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MnO octahedrons with exposed {111} crystal faces have been synthesized in a solvothermal system of Mn(Ac)2 and C2H5OH at 200 °C for 48 h. Formation of the MnO octahedron results from the selective adsorption of -OCH2CH3 and -OH groups on the (111) crystal plane. Responses of the MnO octahedrons towards acetone, triethylamine, ethanol and n-Butylamine are enhanced by increasing numbers of the unsaturated 2, 3 and 5-coordinated Mn atoms on the (111) surface by removing surface C2H5O- and -OH groups through hydrogenation. Thus, the exposed Mn-MnO (111) face is found to be a gas sensing active surface, the unsaturated 2, 3 and 5-coordinated Mn atoms on the (111) surface are evidenced to be the sensing reactive atoms and a detailed sensing mechanism is presented. The unsaturated active Mn atoms produce electrons, adsorb oxygen and catalyze the sensing reactions. The mechanism can deepen the understanding of the nature of oxide semiconductor gas sensing and is helpful to the design of high performance gas sensing materials.

Query auto-completion (QAC) is widely used by modern search engines to assist users by predicting their intended queries. Most QAC approaches rely on deterministic batch learning algorithms trained from past query log data. However, query popularities keep changing all the time and QAC operates in a real-time scenario where users interact with the search engine continually. So, ideally, QAC must be timely and adaptive enough to reflect time-sensitive changes in an online fashion. Second, due to the vertical position bias, a query suggestion with a higher rank tends to attract more clicks regardless of user’s original intention. Hence, in the long run, it is important to place some lower ranked yet potentially more relevant queries to higher positions to collect more valuable user feedbacks. In order to tackle these issues, we propose to formulate QAC as a ranked Multi-Armed Bandits (MAB) problem which enjoys theoretical soundness. To utilize prior knowledge from query logs, we propose to use Bayesian inference and Thompson Sampling to solve this MAB problem. Extensive experiments on large scale datasets show that our QAC algorithm has the capacity to adaptively learn temporal trends, and outperforms existing QAC algorithms in ranking qualities.

Senile cataract is a common age-related disease in ophthalmology. Hsa_circ_0004058 has been reported to be down-regulated in the lens epithelial cells of senile cataract patients, suggesting that hsa_circ_0004058 is associated with senile cataract. However, the underlying mechanism is still unknown. This study attempted to determine the functional role of hsa_circ_0004058 in senile cataract. We treated human lens epithelial cells (SRA01/04) with H2O2 as senile cataract model, and found that cell viability and autophagy of SRA01/04 cells were severely decreased by H2O2 treatment. Hsa_circ_0004058 was notably down-regulated in H2O2-treated SRA01/04 cells. Moreover, hsa_circ_0004058 overexpression reduced apoptotic cells and the expression of Cleaved-caspase-3 and Bax, and enhanced Bcl-2 expression in H2O2-treated SRA01/04 cells. However, hsa_circ_0004058 silencing caused the opposite results. Hsa_circ_0004058 up-regulation accelerated the expression of autophagy-related proteins LC3-II/LC3-I and Beclin-1 in H2O2-treated SRA01/04 cells, which was partly abolished by 3-Methyladenine (autophagy inhibitor). Additionally, hsa_circ_0004058 functioned as a competing endogenous RNA to competitive binding miR-186, and thus accelerated the expression of its down-stream target, ATG7. Hsa_circ_0004058 promoted autophagy of SRA01/04 cells by regulating miR-186/ATG7 axis. In conclusion, these data demonstrates that hsa_circ_0004058 inhibits apoptosis of SRA01/04 cells by promoting autophagy, which attributes to regulate miR-186/ATG7 axis. Thus, hsa_circ_0004058 may be a potential target for senile cataract treatment.

Graphitic carbon nitride (g-C3N4) has been extensively applied for the photocatalytic degradation of pharmaceuticals and personal care products (PPCPs); however, its catalytic performance remains restricted by a poor photoresponse and modest photoredox capacity toward the generation of free radicals. Herein, a novel carbon quantum dots-modified reduced ultrathin g-C3N4 (RUCN/CQD) photocatalyst was successfully synthesized, with the capacity for direct •OH and O2•− yields and a broad-spectrum response. Upon broad-spectrum light irradiation, the RUCN/CQD demonstrated a 100% removal rate for diclofenac (DCF) within six min. This remarkable performance was attributed to a customized band structure with a thermodynamic driving potential for the generation of •OH, CQD with an effective electron transfer capacity for promotional formation of O2•−, and ultrathin porous structure with abundant reaction sites. Simultaneously, the up-converted fluorescent properties of the CQD endowed the photocatalyst with a broad-spectrum response. The RUCN/CQD system also exhibited superior photocatalytic activities under simulated natural conditions, which implied an immense potential for the remediation of PPCPs in ambient waterways.

The hypoxia-inducible factor (HIF) is a heterodimeric transcription factor governing a transcriptional program in response to reduced O2 availability in metazoans. It contributes to physiology and pathogenesis of many human diseases through its downstream target genes. Emerging studies have shown that the transcriptional activity of HIF is highly regulated at multiple levels and the epigenetic regulators are essential for HIF-mediated transactivation. In this review, we will discuss the comprehensive regulation of HIF transcriptional activity by different types of epigenetic regulators.

In this study, a novel visible-light-driven N-doped carbon dot (NCDs)/g-C 3 N 4 composite was successfully synthesized by loading NCDs nanoparticles onto the interlayers and surface of g-C 3 N 4 via a facile polymerized method. The photocatalytic activity of the NCDs/g-C 3 N 4 was remarkably higher than that of g-C 3 N 4 and CDs/g-C 3 N 4 toward the degradation of indomethacin (IDM) under visible light irradiation. With increasing NCDs loading volumes, the photocatalytic activity of NCDs/g-C 3 N 4 initially increased, and then decreased. A very low NCDs content of 1.0 wt% resulted in a 13.6 fold higher reaction rate than that of pristine g-C 3 N 4 . This enhanced photocatalytic activity might have been ascribed to the unique up-converted PL properties, efficient charge separation, as well as bandgap narrowing of the NCDs. Reactive species (RS) scavenging experiments revealed that superoxide radical anions (O 2 −) and photogenerated holes (h + ) played key roles during the photocatalytic degradation of IDM. The quantification of O 2 − showed that NCDs/g-C 3 N 4 formed a larger amount of O 2 − than that of pristine g-C 3 N 4 . Potential photocatalytic pathways of IDM were proposed through the identification of intermediates using HPLC–MS/MS and the prediction of reaction sites based on Frontier Electron Densities (FEDs) calculations, which involved decarboxylation, hydroxylation, as well as the addition and cleavage of indole rings. Toxicity and mineralization evaluations revealed that NCDs/g-C 3 N 4 provided a very desirable performance for the toxicity reduction and mineralization of IDM under longer exposures of visible light irradiation.

