Portable Photoacoustic Analytical System Combined with Wearable Hydrogel Patch for pH Monitoring in Chronic Wounds.

Timely diagnosis, monitoring, and management of chronic wounds play crucial roles in improving patients' quality of life, but clinical evaluation of chronic wounds is still ambiguous and relies heavily on the experience of clinician, resulting in increased social and financial burden and delay of optimal treatment. During the different stages of the healing process, specific and dynamic changes of pH values in the wound exudate can be used as biomarkers to reflect the wound status. Herein, a pH-responsive agent with well-behaved photoacoustic (PA) properties, nitrazine yellow (NY), was incorporated in poly(vinyl alcohol)/sucrose (PVA/Suc) hydrogel to construct a wearable pH-sensing patch (PVA/Suc/NY hydrogel) for monitoring of pH values during chronic wound healing. According to Rosencwaig-Gersho theory and the combination of 3D printing technology, the PA chamber volume and chopping frequency were systematically optimized to improve the sensitivity of the PA analytical system. The prepared PVA/Suc/NY hydrogel patch had excellent mechanical properties and flexibility and could maintain conformal contact with skin. Moreover, combined with the miniaturized PA analytical device, it had the potential to detect pH values (5.0-9.0) free from the color interference of blood and therapeutic drugs, which provides a valuable strategy for wound pH value monitoring by PA quantitation. This strategy of combining the wearable hydrogel patch with portable PA analysis offers broad new prospects for the treatment and management of chronic wounds due to its features of simple operation, time savings, and anti-interference.

Manganese-enriched prussian blue nanohybrids with smaller electrode potential and lower charge transfer resistance to enhance combination therapy.

Prussian blue (PB) is authenticated in clinical treatment, while it generally exhibits unfavorable chemodynamic therapy (CDT) performance. Herein, we developed manganese-doped prussian blue (PBM) nanoparticles to significantly enhance both CDT and photothermal therapy (PTT) effect. The lower redox potential of Mn3+/2+ (0.088 V) in PBM against that of Fe2+/3+ (0.192 V) in PB leads to favorable electron transfer of PBM with respect to PB. Besides, PBM has a lower charge-transfer resistance (Rct) of 2.98 Ω than 4.83 Ω of PB. Once PBM entering the tumor microenvironment (TME), Mn3+ may be readily reduced by glutathione (GSH) and therein to enhance intracellular oxidative stress. Meanwhile, the superoxide dismutase (SOD)-like activity of PBM facilitates the conversion of endogenous superoxide (O2•-) into H2O2. Mn2+ subsequently catalyzes H2O2 to generate toxic hydroxyl radicals (•OH). Notably, the PBM plus laser irradiation can effectively trigger a robust immunogenic cell death (ICD) due to the combination therapy of CDT and PTT. Additionally, the mice treated by PBM followed by laser irradiation efficiently avoided splenomegaly and lung metastasis, along with significant up-regulation of the Stimulator of Interferon Genes (STING) expression. Overall, PBM significantly inhibits tumor growth and metastasis, making it a promising multifunctional nanoplatform for cancer treatment.

Continuous microalgal culture module and method of culturing microalgae containing macular pigment.

This study established and investigated continuous macular pigment (MP) production with a lutein (L):zeaxanthin (Z) ratio of 4-5:1 by an MP-rich Chlorella sp. CN6 mutant strain in a continuous microalgal culture module. Chlorella sp. CN6 was cultured in a four-stage module for 10 days. The microalgal culture volume increased to 200 L in the first stage (6 days). Biomass productivity increased to 0.931 g/L/day with continuous indoor white light irradiation during the second stage (3 days). MP content effectively increased to 8.29 mg/g upon continuous, indoor white light and blue light-emitting diode irradiation in the third stage (1 day), and the microalgal biomass and MP concentrations were 8.88 g/L and 73.6 mg/L in the fourth stage, respectively. Using a two-step MP extraction process, 80 % of the MP was recovered with a high purity of 93 %, and its L:Z ratio was 4-5:1.

Molecular modification and biotechnological applications of microbial aspartic proteases.

