Co-exposure to cadmium and triazophos induces variations at enzymatic and transcriptional levels in Opsariichthys bidens.

Heavy metals and pesticides are significant pollutants in aquatic environments, often leading to combined pollution and exerting toxic effects on aquatic organisms. With the rapid growth of modern industry and agriculture, heavy metal cadmium (Cd) and pesticide triazophos (TRI) are frequently detected together in various water bodies, particularly in agricultural watersheds. However, the combined toxic mechanisms of these pollutants on fish remain poorly understood. This experiment involved a 21-day co-exposure of Cd and TRI to the hook snout carp Opsariichthys bidens to investigate the toxic effects on liver tissues at both enzymatic and transcriptional levels. Biochemical analysis revealed that both individual and combined exposures significantly increased the content or activity of caspase-3 (CASP-3) and malondialdehyde (MDA). Moreover, the impact on these parameters was greater in the combined exposure groups compared to the corresponding individual exposure groups. These findings suggested that both individual and combined exposures could induce mitochondrial dysfunction and lipid peroxidation damage, with combined exposure exacerbating the toxicological effects of each individual pollutant. Furthermore, at the molecular level, both individual and combined exposures upregulated the expression levels of cu-sod, cat, and erß, while downregulating the expression of il-1. Similar to the patterns observed in the biochemical parameters, the combined exposure group exhibited a greater impact on the expression of these genes compared to the individual exposure groups. These results indicated that exposure to Cd, TRI, and their combination induced oxidative stress, endocrine disruption, and immunosuppression in fish livers, with more severe effects observed in the combined exposure group. Overall, the interaction between Cd and TRI appeared to be synergistic, shedding light on the toxic mechanisms by which fish livers responded to these pollutants. These findings contributed to the understanding of mixture risk assessment of pollutants and were valuable for the conservation of aquatic resources.

Epigenetic Reprogramming Potentiates ICAM1 Antibody Drug Conjugates in Preclinical Models of Melanoma.

Therapeutic benefits and underlying biomechanism(s) of antibody drug conjugates (ADC) in combination with other targeted therapeutics are largely unknown. Here, the synergy between ADC and epigenetic drug decitabine (DAC), a clinically approved DNA methylation inhibitor, in multiple preclinical models of melanoma specifically investigated. Mechanistically, the underlying biomechanisms of how DAC cooperatively worked with ICAM1 antibody conjugated DNA topoisomerase I inhibitor DXd (I1-DXd) is elucidated. DAC treatment significantly enhanced anti-tumor efficacy of I1-DXd by upregulating antigen expression, enhancing antibody internalization and potentiating tumor sensitivity by epigenetically reprogramming of melanoma. Meanwhile, I1-DXd/DAC combination also exerted regulatory effects on tumor microenvironment (TME) by enhancing tumor infiltration of innate and adaptive immune cells and improving penetration of ADCs with a boosted antitumor immunity. This study provides a rational ADC combination strategy for solid tumor treatment.

Screening and experimental validation of diagnostic gene in ulcerative colitis with anti-TNF-α therapy.

