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Abstract Fetal macrosomia is associated with maternal and newborn complications due to incorrect fetal weight estimation or inappropriate choice of delivery models. The early screening and evaluation of macrosomia in the third trimester can improve delivery outcomes and reduce complications. However, traditional clinical and ultrasound examinations face difficulties in obtaining accurate fetal measurements during the third trimester of pregnancy. This study aims to develop a comprehensive predictive model for detecting macrosomia using machine learning (ML) algorithms. The accuracy of macrosomia prediction using logistic regression, k-nearest neighbors, support vector machine, random forest (RF), XGBoost, and LightGBM algorithms was explored. Each approach was trained and validated using data from 3244 pregnant women at a hospital in southern China. The information gain method was employed to identify deterministic features associated with the occurrence of macrosomia. The performance of six ML algorithms based on the recall and area under the curve evaluation metrics were compared. To develop an efficient prediction model, two sets of experiments based on ultrasound examination records within 1-7 days and 8-14 days prior to delivery were conducted. The ensemble model, comprising the RF, XGBoost, and LightGBM algorithms, showed encouraging results. For each experimental group, the proposed ensemble model outperformed other ML approaches and the traditional Hadlock formula. The experimental results indicate that, with the most risk-relevant features, the ML algorithms presented in this study can predict macrosomia and assist obstetricians in selecting more appropriate delivery models.

Abstract An improved method for identifying sporadic E (Es) layer properties from radio occultation (RO) electron density profiles (EDPs) is presented. The data used are sourced from COSMIC-1 RO EDPs collected between 2006 and 2019, which cover altitudes from 75 to 145 km. Initially, we evaluate the reliability of EDPs using the International Reference Ionosphere 2016 (IRI-2016) model and select only those profiles with a reliability score of 0.6 or higher (on a scale up to 1) for further analysis. Preliminary Es layer inversion results are obtained and validated against electron density data derived from ionosonde fbEs measurements, demonstrating a linear correlation with a coefficient of 0.72 and a mean absolute percentage error of 36.08%. Further verification using RO S4max data shows that this research method achieved an accuracy of 85.3% in identifying Es events. We perform a detailed analysis of Es layer relative occurrence rates, intensity, and thickness. The Es intensity is expressed by NmμEs (the layer’s maximum electron density (Nm) corresponding to the metal (μ) ion), which is estimated from the measured layer peak electron density NmEs by subtracting the ambient E region electron density NeE(hEs) at the height of the layer’s peak hEs, computed from the IRI-2016 model. Our findings reveal that Es layers predominantly occur in mid-latitude regions during summer, with average intensities between $$5\times {10}^{4 }\text{ and }8\times {10}^{4 }\text{el}/{\text{cm}}^{3}$$ 5 × 10 4 and 8 × 10 4 el / cm 3 . The most likely thickness of Es layers is approximately 1.4 km. Additionally, the present study shows that because NeE(hEs) increases during daytime, which leads to increases in NmEs, confirming that NmμEs is the proper parameter for assessing the Es layer intensity, in line with what is suggested by Haldoupis et al. (Haldoupis et al., J Atmos Sol Terr Phys 206:105327, 2020). Graphical Abstract

AbstractContext Polycystic ovary syndrome (PCOS) is a common and complex disease caused by endocrine and metabolic dysfunction in women of reproductive age. Baicalin is reported to ameliorate PCOS.Objective This study determines whether baicalin could affect the progression of PCOS.Materials and methods To establish an animal model of PCOS, female Sprague-Dawley (SD) rats were subcutaneously injected with dehydroepiandrosterone (DHEA, 60 mg/kg) for 20 days. Next, normal and PCOS mice were divided into 3 groups: control, PCOS, PCOS + Baicalin (20 mg/kg) groups. In addition, the levels of microRNA-874-3p (miR-874-3p) and microRNA-144 (miR-144) in ovarian tissues were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).Results Compared to the PCOS group, baicalin treatment significantly declined free testosterone (33.71 pg/mL vs. 56.05 pg/mL) and luteinizing hormone (LH; 3971.73 pg/mL vs. 5201.50 pg/mL) levels in rats with PCOS. Additionally, compared to the control group, 100 μM baicalin lessened miR-874-3p and miR-144 levels in human ovarian granulosa cells (KGN cells) by 36.87% and 32.57%, respectively. Furthermore, forkhead box O (FOXO) proteins FOXO1 and FOXO3 are the direct targets of miR-144 and miR-874-3p, respectively. Meanwhile, baicalin induced G0-G1 phase arrest (69.56 ± 3.7% at baicalin with 100 μM vs. 51.24 ± 3.2%, control) in KGN cells correlating with decreased p27 Kip1 (FOXO proteins downstream effector gene) expression by 55.5%; however, miR-874-3p or miR-144 overexpression could abolish this effect.Conclusions Baicalin could alleviate the symptoms of PCOS via regulating miR-874-3p/FOXO3 and miR-144/FOXO1 axis, demonstrating its potential utility in PCOS treatment.

