Recent Advances in Imaging Agents Anchored with pH (Low) Insertion Peptides for Cancer Theranostics.

The acidic extracellular microenvironment has become an effective target for diagnosing and treating tumors. A pH (low) insertion peptide (pHLIP) is a kind of peptide that can spontaneously fold into a transmembrane helix in an acidic microenvironment, and then insert into and cross the cell membrane for material transfer. The characteristics of the acidic tumor microenvironment provide a new method for pH-targeted molecular imaging and tumor-targeted therapy. As research has increased, the role of pHLIP as an imaging agent carrier in the field of tumor theranostics has become increasingly prominent. In this paper, we describe the current applications of pHLIP-anchored imaging agents for tumor diagnosis and treatment in terms of different molecular imaging methods, including magnetic resonance T1 imaging, magnetic resonance T2 imaging, SPECT/PET, fluorescence imaging, and photoacoustic imaging. Additionally, we discuss relevant challenges and future development prospects.

Prediction and potential risk factors for electronic cigarette use behaviors among adolescents: a pilot study in Chiayi, Taiwan.

Introduction: Electronic cigarette (e-cigarette) use among adolescents has become increasingly common; therefore, effectively reducing adolescent e-cigarette use is an urgent issue. We aimed to predict and identify potential factors related to adolescent e-cigarette use behaviors. Methods: This cross-sectional study was conducted using anonymous questionnaires given to Taiwanese high school students in 2020. Approximately 1,289 adolescent students completed questions on e-cigarette use, personal characteristics, family environment, and substances used. We performed multivariate logistic regression analyses to assess the model's predictive performance in terms of the area under the receiver operating characteristic curve. Results: We found that 9.3% of adolescent students used e-cigarettes. Tobacco smoking, close friends' reactions to e-cigarette use, and the use of other substances were independent risk factors for adolescent e-cigarette use. Furthermore, relative to tobacco nonuse, tobacco use and tobacco smoking dependence had odds ratios of 76.49 and 113.81, respectively. The predictive accuracy of adolescent e-cigarette use from personal characteristics, family environment, and substance use status was 73.13, 75.91, and 93.80%, respectively. Conclusion: The present study highlights the need for early prevention of e-cigarette use among adolescents, particularly those with a history of using tobacco and other substances and those who have close friends with positive attitudes towards e-cigarette use.

Risk of motor vehicle collisions after methadone use: A systematic review and meta-analysis.

INTRODUCTION: Methadone maintenance therapy is a leading treatment strategy for stabilizing and rehabilitating patients with opioid dependence; however, findings related to the risk of motor vehicle collisions after methadone use have been conflicting. In the present study, we compiled the available evidence on the risk of motor vehicle collisions after methadone use. METHODS: We completed a systematic review and meta-analysis of studies identified on six databases. Two reviewers independently screened the identified epidemiological studies, extracted data, and used the Newcastle-Ottawa Scale to assess the quality of the studies. Risk ratios were retrieved for analysis, conducted using random-effects model. Sensitivity analyses, subgroup analyses, and tests for publication bias were conducted. RESULTS: Among 1446 identified relevant studies, a total of 7 epidemiological studies enrolling 33226142 participants met the inclusion criteria. Overall, study participants with methadone use had a higher risk of motor vehicle collisions than did those without methadone use (pooled relative risk 1.92, 95% CI 1.25-2.95; number needed to harm 11.3, 95% CI 5.3-41.6); the I2 statistic was 95.1%, indicating substantial heterogeneity. Subgroup analyses revealed that database type explained 95.36% of the between-study variance (p = 0.008). Egger's (p = 0.376) and Begg's (p = 0.293) tests revealed no evidence of publication bias. Sensitivity analyses indicated that the pooled results were robust. CONCLUSION: The present review revealed that methadone use is significantly associated with a nearly doubled risk of motor vehicle collisions. Therefore, clinicians should exercise caution in implementing methadone maintenance therapy for drivers.