In clinical practice, the diagnosis of ulcerative colitis (UC) mainly relies on a comprehensive analysis of a series of signs and symptoms of patients. The current biomarkers for diagnosis of UC and prognostic prediction of anti-TNF-α therapy are inaccurate. The present study aimed to perform an integrative analysis of gene expression profiles in patients with UC. A total of seven datasets from the GEO database that met our strict inclusion criteria were included. After identifying differentially expressed genes (DEGs) between UC patients and healthy individuals, the diagnostic and prognostic utility of the DEGs were then analyzed via least absolute shrinkage and selection operator and support-vector machine recursive feature elimination. Subgroup analyses of the treated and untreated groups, as well as the treatment-response group and non-response group, were also performed. Furthermore, the relationship between the expressions of UC-related genes and infiltration of immune cells in the course of treatment was also investigated. Immunohistochemical (IHC) assay was used to verify the gene expression in inflamed UC tissues. When considering all the applied methods, DUOX2, PI3, S100P, MMP7, and S100A8 had priority to be defined as the characteristic genes among DEGs. The area under curve (AUC) of the five genes, which were all consistently over-expressed, based on an external validation dataset, were all above 0.94 for UC diagnosis. Four of the five genes (DUOX2, PI3, MMP7, and S100A8) were down-regulated between treatment-responsive and nonresponsive patients. A significant difference was also observed concerning the infiltration of immune cells, including macrophage and neutrophil, between the two groups (treatment responsive and nonresponsive). The changes in the expression of DUOX2 and MMP7 based on the IHC assay were highly consistent with the results obtained in the current study. This confirmed the mild to moderate diagnostic and predictive value of DUOX2 and MMP7 in patients with UC. The conducted analyses showed that the expression profile of the five identified biomarkers accurately detects UC, whereas four of the five genes evidently predicted the response to anti-TNF-α therapy.

Contextualizing the revised Patient Perception of Patient-Centeredness (PPPC-R) scale in primary healthcare settings: a validity and reliability evaluation study.

BACKGROUND: An English version of the Patient Perception of Patient-Centeredness (PPPC) scale was recently revised, and it is necessary to test this instrument in different primary care populations. AIM: This study aimed to assess the validity and reliability of a Chinese version of the PPPC scale. DESIGN: A mixed method was used in this study. The Delphi method was used to collect qualitative and quantitative data to address the content validity of the PPPC scale by calculating the Content Validity Index, Content Validity Ratio, the adjusted Kappa, and the Item Impact Score. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were used to assess the construct validity of the PPPC scale through a cross-sectional survey. The internal consistency was also assessed. SETTING/PARTICIPANTS: In the Delphi consultation, seven experts were consulted through a questionnaire sent by email. The cross-sectional survey interviewed 188 outpatients in Guangzhou city and 108 outpatients in Hohhot City from community health service centers or stations face-to-face. RESULTS: The 21 items in the scale were relevant to their component. The Item-level Content Validity Index for each item was higher than 0.79, and the average Scale-level content validity index was 0.97 in each evaluation round. The initial proposed 4-factor CFA model did not fit adequately. Still, we found a 3-factor solution based on our EFA model and the validation via the CFA model (model fit: [Formula: see text], P < 0.001, RMSEA = 0.044, CFI = 0.981; factor loadings: 0.553 to 0.888). Cronbach's α also indicated good internal consistency reliability: The overall Cronbach's α was 0.922, and the Cronbach's α for each factor was 0.851, 0.872, and 0.717, respectively. CONCLUSIONS: The Chinese version of the PPPC scale provides a valuable tool for evaluating patient-centered medical service quality.

Squalene epoxidase promotes breast cancer progression by regulating CCNB1 protein stability.

BACKGROUND: Breast cancer (BC) is a prevalent malignancy affecting women, characterized by a substantial occurrence rate. Squalene epoxidase (SQLE) is a crucial regulator of ferroptosis and has been associated with promoting cell growth and invasion in different types of human cancers. This study aimed to investigate the functional significance of SQLE in BC and elucidate the underlying molecular mechanisms involved. METHODS: SQLE expression levels in BC tissues were evaluated using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry. Cell viability, invasion, migration, and cell cycle distribution were assessed using a combination of assays, including the Cell Counting Kit-8, EdU, colony formation, Transwell, and wound healing assays and flow cytometry analysis. Measurement of intracellular reactive oxygen species (ROS), malondialdehyde assay, and glutathione assay were utilized to investigate ferroptosis. Furthermore, co-immunoprecipitation and immunofluorescence assays were conducted to explore the correlation between SQLE and CCNB1. The in vivo tumor growth was evaluated by conducting a xenograft tumorigenicity assay to investigate the impact of SQLE. RESULTS: SQLE expression was significantly increased in BC, and higher SQLE expression levels were significantly associated with an unfavorable prognosis. In vitro functional assays revealed that the overexpression of SQLE markedly enhanced the proliferation, migration, and invasion capacities of BC cells. Furthermore, SQLE overexpression facilitated tumor growth in nude mice. Mechanistically, SQLE alleviated the ubiquitination modification of CCNB1, leading to enhanced stability of the CCNB1 protein and decreased intracellular ROS levels. Ultimately, this inhibited ferroptosis and facilitated the progression of BC. Our findings have provided insights into a crucial pathway by which elevated SQLE expression confers protection to BC cells against ferroptosis, thus promoting cancer progression. SQLE may serve as a novel oncological marker and a potential therapeutic target for BC progression. CONCLUSIONS: In conclusion, this study provides evidence that SQLE plays a regulatory role in BC progression by modulating CCNB1 and ferroptosis. These findings offer valuable insights into the role of SQLE in the pathogenesis of BC and demonstrate its potential as a therapeutic target for treating BC.

