A new perspective in the prevention and treatment of antitumor therapy-related cardiotoxicity: Intestinal microecology.

The continuous development of antitumor therapy has significantly reduced the mortality of patients with malignancies. However, the antitumor-related cardiotoxicity has become the leading cause of long-term mortality in patients with malignancies. Besides, the pathogenesis of antitumor-related cardiotoxicity is still unclear, and practical means of prevention and treatment are lacking in clinical practice. Therefore, the major challenge is how to combat the cardiotoxicity of antitumor therapy effectively. More and more studies have shown that antitumor therapy kills tumor cells while causing damage to sensitive tissues such as the intestinal mucosa, leading to the increased permeability of the intestine and the dysbiosis of intestinal microecology. In addition, the dysbiosis of intestinal microecology contributes to the development and progression of cardiovascular diseases through multiple pathways. Thus, the dysbiosis of intestinal microecology may be a potential mechanism and target for antitumor-related cardiotoxicity. We summarized the characteristics of intestinal microecology disorders induced by antitumor therapy and the association between intestinal microecological dysbiosis and CVD. And on this basis, we hypothesized the potential mechanisms of intestinal microecology mediating the occurrence of antitumor-related cardiotoxicity. Then we reviewed the previous studies targeting intestinal microecology against antitumor-associated cardiotoxicity, aiming to provide a reference for future studies on the occurrence and prevention of antitumor-related cardiotoxicity by intestinal microecology.

Gut microbiota influence frailty syndrome in older adults: mechanisms and therapeutic strategies.

Frailty syndrome denotes a decreased capacity of the body to maintain the homeostasis and stress of the internal environment, which simultaneously increases the risk of adverse health outcomes in older adults, including disability, hospitalization, falls, and death. To promote healthy aging, we should find strategies to cope with frailty. However, the pathogenesis of frailty syndrome is not yet clear. Recent studies have shown that the diversity, composition, and metabolites of gut microbiota significantly changed in older adults with frailty. In addition, several frailty symptoms were alleviated by adjusting gut microbiota with prebiotics, probiotics, and symbiosis. Therefore, we attempt to explore the pathogenesis of frailty syndrome in older people from gut microbiota and summarize the existing interventions for frailty syndrome targeting gut microbiota, with the aim of providing timely and necessary interventions and assistance for older adults with frailty.

Driving force of deteriorated cellular environment in heart failure: Metabolic remodeling.

Heart Failure (HF) has been one of the leading causes of death worldwide. Though its latent mechanism and therapeutic manipulation are updated and developed ceaselessly, there remain great gaps in the cognition of heart failure. High morbidity and readmission rates among HF patients are waiting to be addressed. Recent studies have found that myocardial energy metabolism was closely related to heart failure, in which substrate utilization, as well as intermediate metabolism disorders, insulin resistance, oxidative stress, and mitochondrial dysfunction, might underlie systolic dysfunction and progression of HF. This article centers on the changes and counteraction of cardiac energy metabolism in the failing heart. Therefore, targeting impaired energy provision is of great potential in the treatment of HF. And shifting the objective from traditional neurohormones to improving the cellular environment is expected to further optimize the management of HF.

Driving force of deteriorated cellular environment in heart failure: Metabolic remodeling

Abstract Heart Failure (HF) has been one of the leading causes of death worldwide. Though its latent mechanism and therapeutic manipulation are updated and developed ceaselessly, there remain great gaps in the cognition of heart failure. High morbidity and readmission rates among HF patients are waiting to be addressed. Recent studies have found that myocardial energy metabolism was closely related to heart failure, in which substrate utilization, as well as intermediate metabolism disorders, insulin resistance, oxidative stress, and mitochondrial dysfunction, might underlie systolic dysfunction and progression of HF. This article centers on the changes and counteraction of cardiac energy metabolism in the failing heart. Therefore, targeting impaired energy provision is of great potential in the treatment of HF. And shifting the objective from traditional neurohormones to improving the cellular environment is expected to further optimize the management of HF.

Preparation and Evaluation of Animal Models of Cardiotoxicity in Antineoplastic Therapy.

The continuous development of antineoplastic therapy has significantly reduced the mortality of patients with malignant tumors, but its induced cardiotoxicity has become the primary cause of long-term death in patients with malignant tumors. However, the pathogenesis of cardiotoxicity of antineoplastic therapy is currently unknown, and practical means of prevention and treatment are lacking in clinical practice. Therefore, how to effectively prevent and treat cardiotoxicity while treating tumors is a major challenge. Animal models are important tools for studying cardiotoxicity in antitumor therapy and are of great importance in elucidating pathophysiological mechanisms and developing and evaluating modality drugs. In this paper, we summarize the existing animal models in antitumor therapeutic cardiotoxicity studies and evaluate the models by observing the macroscopic signs, echocardiography, and pathological morphology of the animals, aiming to provide a reference for subsequent experimental development and clinical application.