The growing preference for incorporating microbial aspartic proteases in industries is due to their high catalytic function and high degree of substrate selectivity. These properties, however, are attributable to molecular alterations in their structure and a variety of other characteristics. Molecular tools, functional genomics, and genome editing technologies coupled with other biotechnological approaches have aided in improving the potential of industrially important microbial proteases by addressing some of their major limitations, such as: low catalytic efficiency, low conversion rates, low thermostability, and less enzyme yield. However, the native folding within their full domain is dependent on a surrounding structure which challenges their functionality in substrate conversion, mainly due to their mutual interactions in the context of complex systems. Hence, manipulating their structure and controlling their expression systems could potentially produce enzymes with high selectivity and catalytic functions. The proteins produced by microbial aspartic proteases are industrially capable and far-reaching in regulating certain harmful distinctive industrial processes and the benefits of being eco-friendly. This review provides: an update on current trends and gaps in microbial protease biotechnology, exploring the relevant recombinant strategies and molecular technologies widely used in expression platforms for engineering microbial aspartic proteases, as well as their potential industrial and biotechnological applications.

Harmonization of distributed multi-center analysis based on dried blood spot reference materials supporting the screening of neonatal inherited metabolic disorders.

BACKGROUND: The standardization of quantification data is critical for ensuring the reliability and measurement traceability in the screening of neonatal inherited metabolic disorders. However, the availability of national certified reference materials is limited in China. METHODS: In this study, we developed a series of dried blood spot (DBS) reference materials containing 9 amino acids (AA) and 10 acylcarnitines (AC) for neonatal screening. Four levels of the reference materials were measured with tandem mass spectrometry (MS/MS) by seven laboratories using different commercial In Vitro Diagnostic Device (IVD) kits. Then, 100 clinical samples were measured using both derivatization and non-derivatization methods by the same laboratory. RESULTS: We found high homogeneity and stability at all levels of the reference materials, with the coefficient of variation (CV) of the analytes less than 15%. These reference materials can be used to assess the testing capabilities of different laboratories. Our test also revealed that the correction factors (CF) calculated by the reference materials, along with clinical samples, could increase the consistency for different kits. CONCLUSION: The DBS reference materials proposed in this study provide reliability for the harmonization in multi-center analysis for the screening of neonatal inherited metabolic disorders. And applying our correction method for the screening could improve the data consistency of the DBS samples prepared by different methods.

GSH-depleting metal-polyphenol-network nanoparticles with dual enzyme activities induce enhanced ferroptosis.

Ferroptosis is a non-apoptotic form of regulated cell death. The efficiency of ferroptosis is restrained in the tumor microenvironment (TME) by overexpression of glutathione (GSH) and insufficient production of hydrogen peroxide (H2O2). In this work, theranostic nanoparticles Ce-aMOFs@Fe3+-EGCG, termed MEFs, are developed by coating uniform Ce-based amorphous metal-organic frameworks (Ce-aMOFs) with epigallocatechin gallate (EGCG) and Fe3+. Fe3+ is chelated by the adjacent phenol hydroxyl groups in EGCG. In the tumor cell interior, overexpressed GSH and weak acidic medium degrade the coating to release Fe3+ and EGCG accompanied by exposure of Ce-aMOFs. Fe3+ and EGCG consume GSH along with turning Fe3+ into Fe2+. Ce-aMOFs act as a nanozyme possessing dual-enzymatic activities, i.e. superoxide dismutase (SOD)- and phosphatase-like activities. In the TME, Ce-aMOFs catalyze the conversion of endogenous superoxide (O2˙-) into H2O2, and Fe2+ catalyzes H2O2 to generate toxic hydroxyl radicals (˙OH), which may further induce tumor cell death through ferroptosis. In addition, the phosphatase-like activity of Ce-aMOFs may sustainably dephosphorylate NADPH and effectively inhibit intracellular biosynthesis of GSH. Therefore, MEFs ensure down-regulation of intracellular GSH levels and up-regulation of oxidative pressure, which enhance the ferroptosis effect.

Application Value of 64-slice Multidetector Spiral CT Contrast-enhanced Scan in Maxillofacial Soft Tissue Hypervascular Tumours.

