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Background/purpose: The impact of temporomandibular joint (TMJ) osseous destruction on bone mineral density (BMD) remains unclear due to controversial findings. Besides, no previous study has explored the relationship between idiopathic condylar resorption (ICR) and body composition. This study aimed to investigate the relationship between ICR and BMD or body composition. Materials and methods: Between July 2018 and August 2022, patients evaluated by an experienced dentist and diagnosed with temporomandibular disorders (TMDs) were referred to our center. They were recruited while they received the magnetic resonance image (MRI) examination, BMD and body composition completely. Patients were further categorized into TMDs with or without ICR groups according to MRI findings. One-way analysis of variance was used to compare the variables of BMD and body composition in the two groups. Results: In total, 67 patients were included in the analysis, with 42 categorized as TMDs with ICR and 25 as TMDs without ICR. Patients with ICR had a significantly higher lean mass percentage and lower fat mass percentage; lower android/gynoid fat ratio, and visceral adipose tissue area than those without ICR (P

ABSTRACTBotrytis fruit rot (BFR) causes significant losses in-field and postharvest in strawberries and is mainly managed by fungicides. Strategically applying fungicides only during wet and cool periods would reduce fungicide resistance development and grower costs. A survey of BFR levels in field-grown strawberries with and without fungicide applications was conducted in Santa Maria, California. Weather data were collected to calculate the BFR risk factor using Florida’s Strawberry Advisory System (StAS). There were no significant differences between fungicide and no-fungicide treatments for in-field and postharvest BFR incidence in 2021 and in-field BFR incidence in 2022, while the no-fungicide treatment showed higher postharvest BFR incidence in 2022. Average in-field BFR incidence for fungicide and no-fungicide treatments was 2.6% and 2.5% for 2021 and 3.0% and 3.7% for 2022. Average postharvest BFR incidence for fungicide and no-fungicide treatments was 1.8% and 2.0% for 2021 and 0.6% and 1.5% for 2022. BFR risk factor was significantly associated with BFR incidence in 2021, but not in 2022. StAS predicted a 50% and 44% fungicide application reduction in 2021 and 2022 compared to grower standard treatments. These results indicate the potential of reducing fungicide use without compromising BFR control in California strawberry production.

Abstract Long-term wind power forecasting is a challenging endeavor that requires predictions that span years into the future. Accurate forecasting is crucial for optimizing energy production, grid integration, maintenance scheduling, and financial planning. This study attempts to first develop the long short-term memory networks (LSTM) with a seasonal wavelet transform forecasting model for practical long-term wind power forecasting problems with seasonal and regional influences on wind power and the instability of data signals. This model encapsulates wavelet transformation and seasonal decomposition, and employs LSTM for forecasting. The new prediction model adopted seasonal decompositions and two LSTMs to approach low- and high-frequency series datasets, as well as the wavelet synthesis prediction values. Furthermore, the parameters of the LSTM models are selected using stochastic optimization. For a comprehensive evaluation, the proposed LSTM with seasonal wavelet transform is compared with seven methods, including seasonal LSTM (SLSTM), wavelet LSTM (WLSTM), and the seasonal auto-regressive integrated moving average (SARIMA), back propagation neural network (BPNN), generalized regression neural network (GRNN), least square support vector regression (LSSVR), and support vector regression (SVR) were employed for long-term wind power output forecasting of wind farms. The empirical results underscore that the performance of the proposed forecasting model is better than other methods in terms of forecasting accuracy, which could efficiently provide reliable long-term predictions for long-term wind power output forecasting.

Abstract Pure organic materials with persistent and efficient room‐temperature phosphorescence have recently aroused great research interest due to their vast potential in applications. One crucial design principle for such materials is to suppress as much as possible the non‐radiative decay of the triplet exciton while maintaining a moderate phosphorescent radiative rate. However, molecular engineering often exhibits similar regulation trends for the two processes. Here, we propose that the quantum interference caused by aggregation can be utilized to control the phosphorescent and non‐radiative decay channels. We systematically analyze various constructive and destructive transition pathways in aggregates with different molecular packing types and establish clear relationships between the luminescence characters and the signs of the singlet and triplet excitonic couplings. It is shown that the decay channels can be flexibly switched on or off by regulating the packing type and excitonic couplings. Most importantly, an enhanced phosphorescent decay and a completely suppressed non‐radiative decay can be simultaneously realized in the aggregate packed with inversion symmetry. This work lays the theoretical foundation for future experimental realization of quantum interference effects in phosphorescence.

Postural assessment can help doctors and therapists identify risk factors for low back pain and determine appropriate follow-up treatment. Postural alignment is not perfectly symmetrical, and small asymmetries can instead represent norms and criteria for postural evaluation. It is necessary to comprehensively observe patients’ posture in all directions and analyze the factors related to posture evaluation. The results of reliability show that in general intra-rater reliability is higher than inter-rater reliability, and inclinometers are being more reliable than other instrumentations. Some common postural problems can cause lumbar discomfort, and prolonged poor posture is a potential risk factor for lumbar spine injuries. On the basis of previous studies on posture evaluation, a unified standardized method for posture evaluation must be established in future research.

AIM: To investigate whether the two-step strategy [conjunctival flap covering surgery (CFCS) combined with secondary deep anterior lamellar keratoplasty (DALK)] is effective for patients with high-risk fungal keratitis (FK). METHODS: In this noncomparative, retrospective case series, 10 subjects (6 males, 4 females) with a mean age of 56.5±7.1 (range 47-72)y with high-risk FK undergone the two-step strategy were included. Reported outcome measures were healing of the corneal ulcer, recurrence of FK, reject reaction, improvement in best corrected visual acuity (BCVA) and relevant complications. RESULTS: The average diameter of corneal infiltrates was 7.50±0.39 mm, ranging from 6.94 to 8.13 mm. The mean depth of corneal infiltrates was 422.4±77.1 μm, ranging from 350 to 535 μm. The mean corneal thickness was 597.4±117.3 μm, ranging from 458 to 851 μm. Hypopyon and endothelial plaques were presented in all patients. The period between the two steps was 3.65±0.9 (ranging from 3 to 5)mo. The graft diameter was 7.75±0.39 mm. At the last follow-up (average 9.25±3.39, ranging from 5.5 to 17mo), no fungal recurrence or graft rejection appeared, and all patients showed improvement of BCVA. One patient suffered from liver function impairment due to oral voriconazole for 4wk and recovered spontaneously after 1wk of drug withdrawal. CONCLUSION: The two-step strategy is safe and effective in the treatment of high-risk FK by transforming intentional therapeutic penetrating keratoplasty during acute infection to later optical DALK. It is a practical strategy, especially in areas lacking fresh donor corneas and eye bank services.

