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Traction-force microscopy (TFM) has emerged as a widely used standard methodology to measure cell-generated traction forces and determine their role in regulating cell behavior. While TFM platforms have enabled many discoveries, their implementation remains limited due to complex experimental procedures, specialized substrates, and the ill-posed inverse problem whereby low-magnitude high-frequency noise in the displacement field severely contaminates the resulting traction measurements. Here, we introduce deep morphology traction microscopy (DeepMorphoTM), a deep-learning alternative to conventional TFM approaches. DeepMorphoTM first infers cell-induced substrate displacement solely from a sequence of cell shapes and subsequently computes cellular traction forces, thus avoiding the requirement of a specialized fiduciarily marked deformable substrate or force-free reference image. Rather, this technique drastically simplifies the overall experimental methodology, imaging, and analysis needed to conduct cell-contractility measurements. We demonstrate that DeepMorphoTM quantitatively matches conventional TFM results while offering stability against the biological variability in cell contractility for a given cell shape. Without high-frequency noise in the inferred displacement, DeepMorphoTM also resolves the ill-posedness of traction computation, increasing the consistency and accuracy of traction analysis. We demonstrate the accurate extrapolation across several cell types and substrate materials, suggesting robustness of the methodology. Accordingly, we present DeepMorphoTM as a capable yet simpler alternative to conventional TFM for characterizing cellular contractility in two dimensions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Glaucoma is a leading cause of permanent blindness, affecting 80 million people worldwide. Recent studies have emphasized the importance of neuroinflammation in the early stages of glaucoma, involving immune and glial cells. To investigate this further, we used the GSE27276 dataset from the GEO (Gene Expression Omnibus) database and neuroinflammation genes from the GeneCards database to identify differentially expressed neuroinflammation-related genes associated with primary open-angle glaucoma (POAG). Subsequently, these genes were submitted to Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes for pathway enrichment analyses. Hub genes were picked out through protein-protein interaction networks and further validated using the external datasets (GSE13534 and GSE9944) and real-time PCR analysis. The gene-miRNA regulatory network, receiver operating characteristic (ROC) curve, genome-wide association study (GWAS), and regional expression analysis were performed to further validate the involvement of hub genes in glaucoma. A total of 179 differentially expressed genes were identified, comprising 60 upregulated and 119 downregulated genes. Among them, 18 differentially expressed neuroinflammation-related genes were found to overlap between the differentially expressed genes and neuroinflammation-related genes, with six genes (SERPINA3, LCN2, MMP3, S100A9, IL1RN, and HP) identified as potential hub genes. These genes were related to the IL-17 signaling pathway and tyrosine metabolism. The gene-miRNA regulatory network showed that these hub genes were regulated by 118 miRNAs. Notably, GWAS data analysis successfully identified significant single nucleotide polymorphisms (SNPs) corresponding to these six hub genes. ROC curve analysis indicated that our genes showed significant accuracy in POAG. The expression of these genes was further confirmed in microglia, Müller cells, astrocytes, and retinal ganglion cells in the Spectacle database. Moreover, three hub genes, SERPINA3, IL1R1, and LCN2, were validated as potential diagnostic biomarkers for high-risk glaucoma patients, showing increased expression in the OGD/R-induced glaucoma model. This study suggests that the identified hub genes may influence the development of POAG by regulation of neuroinflammation, and it may offer novel insights into the management of POAG.

Cardiodynamicsgram (CDG) has emerged recently as a noninvasive spatiotemporal electrocardiographic method for subtle cardiac dynamics information analysis within electrocardiogram (ECG). This study explored the feasibility of CDG for detecting radiation-induced heart damage (RIHD) in a rat model. A single radiation dose of 40 Gy was delivered to the cardiac apex of female Wistar rats. First, CDG was generated through dynamic modeling of ECG signals using the deterministic learning algorithm. Furthermore, CDG indexes were calculated using the wavelet transform and entropy. In this model, CDG entropy indexes decreased significantly after radiotherapy. The shape of CDG changed significantly after radiotherapy (irregular shape) compared with controls (regular shape). Macrophage and fibrosis in myocardium of rats increased significantly after radiotherapy. CDG changes after radiotherapy were significantly correlated with histopathological changes and occurred significantly earlier than histopathological changes. This study provides an experimental basis for the clinical application of CDG for the early detection of RIHD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hepatic ischemia-reperfusion injury (HIRI) was widely accepted as a critical complication of liver resection and transplantation. A growing body of evidence suggested that O-sialoglycoprotein endopeptidase (OSGEP) was involved in cell proliferation and mitochondrial metabolism. However, whether OSGEP could mediate the pathogenesis of HIRI has still remained unclarified. This study investigated whether OSGEP could be protective against HIRI and elucidated the potential mechanisms. The OSGEP expression level was detected in cases undergoing ischemia-related hepatectomy and a stable oxygen-glucose deprivation/reoxygenation (OGD/R) condition in hepG2 cells. Additionally, it was attempted to establish a mouse model of HIRI, thus, the function and mechanism of OSGEP could be analyzed. At one day after hepatectomy, the negative association of OSGEP expression level with the elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was noted. Moreover, it was attempted to carry out gain- and loss-of-function analyses of OSGEP in hepG2 cells to reveal its influences on OGD/R-induced injury and relevant signaling pathways. The findings suggested that OSGEP overexpression significantly protected hepG2 cells against ferroptotic cell death, while OSGEP consumption had opposite effects. Consistent with in vitro studies, OSGEP deficiency exacerbated liver functions and ferroptotic cell death in a mouse model of HIRI. The results also revealed that OSGEP mediated the progression of HIRI by regulating the MEK/ERK signaling pathway. Rescue experiments indicated that ERK1/2 knockdown or overexpression reversed the effects of OSGEP overexpression or knockdown on hepG2 cells under OGD/R condition. Taken together, the findings demonstrated that OSGEP could contribute to alleviate HIRI by mediating the MEK-ERK signaling pathway, which may serve as a potential prognostic marker and a therapeutic target for HIRI., (© 2024. The Author(s).)