Myocardial ischemia is a primary cause of sudden death worldwide. Numerous active ingredients of traditional Chinese medicines including danshensu (DSS) and tetramethylpyrazine (TMP) have been widely used for the treatment of myocardial ischemia. To enhance their therapeutic efficacy and improve their drugability, in this work, we designed new DSS and TMP conjugates. Their water solubility and protective effects were studied in vitro and in experimental animal models. The new compounds demonstrated higher activities than the positive control agents acetylated danshensu and tetramethylpyrazine conjugate (ADTM) and salvianolic acid B (SAB) in preventing cells from oxidative insult. Among the new compounds, 14, bearing two glycine moieties, was more water soluble. In addition, compound 14 was much more potent in preventing cells from oxidative injury, at least 10- and 20-fold as potent as ADTM and SAB, respectively. The protective effects of compound 14 may be attributed to its anti-radical activity and anti-apoptotic activity. These results suggest that compound 14 is a promising candidate for the treatment of myocardial ischemia.

Chinatown, as a distinctive urban space, exists in almost all major cities in Western countries. As a richly storied place, Chinatown has been the focus of successive generations of social science ...

TFBSshape (https://tfbsshape.usc.edu) is a motif database for analyzing structural profiles of transcription factor binding sites (TFBSs). The main rationale for this database is to be able to derive mechanistic insights in protein–DNA readout modes from sequencing data without available structures. We extended the quantity and dimensionality of TFBSshape, from mostly in vitro to in vivo binding and from unmethylated to methylated DNA. This new release of TFBSshape improves its functionality and launches a responsive and user-friendly web interface for easy access to the data. The current expansion includes new entries from the most recent collections of transcription factors (TFs) from the JASPAR and UniPROBE databases, methylated TFBSs derived from in vitro high-throughput EpiSELEX-seq binding assays and in vivo methylated TFBSs from the MeDReaders database. TFBSshape content has increased to 2428 structural profiles for 1900 TFs from 39 different species. The structural profiles for each TFBS entry now include 13 shape features and minor groove electrostatic potential for standard DNA and four shape features for methylated DNA. We improved the flexibility and accuracy for the shape-based alignment of TFBSs and designed new tools to compare methylated and unmethylated structural profiles of TFs and methods to derive DNA shape-preserving nucleotide mutations in TFBSs.

Pharmaceuticals and personal care products (PPCPs) are increasingly being scrutinized by the scientific community due to their environmental persistence. Therefore, the development of novel environmentally compatible and energy-efficient technologies for their removal is highly anticipated. In this work, a novel metal-free photocatalytic nanoreactor was successfully synthesized by anchoring carbon dots to hollow carbon nitride nanospheres (HCNS/CDs). The unique structure of these hollow nanospherical HCNS/CDs hybrids endowed them with a high population of reactive sites, while enhancing optical absorption due to internal light reflection. Simultaneously, the CDs served as "artificial antennas" to absorb and convert photons with low energy, due to their superior up-converting properties. Consequently, the HCNS/CDs demonstrated excellent photodegradation activities for the degradation of PPCPs under broad-spectrum irradiation. Remarkedly, 10 mg/L of naproxen (NPX) was completely degraded following 5 min of natural solar irradiation. It was further revealed that the O

The most common known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a hexanucleotide repeat expansion (HRE) in C9ORF72 that contributes to neurodegeneration by both loss-of-function (decreased C9ORF72 protein levels) and gain-of-function (e.g. dipeptide repeat protein production) mechanisms. Although therapeutics targeting the gain-of-function mechanisms are in clinical development, it is unclear if these will be efficacious given the contribution of C9ORF72 loss-of-function processes to neurodegeneration. Moreover, there is a lack of therapeutic strategies for C9ORF72 ALS/FTD with demonstrated efficacy in vivo. Here, we show that small molecule inhibition of PIKFYVE kinase rescues both loss- and gain-of-function C9ORF72 disease mechanisms in vivo. We find that the reduction of C9ORF72 in mouse motor neurons leads to a decrease in early endosomes. In contrast, treatment with the PIKFYVE inhibitor apilimod increases the number of endosomes and lysosomes. We show that reduced C9ORF72 levels increases glutamate receptor levels in hippocampal neurons in mice, and that apilimod treatment rescues this excitotoxicity-related phenotype in vivo. Finally, we show that apilimod also alleviates the gain-of-function pathology induced by the C9ORF72 HRE by decreasing levels of dipeptide repeat proteins derived from both sense and antisense C9ORF72 transcripts in hippocampal neurons in vivo. Our data demonstrate the neuroprotective effect of PIKFYVE kinase inhibition in both gain- and loss-of-function murine models of C9ORF72 ALS/FTD.

Hypoxia is a hallmark of the tumor microenvironment and contributes to tumor malignant phenotypes. Hypoxia-inducible factor (HIF) is a master regulator of intratumoral hypoxia and controls hypoxia-mediated pathological processes in tumors, including angiogenesis, metabolic reprogramming, epigenetic reprogramming, immune evasion, pH homeostasis, cell migration/invasion, stem cell pluripotency, and therapy resistance. In this book chapter, we reviewed the causes and types of intratumoral hypoxia, hypoxia detection methods, and the oncogenic role of HIF in tumorigenesis and chemo- and radio-therapy resistance.

