Relationships Between Meteorological Factors and Mongolian Gerbils and Its Flea Burdens - Xilingol League, Inner Mongolia Autonomous Region, China, 2012-2021.

Introduction: Plague is a significant global infectious disease, its spread is linked to host and flea populations. Meteorological conditions can impact flea populations and host densities, hence influencing plague outbreaks. Investigating the connection between meteorological factors, flea populations, and rodent densities in Inner Mongolia's natural plague foci can aid in predicting and managing plague outbreaks. Methods: Monthly data on flea index, rodent density, meteorological factors, and normalized difference vegetation index (NDVI) were collected for the study area. Generalized additive modeling (GAM) was used to analyze the non-linear and lag effects of meteorological factors on flea index and rodent density. Structural equation modeling (SEM) was employed to investigate the relationships among meteorological factors, NDVI, flea index, and rodent density. Results: GAM analysis revealed that temperature, precipitation, relative humidity, and NDVI had significant linear, non-linear, and time-lagged impacts on the density of Mongolian gerbils and the flea index. SEM analysis indicated that meteorological factors could directly influence the density and flea index of Mongolian gerbils, or indirectly impact NDVI, subsequently influencing gerbil density and the flea index. Conclusions: Meteorological factors primarily influence gerbil density and flea index indirectly by affecting NDVI and the relationship between flea index and gerbil density. This study offers additional support for the significance of meteorological factors and NDVI in influencing the vector-rodent system, offering valuable insights for predicting and managing plague outbreaks.

Understanding consumers' continuous-use intention of crowdsourcing logistics services: Empirical evidence from China.

Crowdsourcing logistics-based O2O (online to offline) has been increasingly implemented to help individuals or merchants tackle down the problem of intra city instant delivery in China. However, since insufficient control is imposed on free couriers, consumers are subjected to certain risks generated by the uneven service quality provided by free couriers, such that the continuous-use intention to adopt crowdsourcing logistics may be affected in an unexpected manner. A sampling survey was carried out in China's first- and second-tier cities, with 292 valid questionnaires collected. On that basis, the corresponding hypotheses were tested using the partial least squares (PLS) method. The findings of this study revealed that trust, perceived value, and satisfaction positively contributed to continuous-use intention, where trust contributed the most. Perceived risk exerted a significant negative effect on continuous use intention. Trust is capable of notably reducing perceived risk. Crowdsourcing logistics service quality is the critical driving variable of perceived value and satisfaction. Perceived risk has a negative moderating effect on satisfaction-continuous-use intention relationship, showing that the higher the perceived risk, the weaker the effect of satisfaction on continuous-use intention. Given perceived risk, a conceptual model was built by integrating e-CSI model (e-Customer Satisfaction Index Model) and PAM-ISC model (Post-acceptance Model of IS Continuance Model). From the integration, the findings of this study are expected to provide decision-making basis for crowdsourcing logistics platforms to help solve the "last mile" delivery problem.

SPOP negatively regulates mTORC1 activity by ubiquitinating Sec13.

The mammalian target of rapamycin complex1 (mTORC1) can response to amino acid to regulate metabolism and cell growth. GATOR2 act as important role in amino acid mediated mTORC1 signaling pathway by repressing GTPase activity (GAP) of GATOR1. However, it is still unclear how GATOR2 regulates mTORC1 signaling pathway. Here, we found that K63-ubiquitination of Sce13, one component of GATOR2, suppresses the mTORC1 activity by lessening the inter-interaction of GATOR2. Mechanistically, the ubiquitination of Sec13 was mediated by SPOP. Subsequently, the ubiquitination of Sec13 attenuated its interaction with the other component of GATOR2, thus suppressing the activity of mTORC1. Importantly, the deficiency of SPOP promoted the faster proliferation and migration of breast cancer cells, which was attenuated by knocking down of Sec13. Therefore, SPOP can act as a tumor suppressor gene by negatively regulating mTORC1 signaling pathway.

Otago Exercises Monitoring for Older Adults by a Single IMU and Hierarchical Machine Learning Models.