Objective: Uptake of the imaging tracers [ 18 F]AlF-NOTA-FAPI-04 and [ 18 F]FDG varies in some inflammatory lesions, which may result in false-positive findings for malignancy on PET/CT. Our aim was to compare the [ 18 F]AlF-NOTA-FAPI-04 and [ 18 F]FDG PET/CT imaging features of malignant and various inflammatory lung lesions and to analyze their value for differential diagnosis., Methods: We retrospectively analyzed [ 18 F]AlF-NOTA-FAPI-04 PET/CT scans from 67 cancer patients taken between December 2020 and January 2022, as well as the scans of 32 patients who also underwent [ 18 F]FDG PET/CT imaging. The maximum and mean standardized uptake values (SUVmax and SUVmean, respectively) and lesion-to-background ratio (LBR) were calculated. The predictive capabilities of semiquantitative PET/CT parameters were analyzed by receiver operating characteristic curve analysis., Results: A total of 70 inflammatory and 37 malignant lung lesions were evaluated by [ 18 F]AlF‑NOTA‑FAPI‑04 PET/CT, and 33 inflammatory and 26 malignant lung lesions also were evaluated by [ 18 F]FDG PET/CT. Inflammatory lesions exhibited lower [ 18 F]AlF-NOTA-FAPI-04 and [ 18 F]FDG uptake compared to malignant lesions, with statistically significant differences in SUVmax, SUVmean, and LBR (all p < 0.001). [ 18 F]AlF-NOTA-FAPI-04 uptake also varied among different types of inflammatory lesions (SUVmax, p = 0.005; SUVmean, p = 0.008; LBR, p < 0.001), with the highest uptake observed in bronchiectasis with infection, followed by postobstructive pneumonia, and the lowest in pneumonia. [ 18 F]FDG uptake was higher in postobstructive pneumonia than in pneumonia (SUVmax, p = 0.009; SUVmean, p = 0.016; LBR, p = 0.004)., Conclusion: [ 18 F]AlF-NOTA-FAPI-04/[ 18 F]FDG PET/CT showed significantly lower uptake in inflammatory lesions than malignancies as well as variation in different types of inflammatory lesions, and thus, may be valuable for distinguishing malignant and various inflammatory findings., Clinical Relevance Statement: Our study confirmed that the uptake of [ 18 F]AlF-NOTA-FAPI-04/[ 18 F]FDG PET/CT in inflammatory and malignant lung lesions is different, which is beneficial to distinguish inflammatory and malignant lung lesions in clinic., Key Points: • Malignant and different inflammatory lung lesions showed varying degrees of uptake of [ 18 F]AlF-NOTA-FAPI-04 and [ 18 F]FDG. • Inflammatory lung lesions showed significantly less uptake than malignancies, and uptake varied among different types of inflammatory lesions. • Both types of PET/CT could differentiate malignant and various inflammatory lung findings., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Saffron ( Crocus sativus L.) is a valuable Chinese herb with high medicinal value. Saffron pistils are used as medicine, so increasing the number of flowers can increase the yield. Plant hormones have essential roles in the growth and development of saffron, as well as the response to biotic and abiotic stresses (especially in floral initiation), which may directly affect the number of flowers. Quantitative analysis of plant hormones provides a basis for more efficient research on their synthesis, transportation, metabolism, and action. However, starch (which interferes with extraction) is present in high levels, and hormone levels are extremely low, in saffron corms, thereby hampering accurate determination of plant-hormone levels in saffron. Herein, we screened an efficient and convenient pre-treatment method for plant materials containing abundant amounts of starch. Also, we proposed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the quantification of abscisic acid (ABA) and auxin (IAA). Then, the method was applied for the detection of hormone-content differences between flowering and non-flowering top buds, as well as between lateral and top buds. Our method showed high sensitivity, reproducibility, and reliability. Specifically, good linearity in the range 2-100 ng ml -1 was achieved in the determination of ABA and IAA, and the correlation coefficient ( R 2 ) was >0.9982. The relative standard deviation was 2.956-14.51% (intraday) and 9.57-18.99% (interday), and the recovery range was 89.04-101.1% ( n = 9). The matrix effect was 80.38-90.50% ( n = 3). The method was thoroughly assessed employing various "green" chemistry evaluation tools: Blue Applicability Grade Index (BAGI), Complementary Green Analytical Procedure Index (Complex GAPI) and Red Green Blue 12 Algorithm (RGB12). These tools revealed the good greenness, analytical performance, applicability, and overall sustainability alignment of our method. Quantitative results showed that, compared with saffron with a flowering phenotype cultivated at 25 °C, the contents of IAA and ABA in the terminal buds of saffron cultivated at 16 °C decreased significantly. When cultivated at 25 °C, the IAA and ABA contents in the terminal buds of saffron were 1.54- and 4.84-times higher than those in the lateral buds, respectively. A simple, rapid, and accurate UPLC-MS/MS method was established to determine IAA and ABA contents. Using this method, a connection between the contents of IAA and ABA and the flowering phenotype was observed in the quantification results. Our data lay a foundation for studying the flowering mechanism of saffron.

Objective: A resting-state functional magnetic resonance imaging (rs-fMRI) approach was used to explore functional connectivity (FC) in language and non-language brain networks in acute post-stroke aphasia (PSA) patients, with a specific focus on the relationship between these fMRI results and patient clinical presentation., Methods: In total, 20 acute PSA patients and 30 age-, sex-, and education level-matched healthy control (HC) participants were recruited and subjected to rs-fMRI imaging. In addition, western aphasia battery analyses（WAB） were used to compute aphasia quotient (AQ) values for PSA patients. Granger causality was employed to examine connections among cognition-associated resting-state brain networks, and the right middle frontal gyrus (RMFG),the mirror brain regions of Broca's area and the Wernicke's area, the right superior temporal gyrus were selected as regions of interest (ROIs). The REST plus software was then used to perform FC analyses of these regions to analyze changes in FC related to PSA pathogenesis., Results: Relative to HC individuals, PSA patients exhibited significantly higher levels of intra-network FC between the right middle frontal gyrus (RMFG) and the left middle occipital gyrus (LMOG), with such FC being positively correlated with the AQ scores (P = 0.018). Moreover, reduced FC was detected between the Broca's area homolog and the left middle frontal gyrus (LMFG), while FC was enhanced between the Wernicke's area homolog and cerebellar vermis, and this FC was similarly positively correlated with patient AQ scores (P = 0.0297)., Conclusion: These results suggest that FC between the bilateral hemispheres of the brain is significantly disrupted in acute PSA patients, interfering with the normal non-specific language network. Aphasia severity was further found to correlate with FC among many of the analyzed regions of the brain., Competing Interests: Declaration of Competing Interest There are no competing interests for all the other authors of this manuscript., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The prevention and treatment of fear-related disorders in offspring affected by pregnancy stress remains challenging at clinic. Here, we examined the effects of gut microbiota of stressed pregnant rats on the fear extinction of their offsprings, and the potential mechanisms. We found that gut microbiota transplantation from rats with pregnancy stress to normal pregnant rats impaired fear extinction, induced microglial activation and synaptic phagocytosis, increased synapse loss in offsprings. Probiotics supplement during pregnancy stress partly normalized pregnancy stress-induced gut microbiota dysbiosis of pregnant rats, and promoted fear memory extinction, inhibited fear memory reappearance, and limited microglial activation and synaptic phagocytosis in offsprings. These data revealed that gut microbiota of stressed pregnant mother improved the development of fear-related disorders of offspring, which may be associated with microglial synaptic pruning., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Glaucoma is similar to a neurodegenerative disorder and leads to global irreversible loss of vision. Despite extensive research, the pathophysiological mechanisms of glaucoma remain unclear, and no complete cure has yet been identified for glaucoma. Recent studies have shown that microRNAs can serve as diagnostic biomarkers or therapeutic targets for glaucoma; however, there are few bibliometric studies that focus on using microRNAs in glaucoma research. Here, we have adopted a bibliometric analysis in the field of microRNAs in glaucoma research to manifest the current tendencies and research hotspots and to present a visual map of the past and emerging tendencies in this field. In this study, we retrieved publications in the Web of Science database that centered on this field between 2007 and 2022. Next, we used VOSviewer, CiteSpace, Scimago Graphica, and Microsoft Excel to present visual representations of a co-occurrence analysis, co-citation analysis, tendencies, hotspots, and the contributions of authors, institutions, journals, and countries/regions. The United States was the main contributor. Investigative Ophthalmology and Visual Science has published the most articles in this field. Over the past 15 years, there has been exponential growth in the number of publications and citations in this field across various countries, organizations, and authors. Thus, this study illustrates the current trends, hotspots, and emerging frontiers and provides new insight and guidance for searching for new diagnostic biomarkers and clinical trials for glaucoma in the future. Furthermore, international collaborations can also be used to broaden and deepen the field of microRNAs in glaucoma research.