Despite the great success of fluorescence sensing array application in bioanalysis, the photo-quenching problem accompanied with high surface fluorophore density has become the bottleneck for its further sensitivity improvement. Herein, a fluorescence polyethylene glycol (PEG) hydrogel array was developed for highly sensitive microRNA detection based on interfacial cation exchange amplification coupled with DNA hybridization chain reaction (HCR). The carboxylate PEG hydrogel array was fabricated on glass slide via photo polymerization and modified with miRNA capture probe, target miRNA binding triggered HCR in hydrogel with biotin labelled DNA probes to generate numerous DNA polymer chains where biotinylated CdS QDs were subsequently conjugated with a streptavidin bridge. Interfacial cation exchange amplification was triggered in hydrogel upon the introduction of Ag+ and Rhod-5N, and abundant Cd2+ was released from CdS to bind with Rhod-5N for substantial fluorescence enhancement. The aqueous-like environment of hydrogel eliminated the fluorescence quenching and simplified experiment process by performing cation exchange reaction at interface with direct result. The linear range for model target miRNA-21 was 1 fM to 500 pM with a detection limit of 0.835 fM. Taking advantage of the nonfouling property of PEG hydrogel, direct quantification of miRNA-21 was achieved from crude cancer cell lysates with a detection limit down to 10 equivalent cells. The expressions of circulating miRNA-21 in clinical serum samples were also assessed with comparable results from RT-PCR. The developed hydrogel array provides a universal platform for highly sensitive fluorescence sensing, and would benefit clinical non-invasive disease diagnosis.

Hypoxia is a hallmark of the tumor microenvironment and contributes to tumor malignant phenotypes. Hypoxia-inducible factor (HIF) is a master regulator of intratumoral hypoxia and controls hypoxia-mediated pathological processes in tumors, including angiogenesis, metabolic reprogramming, epigenetic reprogramming, immune evasion, pH homeostasis, cell migration/invasion, stem cell pluripotency, and therapy resistance. In this book chapter, we reviewed the causes and types of intratumoral hypoxia, hypoxia detection methods, and the oncogenic role of HIF in tumorigenesis and chemo- and radio-therapy resistance.

The effect of recommendation concentration is critical to profit maximization of e-commerce platforms. However, recommendation with high concentration level may not always be a good thing to purchase behavior which researchers know little about. To fill this gap, we develop a stochastic model to capture the state-dependent effect of recommendation concentration on purchase behavior. Specifically, we introduce a hidden Markov model (HMM) to investigate the following research questions: (1) is there any hidden state that potentially governs the dynamic purchase journey? (2) If so, how will concentration-level factors affect purchase behavior given a consumer's hidden state? (3) How does recommendation concentration play a role in transferring consumers among different hidden states? Would concentration levels in different recommendation systems (popularity recommender, content-based recommender and collaborative filtering recommender) make a difference? Based on Bayesian estimation of the model with a granular click-stream dataset from a vertical e-commerce platform of liquors, we identify three consumer states governing the purchase process, which are termed as "awareness'', "interest'' and "desire'' respectively. Our results show that the effects of recommendation concentration on purchase are state-dependent. Concentrated recommendation with focal product is effective to boost the focal product's conversion rate in awareness state, whereas it would depress the conversion rate of the focal product in interest state. In addition, recommendation concentration has a significant impact on moving consumer into a deeper state in which the intrinsic purchase intention is higher. Furthermore, through counterfactual simulations of different concentration strategies, our findings offer implications for e-commerce platforms on when and how recommendation concentration should be introduced dynamically, which stimulates more purchase actions eventually.

Social media-based platforms tend to provide much information and numerous options for users, making choice overload a prevalent issue in many online communities. Online healthcare communities (OHCs), which provide users with various healthcare interventions to promote healthy behavior and improve adherence, are no exception. When faced with too many choices, however, individuals may find it difficult to decide which behavior intervention to take, especially when they lack the experience or knowledge to evaluate different options. Consequently, the choice overload issue may negatively affect users’ engagement in health management in OHCs. In this study, we take a design-science perspective to propose a recommendation framework that helps users to select healthcare interventions. Taking into account that users’ health behaviors can be highly dynamic and diverse, we propose a multi-armed bandit (MAB)-driven recommendation framework, which enables us to adaptively learn users’ preference variations while promoting recommendation diversity in the meantime. To better adapt an MAB to the healthcare context, we synthesize two innovative model components based on prominent health theories. The first component is a deep-learning-based feature engineering procedure, which is designed to learn crucial recommendation contexts in regard to users’ sequential health histories, health-management experiences, preferences, and intrinsic attributes of healthcare interventions. The second component is a diversity constraint, which structurally diversifies recommendations in different dimensions to provide well-rounded support for individuals’ health management. We apply our approach to an online weight management context and evaluate it rigorously through a series of experiments. Our results demonstrate that each of the design components is effective and that our recommendation design outperforms a wide range of state-of-the-art recommendation systems. Our study contributes to the emerging IS research on the application of business intelligence. The results have important implications for multiple stakeholders, including online healthcare platforms, policymakers, and users.

Multiple myeloma is an incurable cancer of bone marrow plasma cells with a median overall survival of 5 years. With newly approved drugs to treat this disease over the last decade, physicians are afforded more opportunities to tailor treatment to individual patients and thereby improve survival outcomes and quality of life. However, since the optimal sequence of therapy is unknown, selecting a treatment that will result in the most effective outcome for each individual patient is challenging. This paper addresses this challenge, considering the problem of designing personalized treatment recommendations for patients with multiple myeloma using a data-driven analytics method. We formulate the treatment recommendation problem as a Bayesian contextual bandit, which sequentially selects treatments based on contextual information about patients and therapies, with the goal of maximizing overall survival outcomes. We developed a multilevel Bayesian linear Thompson sampling to learn patients’ heterogeneous response on treatment decisions, which allows us to flexibly account for patient and line-of-therapy level heterogeneity even in the absence of a large number of observations. Facing the difficulty of evaluating the performance of the policy with only observational data, we propose a causal offline evaluation approach to measure the effect of the treatment in the presence of unmeasured confounders. We evaluate the performance of our policy on clinical data collected from 803 patients treated at Seattle Cancer Care Alliance. Our policy achieved an 19.75\% predicted improvement compared to the current clinical practice, and outperforms other benchmark strategies. Moreover, our policy achieves higher improvement for aging or high-risk patients with more complications by keeping the disease controlled at a relatively stable condition.