Angstrom-confined catalytic water purification within Co-TiOx laminar membrane nanochannels.

The freshwater scarcity and inadequate access to clean water globally have rallied tremendous efforts in developing robust technologies for water purification and decontamination, and heterogeneous catalysis is a highly-promising solution. Sub-nanometer-confined reaction is the ultimate frontier of catalytic chemistry, yet it is challenging to form the angstrom channels with distributed atomic catalytic centers within, and to match the internal mass transfer and the reactive species' lifetimes. Here, we resolve these issues by applying the concept of the angstrom-confined catalytic water contaminant degradation to achieve unprecedented reaction rates within 4.6 Å channels of two-dimensional laminate membrane assembled from monolayer cobalt-doped titanium oxide nanosheets. The demonstrated degradation rate constant of the target pollutant ranitidine (1.06 ms-1) is 5-7 orders of magnitude faster compared with the state-of-the-art, achieving the 100% degradation over 100 h continuous operation. This approach is also ~100% effective against diverse water contaminates with a retention time of <30 ms, and the strategy developed can be also extended to other two-dimensional material-assembled membranes. This work paves the way towards the generic angstrom-confined catalysis and unravels the importance of utilizing angstrom-confinement strategy in the design of efficient catalysts for water purification.

A pH-responsive mesoporous silica nanoparticle-based drug delivery system for targeted breast cancer therapy.

In order to make the drug specifically aggregate at the tumor site, we had developed a targeted drug delivery system based on pH responsive mesoporous silica nanoparticles. Mesoporous silica nanoparticles (MSN-COOH) were prepared and doxorubicin (DOX) was loaded into the pores of MSN-COOH, and then polyethyleneimine (PEI) and anisamide (AA) were modified on the surface of mesoporous silica, named DOX@MSN-PEI-AA(DMPA). DMPA specifically entered tumor cells through AA-mediated receptor endocytosis; PEI dissociated from the surface of the MSN in the acidic environment of cellular lysosomes/endosomes due to protonation of PEI, resulting in steady release of the encapsulated DOX from the pores of MSN in the cytoplasm of the target cells. In vitro and in vivo anti-tumor experiments and hemolytic experiments indicated that DMPA can accurately target breast cancer cells and show excellent safety at the same time, showing great potential for tumor therapy.

Honeycomb-like holey Co3O4 membrane triggered peroxymonosulfate activation for rapid degradation of organic contaminants.

Heterogeneous advanced oxidation processes (AOPs) are commonly employed for the degradation of recalcitrant contaminants, however, practical application of heterogeneous AOPs has been limited by their low activation efficiency and inefficient utilization of radicals. Herein, this study demonstrates for the first time that 2D honeycomb-like holey membranes assembled by Co3O4 nanosheets, serve as an excellent activator for peroxymonosulfate (PMS) and aid in rapid pollutant removal. The Co3O4 membrane achieved 100% target pollutant ranitidine removal and a membrane retention time of only ~385 ms with the degradation rate 3-5 orders of magnitude faster than that achieved by conventional heterogeneous catalysis. Ranitidine degradation was maintained at >90% for 13 h of continuous-flow operation at a high flux of 176 L m-2 h-1 bar-1. Furthermore, the Co3O4 membrane could also effectively degrade several recalcitrant pollutants, including pharmaceutical personal care products, phenols, and dyes. SO4•- and •OH were identified as the primary reactive oxygen species in the Co3O4 membrane/PMS system, with Co providing the active site for PMS activation. This strategy of membrane-based AOP treatment offers helpful guidance for the design of other efficient heterogeneous catalytic systems and presents a novel approach to overcoming the limitations of conventional heterogeneous catalysis.

Physical Activity and its Influencing Factors in Community-Dwelling Older Adults With Dementia: A Path Analysis.

Dementia is prevalent in worldwide, and increases the care burden and potential costs. Physical activity (PA) has been increasingly shown to be beneficial for them. This was a cross-sectional observational study aiming to investigate the status of PA among community-dwelling older adults with dementia in Beijing or Hangzhou, China, and verify the relationships between neuropsychiatric symptoms, activities of daily living (ADL), caregivers' fear of patients' falling and their PA using a path analysis approach. The level of PA among 216 included people with dementia was low. PA was related to the neuropsychiatric symptoms, with ADL and caregivers' fear of patients' falling have mediation roles. The findings indicated that person-centered strategies related to the management of these symptoms might be helpful to improve ADL, relieve caregivers' concerns about them falling and consequently foster positive participation in PA.

