E3 ligase Smurf1 protects against misfolded SOD1 in neuronal cells by promoting its K63 ubiquitylation and aggresome formation.

K63-linked polyubiquitination of the neurodegenerative disease-associated misfolded protein copper-zinc superoxide dismutase 1 (SOD1) is associated with the formation of inclusion bodies. Highly expressed E3 ligase Smad ubiquitylation regulatory factor 1 (Smurf1) promotes cellular homeostasis through the enhanced capability of aggregate degradation. However, it is not well explored the role of Smurf1 in the dynamics of SOD1 aggresomes. In this study, we report that Smurf1 promotes the recruitment of SOD1 to form aggresomes. Mechanistically, Smurf1 interacts with mutant SOD1 to promote aggresome formation by modification of its K63-linked polyubiquitination. Moreover, overexpressed Smurf1 enhances mutant SOD1 aggresome formation and autophagic degradation to prevent cell death. Thus, our data suggest that Smurf1 plays an important role in attenuating protein misfolding-induced cell toxicity by both driving the sequestration of misfolded SOD1 into aggresomes and autophagic degradation.

PCNN Model Guided by Saliency Mechanism for Image Fusion in Transform Domain.

In heterogeneous image fusion problems, different imaging mechanisms have always existed between time-of-flight and visible light heterogeneous images which are collected by binocular acquisition systems in orchard environments. Determining how to enhance the fusion quality is key to the solution. A shortcoming of the pulse coupled neural network model is that parameters are limited by manual experience settings and cannot be terminated adaptively. The limitations are obvious during the ignition process, and include ignoring the impact of image changes and fluctuations on the results, pixel artifacts, area blurring, and the occurrence of unclear edges. Aiming at these problems, an image fusion method in a pulse coupled neural network transform domain guided by a saliency mechanism is proposed. A non-subsampled shearlet transform is used to decompose the accurately registered image; the time-of-flight low-frequency component, after multiple lighting segmentation using a pulse coupled neural network, is simplified to a first-order Markov situation. The significance function is defined as first-order Markov mutual information to measure the termination condition. A new momentum-driven multi-objective artificial bee colony algorithm is used to optimize the parameters of the link channel feedback term, link strength, and dynamic threshold attenuation factor. The low-frequency components of time-of-flight and color images, after multiple lighting segmentation using a pulse coupled neural network, are fused using the weighted average rule. The high-frequency components are fused using improved bilateral filters. The results show that the proposed algorithm has the best fusion effect on the time-of-flight confidence image and the corresponding visible light image collected in the natural scene, according to nine objective image evaluation indicators. It is suitable for the heterogeneous image fusion of complex orchard environments in natural landscapes.

Evaluation of the in vitro performance of generic and original adapalene gel.

OBJECTIVE: The aim was to evaluate the difference of the in vitro behavior between the commercially available generic adapalene gel and original product with Topical Classification System (TCS), and to analyze the effect of changes of excipients on the release behavior. SIGNIFICANCE: Establishing in vitro performance assays to understand the impact of formulation variables on the critical quality attributes (CQA) is critical for the quality assessment of semi-solid generic drug. METHODS: In vitro release (IVR), in vitro permeation (IVP), viscosity, and pH measurement methods for adapalene gels were established and validated. The differences between generic adapalene gel from 7 companies and original products were evaluated by correlation analysis (CA) and principal component analysis (PCA), and the relationship among 4 parameters was elucidated. The effect of excipients on the above variables was examined by univariate tests. RESULTS: There were some differences between the gels of 5 of the 7 imitation enterprises and reference listed drug (RLD). There were varying degrees of correlation between viscosity, pH, the adapalene amount retained in skin and release rate. The result validated the key role of IVR, and identified that pH value, type of suspending agent, the amount of carbomer, etc. had certain effects on the release rate. CONCLUSIONS: The factors mentioned above should be considered when developing and manufacturing generic adapalene gels, and the application of TCS in the evaluation of generic topical drugs was advanced. Additionally, our research revealed some discrepancies from USP<1724>, which could be valuable information for the revision.

Understanding the multi-modal affective expression of net language in computer-mediated communication.