Cardiotoxicity is a well-recognized, serious adverse effect of thoracic radiation therapy. This study aimed to evaluate longitudinal electrocardiogram (ECG) changes in patients receiving thoracic radiation therapy and identify correlating factors that can predict the risk of cardiotoxicity. This retrospective study included 202 patients treated with thoracic radiation therapy, and chemotherapy and targeted therapy were allowed. Mean heart dose (MHD) was evaluated on dose-volume histograms. ECG, high-sensitivity cardiac troponin T (hs-cTnT), and N-terminal B-type natriuretic peptide (NT-proBNP) analyses were conducted before irradiation and during the follow-up period of 6-12 months (average 8 months). Chi square test and logistic regression analysis were applied to identify risk factors associated with ECG changes. At a median time of 3 months postirradiation, 46.5% of patients showed ECG changes, and 33.0% of patients achieved baseline ECG levels during the follow-up period at a median of 5 months postirradiation. Logistic regression analysis identified MHD, hs-cTnT and NT-pro BNP as significant factors associated with ECG changes (P < 0.05). Hs-cTnT and NT-proBNP were increased significantly after radiation therapy compared with baseline levels (P < 0.05), and these increases were observed as a median time of 2 months postirradiation, which was earlier than ECG changes. Higher MHD and elevated hs-cTnT and NT-proBNP levels correlated with an increased risk of ECG changes in patients receiving thoracic radiation therapy. Early identification of patients at high risk of cardiotoxicity and timely intervention might reduce the incidence of radiation-induced cardiac toxicity., (©2023 by Radiation Research Society. All rights of reproduction in any form reserved.)

There is no sensitive and effective method to predict radiation-induced myocardial damage (RIMD). The aim of this study was to explore effective plasma biomarkers for early prediction of RIMD after radiotherapy (RT) in lung cancer patients and in a rat model. Biomarker levels were measured in plasma samples collected before and after thoracic RT from 17 lung cancer patients. For the animal model, a single radiation dose of 40 Gy was delivered to the cardiac apex of female Wistar rats. Control rats received sham irradiation (0 Gy). Dynamic plasma biomarker detection and histopathological analysis to confirm RIMD were performed in rats up to 6 months after RT. In lung cancer patients, the plasma caspase-3 concentration was significantly increased after thoracic RT ( P  = 0.0479), with increasing but nonsignificant trends observed for caspase-1, CCL2, vascular endothelial growth factor (VEGF), interleukin-1β, and IL-6 ( P  > 0.05). Changes in caspase-3, VEGF, and IL-6 correlated significantly with mean heart dose ( P  < 0.05). In the RIMD rat model, caspase-1, caspase-3, CCl-2, VEGF, CCl-5, and TGF-β1 levels were significantly elevated in the first week post-RT ( P  < 0.05), which was earlier than pathological changes. Myocardial tissue of the RIMD rats also showed significant macrophage infiltration at 1 month ( P  < 0.01) and fibrosis at 6 months postradiation ( P  < 0.0001). Macrophage infiltration correlated significantly with plasma caspase-3, CCL2, CCL5, VEGF, and TGF-β1 levels from 3 weeks to 2 months post-RT. Increased plasma caspase-1, caspase-3, CCl-2, and VEGF levels were detected before RIMD-related pathological changes, indicating their clinical potential as biomarkers for early prediction of RIMD.

Background: Glaucoma, a neurodegenerative disease of the retina, is the leading cause of irreversible blindness. Stem cells have therapeutic potential for glaucoma. However, few bibliometric studies have been published in this field. Concerning a visual map, this article aims to characterize the research context, cooperation relationship, hotspots, and trends concerning the application of stem cells in glaucoma research. Methods: Publications focusing on stem cell research and glaucoma were retrieved from the Web of Science Core Collection. VOSviewer, CiteSpace, Microsoft Excel, and Scimago Graphica were used to map the contributions of countries or regions, authors, organizations, and journals. Journal Impact Factor data were obtained from the Web of Science Core Collection. We analyzed the tendencies, hotspots, and knowledge networks using VOSviewer, and CiteSpace. Results: We analyzed 518 articles published from 1999 through 2022. In the first decade, the number of articles in this field increased slowly, and there was a marked acceleration in publication frequency after 2010. The United States, China, and England were the main contributors. Yiqin Du was the most prolific author, and among the top 10 prolific writers, Keith R. Martin's work was cited most frequently. Investigative Ophthalmology and Visual Science , Experimental Eye Research , and Cornea published the most articles in this domain. The three most commonly co-cited journals were Investigative Ophthalmology and Visual Science , Experimental Eye Research , and Proceedings of the National Academy of Sciences of the United States of America . The Central South University, the University of Pittsburgh, and the National Institutes of Health National Eye Institute were highly prolific institutions in this research area. Our keywords analysis with VOSviewer suggested directions of future research and yielded the following recent key themes, extracellular vesicles, exosomes, mitochondria, growth factors, oxidative stress, and ocular diseases. Four co-cited references had a citation burst duration until 2022. Conclusion: With improvements in overall quality of life and demographic transitions toward population aging, research and clinical focus on eye care has increased, with glaucoma as a key area of emphasis. This study added to our understanding of the global landscape and Frontier hotspots in this field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tao, Zhang, Meng and Huang.)

Several studies have found that lactate correlates with surgical outcomes in patients with heart disease. However, the prognostic value of postoperative lactate in patients with acute type A aortic dissection (AAAD) remains unclear. This study aimed to investigate the relationship between postoperative lactate and in-hospital mortality in patients with AAAD. Patients who underwent AAAD surgery at Fujian Cardiac Medical Center from February 2020 to January 2022 were enrolled in this retrospective study. Correlations between in-hospital mortality and various parameters, including lactate, were investigated. A total of 357 patients were included in this study, 58 of which died. Multivariate logistic regression analysis revealed that body mass index (BMI) (odds ratio [OR] = 1.099, 95% confidence interval [CI]: 1.017-1.188, P = 0.017), cardiopulmonary bypass (CPB) time (OR = 1.005; 95% CI: 1.000-1.010, P = 0.039), and lactate (OR = 1.291, 95% CI: 1.182-1.409, P < 0.001) were independent risk factors for in-hospital mortality in AAAD patients. Receiver operating characteristic (ROC) curve analysis showed that lactate had a moderate power for in-hospital mortality (area under the curve [AUC] = 0.729, 95% CI: 0.647-0.810, P < 0.001). Furthermore, the combination of lactate, BMI, and CPB time showed better performance (AUC = 0.780; 95% CI: 0.706-0.854, P < 0.001) in predicting in-hospital mortality than in using these variables independently. Among patients undergoing AAAD surgery, postoperative lactate was significantly associated with in-hospital mortality. Lactate can be used as a potential predictor of in-hospital mortality. The combination of lactate, BMI, and CPB time showed better performance in predicting in-hospital mortality than using single one.

