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Purpose Not all patients benefit from transarterial chemoembolization (TACE) due to the heterogeneity of the tumour burden in intermediate-stage hepatocellular carcinoma (HCC). To compare the outcomes of transarterial chemoembolization (TACE) combined with molecular-targeted agents plus immune checkpoint inhibitors (TACE-MTAs-ICIs) with those of TACE for patients with unresectable hepatocellular carcinoma (uHCC) that were beyond the up-to-seven criteria.Patients and methods Between January 2019 and July 2022, 130 patients diagnosed with uHCC beyond the up-to-seven criteria were retrospectively identified, including 47 patients who received TACE-MTAs-ICIs and 83 patients who received TACE alone. The primary endpoints were overall survival (OS) and progression-free survival (PFS); the secondary endpoints included tumour response and adverse events (AEs).Results There were 43 matched patients. The median OS and PFS times in the TACE-MTAs-ICIs group were significantly longer than those in the TACE group (OS: 27.2 vs. 15.9 months, p = 0.007; PFS: 15.4 months vs. 4.8 months, p

Abstract To explore the role of bronchoscopy for the assessment of checkpoint inhibitor pneumonitis (CIP), a retrospective single-center study was conducted to assess patients diagnosed with CIP at grade 2 or above and also underwent bronchoscopy between January 2020 and December 2022. Clinical data and bronchoscopic findings were recorded. The treatment data and prognosis information were collected. Twenty-one patients who underwent bronchoscopy and were diagnosed with CIP were enrolled in this study. All patients underwent bronchoalveolar lavage fluid (BALF) analysis. Of them, T lymphocyte subsets of BALF were tested in 15 cases. Transbronchial cryobiopsy (TBCB) was performed in 8 patients, and transbronchial lung biopsy was performed in 5 patients. 3 patients developed pneumothorax after TBCB and all recovered without serious compilations.14 patients experienced grade 2 CIP, while 7 patients ≥ grade 3 CIP. Symptoms were improved in 19 (90.5%) patients after standard treatment adhering to CIP guidelines. However, 5 patients relapsed during steroid tapering. Factors related to the severity and recurrence of CIP were analyzed. Patients with previous interstitial lung disease (ILD) were more likely to develop high grade CIP than those without [83.3% (5/6) versus 15.4% (3/15), P = 0.011].The odds ratio (OR) was 32.5 (95% CI 2.284–443.145, P = 0.009). Increased BALF lymphocyte percentage was associated with high grade CIP, OR 1.095 (95% CI 1.001–1.197, P = 0.047), and higher possibility of CIP relapse, OR 1.123 (95% CI, 1.005–1.225, P = 0.040). Lymphocyte subsets were tested in 15 patients. CD4/CD8 > 1 was found in 80% (4/5) of relapsed patients and 20% (2/10) of patients without relapse (P = 0.047). The OR was 16.00 (95% CI 1.093–234.24, P = 0.043). In this retrospective study, patients with previous ILD was more likely to develop high grade CIP. Higher lymphocyte percentage in BALF was associated with high grade CIP and susceptibility to relapse during treatment of CIP. A CD4/CD8 ratio greater than 1 in lymphocyte subsets of BALF was associated with higher possibility of CIP relapse. We found that TBCB is a safe procedure in CIP patients.

Abstract Background Photodynamic therapy (PDT) is a promising interventional treatment approach that contributes to antitumor immunity. It has been reported that PDT can enhance the effectiveness of immune checkpoint inhibitors (ICIs), but its mechanism is yet unclear. Herein, we implemented bioinformatics analysis to detect common pathways and potential biomarkers in non-small cell lung cancer (NSCLC), PDT, and NSCLC immunotherapy to investigate potential links between PDT, immunotherapy and NSCLC, and their clinical impact. Methods Differentially expressed genes in NSCLC- and NSCLC immunotherapy-related data in the GEO database were intersected with PDT-related genes in the GeneCards database to obtain candidate genes and shared pathways. Enrichment analysis and protein–protein interaction were established to identify key genes in functionally enriched pathways. The expression profiles and the prognostic significance of key genes were depicted. Results Bioinformatics analysis showed that HIF-1α was screened as a prognostic gene in hypoxia, HIF-1, and PD-L1-related signaling pathways, which was associated with clinical response in NSCLC patients after PDT and immunotherapy. In vivo experiments showed that PDT could inhibit tumor growth and upregulate HIF-1α and PD-L1 expressions in NSCLC tissues with a positive correlation, which might influence the blocking activity of ICIs on the HIF-1, and PD-L1-related signaling pathways. Conclusions PDT might improve the clinical response of ICIs by upregulating tumor HIF-1α and PD-L1 expressions in NSCLC.