A novel polypeptide vaccine and adjuvant formulation of EV71.

Hand foot and mouth disease (HFMD) is an infectious disease mainly caused by Enterovirus 71 (EV 71). However, the effective treatment is limited currently. The aim of this study was to investigate the activity of the vaccine including the EV71 polypeptides mixed with a novel adjuvant containing CpG oligodeoxynucleotides (CpG ODNs). After collecting mouse sera, we determined the antibody concentration in serum by enzyme-linked immunosorbent assays (ELISA). Then, CD19+CD27+ B cells in the spleen were analysed by flow cytometry. The assay revealed that a substantial increase in antibody titers was achieved. This indicates a high level of immunogenicity for peptide vaccine and the good stability of adjuvant, also suggests that the combination of vaccine and adjuvant can stimulate the production of high-level antibodies and CD19+CD27+ B lymphocytes in mice. Furthermore, the antibody could effectively identify EV71 inactivated virus. The results demonstrated that the autonomous construction of EV71 polypeptide vaccine had a good immunogenicity. Moreover, the peptide vaccine injection with a novel adjuvant, which is easy to prepare, could cause a high antibody level of EV71 and shown a good application prospect.

Plasmonic Hot Hole Extraction from CuS Nanodisks Enables Significant Acceleration of Oxygen Evolution Reactions.

Localized surface plasmon resonance (LSPR) is well known for its unique ability to tune the reactivity of plasmonic materials via photoexcitation; however, it is still an open question as to whether plasmonic holes can be directly extracted to drive valuable chemical reactions. Herein we give an affirmative answer by reporting an illumination-enhanced oxygen evolution reaction (OER) using CuS nanodisks (NDs) alone as the electrocatalyst. Impressively, under 1221 nm laser or xenon lamp illumination, an unprecedented reduction of OER overpotential was observed on the CuS ND-coated electrodes. Transient absorption combined with Mott-Schottky measurements disclosed that near-infrared (NIR) irradiation generated abundant hot holes from LSPR damping in the CuS NDs accounting for the remarkable OER performance enhancement. This is the first report on the direct utilization of plasmonic hot holes in CuS nanomaterials for boosting OER performance, opening up a new route to designing NIR-active photocatalysts/electrocatalysts by exploiting the unique LSPR properties.

Generation and Evaluation of Recombinant Thermostable Newcastle Disease Virus Expressing the HA of H9N2 Avian Influenza Virus.

H9N2 avian influenza virus (AIV) has become endemic in many countries, causing great economic losses when co-infected with other pathogens. So far, several live vaccines based on Newcastle disease virus (NDV) vectors expressing influenza hemagglutinin (HA) have been developed. However, the thermostable recombinant NDV is rarely reported. In this study, using a thermostable NDV rAHR09 strain as the vector, three recombinant NDVs expressing native HA, chimeric HA ectodomain with transmembrane domain/C-terminal cytoplasmic tail domain from fusion protein of NDV, and HA ectodomain were generated, designated rAHR09-HA, rAHR09-HAF, and rAHR09-HAE. The MDT value of three recombinant NDVs was above 120 h, their ICPI value was about 0.03, and the recombinant NDVs were still infectious when treated for 100 min under 56 °C, which demonstrated that the recombinant NDVs kept the lentogenic and thermostable nature of rAHR09. The immunization data showed that rAHR09-HA and rAHR09-HAF induced a higher HI antibody titer against H9N2 AIV and NDV. After being challenged with H9N2 AIV, the rAHR09-HA and rAHR09-HAF could significantly reduce the virus shedding in cloacal and tracheal swab samples. Our results suggest that rAHR09-HA and rAHR09-HAF might be vaccine candidates against H9N2 AIV.

Antitumor effects and mechanisms of CpG ODN combined with attenuated Salmonella-delivered siRNAs against PD-1.

