Solvent-Induced In(III)-MOFs with Controllable Interpenetration Degree Performing High-Efficiency Separation of CO2/N2 and CO2/CH4.

Herein, three In(III)-based metal-organic frameworks (In-MOFs) with different degrees of interpenetration (DOI), namely In-MOF-1, In-MOF-2, and In-MOF-3, constructed by In3+ and Y-shaped ligands 4,4',4″-s-triazine-2,4,6-triyltribenzoate (H3TATB), are successfully synthesized through the ionothermal/solvothermal method. Subsequently, three novel In-MOFs, including noninterpenetration polycatenation, 2-fold interpenetrated, and 4-fold interpenetrated structure, are employed as the platform for systematically investigating the separation efficiency of CO2/N2, CO2/CH4, and CO2/CH4/N2 mixture gas system. Among them, In-MOF-2 shows the highest CO2 uptake capacities at 298 K and simultaneously possesses the low adsorption enthalpy of CO2 (26.4 kJ/mol at low coverage), a feature desirable for low-energy-cost adsorbent regeneration. The CO2/N2 (v: v = 15/85) selectivity of In-MOF-2 reaches 37.6 (at 298 K and 1 bar), also revealing outstanding selective separation ability from flue gases and purifying natural gas, affording a unique robust separation material as it has moderate DOI and pore size. In-MOF-2 shows exceptional stability and feasibility to achieve reproducibility. Aperture adjustment makes In-MOF-2 a versatile platform for selectively capturing CO2 from flue gases or purifying natural gas.

Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities.

HER2-positive (HER2+) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2+ mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions. Focusing on the second-line treatment for HER2+ mBC, e.g., antibody-drug conjugates (ADC), small molecule inhibitors/TKI and chemotherapy, the model accurately predicted the efficacy of various drug combinations and dosing regimens at the in vitro and in vivo levels. Sensitivity analyses and subsequent heterogeneous phenotype simulations revealed important insights into the design of new drug combinations to effectively overcome various resistance scenarios in HER2+ mBC treatments. In addition, the model predicted a better efficacy of the new TKI plus ADC combination which can potentially reduce drug dosage and toxicity, while it also shed light on the optimal treatment ordering of ADC versus TKI plus capecitabine regimens, and these findings were validated by new in vivo experiments. Our model is the first that mechanistically integrates multiple key drug modalities in HER2+ mBC research and it can serve as a high-throughput computational platform to guide future model-informed drug development and clinical translation.

Reusable HNO Sensors Derived from Cu Cyclam: A DFT Study on the Mechanistic Origin of High Reactivity and Favorable Conformation Changes and Potential Improvements.

Nitroxyl (HNO) exhibits unique favorable properties in regulating biological and pharmacological activities. However, currently, there is only one Cu-based HNO sensor that can be recycled for reusable detection, which is a Cu cyclam derivative with a mixed thia/aza ligand. To elucidate the missing mechanistic origin of its high HNO reactivity and subsequent favorable conformation change toward a stable CuI product that is critical to be oxidized back by the physiological O2 level for HNO detection again, a density functional theory (DFT) computational study was performed. It not only reproduced experimental structural and reaction properties but also, more importantly, revealed an unknown role of the coordination atom in high reactivity. Its conformation change mechanism was found to not follow the previously proposed one but involve a novel favorable rotation pathway. Several newly designed complexes incorporating beneficial effects of coordination atoms and substituents to further enhance HNO reactivity while maintaining or even improving favorable conformation changes for reusable HNO detection were computationally validated. These novel results will facilitate the future development of reusable HNO sensors for true spatiotemporal resolution and repeated detection.

Generation and Application of Homoallylic α,α-Diboryl Radicals via Diboron-Promoted Ring-Opening of Vinyl Cyclopropanes: cis-Diastereoselective Borylative Cycloaddition.

Carbon-centered radicals stabilized by adjacent boron atoms are underexplored reaction intermediates in organic synthesis. This study reports the development of vinyl cyclopropyl diborons (VCPDBs) as a versatile source of previously unknown homoallylic α,α-diboryl radicals via thiyl radical catalyzed diboron-directed ring opening. These diboryl stabilized radicals underwent smooth [3+2] cycloaddition with a variety of olefins to provide diboryl cyclopentanes in good to excellent diastereoselectivity. In contrast to the trans-diastereoselectivity observed with most of the dicarbonyl activated VCPs, the cycloaddition of VCPDBs showed a remarkable preference for formation of cis-cyclopentane diastereomer which was confirmed by quantitative NOE and 2D NOESY studies. The cis-stereochemistry of cyclopentane products enabled a concise intramolecular Heck reaction approach to rare tricyclic cyclopentanoid framework containing the diboron group. The mild reaction conditions also allowed a one-pot VCP ring-opening, cycloaddition-oxidation sequence to afford disubstituted cyclopentanones. Control experiments and DFT analysis of reaction mechanism support a radical mediated pathway and provide a rationale for the observed diastereoselectivity. To the authors' knowledge, these are the first examples of the use of geminal diboryl group as an activator of VCP ring opening and cycloaddition reaction of α-boryl radicals.