The fast development of technology and the popularity and prevalence of social media are constantly changing people's way of living especially their communication patterns. Computer-mediated communication facilitates human contact. Meanwhile, net language becomes widely accepted by computer-mediated communicators. Originating from the text-based form, net language evolves into a multi-modal physical form with a combination of texts, symbols, emojis, pictures and other forms of messages. The multi-modality of net language gives rise to difficulties for hearers or readers of the computer-mediated communication to understand the hidden message due to the ambiguous and polysemic nature of symbols. To clarify hearer's understanding and ensure the smooth conduct of computer-mediated communication, the conceptual blending theory will be useful in processing the multi-modal net language. With a four-space network and three operation mechanism, the emergent meaning will be constructed.

Identifying features of source and message that influence the retweeting of health information on social media during the COVID-19 pandemic.

BACKGROUND: Social media has become an essential tool to implement risk communication, giving health information could gain more exposure by retweeting during the COVID-19 pandemic. METHODS: Content analysis was conducted to scrutinize the official (national and provincial) public health agencies' Weibo posts (n = 4396) to identify features of information sources and message features (structure, style content). The Zero-Inflated Negative Binomial (ZINB) model was adopted to analyze the association between these features and the frequency of the retweeted messages. RESULTS: Results indicated that features of source and health information, such as structure, style, and content, were correlated to retweeting. The results of IRR further suggested that compared to provincial accounts, messages from national health authorities' accounts gained more retweeting. Regarding the information features, messages with hashtags#, picture, video have been retweeted more often than messages without any of these features respectively, while messages with hyperlinks received fewer retweets than messages without hyperlinks. In terms of the information structure, messages with the sentiment (!) have been retweeted more frequently than messages without sentiment. Concerning content, messages containing severity, reassurance, efficacy, and action frame have been retweeted with higher frequency, while messages with uncertainty frames have been retweeted less often. CONCLUSIONS: Health organizations and medical professionals should pay close attention to the features of health information sources, structures, style, and content to satisfy the public's information needs and preferences to promote the public's health engagement. Designing suitable information systems and promoting health communication strategies during different pandemic stages may improve public awareness of the COVID-19, alleviate negative emotions, and promote preventive measures to curb the spread of the virus.

Therapeutic Perspective of Temozolomide Resistance in Glioblastoma Treatment.

Glioblastoma (GB) is the most lethal form of primary brain neoplasm. TMZ is the first-line standard treatment, but the strong resistance constrains the efficacy in clinical use. GB contains glioma stem cells (GSCs), which contribute to TMZ resistance, promote cell survival evolvement, and repopulate the tumor mass. This review summarizes the TMZ-resistance mechanisms and discusses several potential therapies from the conservative opinion of GSC-targeted therapy orientation to the current view of TMZ resistance-aimed efficacy, which will provide an understanding of the role of heterogeneity in drug resistance and improve therapeutic efficacy in general.

Clinicopathological characteristics of dysplastic teratomous neuroglia with anti-N-methyl-d-aspartate receptor encephalitis.

In this study, we investigated whether unique pathological characteristics exist in teratomas that can trigger autoimmune anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. We compared a case of retroperitoneal teratoma associated with anti-NMDAR encephalitis and four control cases. The encephalitis-positive case showed that (i) more dysplastic neuroglia with higher Ki-67 labeling index values than the control cases, which met the diagnostic criteria of astrocytoma, (ii) the NMDAR subunit NR1 was expressed more abundantly in neuroglial tissue where many neuroglial cells co-expressed glial fibrillary acidic protein (GFAP) and NR1 and formed abnormally large cellular masses, (iii) intense NR1 expression occurs in squamous epithelium near neuroglial tissue and lymphocyte infiltration. This study showed that dysplastic neuroglial tissue resembling central nervous system tumors, which might promote autoimmunity, distinguished the case with NMDAR encephalitis from the controls. Additionally, abnormal expression of NR1 occurs in non-neural tissues and could be triggered by inflammation and participate in autoimmunity.

Transient supramolecular hydrogels formed by catalytic control over molecular self-assembly.

The present work shows how transient supramolecular hydrogels can be formed by catalytically controlled molecular self-assembly. Catalysis formation of molecular gelators leads the self-assembly along a kinetically favored pathway, resulting in transient hydrogels. This work demonstrates an effective approach towards pathway-dependent supramolecular materials.

A facile approach to obtain highly tough and stretchable LAPONITE®-based nanocomposite hydrogels.