The whole angle mode gyroscope (WAMG) is considered to be the next generation architecture, but it is suffered from the asymmetry errors to conduct real products. This paper proposes a novel high frequency injection based approach for the error parameters online identification for the WAMG. The significance is that it can separate physical and error fingerprints to enable online calibration. The nonlinear WAMG dynamics are discretized to meet the requirement of numerical precision and computation efficiency. The optimized estimation methods are then constructed and compared to track asymmetry error parameters continuously. In the validation part, its results firstly prove that the proposed scheme can accurately identify constant asymmetry parameters with an overall tracking error of less than 1 ppm and the extreme numerical convergence can reach 10−12ppm. Under the dynamic asymmetry variation condition, the root mean square errors (RMSE) indicate that the tracking accuracy can reach the level of 10−3, which shows the robustness of the proposed scheme. In summary, the proposed method can effectively estimate the WAMG asymmetry errors online with satisfied performance and practical values.

Psoriatic disease is a chronic inflammatory disorder with skin and joint manifestations. Due to the persistent inflammatory state exhibited by patients with psoriasis, multiple systemic comorbidities occur more frequently in patients with psoriasis than in the general population, and the risk of cardiovascular (CV) diseases is significantly increased. As the pathophysiology of psoriatic disease is becoming better understood, the sharing of underlying pathogenic mechanisms between psoriatic and CV diseases is becoming increasingly apparent. Consequently, careful attention to CV comorbidities that already exist or may potentially develop is needed in the management of patients with psoriasis, particularly in the screening and primary prevention of CV disease and in treatment selection due to potential drug–drug and drug-disease interactions. Furthermore, as the use of effective biologic therapy and more aggressive oral systemic treatment for psoriatic disease is increasing, consideration of the potential positive and negative effects of oral and biologic treatment on CV disease is warranted. To improve outcomes and quality of care for patients with psoriasis, the Taiwanese Dermatological Association, the Taiwanese Association for Psoriasis and Skin Immunology, and the Taiwan Society of Cardiology established a Task Force of 20 clinicians from the fields of dermatology, cardiology, and rheumatology to jointly develop consensus expert recommendations for the management of patients with psoriatic disease with attention to CV comorbidities.

Purpose: To explore the mandibular condylar movements in patients with temporomandibular joint (TMJ) disorders using kinematic magnetic resonance imaging (MRI). Methods: We retrospectively recruited patients who were clinically diagnosed with internal derangement of the TMJ and referred to our center for MRI examination. The TMJ discs were categorized into normal disc (ND), anteriorly displaced disc (ADD), and disc with destruction (DD) groups using static images obtained in the closed-mouth view. The difference between the “open-mouth” and “closed-mouth” views on kinematic MRI was used to calculate the condylar translation and rotation. Two radiologists consensually performed the image readings and measurements. One-way analysis of variance and chi-squared test were used to compare the variables in the three groups. Pearson's correlation and general linear models were used to evaluate the correlation and differences between condylar translation and rotation in the three groups. Results: This study included 98 TMJs from 54 patients. Twenty-six, 49, and 23 TMJs were classified as ND, ADD, and DD, respectively. Condylar rotation and translation demonstrated a significant correlation in all TMJs examined (r = 0.635, p

This study adopts the hierarchical linear growth modeling approach to analyze the differences in the changes of repeat-sales house prices in Kaohsiung City from 2012 to 2020. The Level 1 time-varying factors include house age and the time of repeat-sales; the Level 2 factors include house attributes such as house area, house type, and house location. Based on the results of the null model, the estimated variance is 0.42816, with a 1% level of significance. This shows that significant differences exist in the mean repeat-sales prices between houses. The interclass correlation coefficient is 91.65%, showing that the interclass variation and intraclass variation of the mean repeat-sales prices are 91.65% and 8.35%, respectively. The estimation results of the non-randomly varying slope model indicate that the sales time and sales time squared significantly affect repeat-sales prices. The annual growth rate and quadratic growth of sales prices do not differ by house type (luxury condominiums and apartment buildings) but are affected by house area and house location. The effect of house age on repeat-sales prices is moderated by house area, house type, and house location.

Abstract Lung cancer is the second most common cancer in Taiwan. After Taiwan implemented the Tobacco Hazards Prevention Act in 1997, smoking rates declined. However, the incidence rates of lung cancer for both sexes are still increasing, possibly due to risk factors other than smoking. We used age–period–cohort analysis to examine the secular trends of lung cancer incidence rates by histological type in Taiwan. A stabilized kriging method was employed to map these lung cancer incidence rates. Lung adenocarcinoma incidence rates increased, but lung squamous cell carcinoma incidence rates decreased, for both the sexes in recent birth cohorts, particularly in women. In Taiwan, the hotspots of lung adenocarcinoma incidence rates were in the northern, northeastern, and western coastal areas; the incidence rates increased rapidly in the western and southern coastal regions and southern mountainous regions. The high incidence rates of lung squamous cell carcinoma in men were in the southwestern and northeastern coastal areas. The incidence rates rapidly increased in the central and southern coastal and mountainous regions. For both sexes in Taiwan, lung squamous cell carcinoma incidence rates declined from 1997 to 2017, but lung adenocarcinoma increased. The increased incidence rates of lung adenocarcinoma may be related to indoor and outdoor air pollution. Some areas in Taiwan have increasing lung cancer incidence rates, including the northwestern and southern coasts and mountains, and warrant particular attention.

Abstract Background To verify efficacy of automatic screening and classification of glaucoma with deep learning system. Methods A cross-sectional, retrospective study in a tertiary referral hospital. Patients with healthy optic disc, high-tension, or normal-tension glaucoma were enrolled. Complicated non-glaucomatous optic neuropathy was excluded. Colour and red-free fundus images were collected for development of DLS and comparison of their efficacy. The convolutional neural network with the pre-trained EfficientNet-b0 model was selected for machine learning. Glaucoma screening (Binary) and ternary classification with or without additional demographics (age, gender, high myopia) were evaluated, followed by creating confusion matrix and heatmaps. Area under receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and F1 score were viewed as main outcome measures. Results Two hundred and twenty-two cases (421 eyes) were enrolled, with 1851 images in total (1207 normal and 644 glaucomatous disc). Train set and test set were comprised of 1539 and 312 images, respectively. If demographics were not provided, AUC, accuracy, precision, sensitivity, F1 score, and specificity of our deep learning system in eye-based glaucoma screening were 0.98, 0.91, 0.86, 0.86, 0.86, and 0.94 in test set. Same outcome measures in eye-based ternary classification without demographic data were 0.94, 0.87, 0.87, 0.87, 0.87, and 0.94 in our test set, respectively. Adding demographics has no significant impact on efficacy, but establishing a linkage between eyes and images is helpful for a better performance. Confusion matrix and heatmaps suggested that retinal lesions and quality of photographs could affect classification. Colour fundus images play a major role in glaucoma classification, compared to red-free fundus images. Conclusions Promising results with high AUC and specificity were shown in distinguishing normal optic nerve from glaucomatous fundus images and doing further classification.

