Anti-aging research has become critical since the elderly population is increasing dramatically in this era. With the establishment of frailty phenotype and frailty index, the importance of ...anti-frailty research is concurrently enlightened. The application of natural phytochemicals against aging or frailty is always intriguing, and abundant related studies have been published. Various models are designed for biological research, and each model has its strength and weakness in deciphering the complex aging mechanisms. In this article, we attempt to show the potential of Caenorhabditis elegans in the study of phytochemicals' effects on anti-aging by comparing it to other animal models. In this review, the lifespan extension and anti-aging effects are demonstrated by various physical, cellular, or molecular biomarkers of dietary phytochemicals, including resveratrol, curcumin, urolithin A, sesamin, fisetin, quercetin, epigallocatechin-3-gallate, epicatechin, spermidine, sulforaphane, along with extracts of broccoli, cocoa, and blueberry. Meanwhile, the frequency of phytochemicals and models studied or presented in publications since 2010 were analyzed, and the most commonly mentioned animal models were rats, mice, and the nematode C. elegans. This up-to-date summary of the anti-aging effect of certain phytochemicals has demonstrated powerful potential for anti-aging or anti-frailty in the human population.
Detection of nodal micrometastasis (tumor size: 0.2–2.0 mm) is challenging for pathologists due to the small size of metastatic foci. Since lymph nodes with micrometastasis are counted as positive ...nodes, detecting micrometastasis is crucial for accurate pathologic staging of colorectal cancer. Previously, deep learning algorithms developed with manually annotated images performed well in identifying micrometastasis of breast cancer in sentinel lymph nodes. However, the process of manual annotation is labor intensive and time consuming. Multiple instance learning was later used to identify metastatic breast cancer without manual annotation, but its performance appears worse in detecting micrometastasis. Here, we developed a deep learning model using whole-slide images of regional lymph nodes of colorectal cancer with only a slide-level label (either a positive or negative slide). The training, validation, and testing sets included 1963, 219, and 1000 slides, respectively. A supercomputer TAIWANIA 2 was used to train a deep learning model to identify metastasis. At slide level, our algorithm performed well in identifying both macrometastasis (tumor size > 2.0 mm) and micrometastasis with an area under the receiver operating characteristics curve (AUC) of 0.9993 and 0.9956, respectively. Since most of our slides had more than one lymph node, we then tested the performance of our algorithm on 538 single-lymph node images randomly cropped from the testing set. At single-lymph node level, our algorithm maintained good performance in identifying macrometastasis and micrometastasis with an AUC of 0.9944 and 0.9476, respectively. Visualization using class activation mapping confirmed that our model identified nodal metastasis based on areas of tumor cells. Our results demonstrate for the first time that micrometastasis could be detected by deep learning on whole-slide images without manual annotation.
The aim of this study was to determine whether low dose doxycycline as an anti-inflammatory agent could improve glucose metabolism in diabetic animals. Therefore, doxycycline was supplemented in ...drinking water to 6-week-old male db/db mice for 10 weeks. Doxycycline reduced perirenal/epididymal fat, Lee's index, and liver cholesterol. Blood HDL-cholesterol increased, but total cholesterol and aspartate transaminase decreased. Glucose and insulin tolerances were improved, accompanying with reduced fasting blood glucose, insulin, HOMA-IR and advanced glycation end products. Islet number, β-cell percentage and mass increased, while islet size decreased. Consistently, less apoptosis but more β-cell proliferation were found in islets of treated mice. Freshly isolated islets from treated mice showed higher insulin content and enhanced glucose stimulated insulin secretion (GSIS). In addition, purified islets of Balb/c mice showed increased GSIS after cultivation in vitro with doxycycline, but not with chloramphenicol and levofloxacin. Inflammation markers, including lipopolysaccharides (LPS) and C-reactive protein (CRP) in serum as well as CD68-positive cells in treated islets, decreased significantly. Finally, LPS stimulated the production of inflammatory factors but inhibited GSIS of MIN6 cells; however, the effects were completely reversed by doxycycline. The results support further study of possible long-term usage of sub-antimicrobial doxycycline in diabetic patients.
The aging population has caused assistive technology (AT) to receive attention. Thus, ensuring accurate user comprehension of AT has become increasingly crucial, and more specialized education for ...students in relevant fields is necessary. The goal of this study was to explore the learning outcomes in the context of AT for older adults and individuals with disabilities through the use of VR experiential learning.