CircSNX25 mediated by SP1 promotes the carcinogenesis and development of triple-negative breast cancer.

Circular RNAs (circRNAs), according to a growing body of research, are thought to be important in the initiation and development of a number of cancers. However, more research is needed to fully understand how circRNAs work at the molecular level in triple-negative breast cancer (TNBC). RNA sequencing was conducted on four sets of TNBC samples and their corresponding adjacent noncancerous tissues (ANTs). The circSNX25 expression was assessed using quantitative real-time PCR in TNBC tissues and cells. Several in vitro and in vivo experiments were conducted in order to examine the function of circSNX25 in TNBC carcinogenesis. Through luciferase reporter and chromatin immunoprecipitation (ChIP) assays, we also investigated the potential regulation of circSNX25 biogenesis by specificity protein 1 (SP1). To further validate the relationship between circSNX25 and COPI coat complex subunit beta 1 (COPB1) in TNBC, we conducted circRNA pull-down and RNA immunoprecipitation (RIP) assays using the MS2/MS2-CP system. Online databases were analyzed to examine the clinical implications and prognostic value of COPB1 in TNBC. A higher circSNX25 expression levels were observed in tissues and cells of TNBC. Silencing circSNX25 notably inhibited TNBC cell proliferation, triggered apoptosis, and hindered tumor growth in vivo. Conversely, upregulation of circSNX25 had the opposite effects. Mechanistically, circSNX25 was found to physically interact with COPB1. Importantly, we identified that SP1 may enhance circSNX25 biogenesis. COPB1 levels were markedly higher in TNBC cells. Analysis of online databases revealed that TNBC patients with elevated COPB1 levels had a poorer prognosis. Our findings demonstrate that SP1-mediated circSNX25 promotes TNBC carcinogenesis and development. CircSNX25 may therefore serve as both a diagnostic and therapeutic biomarker for TNBC patients.

Molecular characteristics and prognosis of breast cancer patients with different level of HER2 positivity after adjuvant and neoadjuvant chemotherapy.

PURPOSE: HER2-low breast cancer (BC) has renewed interests of researchers worldwide. Here, we aimed to investigate the clinicopathological characteristics of patients with HER2-low, HER2-0 and HER2 ultra-low BC and make conclusion. METHODS: We collected cases of patients who were diagnosed as BC at Jingling General hospital. Immunohistochemistry was used to redefine HER2 scores. Kaplan-Meier methods and Cox proportional hazards regression analysis were used to compare survival. RESULTS: We found that HER2-low BC was more frequent in hormone receptor (HR)-positive BC patients and was associated with fewer T3-T4, lower breast conserving surgery rate and higher adjuvant chemotherapy rate. HER2-low BC patients had better overall survival (OS) compared to HER2-0 BC in premenopausal and stage II BC. Furthermore, HER2-0 BC patients had lower Ki-67 expression levels compared to HER2-ultra low and HER2-low BC in HR-negative BC. HER2-0 BC patients also had worse OS rate compared to those with HER2-ultra low BC in HR-positive BC. Finally, HER2-0 BC patients showed a higher pathological response rate compared to those with HER2-low BC after neoadjuvant chemotherapy. CONCLUSIONS: These findings suggest that HER2-low BC has distinct biology and clinical features compared to HER2-0 BC, and more investigation is needed to understand the biology of HER2-ultra low BC.