Purpose: Retrospective analysis revealed increased [ 18 F]AlF-NOTA-FAPI-04 uptake in the myocardium of patients with esophageal squamous cell cancer (ESCC) treated with concurrent chemoradiotherapy (CCRT). This study investigated and verified the feasibility of [ 18 F]AlF-NOTA-FAPI-04 PET/CT for detecting radiation-induced myocardial damage (RIMD)., Methods: Myocardial FAPI uptake was analyzed before and during radiotherapy in thirteen ESCC patients treated with CCRT. In the animal study, a single dose of 50 Gy was delivered to the cardiac apex of Wistar rats (24 rats, including 16 RIMD model rats and 8 control model rats). RIMD model rats were scanned with [ 18 F]AlF-NOTA-FAPI-04 PET/CT weekly for 12 weeks, and left ventricular ejection fraction (LVEF) was measured by magnetic resonance imaging. Dynamic, blocking, and [ 18 F]FDG PET/CT studies (4 rats/group) were performed on RIMD rats at 5 weeks post-radiation, and histopathological analyses were conducted., Results: Increased FAPI uptake in the myocardium was found after CCRT (1.53 ± 0.53 vs 1.88 ± 0.70, P = 0.015). In RIMD rats, significantly increased FAPI uptake in the damaged myocardium was observed from the 2nd week post-radiation exposure and peaked in the 5th week. Significantly more intense tracer accumulation was observed in the damaged myocardium than in the remote myocardium, as identified by decreased [ 18 F]FDG uptake and confirmed by autoradiography, hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining. The LVEF remained unchanged at the 3rd week post-radiation exposure but was remarkably decreased compared with that in the control group at the 8th week., Conclusion: Through clinical phenomena and animal experimental studies, this study indicated that [ 18 F]AlF-NOTA-FAPI-04 PET/CT imaging can detect RIMD noninvasively and before a decrease in LVEF, indicating the clinical potential of [ 18 F]AlF-NOTA-FAPI-04 as a PET/CT tracer for early monitoring of RIMD., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Given the increasing prevalence of autism spectrum disorder (ASD) and the public health problems it creates; early identification and interventions are needed to improve the prognosis of ASD. Hence, this study surveyed different groups of people who are likely to have early contact with autistic children to provide an informed basis for early detection and effective diagnosis and interventions., Methods: Three groups of people were recruited for the study from Changshou District and Wushan County of Chongqing, in Western China: 269 medical workers, 181 educators, and 188 community residents. Their understanding and knowledge of autism was measured using a self-made questionnaire., Results: The positive finding was that the three groups had a certain level of understanding of autism, but they had some misunderstandings of the core problems, and there were significant differences in the understanding of autism among the three groups. Younger medical workers knew more about autism than older ones did. The ability of educators and community residents to identify autistic symptoms was positively related to their level of education and their experience with autistic children. Television and the internet were the main sources of information about autism for participants., Conclusions: The medical workers, educators, and community residents in the investigated areas in western China may be able to identify early signs of autism but have an inadequate understanding of autism. In areas far from cities, it is necessary to strengthen the training of medical workers in primary health care to promote autism screening and referral in educational institutions and communities. Using internet technology to provide public education and professional training about autism in remote areas could be a very promising method in Western China., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wei, Li, Zhang, Luo, Wang, Dong, Tao, Gong, Feng, Shi, Cao, Liu, Chen, Liu, Dai, Qu, Song, Chen, Li and Cheng.)

Individuals who suffer from post-CA (cardiac arrest) brain injury experience higher mortality and more severe functional disability. Neuroinflammation has been identified as a vital factor in cerebral ischemia-reperfusion injury (CIRI) following CA. Pyroptosis induces neuronal death by triggering an excessive inflammatory injury. Chrysophanol possesses robust anti-inflammatory features, and it is protective against CIRI. The purpose of this research was to assess the effect of Chrysophanol postconditioning on CIRI-induced pyroptotic cell death, and to explore its underlying mechanisms. CIRI was induced in rats by CA and subsequent cardiopulmonary resuscitation, and PC12 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to imitate CIRI in vitro. It was found that post-CA brain injury led to a notable cerebral damage revealed by histopathological changes and neurological outcomes. The existence of pyroptosis was also confirmed in in vivo and in vitro CIRI models. Moreover, we further confirmed that Chrysophanol, the main bioactive ingredient of Rhubarb, significantly suppressed expressions of pyroptosis-associated proteins, e.g., NLRP3, ASC, cleaved-caspase-1 and N-terminal GSDMD, and inhibited the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6). Furthermore, NLRP3 overexpression neutralized the neuroprotection of Chrysophanol postconditioning, suggesting that pyroptosis was the major neuronal death pathway modulated by Chrysophanol postconditioning in OGD/R. Additionally, the neuroprotection of Chrysophanol postconditioning was also abolished by gain-of-function analyses of TRAF6. Finally, the results demonstrated that Chrysophanol postconditioning suppressed the interaction between TRAF6 and NLRP3. Taken together, our findings revealed that Chrysophanol postconditioning was protective against CIRI by inhibiting NLRP3-related pyroptosis in a TRAF6-dependent manner., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest with respect to the research, authorship, or publication of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: It has been reported that ubiquitin specific peptidase 4 (USP4) was functional in several tumors, but its function and mechanism in gastric cancer were still unknown., Methods: Bioinformatic tools were used to predict the prognosis of gastric cancer patients and the expression levels of USP4 in gastric cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunoblotting were carried out to detect the messenger RNA (mRNA) and protein levels. Cell viability of gastric cancer was evaluated by Cell Counting Kit-8 (CCK-8) assay. Cell line-derived xenograft models were established to evaluate the tumor growth of gastric cancer. Luciferase assay and immunoblotting were used to determine the activation of nuclear factor kappa B (NF-κB) signaling., Results: The public database Kaplan-Meier Plotter showed that gastric cancer patients with high USP4 expression had a shorter overall survival or post-progression survival than the patients with decreased USP4. Further studies indicated that USP4 was elevated in gastric cancer tumor tissues. In contrast, knockdown of USP4 markedly inhibited gastric cancer cell growth, and suppressed the tumor growth of gastric cancer. Further studies revealed that USP4 knockdown significantly suppressed NF-κB-driven luciferase activity, and inhibited the phosphorylation of NF-κB p65 in gastric cancer cells. Additionally, qRT-PCR analysis showed that USP4 knockdown significantly downregulated the expressions of cyclin D2 (CCND2) and B cell leukemia/lymphoma 2 (BCL2). We also found that USP4 knockdown decreased the expressions of phosphatase of regenerating liver-3 (PRL-3), in contrast, overexpression of PRL-3 attenuated the inhibitory effects of USP4 knockdown on NF-κB signaling and cell viability in gastric cancer cells. Finally, PR-619, which has been proven to inhibit the activities of USP4 and other deubiquitinases, could inhibit cell viability and NF-κB signaling in gastric cancer cells., Conclusions: This study indicated that elevated USP4 predicted a poor index for gastric cancer patients, and mediated gastric cancer cell growth by regulating PRL-3/NF-κB signaling, which suggested USP4 may be a novel therapeutic target for gastric cancer., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