OBJECTIVE: To evaluate the diagnostic ability and clinical imaging features in maxillofacial soft tissue hypervascular tumours by 64-slice multidetector spiral computed tomography (64-MDCT) contrast-enhanced scanning. METHODS: In a retrospective study of 21 cases of hypervascular tumours, the degree of blood supply and indexes were assessed, and the pathological results were used as the diagnostic gold standard to evaluate the sensitivity and specificity of 64-MDCT plain scan and enhanced CT in the diagnosis of oral and maxillofacial soft tissue hypervascular tumours, using the receiver operating characteristic curve to analyse and evaluate the efficacy. RESULTS: Among 21 patients, the diagnostic accuracy of 64-MDCT contrast-enhanced scan was 90.48%, the area under the curve of venous phase CT value was 0.80, the sensitivity was 83.30% and the specificity was 72.73%. CONCLUSION: 64-MDCT contrast-enhanced scan can be used to evaluate the blood supply of maxillofacial soft tissue hypervascular tumours before an operation. The CT value in the venous phase of tumours has the highest diagnostic effectiveness, which can reduce the risk of blood loss during surgery for maxillofacial hypervascular tumours. In addition, it has certain guiding significance for the formulation of clinical treatment plans.

Heme Oxygenase-1 as a Predictive Marker for Spontaneous Bacterial Peritonitis in Cirrhotic Patients with Ascites.

OBJECTIVE: Identifying a predictive biomarker for spontaneous bacterial peritonitis (SBP) is of crucial importance in cirrhotic patients with ascites. This study was designed to identify the predictive value of serum or ascitic heme oxygenase-1 (HO-1) for SBP in this population. METHODS: In this cohort study, 60 patients with liver cirrhosis and ascites accompanied by SBP (studied cohort, n=26) or not (control cohort, n=34) were retrospectively included. HO-1 levels in the serum and ascites were detected by ELISA. The predictive performance of HO-1 was evaluated by calculating the area under the curve (AUC) in receiver operating characteristic (ROC) curve analysis. RESULTS: The HO-1 level of SBP patients was significantly higher than that of non-SBP patients both in the serum and ascites (p<0.001). Serum, ascites HO-1, and their combination displayed an AUC of 0.897 (95% CI, 0.808-0.986), 0.825 (95% CI, 0.708-0.941), and 0.902 (95% CI, 0.817-0.986) for discriminating SBP from non-SBP patients. HO-1 level between serum and ascites had a higher correlation in patients in a Child-Pugh B stage (R=0.691, p<0.001) than in the Child-Pugh C stage (R=0.475, p=0.014). The correlation between HO-1 level and inflammatory factors or biochemical parameters was observed in SBP patients and presented in a Child-Pugh stage-dependent manner. CONCLUSION: HO-1 level has the ability to predict the occurrence of SBP in cirrhotic patients with ascites which has the potential to be a biomarker for the early prediction of SBP and move into the clinical setting. However, the Child-Pugh stage should be considered when using the HO-1 as a predictive biomarker.

A Low-Cost Fertilizer Medium Supplemented with Urea for the Lutein Production of Chlorella sp. and the Ability of the Lutein to Protect Cells against Blue Light Irradiation.

This study aimed to investigate the use of organic fertilizers instead of modified f/2 medium for Chlorella sp. cultivation, and the extracted lutein of the microalga to protect mammal cells against blue-light irradiation. The biomass productivity and lutein content of Chlorella sp. cultured in 20 g/L fertilizer medium for 6 days were 1.04 g/L/d and 4.41 mg/g, respectively. These values are approximately 1.3- and 1.4-fold higher than those achieved with the modified f/2 medium, respectively. The cost of medium per gram of microalgal biomass reduced by about 97%. The microalgal lutein content was further increased to 6.03 mg/g in 20 g/L fertilizer medium when supplemented with 20 mM urea, and the cost of medium per gram lutein reduced by about 96%. When doses of ≥1 µM microalgal lutein were used to protect mammal NIH/3T3 cells, there was a significant reduction in the levels of reactive oxygen species (ROS) produced by the cells in the following blue-light irradiation treatments. The results show that microalgal lutein produced by fertilizers with urea supplements has the potential to develop anti-blue-light oxidation products and reduce the economic challenges of microalgal biomass applied to carbon biofixation and biofuel production.