Microneedles loaded with glutathione-scavenging composites for nitric oxide enhanced photodynamic therapy of melanoma.

Photodynamic therapy (PDT) represents an attractive promising route for melanoma treatment. However, its therapeutic efficacy is compromised by inefficient drug delivery and high glutathione (GSH) levels in cancer cells. To overcome these challenges, microneedles (MNs) system loaded with GSH-scavenging nanocomposites was presented for nitric oxide (NO) enhanced PDT. The nanocomposites consisted of S-nitroso-N-acrylate penicillamine (SNAP; a NO donor) grafted fourth-generation polyamide amine dendrimer (G4) and chlorin e6 (Ce6). Upon local insertion of polyvinylpyrrolidone MNs, G4-SNAP/Ce6 composites were fast delivered and significantly amplified the therapeutic effects during PDT, via GSH depletion and reactive nitrogen species generation. Even with a single administration and low power light exposure, MNs with G4-SNAP/Ce6 effectively halt the tumor progression. The system demonstrated better cancer ablation efficacy than Ce6 alone toward melanoma. The strategy may inspire new ideas for future PDT-related therapy for skin tumors.

Mixture toxic effects of thiacloprid and cyproconazole on honey bees (Apis mellifera L.).

Pesticide exposure remains one of the main factors in the population decline of insect pollinators. It is urgently necessary to assess the effects of mixtures on pollinator risk assessments because they are often exposed to numerous agrochemicals. In the present study, we explored the mixture toxic effects of thiacloprid (THI) and cyproconazole (CYP) on honey bees (Apis mellifera L.). Our findings revealed that THI possessed higher acute toxicity to A. mellifera (96-h LC50 value of 216.3 mg a.i. L-1) than CYP (96-h LC50 value of 601.4 mg a.i. L-1). It's worth noting that the mixture of THI and CYP exerted an acute synergistic effect on honey bees. At the same time, the activities of detoxification enzyme cytochrome P450s (CYP450s) and neuro target enzyme Acetylcholinesterase (AChE), as well as the expressions of seven genes (CRBXase, CYP306A1, CYP6AS14, apidaecin, defensing-2, vtg, and gp-93) associated with detoxification metabolism, immune response, development, and endoplasmic reticulum stress, were significantly altered in the combined treatment compared with the corresponding individual exposures of THI or CYP. These data indicated that a mixture of THI and CYP could disturb the physiological homeostasis of honey bees. Our study provides a theoretical basis for in-depth studies on the impacts of pesticide mixtures on the health of honey bees. Our study also provides important guidance for the rational application of pesticide mixtures to protect pollinators in agricultural production effectively.

Novel n-i CeO2/a-Al2O3 Heterostructure Electrolyte Derived from the Insulator a-Al2O3 for Fuel Cells.

Heterostructure technologies have been regarded as promising methods in the development of electrolytes with high ionic conductivity for low-temperature solid oxide fuel cells (LT-SOFCs). Here, a novel semiconductor/insulator (n-i) heterostructure strategy has been proposed to develop composite electrolytes for LT-SOFCs based on CeO2 and the insulator amorphous alumina (a-Al2O3). The constructed CeO2/a-Al2O3 electrolyte exhibits an ionic conductivity of up to 0.127 S cm-1, and its fuel cell achieves a maximum power density (MPD) of 1017 mW cm-2 with an open-circuit voltage (OCV) of 1.14 V at 550 °C without the short-circuiting problem, suggesting that the introduction of a-Al2O3 can effectively suppress the electron conduction of CeO2. It is found that the potential energy barrier at the heterointerfaces caused by the ultrawide band gap of the insulator a-Al2O3 plays an important role in restraining electron conduction. Simultaneously, the thermoelectric effect of the insulator induces more oxygen vacancies because of interface charge compensation, which further promotes ionic transport and results in high ionic conductivity and fuel cell performance. This study presents a practical n-i heterostructure electrolyte design, and further research confirmed the advanced functionality of the CeO2/a-Al2O3 electrolyte. Our study may open frontiers in the field of developing high-efficiency electrolytes of LT-SOFCs using insulating materials such as amorphous alumina.