Abstract Background Somatosensory deficits and abnormal pain sensitivity are highly prevalent among stroke survivors, which negatively impacts their quality of life and recovery process. However, the factors for pressure pain threshold (PPT) and somatosensory abnormalities in post-stroke elderly remain unknown. The aim of this study was to explore the effects of age, side and other functional conditions, such as spasticity and motor functions, on PPT and sensory abnormalities among elderly after stroke. Methods The cross-sectional study finally included 43 post-stroke elderly aged over 60 and assessed the PPT of 14 bilateral muscles widely located in the whole body by using a digital force gage. Meanwhile, spasticity, motor function, joint pain and activity of daily living (ADL) were evaluated by the Modified Ashworth scale, Fugl-Meyer, and Barthel Index, respectively. All participants were divided into higher-aged and lower-aged groups based on the median age of all of them. Results Higher age tended to be associated with higher sensitivity but not significant except for one upper limb muscle, and the affected side showed significantly higher PPTs than the unaffected side in three out of seven muscles (p

Diabetic retinopathy (DR) is one of the most common complications of diabetes and major cause of blindness among people over 50 years old. Current studies showed that the vascular endothelial growth factor (VEGF) played a central role in the pathogenesis of DR, and application of anti-VEGF has been widely acknowledged in treatment of DR targeting retinal neovascularization. However, anti-VEGF therapy has several limitations such as drug resistance. It is essential to develop new drugs for future clinical practice. The vitreous takes up 80% of the whole globe volume and is in direct contact with the retina, making it possible to explore the pathogenesis of DR by studying related factors in the vitreous. This article reviewed recent studies on DR-related factors in the vitreous, elaborating the VEGF upstream hypoxia-inducible factor (HIF) pathway and downstream pathways phosphatidylinositol diphosphate (PIP2), phosphoinositide-3-kinase (PI3K), and mitogen-activated protein kinase (MAPK) pathways. Moreover, factors other than VEGF contributing to the pathogenesis of DR in the vitreous were also summarized, which included factors in four major systems, kallikrein-kinin system such as bradykinin, plasma kallikrein, and coagulation factor XII, oxidative stress system such as lipid peroxide, and superoxide dismutase, inflammation-related factors such as interleukin-1β/6/13/37, and interferon-γ, matrix metalloproteinase (MMP) system such as MMP-9/14. Additionally, we also introduced other DR-related factors such as adiponectin, certain specific amino acids, non-coding RNA and renin (pro) receptor in separate studies.

In this paper, the authors show that sex differences in mitochondrial DNA levels and function in the heart contribute to sex biases in functions relevant to heart failure, identifying Acsl6 as a mitochondrial sex-biased regulator of diastolic function.

Abstract The Chelonid herpesvirus 5 (ChHV5) infection possibly associated to the fibropapillomatosis (FP) disease in sea turtles worldwide remains largely unknown and limited studies have used serological approaches to detection of antibodies against ChHV5 in sea turtles with or without FP. We aimed to develop diagnostic platforms based on the viral glycoprotein B (gB) for ChHV5 infection. In this study, five recombinant sub-fragments of the gB protein were successfully expressed and subsequently served as antigens for both seroprevalence and antibody production. The results indicated that the five expressed proteins harbored antigenicity, shown by the results of using sera from sea turtles that were PCR-positive for ChHV5. Moreover, seropositive sea turtles were significantly associated with FP (p

Objectives: Chronic low back pain (CLBP) accounts for a majority of the disability associated with LBP, which can produce long-term negative effects. This cross-sectional study aimed to investigate the association between smoking and pain, dysfunction and psychological status in patients with CLBP.Methods: The 54 patients with CLBP were recruited and divided into smoking and non-smoking groups. Their pain, dysfunction, anxiety, depression, fear and quality of life were evaluated. The amount of cigarettes smoked daily was recorded.Results: Significant differences in VAS, ODI, RMDQ and FABQ and the impact of LBP on life and work were found between smoking and non-smoking patients. In addition, a correlation was found between the daily cigarette smoking amount and VASmax, FABQtotal, SDS and FABQ-W. Moreover, a correlation was observed between the amount of cigarettes smoked daily and the degree of impact of low back pain on work.Conclusion: The study found that smoking affected the aggravation of symptoms in patients with CLBP, which indicated that patients with CLBP and people at risk of LBP should be aware of the harm caused by smoking.

Building on attribution theory, this study applied regression analysis and explored the double-edged sword effect of leader self-sacrifice behavior on employee work outcomes, thus revealing the potential negative impacts of such behavior. Specifically, when leadership self-sacrifice was met with low employee authenticity attribution, we found that employees tended to perceive leadership as hypocritical, thus reducing their organizational citizenship behavior. By contrast, when leaders’ self-sacrifice behavior was met with high employee authenticity attribution, employees tended to trust the leader and improve their task performance. Given these findings, we challenge the general scholarly consensus on leadership self-sacrifice behavior, enrich the current literature on leadership self-sacrifice, and emphasize the important role of employee attribution in the relevant leadership process.

We aimed to develop and validate a comprehensive ambient air pollution health literacy instrument. We developed items covering 12 constructs, four information competencies within three health domains. In this population-based telephone interview study, probability proportional to size sampling and random digit dialing were used to determine participants. We conducted confirmatory factor analysis to analyze model fits and used content validity indices and Cronbach's alpha to measure content validity and internal consistency reliability. Twenty-four items were generated, and a total of 1,297 participants were recruited. A theoretically conceived 12-factor model was supported (root mean square error of approximation [RMSEA] = 0.068, comparative fit index [CFI] = 0.039, standardized root mean square residual [SRMR] = 0.934, normed fit index [NFI] = 0.914, Tucker-Lewis index [TLI] = 0.902). Content validity indices for relevance, importance, and unambiguity were 0.97, 0.99, and 0.94, respectively. Internal consistency reliability assessed by Cronbach's alpha was 0.93. The ambient air pollution health literacy instrument is valid and reliable and can be used in community residents. The novel instrument can guide the stakeholders and the authority to tailor and implement effective and appropriate interventions and actions, empowering the public to manage hazardous exposure and improving AAPHL of the public.