IGF2BP2 promotes colorectal cancer progression by upregulating the expression of TFRC and enhancing iron metabolism.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, ranking third for morbidity and mortality worldwide. At present, no effective control method is available for this cancer type. In tumor cells, especially iron metabolization, is necessary for its growth and proliferation. High levels of iron are an important feature to maintain tumor growth; however, the overall mechanism remains unclear. METHODS: We used western blotting, immunohistochemistry (IHC) and real-time quantitative PCR to analyze the expression of IGF2BP2 in cell lines and tissues. Further, RNA-sequencing, RNA immunoprecipitation and methylated RNA immunoprecipitation experiments explored the specific binding of target genes. Moreover, the RNA stability assay was performed to determine the half-life of genes downstream of IGF2BP2. In addition, the Cell Counting Kit-8, colony formation assay, 5-ethynyl-2'-deoxyuridine assay and flow cytometry were used to evaluate the effects of IGF2BP2 on proliferation and iron metabolism. Lastly, the role of IGF2BP2 in promoting CRC growth was demonstrated in animal models. RESULTS: We observed that IGF2BP2 is associated with iron homeostasis and that TFRC is a downstream target of IGF2BP2. Further, overexpression of TFRC can rescue the growth of IGF2BP2-knockdown CRC cells. Mechanistically, we determined that IGF2BP2 regulates TFRC methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Furthermore, using animal models, we observed that IGF2BP2 promotes CRC growth. CONCLUSION: IGF2BP2 regulates TFRC mRNA methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Our study highlights the key roles of IGF2BP2 in CRC carcinogenesis and the iron transport pathways.

[Extracts of Poria cocos polysaccharides improves alcoholic liver disease in mice via CYP2E1 and NF-κB inflammatory pathways].

The present study investigated the effect of extract of Poria cocos polysaccharides(PCP) on cytochrome P450 2 E1(CYP2 E1) and nuclear factor κB(NF-κB) inflammatory signaling pathways in alcoholic liver disease(ALD) mice and explored its protective effect and mechanism. Sixty male C57 BL/6 N mice of SPF grade were randomly divided into a control group, a model group, a positive drug group(bifendate, 200 mg·kg~(-1)), and high-(200 mg·kg~(-1)) and low-dose(50 mg·kg~(-1)) PCP groups. Gao-binge mo-del was induced and the mice in each group were treated correspondingly. Liver morphological and pathological changes were observed and organ index was calculated. Serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected. Malondialdehyde(MDA) and superoxide dismutase(SOD) in liver tissues were detected by assay kits. The levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were detected by ELISA. The activation of macrophages was observed by immunofluorescence staining and protein expression of CYP2 E1, Toll-like receptor 4(TLR4), NF-κB p65, and phosphorylated NF-κB p65(p-NF-κB p65) were analyzed by Western blot. The ALD model was properly induced. Compared with the model group, the PCP groups significantly improved the pathological injury of liver tissues. Immunofluorescence staining revealed that compared with the model group, the groups with drug intervention showed decreased macrophages in liver tissues. Additionally, the PCP groups showed reduced ALT, AST, MDA, IL-6, and TNF-α(P<0.05), and potentiated activity of SOD(P<0.01). PCP extract has the protective effect against alcoholic liver injury in mice, and the underlying mechanism may be related to the regulation of the expression of CYP2 E1 and inhibition of TLR4/NF-κB inflammatory signaling pathway to reduce oxidative stress and inflammatory injury, thereby inhibiting the development of ALD.

Ionic liquids enable the preparation of a copper-loaded gel with transdermal delivery function for wound dressings.