Establishment and Reliability Evaluation of Prognostic Models in Diabetic Foot.

Purpose: To study the risk factors affecting amputation and survival in patients with diabetic foot (DF) and to construct a predictive model using the machine learning technique for DF foot amputation and survival and evaluate its effectiveness. Materials and Methods: A total of 200 patients with DF hospitalized in the First Affiliated Hospital of Shantou University Medical College in China were selected via cluster analysis screening, Kaplan-Meier survival calculation, amputation rate and Cox proportional hazards model investigation of risk factors associated with amputation and death. In addition, we constructed various models, including Cox proportional hazards regression analysis, the deep learning method convolution neural network (CNN) model, backpropagation (BP) neural network model, and backpropagation neural network prediction model after optimizing the genetic algorithm. The accuracy of the 4 prediction models for survival and amputation was assessed, and we evaluated the reliability of these computational models based on the size of the area under the ROC curve (AUC), sensitivity and specificity. Results: We found that the 1-year survival rate in patients with DF was 88.5%, and the 1-year amputation rate was 12.5%. Wagner's Classification of Diabetic Foot Ulcers grade, ankle-brachial index (ABI), low-density lipoprotein (LDL), and percutaneous oxygen partial pressure (TcPO2) were independent risk factors for amputation in patients with DF, while cerebrovascular disease, Sudoscan sweat gland function score, glycated hemoglobin (HbA1c) and peripheral artery disease (PAD) were independent risk factors for death in patients with DF. In addition, our results showed that in the case of amputation, the COX regression predictive model revealed an AUC of 0.788, sensitivity of 74.1% and specificity of 83.6%. The BP neural network predictive model identified an AUC of 0.874, sensitivity of 87.0% and specificity of 87.7%. An AUC of 0.909, sensitivity of 90.7% and specificity of 91.1% were found after optimizing the BP neural network prediction model via genetic algorithm. In the deep learning CNN model, the AUC, sensitivity and specificity were 0.939, 92.6%, and 95.2%, respectively. In the analysis of risk factors for death, the COX regression predictive model identified the AUC, sensitivity and specificity as 0.800, 74.1% and 85.9%, respectively. The BP neural network predictive model revealed an AUC, sensitivity and specificity of 0.937, 93.1% and 94.4%, respectively. Genetic algorithm-based optimization of the BP neural network predictive model identified an AUC, sensitivity and specificity of 0.932, 91.4% and 95.1%, respectively. The deep learning CNN model found the AUC, sensitivity and specificity to be 0.861, 82.8% and 89.4%, respectively. Conclusion: To identify risk factors for death, the BP neural network predictive model and genetic algorithm-based optimizing BP neural network predictive model have higher sensitivity and specificity than the deep learning method CNN predictive model and COX regression analysis.

Toxoplasma gondii Induces Pyroptosis in Human Placental Trophoblast and Amniotic Cells by Inducing ROS Production and Activation of Cathepsin B and NLRP1/NLRP3/NLRC4/AIM2 Inflammasome.

Toxoplasma gondii infection in pregnant women may cause fetal anomalies; however, the underlying mechanisms remain unclear. The current study investigated whether T. gondii induces pyroptosis in human placental cells and the underlying mechanisms. Human placental trophoblast (BeWo and HTR-8/SVneo) and amniotic (WISH) cells were infected with T. gondii, and then reactive oxygen species (ROS) production, cathepsin B (CatB) release, inflammasome activation, and pyroptosis induction were evaluated. The molecular mechanisms of these effects were investigated by treating the cells with ROS scavengers, a CatB inhibitor, or inflammasome-specific siRNA. T. gondii infection induced ROS generation and CatB release into the cytosol in placental cells but decreased mitochondrial membrane potential. T. gondii-infected human placental cells and villi exhibited NLRP1, NLRP3, NLRC4, and AIM2 inflammasome activation and subsequent pyroptosis induction, as evidenced by increased expression of ASC, cleaved caspase-1, and mature IL-1ß and gasdermin D cleavage. In addition to inflammasome activation and pyroptosis induction, adverse pregnancy outcome was shown in a T. gondii-infected pregnant mouse model. Administration of ROS scavengers, CatB inhibitor, or inflammasome-specific siRNA into T. gondii-infected cells reversed these effects. Collectively, these findings show that T. gondii induces NLRP1/NLRP3/NLRC4/AIM2 inflammasome-dependent caspase-1-mediated pyroptosis via induction of ROS production and CatB activation in placental cells. This mechanism may play an important role in inducing cell injury in congenital toxoplasmosis.