Abstract This study uses the three-cornered hat (3CH) method to estimate the observation error variances (ErrVars) of FY-3C RO refractivity, temperature, and specific humidity for the first time. The FY-3C RO data was compared to the three reference datasets including radiosonde observations and NCEP and ERA-Interim reanalyses. The ErrVars of FY-3C RO data are estimated at 18 globally distributed radiosonde stations by using the three reference datasets and are compared to corresponding gridded ErrVars estimated using only the two model datasets as references. The two types of estimates show good correlations at different heights, while the gridded estimates are generally the smaller ones, which may be attributed to the neglection of error correlations among the datasets when applying the 3CH method. Due to the lack of radiosonde data in oceanic and polar regions, the global distributions of FY-3C RO observation errors are presented based on the estimated 5° × 5° gridded ErrVars. The global distribution of the FY-3C RO fractional error standard deviations (ErrSDs) demonstrates that the observation error varies greatly at different pressure levels and latitudes. Specifically, the refractivity ErrSDs at 200 hPa and 50 hPa are significantly higher around 30°N and 30°S than in other areas. The specific humidity ErrSDs generally increase as pressure levels decrease. In addition, statistics show that the fractional ErrSDs of refractivity are generally the lowest between 45° N–75° N and 45° S–75° S at all pressure levels, and land-sea differences exist in the fractional ErrSDs for all three types of RO data.

Introduction Transcatheter aortic valve replacement (TAVR) is a standard treatment for aortic stenosis, particularly in older adults. Reduced exercise capacity and frailty significantly impact outcomes in TAVR patients, yet current management lacks strategies to address these issues. This study aims to assess the effectiveness of home-based mobile-guided exercise-based cardiac rehabilitation in TAVR patients, led by a multidisciplinary team with clear progression milestones.Methods and analysis The study involves 90 patients aged 60–89 in a single centre who will be randomised to a 3-month novel multidomain exercise intervention or routine care. Outcome assessors will be blinded towards group allocation. The primary outcome is the 6-min walk distance at month 3. The secondary outcomes include the 6-min walk distance at month 6, physical function measured by total Short Physical Performance Battery score and exercise adherence measured by the Exercise Adherence Rating Scale at months 3 and 6. Additional outcome measures, including rehospitalisations, death, handgrip strength, frailty (Fried Criteria and Essential Toolset), cognitive function (Mini-Mental State Examination), quality of life (EuroQol 5-Dimension 5-Level), nutritional status (Mini-Nutritional Assessment), anxiety (General Anxiety Disorder-7), depression (Geriatric Depression Scale), sleep (Pittsburgh Sleep Quality Index), functional capacity (Duke Activity Status Index), clinical indices (body mass index, symptoms, signs, left ventricular ejection fraction (LVEF), N-Terminal Pro-Brain Natriuretic Peptide, etc) and social support (Lubben Social Network Scale-6), along with comprehensive cost analysis, enhance the study’s significance. The study’s findings hold crucial implications for crafting an effective exercise-focused cardiac rehabilitation strategy for TAVR patients. Community implementation not only deepens understanding but also fosters the potential integration of exercise-based cardiac rehabilitation into self-care, promising enhanced patient adherence and overall cardiovascular health management.Ethics and dissemination Ethical approval was obtained from the Zhongshan Hospital, Fudan University Ethics Committee (B2022-062R). Results will be disseminated to local stakeholders and the research community through publications and conferences.Trial registration number NCT05989594

