultrathin TC nanosheets, as an electron acceptor to catalyze proton reduction, can promote the separation of photogenerated electron-hole pairs and provide rich active sites for photocatalytic hydrogen production. Moreover, the optimal MCS/TC-10 (10 wt % TC) photocatalyst provides a highly stable photocatalytic H(2 )activity, up to 3730 mu mol h(-1) g(-1), which is 9 times higher than that of Mn0.5Cd0.5S solid solution. This work will inspire the development of design principles for accelerating charge transfer for efficient photocatalytic green H-2 production.

The rational design and fabrication of semiconductor heterojunctions may significantly optimize the photocatalytic activity in the realm of the photodegradation of organic pollutants, yet the construction of ternary heterojunction is rarely investigated. Herein, we report a novel and facile synthesis route that exploits electrostatic spinning combined with hydrothermal strategy to prepare ternary In2S3/CeO2/TiO2 heterojunction photocatalysts. The ternary composites formed among TiO2, CeO2, and In2S3 demonstrate a special energy band relationship, which can significantly expand light absorption to the visible region as well as efficiently separate the photogenerated charge carriers. Detailed characterization of as-obtained samples is carried out employing XRD, XPS, SEM, and TEM to resolve the phase composition and microstructure. Furthermore, UV-vis-DRS and PL indicate that the In2S3/CeO2/TiO2 has the higher light-harvesting efficiency and lower in the electron-hole recombination rate in the In2S3/CeO2/TiO2. Photocatalytic degradation performances and density functional theory calculations verify that the In2S3/CeO2/TiO2 ternary heterojunction with appropriate molar ratio delivers optimal photodegradation performance of tetracycline (95.4%) and methyl orange (96.2%) after 120 min under simulated sunlight irradiation, resulting from the synergistic effects of expanding the sunlight utilization and expediting the charge transfer. This work not only comprehensively investigates the application of ternary heterojunction, covering the preparation of catalysts and photocatalytic mechanisms, but also provides an innovative direction for pollutant removal.

Highly active and stable bifunctional electrocatalysts towards oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are necessary for practical fuel cells, metal-air batteries, and water splitting. Herein, we report a series of bifunctional Co3V2O8-T (T = temperature/degrees C) electrocatalysts by using Co-carbon electrospun nanofiber as a template, followed by a one-step calcination process. As expected, the developed Co3V2O8-400 nanofiber electrocatalyst shows a very small Tafel slope of 43 and 63 mV dec(-1) for the ORR and OER in the alkaline solution, respectively. In addition, density functional theory (DFT) calculations reveal that the metallic conductivity and interface V-Co interaction of Co3V2O8-400 nanofiber boost ORR and OER electrocatalytic reactions.

siRNA interference therapy can silence tumor cell target genes and specifically regulate tumor cell behavior and function, which is an effective antitumor therapy. However, in somatic circulation, naked siRNAs are not only susceptible to degrade, but it is also difficult to realize the tumor cells' internalization. Therefore, novel siRNA delivery vectors that could promote efficacy need to be developed urgently. Here, we designed high-surface gold nanostars (GNS-P) which are decorated with cationic tumor-targeting peptide as an efficient and functional siRNA delivery nanoplatform for tumor therapy. The positively charged amino acid sequence and huge surface area enabled the vector to load a large amount of siRNA, while the tumor-targeting peptide sequence and nano size enabled it to rapidly and precisely target the tumor regions for fast and effective siRNA delivery. This tumor-targeting nanoplatform, GNS-P, displayed good biocompatibility, low toxicity and an extraordinary tumor accumulation capability.

The multi-modal imaging contrast agent has been attracted an increased interest to the tumor detecting and diagnosis in these recent years since the multi-modal imaging technology combines the advantages of several medical imaging modalities. A water-soluble fullerenol probe containing glypican-3 monoclonal antibody (GPC3-mAb) group mAb-GPC3-C60(OH)10-(TMIO)3-(NI)3 was synthesized by the incorporation of 5-formyl-1,1,3,3-tetramethylisoindolin-2-yloxyl (FTMIO), naphthalimide (NI) and GPC3-mAb as a tumor-targeting group into fullerenol C60(OH)11. This nanomaterial was further characterized by FTIR, UV, MS, fluorescence, etc., and then its properties including electron paramagnetic resonance (EPR), particle size, electrophoresis, electrochemical assay, cell cytotoxicity, cell uptake and fluorescent imaging of HeLa tumor cells in vitro were also evaluated. Experiment results indicated that mAb-GPC3-C60(OH)10-(TMIO)3-(NI)3 had similar fluorescent properties as NI and similar electrochemical and redox properties as 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO). Moreover, mAb-GPC3-C60(OH)10-(TMIO)3-(NI)3 possessed low cell cytotoxicity, good fluorescence and good tumor-targeting property. Meanwhile, mAb-GPC3-C60(OH)10-(TMIO)3-(NI)3 can be taken up highly by HeLa tumor cells, achieve good green fluorescent imaging in tumor cells and highly enhance the contrast of fluorescent images. Therefore, mAb-GPC3-C60(OH)10-(TMIO)3-(NI)3 can disperse homogeneously in aqueous solution and be used as a potential tumor-targeting dual-modal contrast agent for EPR imaging/fluorescence imaging (EPRI/FI).

ObjectivesTo investigate the role of hepatocyte growth factor (HGF)/c-Met signaling in oral malignant transformation. MethodsWe used immunohistochemistry to investigate HGF and c-Met expression in 53 oral squamous cell carcinoma (OSCC) specimens and 21 adjacent nontumor specimens and evaluated the associations between HGF and c-Met expression and clinicopathological parameters. Additionally, HGF-overexpression transgenic (HGF-Tg) and wild-type (Wt) mice were treated with 4-nitroquinoline-1-oxide (4NQO) to induce oral carcinogenesis for 16 weeks. At 16, 20, and 24 weeks, tongue lesions were collected for clinical observation; estimation of HGF, c-Met, and PCNA expression; apoptosis (TUNEL) assays; and RNA sequencing (RNA-seq). ResultsHGF and c-Met were positively expressed in 92.5% and 64% of OSCC samples, respectively. High HGF expression was significantly associated with smaller tumor size (p = 0.006) and inferior TNM stage (p = 0.032). No correlation between HGF and c-Met levels and other clinical parameters or prognosis was noted. In addition, HGF and c-Met expression was elevated in 4NQO-induced lesions of Wt mice. Compared with Wt mice, HGF-Tg mice have lower tumor incidence, number, volume, and lesion grade. In addition, the percentage of PCNA-positive cells in Wt mice was significantly higher than that in HGF-Tg mice at different time points. At 16 weeks, HGF-Tg mice exhibited less apoptotic cells compared with Wt mice (p < 0.000), and these levels gradually increased until the levels were greater than that of Wt mice at 24 weeks (p < 0.000). RNA-seq data revealed that 140 genes were upregulated and 137 genes were downregulated in HGF-Tg mice. KEGG enrichment analysis showed that upregulated differentially expressed genes (DEGs) are highly correlated with oxidative and metabolic signaling and that downregulated DEGs are related to MAPK and PI3K-AKT signaling. ConclusionsHGF and c-Met expression is upregulated in OSCC tissues and is associated with the occurrence and development of OSCC. HGF overexpression in normal oral epithelial tissue can inhibit 4NQO-induced tumorigenesis potentially through inhibiting proliferation and accelerating apoptosis via MAPK and PI3K-AKT signaling.