Numerous studies have focused on the treatment of melanoma, but the current therapies for melanoma have limited therapeutic effects. To find a more effective therapy for melanoma, we combined artificially designed CpG ODN (cytosine-phosphate-guanine oligodeoxynucleotides) and siRNAs (small-interfering ribonucleic acids) targeting PD-1 (programmed cell death protein 1), which were delivered by attenuated Salmonella to treat melanoma in mice, and explored the underlying antitumor mechanisms. We found that mice receiving the combination therapy had the smallest tumor size and the longest survival time. The possible mechanisms underlying this phenomenon include pathways mediated by cyclin D1, p-STAT3 (phosphorylated signal transducers and activators of transcription protein 3), MMP2 (matrix metallopeptidase 2) and cleaved caspase 3, since after treatment, the expression of cyclin D1, p-STAT3, and MMP2 decreased but that of cleaved caspase 3 increased; additional mechanisms include increases in the recruitment of immune cells to tumor sites and in the number of immune cells in mouse spleens and the upregulation of TNF-α (tumor necrosis factor) and IL-6 (interleukin 6). We demonstrated that the combination therapy composed of CpG ODN and PD-1-siRNA delivered by attenuated Salmonella exhibited a strong ability to inhibit melanoma and improve the antitumor immune responses of tumor-bearing mice.

A versatile fluorometric in situ hybridization method for the quantitation of hairpin conformations in DNA self-assembled monolayers.

As the performance of hairpin DNA (hpDNA)-based biosensors is highly dependent on the yield of stem-loop (hairpin) conformations, we report herein a versatile fluorometric in situ hybridization protocol for examining hpDNA self-assembled monolayers (SAMs) on popularly used biochip substrates. Specifically, the ratio of fluorescence (FL) intensities of hpDNA SAMs (in an array format) before and after hybridization was adopted as the key parameter for performing such a determination. Upon confirming the existence of mixed and tunable DNA conformations in binary deposition solutions and efficient hybridization of the hairpin strands with the target DNA via gel electrophoresis assays, we tested the fluorometric protocol for determining the coverages of hpDNA in hpDNA/ssDNA SAMs prepared on gold; its accuracy was validated by Exonuclease I (Exo I)-assisted electrochemical quantitation. To further confirm its versatility, this FL protocol was adopted for quantifying hairpin conformations formed on glass and polycarbonate (PC) substrates. The molar ratios of surface-tethered hairpin conformations on the three different substrates were all found to be proportional to but less than those in the binary deposition solutions, and were dependent on the substrate morphology. The findings reported herein are beneficial for the construction of highly efficient DNA hairpin-based sensing surfaces, which essentially facilitates the creation of hpDNA-based biosensors with optimal detection performance.

Exonuclease I-Assisted General Strategy to Convert Aptamer-Based Electrochemical Biosensors from "Signal-Off" to "Signal-On".

In terms of how the signal varies in response to increased concentration of an analyte, sensors can be classified as either "signal-on" or "signal-off" format. While both types hold potentials to be sensitive, selective, and reusable, in many situations "signal-on" sensors are preferred for their low background signal and better selectivity. In this study, with the detection of lysozyme using its DNA aptamer as a trial system, for the first time we demonstrated that such an aptamer-based electrochemical biosensor can be converted from intrinsically "signal-off" to "signal-on" with the aid of a DNA exonuclease. The fact that the stepwise cleavage of antilysozyme aptamer catalyzed by Exonuclease I (Exo I) is entirely inhibited upon binding lysozyme leads to the selective removal of unbound DNA probes (thiolate anti-lysozyme DNA aptamer strands immobilized on gold electrode) upon the introduction of Exo I to the sensor. With the aid of electrostatically bound redox cations ([Ru(NH3)6]3+), we were able to quantitate the number of aptamer strands that are bound with lysozymes via conventional cyclic voltammetry (CV) measurements. We demonstrated that Exo I-assisted signal-on conversion protocol not only improves the sensing performance (10 times better limit of detection) but also promises a versatile strategy for DNA-based biosensor design, i.e., it can be readily adapted to other aptamer-protein binding systems (thrombin, as another example).

Enantioseparation processes and mechanisms in functionalized graphene membranes: Facilitated or retarded transport?

Up to date, functionalized graphene-based membranes have exhibited a promising potential in the enantioseparation. However, since precisely controlling the interlayer distance of two-dimensional materials is a great challenge in practical experiments, the transport mechanism of chiral guests in such membranes, together with various critical parameters that play a controlling role in the transport behaviors of the preferentially binding enantiomer in narrow channels, remains to be explored. The molecular dynamics (MD) simulation, especially using the steered MD (SMD) method, might be an alternative way to investigate the enantioseparation processes and mechanisms of layered membranes with different interlayer distances. In this work, D-alanine modified graphene sheets with different interlayer distances were built as membrane models, whereas D- and L-phenylalanine were selected as chiral probes. The effect of the interlayer distance and the applied external force on the enantioseparation performance was examined. Results show that such two parameters exert a significant influence on the enantioseparation performance: (a) Increasing the interlayer distance would result in a conversion from the retarded to the facilitated mechanism at a proper external force (medium); (b) both the large and small driving forces would only lead to the appearance of the retarded transport for the preferential enantiomer, unlike the moderate force; (c) the interaction energy of L-phenylalanine with D-isomer selector decreases with the rising interlayer distances studied in this work, regardless of what the external force is. Our findings can provide guidance on the practical applications in the membrane-based chiral separation.