Renal cell carcinoma (RCC) is a common urinary tract tumor that arises from the highly heterogeneous epithelium of the renal tubules. The incidence of kidney cancer is second only to the incidence of bladder cancer, and has shown an upward trend over time. Although surgery is the preferred treatment for localized RCC, treatment decisions should be customized to individual patients considering their overall health status and the risk of developing or worsening chronic kidney disease postoperatively. Anticancer drugs are preferred to prevent perioperative and long-term postoperative complications; however, resistance to chemotherapy remains a considerable problem during the treatment process. To overcome this challenge, nanocarriers have emerged as a promising strategy for targeted drug delivery for cancer treatment. Nanocarriers can transport anticancer agents, achieving several-fold higher cytotoxic concentrations in tumors and minimizing toxicity to the remaining parts of the body. This article reviews the use of nanomaterials, such as liposomes, polymeric nanoparticles, nanocomposites, carbon nanomaterials, nanobubbles, nanomicelles, and mesoporous silica nanoparticles, for RCC treatment, and discusses their advantages and disadvantages.

RECQ4 mutations contribute to multiple developmental diseases and tumorigenesis. Here the authors describe how a highly oncogenic RECQ4 mutation alters the control of DNA synthesis, leading to abnormal DNA content and cell growth.

The gravity wave (GW) potential energy (Ep) in the lower stratosphere (LS) of the altitude range between 20 and 30 km over the Indian region (60°E–100°E, 0°–30°N) is retrieved using the dry temperature profiles from the Constellation Observing System for Meteorology Ionosphere and Climate-2 (COSMIC-2) radio occultation (RO) mission from December 2019 to November 2021. Through correlation analysis and dominance analysis (DA) methods, the impacts of multiple influencing factors on the local LS GW activity are quantified and compared. The results demonstrate that in the central and northern part of Indian region, the three factors, including the convective activity (using outgoing long-wave radiation as the proxy) mainly caused by the Indian summer monsoon, the mean zonal wind speed between 15 and 17 km, the height range where the maximum tropical easterly jet (TEJ) wind speed appears, and the mean zonal wind speed between 20 and 30 km, have the greatest impacts on the LS GW activity. In the southern part of the Indian Peninsula and over the Indian Ocean, the mean zonal wind shear between 20 and 30 km plays a dominant role in the LS GW activity, which is due to the fact that the GW energy can be attenuated by large background wind shears. It can be concluded that the LS GW activity in the Indian region is mainly influenced by the Indian summer monsoon, the TEJ, and the wind activity in the LS, while over different local areas, differences exist in which factors are the dominant ones.

Abstract Induction chemotherapy based on high-dose methotrexate is considered as the standard approach for newly diagnosed primary central nervous system lymphomas (PCNSLs). However, the best combination chemotherapeutic regimen remains unclear. This study aimed to determine the efficacy and toxicities of rituximab with methotrexate (R-M regimen). Consecutive 37 Chinese patients receiving R-M regimen as induction chemotherapy were retrospectively identified from January 2015 to June 2020 from our center in eastern China. Fourteen patients receiving rituximab plus methotrexate with cytarabine (R-MA regimen) at the same period were identified as the positive control group. The response rates, survival, toxicities, length of hospital stay (LOS), and cost were compared. Compared with the R-MA regimen, the R-M regimen showed comparable response rate and survival outcomes, but had fewer grade 3–4 hematological toxicities, shorter LOS, lower mean total hospitalization cost and lower mean total antibiotic cost. Complete remission at the end of induction chemotherapy and ECOG > 3 were independent prognostic factors for overall survival. In conclusion, R-M regimen is an effective and cost-effective combination treatment for PCNSLs, which warrants further evaluation in randomized trials.