Otago Exercise Program (OEP) is a rehabilitation program for older adults to improve frailty, sarcopenia, and balance. Accurate monitoring of patient involvement in OEP is challenging, as self-reports (diaries) are often unreliable. The development of wearable sensors and their use in Human Activity Recognition (HAR) systems has lead to a revolution in healthcare. However, the use of such HAR systems for OEP still shows limited performance. The objective of this study is to build an unobtrusive and accurate system to monitor OEP for older adults. Data was collected from 18 older adults wearing a single waist-mounted Inertial Measurement Unit (IMU). Two datasets were recorded, one in a laboratory setting, and one at the homes of the patients. A hierarchical system is proposed with two stages: 1) using a deep learning model to recognize whether the patients are performing OEP or activities of daily life (ADLs) using a 10-minute sliding window; 2) based on stage 1, using a 6-second sliding window to recognize the OEP sub-classes. Results showed that in stage 1, OEP could be recognized with window-wise f1-scores over 0.95 and Intersection-over-Union (IoU) f1-scores over 0.85 for both datasets. In stage 2, for the home scenario, four activities could be recognized with f1-scores over 0.8: ankle plantarflexors, abdominal muscles, knee bends, and sit-to-stand. These results showed the potential of monitoring the compliance of OEP using a single IMU in daily life. Also, some OEP sub-classes are possible to be recognized for further analysis.

Structural analysis of a soluble polysaccharide GSPA-0.3 from the root of Panax ginseng C. A. Meyer and its adjuvant activity with mechanism investigation.

A novel polysaccharide (GSPA-0.3) was isolated and purified from the root of cultivated Panax ginseng C. A. Meyer, and its structure, adjuvant activities, and mechanisms for inducing the maturation of mouse dendritic 2.4 cells (DC2.4) were extensively studied. Fraction GSPA-0.3, mainly composed by the galacturonic acid, galactose, arabinose, glucose, rhamnose, mannose, and xylose, had a molecular weight of 62,722 Da. The main chain of GSPA-0.3 was composed of →3)-α-L-Rhap-(1→, →4)-α-D-GalpA-(1→, and →3, 4)-α-D-GalpA-(1→. Branched chains comprised α-L-Araf-(1→3, 5)-α-L-Araf-(1→5)-α-L-Araf-(1→, α-D-Glcp-(1→6)-α-D-Glcp-(1→6)-α-D-Glcp-(1→, ß-D-Galp-(1→4)-ß-D-Galp-(1→4)-ß-D-Galp-(1→, and α-D-GalpA-(1→ units connected to the C3 position of →3, 4)-α-D-GalpA-(1→. In vivo, GSPA-0.3 was found to stimulate the production of IgG, IgG1, and IgG2a; increase the splenocyte proliferation index; and promote the expression of GATA-3, T-bet, IFN-γ, and IL-4 in H1N1 vaccine-immunized mice. Moreover, GSPA-0.3 significantly increased the levels of neutralizing antibodies in the mice, and its adjuvant activity was found to be superior to aluminum adjuvant (Alum adjuvant). Mechanistic investigations showed that GSPA-0.3 activated the TLR4-dependent pathway by upregulating the expressions of TLR4, MyD88, TRAF-6, and NF-κB proteins and gens. The results presented herein suggested that GSPA-0.3 could significantly promote the efficacy of the H1N1 vaccine by modulating Th1/Th2 response via the TLR4-MyD88-NF-κB signaling pathway.

Empirical analysis of the impact of the digital economy on the green transformation of manufacturing: Evidence from China.

In this study, the entropy method and the Super-SBM model with unexpected output are used at first to calculate the digital economy development index and the level of green transformation in manufacturing. Then, a range of multi-dimensional empirical methods, including fixed effects models, threshold models, and mediation models, are applied to analyze the characteristics shown by the impact of digital economy development on the green transformation of manufacturing. The research results are obtained as follows. Firstly, the digital economy contributes significantly to promoting the green transformation of manufacturing after excluding the macro-system environmental effects, conducting such robustness tests as stepwise regression and introducing instrumental variables. Secondly, there is a nonlinear relationship between the development of the digital economy and the green transformation of manufacturing with an increasing marginal effect. Lastly, it is revealed through mechanism analysis that the digital economy promotes the green transformation of manufacturing by enhancing the capabilities of green technological innovation and rationalizing industrial upgrading, with the partial mediation effects reaching 21.2% and 21.8%, respectively. Despite the contribution of digital economy to the advanced upgrading of industries, there is no mediation effect exhibited. In addition to confirming the path of achieving the green transformation of manufacturing through the digital economy, these results also guide the government on how policies can be formulated and improved to grow the digital economy and promote the green transformation of manufacturing.