Renal Mass Imaging with MRI Clear Cell Likelihood Score: A User's Guide.

Small solid renal masses (SRMs) are frequently detected at imaging. Nearly 20% are benign, making careful evaluation with MRI an important consideration before deciding on management. Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma subtype with potentially aggressive behavior. Thus, confident identification of ccRCC imaging features is a critical task for the radiologist. Imaging features distinguishing ccRCC from other benign and malignant renal masses are based on major features (T2 signal intensity, corticomedullary phase enhancement, and the presence of microscopic fat) and ancillary features (segmental enhancement inversion, arterial-to-delayed enhancement ratio, and diffusion restriction). The clear cell likelihood score (ccLS) system was recently devised to provide a standardized framework for categorizing SRMs, offering a Likert score of the likelihood of ccRCC ranging from 1 (very unlikely) to 5 (very likely). Alternative diagnoses based on imaging appearance are also suggested by the algorithm. Furthermore, the ccLS system aims to stratify which patients may or may not benefit from biopsy. The authors use case examples to guide the reader through the evaluation of major and ancillary MRI features of the ccLS algorithm for assigning a likelihood score to an SRM. The authors also discuss patient selection, imaging parameters, pitfalls, and areas for future development. The goal is for radiologists to be better equipped to guide management and improve shared decision making between the patient and treating physician. © RSNA, 2023 Quiz questions for this article are available in the supplemental material. See the invited commentary by Pedrosa in this issue.

Computational Mechanistic Investigations of Biocatalytic Nitrenoid C-H Functionalizations via Engineered Heme Proteins.

Engineered heme proteins were developed to possess numerous excellent biocatalytic nitrenoid C-H functionalizations. Computational approaches such as density functional theory (DFT), hybrid quantum mechanics/molecular mechanics (QM/MM), and molecular dynamics (MD) calculations were employed to help understand some important mechanistic aspects of these heme nitrene transfer reactions. This review summarizes advances of computational reaction pathway results of these biocatalytic intramolecular and intermolecular C-H aminations/amidations, focusing on mechanistic origins of reactivity, regioselectivity, enantioselectivity, diastereoselectivity as well as effects of substrate substituent, axial ligand, metal center, and protein environment. Some important common and distinctive mechanistic features of these reactions were also described with brief outlook of future development.

A Superhydrophobic Trifluoromethyl-Containing Covalent Organic Framework Membrane for Efficient Oil/Water Separation.

Oily water caused in the process of industry leads to not only the waste of resources, but also environmental pollution. Membrane separation, as a facile and efficient separation technology, has attracted widespread attention in the field of oil/water separation. The development of membrane materials with high separation performance is one of the key elements to improve separation efficiency. In this work, a superhydrophobic membrane composited with a trifluoromethyl-containing covalent organic framework (COF) is prepared, which exhibits excellent performance on separations of oil/water mixtures and water-in-oil emulsions. For different composition of oil/water mixtures, the highest flux of oil is up to 32 000 L m-2  h-1 and oil/water separation efficiency is above 99%. Moreover, the high oil/water separation efficiency remains unchanged after successive cycles. This work provides a feasible scheme for the design of high-efficiency oil/water separation membranes.

Mechanistic Origin of Favorable Substituent Effects in Excellent Cu Cyclam Based HNO Sensors.

HNO has broad chemical and biomedical properties. Metal complexes and derivatives are widely used to make excellent HNO sensors. However, their favorable mechanistic origins are largely unknown. Cu cyclam is a useful platform to make excellent HNO sensors including imaging agents. A quantum chemical study of Cu cyclams with various substitutions was performed, which reproduced diverse experimental reactivities. Structural, electronic, and energetic profiles along reaction pathways show the importance of HNO binding and a proton-coupled electron transfer mechanism for HNO reaction. Results reveal that steric effect is primary and electronic factor is secondary (if the redox potential is sufficient), but their interwoven effects can lead to unexpected reactivity, which looks mysterious experimentally but can be explained computationally. This work suggests rational substituent design ideas and recommends a theoretical study of a new design to save time and cost due to its subtle effect.