A broad cuproptosis landscape in inflammatory bowel disease.

Background: Cuproptosis, a genetic process of copper-dependent cell death linked to mitochondria respiration, demonstrates its correlation with inhibiting tumoral angiogenesis and motility. Recent studies have developed systematic bioinformatics frameworks to identify the association of cuproptosis with tumors but any non-neoplastic diseases. Therefore, against the background of an increased incidence of inflammatory bowel disease (IBD), the landscape of cuproptosis regulation in IBD is a critical need to be investigated. Methods: The differentially expressed cuproptosis-related genes (DECRGs) were identified with human sequencing profiles for four inflammatory digestive disorders. Another four independent IBD datasets from GEO were used as a validation cohort. And experimental mice model provides another validation method. Using single sample gene set enrichment analysis (ssGSEA), receiver operating characteristic (ROC) curve, CIBERSORT, and consensus clustering algorithms, we explored the association between immune score and cuproptosis-related genes, as well as the diagnostic value of these genes. Molecular docking screened potential interaction of IBD drugs with the structural regulator by Autodock Vina. Results: Cuproptosis-related regulators exhibited extensive differential expression in Crohn's Disease (CD), Ulcerative Colitis (UC), Celiac Disease (CEL), and IBD-induced cancer (IBD-CA) that share common differential genes (PDHA1, DBT, DLAT, LIAS). The differential expression of DECRGs was reverified in the validated cohort and immunohistochemistry assay. Moreover, the cell signaling pathways and ontology mainly focused on the mitochondrial respiratory function, which was highly enriched in Gene set enrichment analysis (GSEA). According to ssGSEA and ROC, when considering the four regulators, which showed robust association with immune infiltration in IBD, the area under the ROC (AUC) was 0.743. In addition, two clusters of consensus clustering based on the four regulators exhibit different immune phenotypes. According to molecular docking results, methotrexate gained the highest binding affinity to the main chain of key cuproptosis-related regulators compared with the remaining ten drugs. Conclusion: Cuproptosis-related regulators were widely linked to risk variants, immune cells, immune function, and drug efficacy in IBD. Regulation of cuproptosis may deeply influence the occurrence and development of patients with IBD.

Microneedle patch with "spongy coating" to co-load multiple drugs to treat multidrug-resistant melanoma.

Melanoma is the most aggressive skin malignancy that continues to increase in worldwide. The transferability and multidrug resistance lead to a high fatality rate. Synergistic administration of hydrophilic carboplatin (CBP) and hydrophobic vorinostat (SAHA) can be a reliable way to treat multidrug-resistant melanoma. However, the different physicochemical properties of multiple drugs make it difficult to achieve a convenient co-loading and an ideal synergistic treatment efficacy. To solve the problem, a microneedle patch with a porous "spongy coating" (PF-MNP) was fabricated. Firstly, (polyacrylic acid/polyethyleneimine)10 multilayers were fabricated on polymethyl methacrylate MNP. Then a "spongy coating" was achieved by acid treatment and freeze-drying. Due to the capillary effect, hydrophobic SAHA and hydrophilic CBP could be conveniently adsorbed step-by-step. The two drugs could distribute evenly on the surface, and the morphology of MNP remained good. The loading content of SAHA and CBP was easily regulated by adjusting the concentration of the adsorption solution, and MNP could quickly release most drugs within 30 min. The final in vivo experiments proved that CBP/SAHA co-loaded PF-MNP had the best therapeutic efficiency for multidrug-resistant melanoma. The MNP with a "spongy coating" showed potential to be a safe and efficient transdermal delivery platform for multiple drugs.