Risk of motorcycle collisions among patients with type 2 diabetes: a population-based cohort study with age and sex stratifications in Taiwan.

AIMS: To investigate the overall and sex-age-specific absolute and relative risks of motorcycle collisions at road traffic accidents among patients with type 2 diabetes. METHODS: A cohort study in Taiwan was conducted by following 989,495 patients with type 2 diabetes and the same number of matched controls recruited between 2010 and 2012 to the end of 2016. Collision events by motorcycle driver victims were identified from the Police-reported Traffic Accident Registry. Overall and sex-age-specific incidence rates of collision involving motorcycle driver victims were estimated under Poisson assumption. The Cox proportional hazard regression models were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of collision in association with type 2 diabetes. RESULTS: Over an up to 7 years of follow-up, patients with type 2 diabetes had a higher incidence rate of motorcycle collision than controls at 1.16 and 0.89 per 100 person-years, respectively, which represented a significantly elevated HR of 1.28 (95% CI 1.27-1.30) after adjusting for potential confounders including various diabetic complications. The elevated HR was similarly seen in both men and women patients, and was significantly decreasing with increasing age regardless of sex. Little evidence supported the dose-response relationship between duration of type 2 diabetes and motorcycle collision risk. CONCLUSIONS: After adjustment for common diabetic complications and comorbidities that could impair driving performance, patients with type 2 diabetes still suffered from increased risk of motorcycle collisions, regardless of sex, but was more evident in younger than in older patients.

Schizophrenia, but not depression or bipolar affective disorder, adds additional risk of aspiration pneumonia among stroke survivors: A national cohort study in Taiwan.

OBJECTIVE: Few studies have assessed the sex-specific and age-specific risk of aspiration pneumonia (AP) in patients with stroke and evaluated whether mental disorders may increase this risk. In this population-based cohort study, we investigated the sex-specific and age-specific risk of AP in association with stroke and the joint effects of stroke and mental disorders on the risk of AP. METHODS: We included 23,288 patients with incident stroke admitted between 2005 and 2017 and 68,675 matched nonstroke controls. Information on mental disorders was obtained from medical claims data within the 3 years before the stroke incidence. Cox proportional hazards models considering death as a competing risk event were constructed to estimate the hazard ratio of AP incidence by the end of 2018 associated with stroke and selected mental disorders. RESULTS: After ≤14 years of follow-up, AP incidence was higher in the patients with stroke than in the controls (11.30/1000 vs. 1.51/1000 person-years), representing a covariate-adjusted subdistribution hazard ratio (sHR) of 3.64, with no significant sex difference. The sHR significantly decreased with increasing age in both sexes. Stratified analyses indicated schizophrenia but not depression or bipolar affective disorder increased the risk of AP in the patients with stroke. CONCLUSION: Compared with their corresponding counterparts, the patients with schizophrenia only, stroke only, and both stroke and schizophrenia had a significantly higher sHR of 4.01, 5.16, and 8.01, respectively. The risk of AP was higher in younger stroke patients than those older than 60 years. Moreover, schizophrenia was found to increase the risk of AP in patients with stroke.

Pyroptosis-Related LncRNA Signature Predicts Prognosis and Is Associated With Immune Infiltration in Hepatocellular Carcinoma.

