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Abstract Vascular calcification (VC) arises from the accumulation of calcium salts in the intimal or tunica media layer of the aorta, contributing to higher risk of cardiovascular events and mortality. Despite this, the mechanisms driving VC remain incompletely understood. We previously described that nesfatin-1 functioned as a switch for vascular smooth muscle cells (VSMCs) plasticity in hypertension and neointimal hyperplasia. In this study, we sought to investigate the role and mechanism of nesfatin-1 in VC. The expression of nesfatin-1 was measured in calcified VSMCs and aortas, as well as in patients. Loss- and gain-of-function experiments were evaluated the roles of nesfatin-1 in VC pathogenesis. The transcription activation of nesfatin-1 was detected using a mass spectrometry. We found higher levels of nesfatin-1 in both calcified VSMCs and aortas, as well as in patients with coronary calcification. Loss-of-function and gain-of-function experiments revealed that nesfatin-1 was a key regulator of VC by facilitating the osteogenic transformation of VSMCs. Mechanistically, nesfatin-1 promoted the de-ubiquitination and stability of BMP-2 via inhibiting the E3 ligase SYTL4, and the interaction of nesfatin-1 with BMP-2 potentiated BMP-2 signaling and induced phosphorylation of Smad, followed by HDAC4 phosphorylation and nuclear exclusion. The dissociation of HDAC4 from RUNX2 elicited RUNX2 acetylation and subsequent nuclear translocation, leading to the transcription upregulation of OPN, a critical player in VC. From a small library of natural compounds, we identified that Curculigoside and Chebulagic acid reduced VC development via binding to and inhibiting nesfatin-1. Eventually, we designed a mass spectrometry-based DNA-protein interaction screening to identify that STAT3 mediated the transcription activation of nesfatin-1 in the context of VC. Overall, our study demonstrates that nesfatin-1 enhances BMP-2 signaling by inhibiting the E3 ligase SYTL4, thereby stabilizing BMP-2 and facilitating the downstream phosphorylation of SMAD1/5/9 and HDAC4. This signaling cascade leads to RUNX2 activation and the transcriptional upregulation of MSX2, driving VC. These insights position nesfatin-1 as a potential therapeutic target for preventing or treating VC, advancing our understanding of the molecular mechanisms underlying this critical cardiovascular condition.

Abstract Translational control plays a crucial role in the regulation of apoptosis, with the EIF4 family serving as one of the mRNA translation factors that modulate the process of mRNA translation based on mRNA characteristics. To address this potential causal role of EIF4 family proteins and breast cancer, Mendelian randomization was employed. The study incorporated four sets of genetics instrumental variables, namely EIF4E, EIF4B, EIF4A, and EIF4EBP2. The outcome variables selected for analysis were the BCAC consortium, which included estrogen receptor positive (ER+) and estrogen receptor negative (ER−) samples. To assess the potential violations of the MR assumption, the primary MR analysis employed inverse variance weighted (IVW), and several sensitivity analyses were conducted. The findings of the two-sample MR analysis indicate that EIF4E has an adverse effect on breast cancer risk (p = 0.028). However, the evidence for the relationship between EIF4E and ER status of breast cancer suggests a weak association with ER+ breast cancer (p = 0.054), but not with ER- breast cancer (p > 0.05). The study findings indicate that EIF4A is not causally linked to the risk of ER+ breast cancer, but is significantly associated with an elevated risk of ER− breast cancer (p = 0.028). However, the evidence is inadequate to support the effects of EIF4B and EIF4EBP2 on breast cancer (p > 0.05). Our results suggest that EIF4 may be a potential factor in the occurrence and development of breast cancer, which may lead to a better understanding of its causes and prevention.