Abstract The hemorrhagic progression of a contusion (HPC) after Traumatic brain injury (TBI) is one of the important causes of death in trauma patients. The purpose of this meta-analysis was to evaluate the predictive effect of imaging features of Computed tomography (CT) on HPC after TBI. A comprehensive systematic search was performed using PubMed, EMBASE, and WEB OF SCIENCE databases to identify all relevant literature. A total of 8 studies involving 2543 patients were included in this meta-analysis. Meta-analysis showed that subarachnoid hemorrhage (OR 3.28; 95% CI 2.57–4.20), subdural hemorrhage (OR 4.35; 95% CI 3.29–5.75), epidural hemorrhage (OR 1.47;95% CI 1.15–1.89), contrast extravasation (OR 11.81; 95% CI 4.86–28.71) had a predictive effect on the occurrence of HPC. Skull fracture (OR 1.64; 95% CI 0.84–3.19) showed no statistical significance, and midline displacement > 5 mm (OR 4.66; 95% CI 1.87–11.62) showed high heterogeneity. The results of this meta-analysis showed that some imaging features were effective predictors of HPC after TBI. Well-designed prospective studies are needed to more accurately assess the effective predictors of HPC after TBI.

Abstract Brushless direct current motor is widely used in industrial production because of its simple structure, wide speed range and low noise. To improve the operation efficiency of brushless DC motor and reduce the production and application costs, the optimization of brushless DC motor is analyzed by introducing the JAYA algorithm. This method determines the optimal parameters of a brushless DC motor using the theory of electromagnetic structure parameter selection and efficiency calculation. The population diversity of the JAYA algorithm is improved through an empirical learning strategy, and an adaptive strategy is introduced to balance the development ability and search performance of the algorithm. This ensures population diversity and improves convergence speed. The experiment showcases that the improved JAYA algorithm has a lower rank average in unimodal function operations, demonstrating stronger local development ability and better stability. It exhibits strong search ability in many local optima of multimodal functions. Moreover, the motor's average efficiency after optimization is 94.48%. The algorithm reaches the global optimum after approximately 40 iterations and offers faster convergence speed and higher accuracy. The adaptive JAYA algorithm is stable at around 93% when the number of iterations reaches 90, with a maximum efficiency of 95.3%. It is 5–12 percentage points higher than the other three comparison algorithms. The optimal solution of the motor parameters in the adaptive JAYA algorithm is closest to the theoretical parameter optimization value, meeting both the constraints of variables and the constraints of the model. The stator diameter, tooth magnetic induction, winding current density, air gap magnetic induction, and stator yoke magnetic induction values are 201.5 mm, 1.8 T, 2.049 A/mm2, 0.63 T, and 0.91 T, respectively. The research overcomes the problem of parameter optimization in the optimization design of brushless DC motor, improving their economic value of brushless DC motor in industrial production and application.

Abstract Background and Aims Immune checkpoint inhibitors (ICIs) across multiple treatment lines have not yet been evaluated comprehensively. The purpose of this research was to investigate whether or not continuous cross‐line ICIs therapy is effective in treating non‐small cell lung cancer (NSCLC). Methods We conducted a retrospective investigation into the medical histories of 47 patients diagnosed with advanced NSCLC and treated with ICIs at the Peking University First Hospital between January 2018 and June 2022. Results Due to the progression of their disease, 14 patients were given the same ICIs, 5 patients were given different ICIs, and 6 patients discontinued taking ICIs altogether. The objective response rates were 7.140% in the ICIs cross‐line treatment group, 0% in the replacement of ICIs treatment group, and 0% in the discontinuation of ICIs treatment group. The disease control rates were 64.260% in the ICIs cross‐line treatment group, 60% in the replacement of ICIs treatment group, and 0% in the discontinuation of ICIs treatment group. The average overall survival durations of the three groups were 24.020 (95% confidence interval [CI]: 17.061–30.979), 31.643 (95% CI: 23.513–39.774), and 7.997 (95% CI: 3.746–12.247) months, respectively (p = 0.003). The median second progression‐free survival (PFS2) durations of the three groups were 4.570 (95% CI: 3.276–5.864), 3.530 (95% CI: 0.674–6.386), and 1.570 (95% CI: 0–4.091) months, respectively (p = 0.091). Conclusions Cross‐line ICIs cannot improve the prognosis and PFS2 of patients with NSCLC, but compared to discontinuing ICIs, OS may be prolonged. A few patients may benefit from prolonged ICIs therapy.