Mercuric chloride induces sequential activation of ferroptosis and necroptosis in chicken embryo kidney cells by triggering ferritinophagy.

Mercuric chloride (HgCl2) is an environmental pollutant with serious nephrotoxic effects, but the underlying mechanism of HgCl2 nephrotoxicity is not well understood. Ferroptosis and necroptosis are two programmed cell death (PCD) modalities that have been reported singly in heavy metal-induced kidney injury. However, the interaction between ferroptosis and necroptosis in HgCl2-induced kidney injury is unclear. Here, we established a model of HgCl2-exposed chicken embryo kidney (CEK) cells to dissect the progresses and mechanisms of these two PCDs. We found that ferroptosis was initially activated in CEK cells after HgCl2 exposure for 12 h, and necroptosis was activated subsequently at 24 h. Importantly, further study indicated that the shift from ferroptosis to necroptosis was driven by ROS, which was produced by iron-dependent Fenton reaction, and the iron chelation by DFO prevented the sequential activation of both ferroptosis and necroptosis. To investigate the source of intracellular iron, the regulation of iron homeostasis was first explored and demonstrated a tendency for intracellular iron overload in CEK cells. Interestingly, the cellular ferritin, a free iron depository, decreased in a time-dependent manner. Further studies revealed that the degradation of ferritin was attributed to the activation of selective cargo receptor nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy, and the inhibition of ferritinophagy by CQ prevented the HgCl2-induced cell death. In conclusion, our study demonstrated that HgCl2 released excess free iron via ferritinophagy, led to a sustained accumulation of ROS and ultimately activated ferroptosis and necroptosis sequentially. These findings provide a new understanding for the nephrotoxic mechanism of HgCl2.

Protective mechanism of selenium on mercuric chloride-induced testis injury in chicken via p38 MAPK/ATF2/iNOS signaling pathway.

Mercuric chloride (HgCl2) is a well-known toxic heavy metal contaminant, which causes male reproductive function defects. Selenium (Se) has been recognized as an effective antioxidant against heavy metals-induced male reproductive toxicity. The aim of present study was to explore the potentially protective mechanism of Se on HgCl2-induced testis injury in chicken. Firstly, the results showed that Se mitigated HgCl2-induced testicular injury through increasing the blood-testis barrier (BTB) cell-junction proteins expression of occludin, zonula occludens-1 (ZO-1), connexin 43 (Cx43), and N-cadherin. Secondly, Se alleviated HgCl2-induced oxidative stress through decreasing the malondialdehyde (MDA) content and increasing the superoxidase dismutase (SOD), glutathione peroxidase (GSH-Px) activities as well as the total antioxidant capacity (T-AOC) level. Thirdly, Se inhibited the activation of p38 MAPK signaling through decreasing the proteins expression of phosphorylated-p38 (p-p38) and phosphorylated-ATF2 (p-ATF2), and alleviated inflammation response through decreasing the proteins expression of inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF-κB), tissue necrosis factor-alpha (TNF-α), and cyclooxygenase 2 (COX2). Collectively, these results demonstrated that Se effectively alleviated HgCl2-induced testes injury via improving antioxidant capacity to reduce inflammation mediated by p38 MAPK/ATF2/iNOS signaling pathway in chicken. Our data shed a new light on potential mechanisms of Se antagonized HgCl2-induced male reproductive toxicity.

Comparison of diagnostic validity of two autism rating scales for suspected autism in a large Chinese sample.