Individuals’ engagement in online healthcare communities (OHCs) has attracted a large body of research. However, prior research has mainly studied a single behavioral dimension of online engagement. Given that individuals’ online engagement is a complex process, overlooking certain aspects of engagement may lead to underestimating the effectiveness of OHCs. In addition, due to the progressive nature of chronic disease, chronic disease management needs to be evaluated continuously. These concerns motivate us to develop a framework that accounts for both engagement dimensions and engagement timing for studying chronic disease management in OHCs. Considering that the engagement level of disease management cannot be directly observed, in this study, we propose a multi-dimensional Continuous-Time Hidden Markov Model (CTHMM) that captures individuals’ engagement level as a latent state. We root our research in the context of weight management. Our main findings include: 1) The timing of engagement can affect an individual’s engagement level; for instance, individuals with higher participation frequency are more likely to shift to different engagement levels. 2) Participating in support-exchange activities can shift individuals’ focus from weigh-ins to journals, which are two distinct behavioral dimensions of self-monitoring. Thus, an incomplete characterization of engagement dimensions can underestimate individuals’ activeness in OHCs, which will further lead to underrating the role of OHCs in chronic disease control. 3) Different forms of social support can have statistically different effects on engagement, and these effects are mediated by individuals’ own engagement levels. Individuals need to “smartly” adopt social support tools to improve their health management.

The topological structure of a complex dynamical network plays a vital role in determining the network’s evolutionary mechanisms and functional behaviors, thus recognizing and inferring the network structure is of both theoretical and practical significance. Although various approaches have been proposed to estimate network topologies, many are not well established to the noisy nature of network dynamics and ubiquity of transmission delay among network individuals. This paper focuses on topology inference of uncertain complex dynamical networks. An auxiliary network is constructed and an adaptive scheme is proposed to track topological parameters. It is noteworthy that the considered network model is supposed to contain practical stochastic perturbations, and noisy observations are taken as control inputs of the constructed auxiliary network. In particular, the control technique can be further employed to locate hidden sources (or latent variables) in networks. Numerical examples are provided to illustrate the effectiveness of the proposed scheme. In addition, the impact of coupling strength and coupling delay on identification performance is assessed. The proposed scheme provides engineers with a convenient approach to infer topologies of general complex dynamical networks and locate hidden sources, and the detailed performance evaluation can further facilitate practical circuit design.

Hypoxia-inducible factors (HIFs) control the transcription of genes that are crucial for the pathogenesis of cancer and other human diseases. The transcriptional activity of HIFs is rapidly increased upon exposure to hypoxia, but expression of some HIF target genes decreases during prolonged hypoxia. However, the underlying mechanism for feedback inhibition is not completely understood. Here, we report that peroxiredoxin 2 (PRDX2) and PRDX4 interact with HIF-1α and HIF-2α in vitro and in hypoxic HeLa cells. Prolonged hypoxia increases the nuclear translocation of PRDX2 and PRDX4. As a result, PRDX2 and PRDX4 impair HIF-1 and HIF-2 binding to the hypoxia response elements of a subset of HIF target genes, thereby inhibiting gene transcription in cells exposed to prolonged hypoxia. PRDX2 and PRDX4 have no effect on the recruitment of p300 and RNA polymerase II to HIF target genes and the enzymatic activity of PRDX2 and PRDX4 is not required for inhibition of HIF-1 and HIF-2. We also demonstrate that PRDX2 is a direct HIF target gene and that PRDX2 expression is induced by prolonged hypoxia. These findings uncover a novel feedback mechanism for inhibition of HIF transcriptional activity under conditions of prolonged hypoxia.

Graphene oxide (GO), oxidized unzipped carbon nanotube (O-UCNT), and GO/O-UCNT composites were used as the carbon precursors to synthesize nitrogen-doped graphene (NG), nitrogen-doped unzipped carbon nanotube (NUCNT), and nitrogen-doped graphene/unzipped carbon nanotube (NG-NUCNT) composites. The influence of these carbon precursors on the synthesis of their corresponding nitrogen-doped carbon materials was systematically investigated. The results show that the synthesis of nitrogen-doped carbon materials not only depends upon the structure and composition of their corresponding carbon precursors, but also the morphology and surface property. As for single carbon precursor, the carbon precursor with higher oxygen content tends to make the nitrogen-doped carbon material with higher nitrogen content. Besides, we find that carbon precursor composites with 3D morphology and large specific surface areas contribute to fabricating nitrogen-doped carbon material with sufficient catalytic sites and high nitrogen c...

Doxorubicin (Dox) is an anthracycline antibiotic widely used in clinics as an anticancer agent. However, the use of Dox is limited by its cardiotoxicity. We have previously shown that a Danshensu (DSS) derivative, ADTM, displayed strong cardioprotective effects. With improved chemical stability and activity, a novel DSS derivative, D006, based on the structure of ADTM, was synthesized. In the present study, the protective effects of D006, indexed by attenuation of the cardiotoxicity induced by Dox as well as chemosensitizing effects that increase the antitumor activity of Dox, were investigated. Our results showed that D006 was more potent than either parental compound, or their use in combination, in ameliorating Dox-induced toxicity in H9c2 cells. In our zebrafish model, D006, but not DSS, alone significantly preserved the ventricular function of zebrafish after Dox treatment. Moreover, D006 upregulated mitochondrial biogenesis and increased mtDNA copy number after Dox treatment of H9c2 cells. D006 promoted the expression of HO-1 protein in a time-dependent manner while the HO-1 inhibitor, Znpp, reversed the protective effects of D006. In human breast tumor MCF-7 cells, D006 enhanced Dox-induced cytotoxicity by increasing apoptosis. In conclusion, our results indicate that a new DSS derivative exhibits promising protective effects against Dox-induced cardiotoxicity both in vivo and in vitro, an effect at least partially mediated by induction of HO-1 expression and the activation of mitochondrial biogenesis. Meanwhile, D006 also potentiated the anti-cancer effects of Dox in breast tumor cells.

Sensitivity of the Cu2O octahedral structures towards ethanol, acetone, triethylamine and formaldehyde has been significantly enhanced by increasing the numbers of 1-coordinated Cu (Cu1c) atoms on the (111) facet of Cu2O octahedrons through hydrogenation. The Cu1c atom with one dangling bond is considered to be a reaction active center. The active center has three kinds of functions: adsorbing oxygen, creating free electrons and catalyzing the redox reaction between the adsorbed oxygen and the detected gas. The findings can deepen comprehending gas sensing mechanisms and give guidance to design high performance sensing material. In addition, the hydrogenation surface-engineering strategy can be employed to enhance sensing performances of other materials.