Background Since the Internet dependence of the supply and demand sides of health popularization is increasing, eHealth literacy has become a primary skill that chronic disease patients need to master. Objective To analyze the current situation and existing problems of online health information usage habits and eHealth literacy in middle-aged and elderly residents, and discuss the relationship between online health information usage habits and eHealth literacy, providing a reference for improving the level of eHealth literacy and developing appropriate Internet-based health popularization services for these populations. Methods From June to September 2021, a questionnaire survey was conducted among 1 061 middle-aged and elderly residents in Shanghai communities selected by multistage sampling using the General Information Questionnaire and the Chinese version of the eHealth Literacy Scale (eHEALS-C) to understand their habits of using online health information and levels of eHealth literacy. Stepwise multiple linear regression was used to assess the association of habit of using online health information and other potential candidate factors with the level of eHealth literacy. Results Altogether, 1 019 cases (96.04%) who effectively responded to the survey were included for analysis. Following health care accounts〔411 cases (40.33%) 〕was a major channel used for seeking online health information, followed by the search functionality or engines〔336 cases (32.97%) 〕, while the health apps or mini programs〔254 cases (24.93%) 〕, and online health communities〔65 cases (6.38%) 〕were less used. The online health information was less sourced from medical institutions〔397 cases (38.96%) 〕and medical workers〔187 cases (18.35%) 〕. The average total score of the eHEALS-C for the respondents was (27.62±8.57). The respondents scored lower in item 2〔 (3.36±1.27) points〕and item 6〔 (3.38±1.23) points〕of the eHEALS-C, indicating that they had low awareness of applying online health information to health problems, and low perceived skills at evaluating the online health information. Multiple linear regression analysis showed that age, participation in both basic and commercial medical insurance, using at least two channels for seeking online health information, having at least two sources of online health information, the habit of forwarding and sharing online health information, participation in collective online learning, and having an attitude of acceptance towards online health information were influencing factors of the level of eHealth literacy. Conclusion The eHealth literacy of these middle-aged and elderly residents is at a medium level, which is affected by online health information usage habits and other factors. To help them make better use of online health information and to improve their eHealth literacy, it is suggested to spread integrated authoritative information and retrieval platforms among these populations, give priority to supervision and elderly-oriented transformation of online health information platforms, and mobilize community, family, health associations, and commercial medical insurance institutions to co-deliver health-promotion services targeting these people.

Abstract Objective The objective of this study was to explore the clinical utility of the implementation of expanded carrier screening (ECS) in Chinese population of childbearing age. Materials and methods Based on capillary electrophoresis, a first-generation sequencing technology, a prospective screening study of carriers of 15 single-gene diseases was carried out in 327 subjects in Anhui Province, including 84 couples and 159 women of childbearing age, the disease carrier rate, types of screened pathogenic genes, and incidence of both partners carrying the same pathogenic genes were summarized and analyzed. Results In 320 people with normal phenotypes who underwent ECS for 15 genetic diseases and 7 spouses who underwent targeted gene sequencing, 65 carriers of at least one disease were detected, with a total carrier rate of 20.31% (65/320). Among the 65 carriers, 81.54% (53/65) carried one genetic variant, 16.92% (11/65) carried two genetic variants, and 1.54% (1/65) carried three genetic variants. In this study, the three diseases with the highest carrier rates were hereditary deafness (8.13%, 26/320), Wilson's disease (4.06%, 13/320), and phenylketonuria (3.13%, 10/320). One high-risk couple (1.19%, 1/84) was detected. Conclusions It has certain clinical application value to implement ECS in the population of childbearing age in China.

Objective To explore the therapeutic effects of biofeedback in the treatment of faecal incontinence (FI) after surgery for anorectal malformation (ARM).Methods Clinical data were collected from paediatric patients for postoperative biofeedback due to FI caused by ARM between May 2017 and November 2021. The data included the duration of symptoms, the integrity of the anal sphincter, anorectal manometry parameters, and FI scores. These patients were divided into the low ARM group (group A) and the high ARM group (group B).Results A total of 45 paediatric patients were enrolled in the study. There were 28 cases in group A and 17 cases in group B. The differences in age, gender, and body weight were not statistically significant between the two groups (p > 0.05). The differences in the clinical indicators were also not statistically significant between the two groups at the time of the initial evaluation. The duration of symptoms was 2.21 ± 0.71 years and 4.14 ± 1.89 years in groups A and B. There were 16 cases with an intact anal sphincter in group A and only two cases with an intact anal sphincter in group B. This difference was statistically significant between the two groups (p