Introduction: Low back pain (LBP) is a prevalent and complex condition that poses significant medical, social, and economic burdens worldwide. The accurate and timely assessment and diagnosis of LBP, particularly non-specific LBP (NSLBP), are crucial to developing effective interventions and treatments for LBP patients. In this study, we aimed to investigate the potential of combining B-mode ultrasound image features with shear wave elastography (SWE) features to improve the classification of NSLBP patients.Methods: We recruited 52 subjects with NSLBP from the University of Hong Kong-Shenzhen Hospital and collected B-mode ultrasound images and SWE data from multiple sites. The Visual Analogue Scale (VAS) was used as the ground truth to classify NSLBP patients. We extracted and selected features from the data and employed a support vector machine (SVM) model to classify NSLBP patients. The performance of the SVM model was evaluated using five-fold cross-validation and the accuracy, precision, and sensitivity were calculated.Results: We obtained an optimal feature set of 48 features, among which the SWE elasticity feature had the most significant contribution to the classification task. The SVM model achieved an accuracy, precision, and sensitivity of 0.85, 0.89, and 0.86, respectively, which were higher than the previously reported values of MRI.Discussion: In this study, we aimed to investigate the potential of combining B-mode ultrasound image features with shear wave elastography (SWE) features to improve the classification of non-specific low back pain (NSLBP) patients. Our results showed that combining B-mode ultrasound image features with SWE features and employing an SVM model can improve the automatic classification of NSLBP patients. Our findings also suggest that the SWE elasticity feature is a crucial factor in classifying NSLBP patients, and the proposed method can identify the important site and position of the muscle in the NSLBP classification task.

Atmospheric Phase Screen (APS) is a major noise that suppresses the accuracy of InSAR deformation time series products. Several correction methods have been developed to perform APS reduction in the InSAR analysis, in which an algorithm called Common Scene Stacking (CSS) method draws wide attention in the community as the method was supposed to effectively separate atmospheric contributions without any external data. CSS was initially proposed for solving linearly interseismic deformation. Whether CSS can be applied in nonlinear deformation cases remains unsolved. In this study, we first conduct a series of data simulations including variable elastic deformation components and also propose an iterative strategy to address the inherent weak edge constraint issues in CSS under different deformation conditions. The results show that signal-to-noise ratio (SNR) is a key parameter affecting the performance of CSS in APS separation. For example, the recovery rate of deformation can generally be greater than 80% from datasets with SNR greater than 10 dB. Our results imply that CSS can favor further improvement of InSAR measurement accuracy. The proposed method in this study was applied to assessing deformation history across the 2020 Mw 5.7 Dingjie earthquake, in which logarithmic postseismic deformation history and coseismic contribution can be successfully retrieved once.

Abstract The Global Positioning System (GPS) radio occultation (RO) data provided by the Fengyun-3C (FY-3C) mission during January 2015 to December 2019 are used to detect the existence of sporadic E (Es) layers over the globe, based on which the spatial and temporal distributions of the Es occurrence rates (ORs) are presented and analyzed. The results are compared with the Es morphology obtained using the RO data from the Constellation Observing System for the Meteorology, Ionosphere, and Climate (COSMIC) mission. It is found that the seasonal variation patterns of the spatial distributions of Es ORs derived from the FY-3C RO data, which show clearly the effects of wind shear mechanism and the Earth’s magnetic field on the formation of Es layers, are basically consistent with those derived from the COSMIC RO data. While the limited local time distribution of the FY-3C RO-detected Es occurrences makes it impossible to resolve the complete diurnal variations of Es layers. Detailed comparisons of the Es morphologies derived from the two different RO missions reveal that the magnitudes of the Es ORs derived by FY-3C data are slightly smaller than those derived by COSMIC data in the middle and low latitudes, which is due to that the top heights of the 50 Hz RO data of FY-3C mission are generally lower than those of the COSMIC mission. In the polar regions, the distinctly low ratio of the FY-3C RO 50 Hz measurements which reach the height of 90 km reduces the capability of these observations for Es-layer detections. Graphical Abstract

Abstract Seismologic studies have reported seismic velocities reduction and Vp/Vs ratio changes over damage zones associated with seismogenic faults. The structure and elastic properties of these damage zones indicate the maturity of faults and affect the rupture dynamics of future seismic events. Therefore, they contain critical information about fault properties that could inform seismic hazards. Here we present a geodetic modeling approach to constrain velocity changes and elastic properties of fault damage zones under stress perturbation from nearby earthquakes. Compared to seismic tomographic analysis that is usually limited by resolution, this geodetic approach provides tighter constraints on the elastic properties and geometry of the damage zone at shallow depths. Our results imply that a major component of the shallow strain release is distributed and inelastic. The existence of numerous shallow faults either may indicate a locally detached shallow layer or they are remnants from earlier fault evolution.