The diabetic cognitive impairments are associated with high-glucose (HG)-induced mitochondrial dysfunctions in the brain. Our previous studies demonstrated that long non-coding RNA (lncRNA)-MEG3 alleviates diabetic cognitive impairments. However, the underlying mechanism has still remained elusive. Therefore, this study was designed to investigate whether the mitochondrial translocation of HSP90A and its phosphorylation are involved in lncRNA-MEG3-mediated neuroprotective effects of mitochondrial functions in HG-treated primary hippocampal neurons and diabetic rats. The primary hippocampal neurons were exposed to 75 mM glucose for 72 h to establish a HG model in vitro. Firstly, the RNA pull-down and RNA immunoprecipitation (RIP) assays clearly indicated that lncRNA-MEG3-associated mitochondrial proteins were Annexin A2, HSP90A, and Plectin. Although HG promoted the mitochondrial translocation of HSP90A and Annexin A2, lncRNA-MEG3 over-expression only enhanced the mitochondrial translocation of HSP90A, rather than Annexin A2, in the primary hippocampal neurons treated with or without HG. Meanwhile, Plectin mediated the mitochondrial localization of lncRNA-MEG3 and HSP90A. Furthermore, HSP90A threonine phosphorylation participated in regulating mitochondrial translocation of HSP90A, and lncRNA-MEG3 also enhanced mitochondrial translocation of HSP90A through suppressing HSP90A threonine phosphorylation. Finally, the anti-apoptotic role of mitochondrial translocation of HSP90A was found to be associated with inhibiting death receptor 5 (DR5) in HG-treated primary hippocampal neurons and diabetic rats. Taken together, lncRNA-MEG3 could improve mitochondrial functions in HG-exposed primary hippocampal neurons, and the underlying mechanisms were involved in enhanced mitochondrial translocation of HSP90A via suppressing HSP90A threonine phosphorylation, which may reveal a potential therapeutic target for diabetic cognitive impairments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

During metastasis, all cancer types must migrate through crowded multicellular environments. Simultaneously, cancers appear to change their biophysical properties. Indeed, cell softening and increased contractility are emerging as seemingly ubiquitous biomarkers of metastatic progression which may facilitate metastasis. Cell stiffness and contractility are also influenced by the microenvironment. Stiffer matrices resembling the tumor microenvironment cause metastatic cells to contract more strongly, further promoting contractile tumorigenic phenotypes. Prostate cancer (PCa), however, appears to deviate from these common cancer biophysics trends; aggressive metastatic PCa cells appear stiffer, rather than softer, to their lowly metastatic PCa counterparts. Although metastatic PCa cells have been reported to be more contractile than healthy cells, how cell contractility changes with increasing PCa metastatic potential has remained unknown. Here, we characterize the biophysical changes of PCa cells of various metastatic potential as a function of microenvironment stiffness. Using a panel of progressively increasing metastatic potential cell lines (22RV1, LNCaP, DU145, and PC3), we quantified their contractility using traction force microscopy (TFM), and measured their cortical stiffness using optical magnetic twisting cytometry (OMTC) and their motility using time-lapse microscopy. We found that PCa contractility, cell stiffness, and motility do not universally scale with metastatic potential. Rather, PCa cells of various metastatic efficiencies exhibit unique biophysical responses that are differentially influenced by substrate stiffness. Despite this biophysical diversity, this work concludes that mechanical microenvironment is a key determinant in the biophysical response of PCa with variable metastatic potentials. The mechanics-oriented focus and methodology of the study is unique and complementary to conventional biochemical and genetic strategies typically used to understand this disease, and thus may usher in new perspectives and approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Molter, Muszynski, Tao, Trivedi, Clouvel and Ehrlicher.)

Objective : In the context of the coronavirus disease 2019 (COVID-19) pandemic, telemedicine is a promising tool for providing clinical care for patients. Since the first-line treatment for infertile women with polycystic ovarian syndrome (PCOS) is lifestyle modification, a mobile-based service that provides lifestyle modification education would be helpful in the treatment of PCOS patients. In this observational study, the effect of a mobile Health (mHealth) application for lifestyle modification on PCOS patients undergoing assisted reproductive technology (ART) treatment was evaluated. Methods : A total of 79 overweight/obese patients (40 in the paper group and 39 in the WeChat application group) with PCOS from the First Affiliated Hospital of University of Science and Technology of China were enrolled in the study. The changes in the outcomes of BMI and ART treatment were analyzed between the two groups. Results : After three months of intervention, the BMIs in the control and mHealth groups were 24.5 ± 3.3 and 23.7 ± 3.1, respectively. The percentage of patients who lost weight was higher in the WeChat group than in the control group (87.2% vs. 67.5%). Furthermore, PCOS patients in the WeChat group were found to have a higher live birth rate than those in the control group ( p  = 0.005). Conclusion : Lifestyle modifications for PCOS patients undergoing ART treatment using the WeChat application improved weight loss and oocyte quality. Infertile patients with PCOS were more likely to make lifestyle modifications based on the usage of mobile applications during the COVID-19 pandemic.

Tissue and cell mechanics are crucial factors in maintaining homeostasis and in development, with aberrant mechanics contributing to many diseases. During the epithelial-to-mesenchymal transition (EMT), a highly conserved cellular program in organismal development and cancer metastasis, cells gain the ability to detach from their original location and autonomously migrate. While a great deal of biochemical and biophysical changes at the single-cell level have been revealed, how the physical properties of multicellular assemblies change during EMT, and how this may affect disease progression, is unknown. Here we introduce cell monolayer deformation microscopy (CMDM), a new methodology to measure the planar mechanical properties of cell monolayers by locally applying strain and measuring their resistance to deformation. We employ this new method to characterize epithelial multicellular mechanics at early and late stages of EMT, finding the epithelial monolayers to be relatively compliant, ductile, and mechanically homogeneous. By comparison, the transformed mesenchymal monolayers, while much stiffer, were also more brittle, mechanically heterogeneous, displayed more viscoelastic creep, and showed sharp yield points at significantly lower strains. Here, CMDM measurements identify specific biophysical functional states of EMT and offer insight into how cell aggregates fragment under mechanical stress. This mechanical fingerprinting of multicellular assemblies using new quantitative metrics may also offer new diagnostic applications in healthcare to characterize multicellular mechanical changes in disease., (Copyright © 2022 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

The precise simulation of urban space evolution and grasping of the leading factors are the most important basis for urban space planning. However, the simulation ability of current models is lacking when it comes to complicated/unpredictable urban space changes, resulting in flawed government decision-making and wasting of urban resources. In this study, a macro-micro joint decision model was proposed to improve the ability of urban space evolution simulation. The simulation objects were unified into production, living and ecological space to realize "multiple planning in one". For validation of the proposed model and method, remote sensing images, geographic information and socio-economic data of Xuzhou, China from 2000 to 2020 were collected and tested. The results showed that the simulation precision of the cellular automata (CA) model was about 87% (Kappa coefficient), which improved to 89% if using a CA and multi-agent system (MAS) joint model. The simulation precision could be better than 92% using the prosed model. The result of factor weight determination indicated that the micro factors affected the evolution of production and living space more than the macro factors, while the macro factors had more influence on the evolution of ecological space than the micro factors. Therefore, active policies should be formulated to strengthen the ideological guidance towards micro individuals (e.g., a resident, farmer, or entrepreneur), and avoid disordered development of living and production space. In addition, ecological space planning should closely link with the local environment and natural conditions, to improve urban ecological carrying capacity and realize urban sustainable development.

