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ObjectiveTo analyze the characteristics of adverse events following immunization (AEFI) after the administration of the bivalent human papillomavirus vaccine (HPV2) and the recombinant human papillomavirus 9-valent vaccine (HPV9) in Hebei province, and to evaluate the post-marketing safety of HPV2 and HPV9. MethodsData on AEFI cases following HPV2 and HPV9 vaccination from October 1, 2018, to December 31, 2022, were collected from the AEFI monitoring module of the China Information System for Disease Control and Prevention. The incidence of AEFI reports for HPV2 and HPV9 were compared and analyzed. ResultsFrom October 1, 2018, to December 31, 2022, the average annual incidence of total AEFI reports following HPV2 and HPV9 vaccination in Hebei province was 2.76 per 100 000 doses, with HPV2 and HPV9 at 3.38 per 100 000 doses and 2.39 per 100 000 doses respectively (χ2 = 2.422, P > 0.05). The AEFI mainly comprised adverse reactions, with a total incidence of 2.69 per 100 000 doses, including common reactions and abnormal reactions at 2.42 per 100 000 doses and 0.28 per 100 000 doses respectively. For HPV2, the rates of common reactions and abnormal reactions were 2.22 per 100 000 doses and 0.11 per 100 000 doses respectively, while for HPV9 they were 2.74 per 100 000 doses and 0.55 per 100 000 doses respectively. The differences in the rates of common reactions and abnormal reactions between the two vaccines were not statistically significant (χ2 = 0.757, 3.256, P > 0.05 for both). The most common reaction was local redness and swelling (1.28 per 100 000 doses), and the primary abnormal reaction was anaphylactic shock (0.07 per 100 000 doses), mostly occurring within 24 hours post-vaccination. Ninety percent of individuals with AEFI recovered or showed improvement.ConclusionsAs of the end of 2022, the overall safety of HPV2 and HPV9 vaccinations in Hebei province was favorable, with a very low incidence rate of abnormal reactions.

Abstract Background To understand the clinical characteristics and prognosis of respiratory syncytial virus (RSV)-related encephalopathy in children. Methods A retrospective analysis of the data of children who were diagnosed with RSV-related encephalopathy and admitted to the paediatric intensive care unit (PICU) of Beijing Children’s Hospital between November 2016 and November 2023 was performed. Results Four hundred and sixty-four children with RSV infection were treated in the PICU, and eight of these patients (1.7%) were diagnosed with RSV-related encephalopathy. The mean age of the patients was 24.89 (5.92 ∼ 36.86) months. Two patients had underlying diseases. The time from the onset of illness to impaired consciousness was 3 (1.88–3.75) days. Five patients had convulsions, and three patients had an epileptic status. The serum procalcitonin (PCT) level was 1.63 (0.24, 39.85) ng/ml for the eight patients, and the cerebrospinal fluid (CSF) protein level was 232 (163 ∼ 848) g/L. Among the 8 patients, four patients underwent electroencephalogram (EEG) monitoring or examination. One patient showed continuous low-voltage, nonresponsive activity, and another patient displayed persistent slow waves, the remaining two patients had negative results. One patient had a combination of acute necrotizing encephalopathy (ANE) and acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). Additionally, one patient had ANE, and another had acute brain swelling (ABS). One patient died in the hospital, and the other seven patients were discharged with improvement. Routine follow-up was conducted for 4.58(0.5 ∼ 6.50) years, and all patients fully recovered. Conclusions RSV-related encephalopathy could have varying clinical manifestations, and some types, such as ANE and ABS, are dangerous and can lead to death.

The aim of this study was to analyze the incidence and characteristics of adverse events following immunization (AEFI) with post-licensure vaccines used in Hebei province from 2018 to 2020 and to evaluate the safety of vaccines. All information of AEFI was gained from national adverse event following immunization surveillance system (NAEFISS) in Hebei Province from 2018 to 2020. Descriptive epidemiology method was used to analyze the data about AEFI in Hebei province. Reporting rates of AEFI were calculated by sex, age, city, categories of AEFI, severity of AEFI, reaction categories, etc. A total of 35,999 AEFI were reported through NAEFISS, and the average annual rate was 47.64/100,000 doses. The reporting rates of common adverse reactions and rare adverse reactions were 46.37/100,000 doses and 1.05/100,000 doses. The male-to-female ratio was 1.26:1. Most of the AEFI were concentrated in the ≤1 year age group and were reported in the second quarter and third quarter. The majority of AEFI were reported to be recovered or improved, and about 62% of the AEFI occurred within 24 hours after vaccination. Vaccines associated with the highest reporting rate of AEFI were diphtheria, tetanus and acellular pertussis combined vaccine (DTaP, 170.45/100,000 doses). The reporting rate of allergic rash was found to be the highest in the adverse reactions (0.29/100,000 doses). The majority of AEFI cases were common adverse reactions, while serious rare adverse reactions caused by vaccines were extremely uncommon, and all vaccines used in Hebei Province were safe.

Development of optimal therapeutics for disease states that can be associated with increased membrane cholesterol requires better molecular understanding of lipid modulation of the drug target. Type 1 cholecystokinin receptor (CCK1R) agonist actions are affected by increased membrane cholesterol, enhancing ligand binding and reducing calcium signaling, while agonist actions of the closely related CCK2R are not. In this work, we identified a set of chimeric human CCK1R/CCK2R mutations that exchange the cholesterol sensitivity of these 2 receptors, providing powerful tools when expressed in CHO and HEK-293 model cell lines to explore mechanisms. Static, low energy, high-resolution structures of the mutant CCK1R constructs, stabilized in complex with G protein, were not substantially different, suggesting that alterations to receptor dynamics were key to altered function. We reveal that cholesterol-dependent dynamic changes in the conformation of the helical bundle of CCK receptors affects both ligand binding at the extracellular surface and G protein coupling at the cytosolic surface, as well as their interrelationships involved in stimulus-response coupling. This provides an ideal setting for potential allosteric modulators to correct the negative impact of membrane cholesterol on CCK1R.