Influence of Host-Guest Interaction between Chiral Selectors and Probes on the Enantioseparation Properties of Graphene Oxide Membranes.

Graphene oxide (GO)-based membranes have displayed superior performances in the chiral resolution compared with conventional polymer-based and inorganic membranes. However, the effect of the host-guest interaction between chiral selectors and probes on the enantioseparation properties of GO-based membranes remains to be established. In this work, l-phenylalanine (l-Phe, as the chiral selector)-modified GO-based (l-Phe-GO) membranes were fabricated, and their enantioseparation performances toward various enantiomers, that is, d- and l-phenylalanine (d- and l-Phe), d- and l-methionine (d- and l-Met), N-acyl-d-phenylalanine (N-acyl-d-Phe) and N-acyl-l-phenylalanine (N-acyl-l-Phe), and N-acyl-d-methionine (N-acyl-d-Met) and N-acyl-l-methionine (N-acyl-l-Met), were detected. Results show that (i) l-Phe is preferential to transport d-enantiomers relative to l-enantiomers; (ii) as far as d-enantiomers are concerned, the d-Phe-like enantiomers move faster than d-Met-like ones through the l-Phe-GO membrane owing to their different host-guest interactions. The strength of interactions between chiral selectors and probes was further confirmed from both experimental and theoretical standpoints. In the former case, the enantioselective adsorption of l-Phe-GO nanosheets toward the aforementioned enantiomers demonstrates that l-Phe delivers a higher adsorption capacity to d-enantiomers relative to l-enantiomers, and meanwhile, d-Phe-like enantiomers are better than d-Met-like enantiomers in the adsorption capacity. In the latter case, the chiral separation mechanism is clarified using the periodical density functional theory (DFT) calculation, indicating that l-Phe interacts with d-enantiomers more strongly than l-enantiomers. Especially, our calculations unveil that the difference in the interaction strength is principally dominated by the nonstereoselective interactions between chiral probes and the GO surface. Therefore, our findings suggest that the nonstereoselective weak interaction can be employed to improve the enantioselectivity of GO-based membranes.

Lattice Engineering on Metal Cocatalysts for Enhanced Photocatalytic Reduction of CO2 into CH4.

Photocatalytic conversion of CO2 into CH4 represents an appealing approach to alleviate the world's continued reliance on fossil fuels and global warming resulting from increasing CO2 concentrations in the atmosphere. However, its practical application is greatly limited by serious electron-hole recombination in the photocatalysts and the production of CO and H2 as side reactions. Herein, for the first time, it is demonstrated that the photocatalytic reduction of CO2 to CH4 can be significantly improved through the simultaneous alloying and hydriding of metal cocatalysts. The isolation of Cu and H atoms in Pd lattices play three roles in the enhancement of CO2 to CH4 conversion: 1) Cu atoms provide catalytic sites to reduce CO2 into CO and then to CH4 to suppress H2 evolution; 2) H atoms improve the electron-trapping ability of cocatalysts; and 3) H atoms accelerate the reduction of CO to CH4 , which is the rate-limiting procedure in the conversion of CO2 into CH4 . Arising from the synergistic interplay between Pd-H and Cu-CO sites, C3 N4 -Pd9 Cu1 Hx (15 mg) achieves 100 % selectivity for CH4 production with an average rate of 0.018 µmol h-1 under visible-light irradiation. This work provides insights into the design of a cocatalyst for highly selective CO2 conversion through lattice engineering at atomic precision.

Quantifying the sources of the severe haze over the Southern Hebei using the CMAQ model.

The Southern Hebei of China has experienced an obvious increase of the haze occurrence frequency in the recent years. It has turned out to be one of the most seriously polluted areas in China. This study is aimed at quantifying the sources of the serious haze pollution over the Southern Hebei area, using the Mesoscale Modeling System Generation 5 (MM5) and the Models-3/Community Multiscale Air Quality Model (CMAQ) modeling system. The sectoral contributions by the local and the surrounding regions to the fine particulate matter (PM2.5) concentrations in the two representative cities, Shijiazhuang and Xingtai, were analyzed by applying the method of scenario analysis. It will provide useful information to the policy making in the severe air pollution control in the Southern Hebei area.