Polyamine synthesis enzyme AMD1 is closely related to the tumorigenesis and prognosis of human breast cancer.

Adenosylmethionine decarboxylase 1 (AMD1) has been implicated in carcinogenesis and tumor progression. However, the potential biomechanism and biological implications of AMD1 in breast cancer (BC) remain unclear. The purpose of this study was to investigate the effect of abnormal expression of AMD1 in BC. The expression of AMD1 in different human BC cell lines was studied by using western blotting and qRT-PCR. In vitro cell proliferation, clone formation, cell cycle and apoptosis assays were performed to explore the effect of AMD1 on cellular proliferation. Xenograft mouse models were established to elucidate the role of AMD1 in BC growth. The expression profiles of AMD1 in 28 pairs of BC tissues and adjacent noncancerous tissues (ANTs) were investigated by using western blotting and immunohistochemistry. The clinical implication and prognostic evaluation of AMD1 in BC were examined by excavating the online database. We found that the expression levels of AMD1 in BC cell lines were significantly higher than those in the normal human breast epithelial cell line MCF-10A. In addition, AMD1 potentiated proliferation, induced cell cycle progression and inhibited apoptosis in BC cells. Subcutaneous tumor xenografts also supported the promotive role of AMD1 in BC growth. We discovered that the level of AMD1 in BC tissues was significantly higher than that in ANTs. Using the online database, increased AMD1 was found to be associated with clinical indicators and predicted a poor prognosis in patients with BC. Our findings indicate that AMD1 elicits potent oncogenic effects on the malignant progression of BC. AMD1 might serve as a promising diagnostic biomarker and therapeutic target for patients with BC.

Polystyrene microplastics exacerbate experimental colitis in mice tightly associated with the occurrence of hepatic inflammation.

The potential health effects of microplastics (MPs) have become a public concern due to their ubiquitousness in the environment and life. Numerous studies have demonstrated that a high dose of MPs can adversely affect gastrointestinal health. However, few studies have focused on the impact of microplastics on patients' health with respect to gastrointestinal diseases. Inflammatory bowel disease (IBD) has emerged as a global disease with a rapidly increasing incidence. IBD, a specific gastrointestinal illness characterized by acute, chronic inflammation and intestinal barrier dysfunction, might increase sensitivity to MPs exposure. Herein, we investigated the impact and mechanism of PS-MPs on dextran sodium sulfate (DSS)-induced colitis. The results demonstrated that gavage with PS-MPs alone caused minimal effects on the intestinal barrier and liver status of mice. For mice with colitis, additional PS-MPs exposure caused a shorter colon length, aggravated histopathological damage and inflammation, reduced mucus secretion, and increased the colon permeability. Furthermore, PS-MPs exposure also increased the risk of secondary liver injury associated with inflammatory cell infiltration. These findings provide more histopathological evidence and suggest a need for more research on the health risk of MPs for sensitive individuals.

Dissolving microneedles with a biphasic release of antibacterial agent and growth factor to promote wound healing.

Infected wound healing is a complex and dynamic process affecting millions of people. Since wound healing contains multiple stages, it requires staged management to realize the early inhibition of infection and the subsequent promotion of wound healing. A key point is to design a biphasic release system with antibacterial agents and growth factors to promote wound regeneration. As a safe, efficient and painless transdermal drug delivery method, microneedles (MNs) have attracted widespread attention. Herein, we present dissolving MNs with the biphasic release of an antibacterial agent and a growth factor to promote wound healing. bFGF was first encapsulated in PLGA microspheres (bFGF@PLGA) and then co-loaded with free ofloxacin onto polyvinylpyrrolidone MNs. Owing to the fast dissolution of the substrate, ofloxacin was quickly released to rapidly inhibit infection, while the PLGA microspheres were left in the wound. Due to the slow degradation of PLGA, bFGF encapsulated in the PLGA microspheres was slowly released to further promote wound healing. In vivo studies demonstrated that the MNs with the biphasic release of antibacterial agent and growth factor exhibited a superior capability to promote wound healing. This biphasic release system combined with microneedles has a bright future in wound healing.