ObjectiveTo investigate adverse reactions to three sequential schedules of polio vaccination among small children. MethodsTotally 216 healthy infants of two month-old and above were recruited from November to December 2018 at 8 immunization clinics in Feixiang district, Handan city, Hebei province and randomly divided into three groups (72 infants in each group) for different sequential schedules of polio vaccinations at 2, 3, and 4 month-old: group A (administered sequentially with inactivated poliovirus vaccine [IPV], bivalent oral poliovirus vaccine of types I and III [bOPV], and bOPV), group B (with IPV, IPV and bOPV), and group C (with three doses of IPV sequentially). Information on suspected adverse events following immunization (AEFI) among the vaccinees were collected through 30 minutes observation after the inoculation, telephone or household interview at 1, 3, 7, 15, 30 days after the vaccina-tion. The observed adverse reactions were classified according to the National Surveillance Plan for Suspected Adverse Events Following Immunization and the incidence rates of AEFI were compared among the three vaccination groups. Results Totally 16 cases of AEFI were reported, with an overall AEFI reporting rate of 2.52/100 doses. The reported number (incidence rate/100 doses) of AEFI in the infants of groups A, B, and C were 5 (2.23), 2 (0.97), and 9 (4.41), respectively. There were no statistically significant differences in the reported AEFI rates between group A and group B and between group A and group C (χ2 = 1.079, 1.603, P > 0.05); but the reported rate of the group B was significantly lower than that of group C (χ2 = 4.683, P < 0.05); there was also no significant difference between the reported rate of the male infants (4 cases, 1.57/100 doses) and that of the female infants (12 cases, 3.16/100 doses) (χ2 = 1.569, P > 0.05) . All the reported AEFI were febrile reactions, including 1 case of low-grade fever (0.16/100 doses), 11 cases of moderate fever (1.73/100 doses), and 4 cases of high fever (0.63/100 doses) and no rare serious adverse reactions was observed among the infants. All the reported AEFI occurred after the inoculations of first dose (13 cases, 6.02/100 doses) and second dose (3 cases, 1.43/100 doses) of vaccine, and the incidence rate of AEFI for the first dose vaccination was significntly higher than that for the second dose vaccination (χ2 = 6.206, P < 0.05). All the 16 cases of AEFI occurred within 15 – 30 days after the vaccinations and recovered after symptomatic treatment. ConclusionThe three sequential schedules of IPV and bOPV vaccination are safe among 2 – 4 month-old infants and the reported incidence rate of AEFI is relatively low for the schedule of two sequential doses of IPV followed by one dose bOPV vaccination.

ObjectiveTo explore the feasibility of predicting the trend of measles epidemic using long short-term memory (LSTM) neural network model for conducting prevention and control of measles. MethodsThe data on 51 012 measles cases reported in Hebei province form 2004 through 2020 were collected from China Information System for Disease Control and Prevention. The LSTM neural network model was constructed and the optimal model was selected to predict the trend of measles epidemic in the province. Rooted mean squared error (RMSE) and mean absolute error (MAE) were used to evaluate the prediction of model established. ResultsThe annual number of measles cases reported in the province during the 17-year period were 950, 4 837, 7 953, 4 973, 2 273, 3 359, 14 457, 79, 38, 353, 5 365, 3 825, 1 825, 287, 241, 130, and 67, respectively, with a persistent decline since 2015. In addition, an obvious seasonality was observed in the incidence of measles. Using the collected data of 2017, the window length of 3 was determined for the constructed LSTM neural network model, with the RMSE of 17.288 and the MAE of 12.334, and the model was adopted to predict monthly number of measles cases from 2017 through 2020. The predicted monthly numbers of measles incidence were basically consistent with the number observed and the values of RMSE and MAE for years of 2017, 2019 and 2020 were all below 10, but the values for 2018 were slightly higher. ConclusionThe constructed LSTM neural network model in this study showed a good efficiency in predicting monthly measles incidence in Hebei province and the model could be used in the analysis on measles incidence trend and epidemic risk assessment.

Abstract Background Ligilactobacillus salivarius has been frequently isolated from the gut microbiota of humans and domesticated animals and has been studied as a candidate probiotic. Badger (Meles meles) is known as a “generalist” species that consumes complex foods and exhibits tolerance and resistance to certain pathogens, which can be partly attributed to the beneficial microbes such as L. salivarius in the gut microbiota. However, our understanding of the beneficial traits and genomic features of badger-originated L. salivarius remains elusive. Results In this study, nine L. salivarius strains were isolated from wild badgers' feces, one of which exhibited good probiotic properties. Complete genomes of the nine L. salivarius strains were generated, and comparative genomic analysis was performed with the publicly available complete genomes of L. salivarius obtained from humans and domesticated animals. The strains originating from badgers harbored a larger genome, a higher number of protein-coding sequences, and functionally annotated genes than those originating from humans and chickens. The pan-genome phylogenetic tree demonstrated that the strains originating from badgers formed a separate clade, and totally 412 gene families (12.6% of the total gene families in the pan-genome) were identified as genes gained by the last common ancestor of the badger group. The badger group harbored significantly more gene families responsible for the degradation of complex carbohydrate substrates and production of polysaccharides than strains from other hosts; many of these were acquired by gene gain events. Conclusions A candidate probiotic and nine L. salivarius complete genomes were obtained from the badgers’ gut microbiome, and several beneficial genes were identified to be specifically present in the badger-originated strains that were gained in the evolution. Our study provides novel insights into the adaptation of L. salivarius to the intestinal habitat of wild badgers and provides valuable strain and genome resources for the development of L. salivarius as a probiotic.

Introduction: The clinicopathological features of segmental membranous glomerulopathy (SMGN) have not been well characterized. The aim of this study was to investigate the prevalence and clinicopathological features of SMGN in adults. Methods: Adult patients with biopsy-confirmed SMGN in the native kidney at our center between January 2017 to September 2020 were identified. The clinicopathological features of SMGN were collected. The glomerular deposition of IgG subclasses, M-type phospholipase A2 receptor 1 (PLA2R), thrombospondin type 1 domain-containing 7A (THSD7A), and neural epidermal growth factor-like 1 protein (NELL1) were tested. Clinical and pathologic features were comparable between NELL1-positive and NELL1-negative SMGN. Results: A total of 167 patients with biopsy-proven SMGN were enrolled. During the same period, 32,640 (33.0%) out of 98,939 renal biopsies were diagnosed with membranous nephropathy (MN) in adults. SMGN accounted for 0.17% of total kidney biopsies and 0.51% of MN in adults. One hundred and fifty (89.8%) cases were isolated SMGN, and 17 (10.2%) cases were complicated with other kidney disease. Clinically, the median age of isolated SMGN patients was 41.5 years, with female (74%) predominance, and 33.1% had full nephrotic syndrome. Pathologically, IgG1 was the dominant subclass (92.5%), followed by IgG4 (45.0%). PLA2R and THSD7A staining were done in 142 and 136 isolated SMGN cases, respectively, in which, all the cases showed negative. NELL1 staining was done in 135 isolated SMGN cases; 58 cases (43.0%) showed positive. Fifty-eight patients (41.1%) had diffuse (≥90%) foot process effacement, and 119 patients (83.8%) had either stage I (38.0%) or stage II (45.8%) membranous alterations in patients with SMGN. Most patients with NELL1-positive SMGN were female. Patients with NELL1-positive SMGN were more likely with lower prevalence of full nephrotic syndrome than NELL1-negative SMGN. Conclusions: SMGN is a relatively rare pathological type. Majority of patients with isolated SMGN were female, with a median age of 41.5 years, 33.1% had full nephrotic syndrome, absence of PLA2R and THSD7A, 43.0% with NELL1-positive, and mainly stage I or II MN (83.8%). NELL1 is the major target antigen of SMGN in adults.