Pyroptosis is an inflammatory form of programmed cell death that is involved in various cancers, including hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) were recently verified as crucial mediators in the regulation of pyroptosis. However, the role of pyroptosis-related lncRNAs in HCC and their associations with prognosis have not been reported. In this study, we constructed a prognostic signature based on pyroptosis-related differentially expressed lncRNAs in HCC. A co-expression network of pyroptosis-related mRNAs-lncRNAs was constructed based on HCC data from The Cancer Genome Atlas. Cox regression analyses were performed to construct a pyroptosis-related lncRNA signature (PRlncSig) in a training cohort, which was subsequently validated in a testing cohort and a combination of the two cohorts. Kaplan-Meier analyses revealed that patients in the high-risk group had poorer survival times. Receiver operating characteristic curve and principal component analyses further verified the accuracy of the PRlncSig model. Besides, the external cohort validation confirmed the robustness of PRlncSig. Furthermore, a nomogram based on the PRlncSig score and clinical characteristics was established and shown to have robust prediction ability. In addition, gene set enrichment analysis revealed that the RNA degradation, the cell cycle, the WNT signaling pathway, and numerous immune processes were significantly enriched in the high-risk group compared to the low-risk group. Moreover, the immune cell subpopulations, the expression of immune checkpoint genes, and response to chemotherapy and immunotherapy differed significantly between the high- and low-risk groups. Finally, the expression levels of the five lncRNAs in the signature were validated by quantitative real-time PCR. In summary, our PRlncSig model shows significant predictive value with respect to prognosis of HCC patients and could provide clinical guidance for individualized immunotherapy.

Prediction of Number of Cases of 2019 Novel Coronavirus (COVID-19) Using Social Media Search Index.

Predicting the number of new suspected or confirmed cases of novel coronavirus disease 2019 (COVID-19) is crucial in the prevention and control of the COVID-19 outbreak. Social media search indexes (SMSI) for dry cough, fever, chest distress, coronavirus, and pneumonia were collected from 31 December 2019 to 9 February 2020. The new suspected cases of COVID-19 data were collected from 20 January 2020 to 9 February 2020. We used the lagged series of SMSI to predict new suspected COVID-19 case numbers during this period. To avoid overfitting, five methods, namely subset selection, forward selection, lasso regression, ridge regression, and elastic net, were used to estimate coefficients. We selected the optimal method to predict new suspected COVID-19 case numbers from 20 January 2020 to 9 February 2020. We further validated the optimal method for new confirmed cases of COVID-19 from 31 December 2019 to 17 February 2020. The new suspected COVID-19 case numbers correlated significantly with the lagged series of SMSI. SMSI could be detected 6-9 days earlier than new suspected cases of COVID-19. The optimal method was the subset selection method, which had the lowest estimation error and a moderate number of predictors. The subset selection method also significantly correlated with the new confirmed COVID-19 cases after validation. SMSI findings on lag day 10 were significantly correlated with new confirmed COVID-19 cases. SMSI could be a significant predictor of the number of COVID-19 infections. SMSI could be an effective early predictor, which would enable governments' health departments to locate potential and high-risk outbreak areas.

Honokiol antagonizes doxorubicin­induced cardiomyocyte senescence by inhibiting TXNIP­mediated NLRP3 inflammasome activation.

Senescence of cardiomyocytes is considered a key factor for the occurrence of doxorubicin (Dox)­associated cardiomyopathy. The NOD­like receptor family pyrin domain­containing 3 (NLRP3) inflammasome is reported to be involved in the process of cellular senescence. Furthermore, thioredoxin­interactive protein (TXNIP) is required for NLRP3 inflammasome activation and is considered to be a key component in the regulation of the pathogenesis of senescence. Studies have demonstrated that pretreatment with honokiol (Hnk) can alleviate Dox­induced cardiotoxicity. However, the impact of Hnk on cardiomyocyte senescence elicited by Dox and the underlying mechanisms remain unclear. The present study demonstrated that Hnk was able to prevent Dox­induced senescence of H9c2 cardiomyocytes, indicated by decreased senescence­associated ß­galactosidase (SA­ß­gal) staining, as well as decreased expression of p16INK4A and p21. Hnk also inhibited TXNIP expression and NLRP3 inflammasome activation in Dox­stimulated H9c2 cardiomyocytes. When TXNIP expression was enforced by adenovirus­mediated gene overexpression, the NLRP3 inflammasome was activated, which led to inhibition of the anti­inflammation and anti­senescence effects of Hnk on H9c2 cardiomyocytes under Dox treatment. Furthermore, adenovirus­mediated TXNIP­silencing inhibited the NLRP3 inflammasome. Consistently, TXNIP knockdown enhanced the anti­inflammation and anti­senescence effects of Hnk on H9c2 cardiomyocytes under Dox stimulation. In summary, Hnk was found to be effective in protecting cardiomyocytes against Dox­stimulated senescence. This protective effect was mediated via the inhibition of TXNIP expression and the subsequent suppression of the NLRP3 inflammasome. These results demonstrated that Hnk may be of value as a cardioprotective drug by inhibiting cardiomyocyte senescence.