Abstract Lung cancer still contributes to nearly one‐quarter cancer‐related deaths in the past decades, despite the rapid development of targeted therapy and immunotherapy in non‐small cell lung cancer (NSCLC). The development and availability of comprehensive genomic profiling make the classification of NSCLC more precise and personalized. Most treatment decisions of advanced‐stage NSCLC have been made based on the genetic features and PD‐L1 expression of patients. For the past 2 years, more than 10 therapeutic strategies have been approved as first‐line treatment for certain subgroups of NSCLC. However, some major challenges remain, including drug resistance and low rate of overall survival. Therefore, we discuss and review the therapeutic strategies of NSCLC, and focus on the development of targeted therapy and immunotherapy in advanced‐stage NSCLC. Based on the latest guidelines, we provide an updated summary on the standard treatment for NSCLC. At last, we discussed several potential therapies for NSCLC. The development of new drugs and combination therapies both provide promising therapeutic effects on NSCLC.

Abstract Higher magnetic fields are always favoured in the magnetoplasmadynamic thruster (MPDT) due to its superior control of the plasma profile and acceleration process. This paper introduces the world's first integrated study on the 150 kW level AF-MPDT equipped with a superconductive coil. A completely new way of using superconducting magnet technology to confine plasma with high energy and extremely high temperatures is proposed. Using the PIC method of microscopic particle simulation, the plasma magnetic nozzle effect and performance of the MPDT under different magnetic-field conditions were studied. The integrated experiment used demonstrated that, in conjunction with the superconducting coil, greater homogeneity and a stronger magnetic field not only caused more even cathode ablation and improved its lifespan but also improved the performance of the MPDT (maximum thrust was 4 N at 150 kW, 0.56 T). Maximum thrust efficiency reached 76.6% and the specific impulse reached 5714 s.

Abstract. Background. The coronavirus disease 2019 (COVID-19) outbreak occurred during the flu season around the world. This study aimed to analyze the impact of influenza A virus (IAV) exposure on COVID-19. Methods. Seventy COVID-19 patients admitted to the hospital during January and February 2020 in Wuhan, China were included in this retrospective study. Serum tests including respiratory pathogen immunoglobulin M (IgM) and inflammation biomarkers were performed upon admission. Patients were divided into common, severe, and critical types according to disease severity. Symptoms, inflammation indices, disease severity, and fatality rate were compared between anti-IAV IgM-positive and anti-IAV IgM-negative groups. The effects of the empirical use of oseltamivir were also analyzed in both groups. For comparison between groups, t tests and the Mann-Whitney U test were used according to data distribution. The Chi-squared test was used to compare disease severity and fatality between groups. Results. Thirty-two (45.71%) of the 70 patients had positive anti-IAV IgM. Compared with the IAV-negative group, the positive group showed significantly higher proportions of female patients (59.38% vs. 34.21%, χ2 = 4.43, P = 0.035) and patients with fatigue (59.38% vs. 34.21%, χ2 = 4.43, P = 0.035). The levels of soluble interleukin 2 receptor (median 791.00 vs. 1075.50 IU/mL, Z = −2.70, P = 0.007) and tumor necrosis factor α (median 10.75 vs. 11.50 pg/mL, Z = −2.18, P = 0.029) were significantly lower in the IAV-positive group. Furthermore, this group tended to have a higher proportion of critical patients (31.25% vs. 15.79%, P = 0.066) and a higher fatality rate (21.88% vs. 7.89%, P = 0.169). Notably, in the IAV-positive group, patients who received oseltamivir had a significantly lower fatality rate (0 vs. 36.84%, P = 0.025) compared with those not receiving oseltamivir. Conclusions. The study suggests that during the flu season, close attention should be paid to the probability of IAV exposure in COVID-19 patients. Prospective studies with larger sample sizes are needed to clarify whether IAV increases the fatality rate of COVID-19 and to elucidate any benefits of empirical usage of oseltamivir.