LAPONITE® sheets have been widely used for the preparation of tough nanocomposite hydrogels for enticing applications; however, their inferior dispersion in aqueous media resulting from electrostatic interactions between the nanosheets remarkably limits further improvements in the mechanical performances of the nanocomposite hydrogels. Here, we show a simple approach to dramatically accelerate the dispersion of LAPONITE® sheets in water, and in turn further improve the mechanical performances of the resulting nanocomposite hydrogels. Upon addition of poly(acrylic acid) (PAA), the electrostatic interactions between the LAPONITE® sheets were effectively reduced due to the adsorption of PAA onto the positively charged edges of the LAPONITE® sheets, thereby accelerating the dispersion of the LAPONITE® sheets in water. On this basis, a series of polyacrylamide (PAAm) hydrogels with a high content of LAPONITE® sheets was prepared, showing excellent tensile strength, stretchability, and anti-fatigue properties. This study will be beneficial for the preparation of LAPONITE®-based nanocomposite hydrogels bearing excellent mechanical properties for new applications.

A rare case of pediatric moyamoya disease with reversible white matter lesions in a 3-year-old Chinese girl.

Moyamoya disease is a chronic cerebral vascular disease characterized by progressive occlusion of the cerebral arteries and resulting in the development of abnormal collateral circulation. We report a case of moyamoya disease in a 3-year-old Chinese girl with partly reversible white matter lesions. This case indicates that, in pediatric moyamoya disease, white matter lesions may be associated with cerebral ischemia, and they may be reversible after treatment.

Research progress in nervous system damage caused by SARS-CoV-2. / SARS-CoV-2å¯¹ç¥žç»ç³»ç»ŸæŸå®³çš„ç ”ç©¶è¿›å±•.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major outbreak in the world. SARS-CoV-2 infection can not only involve in the respiratory system, but also cause severe nervous system damage. Studies have shown that SRAS-CoV-2 can invade the nervous system through hematogenous and transneuronal pathways, and may cause nervous system damage in patients with COVID-19 by inhibiting cellular immunity, hypoxemia, inflammation, inducing neuronal degeneration and apoptosis, and angiotensin converting enzyme 2 (ACE2) mechanism. It can lead to intracranial infection, toxic encephalopathy, acute cerebrovascular disease, muscle damage, peripheral nervous system injury, acute myelitis, demyelination disease or other nervous system diseases.

Clinical characteristics of anti-N-methyl-D-aspartate receptor encephalitis in children. / 儿童抗N-甲基-D-å¤©å†¬æ°¨é ¸å—ä½“è„‘ç‚Žçš„ä¸´åºŠç‰¹å¾.

OBJECTIVES: To analyze the clinical characteristics and prognosis of children with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and to provide a basis for early clinical identification of this disease. METHODS: The clinical data of 42 cases of anti-NMDAR encephalitis at Department of Pediatrics, Second Xiangya Hospital, Central South University from January 2015 to March 2018 were collected. The clinical features and followed-up outcomes were analyzed retrospectively. RESULTS: There were 15 cases (35.7%) of males and 27 cases (64.3%) of females in 42 children, with a ratio of 1꞉1.8. They were aged from 4 months to 17 years, with an average of (9.20±4.66) years. The most common initial symptoms were seizures (47.6%, 20/42) and mental behavior disorder (35.7%, 15/42). During the course of the disease, 85.7% patients(36/42) had mental and behavior disorder, 85.7% patients (36/42) had epilepsy, 76.2% (32/42) had speech disorder, 66.7% patients (28/42) had dyskinesia, 66.7% patients (28/42) had the decreased level of consciousness, 61.9% patients (26/42) had autonomic instability, and 57.1% (24/42) patients had sleep disorder. All the children had positive antibody against NMDA receptor resistance encephalitis in cerebrospinal fluid. Head MRI showed the abnormal incidence was 50.0% (21/42), and the lesions involved in parietal lobe, frontal lobe, temporal lobe, occipital lobe, midbrain, thalamus, basal ganglia and optic nerve. There was a patient with optic nerve damage combined with myelin oligodendrocyte glycoprotein (MOG) antibody positive. Forty cases were examined by electroencephalogram (EEG), 92.5% cases (37/40) were abnormal, mainly showing diffuse slow waves, and δ brushes could be seen in severe cases. And there was 1 patient (2.4%) complicated with mesenteric teratoma. The mRS score (2.14±1.46) at discharge was significantly lower than the highest mRS score (3.88±1.38) during hospitalization (P<0.05). After 3-39 months of follow-up, mRS score at 3 months after discharge was only 0.81±1.29, which was still improved compared with that at discharge, 76.2% cases (32/42) experienced complete or near-complete recovery (mRS score≤2), and 4.8% (2/42) cases relapsed. There was no mortality; the initial time of immunotherapy and the highest mRS score in the course of the disease were the factors affecting the prognosis. The earlier the starting time for immunotherapy and the lower mRS score in the course of the disease were, the better the prognosis was. CONCLUSIONS: Seizures, mental and behavior disorder, dyskinesias, speech disorder and autonomic instability are common clinical manifestations of anti-NMDAR encephalitis in children. The effect of immunotherapy is significant, and the time to start immunotherapy and the severity of the disease are important factors affecting the prognosis. Anti-NMDAR encephalitis can be combined with other autoantibodies, but its clinical significance and mechanism need further study.