Fluorescence and antioxidant activity of heterologous expression of phycocyanin and allophycocyanin from Arthrospira platensis.

Phycocyanin and allophycocyanin are important active substances in Arthrospira platensis, because of their fluorescent characteristic and antioxidant capacity. In order to solve the problem of insufficient production and inconvenient modification of natural protein, recombinant expression was performed and the fluorescence activity and antioxidant activity was analyzed to meet the demand for phycocyanin and allophycocyanin. A total of seven recombinant strains were constructed in this study, including individual phycocyanin or allophycocyanin, co-expression of phycocyanin-allophycocyanin, and their co-expression with chromophore, and the expression strain for individual chromophore. Different molecular weights of phycocyanin and allophycocyanin were detected in the recombinant strains, which indicated the different polymers expressed. Through mass spectrometry identification, phycocyanin and allophycocyanin may form a dimer of 66 kDa and a polymer of 300 kDa. The results of fluorescence detection showed that phycocyanin and allophycocyanin combined with phycocyanobilin to show fluorescence activity. The fluorescence peak of recombinant phycocyanin was mainly concentrated at 640 nm, which was similar to natural phycocyanin, the fluorescence peak of purified recombinant allophycocyanin was at about 642 nm. The fluorescence peak of the co-expressed recombinant phycocyanin-allophycocyanin is located at 640 nm, and the fluorescence intensity is between the recombinant phycocyanin and the recombinant allophycocyanin. After purification, the fluorescence peak of the recombinant phycocyanin is more concentrated and the fluorescence intensity is higher, which is about 1.3 times of recombinant phycocyanin-allophycocyanin, 2.8 times of recombinant allophycocyanin, indicating that phycocyanin may be more suitable to be used as fluorescence probe in medicine. The antioxidant capacity was measured by using total antioxidant capacity (T-AOC) and DPPH (2,2'-diphenyl-1-triphenylhydrazino) free radical scavenging method, and the recombinant phycobiliprotein showed antioxidant activity. Phycocyanobilin also has certain antioxidant activity and could enhance the antioxidant activity of phycobiliprotein to a certain extent. Recombinant phycocyanin-allophycocyanin polymer has stronger T-AOC, which is about 1.17-2.25 times that of the other five recombinant proteins. And recombinant phycocyanin has stronger DPPH antioxidant activity, which is about 1.2-2.5 times that of the other five recombinant proteins. This study laid the foundation for the application of recombinant phycocyanin and allophycocyanin in medical detection and drug development.

Genetic associations between bipolar disorder and brain structural phenotypes.

Patients with bipolar disorder (BD) and their first-degree relatives exhibit alterations in brain volume and cortical structure, whereas the underlying genetic mechanisms remain unclear. In this study, based on the published genome-wide association studies (GWAS), the extent of polygenic overlap between BD and 15 brain structural phenotypes was investigated using linkage disequilibrium score regression and MiXeR tool, and the shared genomic loci were discovered by conjunctional false discovery rate (conjFDR) and expression quantitative trait loci (eQTL) analyses. MiXeR estimated the overall measure of polygenic overlap between BD and brain structural phenotypes as 4-53% on a 0-100% scale (as quantified by the Dice coefficient). Subsequent conjFDR analyses identified 54 independent loci (71 risk single-nucleotide polymorphisms) jointly associated with BD and brain structural phenotypes with a conjFDR < 0.05, among which 33 were novel that had not been reported in the previous BD GWAS. Follow-up eQTL analyses in respective brain regions both confirmed well-known risk genes (e.g. CACNA1C, NEK4, GNL3, MAPK3) and discovered novel risk genes (e.g. LIMK2 and CAMK2N2). This study indicates a substantial shared genetic basis between BD and brain structural phenotypes, and provides novel insights into the developmental origin of BD and related biological mechanisms.