This research sought to ascertain the relationship between hematocrit (HCT) and mortality in patients with sepsis.MethodsA retrospective analysis was conducted on the clinical data of septic patients who were hospitalized between 2008 and 2019 in an advanced academic medical center in Boston, Massachusetts, registered in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, We analyzed basic information including gender, age, race, and types of the first admission, laboratory indicators including HCT, platelets, white blood cells, albumin, bilirubin, hemoglobin, and serum creatinine, and 30-day mortality. A Cox proportional hazards regression model was utilized to analyze the relationship between HCT and 30-day mortality in patients with sepsis.ResultsThis research recruited 2057 patients who met the research requirements from 2008 to 2019. According to the HCT level, it was classified into the low HCT level, the regular HCT level, and the high HCT level. The 30-day mortality rate was 62.6%, 27.5%, and 9.9% for patients with the low HCT level, the regular HCT level, and the high HCT level, respectively (p < 0.05). The multivariate Cox proportional hazard regression model analysis displayed that compared with patients with the regular HCT level, the 30-day mortality of patients with the low HCT level increased by 58.9% (hazard ratio = 1.589, 95% confidence interval (CI) = 1.009-2.979, p < 0.05).ConclusionThe low HCT level is an independent risk factor for the increase of the 30-day mortality in patients with sepsis and can be used as a significant predictor of the clinical outcome of sepsis.

Based on expectation states theory, we examined the mechanism underlying the effect of employees' sense of power on supervisors' voice endorsement, and tested our hypothesized model on a sample of 307 employees from 60 work teams. We used a two-time lagged design and paired questionnaire survey. Our analysis indicated that employees' sense of power enhanced supervisors' voice endorsement, and supervisors' perceived voice constructiveness mediated this relationship. Multilevel analyses showed that power distance negatively moderated the influence of sense of power on perceived voice constructiveness and negatively moderated its indirect effect on voice endorsement.

Contrary to the common expectation that the reference evapotranspiration (ETo), which is an indicator of the atmospheric evaporation capability, increases in warming climate, the decline of the ETo has been reported worldwide, and this contradiction between the expected increasing ETo and the observed decreasing one is now termed the "evaporation paradox". Based on the updated meteorological data (1960-2019), we separately detected the spatiotemporal characteristics and the causes of the "evaporation paradox" in three subregions, namely Huaibei, Jianghuai, and Sunan, and throughout the entire province of Jiangsu in southeastern China. Different from the reported continuous unidirectional variations in the ETo, in the province of Jiangsu, it generally showed a decreasing trend before 1990 but followed an increasing trend from 1990 to 2019, which led to the different characteristics of the "evaporation paradox" in the periods from 1960 to 1989, from 1990 to 2019, and from 1960 to 2019. In the first 30 years, the reduction of the wind speed (WS) was the main reason for the decreased ETo, which consequently gave rise to the "evaporation paradox" in spring and winter in the Huaibei region and only in winter in the two other subregions and throughout the entire province. We noticed that the "evaporation paradox" in spring in the Sunan region was expressed by the decreased daily mean air temperature (Tmean) and the increased ETo which was chiefly induced by the decreased relative humidity (RH) and the increased vapor pressure deficit (VPD). After 1990, the decreased WS also dominated the decreased ETo and resulted in the "evaporation paradox" in winter in the Jianghuai region. Furthermore, the decreased sunshine hour (SH) was the main factor influencing the decreased ETo, thereby inducing the "evaporation paradox" in summer and autumn in the Jianghuai region and only in autumn in the Huaibei region and throughout the whole province from 1990 to 2019. In the whole study period from 1960 to 2019, the decreased SH was also found to be responsible for the decreased ETo and for the "evaporation paradox" in summer in all the subregions and throughout the whole province. However, regarding the "evaporation paradox" in autumn, in winter, and in the entire year in the Huaibei region and throughout the whole province, the observed decreased ETo was largely due to the reduced WS from 1960 to 2019. In summary, in addition to the air temperature, the ETo has shifted due to the other meteorological variables (especially the WS, the SH, and the VPD) and shaped the unique spatiotemporal characteristics of the "evaporation paradox" in the province of Jiangsu in southeastern China. Moreover, future studies and simulations addressing the regional climate change and hydrological cycles should take account of the changeable key meteorological variables in different subregions and seasons of the province of Jiangsu.

The plant DNA-binding with one finger (Dof) gene family is a class of plant-specific transcription factors that play vital roles in many biological processes and stress responses. In the present study, a total of 36 ClDof genes were identified in the watermelon genome, which were unevenly distributed on 10 chromosomes. Phylogenetic analysis showed that the ClDof proteins could be divided into nine groups, and the members in a particular group had similar motif arrangement and exon–intron structure. Synteny analysis indicated the presence of a large number of syntenic relationship events between watermelon and cucumber. In promoter analysis, five kinds of stress-related and nine kinds of hormone-related cis-elements were identified in the promoter regions of ClDof genes. We then analyzed the expression patterns of nine selected ClDof genes in eight specific tissues by qRT-PCR, and the results showed that they have tissue-specific expression patterns. We also evaluated the expression levels of 12 selected ClDof genes under salt stress and ABA treatments using qRT-PCR. As a result, they showed differential expression under these treatments, suggesting their important roles in stress response. Taken together, our results provide a basis for future research on the biological functions of Dof genes in watermelon.