Pharmaceuticals and personal care products (PPCPs) are increasingly being scrutinized by the scientific community due to their environmental persistence. Therefore, the development of novel environmentally compatible and energy-efficient technologies for their removal is highly anticipated. In this work, a novel metal-free photocatalytic nanoreactor was successfully synthesized by anchoring carbon dots to hollow carbon nitride nanospheres (HCNS/CDs). The unique structure of these hollow nanospherical HCNS/CDs hybrids endowed them with a high population of reactive sites, while enhancing optical absorption due to internal light reflection. Simultaneously, the CDs served as “artificial antennas” to absorb and convert photons with low energy, due to their superior up-converting properties. Consequently, the HCNS/CDs demonstrated excellent photodegradation activities for the degradation of PPCPs under broad-spectrum irradiation. Remarkedly, 10 mg/L of naproxen (NPX) was completely degraded following 5 min of natural solar irradiation. It was further revealed that the O2•- played a significant role during the photocatalytic process, which could lead to the decomposition of NPX. The effects of natural water matrices and the degradation of trace PPCPs further supported that this photocatalytic system may be efficaciously applied for the remediation of PPCPs contamination in ambient waterways.

As a surface optimization strategy, hydrogenation has been successfully used to enhancing the responses of CdO octahedrons sensors to acetone, ethanol and triethylamine by increasing the numbers of 3-coordinate Cd (Cd3c) atoms on the CdO (111) surface. The Cd3c atom with three dangling bonds at Cd-CdO (111) surface is considered to be a reactive center for gas sensing, which has three functions: adsorbing oxygen from air, generating free electrons, and catalyzing the redox reaction of the target gas with adsorbed oxygen. The sensing mechanism of surface Cd3c atom acting as a reactive center can not only deepen understanding the mechanisms of gas sensing and heterogeneous catalytic reactions, but also provide a new insight for developing highly performance sensing and catalytic materials. In addition, hydrogenation may be a general effective strategy for improving sensing and catalytic performances of semiconductor materials.

Hypoxia-inducible factor-1 (HIF-1) is a key regulator of erythropoiesis. In this article, we report 3 novel mutations, P378S, A385T, and G206C, on the EGLN1 gene encoding the negative HIF-1α regulator prolyl hydroxylase domain-2 (PHD2) in 3 patients with isolated erythrocytosis. These mutations impair PHD2 protein stability and partially reduce PHD2 activity, leading to increased HIF-1α protein levels in cultured cells.

Enabling the optimal usage of solar energy is considered to be one of the most pressing challenges in the photocatalytic remediation of water resident contaminants. Herein, a single-atom dispersed Ag loaded ultrathin g-C3N4 hybrid (AgTCM/UCN) was prepared through a facile co-polymerization of dicyandiamide with silver tricyanomethanide (AgTCM) and NH4Cl, and used as a visible light driven photocatalyst for the degradation of sulfamethazine (SMT) in the presence of peroxymonosulfate (PMS). Under UV light, visible light and simulated sunlight irradiation, the AgTCM/UCN/PMS process showed higher efficiency for SMT degradation than AgTCM/UCN, UCN/PMS, and g-C3N4/PMS systems. This enhanced photocatalytic activity may be attributed to the synergistic effects encompassing the surface plasmon resonance (SPR) of Ag, high surface area of UCN, and efficient charge separation of PMS. Electron-spin resonance (ESR) and reactive species (RSs) scavenger-quenching experiments revealed that SO4˙- was generated following the addition of PMS, whereas O2˙- and h+ were predominantly responsible for the degradation of SMT. Three degradation pathways of SMT were deduced, including the cleavage of sulfonamide bonds, SO2 extrusion, and the oxidation of the aniline moiety, based on mass spectrometry and theoretical calculations. The degradation of SMT in ambient water revealed that the AgTCM/UCN/PMS photocatalytic process can be efficaciously applied for the remediation of SMT contaminated natural waters, particularly sea water.

The development of facile and efficient synthetic approaches of carbon quantum dots loaded with mesoporous g-C

Users’ participation in virtual communities is a complex process. On the one hand, there exist more than one dynamic sources, such as sequential dynamics and temporal dynamics. On the other hand, users may develop different participation focuses through the participation process. These aspects are underexplored in the extant literature. This research gap motivates us to develop an effective approach to calibrate users’ online behaviors. Specifically, we develop a multi-dimensional continuous-time hidden Markov model (HMM). This model is able to control both sequential and temporal dynamics of users’ online behaviors. In addition, it allows us to explore users’ multiple correlated behavioral dimensions at the same time. To gauge the effectiveness of our approach, we root our research in the context of weight management. The data is collected from a leading online weight-loss community in the US. Our main findings include 1). Timing information can bring valuable insights on users’ participation pattern in virtual communities, and it improves our model forecast performance. 2). Users may shift their participation focuses during the participation process. 3). Different social-support exchange strategies have statistically different effects on users’ weight management, and these effects are mediated by users’ community commitment. Together, these findings suggest that overlooking information imbedded in observed behaviors of users may result in inaccurate or even falsified conclusions on participation pattern. In addition, personalized health care strategy need to be implemented when individual’s condition is complicated and varying with time, such as chronic diseases like obesity and diabetes. Further, we provide several application examples to illustrate the practical values of our study, in which we combine our empirical model with machine learning techniques. These examples can be readily applied to a variety of business settings such as personalized recommendation, precision marketing and user characterization.

Based on the data at the end of 2016 and selecting 12 variables such as building area and paper resource purchase fee, this paper uses principal component analysis and cluster analysis to evaluate the support ability and overall strength of 42 universities and colleges under “double-first class” construction. At last, ranking and classifying the university libraries according to the research results. This study has shown that the number of staff members, the purchase fee of electronic resources, paper resources, literature resources, the number of published paper and the number of paper resources are the main factors affecting the construction of university libraries. The gap in support ability among university libraries in the same region, different provinces and cities, and different types are obvious; the imbalance of libraries' own strength leads to their inefficiency; the strength of university libraries does not match the strength of scientific research. It is recommended that universities and colleges should allocate funds reasonably, increase the investment and attention in libraries, and strengthen exchanges and cooperation between university libraries in and between regions.