Abstract Stroke is one of the major causes of death worldwide, and is closely associated with atherosclerosis of the carotid artery. Panoramic radiographs (PRs) are routinely used in dental practice, and can be used to visualize carotid artery calcification (CAC). The purpose of this study was to automatically and robustly classify and segment CACs with large variations in size, shape, and location, and those overlapping with anatomical structures based on deep learning analysis of PRs. We developed a cascaded deep learning network (CACSNet) consisting of classification and segmentation networks for CACs on PRs. This network was trained on ground truth data accurately determined with reference to CT images using the Tversky loss function with optimized weights by balancing between precision and recall. CACSNet with EfficientNet-B4 achieved an AUC of 0.996, accuracy of 0.985, sensitivity of 0.980, and specificity of 0.988 in classification for normal or abnormal PRs. Segmentation performances for CAC lesions were 0.595 for the Jaccard index, 0.722 for the Dice similarity coefficient, 0.749 for precision, and 0.756 for recall. Our network demonstrated superior classification performance to previous methods based on PRs, and had comparable segmentation performance to studies based on other imaging modalities. Therefore, CACSNet can be used for robust classification and segmentation of CAC lesions that are morphologically variable and overlap with surrounding structures over the entire posterior inferior region of the mandibular angle on PRs.

Abstract Sex determination is essential for identifying unidentified individuals, particularly in forensic contexts. Traditional methods for sex determination involve manual measurements of skeletal features on CBCT scans. However, these manual measurements are labor-intensive, time-consuming, and error-prone. The purpose of this study was to automatically and accurately determine sex on a CBCT scan using a two-stage anatomy-guided attention network (SDetNet). SDetNet consisted of a 2D frontal sinus segmentation network (FSNet) and a 3D anatomy-guided attention network (SDNet). FSNet segmented frontal sinus regions in the CBCT images and extracted regions of interest (ROIs) near them. Then, the ROIs were fed into SDNet to predict sex accurately. To improve sex determination performance, we proposed multi-channel inputs (MSIs) and an anatomy-guided attention module (AGAM), which encouraged SDetNet to learn differences in the anatomical context of the frontal sinus between males and females. SDetNet showed superior sex determination performance in the area under the receiver operating characteristic curve, accuracy, Brier score, and specificity compared with the other 3D CNNs. Moreover, the results of ablation studies showed a notable improvement in sex determination with the embedding of both MSI and AGAM. Consequently, SDetNet demonstrated automatic and accurate sex determination by learning the anatomical context information of the frontal sinus on CBCT scans.

Abstract Clarifying the relationship between the man–machine environment and its impact on the tunnel wall drilling task performance (TWDTP) is crucial for enhancing the task performance. Based on a questionnaire survey, indicators of the man–machine environment that affect the TWDTP were proposed in this study, and exploratory factor analysis and a structural equation model were employed to examine the potential factors influencing the task performance and their degrees of influence. By comparing the discrepancy between the perceived performance and importance, the satisfaction of potential factors was evaluated, and the priority order for optimizing these factors was determined by considering the degree of influence and dissatisfaction. The results of survey data analysis based on actual tunnel drilling operation scenarios indicated that tools had the greatest impact on the TWDTP, followed by the quality of the physical environment, while human factors had the least influence on the task performance. Convenient functional maintenance is the key to improving the TWDTP, along with enhancing the quality of the working environment. Once these main aspects are optimized, it is important to consider additional factors such as availability of spare tools, efficient personnel organization, man–tool matching, and safety and health assurance. This research approach provides significant guidance in understanding the relationships between the man–machine environmental factors affecting the performance of complex engineering tasks and identifying key influencing factors, thus providing essential insights for optimizing the TWDTP.

Abstract There is a lack of studies that concurrently differentiate the effect of the holiday season from the weekend effect on mortality risk in patients with acute myocardial infarction (AMI). We evaluated the mortality risk among patients admitted with AMI who underwent percutaneous coronary intervention, using data from the Taiwan National Health Insurance Research Database. Adult AMI patients admitted during January and February between 2013 and 2020 were enrolled and classified into the holiday season (using the Chinese New Year holiday seasons as an indicator) (n = 1729), weekend (n = 4725), and weekday (n = 14,583) groups according to the first day of admission. A multivariable logistic regression model was used to assess the risk. With the weekday group or the weekend group as the reference, the holiday season group did not have increased risks of in-hospital mortality (adjusted odds ratio [aOR] 1.15; 95% confidence intervals [CI] 0.93–1.42 or aOR 1.23; 95% CI 0.96–1.56) and 7-day mortality (aOR 1.20; 95% CI 0.90–1.58 or aOR 1.24; 95% CI 0.90–1.70). Stratified and subgroup analyses showed similar trends. We conclude that holiday season-initiated admissions were not associated with higher mortality risks in AMI admission cases than weekday or weekend admissions.