We propose an enhanced floor field model (FFM) to analyze the behavioral characteristics of crowds with varying attributes proportions during evacuation. This model governs pedestrian movement through the Dynamic Floor Field (DFF) and the Static Floor Field (SFF). The DFF takes into account individual factors such as the gender, familiarity with the environment, and social relationships of evacuees, which influence safe evacuation. Concurrently, the SFF encapsulates the impact of environmental factors like obstacles, exits, and guidance effects. Subsequently, this refined FFM was applied and validated using a sports center evacuation scenario. The results demonstrated that the enhanced FFM accurately replicated evacuees' asymmetric behavior and queuing, and aligned well with other models when the number of evacuees fluctuated over time. In the absence of guidance, both environmental familiarity and gender emerged as primary factors influencing partial evacuation. Additionally, the gender of pedestrians significantly affected the overall evacuation. Notably, compared to pre-existing environmental information available to evacuees, the implementation of guidance to augment pedestrians' environmental familiarity resulted in a more efficient evacuation. The FFM model and these findings could be instrumental in simulating personnel evacuation and formulating emergency management strategies in crowded areas.

To better understand the research progress and trends in the mechanical properties of coal, and to promote theoretical research on the prevention and control of dynamic disasters, we employed the bibliometric method to analyze the research progress in this field. A total of 3450 documents from the Web of Science (WOS) core database were reviewed and analyzed. Our analysis focused on the annual distribution of literature, the distribution by country/region, organization, and author, as well as the distribution of significant source journals. We also identified research hotspots and frontiers. The results indicate a significant increase in the number of research papers on the mechanical properties of coal. China, America, Australia, India, Spain, Poland, England, Japan, South Korea, and Turkey were found to be the most active countries in this research area. The research results from China, America, and Australia were found to be the most influential, and C&BM, FUEL, INT J ROCK MECH MIN, INT J COAL GEOL, RM&RE, C&CR, and JCP were identified as the primary sources of research publications on the mechanical properties of coal. The basic theory and research system of coal mechanical properties investigation have been established, and there are numerous future research directions and areas to explore. Some current hotspots include the development of coal mechanical property models, permeability models related to mechanical properties, establishment and prediction of coal strength-temperature relationships, investigation of the proportioning scheme of granite and coal bottom ash in concrete mixes, and research on the improvement effect of fly ash on concrete manufacturing properties.

Objectives The long-term clinical trajectory of chronic obstructive pulmonary disease (COPD) in terms of year-to-year hospital utilisation rates can be highly variable and is not well studied. We investigated year-to-year trends of hospitalisation or emergency department (ED) visits among patients with COPD over 3 years, identified distinct trajectories and examined associated predictive factors.Design A retrospective cohort study.Setting Data were extracted from the Changi General Hospital, Singapore COPD data warehouse.Participants Patients with COPD aged ≥40 years with 3 years of follow-up data.Primary and secondary outcome measures The yearly rates of hospitalisations or ED visits, stratified by COPD-related or all-cause, were described. Group-based trajectory modelling was used to identify clinically distinct trajectories year-by-year. Baseline predictive factors associated with different trajectories were examined.Results In total, 396 patients were analysed (median age 70 years; 87% male). Four trajectories were generated for year-to-year trends in COPD-related hospitalisations/ED visits (C1–C4: consistently frequent, consistently infrequent, improving and worsening); post-bronchodilator forced expiratory volume in 1 second (FEV1) was a significant predictor of trajectory, with worse lung function being the main factor associated with less favourable trajectories. For all-cause hospitalisations/ED visits, four trajectories were identified (A1–A4: infrequent and stable, frequent and stable, frequent and decreasing, frequent and increasing); significant differences in age (p=0.041), sex (p=0.016) and ethnicity (p=0.005) were found between trajectories. Higher overall comorbidity burden was a key determinant in less favourable trajectories of all-cause hospitalisations/ED visits.Conclusions Distinct trajectories were demonstrated for hospitalisations/ED visits related to COPD or all causes, with predictive associations between FEV1 and COPD trajectory and between comorbidities and all-cause trajectory. Trajectories carry nuanced prognostic information and may be useful for clinical risk stratification to identify high-risk individuals for preventative treatments.

Abstract The growth of the self-concept through increasing perspectives, identities, resources, and efficacy is known as self-expansion and typically involves novelty, challenge, interest, and/or excitement. Self-expansion is positively associated with health factors including self-reported physical activity (PA). This study is the first to investigate self-expansion and daily PA, and with a PA monitor. Fifty community participants completed baseline questionnaires, wore a Fitbit One and completed daily self-report questionnaires for 28 days, and completed follow-up questionnaires. Daily surveys included questions about both general and PA-specific self-expansion. Across the 4 weeks, steps taken was positively correlated with both general (all maximum likelihood r = 0.17) and PA-specific self-expansion (maximum likelihood rs of 0.15 and 0.16), and PA-specific self-expansion was positively correlated (maximum likelihood rs of 0.38 and 0.50) with aerobic activity. Future research should investigate this relationship in a larger more diverse sample and test whether PA-specific self-expansion can be utilized as an acceptable, feasible, and effective intervention to increase daily steps and other forms of PA.