Cardiomyocyte PAI-1 influences the cardiac transcriptome and limits the extent of cardiac fibrosis in response to left ventricular pressure overload.

Plasminogen activator inhibitor-1 (PAI-1) is a specific and rapid-acting inhibitor of endogenous plasminogen activators (uPA and tPA). The global PAI-1 knockout mice (PAI-1KO) develop age-dependent cardiac-selective fibrosis, and young global PAI-1KO mice exhibit augmented susceptibility to developing cardiac fibrosis in response to hypertension. Here, we tested the hypothesis that cardiomyocyte PAI-1 is necessary to provide cardioprotective effects in a left ventricular pressure overload-induced murine model of cardiac hypertrophy and fibrosis using cardiomyocyte-specific PAI-1 knockout (cmPAI-1KO) mice. The results revealed that cmPAI-1KO mice display significantly worse cardiac fibrosis than controls. To investigate the molecular mechanisms responsible for these effects, genome-wide cardiac transcriptome analysis was performed. Loss of cardiomyocyte PAI-1 led to differential expression of 978 genes compared to controls in response to left ventricular pressure overload. Pathway enrichment analysis identified the inflammatory response, cell substrate adhesion, regulation of cytokine production, leukocyte migration, extracellular matrix organization, and cytokine-mediated signaling pathways as being significantly upregulated in cmPAI-1KO hearts. Conversely, specific epigenetic repressors, cation transmembrane transport, muscle system processes, and nitric oxide signaling were significantly downregulated in cmPAI-1KO hearts compared to control hearts in response to left ventricular pressure overload. Collectively, the present study provides strong evidence of the impact of cardiomyocyte PAI-1 in regulation of the transcriptome network involved in the cardiac stress response. In response to stress, the deregulatory impact of cardiomyocyte PAI-1 loss on the cardiac transcriptome may be the underlying cause of cardiac-selective accelerated fibrogenesis in global PAI-1-deficient mice.

Influencing factors of users' shift to buying expensive virtual gifts in live streaming: Empirical evidence from China.

The market size of live streaming on the Internet, in which the streamer earns profit by prompting users to give virtual gifts through emotional labor, is getting bigger and bigger. However, most users will only buy cheap virtual gifts in live streaming, therefore exploring how to promote users to buy expensive virtual gifts is a valuable topic in live commerce research. Based on social presence theory and information overload theory, this study used the PLS-SEM method to investigate the factors influencing live streaming users to shift from buying cheap virtual gifts to buying expensive virtual gifts, and analyzed the moderating role of information overload in these relationships. The results show that immediate interaction anxiety, verbal intimacy, and virtual physical intimacy positively influence users' shift to purchasing expensive virtual gifts, and that perceived network size and perceived financial risk are negative factors in users' shift to purchasing expensive virtual gifts. Information overload has a moderating role in the relationship between immediate interaction anxiety and switch intention, and it also plays a moderating role in the relationship between perceived network size and perceived financial risk on users' switch intention.

Bidirectional genetic overlap between bipolar disorder and intelligence.

BACKGROUND: Bipolar disorder (BD) is a highly heritable psychiatric illness exhibiting substantial correlation with intelligence. METHODS: To investigate the shared genetic signatures between BD and intelligence, we utilized the summary statistics from genome-wide association studies (GWAS) to conduct the bivariate causal mixture model (MiXeR) and conjunctional false discovery rate (conjFDR) analyses. Subsequent expression quantitative trait loci (eQTL) mapping in human brain and enrichment analyses were also performed. RESULTS: Analysis with MiXeR suggested that approximately 10.3K variants could influence intelligence, among which 7.6K variants were correlated with the risk of BD (Dice: 0.80), and 47% of these variants predicted BD risk and intelligence in consistent allelic directions. The conjFDR analysis identified 37 distinct genomic loci that were jointly associated with BD and intelligence with a conjFDR < 0.01, and 16 loci (43%) had the same directions of allelic effects in both phenotypes. Brain eQTL analyses found that genes affected by the "concordant loci" were distinct from those modulated by the "discordant loci". Enrichment analyses suggested that genes related to the "concordant loci" were significantly enriched in pathways/phenotypes related with synapses and sleep quality, whereas genes associated with the "discordant loci" were enriched in pathways related to cell adhesion, calcium ion binding, and abnormal emotional phenotypes. CONCLUSIONS: We confirmed the polygenic overlap with mixed directions of allelic effects between BD and intelligence and identified multiple genomic loci and risk genes. This study provides hints for the mesoscopic phenotypes of BD and relevant biological mechanisms, promoting the knowledge of the genetic and phenotypic heterogeneity of BD. The essential value of leveraging intelligence in BD investigations is also highlighted.