Patients with cholangiocarcinoma (CCA) often have an unfavorable prognosis because of its insidious nature, low resectability rate, and poor response to anticancer drugs and radiotherapy, which makes early detection and treatment difficult. At present, CCA has a five-year overall survival rate (OS) of only 5%, despite advances in therapies. New an increasing number of evidence suggests that nanoplatforms may play a crucial role in enhancing the pharmacological effects and in reducing both short- and long-term side effects of cancer treatment. This document reviews the advantages and shortcomings of nanoparticles such as liposomes, polymeric nanoparticle，inorganic nanoparticle, nano-metals and nano-alloys, carbon dots, nano-micelles, dendrimer, nano-capsule, bio-Nanomaterials in the diagnosis and treatment of CCA and discuss the current challenges in of nanoplatforms for CCA.

Abstract The S4max data retrieved from the Constellation Observing System for the Meteorology, Ionosphere, and Climate (COSMIC) radio occultation (RO) measurements during 2007 to 2015 is adopted to investigate the global distribution and seasonal variation of the sporadic E (Es) layers in the present work. The long-term and short-term global Es occurrence maps are presented and the spatial and temporal distributions of Es occurrence rates (ORs) are further confirmed and studied. The International Geomagnetic Reference Field model (IGRF12) is used to calculate the horizontal intensity and inclination of the Earth’s magnetic field. The analysis shows that the Earth’s magnetic field is one of the fundamental reasons for the global distribution of the Es layers. In addition, the Horizontal Wind Field model HWM14 and the IGRF12 model were employed to calculate the vertical ion convergence (VIC) to examine the role of neutral wind shear in the global distribution of the Es ORs. The results reveal that the middle latitude distribution of simulated vertical concentration of Fe+ is similar to that of Es ORs, which indicates that the VIC induced by the neutral wind shear is an important factor in determining the geographical distribution, summer maximum (or winter minimum) and diurnal characteristics of Es ORs in middle latitudes. The new findings mainly include the following two aspects: (1) in summer over mid-latitudes, VIC peaks in the morning and afternoon to evening, which explains the semidiurnal behavior of Es ORs; (2) VIC reaches its minimum value in low-altitude (100 km) areas, which is the reason for the significant decrease in Es ORs in low-altitude areas. The disagreements between the VIC and Es ORs indicate that other processes, such as the meteor influx rate, the ionospheric electric fields and atmospheric tides, should also be considered as they may have an important impact on the variation of Es layers. Graphical Abstract

Background: It is critical to train future nursing managers in advance for the prospective development of healthcare organizations, but a widely recognized curriculum content structure for leadership and management competency development for nurturing future nurse managers was lacking in China. Objective: To establish a curriculum content structure for the leadership and management competency cultivation for future nurse managers in Chinese healthcare setting. Methods: A modified Delphi study was conducted. 22 experts who have in-depth knowledge of nursing leadership and management from 4 main geographical regions in China were included. The initial curriculum content structure was constructed based on a previous qualitative study and two team meetings. Subsequently, a two-round Delphi survey was conducted with 22 panelists in the first round and 19 in the second round. Scores of importance and textual comments were collected and used to judge the achievement of consensus. Results: After the two-round Delphi process, consensus was reached, as each item was rated ≥4 by 84.21–100% of the experts and each one had a coefficient of variance (CV) ≤ 0.174. The finalized curriculum content contains 9 modules and 27 items. Conclusions: This study formed a curriculum content structure for leadership and management competency training for nurses preparing for managerial roles, which contribute to the establishment of a nursing management talent pipeline to meet the needs of healthcare institutions for contemporary nurse managers.