Recently, alkaline direct methanol fuel cells have made great progress with the development of alkaline electrocatalysis, and a wide variety of catalysts have been explored for methanol oxidation reaction (MOR)and oxygen reduction reaction (ORR). However, the slow kinetics of the MOR and ORR remain a great challenge. In this paper, self-supported defect-rich AuCu was obtained by a convenient one-pot strategy. Self-supported AuCu presented a branched, porous nanostructure. The nanobranch consisted of several 13 nm skeletons, which connected in the kink of the structure. Different growth directions co-existed at the kink, and the twin boundaries and dislocations as defects were observed. When the Au-based nanostructure functioned as an electrocatalyst, it showed robust MOR and ORR performance. For the MOR, the forward peak current was 2.68 times greater than that of Au/C; for the ORR, the activity was close to that of Pt/C and significantly better than that of Au/C. In addition, it possessed superior electrochemical stability for MOR and ORR. Finally, an in-depth exploration of the impact of surface defects and electrochemical Cu removal on MOR and ORR activity was carried out to explain the MOR and ORR's catalytic performance.

Background: The role of sexually transmitted infections (STIs) in semen parameters and male infertility is still a controversial area. Previous studies have found bacterial infection in a minority of infertile leukocytospermic males. This study aims to investigate the prevalence of STIs in semen from subfertile men with leukocytospermia (LCS) and without leukocytospermia (non-LCS) and their associations with sperm quality., Methods: Semen samples were collected from 195 men who asked for a fertility evaluation. Infection with the above 6 pathogens was assessed in each sample. Sperm quality was compared in subfertile men with and without LCS., Results: The LCS group had significantly decreased semen volume, sperm concentration, progressive motility, total motility and normal morphology. The infection rates of Ureaplasma urealyticum (Uuu), Ureaplasma parvum (Uup), Mycoplasma hominis (MH), Mycoplasma genitalium (MG), Chlamydia trachomatis (CT), herpes simplex virus-2 (HSV-2) and Neisseria gonorrhoeae (NG) were 8.7 %, 21.0 %, 8.2 %, 2.1 %, 3.6 %, 1.0 and 0 %, respectively. The STI detection rates of patients with LCS were higher than those of the non-LCS group (52.3 % vs. 39.3 %), although there was no statistically significant difference between the two groups (P = 0.07). All semen parameters were not significantly different between LCS with STIs and without STIs, except the semen volume in the MG-infected patients with LCS was significantly lower than that in the noninfected group., Conclusions: LCS was associated with a reduction in semen quality, but was not associated with STIs.

Background: Scabies is caused by burrowing of the mite Sarcoptes scabiei into the stratum corneum. Currently, diagnosis via routine skin scraping is very difficult, and information on the allergenic identification of S. scabiei remains limited., Methods: We performed comparative analysis of the serological diagnostic potential of recombinant S. scabiei chitinase-like protein-5 (rSsCLP5) and recombinant S. scabiei chitinase-like protein-12 (rSsCLP12) by measuring the levels of serum-specific IgG and IgE antibodies (Abs) as diagnostic markers. In addition, the allergenic characteristics of rSsCLP5 and rSsCLP12 were evaluated using IgE-binding experiments and skin tests., Results: The IgE Abs-based indirect enzyme-linked immunosorbent assay (ELISA) methods showed high sensitivity and specificity: the rSsCLP5-based assay had 93.5% sensitivity and 94.4% specificity; the rSsCLP12-based assay had 100% sensitivity and 98.1% specificity. The specific IgE Abs in infested mouse sera could bind rSsCLP5 and rSsCLP12. In skin tests, rabbits in the rSsCLP5 and rSsCLP12 groups and positive control (histamine) groups exhibited allergic reactions. Most test sites in the rSsCLP12 group had edema, bleeding spots, and even ulcers or scabs, but such allergy symptoms were rare in the rSsCLP5 group. Moreover, the allergic history rabbit group had more severe allergic reactions and lower levels of IgE Abs compared to the healthy rabbit group in the same protein group., Conclusions: These findings validate the use of IgE Abs to rSsCLP5 and rSsCLP12 as potentially useful markers for diagnosing scabies. Moreover, both rSsCLP5 and rSsCLP12 have allergenic properties, and the potential allergen rSsCLP12 is a stronger allergen than rSsCLP5.

Spinal cord injury (SCI) is a devastating medical condition with profound social and economic impacts. Although research is ongoing, current treatment options are limited and do little to restore functionality. However, recent studies suggest that mesenchymal stem cell-derived exosomes (MSC-exosomes) may hold the key to exciting new treatment options for SCI patients. MSCs are self-renewing multipotent stem cells with multi-directional differentiation and can secrete a large number of exosomes (vesicles secreted into the extracellular environment through endocytosis, called MSC-exosomes). These MSC-exosomes play a critical role in repairing SCI through promoting angiogenesis and axonal growth, regulating inflammation and the immune response, inhibiting apoptosis, and maintaining the integrity of the blood-spinal cord barrier. Furthermore, they can be utilized to transport genetic material or drugs to target cells, and their relatively small size makes them able to permeate the blood-brain barrier. In this review, we summarize recent advances in MSC-exosome themed SCI treatments and cell-free therapies to better understand this newly emerging methodology.

Eimeria stiedai is an apicomplexan protozoan parasite that invades the liver and bile duct epithelial cells in rabbits and causes severe hepatic coccidiosis, resulting in significant economic losses in the domestic rabbit industry. Hepatic coccidiosis lacks the typical clinical symptoms and there is a lack of effective premortem tools to timely diagnose this disease. Therefore, in the present study we cloned and expressed the two microneme proteins i.e., microneme protein 1 ( EsMIC1 ) and microneme protein 3 ( EsMIC3 ) from E. stiedai and used them as recombinant antigens to develop a serodiagnostic method for an effective diagnosis of hepatic coccidiosis. The cDNAs encoding EsMIC1 and EsMIC3 were cloned and the mRNA expression levels of these two genes at different developmental stages of E. stiedai were determined by quantitative real-time PCR analysis (qRT-PCR). The immunoreactivity of recombinant EsMIC1 (rEsMIC1) and EsMIC3 (rEsMIC3) proteins were detected by Western blotting, and indirect enzyme-linked immunosorbent assays (ELISAs) based on these two recombinant antigens were established to evaluate their serodiagnostic potential. Our results showed that the proteins encoded by the ORFs of EsMIC1 (711 bp) and EsMIC3 (891 bp) were approximately 25.89 and 32.39 kDa in predicted molecular weight, respectively. Both EsMIC1 and EsMIC3 showed the highest mRNA expression levels in the merozoites stage of E. stiedai . Western blotting analysis revealed that both recombinant proteins were recognized by E. stiedai positive sera, and the indirect ELISAs using rEsMIC1 and rEsMIC3 were developed based on their good immunoreactivity, with 100% (48/48) sensitivity and 97.9% (47/48) specificity for rEsMIC1 with 100% (48/48) sensitivity and 100% (48/48) specificity for rEsMIC3, respectively. Moreover, rEsMIC1- and rEsMIC3-based indirect ELISA were able to detect corresponding antibodies in sera at days 6, 8, and 10 post E. stiedai infection, with the highest positive diagnostic rate (62.5% (30/48) for rEsMIC1 and 66.7% (32/48) for rEsMIC3) observed at day 10 post infection. Therefore, both EsMIC1 and EsMIC3 can be used as potential serodiagnostic candidate antigens for hepatic coccidiosis caused by E. stiedai .