In this work, a nitrogen-doped unzipped carbon nanotube/sulfur (NUCNT/S) composite was initially synthesized by a low-cost and scalable process and investigated as a cathode material for lithium–sulfur batteries. The morphology, structure and composition of the obtained NUCNT/S electrode were studied. Meanwhile, the effect of nitrogen doping on the electrochemical performance of the NUCNT/S cathode was discussed in detail. The results show that the NUCNT/S cathode presents excellent cyclability and rate capability, and the superior electrochemical properties of the NUCNT/S cathode can be attributed to the co-effect of rational design of the cathode nanostructure and successful nitrogen doping in the carbon matrix. On the one hand, NUCNTs with large surface areas and a special unzipped structure have a good effect on wrapping S particles. On the other hand, N doping can not only promote the distribution of sulfur particles and the electronic conductivity of the carbon matrix, but also immobilize the sulfur particles and polysulfides, which results in good sulfur utilization and long cycle life of the cathode. Therefore, the design of the NUCNT/S composite provides a promising candidate for the cathode material for lithium–sulfur batteries, and it also offers a strategy to prepare a sulfur cathode with a novel structure and advanced performance.

We consider the nested-batch decision problem where we need to make a first stage choice (e.g., the size of a nanoparticle), after which we then need to run a series of experiments in batches selecting several second stage choices (e.g., testing different densities of the nanoparticle). Since these experiments are time consuming and expensive, we propose to estimate the value of information from the choice of the first stage decision (the size), to help guide the scientist in the selection of the next batch of experiments to run. The batch experiments are designed assuming that we maximize the value of information for an entire batch. The value of information, known as the knowledge gradient, requires calculating the expected maximum of a function. Since the calculation of the expected maximum is computationally intractable, we propose a Monte Carlo--based approach to address this hurdle in the context of both the batch and nested-batch problems. We empirically demonstrate the effectiveness of our approac...

The aim of this study was to investigate the photolysis mechanism of ketoprofen (KET) under simulated sunlight. The results demonstrated that the photolysis of KET aligned well with pseudo first-order kinetics. Radical scavenging experiments and dissolved oxygen experiments revealed that the superoxide anion radical (O2˙−) played a primary role in the photolytic process in pure water. Bicarbonate slightly increased the photodegradation of KET through generating carbonate radicals, while DOM inhibited the photolysis via both attenuating light and competing radicals. Moreover, Zhujiang river water inhibited KET phototransformation. Potential KET degradation pathways were proposed based on the identification of products using LC/MS/MS and GC/MS techniques. The theoretical prediction of reaction sites was derived from Frontier Electron Densities (FEDs), which primarily involved the KET decarboxylation reaction. The ecotoxicity of the treated solutions was evaluated by employing Daphnia magna and V. fischeri as biological indicators. Ecotoxicity was also hypothetically predicted through the “ecological structure–activity relationship” (ECOSAR) program, which revealed that toxic products might be generated during the photolysis process.

The sharing economy has experienced rapid growth in recent years. Despite the social and economic impact, the sharing economy platform suffers from information asymmetry and a lack of government enforcement. Apart from customer reviews, platform disclosure is also a valuable source to provide quality signals. While most platforms use badges to help with consumer decisions, more platforms have started disclosing picture information. We investigate how picture disclosure would influence the consumer behavior and the role of platform disclosure among other quality-enhancing mechanisms such as reputation and market competition. Our analysis is based on the data from a large peer-to-peer meal-sharing platform in China. The platform conducts onsite hygiene inspection to evaluate the suppliers' hygiene quality and discloses kitchen pictures as the hygiene quality signal. We integrate an econometric analysis method with deep-learning and computer-vision techniques and find that, although the disclosure leads to an overall sales increase, suppliers with a passing but relatively low hygiene quality suffers from a sales decrease. Besides, disclosing images can create misinterpretation due to the noise in the quality signal, resulting in a non-monotonic sales impact as related to the platform evaluated hygiene quality. We also find that the effect is attenuated when market competition is intense or when the supplier's reputation on hygiene quality is high. Our work extends the previous studies, which focus on the positive role of platform disclosure, by highlighting that the informative effect of disclosing pictures overweighs the qualification effect and that the noise in pictures can still lead to suboptimal outcomes. It also integrates the enforcement method from the three main parts of the sharing economy ecosystem suppliers in terms of market competition, consumers in terms of online review, and the platform in terms of picture disclosure. Business and technical contributions are also discussed.

Summary The conventional double hysteresis control method for unified power quality controller (UPQC) is used to get the optimal voltage that can control the error of phase current quickly according to the distribution of reference voltage, the location of current error and whether the current error is beyond the limits. Although this method can provide fast current response and decrease high-order harmonics and switching frequency, it decreases the compensation accuracy because when the current error is in the inner loop, the inverter does no actions. In this paper, a modified double hysteresis current control method is proposed to improve the performance of UPQC, the active disturbance rejection controller (ADRC) is innovatively introduced to the inner control of double hysteresis current control for UPQC, both inner uncertainty and external uncertainty are treated as unified unknown disturbances that are estimated by the extended state observer and are compensated by the nonlinear state error feedback control law, and the algorithm of particle swarm optimization (PSO) is used to optimize the ADRC parameters. Therefore, the proposed method offers the following additional benefits: the complicated calculation is avoided; the accurate measurement of harmonics is not required; the utilization ratio of voltage is improved; and the adaptability of control system is strong. The simulation results show that the proposed method has good static/dynamic performance and strong robustness. Copyright © 2014 John Wiley & Sons, Ltd.

Actin filament formation plays an essential role in cell movement, and posttranslational modifications regulate actin filament assembly. Prolyl hydroxylase 3 (PHD3) interacts with nonmuscle actins in HeLa cells and catalyzes prolyl hydroxylation of actin. Inhibition of PHD3 activity or expression increases F-actin formation and cell motility., Actin filaments play an essential role in cell movement, and many posttranslational modifications regulate actin filament assembly. Here we report that prolyl hydroxylase 3 (PHD3) interacts with nonmuscle actin in human cells and catalyzes hydroxylation of actin at proline residues 307 and 322. Blocking PHD3 expression or catalytic activity by short hairpin RNA knockdown or pharmacological inhibition, respectively, decreased actin prolyl hydroxylation. PHD3 knockdown increased filamentous F-actin assembly, which was reversed by PHD3 overexpression. PHD3 knockdown increased cell velocity and migration distance. Inhibition of PHD3 prolyl hydroxylase activity by dimethyloxalylglycine also increased actin polymerization and cell migration. These data reveal a novel role for PHD3 as a negative regulator of cell motility through posttranslational modification of nonmuscle actins.

Poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) acts as a DNA damage sensor. It recognizes DNA damage and facilitates DNA repair by recruiting DNA repair machinery to damage sites. Recent studies reported that PARP-1 also plays an important role in DNA replication by recognizing the unligated Okazaki fragments and controlling the speed of fork elongation. On the other hand, emerging evidence reveals that excessive activation of PARP-1 causes chromatin DNA fragmentation and triggers an intrinsic PARP-1-dependent cell death program designated parthanatos, which can be blocked by genetic deletion or pharmacological inhibition of PARP-1. Therefore, PARP-1 plays an essential role in maintaining genomic stability by either facilitating DNA repair/replication or triggering DNA fragmentation to kill cells. A group of structure-specific nucleases is crucial for executing DNA incision and fragmentation following PARP-1 activation. In this review, we will discuss how PARP-1 coordinates with its associated nucleases to maintain genomic integrity and control the decision of cell life and death.

DNA damage-activated nuclease identified Cells that experience stresses and accumulate excessive damage to DNA undergo cell death mediated by a nuclear enzyme known as PARP-1. During this process, apoptosis-inducing factor (AIF) translocates to the nucleus and activates one or more nucleases to cleave DNA. Wang et al. found that macrophage migration inhibitory factor (MIF) is an AIF-associated endonuclease that contributes to PARP-1-induced DNA fragmentation (see the Perspective by Jonas). In mouse neurons in culture, loss of MIF protected neurons from cell death caused by excessive stimulation. Targeting MIF could thus provide a therapeutic strategy against diseases in which PARP-1 activation is excessive. Science , this issue p. 82 ; see also p. 36

This paper investigates topology identification of two-layer unidirectional complex dynamical networks based on auxiliary-system approach. Particularly, consider the interested layer as response layer, the other layer as drive layer, then construct a auxiliary layer which is driven by the driving signal as an identical duplication of the response layer. Based on the theory of Barbalat's lemma, some control inputs and updating laws are designed so that nodes in the auxiliary layer reaches complete synchronization with their counterparts in the response layer and the unknown topology of the response layer can be adaptively identified, meanwhile, the drive layer and the response layer achieve generalized synchronization. Numerical simulations are provided to illustrate the effectiveness of the proposed method. We expect that the analysis in this paper could prompt attention and provide basic insight into further research on detecting the route and the source of rumor and pseudo news spreading.

The defining anatomical feature of Parkinson's disease (PD) is the degeneration of substantia nigra pars compacta (SNc) neurons, resulting in striatal dopamine (DA) deficiency and in the subsequent alteration of basal ganglia physiology. Treatments targeting the dopaminergic system alleviate PD symptoms but are not able to slow the neurodegenerative process that underlies PD progression. The nucleus striatum comprises a complex network of projecting neurons and interneurons that integrates different neural signals to modulate the activity of the basal ganglia circuitry. In this review we describe new potential molecular and synaptic striatal targets for the development of both symptomatic and neuroprotective strategies for PD. In particular, we focus on the interaction between adenosine A2A receptors and dopamine D2 receptors, on the role of a correct assembly of NMDA receptors, and on the sGC/cGMP/PKG pathway. Moreover, we also discuss the possibility to target the cell death program parthanatos and the kinase LRRK2 in order to develop new putative neuroprotective agents for PD acting on dopaminergic nigral neurons as well as on other basal ganglia structures.

A novel amphoteric polycarboxylic (APC) acid-based superplasticizer was prepared by solution copolymerization from maleic anhydride, allyl polyethylene glycol, and methacryloxyethyltrimethyl ammonium chloride (DMC). The cationic monomer DMC was introduced for improving the performances of sulfoaluminate cement (SAC) with APC. The condition on preparation of APC was determined by the orthogonal experiment, and the performances of fresh and hardened superplasticized mortars were assessed. APC was characterized by FTIR spectra. Adsorption amount and dispersing effectiveness of APC were also investigated. Results indicated that APC could improve the fluidity and enhance the mechanical performances of SAC mortars. Adsorption amount of APC in SAC is large. Compared with an anionic PC superplasticizer and a commercial superplasticizer Visco Crete 3390, APC has the better performance. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

We recently characterized the proteinase-activated receptor (PAR)-2, a G protein-coupled receptor (GPCR), as the first cargo protein recognized by p24A. Here, we demonstrate that p24A binds to several other GPCRs, including PAR-1, the nucleotide receptors P2Y(1), P2Y(2), P2Y(4), and P2Y(11), as well as the μ-opioid receptor 1B. The acidic amino acid residues Glu and Asp at the second extracellular loop of GPCRs are essential for interaction with p24A. p23, another member of the p24 family, also interacts with GPCRs, similar to p24A. However, p23 shows a delayed dissociation from PAR-2 after activation of PAR-2, compared to the dissociation between PAR-2 and p24A. p24A and p23 arrest both P2Y(4) receptor and μ-opioid receptor 1B at the intracellular compartments, as observed for PAR-2. A comparable result was obtained when we studied primary rat astrocytes in culture. Over-expression of the N-terminal p24A fragment impairs PAR-2 resensitization in astrocytes that extends our findings to a native system. In summary, we demonstrate that p24A and p23 are specific cargo receptors of GPCRs and differentially control GPCR trafficking in the biosynthetic pathway, and thereby, p24A and p23 regulate GPCR signaling in astrocytes.