BACKGROUND: Autism is the most common clinical developmental disorder in children. The childhood autism rating scale (CARS) and autistic autism behavior checklist (ABC) are the most commonly used assessment scales for diagnosing autism. However, the diagnostic validations and the corresponding cutoffs for CARS and ABC in individuals with suspected autism spectrum disorder (ASD) remain unclear. Furthermore, for suspected ASD in China, it remains unclear whether CARS is a better diagnostic tool than ABC. Also unclear is whether the current cutoff points for ABC and CARS are suitable for the accurate diagnosis of ASD. AIM: To investigate the diagnostic validity of CARS and ABC based on a large Chinese sample. METHODS: A total of 591 outpatient children from the ASD Unit at Beijing Children's Hospital between June and November 2019 were identified. First, the Clancy autism behavior scale (CABS) was used to screen out suspected autism from these children. Then, each suspected ASD was evaluated by CARS and ABC. Receiver operating characteristic (ROC) curve analysis was used to compare diagnostic validations. We also calculated the area under the curve (AUC) for both CARS and ABC. RESULTS: We found that the Cronbach alpha coefficients of CARS and ABC were 0.772 and 0.426, respectively. Therefore, the reliability of the CARS was higher than that of the ABC. In addition, we found that the correlation between CARS and CABS was 0.732. Next, we performed ROC curve analysis for CARS and ABC, which yielded AUC values of 0.846 and 0.768, respectively. The cutoff value, which is associated with the maximum Youden index, is usually applied as a decision threshold. We found that the cutoff values of CARS and ABC were 34 and 67, respectively. CONCLUSION: This result indicated that CARS is superior to ABC in the Chinese population with suspected ASD.

Antagonistic effect of selenium on mercuric chloride in the central immune organs of chickens: The role of microRNA-183/135b-FOXO1/TXNIP/NLRP3 inflammasome axis.

Mercury (Hg) is a persistent environmental and industrial pollutant that accumulated in the body and induces oxidative stress and inflammation damage. Selenium (Se) has been reported to antagonize immune organs damage caused by heavy metals. Here, we aimed to investigate the prevent effect of Se on mercuric chloride (HgCl2 )-induced thymus and bursa of Fabricius (BF) damage in chickens. The results showed that HgCl2 caused immunosuppression by reducing the relative weight, cortical area of the thymus and BF, and the number of peripheral blood lymphocytes. Meanwhile, HgCl2 induced oxidative stress and imbalance in cytokines expression in the thymus and BF. Further, we found that thioredoxin-interacting protein (TXNIP) and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome mediated HgCl2 -induced oxidative stress and inflammation. Mechanically, the targeting and inhibitory effect of microRNA (miR)-135b/183 on forkhead box O1 (FOXO1) were an upstream event for HgCl2 -activated TXNIP/NLRP3 inflammasome pathway. Most importantly, Se effectively attenuated the aforementioned damage in the thymus and BF caused by HgCl2 and inhibited the TXNIP/NLRP3 inflammasome pathway by reversing the expression of FOXO1 through inhibiting miR-135b/183. In conclusion, the miR-135b/183-FOXO1/TXNIP/NLRP3 inflammasome axis might be a novel mechanism for Se to antagonize HgCl2 -induced oxidative stress and inflammation in the central immune organs of chickens.

Selenium ameliorates mercuric chloride-induced brain damage through activating BDNF/TrKB/PI3K/AKT and inhibiting NF-κB signaling pathways.

Mercuric chloride (HgCl2), a heavy metal compound, causes neurotoxicity of animals and humans. Selenium (Se) antagonizes heavy metal-induced organ damage with the properties of anti-oxidation and anti-inflammation. Nevertheless, the molecular mechanism underlying the protective effects of sodium selenite (Na2SeO3) against HgCl2-induced neurotoxicity remains obscure. Therefore, the present study aimed to explore the protective mechanism of Na2SeO3 on HgCl2-induced brain damage in chickens. Morphological observations showed that Na2SeO3 alleviated HgCl2-induced brain tissues damage. The results also showed that Na2SeO3 decreased the protein expression of S100 calcium binding protein B (S100B), and increased the levels of nerve growth factors (NGF), doublecortin domain containing 2 (DCDC2), as well as neurotransmitter to reverse HgCl2-induced brain dysfunction. Further, Na2SeO3 attenuated HgCl2-induced oxidative stress by decreasing the level of malondialdehyde (MDA) and increasing the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC). Mechanistically, Na2SeO3 activated the brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase receptor type B (TrKB)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and suppressed the nuclear factor kappa B (NF-κB) signaling pathway to inhibit apoptosis and inflammation caused by HgCl2 exposure. In summary, Na2SeO3 ameliorated HgCl2-induced brain injury via inhibiting apoptosis and inflammation through activating BDNF/TrKB/PI3K/AKT and suppressing NF-κB pathways.

Aberrant Gene Expression of Selenoproteins in Chicken Spleen Lymphocytes Induced by Mercuric Chloride.