Antibacterial hydrogel dressings play an important role in wound healing and infection treatment. The majority of hydrogels are obtained through chemical cross-linking and complex synthesis or processing. Copper ions (Cu2+) have been involved in sterilization; however, their direct use may lead to high local concentrations and heavy metal toxic side effects. Herein, dopamine (DA) was polymerized in situ along a polyvinyl alcohol (PVA) chain and chelated copper ions (Cu2+) to form a mixture. Ionic liquid (IL) choline-glycolate (CGLY) was added to the mixture to form an ionic gel. CGLY promotes gel formation through intermolecular hydrogen bonds with the polymer chains and avoids the use of toxic chemical crosslinking agents. Meanwhile, CGLY can also promote the release of Cu2+ and generate hydrogel free radicals (˙OH) in the wound through chemodynamic therapy to kill drug-resistant bacteria. In addition, the excellent transdermal property of CGLY enables the released Cu2+ to stimulate cell migration and accelerate wound healing. The gel exhibits favorable biocompatibility and its use has been demonstrated in skin infection therapy of mice.

Chalcone derivatives ameliorate lipopolysaccharide-induced acute lung injury and inflammation by targeting MD2.

Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are known as the common causes of respiratory failure in critically ill patients. Myeloid differentiation 2 (MD2), a co-receptor of toll like receptor 4 (TLR4), plays an important role in LPS-induced ALI in mice. Since MD2 inhibition by pharmacological inhibitors or gene knockout significantly attenuates ALI in animal models, MD2 has become an attractive target for the treatment of ALI. In this study we identified two chalcone-derived compounds, 7w and 7x, as new MD2 inhibitors, and investigated the therapeutic effects of 7x and 7w in LPS-induced ALI mouse model. In molecular docking analysis we found that 7w and 7x, formed pi-pi stacking interactions with Phe151 residue of the MD2 protein. The direct binding was confirmed by surface plasmon resonance analysis (with KD value of 96.2 and 31.2 µM, respectively) and by bis-ANS displacement assay. 7w and 7x (2.5, 10 µM) also dose-dependently inhibited the interaction between lipopolysaccharide (LPS) and rhMD2 and LPS-MD2-TLR4 complex formation. In mouse peritoneal macrophages, 7w and 7x (1.25-10 µM) dose-dependently inhibited LPS-induced inflammatory responses, MAPKs (JNK, ERK and P38) phosphorylation as well as NF-κB activation. Finally, oral administration of 7w or 7x (10 mg ·kg-1 per day, for 7 days prior LPS challenge) in ALI mouse model significantly alleviated LPS-induced lung injury, pulmonary edema, lung permeability, inflammatory cells infiltration, inflammatory cytokines expression and MD2/TLR4 complex formation. In summary, we identify 7w and 7x as new MD2 inhibitors to inhibit inflammatory response both in vitro and in vivo, proving the therapeutic potential of 7w and 7x for ALI and inflammatory diseases.

Early life exposure to air pollution and cell-mediated immune responses in preschoolers.

BACKGROUND: Exposure to air pollution has been linked with altered immune function in adults, but little is known about its effects on early life. This study aimed to investigate the effects of exposure to air pollution during prenatal and postnatal windows on cell-mediated immune function in preschoolers. METHODS: Pre-school aged children (2.9 ± 0.5 y old, n = 391) were recruited from a mother-child cohort study in Wuhan, China. We used a spatial-temporal land use regression (LUR) model to estimate exposures of particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5) and ≤10 µm (PM10), and nitrogen dioxide (NO2) during the specific trimesters of pregnancy and the first two postnatal years. We measured peripheral blood T lymphocyte subsets and plasma cytokines as indicators of cellular immune function. We used multiple informant models to examine the associations of prenatal and postnatal exposures to air pollution with cell-mediated immune function. RESULTS: Prenatal exposures to PM2.5, PM10, and NO2 during early pregnancy were negatively associated with %CD3+ and %CD3+CD8+ cells, and during late pregnancy were positively associated with %CD3+ cells. Postnatal exposures to these air pollutants during 1-y or 2-y childhood were positively associated with IL-4, IL-5, IL-6, and TNF-α. We also observed that the associations of prenatal or postnatal air pollution exposures with cellular immune responses varied by child's sex. CONCLUSIONS: Our results suggest that exposure to air pollution during different critical windows of early life may differentially alter cellular immune responses, and these effects appear to be sex-specific.