[Vasovagal syncope or postural orthostatic tachycardia syndrome in children with neurological symptoms at disease onset: a clinical analysis of 88 cases].

OBJECTIVE: To study the clinical features of vasovagal syncope (VVS) and postural orthostatic tachycardia syndrome (POTS) in children with neurological symptoms at disease onset. METHODS: A retrospective analysis was performed on the medical data of 88 children with the initial symptoms of the nervous system, such as transient loss of consciousness, dizziness, headache, and convulsion, who were finally diagnosed with VVS or POTS. RESULTS: Of the 88 children, there were 35 boys (40%) and 53 girls (60%), with an age of 4-15 years. The peak age of onset was between 10 and 13 years. All the children had the initial symptoms of transient loss of consciousness, dizziness, headache, and convulsion. Nervous system diseases were excluded by electroencephalography, cerebrospinal fluid examination, and cranial MRI. Of the 88 children, 53 (60%) were confirmed with VVS, and 35 (40%) with POTS, according to the results of head-up tilt test (HUTT). Five children with the initial symptom of transient loss of consciousness were misdiagnosed with epilepsy. Predisposing factors were determined for 59 children (67%), and prolonged standing was the most common factor, followed by change in body position and strenuous exercise. Premonitory symptoms were observed in 66 children (75%), among which chest discomfort was the most common symptom, followed by gastrointestinal symptoms (nausea, vomiting, and abdominal pain) and pale complexion. All 88 children received health education and exercise for autonomic nerve function, among whom 53 children with VVS were given oral rehydration salts and 35 children with POTS were given oral rehydration salts and metoprolol. All 88 children were followed up for 18 months, and the response rates to the above treatment at 3, 6, 12, and 18 months of follow-up were 87%, 93%, 93%, and 90% respectively. CONCLUSIONS: In addition to nervous system diseases, functional cardiovascular diseases including VVS and POTS should be considered for children with the initial symptoms of transient loss of consciousness, dizziness, headache, and convulsion. HUTT can be used to make a confirmed diagnosis, and the early treatment can achieve a good outcome.

Black carp PRMT6 inhibits TBK1-IRF3/7 signaling during the antiviral innate immune activation.

Protein arginine methylation is a prevalent posttranslational modification and protein arginine methyltransferases 6 (PRMT6) has been identified as a suppressor of TBK1/IRF3 in human and mammals. To explore the role of PRMT6 in teleost fish, PRMT6 homologue of black carp (Mylopharyngodon piceus) has been cloned and characterized in this study. Black carp PRMT6 (bcPRMT6) transcription in host cells varies in response to different stimuli and bcPRMT6 migrates around 43 kDa in the immunoblot assay. Like its mammalian counterpart, bcPRMT6 has been identified to distribute majorly in the nucleus through the immunofluorescent staining assay. bcPRMT6 shows little interferon (IFN) promoter-inducing activity in the reporter assay and bcPRMT6 shows no antiviral activity against either grass carp reovirus (GCRV) or spring viremia of carp virus (SVCV) in plaque assay. When co-expressed with bcPRMT6, the IFN promoter-inducing abilities of black carp TBK1 (bcTBK1) and IRF3/7 (bcIRF3/7) are fiercely attenuated. Accordingly, bcTBK1-mediated antiviral activity in EPC cells is obviously dampened by bcPRMT6. The interaction between bcPRMT6 and bcIRF3/7 has been identified by co-immunoprecipitation assay; however, no direct association between bcPRMT6 and bcTBK1 has been detected. Taken together, our data elucidates for the first time in teleost fish that PRMT6 suppresses TBK1-IRF3/7 signaling during host antiviral innate immune activation.