Abstract Aspiration due to dysphagia can lead to aspiration, which negatively impacts a patient’s overall prognosis. Clinically, videofluoroscopic swallow study (VFSS) is considered the gold-standard instrument to determine physiological impairments of swallowing. According to previously published literature, kinematic analyses of VFSS might provide further information regarding aspiration detection. In this study, 449 files of VFSS studies from 232 patients were divided into three groups: normal, aspiration, and pyriform sinus stasis. Kinematic analyses and between-group comparison were conducted. Significant between-group differences were noted among parameters of anterior hyoid displacement, maximal hyoid displacement, and average velocity of hyoid movement. No significant difference was detected in superior hyoid displacement. Furthermore, receiver-operating characteristic (ROC) analyses of anterior hyoid displacement, velocity of anterior hyoid displacement, and average velocity of maximal hyoid displacement showed acceptable predictability for detecting aspiration. Using 33.0 mm/s as a cutoff value of average velocity of maximal hyoid displacement, the sensitivity of detecting the presence of aspiration was near 90%. The investigators therefore propose that the average velocity of maximal hyoid displacement may serve as a potential screening tool to detect aspiration.

ObjectiveTo implement an all-day online artificial intelligence (AI)-assisted detection of ST-elevation myocardial infarction (STEMI) by prehospital 12-lead electrocardiograms (ECGs) to facilitate patient triage for timely reperfusion therapy.MethodsThe proposed AI model combines a convolutional neural network and long short-term memory (CNN-LSTM) to predict STEMI on prehospital 12-lead ECGs obtained from mini-12-lead ECG devices equipped in ambulance vehicles in Central Taiwan. Emergency medical technicians (EMTs) from the 14 AI-implemented fire stations performed the on-site 12-lead ECG examinations using the mini portable device. The 12-lead ECG signals were transmitted to the AI center of China Medical University Hospital to classify the recordings as “STEMI” or “Not STEMI”. In 11 non-AI fire stations, the ECG data were transmitted to a secure network and read by available on-line emergency physicians. The response time was defined as the time interval between the ECG transmission and ECG interpretation feedback.ResultsBetween July 17, 2021, and March 26, 2022, the AI model classified 362 prehospital 12-lead ECGs obtained from 275 consecutive patients who had called the 119 dispatch centers of fire stations in Central Taiwan for symptoms of chest pain or shortness of breath. The AI's response time to the EMTs in ambulance vehicles was 37.2 ± 11.3 s, which was shorter than the online physicians' response time from 11 other fire stations with no AI implementation (113.2 ± 369.4 s, P < 0.001) after analyzing another set of 335 prehospital 12-lead ECGs. The evaluation metrics including accuracy, precision, specificity, recall, area under the receiver operating characteristic curve, and F1 score to assess the overall AI performance in the remote detection of STEMI were 0.992, 0.889, 0.994, 0.941, 0.997, and 0.914, respectively. During the study period, the AI model promptly identified 10 STEMI patients who underwent primary percutaneous coronary intervention (PPCI) with a median contact-to-door time of 18.5 (IQR: 16–20.8) minutes.ConclusionImplementation of an all-day real-time AI-assisted remote detection of STEMI on prehospital 12-lead ECGs in the field is feasible with a high diagnostic accuracy rate. This approach may help minimize preventable delays in contact-to-treatment times for STEMI patients who require PPCI.

Abstract Objective To investigate the level of and covariates associated with ambient air pollution health literacy (AAPHL) among adult residents of Taiwan. Methods With a cross-sectional study design, we conducted telephone interviews using a Chinese version AAPHL scale, which consisted of 24 items assessing 12 subdomains of AAPHL formed by 4 information processing competence matrices (i.e., access, understand, appraise, and apply) and 3 health contexts (i.e., healthcare, disease prevention, and health promotion). The AAPHL was with the lowest and highest score at 1 to 4, respectively. Between September and November 2020, a sample of 1017 and 280 adults was successfully interviewed via home phones and mobile phones, respectively. We employed multiple linear regression models to identify covariates significantly associated with overall and 4 matric-specific AAPHL scores. Results The mean and standard deviation (±SD) of overall AAPHL score was considered as moderate at 2.90 (±0.56), with the highest and lowest metric-specific score for “apply” (3.07 ± 0.59) and “appraise” (2.75 ± 0.66). Lower education was significantly associated with a lower overall score; and living with children

Abstract Background Primary urethral carcinoma (PUC) is a rare genitourinary malignancy with a relatively poor prognosis. The aim of this study was to examine the impact of surgery on survival of patients diagnosed with PUC. Methods A total of 1544 PUC patients diagnosed between 2004 and 2016 were identified based on the SEER database. The Kaplan-Meier estimate and the Fine and Gray competing risks analysis were performed to assess overall survival (OS) and cancer-specific mortality (CSM). The multivariate Cox regression model and competing risks regression model were used to identify independent risk factors of OS and cancer-specific survival (CSS). Results The 5-yr OS was significantly better in patients who received either local therapy (39.8%) or radical surgery (44.7%) compared to patients receiving no surgery of the primary site (21.5%) (p

Summary: Allo-HSCT is a curative therapy for hematologic malignancies owing to GvL effect mediated by alloreactive T cells; however, the same T cells also mediate GvHD, a severe side effect limiting the widespread application of allo-HSCT in clinics. Invariant natural killer T (iNKT) cells can ameliorate GvHD while preserving GvL effect, but the clinical application of these cells is restricted by their scarcity. Here, we report the successful generation of third-party HSC-engineered human iNKT (3rdHSC-iNKT) cells using a method combining HSC gene engineering and in vitro HSC differentiation. The 3rdHSC-iNKT cells closely resembled the CD4−CD8−/+ subsets of endogenous human iNKT cells in phenotype and functionality. These cells displayed potent anti-GvHD functions by eliminating antigen-presenting myeloid cells in vitro and in xenograft models without negatively impacting tumor eradication by allogeneic T cells in preclinical models of lymphoma and leukemia, supporting 3rdHSC-iNKT cells as a promising off-the-shelf cell therapy candidate for GvHD prophylaxis.

The vacuole is an important organelle with multiple functions in plants, and the tonoplast that wraps the vacuole also plays essential roles in intracellular trafficking and ion homeostasis. Previous studies found that tonoplast proton pumps regulate embryo development and morphogenesis through their effects on vacuole biogenesis and distribution, as well as polar auxin transport and concomitant auxin gradient. However, the precise roles of the tonoplast proton pumps in gametophyte development remain unclear. Here we demonstrated that the lack of two types of tonoplast proton pumps or the absence of V-ATPase alone leads to abnormal development and nuclear localization of female gametophyte (FG), and slowed endosperm nuclei division after fertilization of the central cell. We further revealed that V-ATPase regulates auxin levels in ovules through coordinating the content and localization of PIN-FORMED 1 (PIN1) protein, hence influencing nuclear spacing between centra cell and egg cell, and subsequent endosperm development. Collectively, our findings revealed a crucial role of V-ATPase in auxin-mediated FG development in Arabidopsis and expanded our understanding of the functions of tonoplast proton pumps in seed plants reproductive development.