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Are Gyroscopes an Added Value in Leave-One-Subject-Out Activity Recognition with IMUs?

Inertial sensors have played a key role in the development of Human Activity Recognition (HAR) systems. Adding gyroscopes in HAR systems leads to increased battery and processing resources. Therefore, it is important to explore their added value compared with using accelerometers only. This study evaluates the added value of gyroscopes in activity recognition. Two public available datasets recorded by accelerometers and gyroscopes were studied. These datasets focus on multiple types of activities: UCI HAR dataset includes walking, walking upstairs, walking downstairs, sitting, standing, laying and WISDM dataset includes 18 hand-oriented and non-hand-oriented activities. Several machine learning models were applied to both datasets for activity recognition. Leave-one-subject-out cross-validation (LOSO) was applied to evaluate the models, where the training set and test set were from different subjects. For UCI HAR dataset, the multilayer perceptron (MLP) model obtained the highest f1-scores. Adding a gyroscope on the waist significantly improved the f1-scores of sitting and laying (both ). For WISDM dataset, the support vector machines (SVM) model obtained the highest f1-scores. The gyroscope on the wrist improved hand-oriented activities while the gyroscope in the pockets improved non-hand-oriented activities (all . The results showed the improvement for recognition performance by adding gyroscopes. However, the improvement was dependent on the type of activity and the mounting place of the gyroscope. Clinical relevance- Gyroscopes are common sensors for activity recognition in wearable healthcare systems. This study proves the added value by adding gyroscopes on different mounting places for recognition performance.

The Impact of Digital Contact Tracing Apps Overuse on Prevention of COVID-19: A Normative Activation Model Perspective.

During the COVID-19 pandemic, many countries have used digital contact tracing apps (DCTAs) to implement contact tracing. Although the use of DCTAs has contributed to the prevention and control of COVID-19, there are doubts in academia about their actual effectiveness. In this study, the role of DCTAs in the prevention of COVID-19 was analyzed in terms of both the responsibility and inconvenience to life in a large-scale DCTA overuse environment, based on the normative activation model. The findings suggest that the overuse of a DCTA activates people's personal norms by triggering awareness of the consequences and ascription of responsibility, leading people to consistently cooperate with the government to prevent COVID-19. However, the inconvenience of living with DCTA overuse weakens the effect of the awareness of consequences and ascription of responsibility and the role of the ascription of responsibility in influencing personal norms. These effects may bear on people's willingness to consistently cooperate with the government to prevent COVID-19. The results of this study confirm the effectiveness of DCTA in counteracting pandemics from a social responsibility perspective in a large-scale environment where DCTA is used, enriching the literature on DCTA research in the COVID-19 pandemic. The results of this study can also help governments develop and improve policies to prevent COVID-19, as well as improve the DCTAs' operating patterns.

Photonic crystal sensor for melamine based on magnetic molecularly imprinted nanoparticles self-assembled with an amphiphilic random copolymer.