Abstract Background Multiple inhaler triple therapy (MITT), comprising inhaled corticosteroids (ICS), long-acting beta-agonists (LABA), and long-acting muscarinic antagonists (LAMA), has been used as an escalation treatment for patients with chronic obstructive pulmonary disease (COPD). However, real-world use of MITT has not been investigated in Asia, including South Korea. This study reports baseline characteristics of patients with COPD initiated on MITT in South Korea, and their treatment patterns. Healthcare resource utilization (HRU) and costs associated with COPD exacerbations following MITT initiation were also assessed. Methods This was a retrospective cohort study using the South Korea National Health Insurance database (2014–2018). Included patients were ≥ 40 years, had a COPD diagnosis, were newly initiated on MITT and had ≥ 12 months’ data both before (baseline) and after index date (the first day with overlapping supply of all MITT components). Treatment immediately before initiation and immediately following discontinuation of MITT were identified, and proportion of days covered (PDC) by MITT was calculated. HRU and costs (per person per year [PPPY]) associated with exacerbations were identified following MITT initiation; costs were calculated using the average 2020 exchange rate (0.0008 USD/KRW). Results Among 37,400 patients, the mean age was 69 (SD 10) years and 73% were males; 56% had ≥ 1 COPD exacerbation during the baseline period, with a mean of 2 (SD 5) events/year. ICS/LABA was the most frequent regimen prescribed immediately before initiation (37%) and immediately following discontinuation (41% of 34,264 patients) of MITT. At 3, 6, and 12 months from treatment initiation, mean PDC was 81%, 63% and 49%, respectively; median treatment duration was 102 days. The mean (95% confidence interval [CI]) number of total visits for severe COPD exacerbations was 0.77 PPPY (0.75–0.78); mean PPPY total healthcare costs were 2093 USD. Conclusions Patients with COPD in South Korea experienced frequent exacerbations prior to MITT, and PDC by MITT was low. Patients may benefit from early optimization of COPD therapy, and greater emphasis on adherence to inhaled COPD therapy. Severe exacerbations were found to incur substantial costs; treatment alternatives that can reduce the rate of severe exacerbations are likely to minimize healthcare costs.

Abstract The course of REM sleep behavior disorder (RBD) variates in the early stage of Parkinson’s disease. We aimed to delineate the association between the evolution pattern of probable RBD (pRBD) and the progression of Parkinson’s disease (PD). 281 de novo PD patients from the Parkinson’s Progression Markers Initiative database were included. Patients were followed up for a mean of 6.8 years and were classified into different groups according to the evolution patterns of pRBD. Disease progression was compared among groups using survival analysis, where the endpoint was defined as progression to Hoehn-Yahr stage 3 or higher for motor progression and progression to mild cognitive impairment for cognitive decline. At the 4th year of follow-up, four types of pRBD evolution patterns were identified: (1) non-RBD-stable (55.5%): patients persistently free of pRBD; (2) late-RBD (12.1%): patients developed pRBD during follow-up; (3) RBD-stable (24.9%): patients showed persistent pRBD, and (4) RBD-reversion (7.5%): patients showed pRBD at baseline which disappeared during follow-up. The RBD-reversion type showed the fastest motor progression while the RBD-stable type showed the fastest cognitive decline. At baseline, the RBD-reversion type showed the most severe gray matter atrophy in the middle frontal gyrus, while the RBD-stable type showed gray matter atrophy mainly in the para-hippocampal gyrus. Four types of early pRBD evolution patterns featured different brain lesions and predicted different courses of motor and cognitive decline in PD.

Abstract To explore the inhibitory effect of argon gas and explosion-eliminating chamber on methane-air deflagration flame propagation in the tube, based on the Φ = 120 mm, L = 5.5 m stainless steel pipeline test system to measure methane-air deflagration flame structure, flame propagation speed, and deflagration pressure. The results show that: 10–30% argon is mixed into the methane-air premixed gas with different equivalent ratios. With the increase in the mixed argon content, the tensile distortion and instability of the flame front increase, and the average value of flame propagation speed decreases by 2.52–60.0%. The first and second deflagration pressure peaks are reduced by about 13.1–62% and 17.7–86.5% respectively. The average value of the methane-air deflagration flame propagation velocity was reduced by 5.7–37.0% with the explosion-eliminating chamber laid at the nozzle. The second and third deflagration pressure peaks are reduced by about 10–30% and 50–90% respectively. The inhibitory effect of argon on the propagation of methane-air flame is considered better than the laying of the explosion-eliminating chamber under the experimental conditions.

Abstract Background Salmonella Derby is one of the most predominant Salmonella serotypes that seriously threatens food safety. This bacterium can be further differentiated to sub-populations with different population sizes; however, whether and how the S. Derby–gut microbiota interactions affect epidemic patterns of S. Derby sub-populations remain largely unknown. Results We selected two representative strains, 14T and 14C, which represent rarely distributed and prevalent sub-populations of the S. Derby ST40 group, respectively, to address this question using a mouse model. Effects of oral administration of both strains was monitored for 14 days. Alpha diversity of gut microbiota at early stages of infection (4 h post infection) was higher in 14C-treated mice and lower in 14T-treated mice compared with controls. Strain 14T triggered stronger inflammation responses but with lower pathogen titer in spleen compared with strain 14C at 14 days post infection. Certain known probiotic bacteria that can hinder colonization of Salmonella, such as Bifidobacteriaceae and Akkermansiaceae, exhibited increased relative abundance in 14T-treated mice compared with 14C-treated mice. Our results also demonstrated that Ligilactobacillus strains isolated from gut microbiota showed stronger antagonistic activity against strain 14T compared with strain 14C. Conclusions We identified how S. Derby infection affected gut microbiota composition, and found that the 14T strain, which represented a rarely distributed S. Derby sub-population, triggered stronger host inflammation responses and gut microbiota disturbance compared with the 14C strain, which represented a prevalent S. Derby sub-population. This study provides novel insights on the impacts of gut microbiota on the epidemic patterns of Salmonella populations.

Understanding the creep behavior of shale is essential to precisely predict borehole instability issues and model fracturing of unconventional shale reservoirs. In this study, the creep behavior of shale in micron scale is investigated by integrating the nano-dynamic mechanical analysis (nano-DMA) grid nanoindentation (15 × 15 indents) and data clustering techniques. The results showed that the creep displacement, the creep rate, and hardness, both can be related through a logarithmic function with creep time. Furthermore, contact creep modulus increased as the hardness or Young’s modulus increased. The clustering analysis revealed that three separate phases are present in the samples where Phase 1(clay/organic matter) has the smallest contact creep modulus and Phase 3 (quartz) the largest. While creep is in progress, the creep displacement, hardness and contact creep modulus of all three phases obey the logarithmic function. Under the same creep time, reduction in the contact creep modulus of Phase 3 appears to be faster than Phase 1 while the creep rate of Phase 3 is much less than Phase 1. Ultimately, contact creep modulus is better correlated with hardness than Young’s modulus.