Metastatic breast cancer is lethal and incurable. The major obstacle to ending this aggressive disease is the absence of definitive prognostic biomarker and effective therapeutic target. Epigenetic dysregulation plays a crucial role in breast cancer metastasis. However, how epigenetic dysregulation under tumor hypoxia stimulates breast cancer progression and metastasis remains unknown. We recently identified the epigenetic reader ZMYND8 as a novel HIF target gene by analyzing expression changes of 720 epigenetic genes in three microarray gene expression and mRNA sequencing datasets. Analysis of a human breast cancer tissue microarray revealed that ZMYND8 is highly expressed in invasive breast tumors and high levels of ZMYND8 are significantly correlated with poor clinical outcomes in patients with breast cancer. ZMYND8 depletion significantly suppresses colony formation, invasion, and migration of breast cancer cells in vitro, and inhibits breast tumor growth and metastasis in mice. To figure out the underlying mechanism, we performed co-immunoprecipitation, chromatin immunoprecipitation, and quantitative PCR assays and found that ZMYND8 interacts with HIF complex and acetyl lysine 16 of histone H3 at the hypoxia response elements (HREs) to stimulate the expression of HIF target genes LOX, AGR2, AQP1, and VEGFA. HIF is required for ZMYND8-mediated breast cancer growth and metastasis in mice. We further found that p300 binds and acetylates ZMYND8 in breast cancer cells. Acetylated ZMYND8 interacts with the bromodomains of BRD4 and recruits BRD4 to the HREs to stimulate RNA polymerase II phosphorylation and subsequent transcriptional elongation of HIF target genes. ZMYND8 acetylation is necessary and sufficient for breast tumor growth and metastasis in vitro and in mice. Together, these findings indicate that p300-acetylated ZMYND8 mediates breast cancer progression and metastasis by BRD4-dependent activation of HIF. In summary, ZMYND8 represents a positive-feedback mechanism that amplifies HIF-mediated breast cancer progression and metastasis, and may be a potential epigenetic target for the prognosis and treatment of breast cancer. Citation Format: Yan Chen, Bo Zhang, Lei Bao, Lai Jin, Mingming Yang, Yan Peng, Jennifer Wang, Chenliang Wang, Xuan Zou, Yingfei Wang, Weibo Luo. HIF-ZMYND8-BRD4 axis mediates breast cancer progression and metastasis [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr B52.

Epigenetic regulator plays a pivotal role in breast cancer progression. We recently demonstrated that the epigenetic reader zinc finger MYND-type containing 8 (ZMYND8) mediates breast cancer progression and metastasis by activating hypoxia-inducible factor (HIF). This discovery provides new insights into the molecular mechanism underlying HIF activation and breast cancer progression.

Metastatic breast cancer has high rates of relapse and mortality. The absence of definitive prognostic biomarker and effective therapeutic target is the major obstacle to end this aggressive disease. Epigenetic dysregulation plays a crucial role in breast cancer metastasis. However, the mechanism by which epigenetic dysregulation stimulates the hypoxia-mediated breast cancer progression and metastasis remains unknown. Based on luciferase reporter assays and analysis of expression changes of 720 epigenetic genes in three microarray datasets, we identified epigenetic reader ZMYND8 as a novel hypoxia-inducible factor (HIF) target gene. Human breast cancer tissue microarray data indicated that ZMYND8 is highly expressed in invasive breast tumors and this overexpression is significantly correlated with poor clinical outcomes in patients with breast cancer. ZMYND8 depletion dramatically attenuates the tumorigenic potential of breast cancer cells in colony formation, migration and invasion in vitro, and suppresses breast tumor growth and metastasis in mice. To elucidate the underlying mechanism, we performed co-immunoprecipitation, chromatin immunoprecipitation and quantitative PCR assays and found that ZMYND8 interacts with HIF complex and acetyl lysine 16 of histone H3 at the hypoxia inducible elements (HREs) to provoke the expression of HIF target genes LOX, AGR2, AQP1 and VEGFA. ZMYND8 controls breast cancer growth and metastasis through HIF in mice. We further found that p300 binds and acetylates ZMYND8 in breast cancer cells. Acetylated ZMYND8 interacts with and recruits BRD4 to the HREs to stimulate RNA polymerase II phosphorylation, thereby promoting transcriptional elongation of HIF target genes. ZMYND8 acetylation is necessary and sufficient for breast tumor growth and metastasis in vitro and in mice. Together, p300-ZMYND8-BRD4-HIF axis is critical for breast cancer progression and metastasis. In summary, ZMYND8 represents a positive feedback mechanism that amplifies HIF-mediated breast cancer progression and metastasis, and provides a potential epigenetic target for the prognosis and treatment of breast cancer. Citation Format: Yan Chen, Bo Zhang, Lei Bao, Lai Jin, Mingming Yang, Yan Peng, Jennifer Wang, Chenliang Wang, Xuan Zou, Yingfei Wang, Weibo Luo. Epigenetic reader ZMYND8 bridges BRD4 and hypoxia-inducible factors to mediate breast cancer progression and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 82.

Hypoxia-inducible factor 1 (HIF-1) is a main regulator of cellular response to hypoxia and its transcriptional activity is crucial for cancer cell migration and invasion. Post-translational modifications of the α subunit of HIF-1 (HIF-1α) play dominant roles in regulating its function. In this study, we demonstrated that the lysine methyltransferases G9a and GLP catalyzed mono- and di-methylation of HIF-1α at lysine (K) 674 in vitro and in vivo. Functionally, K674 methylation suppressed HIF-1 transcriptional activity as well as expression of the HIF-1 target genes including PTGS1, NDNF, SLC6A3, and Linc01132 in human glioblastoma U251MG cells. Moreover, mutation of K674 of HIF-1α significantly enhanced U251MG cell migration under hypoxia. Importantly, we found that G9a level was downregulated by hypoxia in glioblastoma, which was negatively correlated with PTGS1 expression and survival rate in glioblastoma patients. These findings reveal a novel naturally existing negative feedback mechanism that maintains high activity of HIF-1 and cell mobility in human glioblastoma. Citation Format: Lei Bao, Yan Chen, Hsien-Tsung Lai, Cheng-Ming Chiang, Gregg L. Semenza, Yingfei Wang, Weibo Luo. Inhibition of hypoxia-inducible factor 1 (HIF-1) transcriptional activity and cell mobility via G9a/GLP-mediated methylation of HIF-1α [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5427.

Poly(ADP-ribose) polymerase-1 (PARP-1) plays a pivotal role in multiple neurologic diseases by mediating caspase-independent cell death, which has recently been designated parthanatos to distinguish it from other forms of cell death such as apoptosis, necrosis and autophagy. Mitochondrial apoptosis-inducing factor (AIF) release and translocation to the nucleus is the commitment point for parthanatos. This process involves a pathogenic role of poly (ADP-ribose) (PAR) polymer. It generates in the nucleus and translocates to the mitochondria to mediate AIF release following lethal PARP-1 activation. PAR polymer itself is toxic to cells. Thus, PAR polymer signaling to mitochondrial AIF is the key event initiating the deadly crosstalk between the nucleus and the mitochondria in parthanatos. Targeting PAR-mediated AIF release could be a potential approach for the therapy of neurologic disorders.