Abstract Medication-related osteonecrosis of the jaw (MRONJ) poses a challenging form of osteomyelitis in patients undergoing antiresorptive therapies in contrast to conventional osteomyelitis. This study aimed to compare the clinical and radiological features of MRONJ between patients receiving low-dose medications for osteoporosis and those receiving high-dose medications for oncologic purposes. The clinical, panoramic radiographic, and computed tomography data of 159 patients with MRONJ (osteoporotic group, n = 120; oncologic group, n = 39) who developed the condition after using antiresorptive medications for the management of osteoporosis or bone malignancy were analyzed. The osteoporotic group was older (75.8 vs. 60.4 years, p

Abstract Background Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. Methods Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. Results Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. Conclusions Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.

Abstract This study investigated the impact of subway car interior design on passenger evacuation and boarding/alighting efficiency. The usability of pedestrian agent models was verified through real-life experiments. A seven-factor orthogonal simulation experiment was designed, using key geometric features of the subway car interior as variables. The results of the computer simulation showed that the impact of subway car interior design factors on evacuation and boarding/alighting time was not entirely consistent, with seat layout and door width being the most important factors affecting passenger movement. In the evacuation scenario, only the connectivity of the subway car has no effect on evacuation time, while in the boarding and alighting scenario, seat layout, car type, door width, and foyer width all significantly affect boarding and alighting time. Multivariate regression models were established to predict evacuation and boarding/alighting times through design features, which can explain 86.7% and 58.9% of the time variation, respectively. The research results were used to guide subway car design, and the proposed new scheme demonstrated better performance.

The Chinese caterpillar mushroom, Ophiocordyceps sinensis (O. sinensis), is a rarely medicinal fungus in traditional chinese herbal medicine due to its unique medicinal values, and the expression stability of reference genes is essential to normalize its gene expression analysis. In this study, BestKeeper, NormFinder and geNorm, three authoritative statistical arithmetics, were applied to evaluate the expression stability of sixteen candidate reference genes (CRGs) in O. sinensis under different stress [low temperature (4°C), light treatment (300 lx), NaCl (3.8%)] and different development stages (mycelia, primordia and fruit bodies) and formation of morphologic mycelium (aeriasubstrate, hyphae knot mycelium). The paired variation values indicated that two genes could be enough to accurate standardization exposed to different conditions of O.sinensis. Among these sixteen CRGs, 18S ribosomal RNA (18S rRNA) and beta-Tubulin (β-TUB) showed the topmost expression stability in O.sinensis exposed to all conditions, while glutathione hydrolase proenzym (GGT) and Phosphoglucose isomerase (PGI) showed the least expression stability. The optimal reference gene in different conditions was various. β-TUB and Ubiquitin (UBQ) were identified as the two most stable genes in different primordia developmental stage, while phosphoglucomutase (PGM) with elongation factor 1-alpha (EF1-α) and 18S rRNA with UBQ were the most stably expressed for differentially morphologic mycelium stages and different stresses, respectively. These results will contribute to more accurate evaluation of the gene relative expression levels in O.sinensis under different conditions using the optimal reference gene in real-time quantitative PCR (RT-qPCR) analysis.

Heart failure (HF) is a complicated clinical syndrome caused by abnormal cardiac structure and/or function, leading to ventricular filling and/or ejection dysfunction. Pyroptosis is a newly identified form of programmed cell death often accompanied by inflammation during HF. The NLRP3 inflammasome, acting as a caspase-1 activation platform, plays a critical role in the production of key pro-inflammatory cytokines and pyroptosis. Therefore, cell death and inflammasomes are involved in the pathophysiological process of HF. Our paper will review the latest research progress on the relationship among pyroptosis, inflammasomes, and HF.

Abstract The Indian and Pacific Oceans surround the Maritime Continent (MC). Major modes of sea surface temperature variability in both oceans, including the Indian Ocean Dipole (IOD) and El Niño–Southern Oscillation (ENSO), can strongly affect precipitation on the MC. The prevalence of fires in the MC is closely associated with precipitation amount and terrestrial water storage in September and October. Precipitation and terrestrial water storage, which is a measurement of hydrological drought conditions, are significantly modulated by Indian Ocean Dipole (IOD) and El Niño events. We utilize long-term datasets to study the combined effects of ENSO and the IOD on MC precipitation during the past 100 years (1900–2019) and find that the reductions in MC precipitation and terrestrial water storage are more pronounced during years when El Niño and a positive phase of the IOD (pIOD) coincided. The combined negative effects are produced mainly through an enhanced reduction of upward motion over the MC. Coincident El Niño-pIOD events have occurred more frequently after 1965. However, climate models do not project a higher occurrence of coincident El Niño-pIOD events in a severely warming condition, implying that not the global warming but the natural variability might be the leading cause of this phenomenon.