Mercury (Hg) is a heavy metal widely distributed in ecological environment, poisoning the immune system of humans and animals. Selenium (Se) is an essential microelement and selenoproteins involved in the procedure of Se antagonizing organ toxicity induced by heavy metals. The aim of this research was to investigate the changes of gene expression profile of selenoproteins induced by mercuric chloride (HgCl2) in chicken spleen lymphocytes. We established cytotoxicity model of chicken spleen lymphocytes by HgCl2 exposure, the messenger RNA (mRNA) expression levels of 25 selenoproteins in spleen lymphocytes were analyzed by real-time quantitative PCR (qPCR), and the gene expression pattern of selenoproteins was revealed by principal component analysis (PCA). The results showed that the mRNA expression levels of 13 selenoproteins (GPX3, GPX4, TXNRD2, TXNRD3, DIO2, SELENOS, SELENON, SELENOT, SELENOO, SELENOP, SELENOP2, MSRB1, and SEPHS2) were decreased in HgCl2 treatment group, and there was strong positive correlation between these selenoproteins and component 1 as well as component 2 of the PCA. At the same time, the protein expression levels of GPX4, TXNRD1, TXNRD2, SELENOM, SELENOS, and SELENON were detected by Western blotting, which were consistent with the changes of gene expression. The results showed that the expression levels of selenoproteins were aberrant in response to HgCl2 toxicity. The information presented in this study provided clues for further research on the interaction between HgCl2 and selenoproteins, and the possible mechanism of immune organ toxicity induced by HgCl2.

Selenium alleviates mercury chloride-induced liver injury by regulating mitochondrial dynamics to inhibit the crosstalk between energy metabolism disorder and NF-κB/NLRP3 inflammasome-mediated inflammation.

Mercury (Hg) is a persistent heavy metal contaminant with definite hepatotoxicity. Selenium (Se) has been shown to alleviate liver damage induced by heavy metals. Therefore, the present study aimed to explore the mechanism of the antagonistic effect of Se on mercury chloride (HgCl2)-induced hepatotoxicity in chickens. Firstly, we confirmed that Se alleviated HgCl2-induced liver injury through histopathological observation and liver function analyzation. The results also showed that Se prevented HgCl2-induced liver lipid accumulation and dyslipidemia by regulating the gene expression related to lipid as well as glucose metabolism. Moreover, Se blocked the nuclear factor kappa B (NF-κB)/NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathway, which was the key to alleviate the inflammation caused by HgCl2. Mechanically, Se inhibited immoderate mitochondrial division, fusion, and biogenesis caused by HgCl2, and also improved mitochondrial respiration, which were essential for preventing energy metabolism disorder and inflammation. In conclusion, our results suggested that Se inhibited energy metabolism disorder and inflammation by regulating mitochondrial dynamics, thereby alleviating HgCl2-induced liver injury in chickens. These results are expected to provide potential intervention and therapeutic targets for diseases caused by inorganic mercury poisoning.

Prussian Blue and Carbon-Dot Hybrids for Enhanced Electrochromic Performance.

In this study, Prussian blue@Carbon-dot (PB@C-dot) hybrids have been developed by one-step hydrothermal method. The incorporation of C-dots into Prussian blue thin film as a way of improving its electrochromic performance was investigated. The structure of the PB@C-dot hybrid was characterized through X-ray diffraction, Raman spectroscopy and scanning electron microscopy. The electrochromic properties showed that incorporation of 10 mL C-dots into the film showed higher optical contrast of 1.6 and superior coloration/bleaching response of 10 and 3 s. It is proposed that the C-dots component used in the construction of the PB@C-dot hybrid plays a key role to achieve superior electrochromic performance.

Silver nanoparticles induce apoptosis via NOX4-derived mitochondrial reactive oxygen species and endoplasmic reticulum stress in colorectal cancer cells.

Aim: To investigate the anticancer mechanisms of silver nanoparticles (AgNPs) in colorectal cancer. Methods: Anticancer effects of AgNPs were determined in colorectal cancer HCT116 cells and xenograft mice using cellular and molecular methods. Results: AgNPs induced mitochondrial reactive oxygen species production, mitochondrial dysfunction and endoplasmic reticulum (ER) stress responses through NOX4 and led to HCT116 cell apoptosis. Pretreatment with DPI or 4-PBA significantly inhibited mitochondrial reactive oxygen species production, apoptosis, ER stress response, NOX4 expression and mitochondrial dysfunction in AgNP-treated HCT116 cells. AgNPs also significantly suppressed HCT116 cell-based xenograft tumor growth in nude mice by inducing apoptosis and ER stress responses. Conclusion: AgNPs exert anticancer effects against colorectal cancer via ROS- and ER stress-related mitochondrial apoptosis pathways.