ObjectiveMetabolic syndrome (MetS) is a global problem that increasingly violates human health and quality of life. We explored the relationship between dietary inflammatory potential represented by dietary inflammatory index (DII) and the occurrence of MetS to provid data support for the prevention of it through dietary structure intervention.MethodsThe data was come from National Health and Nutrition Examination Survey 2007–2018, including demographic, dietary, questionnaire variables and laboratory indicators. MetS was defined according to the criteria proposed by the American Endocrine Association (ACE) and the American Society of Clinical Endocrinology (ACCE). DII was calculated using the scoring method established by Shivappa. We divided DII scores into 4 quartiles, the chi-square test was used to compare the variable difference between DII quartiles groups. A logistic regression model was used to analyze the association between DII and MetS. We also performed subgroup analysis. A generalized linear regression model was used to explore the association of DII level and the levels of seven MetS related biochemical indicators.ResultsThe final sample size was 8,180, and the DII scores of the subjects were −5.50 to 5.22. The proportions of men, young people, non-Hispanic blacks, poor people, smokers, and MetS patients in the Q1–Q4 DII quantiles groups were gradually increased. The risk of MetS in the Q4 group which had highest dietary inflammatory degree was 1.592 (1.248, 2.030) times higher than that in the Q1 group, respectively (P < 0.001). After subgroup analysis, women, youth, non-smokers and alcohol drinkers were found to be more sensitive to the dietary inflammation. Then we found that the level of DII was significantly positively correlated with waist circumference (WC), body mass index (BMI), triglyceride (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP), but negatively correlated with high density lipoprotein cholesterol (HDL-C).ConclusionsIn the research subjects, the degree of dietary inflammation was associated with the occurrence of MetS and significantly affected WC, BMI, blood pressure, and blood lipid levels. It is necessary to conduct investigations and early dietary interventions for women and young people to prevent the occurrence of chronic metabolic diseases.

To reduce the thermal runaway risk of lithium-ion batteries, a good thermal management system is critically required. As phase change materials can absorb a lot of heat without the need for extra equipment, they are employed in the thermal management of batteries. The thermal management of a Sanyo 26,650 battery was studied in this work by using different composite phase change materials (CPCMs) at different charge–discharge rates. The thorough analysis on the thermal conductivity of CPCMs and the effect of CPCMs was conducted on the maximum surface temperature while charging and discharging. The findings demonstrate the ability of the composite thermal conductivity filler to increase thermal conductivity. It is increased to 1.307 W/(m K) as the ratio of silica and graphene is 1:1 (CPCM-3). The CPCMs can reduce the surface temperature of the cell, and the cooling effect of CPCM-3 is the most obvious, which can reduce the maximum temperature of the cell surface by 13.7 °C and 19 °C under 2 C and 3 C conditions. It is also found that the risk of thermal runaway of batteries under CPCMs thermal management is effectively reduced, ensuring the safe operation of the battery. This research can assist in the safe application of batteries and the development of new energy sources.

ObjectiveThe study aimed to clarify the association of the 21 single nucleotide polymorphisms (SNPs) with Alzheimer’s disease (AD) in the population of southern China.MethodsA case-control study was conducted with a total sample size of 490 subjects (246 patients with AD and 244 age- and gender-matched healthy controls) enrolled in this study. Twenty-one selected SNPs were detected using SNaPshot assay and polymerase chain reaction (PCR) technique. Then, we assessed how these SNPs correlated with AD susceptibility.ResultsThe results showed that rs3764650 of ABCA7 was closely correlated with risen AD morbidity in the allele [P = 0.010, odds ratio (OR) = 1.43, 95% confidence interval (CI) 1.09–1.89], dominant (P = 0.004, OR = 1.71, 95% CI 1.19–2.46), and additive (P = 0.012, OR = 1.42, 95% CI 1.08–1.86) models. However, rs4147929 of ABCA7 was related to higher AD risk in the allele (P = 0.006, OR = 1.45, 95% CI 1.11–1.89), dominant (P = 0.012, OR = 1.59, 95% CI 1.11–2.27), and additive (P = 0.010, OR = 1.40, 95% CI 1.08–1.81) models. In addition, the frequencies of the G-allele at rs3764650 (P = 0.030) and the A-allele at rs4147929 (P = 0.001) in AD were statistically higher in APOE ε4 carriers in comparison to non-carriers.ConclusionThis study demonstrated that the G-allele at rs3764650 and the A-allele at rs4147929 appeared at higher risk for developing AD, particularly in APOE ε4 carriers. Moreover, it was observed that rs3764650 and rs4147929 of ABCA7 were linked to AD. More in-depth research with a relatively large sample is needed to make the results more convincing.

Background and ObjectivesThe study aims to test the hypotheses that a higher burden of cerebral small vascular disease (CSVD) predicts major adverse cardiac and cerebrovascular events (MACCE) in patients with hypertension (HTN) and that abnormal blood pressure variability (BPV) pattern aggravates total CSVD burden.MethodsWe retrospectively reviewed patients with HTN prospectively selected between February 2015 and February 2019 from three participating centers. Patients were included if they had HTN for over 1 year and had at least one MRI feature of CSVD. Independent predictors were found using multivariate logistic regression.ResultsAmong the 908 patients who finally enrolled in the study, the number of CSVD markers (OR = 1.940; 95% CI = 1.393–2.703; P < 0.001) independently predicted MACCE with acceptable predictive value (C-statistic = 0.730; 95% CI = 0.669–0.791; P < 0.001). An abnormal BPV pattern was identified as an independent risk factor for increased CSVD burden. Among them, reverse-dipper subtype demonstrated the most significant relationship (OR = 1.725; 95% CI = 1.129–2.633; P = 0.012).ConclusionTotal CSVD burden predicts an increased risk of composite MACCE independently. An abnormal BPV pattern is associated with a higher burden of CSVD.

Abstract Background Cerebral-cardiac syndrome, newly developed cardiac damage manifestations subsequent to cerebral injuries, is a common complication of stroke and leads to increased morbidity and mortality. The current study is aimed to develop a risk prediction scale to stratify high-risk population of CCS among ischemic stroke patients. Methods The study included 410 cases from four tertiary medical centers from June 2018 to April 2019. The risk prediction model was established via logistic regression from the derivation cohort including 250 cases admitted between June 2018 and December 2018. Another 160 cases admitted from January 2019 to April 2019 were included as the validation cohort for external validation. The performance of the model was determined by the area under curve of the receiver operating characteristic curve. A rating scale was developed based on the magnitude of the logistic regression coefficient. Results The prevalence of CCS was 55.2% in our study. The predictive model derived from the derivation cohort showed good calibration by Hosmer-Lemeshow test (P = 0.492), and showed sensitivity of 0.935, specificity of 0.720, and Youden index of 0.655. The C-statistic for derivation and validation cohort were 0.888 and 0.813, respectively. Our PANSCAN score (0 to 10 points) was then established, which consists of the following independent risk factors: PT(12 s–14 s = 0; otherwise = 1), APTT(30s–45s = 0, otherwise = 1), Neutrophils(50–70% = 0; otherwise = 1), Sex(female = 1), Carotid artery stenosis(normal or mild = 0; moderate to severe = 2), Age(≥65 years = 1), NIHSS score(1 to 4 = 2; ≥5 = 3). Patients scored 3 or more points were stratified as high risk. Conclusion The risk prediction model showed satisfactory prediction effects. The PANSCAN scale provides convenient reference for preventative treatment and early management for high-risk patients. Trial registration The study was retrospectively registered in Chinese Trial Registry. The date of registration is April 17, 2019. Trial registration number: ChiCTR1900022587 .