Abstract This study investigated the impact of experience on the visual behavior and driving performance of high-speed train drivers, and explored the correlation between visual behavior and driving performance. Through a simulated driving task, eye movement data and operating data of novice drivers, trainee drivers, and experienced drivers in the traction stage, normal operation process stage, and braking stage were collected. Variance and linear regression were used to analyze the difference and correlation between indicators. The results show that experience could change the driver’s information collection method from long fixation to multi-frequency. Experience also increased the consistency of group operations and reduced the likelihood of hazard occurrences. Therefore, driving performance can be improved by reducing the average fixation duration of information through interface optimization.

Abstract We aimed to determine whether hospital admissions during an extended holiday period (Chinese New Year) and weekends were associated with increased mortality risk from pulmonary embolism (PE), compared to admissions on weekdays. We conducted a nationwide retrospective cohort study using Taiwan’s National Health Insurance Research Database. Data of newly diagnosed PEs during the months of January and February from 2001 to 2017 were obtained from patient records and classified into three admission groups: Chinese New Year (≥ 4 consecutive holiday days), weekends, and weekdays. The adjusted odds ratios (aORs) (95% confidence intervals [CIs]) for 7-day and in-hospital mortality were calculated using multivariable logistic regression models. The 7-day and in-hospital mortality risks were higher for patients admitted during the Chinese New Year holiday (10.6% and 18.7%) compared to those admitted on weekends (8.4% and 16.1%) and weekdays (6.6% and 13.8%). These higher mortality risks for holiday admissions compared to weekday admissions were confirmed by multivariable analysis (7-day mortality: aOR = 1.68, 95% CI 1.15–2.44, P = 0.007; in-hospital mortality: aOR = 1.41, 95% CI 1.05–1.90, P = 0.022), with no subgroup effects by sex or age. Hospital admission for PE over an extended holiday period, namely Chinese New Year, was associated with an increased risk of mortality.

Introduction Fracture is a disease with a high incidence worldwide. Foot and ankle fractures are common among fractures of the lower extremities. Foot and ankle fractures usually require surgical fixation and a period of fixed treatment, which can lead to decreased bone density. Although transcutaneous electrical acupoint stimulation (TEAS) is widely used for movement system diseases, there is minimal evidence to show the effectiveness of TEAS on patients after surgical fixation of ankle and foot fractures. This trial aims to evaluate whether TEAS can reduce bone loss in patients with immobilisation after ankle and foot fractures.Methods and analysis A randomised controlled trial will be conducted in which 60 patients will be randomly divided into two groups: (a) the control group will be treated according to the routine procedures of basic orthopaedics treatment; (b) in the treatment group, bilateral SP36, BL23 and ST36 will be performed on the basis of the control group, and the test will be performed for 30 min every other day for a total of 8 weeks. Bone turnover markers will be used as primary outcome. Secondary outcomes are composed of blood phosphorus, blood calcium and bone mineral density. Treatment safety will be monitored and recorded.Ethics and dissemination This trial is approved by the Ethics Committee of Beijing University of Chinese Medicine (2020BZYLL0611) and the Ethics Committee of Beijing Luhe Hospital (2020-LHKY-055-02), and inpatients who meet the following diagnostic and inclusion criteria are eligible to participate in this study.Trial registration number ChiCTR 2000039944.