Magnetic molecularly imprinted nanoparticles (MMINPs) were obtained with a one-step process through miniemulsion self-assembly using an amphiphilic random copolymer as both an emulsifier and MMINP coating, oleic acid-modified magnetite nanoparticles as magnetic cores, and melamine (MEL) as the template molecule. MMINPs were assembled under an external magnetic field to construct photonic crystal (PC) sensor for naked-eye detection of MEL. The MMINPs were characterized by FT-IR, TEM, TGA, and VSM. The analytical performances of the magnetic molecularly imprinted PC sensor for MEL (MEL-MMIPCs) were investigated with respect to sensitivity, response time, selectivity, and stability. As the MEL concentration increases from 1.0 to 1.0 × 106 µg/l, the reflection wavelength of MEL-MMIPCs shifted from 497 to 709 nm, and was linear with the logarithm of MEL concentration in this range. The detection limit was 0.21 µg/l (S/N = 3) and response time was within 30 s. The MEL-MMIPC sensor had an imprinting factor of 5.09, and selectivity factors for the analogs cyanuric acid and atrazine were 8.76 and 5.75, respectively, indicating the high sensitivity and selectivity. After 10 cycles of elution/response, MEL-MMIPCs still had a good ability to recognize MEL.

Adeno-associated virus vector intraperitoneal injection induces colonic mucosa and submucosa transduction and alters the diversity and composition of the faecal microbiota in rats.

Background: Viral vector technology, especially recombinant adeno-associated virus vector (rAAV) technology, has shown great promise in preclinical research for clinical applications. Several studies have confirmed that rAAV can successfully transduce the enteric nervous system (ENS), and rAAV gene therapy has been approved by the Food and Drug Administration (FDA) for the treatment of the early childhood blindness disease Leber congenital amaurosis and spinal muscular atrophy (SMA). However, until now, it has not been possible to determine the effect of AAV9 on intestinal microbiota. Methods: We examined the efficiency of AAV9-mediated ascending colon, transverse colon and descending colon transduction through intraperitoneal (IP) injection, performed 16S rRNA gene amplicon sequencing and analysed specific faecal microbial signatures following AAV9 IP injection via bioinformatics methods in Sprague-Dawley (SD) rats. Results: Our results showed (1) efficient transduction of the mucosa and submucosa of the ascending, transverse, and descending colon following AAV9 IP injection; (2) a decreased alpha diversity and an altered overall microbial composition following AAV9 IP injection; (3) significant enrichments in a total of 5 phyla, 10 classes, 13 orders, 15 families, 29 genera, and 230 OTUs following AAV9 IP injection; and (4) AAV9 can significantly upregulate the relative abundance of anaerobic microbiota which is one of the seven high-level phenotypes that BugBase could predict. Conclusion: In summary, these data show that IP injection of AAV9 can successfully induce the transduction of the colonic mucosa and submucosa and alter the diversity and composition of the faecal microbiota in rats.

Research progress of endothelial-to-mesenchymal transition in ocular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Endothelial-to-mesenchymal transition(EndoMT)is a change in the transformation or differentiation of endothelial cells into mesenchymal cells under physiological or pathological conditions, accompanied by changes in phenotype and function, and is an important part of fiber repair. It is widely involved in the pathophysiological process of embryonic development, tumor invasion and a variety of fibrotic diseases. Research on the role of EndoMT in ocular diseases has also made some progress. This article will review the basic biological characteristics, mechanism and research results of EndoMT in ophthalmological diseases, intending to theoretically reveal its possibility as a treatment target and a key point of regenerative medicine technology in related diseases, provide a reference for clinical practice and scientific research.

Toward street vending in post COVID-19 China: Social networking services information overload and switching intention.

With the progress of epidemic containment, the Chinese government has relaxed its regulatory policies on street vending, hoping to help people who have lost their livelihoods and to assist in the restoration of social and economic order. In response, Chinese people poured into the stall economy, especially individual peddlers, with great expectations for street vending. Street vending has become a hot topic on Chinese social network sites (SNSs). Based on the push-pull-mooring framework, SNS information overload theory was introduced and combined with the actual situations of street vending in China, and a structural equation model was established to study factors affecting individual Chinese peddlers' intention to engage in street vending and the effects of SNS information overload on these factors. Results revealed that perceived policy benefits, subjective norms, and switching cost perceptions of individual peddlers were positive factors affecting their intention to engage in street vending. SNS information overload positively affected individual peddlers' dissatisfaction with their original business model, anxieties over their livings, perception of policy benefits, and subjective norms but negatively affected individual peddlers' perception of switching costs.

Bathroom activities monitoring for older adults by a wrist-mounted accelerometer using a hybrid deep learning model.