G protein-coupled receptors (GPCRs) are critical regulators of cellular function acting via heterotrimeric G proteins as their primary transducers with individual GPCRs capable of pleiotropic coupling to multiple G proteins. Structural features governing G protein selectivity and promiscuity are currently unclear. Here, we used cryo-electron microscopy (cryo-EM) to determine structures of the cholecystokinin (CCK) type 1 receptor (CCK1R) bound to the CCK peptide agonist, CCK-8 and 2 distinct transducer proteins, its primary transducer Gq, and the more weakly coupled Gs. As seen with other Gq/11-GPCR complexes, the Gq-α5 helix (αH5) bound to a relatively narrow pocket in the CCK1R core. Surprisingly, the backbone of the CCK1R and volume of the G protein binding pocket were essentially equivalent when Gs was bound, with the Gs αH5 displaying a conformation that arises from "unwinding" of the far carboxyl-terminal residues, compared to canonically Gs coupled receptors. Thus, integrated changes in the conformations of both the receptor and G protein are likely to play critical roles in the promiscuous coupling of individual GPCRs.

Abstract Background Functions of astrocytes in the rehabilitation after ischemic stroke, especially their impacts on inflammatory processes, remain controversial. This study uncovered two phenotypes of astrocytes, of which one was helpful, and the other harmful to anoxic neurons after brain ischemia. Methods We tested the levels of inflammatory factors including TNF-a, IL-6, IL-10, iNOS, IL-1beta, and CXCL10 in primary astrocytes at 0 h, 6 h, 12 h, 24 h, and 48 h after OGD, grouped the hypoxia astrocytes into iNOS-positive (iNOS(+)) and iNOS-negative (iNOS(−)) by magnetic bead sorting, and then co-cultured the two groups of cells with OGD-treated neurons for 24 h. We further verified the polarization of astrocytes in vivo by detecting the co-localization of iNOS, GFAP, and Iba-1 on MCAO brain sections. Lentivirus overexpressing LCN2 and LCN2 knockout mice (#024630. JAX, USA) were used to explore the role of LCN2 in the functional polarization of astrocytes. 7.0-T MRI scanning and the modified Neurological Severity Score (mNSS) were used to evaluate the neurological outcomes of the mice. Results After oxygen-glucose deprivation (OGD), iNOS mRNA expression increased to the peak at 6 h in primary astrocytes, but keep baseline expression in LCN2-knockout astrocytes. In mice with transient middle cerebral artery occlusion (tMCAO), LCN2 was proved necessary for astrocyte classical activation. In LCN2 knockout mice with MCAO, no classically activated astrocytes were detected, and smaller infarct volumes and better neurological functions were observed. Conclusions The results indicated a novel pattern of astrocyte activation after ischemic stroke and lipocalin-2 (LCN2) plays a key role in polarizing and activating astrocytes.

New materials and technologies facilitate the design of thermochromic dynamic paintings. However, creating a thermochromic painting requires knowledge of electrical engineering and computer science, which is a barrier for artists and enthusiasts with non-technology backgrounds. Existing toolkits only support limited design space and fail to provide usable solutions for independent creation and for meeting the needs of the artists. We present ViviPaint, a toolkit that assists artists and enthusiasts in creating thermochromic paintings easily and conveniently. We summarized the pain points and challenges by observing a professional artist’s entire thermochromic painting creation process. We then designed ViviPaint consisting of a design tool and a set of hardware components. The design tool provides a GUI animation choreography interface, hardware assembly guidance, and assistance in assembly process. The hardware components comprise an augmented picture frame with a detachable structure and 24 temperature-changing units using Peltier elements. The results of our evaluation study (N = 8) indicate that our toolkit is easy to use and effectively assists users in creating thermochromic paintings.

This study examined concordance between caregiver-reported and physician-rated estimates of severity of atopic dermatitis (AD) in paediatric patients and explored potential explanatory factors. Physician-reported severity of AD was retrieved from medical records, while caregiver-reported disease severity and sociodemographic data were obtained through a survey that also collected information on out-of-pocket expenses due to AD. There was 38.5% (95% confidence interval (95% CI) 30.1, 43.5) disagreement between physician and caregivers with regards to both underestimating and overestimating the condition. A duration since AD diagnosis shorter than 6 months showed higher concordance (kappa: 44.4%; 95% CI 30.6, 58.2) between caregiver and physician estimates of AD severity compared with a duration of 6 months or longer. Caregivers underestimating their child’s AD accounted for 27.7% among all participants, while 10.8% overestimated the severity of AD compared with physicians. Factors significantly associated with caregiver’s underestimation of disease severity were age of the child and time since disease diagnosis. Comparison of concordance between caregiver-reported and physician-rated estimates of severity of AD in paediatric patients revealed a tendency amongst caregivers to underestimate severity of AD. This information may have clinical implications for treatment outcomes if caregivers fail to adhere to medical advice.

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Background: The formation of productive academic research groups can be difficult, especially in environments without a robust and existing research infrastructure. Idaho and Alaska, are Institutional Development Award (IDeA)-eligible states, historically receiving low levels of funding from the National Institutes of Health (NIH). Purpose/Methods: We present a case study highlighting an academic research collaboration established across two-disciplines, three-career stages, and three-campuses utilizing distance technology. Results: One lesson learned from our experiences is that regardless of position (junior or senior faculty) or time at the institution/department (new or established), it is important to reach out to others. Collaborations require conscientious effort to establish and maintain. Second, a psychologically safe space must be created, establishing trust. Lastly, in order to eliminate distractions, optimize team performance, and improve deliverables, the team must have a shared mission. Team members must recognize, appreciate, and fully utilize each other and available resources. Conclusion: Our experiences and lessons learned can be utilized by others to strengthen opportunities to form and grow interdisciplinary research collaborations and develop a stronger research infrastructure. Article Type: Note

To investigate the dose-effect relationship of sea cucumber peptides on memory function improvement, animal experiments, behavioral experiments, ACh content, AChE activity, hippocampal morphology, and protein modifications were detected. Sea cucumber peptides (650 mg/kg, 1300 mg/kg, 2600 mg/kg body weight) and piracetam (400 mg/kg) were gavaged into the mice. Scopolamine (5 mg/kg) were administered intraperitoneally to mice. In behavioral experiments, the escape latency and the shocked time of sea cucumber peptides (SCP) groups were significantly reduced (P

Digital health education is a new approach that is receiving increasing attention with advantages such as scalability and flexibility of education. This study employed a Cochrane review approach to assess the evidence for the effectiveness of health professions’ digital education in dermatology to improve knowledge, skills, attitudes and satisfaction. Twelve trials (n = 955 health professionals) met our eligibility criteria. Nine studies evaluated knowledge; of those two reported that digital education improved the outcome. Five studies evaluated skill; of those 3 studies stated that digital education improved this outcome whereas 2 showed no difference when compared with control. Of the 5 studies measuring learners’ satisfaction, 3 studies claimed high satisfaction scores. Two studies reported that when compared with traditional education, digital education had little effect on satisfaction. The evidence for the effectiveness of digital health education in dermatology is mixed and the overall findings are inconclusive, mainly because of the predominantly very low quality of the evidence. More methodologically robust research is needed to further inform clinicians and policymakers.