Objectives To assess participants’ satisfaction with and predictors of upper gastrointestinal cancer screening in rural areas.Design Cross-sectional study.Setting Ten screening centres in seven cities across five provinces in China.Participants Of the 452 participants screened during the survey period, 438 completed the survey (response rate: 96.90%).Primary outcome measures Screening satisfaction was the primary outcome and it was assessed using the Patient Satisfaction Questionnaire-18. Ordinal logistic regression analysis was used to analyse the predictors of satisfaction.Results The percentages of satisfaction with the General Satisfaction, Technical Quality, Interpersonal Manner, Communication, Financial Aspects, Time Spent With Doctor, and Convenience and Accessibility dimensions were 95.89%, 79.68%, 88.36%, 83.56%, 75.11%, 82.19% and 66.44%, respectively. Education (OR 0.25, 95% CI 0.07 to 0.90), health self-assessment (OR 15.29, 95% CI 2.86 to 81.78) and family history of cancer (OR 4.20, 95% CI 1.29 to 13.71) were associated with General Satisfaction. Residence (OR 4.31, 95% CI 1.89 to 9.81) was associated with Technical Quality. Occupation (OR 0.27, 95% CI 0.08 to 0.88), health self-assessment (OR 11.30, 95% CI 3.94 to 32.43), screening purpose (OR 0.18, 95% CI 0.03 to 0.92) and distance from the screening centre (OR 4.59, 95% CI 1.35 to 15.61) were associated with interpersonal manner. Gender (OR 1.85, 95% CI 1.02 to 3.34), residence (OR 3.23, 95% CI 1.23 to 8.53) and endoscopy in the previous year (OR 2.79, 95% CI 1.13 to 6.90) were associated with Communication. Body mass index (BMI; OR 5.06, 95% CI 1.40 to 18.25) and health self-assessment (OR 2.09, 95% CI 1.12 to 3.88) were associated with financial aspects. Gender (OR 1.90, 95% CI 1.07 to 3.38), residence (OR 3.19, 95% CI 1.30 to 7.79), BMI (OR 5.26, 95% CI 1.14 to 24.34) and health self-assessment (OR 2.14, 95% CI 1.06 to 4.34) were associated with time spent with doctor. Gender (OR 1.64, 95% CI 1.04 to 2.60) and residence (OR 3.17, 95% CI 1.46 to 6.88) were associated with convenience and accessibility.Conclusion There was heterogeneity across the dimensions of satisfaction with rural upper gastrointestinal cancer screening. Project manager should prioritise improving the aspects related to the convenience and accessibility dimension. Furthermore, to improve the efficiency of potential interventions, the predictors of the various dimensions should be considered.

Abstract The purpose of this study was to directly and quantitatively measure BMD from Cone-beam CT (CBCT) images by enhancing the linearity and uniformity of the bone intensities based on a hybrid deep-learning model (QCBCT-NET) of combining the generative adversarial network (Cycle-GAN) and U-Net, and to compare the bone images enhanced by the QCBCT-NET with those by Cycle-GAN and U-Net. We used two phantoms of human skulls encased in acrylic, one for the training and validation datasets, and the other for the test dataset. We proposed the QCBCT-NET consisting of Cycle-GAN with residual blocks and a multi-channel U-Net using paired training data of quantitative CT (QCT) and CBCT images. The BMD images produced by QCBCT-NET significantly outperformed the images produced by the Cycle-GAN or the U-Net in mean absolute difference (MAD), peak signal to noise ratio (PSNR), normalized cross-correlation (NCC), structural similarity (SSIM), and linearity when compared to the original QCT image. The QCBCT-NET improved the contrast of the bone images by reflecting the original BMD distribution of the QCT image locally using the Cycle-GAN, and also spatial uniformity of the bone images by globally suppressing image artifacts and noise using the two-channel U-Net. The QCBCT-NET substantially enhanced the linearity, uniformity, and contrast as well as the anatomical and quantitative accuracy of the bone images, and demonstrated more accuracy than the Cycle-GAN and the U-Net for quantitatively measuring BMD in CBCT.

Abstract Patients with hepatocellular carcinoma (HCC) might be more vulnerable to develop stroke than other cancer patients because of HCC-associated coagulation dysfunction. However, limited studies have investigated the relationship between HCC and stroke. This nationwide population-based cohort study enrolled all patients with HCC diagnosed between 2011 and 2015 from the Taiwan Cancer Registry and Taiwan National Health Insurance Research Database; an age- and sex-matched cohort without cancer was included. The primary outcome was the 1-year risk for first-ever stroke after the index date. The Fine and Gray competing risk regression model was used to estimate the 1-year stroke risk with adjusted hazard ratios (aHRs). After propensity score matching, each cohort has 18,506 patients with similar baseline characteristics. Compared with the cancer-free cohort, the aHRs in the HCC cohort for overall, ischemic, and hemorrhagic strokes were 1.59 [95% confidence interval (CI), 1.35–1.88], 1.38 [95% CI, 1.15–1.65], and 2.62 [95% CI, 1.79–3.84], respectively. On subgroup analysis, HCC patients without cirrhosis, those with stage 3 or 4 cancer had a higher stroke risk than cancer-free cohort. Therefore, stroke prevention should be considered in patients with HCC, especially in those without cirrhosis and with stage 3 or 4 cancer.