In clinical pharmacology, the free drug hypothesis has been widely applied in the interpretation of the relationship between pharmacokinetics and pharmacodynamics (PK/PD). The free drug hypothesis assumes that the unbound drug concentration in blood is the same as that in the site of action at steady state. The objective of this study is to demonstrate whether the free drug hypothesis is universally applicable for all drugs. The unbound concentrations of the 18 compounds in blood and in brain interstitial fluids (ISF) at steady state following constant intravenous infusion were simultaneously monitored up to 6 hours via in vivo microdialysis technique. Based on the permeability and efflux ratio (ER), the test compounds can be divided into two classes. Class I includes the compounds with good membrane permeability that are not substrates of efflux transporters (eg, P-gp, BCRP, and MRPs), whereas Class II includes the compounds that are substrates of efflux transporters. The steady-state unbound drug concentrations in blood, brain, and CSF are quantitatively very similar for Class I compounds, whereas the steady-state unbound concentrations in the brain and CSF are significantly lower than those in blood for Class II compounds. These results strongly suggest that the free drug hypothesis is not universal for all drugs but is only applicable for drugs with good permeability that are not substrates of efflux transporters., (© 2020 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Scabies is a highly contagious disease caused by Sarcoptes scabiei which burrows into stratum corneum of host's skin. In this study, after optimizing vaccination schedule, a vaccination trial is comprised of three test groups of rabbits ( n = 10/group) by immunization with (1) rSsCLP5; (2) rSsCLP12; or (3) a mixture of rSsCLP5 and rSsCLP12, three biological replicates groups ( n = 10/group) and three control groups ( n = 10/group). Levels of specific IgG, total IgE and cytokines in sera were detected and histopathologically analyzed as indicators of vaccine effects. The results showed that 85% (17/20) of rabbits exhibited no detectable skin lesions of S. scabiei infestation in mixed protein groups compared to single protein groups with 75% (15/20) and 70% (14/20), respectively. Moreover, the deworming rates of mixed groups are increased by 10%-20% compared with that of single groups. Each of six groups immunized with rSsCLP displayed significant increases of specific IgG, total IgE, IL-10, and TNF-α. The degree of skin damage in test groups also significantly lower than that of control groups. Thus, purified rSsCLP5 and rSsCLP12 subunit cocktail vaccine induced robust immune protection and could significantly decrease mite populations to reduce the direct transmission between rabbits.

Kaolin, a natural and inexpensive clay mineral, is ubiquitous in soil, dirt, and airborne particles. Amongst four commonly available clay minerals, kaolin, as a result of its layered structure, is the most efficient natural gaseous Hg adsorbent to date (Langmuir maximum adsorption capacity Q m =574.08 μg g -1 and Freundlich Q m =756.49 μg g -1 ). The Hg uptake proceeds by homogeneous monolayer and heterogeneous processes. Hg physisorption on kaolin occurs in the dark, yet the adsorption rate is enhanced upon irradiation. The effects of several metal complexes, salts, halides and solvents on the Hg uptake were examined. The addition of CuCl 2 particles leads to a significant enhancement of the Hg uptake capacity (>30 times) within second timescales and without irradiation. The physisorption with kaolin is switched to chemisorption upon the addition of CuCl 2 to kaolin. This process is entirely reversible upon the addition of Zn/Sn granules at room temperature without any added energy. However, the investment of a small amount of renewable energy can speed up the process. This technology demonstrates the facile and efficient capture and recycling of elemental Hg 0 from air. A wide range of metal particles and diverse physicochemical processes, which include the microphysics of nucleation, are herein examined to explore the potential reaction mechanism by using a suite of complementary analytical techniques. These new mechanistic insights open a new era of energy-neutral environmental remediation based on natural soil/airborne particles., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Synthesis and self-assembly of bioconjugates composed of proteins and synthetic molecules have been widely studied because of the potential applications in medicine, biotechnology, and nanotechnology. One of the challenging research studies in this area is to develop organic solvent-free approaches to the synthesis and self-assembly of amphiphilic bioconjugates. In this research, dialysis-assisted approach, a method based on unimer-aggregate equilibrium, was applied in the coassembly of lysozyme and conjugate of cholesterol and glutathione (Ch-GSH). In phosphate buffer solution, amphiphilic Ch-GSH conjugate self-assembles into vesicles, and the vesicle solution is dialyzed against lysozyme solution. Negatively charged Ch-GSH unimers produced in the unimer-vesicle exchange equilibrium, diffuse across the dialysis membrane and have electrostatic interaction with positively charged lysozyme, resulting in the formation of Ch-GSH-lysozyme bioconjugate. Above a critical concentration, the three-component bioconjugate molecules self-assemble into bioactive vesicles.

Harmful algal blooms have become a great challenge to global aquatic ecosystems over the past decades. Given their low toxicity, high selectivity, and environment-friendly properties, the use of natural products and their analogues as algicides has proven to be particularly efficient. In the present study, algicidal activity of naturally occurring bacillamides A-C, alkaloid ( 1 ), and neobacillamide A, as well as their synthetic analogues were investigated intensively. Bioassay results showed that, relative to natural bacillamide alkaloids, aniline-derived analogue ( 10d ) exhibited higher algicidal potential against three freshwater harmful algae Mycrocyctis aeruginosa, Scenedesmus obliquus, and Chlorella pyrenoidosa , suggesting that it could be used as a promising lead compound to develop novel algicide for controlling harmful algal blooms., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Purpose: To test whether employer matching of employees' monetary contributions increases employees' (1) participation in deposit contracts to promote weight loss and (2) weight loss., Design: A 36-week randomized trial., Setting: Large employer in the northeast United States., Participants: One hundred thirty-two obese employees., Interventions: Over 24 weeks, participants were asked to lose 24 pounds and randomized to monthly weigh-ins or daily weigh-ins with monthly opportunities to deposit $1 to $3 per day that was not matched, matched 1:1, or matched 2:1. Deposits and matched funds were returned to participants for each day they were below their goal weight., Measures: Rates of making ≥1 deposit, weight loss at 24 weeks (primary outcome), and 36 weeks., Analysis: Deposit rates were compared using χ(2) tests. Weight loss was compared using t tests., Results: Among participants eligible to make deposits, 29% made ≥1 deposit and matching did not increase participation. At 24 weeks, control participants gained an average of 1.0 pound, whereas 1:1 match participants lost an average of 5.3 pounds (P = .005). After 36 weeks, control participants gained an average of 2.1 pounds, whereas no match participants lost an average of 5.1 pounds (P = .008)., Conclusion: Participation in deposit contracts to promote weight loss was low, and matching deposits did not increase participation. For deposit contracts to impact population health, ongoing participation will need to be higher., (© The Author(s) 2016.)