A parallel-group design was used. Sixty third-year university students studying gerontology and long-term-care-related subjects in Taiwan were enrolled, with the experimental (VR) and control (two-dimensional 2D video) groups each comprising 30 participants. Both groups received the same 15-minute lecture. Subsequently, the experimental group received experiential learning through a VR intervention, whereas the control group watched a 2D video to learn. The students' knowledge of AT was assessed using a pretest and posttest. Additionally, their skills in evaluation of residential environments were assessed using the Residential Environment Assessment (REA) Form for Older Adults. All data analyses were performed with SPSS version 22.
In the posttest conducted after the intervention, the experimental group exhibited a significant 20.67 point improvement (p < 0.05), whereas the control group only exhibited improvement of 3.67 points (p = 0.317). Furthermore, the experimental group demonstrated a significantly higher score (+ 2.17 points) on the REA Form for Older Adults than did the control group (p < 0.05).
VR experiential learning can significantly improve undergraduate students' knowledge and evaluation skills in relation to AT for older adults and individuals with disabilities.
Enterovirus A71 (EV-A71) is a human pathogen causing hand, foot, and mouth disease (HFMD) in children. Its infection can lead to severe neurological diseases or even death in some cases. While being ...produced in a large quantity during infection, viral proteins often require the assistance from cellular chaperones for proper folding. In this study, we found that heat shock protein A6 (HSPA6), whose function in viral life cycle is scarcely studied, was induced and functioned as a positive regulator for EV-A71 infection. Depletion of HSPA6 led to the reductions of EV-A71 viral proteins, viral RNA and virions as a result of the downregulation of internal ribosomal entry site (IRES)-mediated translation. Unlike other HSP70 isoforms such as HSPA1, HSPA8, and HSPA9, which regulate all phases of the EV-A71 life, HSPA6 was required for the IRES-mediated translation only. Unexpectedly, the importance of HSPA6 in the IRES activity could be observed in the absence of viral proteins, suggesting that HSPA6 facilitated IRES activity through cellular factor(s) instead of viral proteins. Intriguingly, the knockdown of HSPA6 also caused the reduction of luciferase activity driven by the IRES from coxsackievirus A16, echovirus 9, encephalomyocarditis virus, or hepatitis C virus, supporting that HSPA6 may assist the function of a cellular protein generally required for viral IRES activities.
The application of artificial intelligence (AI) to health has increased, including to COVID-19. This study aimed to provide a clear overview of COVID-19-related AI publication trends using ...longitudinal bibliometric analysis. A systematic literature search was conducted on the Web of Science for English language peer-reviewed articles related to AI application to COVID-19. A search strategy was developed to collect relevant articles and extracted bibliographic information (e.g., country, research area, sources, and author). VOSviewer (Leiden University) and Bibliometrix (R package) were used to visualize the co-occurrence networks of authors, sources, countries, institutions, global collaborations, citations, co-citations, and keywords. We included 729 research articles on the application of AI to COVID-19 published between 2020 and 2021.
(33/729, 4.52%),
(29/729, 3.97%), and
(29/729, 3.97%) were the most common journals publishing these articles. The Republic of China (190/729, 26.06%), the USA (173/729, 23.73%), and India (92/729, 12.62%) were the most prolific countries of origin. The
,
, and
were the most productive institutions. This is the first study to show a comprehensive picture of the global efforts to address COVID-19 using AI. The findings of this study also provide insights and research directions for academic researchers, policymakers, and healthcare practitioners who wish to collaborate in these domains in the future.
Rapid and large area acquisition of nitrogen (N) deficiency status is important for achieving the optimal fertilization of rice. Most existing studies, however, focus on the use of unmanned aerial ...vehicle (UAV) remote sensing to diagnose N nutrition in rice, while there are fewer studies on the quantitative description of the degree of N deficiency in rice, and the effects of the critical N concentration on the spectral changes in rice have rarely been explored. Therefore, based on the canopy spectral data obtained by remotely-sensed UAV hyperspectral images, the N content in rice was obtained through field sampling. The construction method of the rice curve for the northeastern critical N concentration was studied, and on this basis, N deficiency was determined. Taking the spectrum of the critical N concentration state as the standard spectrum, the spectral reflectivity data were transformed by the ratios and differences, and the feature extraction of the spectral data was carried out by the successive projections algorithm (SPA). Finally, by taking the characteristic band as the input variable and N deficiency as the output variable, a set of multivariate linear regression (MLR), long short-term memory (LSTM) inversion models based on extreme learning machine (ELM), and the non-dominated sorting genetic algorithm III extreme learning machine (NSGA-III-ELM) were constructed. The results showed two key aspects of this system: 1) The correlation between the N deficiency data and original spectrum was poor, but the correlation between the N deficiency data and N deficiency could be improved by a difference change and ratio transformation; 2) The inversion results based on the ratio spectrum and NSGA-III-ELM algorithm were the best, as the R2 values of the training set and validation set were 0.852 and 0.810, and the root mean square error (RMSE) values were 0.291 and 0.308, respectively. From the perspective of the spectral data, the inversion accuracy of the ratio spectrum was better than the accuracy of the original spectrum or difference spectrum. At the algorithm level, the model inversion results based on LSTM algorithms showed a serious overfitting phenomenon and poor inversion effect. The inversion accuracy based on the NSGA-III-ELM algorithm was better than the accuracy of the MLR algorithm or the ELM algorithm. Therefore, the inversion model based on the ratio spectrum and NSGA-III-ELM algorithm could effectively invert the N deficiency in rice and provide critical technical support for accurate topdressing based on the N status in the rice.