Background: Contribution of model for end-stage liver disease incorporating with serum sodium (MELD-Na) score in predicting acute kidney injury (AKI) after orthotopic liver transplantation (OLT) is yet to be identified. This study assessed the prognostic value of MELD-Na score for the development of AKI following OLT. Methods: Preoperative and surgery-related variables of 321 adult end-stage liver disease patients who underwent OLT in Fuzhou General Hospital were collected. Postoperative AKI was defined and staged in accordance with the clinical practice guidelines developed by Kidney Disease: Improving Global Outcomes. Univariate and multivariate analysis was performed to determine the risk factors for AKI following OLT. The discriminating power of MELD/MELD-Na score on AKI outcome was evaluated by receiver operating characteristic (ROC) curve. Spearman's correlation analysis was used for identifying the correlated relationship between MELD/MELD-Na score and the severity levels of AKI. Results: The prevalence of AKI following OLT was in 206 out of 321 patients (64.2%). Three risk factors for AKI post-OLT were presented, preoperative calculated MELD score (odds ratio [OR] = 1.048, P = 0.021), intraoperative volume of red cell suspension transfusion (OR = 1.001, P = 0.002), and preoperative liver cirrhosis (OR = 2.015, P = 0.012). Two areas under ROC curve (AUCs) of MELD/MELD-Na score predicting AKI were 0.688 and 0.672, respectively; the difference between two AUCs was not significant (Z = 1.952, P = 0.051). The Spearman's correlation coefficients between MELD/MELD-Na score and the severity levels of AKI were 0.406 and 0.385 (P = 0.001, 0.001), respectively. Conclusions: We demonstrated that preoperative MELD score, intraoperative volume of red cell suspension transfusion and preoperative liver cirrhosis were risk factors for AKI following OLT. Furthermore, we preliminarily validated that MELD score seemed to have a stronger power discriminating AKI post-OLT than that of novel MELD-Na score.

Abstract TMEM230 mutations have been recently reported to cause autosomal dominant Parkinson’s disease (PD). However, there are limited studies from different ethnic populations to support the role of TMEM230 in sporadic PD. In this study, we performed a comprehensive TMEM230 mutation screening in 550 sporadic PD patients and 560 controls to elaborate the genetic contribution of TMEM230 to sporadic PD. Overall, we did not find any pathogenic mutations in the coding sequence, while we identified four variants (c.68 + 182G > A, c.78A > G, c.552 + 11A > G and c.174 + 11C > T) both in the patients and controls, and c.68 + 182G > A appeared to be associated with an increased risk of PD (odds ratio 1.782, 95% confidence interval 1.035–3.067, p A had no significant association with sporadic PD (p c = 0.136, p c > 0.05). Thus our results suggest that TMEM230 gene mutations may be rare in Chinese populations, and the variability of TMEM230 gene may not be a main factor for sporadic PD patients in Chinese Han populations. More evidence is still needed to clarify this question.

There is great debate surrounding the demographic impact of China's population control policies, especially the one-birth restrictions, which ended only recently. We apply an objective, data-driven method to construct the total fertility rates and population size of a 'synthetic China', which is assumed to be not subjected to the two major population control policies implemented in the 1970s. We find that while the earlier, less restrictive 'later-longer-fewer' policy introduced in 1973 played a critical role in driving down the fertility rate, the role of the 'one-child policy' introduced in 1979 and its descendants was much less significant. According to our model, had China continued with the less restrictive policies that were implemented in 1973 and followed a standard development trajectory, the path of fertility transition and total population growth would have been statistically very similar to the pattern observed over the past three decades.