Lowering energy consumption for fermentable sugar production from Ramulus mori: Engineered xylanase synergy and improved pretreatment strategy.

Biorefinery of Ramulus mori with lower energy consumption through improved enzyme and pretreatment strategies was reported. Directed evolution and saturation mutagenesis were used for the modification of xylanase, the yield of fermentable sugars and the degree of synergy (DS) were determined for different pretreatment (seawater/non-seawater) and enzyme treatment groups (xylanase/cellulase/co-treatment). The dominant mutant I133A/Q143Y of Bispora sp. xylanase XYL10C_ΔN was obtained with improved specific activity (1860 U/mg), catalytic efficiency (1150 mL/s∙mg) at 40 °C, and thermostability (T50 increased by 7 °C). With the pretreatment of seawater immersion, the highest yield of fermentable sugars for Ramulus mori at 40 °C reached 199 µmol/g when hydrolyzed with cellulase and I133A/Q143Y, with the highest DS of 2.6; this was 4.5-fold that of the group hydrolyzed by cellulase alone with non-seawater pretreatment. Thus, bioconversion of reducing sugar from Ramulus mori was improved significantly at lower temperatures, which provides an efficient and energy-saving wayfor biofuel production.

Loop engineering of a thermostable GH10 xylanase to improve low-temperature catalytic performance for better synergistic biomass-degrading abilities.

Lignocellulosic biorefining for producing biofuels poses technical challenges. It is usually conducted over a long time using heat, making it energy intensive. In this study, we lowered the energy consumption of this process through an optimized enzyme and pretreatment strategy. First, the dominant mutant M137E/N269G of Bispora sp. MEY-1XYL10C_ΔN was obtained by directed evolution with highcatalytic efficiency (970 mL/s∙mg)and specific activity (2090 U/mg)at 37 °C, and thermostability was improved (T50 increased by5 °C). After pretreatment with seawater immersionfollowing steam explosion,bagasse was co-treated with cellulase and M137E/N269G under mild conditions (37 °C), the resulting highest yield of fermentable sugars reached 219 µmol/g of bagasse,46% higher than that of the non-seawater treatment group, with the highest degree of synergy of 2.0. Pretreatment with seawater following steam explosion and synergistic hydrolysis through high activity xylanase and cellulase helped to achieve low energy degradation of lignocellulosic biomass.

Mutual Benefit between Cu(II) and Polydopamine for Improving Photothermal-Chemodynamic Therapy.

Combination therapy has attracted extensive interest in alleviating the shortcomings of monotherapy and enhancing the treatment efficacy. In this work, hollow mesoporous silica nanoparticles (HMSNs) play the role of nanocarriers in the delivery of Cu(II)-doped polydopamine (PDA), termed as HMSNs@PDA-Cu, for synergistic therapy. PDA acts as a traditional photothermal agent to realize photothermal treatment (PTT). Chemodynamic therapy (CDT) is realized by the reaction of Cu(II) with intracellular glutathione (GSH), and subsequently, the generated Cu(I) reacts with H2O2 to produce toxic hydroxyl radical (•OH) through a Fenton-like reaction. The photothermal performance of PDA is improved after its coordination with Cu(II). On the other hand, PDA exhibits superoxide dismutase (SOD)-mimicking activity. PDA converts O2•- to H2O2 and improves the production of H2O2, which promotes the therapeutic effect of CDT. Moreover, the high temperature caused by PTT further enhances the yield of •OH for CDT. This nanotheranostic platform perfectly applied to the tumor depletion of mice, presenting great potential for cancer metastasis therapy in vitro and in vivo.

Lycorine hydrochloride induces reactive oxygen species-mediated apoptosis via the mitochondrial apoptotic pathway and the JNK signaling pathway in the oral squamous cell carcinoma HSC-3 cell line.