MAOIs, a well-established class of antidepressant that operate through the inhibition of monoamine oxidase to increase available serotonin, have recently been identified as a surprisingly effective candidate for the circumvention of tumor-induced immune suppression due to their abilities to enhance antitumor T cell activity through autocrine serotonin signaling and depolarize alternatively activated tumor-associated macrophages through a reduction in reactive oxygen species production. However, this impressive class of antidepressants-turned-cancer-drugs can induce aggressive behavioral side effects when administered in immunotherapeutic doses. In this study, we investigated the possibility of avoiding these neurological side effects while simultaneously improving antitumor activity by establishing crosslinked multilamellar liposomal vesicles (cMLVs) containing the MAOI phenelzine (PLZ). Our results showed that cMLV-PLZ treatment increases antitumor efficacy in a B16-OVA mouse melanoma model compared to treatment with free phenelzine. We also found that nanoformulation resulted in the complete elimination of MAOI-related aggression. These findings suggest a promising direction for the future of MAOIs repurposed for cancer immunotherapies.

BackgroundIncreased social distance is one of the manifestations of social impairment. Chronic low back pain (CLBP) is one of factors associated with increased social distance and social withdrawal. Exercise therapy is an effective means to social impairment. However, whether exercise could reduce social distance in patients with CLBP remains unknown. This study aimed to investigate the effect of exercise on social distance in middle-aged and elderly patients with CLBP.MethodsThe longitudinal intervention recruited 29 middle-aged and elderly patients with CLBP from various communities in Yangpu District, Shanghai, China. The participants received exercise intervention for 8 weeks. The assessments were conducted before and after the intervention, including social distance, pain intensity, unpleasantness of pain, Roland-Morris Questionnaire (RMDQ), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS). Intention to treat analysis was performed.ResultsAfter the 8-week exercise intervention, the social distance of patients with CLBP was shorter than that before intervention and showed significant difference (p < 0.05). The scores of pain intensity, unpleasantness of pain, RMDQ, SAS, and SDS also decreased and were significantly different between pre- and post-intervention (p < 0.05). In addition, the social distance, pain intensity, unpleasantness of pain, RMDQ, SAS, and SDS scores of the moderate CLBP group decreased more after the intervention compared with those of the mild CLBP group.ConclusionThe 8-week exercise intervention cannot only shorten the social distance in middle-aged and elderly patients with CLBP but also relieve pain, disability, and negative emotions.

BackgroundAcute ST-elevation myocardial infarction (STEMI) elicits a robust cardiomyocyte death and inflammatory responses despite timely revascularization.ObjectivesThis phase 1, open-label, single-arm, first-in-human study aimed to assess the safety and efficacy of combined intracoronary (IC) and intravenous (IV) transplantation of umbilical cord-derived mesenchymal stem cells (UMSC01) for heart repair in STEMI patients with impaired left ventricular ejection fraction (LVEF 30-49%) following successful reperfusion by percutaneous coronary intervention.MethodsConsenting patients received the first dose of UMSC01 through IC injection 4-5 days after STEMI followed by the second dose of UMSC01 via IV infusion 2 days later. The primary endpoint was occurrence of any treatment-related adverse events and the secondary endpoint was changes of serum biomarkers and heart function by cardiac magnetic resonance imaging during a 12-month follow-up period.ResultsEight patients gave informed consents, of whom six completed the study. None of the subjects experienced treatment-related serious adverse events or major adverse cardiovascular events during IC or IV infusion of UMSC01 and during the follow-up period. The NT-proBNP level decreased (1362 ± 1801 vs. 109 ± 115 pg/mL, p = 0.0313), the LVEF increased (52.67 ± 12.75% vs. 62.47 ± 17.35%, p = 0.0246), and the wall motion score decreased (26.33 ± 5.57 vs. 22.33 ± 5.85, p = 0.0180) at the 12-month follow-up compared to the baseline values. The serial changes of LVEF were 0.67 ± 3.98, 8.09 ± 6.18, 9.04 ± 10.91, and 9.80 ± 7.56 at 1, 3, 6, and 12 months, respectively as compared to the baseline.ConclusionThis pilot study shows that combined IC and IV transplantation of UMSC01 in STEMI patients with impaired LVEF appears to be safe, feasible, and potentially beneficial in improving heart function. Further phase 2 studies are required to explore the effectiveness of dual-route transplantation of UMSC01 in STEMI patients.

Monoamine oxidase A (MAO-A) is an outer mitochondrial membrane-bound enzyme best known for its function in the brain, but also linked to cancer progression. Here, the authors show that MAO-A is expressed in tumor associated macrophages, promoting their immunosuppressive properties, and that MAO inhibition suppresses tumor growth in preclinical models.

In the present study, the complete mitochondrial genome of Pycanum ochraceum was identified for the first time. The entire genome is 17,198 bp in length with 73.6% A + T content. It contains 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), 13 protein-coding genes (PCGs) and 1 noncoding control region (D-loop). Phylogenetic analysis showed that Tessaratomidae bugs are monophyletic. This study can provide essential DNA molecular data for further phylogenetic and evolutionary analysis for Heteroptera.

The research and clinical application of the noninvasive brain stimulation (NIBS) technique in the treatment of neuropathic pain (NP) are increasing. In this review article, we outline the effectiveness and limitations of the NIBS approach in treating common central neuropathic pain (CNP). This article summarizes the research progress of NIBS in the treatment of different CNPs and describes the effects and mechanisms of these methods on different CNPs. Repetitive transcranial magnetic stimulation (rTMS) analgesic research has been relatively mature and applied to a variety of CNP treatments. But the optimal stimulation targets, stimulation intensity, and stimulation time of transcranial direct current stimulation (tDCS) for each type of CNP are still difficult to identify. The analgesic mechanism of rTMS is similar to that of tDCS, both of which change cortical excitability and synaptic plasticity, regulate the release of related neurotransmitters and affect the structural and functional connections of brain regions associated with pain processing and regulation. Some deficiencies are found in current NIBS relevant studies, such as small sample size, difficulty to avoid placebo effect, and insufficient research on analgesia mechanism. Future research should gradually carry out large-scale, multicenter studies to test the stability and reliability of the analgesic effects of NIBS.