Abstract The purpose of the retrospective study was to investigate the long-term result of implant-induced injury on the adjacent tooth. The subjects of this retrospective study were patients who had received implants and had tooth injury; direct invasion of root (group I), root surface contact (group II), or

Objective To investigate whether recombinant globular adiponectin can reduce kidney injury in diabetic mice by regulating autophagy and endoplasmic reticulum stress. Methods Mice were randomly divided into control group,diabetic model group, low and high dose of adiponectin group (5 and 15 μg/kg dose of recombinant globular adiponectin was injected). There were 8 mice in each group. After eight weeks, blood samples were collected to determine the level of blood glucose, urea nitrogen and creatinine by biochemical method and the level of insulin was measured by enzyme-linked immunosorbent assay. Bilateral kidneys were taken to calculate the ratio of the kidney mass to body mass. The renal cortex tissue samples were stained with HE, and the rest were kept at -70 ℃. The mRNA expression of endoplasmic reticulum stress indicators (GRP78, CHOP and caspase-12) and autophagy indicators (LC3, Beclin1 and p62) was determined by real-time quantitative PCR. Results Compared with control group, the level of blood glucose, creatinine and urea nitrogen, and the ratio of the kidney/body mass were significantly increased (P＜0.05), and the level of blood insulin was significantly reduced (P＜0.05) in model group. There were significant pathological changes in kidney in diabetic mice in model group compared with control group. The mRNA expression of GRP78, CHOP, caspase-12 and p62 was significantly increased (P＜0.05), and the mRNA expression of LC3 and Beclin1 was significantly reduced(P＜0.05) in kidney in model group compared with control group. Compared with model group, adiponectin can significantly relieve the changes in model group (P＜0.05). Conclusions Recombinant globular adiponectin may alleviate the renal injury in diabetic mice by regulating autophagy and endoplasmic reticulum stress.

Oplopanax elatus (Nakai) Nakai, in the Araliaceae family, has been used in traditional Chinese medicine (TCM) to treat diseases as an adaptogen for thousands of years. This study established an ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) method to identify chemical components and biotransformation metabolites of root bark extract from O. elatus. A total of 18 compounds were characterized in O. elatus extract, and 62 metabolites by human intestinal microbiota were detected. Two polyynes, falcarindiol and oplopandiol were recognized as the main components of O. elatus, whose metabolites are further illustrated. Several metabolic pathways were proposed to generate the detected metabolites, including methylation, hydrogenation, demethylation, dehydroxylation, and hydroxylation. These findings indicated that intestinal microbiota might play an essential role in mediating the bioactivity of O. elatus.

Abstract Interbasin interactions have been increasingly emphasized in recent years due to their roles in shaping climate trends and the global warming hiatus in the northern hemisphere. The profound influence from the North Atlantic on the Tropical Pacific has been a primary focus. In this study, we conducted observational analyses and numerical modeling experiments to show that the North Atlantic has also strongly influenced the Extratropical North Pacific. A rapid and synchronous change in the atmospheric and oceanic circulations was observed in the North Pacific during the late 1990s. The change was driven by the transbasin influence from the Atlantic Ocean. During the positive phase of the Atlantic Multidecadal Oscillation (AMO) since the 1990s, the anomalously warm North Atlantic triggers a series of zonally symmetric and asymmetric transbasin teleconnections involving the Inter-tropical Convergence Zone (ITCZ), Walker and Hadley circulations, and Rossby wave propagation that lead to a decrease in wind stress curls over the Pacific subtropics, resulting in an abrupt weakening in the North Pacific subtropical gyre (NPSG) and the Kuroshio Current.