Abstract Background Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) near chromosome 9p21 have been associated with both atherosclerosis and artery calcification, but the underlying mechanisms remained largely unknown. Considering that CDKN2A/2B is a frequently reported site for DNA methylation, this study aimed to evaluate whether carotid artery calcification (CarAC) is related to methylation levels of CDKN2A/2B in patients with ischemic stroke. Methods DNA methylation levels of CDKN2A/2B were measured in 322 ischemic stroke patients using peripheral blood leukocytes. Methylation levels of 36 CpG sites around promoter regions of CDKN2A/2B were examined with BiSulfite Amplicon Sequencing. CarAC was quantified with Agatston score based on results of computed tomography angiography. Generalized liner model was performed to explore the association between methylation levels and CarAC. Results Of the 322 analyzed patients, 187 (58.1%) were classified as with and 135 (41.9%) without evident CarAC. The average methylation levels of CDKN2B were higher in patents with CarAC than those without (5.7 vs 5.4, p = 0.001). After adjustment for potential confounders, methylation levels of CDKN2B were positively correlated with cube root transformed calcification scores (β = 0.591 ± 0.172, p = 0.001) in generalized liner model. A positive correlation was also detected between average methylation levels of CDKN2B and cube root transformed calcium volumes (β = 0.533 ± 0.160, p = 0.001). Conclusions DNA methylation of CDKN2B may play a potential role in artery calcification.

Research utilizing repeated-measures such as daily assessments with self-report and/or objective measures [e.g., physical activity (PA) monitors] are important in understanding health behaviors and informing practice and policy. However, studies that utilize daily assessment often encounter issues with attrition and non-compliance. The current research yielded high levels of retention and adherence with both self-report and objective daily measures. The purpose of this paper is to highlight and discuss strategies utilized in maximizing retention, minimizing missing data, and some lessons learned from the research experience. Fifty community participants took part in a 4-week study utilizing both daily self-report questionnaires and daily use of PA monitors (Fitbit One™). This study focused on typical daily PA and was not an intervention study (e.g., participants were not randomized nor asked to change their PA behavior). Participants completed the study in two waves (wave 1 n = 10, wave 2 n = 40). The research team utilized several retention strategies including automating the data collection process, a prorated incentive structure, having a dedicated and responsive study staff, and utilizing the 2-wave process to optimize data collection during the 2nd wave. The study had 100% retention and generally positive anonymous feedback post-study. Overall, participants completed the vast majority of daily surveys (97%) and wore their Fitbits (for at least part of the day) on almost all days (99.57%) of the study, although there were individual differences. The strategies discussed and lessons learned may be useful to other researchers using daily measurements for whom adherence and retention are important issues. Future research employing these strategies in different populations, with different measurements, and for longer durations is warranted to determine generalizability.

Endophytic bacteria have received attention for their ability to promote plant growth and enhance phytoremediation, which may be attributed to their ability to produce indole-3-acetic acid (IAA). As a signal molecular, IAA plays a key role on the interaction of plant and its endomicrobes. However, the different effects that endophytic bacteria and IAA may have on plant growth and heavy metal uptake is not clear. In this study, the endophytic bacterium Pseudomonas fluorescens Sasm05 was isolated from the stem of the zinc (Zn)/cadmium (Cd) hyperaccumulator Sedum alfredii Hance. The effects of Sasm05 and exogenous IAA on plant growth, leaf chlorophyll concentration, leaf Mg2+-ATPase and Ca2+-ATPase activity, cadmium (Cd) uptake and accumulation as well as the expression of metal transporter genes were compared in a hydroponic experiment with 10 μM Cd. The results showed that after treatment with 1 μM IAA, the shoot biomass and chlorophyll concentration increased significantly, but the Cd uptake and accumulation by the plant was not obviously affected. Sasm05 inoculation dramatically increased plant biomass, Cd concentration, shoot chlorophyll concentration and enzyme activities, largely improved the relative expression of the three metal transporter families ZRT/IRT-like protein (ZIP), natural resistance associated macrophage protein (NRAMP) and heavy metal ATPase (HMA). Sasm05 stimulated the expression of the SaHMAs (SaHMA2, SaHMA3, and SaHMA4), which enhanced Cd root to shoot translocation, and upregulated SaZIP, especially SaIRT1, expression to increase Cd uptake. These results showed that although both exogenous IAA and Sasm05 inoculation can improve plant growth and photosynthesis, Sasm05 inoculation has a greater effect on Cd uptake and translocation, indicating that this endophytic bacterium might not only produce IAA to promote plant growth under Cd stress but also directly regulate the expression of putative key Cd uptake and transport genes to enhance Cd accumulation of plant.

Background: Early pleural tuberculosis (TB) diagnosis is particularly difficult. The aim of this study was to investigate the diagnostic accuracy of the Xpert MTB/RIF (Xpert) (Cepheid, Sunnyvale, CA) assay using pleural biopsy and pleural fluid specimens in patients with suspected pleural TB but who had a negative sputum acid-fast bacilli (AFB) smear. Materials and Methods: In this study, 134 sputum smear-negative suspected pleural TB patients were selected. Paired pleural fluid and pleural biopsy specimens were tested for Mycobacterium tuberculosis by standard smear-microscopy, Lowenstein-Jensen and mycobacterial growth indicator tube (MGIT) culture, and the Xpert assay. Mycobacterial culture from pleural biopsy specimens was used as a reference standard for sensitivity and specificity calculations. Detection of rifampicin resistance was compared with the MGIT method. Results: Of 126 evaluable patients, 55 received a diagnosis of pleural TB. The sensitivity of the Xpert assay using pleural biopsy specimens for the diagnosis of pleural TB was 85.5%, and specificity was 97.2%. The sensitivity and specificity of the Xpert assay in pleural fluid were 43.6% and 98.6%, respectively. The Xpert assay correctly identified 90.0% of phenotypic rifampicin-resistant cases and 93.9% of phenotypic rifampicin-susceptible cases. Conclusion: The Xpert assay on pleural biopsy specimens may provide an accurate diagnosis of pleural TB in patients who had a negative AFB smear.