Cosmology constraints serve as a crucial criterion in discriminating cosmological models. The traditional combined method to constrain the cosmological parameters designates the corresponding theoretical value and observational data as functions of redshift; however, sometimes the redshift cannot be measured directly, or the measurement error is large, or the definition of redshift is controversial. In this paper, we propose a novel joint method to constrain parameters that eliminates the redshift z and makes full use of the multiple observables $\left\{{{ \mathcal F }}_{1,\mathrm{obs}},{{ \mathcal F }}_{2,\mathrm{obs}},\cdots ,{{ \mathcal F }}_{M,\mathrm{obs}}\right\}$ spanning in M -dimensional joint observable space. Considering the generality of the mathematical form of the cosmological models and the guidance from low to high dimensions, we first validate our method in a 3D joint observable space spanned by H ( z ), f σ _8 ( z ), and D _A ( z ), where the three coordinates can be considered redshift-free measurements of the same celestial body (or shared-redshift data-reconstructed model independently). Our results are consistent with the traditional combined method but with lower errors, yielding H _0 = 68.7 ± 0.1 km s ^−1 Mpc ^−1 , Ω _m _0 = 0.289 ± 0.003, and σ _8 = 0.82 ± 0.01 and showing alleviated parametric degeneracies to some extent. In principle, our joint constraint method allows an extended form keeping the redshift information as an independent coordinate and can also be readily degraded to the form of a traditional combined method to constrain parameters.

The search for extraterrestrial intelligence (SETI) commensal surveys aim to scan the sky to find possible technosignatures from an extraterrestrial intelligence (ETI). The mitigation of radio frequency interference (RFI) is an important step, especially for the most sensitive Five-hundred-meter Aperture Spherical radio Telescope (FAST), which can detect more weak RFI. In this paper, we propose several new techniques for RFI mitigation and use our procedure to search for ETI signals from the archival data of FAST’s first SETI commensal survey. We detect the persistent narrowband RFI by setting a threshold of the signals’ sky separation and detect the drifting RFI (and potentially other types of RFI) using the Hough transform. We also use the clustering algorithms to remove more RFI and select candidates. The results of our procedure are compared to the earlier work on the same FAST data. We find that our methods, though relatively simpler in computation, remove more RFI (99.9912% compared to 99.9063% in the earlier work) but preserve the simulated ETI signals, except for those (5.1%) severely affected by the RFI. We also report more interesting candidate signals, about a dozen of which are new candidates that were not previously reported. In addition, we find that the proposed Hough transform method, with suitable parameters, also has the potential to remove the broadband RFI. We conclude that our methods can effectively remove the vast majority of the RFI while preserving and finding the candidate signals that we are interested in.

The Gaussian process (GP) has gained much attention in cosmology due to its ability to reconstruct cosmological data in a model-independent manner. In this study, we compare two methods for GP kernel selection: approximate Bayesian computation (ABC) rejection and nested sampling. We analyze three types of data: cosmic chronometer data, type Ia supernovae data, and gamma-ray burst data, using five kernel functions. To evaluate the differences between kernel functions, we assess the strength of evidence using Bayes factors. Our results show that, for ABC rejection, the Matérn kernel with ν = 5/2 (M52 kernel) outperformes the commonly used radial basis function (RBF) kernel in approximating all three data sets. Bayes factors indicate that the M52 kernel typically supports the observed data better than the RBF kernel but with no clear advantage over other alternatives. However, nested sampling gives different results, with the M52 kernel losing its advantage. Nevertheless, Bayes factors indicate no significant dependence of the data on each kernel.

Abstract Background Sarcopenia and dysphagia are prevalent health issues as the elderly population continues to grow. However, whether sarcopenia, defined by either reduced handgrip strength or gait speed, would lead to pathological effects on swallowing function is still a matter of debate. Studies focusing on subclinical changes in the swallowing function in the sarcopenic elderly are lacking. This study evaluates the swallowing function in the sarcopenic elderly without dysphagia. Methods: A cross-sectional study was conducted including subjects recruited from the community. Ninety-four individuals aged 65 and older without dysphagia were divided into two groups: sarcopenia and nonsarcopenia. The swallowing assessment included tongue pressure measurement, hyoid displacement (HD), hyoid velocity (HV) measurement with submental ultrasonography, 100-ml water-swallowing test, and the 10-item Eating Assessment Tool (EAT-10). Results The average tongue pressure was 47.0 ± 13.7 and 48.6 ± 11.5 kPa in the sarcopenia and nonsarcopenia groups, respectively (p = 0.55), whereas the average HD during swallowing was 15.3 ± 4.4 and 13.0 ± 4.2 mm in the sarcopenia and nonsarcopenia groups, respectively (p

Atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease, cerebrovascular disease, and peripheral artery disease, carries a high morbidity and mortality. Risk factor control is especially important for patients with ASCVD to reduce recurrent cardiovascular events. Clinical guidelines have been developed by the Taiwan Society of Cardiology, Taiwan Society of Lipids and Atherosclerosis, and Diabetes Association of Republic of China (Taiwan) to assist health care professionals in Taiwan about the control of hypertension, hypercholesterolemia and diabetes mellitus. This article is to highlight the recommendations about blood pressure, cholesterol, and sugar control for ASCVD. Some medications that are beneficial for ASCVD were also reviewed. We hope the clinical outcomes of ASCVD can be improved in Taiwan through the implementation of these recommendations. Keywords: Atherosclerosis, Risk factors, Performance guide

Abstract Background Pelvic lymphadenectomy (PLND) is an integral part of curative surgery for high-risk non-muscle invasive and muscle-invasive bladder cancer. The therapeutic value of extended PLND is controversial. Methods We conducted a comprehensive online search in PubMed, EMBASE, and the Cochrane Library databases for relevant literature directly comparing extended PLND (e-PLND) with non-extended PLND (ne-PLND) from database inception to June 2019. We performed the meta-analysis to evaluate the impact of PLND templates on recurrence-free survival (RFS), disease-specific survival (DSS), overall survival (OS), rates of postoperative major complications, and mortality within 90 days of surgery. Results A total of 10 studies involving 3979 patients undergoing either e-PLND or ne-PLND were included. The results showed that e-PLND was significantly associated with better RFS (HR 0.74, 95% CI 0.62–0.90, p = 0.002) and DSS (HR 0.66, 95% CI 0.55–0.79, p < 0.001). However, no correlation was found between e-PLND template and a better OS (HR 0.93, 95% CI 0.55–1.58, p = 0.79). Postoperative major complications were similar between e-PLND group and ne-PLND group, as was mortality within 90 days of surgery. Conclusion e-PLND template is correlated with favorable RFS and DSS outcomes for patients with bladder cancer. e-PLND did not have more postoperative major complications than did ne-PLND.