Patients with cancer-associated ischemic stroke pose similar clinical manifestations and image characteristics, mainly embolic infarction, as patients with atrial fibrillation do. D-dimer, a degraded product of fibrin polymer, is a useful indicator of hypercoagulability, which frequently increases in cancer-associated stroke, but not in stroke resulted from atrial fibrillation. The level of serum D-dimer is associated with mortality, prognosis, and recurrence of systemic thromboembolism in these patients. Theoretically, drugs block coagulation cascade, such as heparin and low-molecular-weight-heparin (LMWH), oral direct anticoagulants, could attenuate the status of hypercoagulation and decrease the amount of D-dimer. These drugs may be helpful to prevent thromboembolic events in patients with cancer-associated hypercoagulability. Vitamin K antagonist, warfarin, decreases the production of coagulation factors, but not interrupts coagulation cascade may not be helpful to decrease hypercoagulability, but increase the risk of bleeding. However, the treatment of cancer-associated embolic stroke is still controversial. This article reviews relevant clinical studies and proposes the applicability of direct oral anticoagulants from the pathophysiological mechanism.

BackgroundAcute aortic dissection is a life-threatening condition associated with high mortality rate. Findings from previous studies addressing the "weekend effect" on the mortality rate from an acute aortic dissection mortality have been inconsistent. Furthermore, the effect of admission for acute aortic dissection during the holiday season has not been previously investigated.ObjectiveOur aim was to evaluate the effect of admission for acute aortic dissection during holiday season or weekends on the risk of mortality.MethodsWe conducted a retrospective analysis of nationwide cohort data from the Taiwan's National Health Insurance Research Database. We collected data on all adult patients hospitalized for acute aortic dissection between 2001 and 2017 in Taiwan and classified them into the following three groups based on day of admission: holiday season (at least 4 consecutive days; n = 280), weekend (n = 1 041), and weekday (n = 3 109). The following three outcomes were evaluated: in-hospital mortality, 7-day mortality, and 180-day mortality.ResultsA multivariable logistic regression was used to adjust for possible cofounders on the measured outcomes. Compared to weekday admissions for acute aortic dissection, weekend admissions resulted in a 29% increase in the risk of in-hospital death (aOR = 1.29; 95% CI, 1.05-1.59; P = 0.0153), with a 25% increase in the 7-day (aOR = 1.25; 95% CI, 1.001-1.563; P = 0.0492) and 20% increase in the 180-day mortality risk (aOR = 1.20; 95% CI, 1.01-1.42; P = 0.0395). Of note, admission over the holiday season did not result in a higher mortality risk than for weekday admissions; this finding, however, might reflect insufficient statistical power on subgroup analysis.ConclusionPatients admitted for acute aortic dissection during the weekends are at higher risk of mortality compared to those admitted on weekdays. Our finding likely reflects inadequate staffing and team experience of weekend staff and can guide healthcare policy makers to improve patient outcomes.

Although high mortality of lung cancer is greatly due to distant metastasis, the mechanism of this metastasis remains unclear. Here, we investigate in lung cancer that SOX30 is sharply under-expressed in metastatic tumors compared with non-metastatic tumors, and suppresses plenty of metastasis related processes or pathways. SOX30 strongly inhibits tumor cell metastasis in vitro and in vivo. Sox30 deficiency promotes lung metastasis in Sox30−/− mice and this uncontrollable lung-metastasis is re-inhibited upon Sox30 re-expression. Mechanistically, SOX30 diminishes Wnt-signaling via directly transcriptional repressing β-catenin or interacting with β-catenin to compete with TCF for binding to β-catenin. The carboxyl-terminus of SOX30 is required for attenuating β-catenin transcriptional activity, whereas the amino-terminus of SOX30 is required for its interaction with β-catenin protein. Enhance of β-catenin attenuates the anti-metastatic role of SOX30. Moreover, Sox30 deficiency promotes tumor metastasis and reduces survival of mice. In addition, nuclear SOX30 expression is closely associated with metastasis and represents a favorable independent prognostic biomarker of lung cancer patients. Altogether, these results highlight an important role and mechanism of SOX30 in lung cancer metastasis, providing a potential therapeutic target for anti-metastasis. Keywords: Lung cancer, Metastasis, SOX30, Wnt-signaling, Molecular mechanism