Polydopamine nanoparticles with different sizes for NIR-promoted gene delivery and synergistic photothermal therapy.

The combination of photothermal therapy and gene therapy has received increasing attention in tumor treatment. However, how to improve synergistic efficacy has become a new challenge. NIR light has a great potential in tumor treatment because of its considerable penetration depth and spatiotemporal controllability. Polydopamine is a popular photothermal conversion agent, which has desirable photothermal conversion ability and good biocompatibility. In this research, polydopamine-polyethyleneimine nanoparticles with diameters of 13 nm (SPPNPs) and 236 nm (LPPNPs) were prepared as gene carriers. The size of polydopamine nanoparticles had great effect on the complexes formation, photothermal conversion ability and gene transfection efficiency. After loading gene, the SPPNPs/gene and LPPNPs/gene complexes were about 60-80 nm and 240 nm respectively, indicating different styles of complexes formation. Both SPPNPs/gene and LPPNPs/gene complexes without NIR irradiation could achieve similar gene transfection efficiency as commercial lipofectamine 2000, while with lower cytotoxicity. Due to better photothermal conversion ability, the transfection level of LPPNPs/pGL-3 complexes increased to 4.5 times after NIR irradiation (2.6 W/cm2, 15 min), which ascribed to the quick escape of gene complexes from the endosome. The produced heat under NIR irradiation could also ablate tumor cells. So LPPNPs were chosen to deliver tumor suppressor gene p53 DNA to investigate the synergistic efficacy of gene/photothermal therapy. The tumor in KB tumor-bearing mice was almost eliminated after intratumoral injection, and the tumor inhibition efficacy of gene/photothermal synergistic therapy achieved to 99%. By combining NIR-promoted gene transfection and gene/photothermal synergistic therapy, the LPPNPs hold great promise in practical tumor treatment.

High Performance Low-Temperature Solid Oxide Fuel Cells Based on Nanostructured Ceria-Based Electrolyte.

Ceria based electrolyte materials have shown potential application in low temperature solid oxide fuel cells (LT-SOFCs). In this paper, Sm3+ and Nd3+ co-doped CeO2 (SNDC) and pure CeO2 are synthesized via glycine-nitrate process (GNP) and the electro-chemical properties of the nanocrystalline structure electrolyte are investigated using complementary techniques. The result shows that Sm3+ and Nd3+ have been successfully doped into CeO2 lattice, and has the same cubic fluorite structure before, and after, doping. Sm3+ and Nd3+ co-doped causes the lattice distortion of CeO2 and generates more oxygen vacancies, which results in high ionic conductivity. The fuel cells with the nanocrystalline structure SNDC and CeO2 electrolytes have exhibited excellent electrochemical performances. At 450, 500 and 550 °C, the fuel cell for SNDC can achieve an extraordinary peak power densities of 406.25, 634.38, and 1070.31 mW·cm-2, which is, on average, about 1.26 times higher than those (309.38, 562.50 and 804.69 mW·cm-2) for pure CeO2 electrolyte. The outstanding performance of SNDC cell is closely related to the high ionic conductivity of SNDC electrolyte. Moreover, the encouraging findings suggest that the SNDC can be as potential candidate in LT-SOFCs application.

A gene-coated microneedle patch based on industrialized ultrasonic spraying technology with a polycation vector to improve antitumor efficacy.