Background: Periodization of exercise is a method typically used in sports training, but the impact of periodized exercise on health outcomes in untrained adults is unclear. Purpose: This review aims to summarize existing research wherein aerobic or resistance exercise was prescribed to inactive adults using a recognized periodization method. Methods: A search of relevant databases, conducted between January and February of 2014, yielded 21 studies published between 2000 and 2013 that assessed the impact of periodized exercise on health outcomes in untrained participants. Results: Substantial heterogeneity existed between studies, even under the same periodization method. Compared to baseline values or non-training control groups, prescribing periodized resistance or aerobic exercise yielded significant improvements in health outcomes related to traditional and emerging risk factors for cardiovascular disease, low-back and neck/shoulder pain, disease severity, and quality of life, with mixed results for increasing bone mineral density. Conclusions: Although it is premature to conclude that periodized exercise is superior to non-periodized exercise for improving health outcomes, periodization appears to be a feasible means of prescribing exercise to inactive adults within an intervention setting. Further research is necessary to understand the effectiveness of periodizing aerobic exercise, the psychological effects of periodization, and the feasibility of implementing flexible non-linear methods.

Despite the crucial role of mentoring, little literature exists that addresses distance mentoring among health researchers. This article provides three case studies showcasing protégés at different stages of career development (one in graduate school, one as an early-stage researcher, and one as an established researcher). Each case study provides a brief history of the relationship, examines the benefits and challenges of working together at a distance, and discusses the lessons learned from both the mentor and the protégé over the course of these relationships. A mentoring model, examples of mentoring communications, and potential promising practices are also provided and discussed.

Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum, rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding.

With the decline of shallow coal reserves and increase in demand of coal consumption, the hazard of coal and rock dynamic disasters is expanding. In this paper, we conducted some laboratory scale tests on coal, cement, and glass materials to figure out the microseismic (MS) characteristic differences among materials. A new method, denoted as WPT-LMD, is proposed to conduct signal denoising and analysis work. A series of basic analyses regarding MS are conducted, including the relationships between MS characteristics and loading rate, coal powder particle size, loading stage, and MS event statistics. Research results show that the damage of all these three materials is accompanied with MS events, abundant with low frequency component (0–200 Hz). But cement and coal specimens produce with relative wide frequency distribution in sample frequency domain, while glass specimens were found to only produce low frequency event. The powder particle sizes have obvious influence on the strength of coal specimen, but the loading rate seems to have no influence on the MS characteristics. The outcome of the paper will further provide a theoretical basis for understanding the mechanism of MS activities and has great significance to improve the coal mining safety.

The limited resource or strength model of self-control posits that the use of self-regulatory resources leads to depletion and poorer performance on subsequent self-control tasks. We conducted four studies (two with community samples, two with young adult samples) utilizing a frequently used depletion procedure (crossing out letters protocol) and the two most frequently used dependent measures of self-control (handgrip perseverance and modified Stroop). In each study, participants completed a baseline self-control measure, a depletion or control task (randomized), and then the same measure of self-control a second time. There was no evidence for significant depletion effects in any of these four studies. The null results obtained in four attempts to replicate using strong methodological approaches may indicate that depletion has more limited effects than implied by prior publications. We encourage further efforts to replicate depletion (particularly among community samples) with full disclosure of positive and negative results.

Engaging in novel/exciting ("self-expanding") activities activates the mesolimbic dopamine pathway, a brain reward pathway also associated with the rewarding effects of nicotine. This suggests that self-expanding activities can potentially substitute for the reward from nicotine. We tested this model among nicotine-deprived smokers who, during fMRI scanning, played a series of two-player cooperative games with a relationship partner. Games were randomized in a 2 (self-expanding vs. not) x 2 (cigarette cue present vs. absent) design. Self-expansion conditions yielded significantly greater activation in a reward region (caudate) than did non-self-expansion conditions. Moreover, when exposed to smoking cues during the self-expanding versus the non-self-expanding cooperative games, smokers showed less activation in a cigarette cue-reactivity region, a priori defined [temporo-parietal junction (TPJ)] from a recent meta-analysis of cue-reactivity. In smoking cue conditions, increases in excitement associated with the self-expanding condition (versus the non-self-expanding condition) were also negatively correlated with TPJ activation. These results support the idea that a self-expanding activity promoting reward activation attenuates cigarette cue-reactivity among nicotine-deprived smokers. Future research could focus on the parameters of self-expanding activities that produce this effect, as well as test the utility of self-expansion in clinical interventions for smoking cessation.

The underlying mechanism of ischemic stroke is not completely known. Regulatory T cells (Tregs), a subset of T cells, play a pivotal role in the pathophysiological process of ischemic stroke. However, there is also controversy over the role of Tregs in stroke. Hence, the function of Tregs in ischemic stroke has triggered a heated discussion recently. In this paper, we reviewed the current lines of evidence to describe the full view of Tregs in stroke. We would like to introduce the basic concepts of Tregs and then discuss their paradox function in ischemic stroke. On one side, Tregs could protect brain against ischemic injury via modulating the inflammation process. On the other side, they exaggerated the insult by causing microvascular dysfunction. They also interfered with the neurological function recovery. In addition, the reasons for this paradox role would be discussed in the review and the prospective of the clinical application of Tregs was also included. In conclusion, Tregs contributed to the outcome of ischemic stroke, while more lines of evidence are needed to understand how Tregs regulate the immune system and influence the outcome of stroke.

Self-expanding experiences like falling in love or engaging in novel, exciting and interesting activities activate the same brain reward mechanism (mesolimbic dopamine pathway) that reinforces drug use and abuse, including tobacco smoking. This suggests the possibility that reward from smoking is substitutable by self-expansion (through competition with the same neural system), potentially aiding cessation efforts. Using a model of self-expansion in the context of romantic love, the present fMRI experiment examined whether, among nicotine-deprived smokers, relationship self-expansion is associated with deactivation of cigarette cue-reactivity regions. Results indicated that among participants who were experiencing moderate levels of craving, cigarette cue-reactivity regions (e.g., cuneus and posterior cingulate cortex) showed significantly less activation during self-expansion conditions compared with control conditions. These results provide evidence that rewards from one domain (self-expansion) can act as a substitute for reward from another domain (nicotine) to attenuate cigarette cue reactivity.