Background: Financial incentives and peer networks could be delivered through eHealth technologies to encourage older adults to walk more., Methods: We conducted a 24-week randomized trial in which 92 older adults with a computer and Internet access received a pedometer, daily walking goals, and weekly feedback on goal achievement. Participants were randomized to weekly feedback only (Comparison), entry into a lottery with potential to earn up to $200 each week walking goals were met (Financial Incentive), linkage to four other participants through an online message board (Peer Network), or both interventions (Combined). Main outcomes were the proportion of days walking goals were met during the 16-week intervention and 8-week follow-up. We conducted a content analysis of messages posted by Peer Network and Combined arm participants., Results: During the 16-week intervention, there were no differences in the proportion of days walking goals were met in the Financial Incentive (39.7%; p = .78), Peer Network (24.9%; p = .08), and Combined (36.0%; p = .77) arms compared with the Comparison arm (36.0%). During 8 weeks of follow-up, the proportion of days walking goals were met was lower in the Peer Network arm (18.7%; p = .025) but not in the Financial Incentive (29.3%; p = .50) or Combined (24.8%; p = .37) arms, relative to the Comparison arm (34.5%). Messages posted by participants focused on barriers to walking and provision of social support., Conclusions: Financial incentives and peer networks delivered through eHealth technologies did not result in older adults walking more., (© 2014 Society for Public Health Education.)

Background: Patient safety and sleep experts advocate a protected sleep period for residents., Objective: We examined whether interns scheduled for a protected sleep period during overnight call would have better end-of-rotation assessments of burnout, depression, and empathy scores compared with interns without protected sleep periods and whether the amount of sleep obtained during on call predicted end-of-rotation assessments., Methods: We conducted a randomized, controlled trial with internal medicine interns at the Philadelphia Veterans Affairs Medical Center (PVAMC) and the Hospital of the University of Pennsylvania (HUP) in academic year 2009-2010. Four-week blocks were randomly assigned to either overnight call permitted under the 2003 duty hour standards or a protected sleep period from 12:30 am to 5:30 am. Participants wore wrist actigraphs. At the beginning and end of the rotations, they completed the Beck Depression Inventory (BDI-II), Maslach Burnout Inventory (MBI-HSS), and Interpersonal Reactivity Index (IRI)., Results: A total of 106 interns participated. There were no significant differences between groups in end-of-rotation BDI-II, MBI-HSS, or IRI scores at either location (P > .05). Amount of sleep while on call significantly predicted lower MBI-Emotional Exhaustion (P < .003), MBI-Depersonalization (P < .003), and IRI-Personal Distress (P < .006) at PVAMC, and higher IRI-Perspective Taking (P < .008) at HUP., Conclusions: A protected sleep period produced few consistent improvements in depression, burnout, or empathy, although depression was already low at baseline. Possibly the amount of protected time was too small to affect these emotional states or sleep may not be directly related to these scores.

Background: Home wireless device monitoring could play an important role in improving the health of patients with poorly controlled chronic diseases, but daily engagement rates among these patients may be low., Objective: To test the effectiveness of two different magnitudes of financial incentives for improving adherence to remote-monitoring regimens among patients with poorly controlled diabetes., Design: Randomized, controlled trial. (Clinicaltrials.gov Identifier: NCT01282957)., Participants: Seventy-five patients with a hemoglobin A1c greater than or equal to 7.5% recruited from a Primary Care Medical Home practice at the University of Pennsylvania Health System., Interventions: Twelve weeks of daily home-monitoring of blood glucose, blood pressure, and weight (control group; n = 28); a lottery incentive with expected daily value of $2.80 (n = 26) for daily monitoring; and a lottery incentive with expected daily value of $1.40 (n = 21) for daily monitoring., Main Measures: Daily use of three home-monitoring devices during the three-month intervention (primary outcome) and during the three-month follow-up period and change in A1c over the intervention period (secondary outcomes)., Key Results: Incentive arm participants used devices on a higher proportion of days relative to control (81% low incentive vs. 58%, P = 0.007; 77% high incentive vs. 58%, P = 0.02) during the three-month intervention period. There was no difference in adherence between the two incentive arms (P = 0.58). When incentives were removed, adherence in the high incentive arm declined while remaining relatively high in the low incentive arm. In month 6, the low incentive arm had an adherence rate of 62% compared to 35% in the high incentive arm (P = 0.015) and 27% in the control group (P = 0.002)., Conclusions: A daily lottery incentive worth $1.40 per day improved monitoring rates relative to control and had significantly better efficacy once incentives were removed than a higher incentive.

Background: Data on the effectiveness of employer-sponsored financial incentives for employee weight loss are limited., Objective: To test the effectiveness of 2 financial incentive designs for promoting weight loss among obese employees., Design: Randomized, controlled trial. (ClinicalTrials.gov: NCT01208350), Setting: Children's Hospital of Philadelphia., Participants: 105 employees with a body mass index between 30 and 40 kg/m2., Intervention: 24 weeks of monthly weigh-ins (control group; n = 35); individual incentive, designed as $100 per person per month for meeting or exceeding weight-loss goals (n = 35); and group incentive, designed as $500 per month split among participants within groups of 5 who met or exceeded weight-loss goals (n = 35)., Measurements: Weight loss after 24 weeks (primary outcome) and 36 weeks and changes in behavioral mediators of weight loss (secondary outcomes)., Results: Group-incentive participants lost more weight than control participants (mean between-group difference, 4.4 kg [95% CI, 2.0 to 6.7 kg]; P < 0.001) and individual-incentive participants (mean between-group difference, 3.2 kg [CI, 0.9 to 5.5 kg]; P = 0.008). Twelve weeks after incentives ended and after adjustment for 3-group comparisons, group-incentive participants maintained greater weight loss than control group participants (mean between-group difference, 2.9 kg [CI, 0.5 to 5.3 kg]; P = 0.016) but not greater than individual-incentive participants (mean between-group difference, 2.7 kg [CI, 0.4 to 5.0 kg]; P = 0.024)., Limitation: Single employer and short follow-up., Conclusion: A group-based financial incentive was more effective than an individual incentive and monthly weigh-ins at promoting weight loss among obese employees at 24 weeks., Primary Funding Source: National Institute on Aging.

Cranberry juice cocktail (CJC) has been shown to inhibit the formation of biofilm by uropathogenic Escherichia coli. In order to investigate whether the anti-adhesive components could reach the urinary tract after oral consumption of CJC, a volunteer was given 16 oz of either water or CJC. Urine samples were collected at 0, 2, 4, 6, and 8 hours after consumption of a single dose. The ability of compounds in the urine to influence bacterial adhesion was tested for six clinical uropathogenic E. coli strains, including four P-fimbriated strains (B37, CFT073, BF1023, and J96) and two strains not expressing P-fimbriae but exhibiting mannose-resistant hemagglutination (B73 and B78). A non-fimbriated strain, HB101, was used as a control. Atomic force microscopy (AFM) was used to measure the adhesion force between a silicon nitride probe and bacteria treated with urine samples. Within 2 hours after CJC consumption, bacteria of the clinical strains treated with the corresponding urine sample demonstrated lower adhesion forces than those treated with urine collected before CJC consumption. The adhesion forces continued decreasing with time after CJC consumption over the 8-hour measurement period. The adhesion forces of bacteria after exposure to urine collected following water consumption did not change. HB101 showed low adhesion forces following both water and CJC consumption, and these did not change over time. The AFM adhesion force measurements were consistent with the results of a hemagglutination assay, confirming that oral consumption of CJC could act against adhesion of uropathogenic E. coli.