IFNb of black carp functions importantly in host innate immune response as an antiviral cytokine.

Type I interferons (IFN-Is) play an important role in the antiviral immune response in teleost fishes. In this study, one type I interferon (bcIFNb) from black carp (Mylopharyngodon piceus) has been cloned and characterized. The full-length cDNA of bcIFNb gene consists of 806 nucleotides and the predicted bcIFNb protein contains 188 amino acids. Basing on the cysteine number and evolutionary position, bcIFNb was classified into group II type I IFN. q-PCR analysis demonstrated that bcIFNb mRNA level varied in vivo and ex vivo in response to different stimuli. bcIFNb was detected in both the whole cell lysate and the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay. IFN stimulated genes (ISGs) were greatly upregulated when the host cells were treated with the bcIFNb-containing conditioned media. EPC cells showed greatly enhanced antiviral ability when the cells were transfected with bcIFNb or treated with the bcIFNb-containing conditioned media before GCRV or SVCV infection. Glycosidase digestion analysis determined that bcIFNb was modified with N-linked glycosylation, which occurred on the Asn (N) of 92 site of this cytokine. The un-glycosylated mutant bcIFNb-N92Q presented the similar antiviral ability as that of wild type bcIFNb, which demonstrated that N-linked glycosylation did not contribute directly to the antiviral property of this fish cytokine.

Restorable piezochromism phenomenon in an AIE molecular crystal: combined synchronous Raman scattering.

Many AIE active molecules have been designed and synthesized, and have been found to possess many interesting characteristics. In recent years, research into AIE crystals has increased, and it has been clearly shown that the piezochromic effect of AIE crystals depends on their structure. While most of the related research has given qualitative results, to quantitatively reveal molecular conditions under different pressure conditions, crystals of an AIE material (2Z,2'Z)-3,3'-(1,4-phenylene)bis(2-(naphthalen-2-yl)acrylonitrile) were investigated by synchronous Raman scattering and fluorescence spectroscopies. The molecular structure of the crystal changed during the process of pressurizing and then depressurizing under hydrostatic pressure, and a 142 nm red-shift value was observed in the emission spectrum of the PBNA crystal. The crystal was transformed into a new phase when the pressure was above 1.03 GPa and returned to the original phase when the pressure was decreased. The unique restorable phase transformation process of the crystal of this AIE active material could be used for erasable optical information storage and stress sensing devices.

E/Z isomerization, solvatachromism and aggregation-induced emission enhancement of donor-acceptor type oligo(p-phenylene vinylene)s.

A donor-acceptor molecule, PICNDSB, with cyclopenta[b]indole as the donor and (1,4-phenylene)bis(3-phenylacrylonitrile) as the acceptor, is designed and synthesized. PICNDSB shows typical aggregation-induced emission characteristics. The photoluminescence quantum yield of PICNDSB in dilute THF was only 0.7% and reaches 51.4% in the solid state. Compared with its analogue CzCNDSB, PICNDSB possesses stronger intramolecular charge transfer properties, as revealed from CV measurements, theoretical calculations, and their fluorescence behaviors. Correspondingly, the relatively more efficient electron-donating terminal group of cyclopenta[b]indole endows the molecule with a much higher two-photon absorption cross section of 1286 GM compared to CzCNDSB (357 GM).

A Parkinson's disease gene regulatory network identifies the signaling protein RGS2 as a modulator of LRRK2 activity and neuronal toxicity.

Mutations in LRRK2 are one of the primary genetic causes of Parkinson's disease (PD). LRRK2 contains a kinase and a GTPase domain, and familial PD mutations affect both enzymatic activities. However, the signaling mechanisms regulating LRRK2 and the pathogenic effects of familial mutations remain unknown. Identifying the signaling proteins that regulate LRRK2 function and toxicity remains a critical goal for the development of effective therapeutic strategies. In this study, we apply systems biology tools to human PD brain and blood transcriptomes to reverse-engineer a LRRK2-centered gene regulatory network. This network identifies several putative master regulators of LRRK2 function. In particular, the signaling gene RGS2, which encodes for a GTPase-activating protein (GAP), is a key regulatory hub connecting the familial PD-associated genes DJ-1 and PINK1 with LRRK2 in the network. RGS2 expression levels are reduced in the striata of LRRK2 and sporadic PD patients. We identify RGS2 as a novel interacting partner of LRRK2 in vivo. RGS2 regulates both the GTPase and kinase activities of LRRK2. We show in mammalian neurons that RGS2 regulates LRRK2 function in the control of neuronal process length. RGS2 is also protective against neuronal toxicity of the most prevalent mutation in LRRK2, G2019S. We find that RGS2 regulates LRRK2 function and neuronal toxicity through its effects on kinase activity and independently of GTPase activity, which reveals a novel mode of action for GAP proteins. This work identifies RGS2 as a promising target for interfering with neurodegeneration due to LRRK2 mutations in PD patients.