Nrf2 protects against diabetic dysfunction of endothelial progenitor cells via regulating cell senescence.

Diabetes is associated with an increased risk of cardiovascular disease. A decrease in the number and functionality of endothelial progenitor cells (EPCs) leads to reduced endothelial repair and the development of cardiovascular disease. The aim of the present study was to explore the effect and underlying mechanisms of nuclear factor erythroid 2­related factor 2 (Nrf2) on EPC dysfunction caused by diabetic mellitus. The biological functions of EPCs in streptozotocin­induced diabetic mice were evaluated, including migration, proliferation, angiogenesis and the secretion of vascular endothelial growth factor (VEGF), stromal­derived growth factor (SDF) and nitric oxide (NO). Oxidative stress levels in diabetic EPCs were also assessed by detecting intracellular reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA). EPC senescence was evaluated by measuring p16 and b­gal expression and observing the senescence­associated secretory phenotype. In addition, the function of EPCs and level of oxidative stress were assessed following Nrf2 silencing or activation. Nrf2 silencing resulted in a decrease of EPC biological functions, accelerated cell senescence and increased oxidative stress, as indicated by ROS and MDA upregulation accompanied with decreased SOD activity. Furthermore, Nrf2 silencing inhibited migration, proliferation and secretion in EPCs, while it increased oxidative stress and cell senescence. Nrf2 activation protected diabetic EPCs against the effects of oxidative stress and cell senescence, ameliorating the biological dysfunction of EPCs derived from mice with diabetes. In conclusion, Nrf2 overexpression protected against oxidative stress­induced functional damage in EPCs derived from diabetic mice by regulating cell senescence.

Serum nerve grow factor and brain-derived neurotrophic factor profiles in Sjögren's syndrome concomitant with interstitial lung disease.

The aim of this study is to investigate the serum levels and clinical significance of nerve grow factor (NGF) and brain-derived neurotrophic factor (BDNF) in Sjogren's syndrome (SS) with interstitial lung disease (ILD). Fifty two untreated patients with SS were enrolled in the study. Of them, 25 patients only displayed salivary glands damage and/or lacrimal gland injury (simple SS group). The other 27 patients were lacrimal and/or salivary gland involvement as well as being concomitant only with intestinal lung disease (ILD group). Twenty-five serum samples from healthy volunteers were examined as controls. We measure serum NGF and BDNF levels by ELISA and correlate them with clinical data. Serum NGF levels were significantly higher in ILD patients (372 ± 129 pg/ml) and simple SS patients (293 ± 72 pg/ml) when compared with healthy controls (187 ± 47 pg/ml) (both p < 0.01). Significant difference were also found between the two patient groups (p < 0.01). In contrast, BDNF were significantly decreased in ILD patients (1,005 ± 143 pg/ml) when compared with either simple SS patients (1,204 ± 176 pg/ml, p < 0.01) or healthy controls (1,217 ± 155 pg/ml, p < 0.01). Correlation analysis showed NGF levels in ILD patient were positively correlated with serum levels of C-reactive protein and IgG (both p < 0.05). The abnormal NGF and BDNF in sera may be a potential character of ILD secondary to pSS.