Background Obesity is a key public health problem. The advancement of gut microbiota research sheds new light on this field. This article aims to present the research trends in global intestinal microbiota studies within the domain of obesity research. Methods Bibliographic information of the publications on intestinal microbiota and obesity was retrieved from the Scopus database, and then analyzed by using bibliometric approaches. Results A total of 3,446 references were retrieved; the data indicated a steady growth and an exponential increase in publication numbers. The references were written in 23 different languages (93.8% in English). A number of 3,056 English journal papers were included in the further analyses. Among the 940 journals, the most prolific ones were PLOS ONE, Scientific Reports, and British Journal of Nutrition. North America and Europe were the highest publication output areas. The US (995 publications) ranked first in the number of publications, followed by the China (243 publications) and France (242 publications). The publication numbers were significantly correlated with gross domestic product (GDP), human development index (HDI), and population number (PN). International collaboration analysis also shows that most of the collaborations are among developed countries. Discussion This comprehensive bibliometric study indicates that gut microbiota is a significant topic in the obesity research. The structured information may be helpful in understanding research trends, and locating research hot spots and gaps in this domain.

AIM:To assess the effects of differential exposure to antenatal corticosteroid (ACS) on short- and long-term outcomes of infants born before 24 weeks of gestation. METHODS:This is a retrospective cohort study of 147 infants delivered by 116 women at 21-23 weeks of gestation between January 2001 and December 2016 at a tertiary referral hospital in Seoul, Korea. Eligible subjects were categorized into the following three groups according to ACS exposure: non-user (n = 53), partial-course (n = 44), and complete-course (n = 50). Univariable and multivariable analyses were used to compare neonatal mortality, neonatal morbidities including intraventricular hemorrhage (IVH), and neurodevelopmental impairment including cerebral palsy among the three groups. RESULTS:Neonatal mortality rate was significantly lower in the ACS-user groups (non-user, 52.8%; partial-course, 27.3%; complete-course, 28.0%; P = 0.01), but complete-course of ACS therapy had no advantages over partial-course. A lower incidence of IVH was observed in the complete-course group (non-users, 54.8%; partial-course, 48.6%; complete-course, 20.5%; P = 0.003). Multiple logistic regression analysis showed that ACS therapy, either partial- or complete-course, was associated with a lower rate of neonatal mortality (adjusted odds ratio (aOR) 0.375; 95% confidence interval (CI) 0.141-0.996 in partial-course; aOR 0.173; 95% CI 0.052-0.574) in complete-course). IVH (aOR 0.191; 95% CI 0.071-0.516) was less likely to occur in the complete-course group than in the non-user group. Neurodevelopmental impairment of survivors at 18-22 month after birth was not significantly different among the three groups. CONCLUSION:ACS therapy in preterm births at 21-23 weeks of gestation was associated with significantly reduced rates of neonatal mortality and IVH, especially with complete administration.

Despite a plethora of literature has documented that osteoarthritis (OA) is veritably associated with oxidative stress-mediated chondrocyte death and matrix degradation, yet the possible involvement of synoviocyte abnormality as causative factor of OA has not been thoroughly investigated. For this reason, we conduct the current studies to insight into how synoviocytes could respond to an episode of folate-deprived (FD) condition. First, when HIG-82 synoviocytes were cultivated under FD condition, a time-dependent growth impediment was observed and the demise of these cells was demonstrated to be apoptotic in nature mediated through FD-evoked overproduction of reactive oxygen species (ROS) and drastically released of cytosolic calcium (Ca2+) concentrations. Next, we uncovered that FD-evoked ROS overproduction could only be strongly suppressed by either mitochondrial complex II inhibitors (TTFA and carboxin) or NADPH oxidase (NOX) inhibitors (AEBSF and apocynin), but not by mitochondrial complex I inhibitor (rotenone) and mitochondrial complex III inhibitor (antimycin A). Interestingly, this selective inhibition of FD-evoked ROS by mitochondrial complex II and NOX inhibitors was found to correlate excellently with the suppression of cytosolic Ca2+ release and reduced the magnitude of the apoptotic TUNEL-positive cells. Taken together, we present the first evidence here that FD-triggered ROS overproduction in synoviocytes is originated from mitochondrial complex II and NOX. Both elevated ROS in tandem with cytosolic Ca2+ overload serve as final arbitrators for apoptotic lethality of synoviocytes cultivated under FD condition. Thus, folate supplementation may be beneficial to patients with OA.