Background: The effects of near-road pollution on lung function in China have not been well studied. We aimed to investigate the effects of long-term exposure to traffic-related air pollution on lung function, airway inflammation, and respiratory symptoms. Methods: We enrolled 1003 residents aged 57.96 ± 8.99 years living in the Shichahai Community in Beijing. Distances between home addresses and the nearest major roads were measured to calculate home-road distance. We used the distance categories 1, 2, and 3, representing 200 m, respectively, as the dose indicator for traffic-related air pollution exposure. Lung function, exhaled breath condensate (EBC) pH, and interleukin 6 levels were measured. As a follow-up, 398 participants had a second lung function assessment about 3 years later, and lung function decline was also examined as an outcome. We used regression analysis to assess the impacts of home-road distance on lung function and respiratory symptoms. As the EBC biomarker data were not normally distributed, we performed correlation analysis between home-road distance categories and EBC biomarkers. Results: Participants living a shorter distance from major roads had lower percentage of predicted value of forced expiratory volume in 1 s (FEV1% −1.54, 95% confidence interval [CI]: −0.20 to −2.89). The odds ratio for chronic cough was 2.54 (95% CI: 1.57–4.10) for category 1 and 1.97 (95% CI: 1.16–3.37) for category 2, compared with category 3. EBC pH was positively correlated with road distance (rank correlation coefficient of Spearman [rs] = 0.176, P < 0.001). Conclusions: Long-term exposure to traffic-related air pollution in people who live near major roads in Beijing is associated with lower lung function, airway acidification, and a higher prevalence of chronic cough. EBC pH is a potential useful biomarker for evaluating air pollution exposure.

Mammalian target of rapamycin (mTOR) is a serine/threonine kinase and mTOR signaling is important in regulating cell growth and proliferation. Recent studies using oocyte- and granulosa cell-specific deletion of mTOR inhibitor genes TSC1 or TSC2 demonstrated the important role of mTOR signaling in the promotion of ovarian follicle development. We now report that treatment of ovaries from juvenile mice with an mTOR activator MHY1485 stimulated mTOR, S6K1 and rpS6 phosphorylation. Culturing ovaries for 4 days with MHY1485 increased ovarian explant weights and follicle development. In vivo studies further demonstrated that pre-incubation of these ovaries with MHY1485 for 2 days, followed by allo-grafting into kidney capsules of adult ovariectomized hosts for 5 days, led to marked increases in graft weights and promotion of follicle development. Mature oocytes derived from MHY1485-activated ovarian grafts could be successfully fertilized, leading the delivery of healthy pups. We further treated ovaries with the mTOR activator together with AKT activators (PTEN inhibitor and phosphoinositol-3-kinase stimulator) before grafting and found additive enhancement of follicle growth. Our studies demonstrate the ability of an mTOR activator in promoting follicle growth, leading to a potential strategy to stimulate preantral follicle growth in infertile patients.

Understanding the emergence of cooperation in spatial public goods game remains a grand challenge across disciplines. In most previous studies, it is assumed that the investments of all the cooperators are identical, and often equal to 1. However, it is worth mentioning that players are diverse and heterogeneous when choosing actions in the rapidly developing modern society and researchers have shown more interest to the heterogeneity of players recently. For modeling the heterogeneous players without loss of generality, it is assumed in this work that the investment of a cooperator is a random variable with uniform distribution, the mean value of which is equal to 1. The results of extensive numerical simulations convincingly indicate that heterogeneous investments can promote cooperation. Specifically, a large value of the variance of the random variable can decrease the two critical values for the result of behavioral evolution effectively. Moreover, the larger the variance is, the better the promotion effect will be. In addition, this article has discussed the impact of heterogeneous investments when the coevolution of both strategy and investment is taken into account. Comparing the promotion effect of coevolution of strategy and investment with that of strategy imitation only, we can conclude that the coevolution of strategy and investment decreases the asymptotic fraction of cooperators by weakening the heterogeneity of investments, which further demonstrates that heterogeneous investments can promote cooperation in spatial public goods game.

The limitations in general methods to evaluate clustering will remain difficult to overcome if verifying the clustering validity continues to be based on clustering results and evaluation index values. This study focuses on a clustering process to analyze crisp clustering validity. First, we define the properties that must be satisfied by valid clustering processes and model clustering processes based on program graphs and transition systems. We then recast the analysis of clustering validity as the problem of verifying whether the model of clustering processes satisfies the specified properties with model checking. That is, we try to build a bridge between clustering and model checking. Experiments on several datasets indicate the effectiveness and suitability of our algorithms. Compared with traditional evaluation indices, our formal method can not only indicate whether the clustering results are valid but, in the case the results are invalid, can also detect the objects that have led to the invalidity.

Hippo pathway controls the organ size by modulating cell proliferation and apoptosis. However, the upstream regulation of hippo signaling by actin cytoskeleton is not clear. To elucidate the role of actin as an upstream regulator of Hippo signaling, the levels of F (filamentous)-actin in cells were elevated using jasplakinolide, an actin-stabilizing drug. Induction of F-actin formation in HeLa cells resulted in decreased phosphorylation of YAP, a key effector molecule for Hippo signaling. The activated YAP is localized to the cell nucleus and YAP increase was associated with increased expression of downstream CCN growth factors CCN1/CYR61 and CCN2/CTGF. The effect of the actin-stabilizing drug was blocked when YAP levels were suppressed in YAP "knock-down" cells. In summary, using an actin-stabilizing drug we show that actin cytoskeleton is one of the upstream regulators of Hippo signaling capable of activating YAP and increasing its downstream CCN growth factors.