MicroRNA-34b mediates hippocampal astrocyte apoptosis in a rat model of recurrent seizures.

BACKGROUND: Recurrent convulsions can cause irreversible astrocyte death, impede neuron regeneration, and further aggravate brain damage. MicroRNAs have been revealed as players in the progression of numerous diseases including cancer and Alzheimer's disease. Particularly, microRNA has been found linked to seizure-induced neuronal death. In this study, a rat model of recurrent convulsions induced by flurothyl treatments was utilised to assess the alterations of microRNA expressions in hippocampus tissues. We also applied an in vitro model in which primary astrocytes were exposed to kainic acid to verify the targets of miR-34b-5p identified in the animal model. RESULTS: We discovered that miR-34b-5p, a member of the miR-34 family, increased significantly in flurothyl-treated rat hippocampus tissue. More surprisingly, this upregulation occurred concurrently with accumulating astrocyte apoptosis, indicating the involvement of miR-34b-5p in seizures caused astrocyte apoptosis. Results from the in vitro experiments further demonstrated that miR-34b-5p directly targeted Bcl-2 mRNA, translationally repressed Bcl-2 protein, and thus modulated cell apoptosis by influencing Bcl-2, Bax, and Caspase-3. CONCLUSION: Our findings prove microRNAs play a role in mediating recurrent convulsions-induced astrocyte death and further indicate that miR-34b-5p could acts as a regulator for astrocyte apoptosis induced by recurrent seizures.

Short-term effects of fine particulate air pollution on cardiovascular hospital emergency room visits: a time-series study in Beijing, China.

BACKGROUND: The link between particulate matter (PM) and cardiovascular morbidity has been investigated in numerous studies. Less evidence exists, however, about how age, gender and season may modify this relationship. The aim of this study was to evaluate the association between ambient PM2.5 (PM ≤ 2.5 µm) and daily hospital emergency room visits (ERV) for cardiovascular diseases in Beijing, China. Moreover, potential effect modification by age, gender, season, air mass origin and the specific period with 2008 Beijing Olympic were investigated. Finally, the temporal lag structure of PM2.5 has also been explored. METHODS: Daily counts of cardiovascular ERV were obtained from the Peking University Third Hospital from January 2007 to December 2008. Concurrently, data on PM2.5, PM10 (PM ≤ 10 µm), nitrogen dioxide and sulfur dioxide concentrations were obtained from monitoring networks and a fixed monitoring station. Poisson regression models adjusting for confounders were used to estimate immediate, delayed and cumulative air pollution effects. The temporal lag structure was also estimated using polynomial distributed lag (PDL) models. We calculated the relative risk (RR) for overall cardiovascular disease ERV as well as for specific causes of disease; and also investigated the potential modifying effect of age, gender, season, air mass origin and the period with 2008 Beijing Olympics. RESULTS: We observed adverse effects of PM2.5 on cardiovascular ERV--an IQR increase (68 µg/m(3)) in PM2.5 was associated with an overall RR of 1.022 (95% CI 0.990-1.057) obtained from PDL model. Strongest effects of PM2.5 on cardiovascular ERV were found for a lag of 7 days; the respective estimate was 1.012 (95% CI 1.002-1.022). The effects were more pronounced in females and in spring. Arrhythmia and cerebrovascular diseases showed a stronger association with PM2.5. We also found stronger PM-effects for stagnant and southern air masses and the period of Olympics modified the air pollution effects. CONCLUSIONS: We observed a rather delayed effect of PM2.5 on cardiovascular ERV, which was modified by gender and season. Our findings provide new evidence about effect modifications and may have implications to improve policy making for particulate air pollution standards in Beijing, China.