Summary: Cell-based immunotherapy has become the new-generation cancer medicine, and “off-the-shelf” cell products that can be manufactured at large scale and distributed readily to treat patients are necessary. Invariant natural killer T (iNKT) cells are ideal cell carriers for developing allogeneic cell therapy because they are powerful immune cells targeting cancers without graft-versus-host disease (GvHD) risk. However, healthy donor blood contains extremely low numbers of endogenous iNKT cells. Here, by combining hematopoietic stem cell (HSC) gene engineering and in vitro differentiation, we generate human allogeneic HSC-engineered iNKT (AlloHSC-iNKT) cells at high yield and purity; these cells closely resemble endogenous iNKT cells, effectively target tumor cells using multiple mechanisms, and exhibit high safety and low immunogenicity. These cells can be further engineered with chimeric antigen receptor (CAR) to enhance tumor targeting or/and gene edited to ablate surface human leukocyte antigen (HLA) molecules and further reduce immunogenicity. Collectively, these preclinical studies demonstrate the feasibility and cancer therapy potential of AlloHSC-iNKT cell products and lay a foundation for their translational and clinical development.

Purpose: This study aimed to investigate the prognostic factors of patients with lymphoepithelioma-like carcinoma of the urinary bladder (LELCB) and explore the value of surgical treatment.Methods: Data of patients with LELCB were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The multivariate analysis was performed using the stepwise Cox proportional hazards regression model and conditional inference tree method to identify significant prognosticators of overall survival (OS) from the parameters such as age, gender, lymph node involvement, tumor extent, radiation, chemotherapy, and surgery type. Literature review (LR) was performed, and eligible cases were used to validate prognostic classification using the Kaplan–Meier method with log-rank tests.Results: Sixty patients with a median age of 69.5 years were identified from the SEER database and 91 patients through LR. The Cox analysis identified age, gender, lymph node involvement, and surgical approach as independent prognosticators of OS. Based on the nomogram scores, patients were stratified into three prognostic groups: (I) patients younger than 70 years; (II) patients older than 70 years, who received bladder-sparing therapy (BST); and (III) patients older than 70 years undergoing radical cystectomy (RC). Patients in group II had the worst outcomes in terms of OS compared with patients in groups I and III (p < 0.001 and p = 0.03, respectively). A similar survival pattern was found in the LR cohort.Conclusion: The nomogram provided individualized prognostic quantification of OS in patients with LELCB. BST could yield favorable outcomes when treating LELCB, especially for younger patients, whereas older patients might derive more survival benefit from RC.

BackgroundSomatosensory impairments and pain are common symptoms following stroke. However, the condition of perception and pain threshold for pressure stimuli and the factors that can influence this in individuals with stroke are still unclear. This study aimed to investigate the gender differences in pressure pain threshold (PPT) and positive somatosensory signs for pressure stimuli, and explore the effects of joint pain, motor function, and activities of daily living (ADL) on pain threshold in post-stroke patients.DesignA cross-sectional study.MethodsA total of 60 participants with stroke were recruited, and their pain condition, motor functions, and ADL were evaluated by the Fugl-Meyer assessment of joint pain scale, motor function scale, and Barthel index, respectively. PPTs in eight tested points at the affected and unaffected sides were assessed.ResultsSignificant differences in PPTs were found between male and female patients in all measured muscles (p < 0.05). Positive somatosensory signs for pressure stimuli, including hypoalgesia and hyperalgesia, were frequently found at the affected side, particularly in the extremity muscles, but such signs were not significantly influenced by gender (p > 0.05). More equal PPTs between both sides and relatively lower PPTs at the affected side in the trunk and medial gastrocnemius muscles (p < 0.05) were observed in patients with less pain, better motor functions, and ADL.ConclusionGender differences widely exist in post-stroke survivors either at the affected or unaffected side, which are multifactorial. Sensory loss and central and/or peripheral sensitization, such as hypoalgesia and hyperalgesia for pressure stimuli, caused by a brain lesion are common signs in male and female stroke patients. Moreover, patients who are in a better condition show a more symmetrical pain sensitivity between both sides in the trunk and in female lower extremities, indicating the bidirectional improvement of somatosensory abnormalities caused by a possible neural plasticity.

With the rapid development of information technology and widespread use of the Internet of Things, machine intelligence will undoubtedly emerge as a leading research topic in the future. The main purpose of the present research is to incorporate an image recognition system into a robotic arm motion to achieve automatic classification. First, we upload captured images to a PC for classification process and use chess patterns to conduct a sampling test. Next, when the system identifies these patterns as proper chess patterns, the robotic arm grabs the objects and moves them to designated locations. The project is divided into two main sections: image recognition and robotic arm motion. In the image recognition section, we use Keras and the Tensorflow open source learning machine to build a convolutional neural network model. Then, we use a learning model network that is a considerably more compact variant of the VGGNet network in the image recognition system. With this model, we achieve a recognition accuracy of 95%. In the robotic arm section, we use a five-axis robotic arm and an Arduino Uno board as the controller. We design the Denavit–Hartenberg parameters of the arm and calculate the direct (inverse) kinematics parameters to plan its trajectory. Thereafter, we use MATLAB software to simulate prototype processes, such as grabbing, moving, and placing. Finally, we import the program into the controller so that the robotic arm can execute classification based on the chess pattern.

BackgroundThis study aimed to assess the prognostic value of various diagnostic immunohistochemical (IHC) markers and develop an IHC-based classifier to predict the disease-free survival (DFS) of patients with bladder cancer undergoing radical cystectomy.MethodsIHC was performed on tumor specimens from 366 patients with transitional cell bladder cancer. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to develop a multi-marker classifier for predicting DFS of patients with bladder cancer. The Kaplan–Meier estimate was performed to assess DFS, and unadjusted and adjusted Cox regression models were used to identify independent risk factors to predict DFS of patients with bladder cancer.ResultsBased on the LASSO Cox regression model, nine prognostic markers were identified in the training cohort. Patients were stratified into low- and high-risk groups using the IHC-based classifier. In the training cohort, the 10-year DFS was significantly better in low-risk patients (71%) compared with high-risk patients (18%) (p < 0.001); in the validation cohort, the 10-year DFS was 86% for the low-risk group and 20% for the high-risk group (p < 0.001). Multivariable Cox regression analyses showed that the high-risk group based on the classifier was associated with poorer DFS adjusted by clinicopathological characteristics. Finally, a nomogram comprising the classifier and clinicopathological factors was developed for clinical application.ConclusionThe nine-IHC-based classifier is a reliable prognostic tool, which can eventually guide clinical decision making regarding treatment strategy and follow-up scheduling of bladder cancer.

The unique characteristics of patients with acute coronary syndrome in the Asia-Pacific region mean that international guidelines on the use of dual antiplatelet therapy (DAPT) cannot be routinely applied to these populations. Newer generation P2Y12 inhibitors (i.e. ticagrelor and prasugrel) have demonstrated improved clinical outcomes compared with clopidogrel. However, low numbers of Asian patients participated in pivotal studies and few regional studies comparing DAPTs have been conducted. This article aims to summarise current evidence on the use of newer generation P2Y12 inhibitors in Asian patients with acute coronary syndrome and provide recommendations to assist clinicians, especially cardiologists, in selecting a DAPT regimen. Guidance is provided on the management of ischaemic and bleeding risks, including duration of therapy, switching strategies and the management of patients with ST-elevation and non-ST-elevation MI or those requiring surgery. In particular, the need for an individualised DAPT regimen and considerations relating to switching, de-escalating, stopping or continuing DAPT beyond 12 months are discussed.