Monitoring activities of daily life (ADLs) allows to evaluate health conditions for older adults. However, there are still a limited number of studies on bathroom activities monitoring using a wrist-mounted accelerometer. To fill this gap, in this study, researchers collected data from 15 older adults wearing a wrist-mounted accelerometer. Six bathroom activities, i.e., dressing, undressing, brushing teeth, using toilet, washing face, and washing hands, were investigated. In total, 49.4-hour data for bathroom activities were collected. A hybrid convolutional neural network (CNN) is introduced for bathroom activity recognition. This hybrid CNN model is developed using both hand-crafted and CNN-based features as input. The proposed hybrid CNN model is compared to four machine learning models, i.e., Multilayer Perceptron (MLP), Support Vector Machines (SVM), K-nearest Neighbors (KNN), and Decision Trees (DT), and a conventional CNN model. Based on the classification results of leave-one-subject-out cross-validation (LOSO), the hybrid CNN model outperformed the other models. The hybrid CNN model is also tested based on a transfer learning method. As a calibration step based on LOSO, the transfer learning method additionally trains the model with an example of each activity from the test subject. The transfer learning method obtained better classification performance than LOSO. With transfer learning, the f1-score for using toilet was improved from 0.7784 to 0.8437. This study proposes a deep learning model fusing hand-crafted features and CNN-based features. Besides, the transfer learning method offers a way to build subject-dependent models to improve the classification performance.Clinical relevance -This provides a model that helps monitoring older adults' bathroom activities using a single wrist-mounted accelerometer.

Pharmacological inhibition of PAI-1 alleviates cardiopulmonary pathologies induced by exposure to air pollutants PM2.5.

Numerous studies have established that acute or chronic exposure to environmental pollutants like particulate matter (PM) leads to the development of accelerated aging related pathologies including pulmonary and cardiovascular diseases, and thus air pollution is one of the major global threats to human health. Air pollutant particulate matter 2.5 (PM2.5)-induced cellular dysfunction impairs tissue homeostasis and causes vascular and cardiopulmonary damage. To test a hypothesis that elevated plasminogen activator inhibitor-1 (PAI-1) levels play a pivotal role in air pollutant-induced cardiopulmonary pathologies, we examined the efficacy of a drug-like novel inhibitor of PAI-1, TM5614, in treating PM2.5-induced vascular and cardiopulmonary pathologies. Results from biochemical, histological, and immunohistochemical studies revealed that PM2.5 increases the circulating levels of PAI-1 and thrombin and that TM5614 treatment completely abrogates these effects in plasma. PM2.5 significantly augments the levels of pro-inflammatory cytokine interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF), and this also can be reversed by TM5614, indicating its efficacy in amelioration of PM2.5-induced increases in inflammatory and pro-thrombotic factors. TM5614 reduces PM2.5-induced increased levels of inflammatory markers cluster of differentiation 107 b (Mac3) and phospho-signal transducer and activator of transcription-3 (pSTAT3), adhesion molecule vascular cell adhesion molecule 1 (VCAM1), and apoptotic marker cleaved caspase 3. Longer exposure to PM2.5 induces pulmonary and cardiac thrombosis, but TM5614 significantly ameliorates PM2.5-induced vascular thrombosis. TM5614 also reduces PM2.5-induced increased blood pressure and heart weight. In vitro cell culture studies revealed that PM2.5 induces the levels of PAI-1, type I collagen, fibronectin (Millipore), and sterol regulatory element binding protein-1 and 2 (SREBP-1 and SREBP-2), transcription factors that mediate profibrogenic signaling, in cardiac fibroblasts. TM5614 abrogated that stimulation, indicating that it may block PM2.5-induced PAI-1 and profibrogenic signaling through suppression of SREBP-1 and 2. Furthermore, TM5614 blocked PM2.5-mediated suppression of nuclear factor erythroid related factor 2 (Nrf2), a major antioxidant regulator, in cardiac fibroblasts. Pharmacological inhibition of PAI-1 with TM5614 is a promising therapeutic approach to control air pollutant PM2.5-induced cardiopulmonary and vascular pathologies.