[This corrects the article on p. e73763 in vol. 8.].

Postoperative cognitive dysfunction (POCD) is a clinical phenomenon characterized by cognitive deficits in patients after anesthesia and surgery, especially in geriatric surgical patients. Although it has been documented that isoflurane exposure impaired cognitive function in several aged animal models, there are few clinical interventions and treatments available to prevent this disorder. Minocycline has been well established to exert neuroprotective effects in various experimental animal models and neurodegenerative diseases. Therefore, we hypothesized that pretreatment with minocycline attenuates isoflurane-induced cognitive decline in aged rats. In the present study, twenty-month-old rats were administered minocycline or an equal volume of saline by intraperitoneal injection 12 h before exposure to isoflurane. Then the rats were exposed to 1.3% isoflurane for 4 h. Two weeks later, spatial learning and memory of the rats were examined using the Morris Water Maze. We found that pretreatment with minocycline mitigated isoflurane-induced cognitive deficits and suppressed the isoflurane-induced excessive release of IL-1β and caspase-3 in the hippocampal CA1 region at 4 h after isoflurane exposure, as well as the number of TUNEL-positive nuclei. In addition, minocycline treatment also prevented the changes of synaptic ultrastructure in the hippocampal CA1 region induced by isoflurane. In conclusion, pretreatment with minocycline attenuated isoflurane-induced cognitive impairment in aged rats.

Studies using animal models demonstrated the importance of autocrine/paracrine factors secreted by preimplantation embryos and reproductive tracts for embryonic development and implantation. Although in vitro fertilization-embryo transfer (IVF-ET) is an established procedure, there is no evidence that present culture conditions are optimal for human early embryonic development. In this study, key polypeptide ligands known to be important for early embryonic development in animal models were tested for their ability to improve human early embryo development and blastocyst outgrowth in vitro. We confirmed the expression of key ligand/receptor pairs in cleavage embryos derived from discarded human tri-pronuclear zygotes and in human endometrium. Combined treatment with key embryonic growth factors (brain-derived neurotrophic factor, colony-stimulating factor, epidermal growth factor, granulocyte macrophage colony-stimulating factor, insulin-like growth factor-1, glial cell-line derived neurotrophic factor, and artemin) in serum-free media promoted >2.5-fold the development of tri-pronuclear zygotes to blastocysts. For normally fertilized embryos, day 3 surplus embryos cultured individually with the key growth factors showed >3-fold increases in the development of 6-8 cell stage embryos to blastocysts and >7-fold increase in the proportion of high quality blastocysts based on Gardner's criteria. Growth factor treatment also led to a 2-fold promotion of blastocyst outgrowth in vitro when day 7 surplus hatching blastocysts were used. When failed-to-be-fertilized oocytes were used to perform somatic cell nuclear transfer (SCNT) using fibroblasts as donor karyoplasts, inclusion of growth factors increased the progression of reconstructed SCNT embryos to >4-cell stage embryos. Growth factor supplementation of serum-free cultures could promote optimal early embryonic development and implantation in IVF-ET and SCNT procedures. This approach is valuable for infertility treatment and future derivation of patient-specific embryonic stem cells.

Interleukin 22 (IL-22) is a T-cell secreted cytokine that modulates inflammatory response in nonhematopoietic tissues such as epithelium and liver. The function of IL-22 in adipose tissue is currently unknown. We generated a transgenic mouse model with overexpression of IL-22 specifically in adipose tissue. The IL-22 transgenic mice had no apparent changes in obesity and insulin resistance after feeding with high fat diet (HFD). Unexpectedly, all the IL-22 transgenic mice fed with HFD for four months developed spontaneous tumors in epididymal adipose tissue. Histological analysis indicated that the tumors were well-differentiated liposarcomas with infiltration of inflammatory cells. IL-22 overexpression promotes production of inflammatory cytokines such as IL-1β and IL-10 and stimulates ERK phosphorylation in adipose tissue. Furthermore, IL-22 treatment in differentiated 3T3-L1 adipocytes could induce IL-1β and IL-10 expression, together with stimulation of ERK phosphorylation. Taken together, our study not only established a novel mouse model with spontaneous liposarcoma, but also revealed that IL-22 overexpression may collaborate with diet-induced obesity to impact on tumor development in mouse.