Poor drug efficacy is a prominent cause of oral squamous cell carcinoma (OSCC) treatment failure. Although increased efforts in developing OSCC therapeutic strategies have been achieved in recent decades, the 5-year survival rate of patients with OSCC remains poor and effective drugs to treat OSCC are lacking. The aim of the present study was to investigate the apoptotic effect caused by lycorine hydrochloride (LH) and to identify its mechanism in the OSCC HSC-3 cell line. The findings demonstrated that LH effectively induced HSC-3 cell apoptosis and cell cycle arrest at the G0/G1 phase, resulting in the inhibition of cell proliferation. Furthermore, it was found that LH increased reactive oxygen species (ROS) production, triggered mitochondrial membrane potential (MMP) disorder, enhanced the protein expression levels of Bax, Bim, cleaved caspase-9, caspase-3 and poly(ADP-ribose) polymerase 1 and decreased Mcl-1 expression. The protein expression levels of important members of the JNK signaling pathway, including phosphorylated (p)-JNK, p-mitogen-activated protein kinase kinase 4 and p-c-Jun, were significantly increased in LH-treated cells, accompanied by an increase in ROS. However, N-acetyl cysteine (NAC), a potent antioxidant, reversed the upregulated mRNA expression of c-Jun, as well as the enhanced ROS production, the disorder of MMP and the apoptosis of HSC-3 cells induced by LH. These results suggested that LH may induce HSC-3 cell apoptosis via the ROS-mediated mitochondrial apoptotic pathway and the JNK signaling pathway, which indicated that LH may be a potential drug candidate for anti-OSCC therapy.

State-of-the-art advances of copper-based nanostructures in the enhancement of chemodynamic therapy.

Chemodynamic therapy (CDT) is a new emerging strategy for the in situ treatment of tumors. In the microenvironment of tumor cells, CDT may be achieved through the generation of reactive oxygen species (ROS), e.g., hydroxyl radicals (˙OH) and singlet oxygen (1O2), which induce the death of tumor cells. Copper (Cu) or other transition-metal ions catalyze the production of ˙OH by hydrogen peroxide (H2O2) through Fenton or Fenton-like reactions. With the development of advanced nanotechnology, nanotherapeutic systems with Cu-based nanostructures have received extensive attention and have been demonstrated for their wide applications in the design and construction of nanotherapeutic systems for CDT, along with multimodal synergistic therapy. Herein, the cutting-edge developments of Cu-based nanostructures in CDT are reviewed and discussed, by focusing on the monotherapy of CDT as well as synergistic treatments by hyphenating CDT with various therapeutic protocols, e.g., photothermal therapy (PTT), photodynamic therapy (PDT), sonodynamic therapy (SDT), and so on. In addition, the potential challenges and future perspectives are described in the improvement of CDT therapeutic efficacy, the enhancement of targeting capability, and mechanistic investigations on CDT therapy.

Poly(ionic liquid)-Gated CuCo2S4 for pH-/Thermo-Triggered Drug Release and Photoacoustic Imaging.

A novel hybrid drug nanocarrier is developed with CuCo2S4 nanoparticles as the core to be encapsulated by poly(ionic liquid) (PIL), that is, poly(tetrabutylphosphonium styrenesulfonate) (P[P4,4,4,4][SS]), as the shell. Doxorubicin (DOX) is loaded onto the PIL shell via electrostatic attraction involving amine in DOX and styrenesulfonate in PIL. pH- and thermal-responsive characteristics of P[P4,4,4,4][SS] endow the multifunctional hybrid nanocarrier system DOX-CuCo2S4@PIL with sensitive dual-stimuli-triggered drug release behaviors. The CuCo2S4 core converts near-infrared (NIR) irradiation into thermal energy to trigger the shrinkage of the PIL shell, which subsequently promotes drug release, and the pH-responsive release of DOX involves pH-sensitive electrostatic interaction of the PIL shell with DOX. A favorable controlled release of 90.5% is achieved under pH/thermo dual stimuli. In vitro experiments with MCF-7 cells well demonstrated that the drug release is controlled by the acidic intracellular environment with NIR irradiation. The CuCo2S4 core also serves as a photoacoustic (PA) imaging contrast agent, as demonstrated by in vivo treatment of the MCF-7-carrying mice.