Background: Of patients with upper urinary tract urothelial carcinoma (UTUC), 22–47% developed bladder recurrence after radical nephroureterectomy. Furthermore, the effect of surgery for UTUC-bladder cancer (BC) has not been well validated. The aim of this study was to assess the impact of standard primary BC surgical strategy on survival of patients diagnosed with UTUC-BC.Patients and Methods: A total of 676 UTUC-BC patients and 197,753 primary BC patients diagnosed from 2004 to 2016, were identified based on the SEER database. The Kaplan-Meier method and the Fine and Gray competing risks analysis were performed to assess overall survival (OS) and cancer-specific mortality (CSM). Multivariate Cox regression model and competing risks regression model were used to identify independent risk factors. Propensity score matching (PSM) was also performed to adjust potential confounding factors.Results: The baseline characteristics and survival outcomes of the two BC patient cohorts are quite different. For UTUC-BC patients, no significant difference in OS (NMIBC: p = 0.88; MIBC: p = 0.98) or cumulative incidence of CSM (NMIBC: p = 0.12; MIBC: p = 0.96) were noted for various surgical procedures. Local tumor treatment and partial cystectomy for UTUC-NMIBC patients produced lower 1-year (6.1%) and 3-year CSM (16.2%). Radical cystectomy for UTUC-MIBC patients produced lower 1-year (11.8%) but higher 3-year CSM (62.7%). After PSM for covariates, UTUC-BC patients still had a worse prognosis after surgery compared with primary BC patients. Based on regression models, older age, advanced T stage, N positive disease, M positive disease, and shorter interval between UTUC and BC were identified as independent risk factors for UTUC-BC patients.Conclusion: Standard primary BC surgical strategy did not provide significant survival benefit for UTUC-BC patients. Compared with primary BC patients, UTUC-BC patients had a worse prognosis after surgery, suggesting that current primary BC surgical guidelines are not entirely appropriate for UTUC-BC patients. Our findings underscore the continued importance and need for better prognosis and improved guidelines for management of UTUC-BC patients.

Extrapulmonary manifestations of COVID-19 are associated with a much higher mortality rate than pulmonary manifestations. However, little is known about the pathogenesis of systemic complications of COVID-19. Here, we create a murine model of SARS-CoV-2–induced severe systemic toxicity and multiorgan involvement by expressing the human ACE2 transgene in multiple tissues via viral delivery, followed by systemic administration of SARS-CoV-2. The animals develop a profound phenotype within 7 days with severe weight loss, morbidity, and failure to thrive. We demonstrate that there is metabolic suppression of oxidative phosphorylation and the tricarboxylic acid (TCA) cycle in multiple organs with neutrophilia, lymphopenia, and splenic atrophy, mirroring human COVID-19 phenotypes. Animals had a significantly lower heart rate, and electron microscopy demonstrated myofibrillar disarray and myocardial edema, a common pathogenic cardiac phenotype in human COVID-19. We performed metabolomic profiling of peripheral blood and identified a panel of TCA cycle metabolites that served as biomarkers of depressed oxidative phosphorylation. Finally, we observed that SARS-CoV-2 induces epigenetic changes of DNA methylation, which affects expression of immune response genes and could, in part, contribute to COVID-19 pathogenesis. Our model suggests that SARS-CoV-2–induced metabolic reprogramming and epigenetic changes in internal organs could contribute to systemic toxicity and lethality in COVID-19.

Measuring high energy cosmic ray electrons/positrons (CRE) provides important means for the dark matter (DM) indirect detection and for probing the nearby galactic sources. In this work, we perform a systematic analysis of the flavor structure of DM annihilations into charged leptons based on the cosmic ray CRE spectra measured by DAMPE, Fermi-LAT, AMS-02, and CALET experiments. We study the annihilations of possible TeV scale DM particles in a nearby subhalo, which is proposed to explain the possible peak-like structure of the DAMPE CRE data. We pay special attention to the possible non-resonant excess (besides the possible peak-like structure) and demonstrate that such non-resonant excess can mainly arise from the decay of muons produced by the DM annihilations in the subhalo. With these we study the flavor composition of the lepton final states from DM annihilations χχ→e+e−,μ+μ−,τ+τ− by fitting the CRE data. We demonstrate that decays of the final states μ+μ− and τ+τ− can provide the non-resonant excess, while the peak excess arises from the e+e− final state. We further analyze the constraints on the lepton flavor composition using the Fermi-LAT γ-ray measurements. We find that the flavor composition is consistent with the Fermi-LAT data at relatively low Galactic latitudes, while the fraction of the final state τ± is severely bounded.

Background The circulating level of soluble lectin‐like oxidized low‐density lipoprotein receptor‐1 (sLOX‐1) is a valuable biomarker of acute myocardial infarction (AMI). The most electronegative low‐density lipoprotein, L5, signals through LOX‐1 to trigger atherogenesis. We examined the characteristics of LOX‐1 and the role of L5 in aspirated coronary thrombi of AMI patients. Methods and Results Intracoronary thrombi were aspirated by performing interventional thrombosuction in patients with ST‐segment–elevation myocardial infarction (STEMI; n=32) or non–ST‐segment–elevation myocardial infarction (n=12). LOX‐1 level and the ratio of sLOX‐1 to membrane‐bound LOX‐1 were higher in thrombi of STEMI patients than in those of non–ST‐segment–elevation myocardial infarction patients. In all aspirated thrombi, LOX‐1 colocalized with apoB100. When we explored the role of L5 in AMI, deconvolution microscopy showed that particles of L5 but not L1 (the least electronegative low‐density lipoprotein) quickly formed aggregates prone to retention in thrombi. Treating human monocytic THP‐1 cells with L5 or L1 showed that L5 induced cellular adhesion and promoted the differentiation of monocytes into macrophages in a dose‐dependent manner. In a second cohort of AMI patients, the L5 percentage and plasma concentration of sLOX‐1 were higher in STEMI patients (n=33) than in non–ST‐segment–elevation myocardial infarction patients (n=25), and sLOX‐1 level positively correlated with L5 level in AMI patients. Conclusions The level of LOX‐1 and the ratio of sLOX‐1 to membrane‐bound LOX‐1 in aspirated thrombi, as well as the circulating level of sLOX‐1 were higher in STEMI patients than in non–ST‐segment–elevation myocardial infarction patients. L5 may play a role in releasing a high level of sLOX‐1 into the circulation of STEMI patients.