The activation of p38 mitogen-activated protein kinases (MAPKs) through a phosphorylation cascade is the canonical mode of regulation. Here, we report a novel activation mechanism for p38α. We show ...that Arg49 and Arg149 of p38α are methylated by protein arginine methyltransferase 1 (PRMT1). The non-methylation mutations of Lys49/Lys149 abolish the promotive effect of p38α on erythroid differentiation. MAPK kinase 3 (MKK3) is identified as the major p38α upstream kinase and MKK3-mediated activation of the R49/149K mutant p38α is greatly reduced. This is due to a profound reduction in the interaction of p38α and MKK3. PRMT1 can enhance both the methylation level of p38α and its interaction with MKK3. However, the phosphorylation of p38α by MKK3 is not a prerequisite for methylation. MAPK-activated protein kinase 2 (MAPKAPK2) is identified as a p38α downstream effector in the PRMT1-mediated promotion of erythroid differentiation. The interaction of MAPKAPK2 with p38α is also significantly reduced in the R49/149K mutant. Together, this study unveils a novel regulatory mechanism of p38α activation via protein arginine methylation on R49/R149 by PRMT1, which impacts partner interaction and thus promotes erythroid differentiation. This study provides a new insight into the complexity of the regulation of the versatile p38α signaling and suggests new directions in intervening p38α signaling.
Heart failure (HF) and cancer have similar risk factors. HMG-CoA reductase inhibitors, also known as statins, are chemoprotective agents against carcinogenesis. We aimed to evaluate the ...chemoprotective effects of statins against liver cancer in patients with HF. This cohort study enrolled patients with HF aged ≥20 years between 1 January 2001 and 31 December 2012 from the National Health Insurance Research Database in Taiwan. Each patient was followed to assess liver cancer risk. A total of 25,853 patients with HF were followed for a 12-year period; 7364 patients used statins and 18,489 did not. The liver cancer risk decreased in statin users versus non-users (adjusted hazard ratio (aHR) = 0.26, 95% confidence interval (CI): 0.20-0.33) in the entire cohort in the multivariate regression analysis. In addition, both lipophilic and hydrophilic statins reduced the liver cancer risk in patients with HF (aHR 0.34, 95% CI: 0.26-0.44 and aHR 0.42, 95% CI: 0.28-0.54, respectively). In the sensitivity analysis, statin users in all dose-stratified subgroups had a reduced liver cancer risk regardless of age, sex, comorbidity, or other concomitant drug use. In conclusion, statins may decrease liver cancer risk in patients with HF.
Chronic kidney disease (CKD) is significantly associated with lung cancer incidence. The aim of this study was to elucidate whether influenza vaccination reduces the incidence of lung cancer in ...patients with CKD. This cohort study enrolled patients with a record of CKD diagnosis from 2000 to 2012 in Taiwan’s National Health Insurance Research Database. Included patients were divided into vaccinated and unvaccinated groups. In total 12,985 patients with CKD were enrolled. Among these patients, 5495 were vaccinated and 7490 were unvaccinated. The risk of lung cancer was significantly lower in the influenza vaccination group after adjusting for age, sex, dialysis status, lung diseases, comorbidities, level of urbanization, and monthly income (adjusted hazard ratio (HR): 0.50, 95% confidence interval (CI; 0.38−0.65), p < 0.05). Lower risk of lung cancer was observed in both sexes, all age groups, dialysis status and co-existed lung diseases. The association between the risk of lung cancer and vaccination appeared to be dose-dependent (adjusted HRs: 0.91 (0.66−1.25), 0.49 (0.34−0.71), and 0.25 (0.17−0.38) for patients who received 1, 2 or 3, and ≥4 vaccinations during the follow-up period, respectively). In conclusion, Influenza vaccination decreased the risk of lung cancer in patients diagnosed with CKD. This potentially protective effect against lung cancer appeared to be dose dependent.
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