A coated microneedle patch is a reliable way to load gene on a surface as a transdermal gene delivery platform. But there are many limitations to the traditional methods to fabricate a coated microneedle patch, such as the fact that they are time consuming or the difficulty in controlling the loading content. In this research, ultrasonic spraying technology, as an industrialized production method, was first used to fabricate a gene-coated microneedle patch. First, the p53 expression plasmid (p53 DNA) was ultrasonically sprayed on a polycaprolactone (PCL) microneedle patch (D@MNP). To promote the transfection efficiency, polycation polyethylenimine (PEI), as a vector, was then ultrasonically sprayed on D@MNP (P@D@MNP). From the experimental results, although two layers were sprayed step by step, no obvious stratification could be observed. The vector PEI interweaved with genes and inhibited the gene release profile, but it changed the released naked genes to positively charged complexes, which would promote gene transfection efficiency. In subsequent in vivo experiments, the anti-tumor efficacy of the "P@D@MNP treated group" could reach 84.7%, although it had the lowest gene release profile. In contrast, the anti-tumor efficacy of the "intravenous injection group" and "D@MNP treated group" was only 24.3% and 59.3%, respectively. Overall, P@D@MNP was a safe and efficient device to treat the subdermal tumor. Ultrasonic spraying technology provided an industrialized method to fabricate the coated microneedle patch as a transdermal gene/drug delivery platform.

Build an implanted "arsenal": detachable microneedles for NIR-triggered cancer photothermo-chemotherapy.

The current trend in tumor research is shifting from monotherapy to multimodal therapy. However, how to achieve on-demand drug delivery and minimize the invasiveness of treatment are still big challenges. Herein, we present a detachable microneedles (MNs) system, which consists of polycaprolactone (PCL) needles and polyvinylpyrrolidone/poly (vinyl alcohol) substrate, to build an implanted drug depot for on-demand photothermo-chemotherapy. Owing to the dissolvability of the substrate, detachable MNs can intradermally implant PCL needles loaded with photothermal conversion agent Prussian blue nanocubes (PB NCs) and chemotherapeutics doxorubicin hydrochloride (Dox·HCl). Once near-infrared light irradiates, PB NCs could translate light to local regional hyperthermia, which not only ablates cancer cells but also meltPCL to accelerate the diffusion of Dox·HCl. These MNs displayed a stable and repeatable photothermal effect under NIR irradiation. The ex vivo experiments using isolated swine skin demonstrated the as needed Dox·HCl delivery triggered by NIR light. Moreover, the robust antitumor efficacy of the MN system was proved in KB tumor-bearing nude mice under three timed NIR irradiation. Therefore, the developed detachable MNs which could build implanted "arsenal" for on-demand photothermo-chemotherapy have a bright future in tumor suppression.

Combined toxic impacts of thiamethoxam and four pesticides on the rare minnow (Gobiocypris rarus).

To examine pesticide mixture toxicity to aqueous organisms, we assessed the single and combined toxicities of thiamethoxam and other four pesticides (chlorpyrifos, beta-cypermethrin, tetraconazole, and azoxystrobin) to the rare minnow (Gobiocypris rarus). Data from 96-h semi-static toxicity assays of various developmental phases (embryonic, larval, juvenile, and adult phases) showed that beta-cypermethrin, chlorpyrifos, and azoxystrobin had the highest toxicities to G. rarus, and their LC50 values ranged from 0.0031 to 0.86 mg a.i. L-1, from 0.016 to 6.38 mg a.i. L-1, and from 0.39 to 1.08 mg a.i. L-1, respectively. Tetraconazole displayed a comparatively high toxicity, and its LC50 values ranged from 3.48 to 16.73 mg a.i. L-1. By contrast, thiamethoxam exhibited the lowest toxic effect with LC50 values ranging from 37.85 to 351.9 mg a.i. L-1. Rare minnow larvae were more sensitive than embryos to all the pesticides tested. Our data showed that a pesticide mixture of thiamethoxam-tetraconazole elicited synergetic toxicity to G. rarus. Moreover, pesticide mixtures containing beta-cypermethrin in combination with chlorpyrifos or tetraconazole also had synergetic toxicities to fish. The majority of pesticides are presumed to have additive toxicity, while our data emphasized that the concurrent existence of some chemicals in the aqueous circumstance could cause synergetic toxic effect, leading to severe loss to the aqueous environments in comparison with their single toxicities. Thence, the synergetic impacts of chemical mixtures should be considered when assessing the ecological risk of chemicals.