In recent years, intelligent diagnosis and intelligent medical treatment based on big data of medical examinations have become the main trend of medical development in the future. In this paper, we propose a method for analyzing the difference between males and females in medical examination items (medical attributes) and find that males and females of different ages have differences in medical attributes. Then, the cluster analysis method is used to further analyze the differences between male and female in medical examination items, such that some common important attributes (CIAs) that can be used for gender recognition are found within a specific age range. Following, we propose two gender recognition models (GRMs) by using the found CIAs to identify the gender. A large number of experimental results are provided to validate the effectiveness of the proposed GRMs. Experimental results show that the medical attributes with a large value of difference really contribute to gender recognition. Within a certain age range, such as 17 to 51 years old, the proposed GRM can reach 92.8% accuracy using only six medical attributes.

Tumor protein 53 (TP53) mutation predicts an unfavorable prognosis in diffuse large B-cell lymphoma (DLBCL), but the molecular basis for this association remains unclear. In several malignancies, the cytidine deaminase apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B) has been reported to be associated with the TP53 G/C-to-A/T mutation. Here, we show that the frequency of this mutation was significantly higher in relapsed/refractory (R/R) than in non-R/R DLBCL, which was positively associated with the APOBEC3B expression level. APOBEC3B overexpression induced the TP53 G/C-to-A/T mutation in vitro, resulting in a phenotype similar to that of DLBCL specimens. Additionally, APOBEC3B-induced p53 mutants promoted the growth of DLBCL cells and enhanced drug resistance. These results suggest that APOBEC3B is a critical factor in mutant p53-driven R/R DLBCL and is therefore a potential therapeutic target.

AimsWe evaluated the efficacy and significant changes in the levels of retinol-binding protein 4 (RBP-4) and insulin resistance in patients with type 2 diabetes mellitus (T2DM) treated with chiglitazar versus sitagliptin.MethodsEighty-one T2DM patients with haemoglobin A1c (HbA1c) level of 7.5%–10.0% were selected. Based on the study criteria, patients were randomly assigned to receive chiglitazar (32 mg), chiglitazar (48 mg), or sitagliptin (100 mg) orally for 24 weeks. Sociodemographic and anthropometric characteristics, lipid profiles, glucose profiles, and serum RBP-4 levels were determined at baseline and at the end of the therapy.ResultsAfter treatment for 24 weeks, significant changes in fasting blood glucose (FBG), fasting insulin (Fins), 2 h-blood glucose (2h-BG), the score values of insulin resistance/insulin secretion/β cell function (HOMA-IR, HOMA-IS, and HOMA-β), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein cholesterol (HDL-C), and RBP-4 levels were detected in patients with chiglitazar administration and sitagliptin administration. Changes in RBP-4 levels were positively correlated with changes in HOMA-IR and 2 h-BG in linear regression.ConclusionsChiglitazar showed a greater improvement in parameters of diabetes than sitagliptin, and changes in serum RBP-4 levels were associated with changes in insulin-sensitizing parameters.Clinical Trial RegistrationClinicalTrials.gov, CT.gov identifier: NCT02173457.

Background: Post-traumatic stress disorder (PTSD) is the most common psychiatric sequelae among novel coronavirus disease (COVID-19) patients. The aim of this study was to determine the prevalence of PTSD symptoms, PTSD-related factors, and its relationship with quality of life at long-term follow-up in hospitalized COVID-19 survivors.Methods: A cross-sectional study was undertaken to evaluate the health consequences of hospitalized COVID-19 survivors. All participants were interviewed face-to-face through a series of questionnaires: a researcher-developed symptom questionnaire, the Post-traumatic Stress Disorder Checklist–Civilian Version, the Generalized Anxiety Disorder 7-item, and the 36-item Short Form.Results: A total of 574 participants were enrolled with an average age of 57 years. The median follow-up time post-discharge was 193.9 days (SD = 15.32). Among the participants, 77.9% of survivors presented with at least one symptom, where fatigue or muscle weakness (47.9%) was reported the most frequently, followed by chest distress (29.4%) and sleep difficulty (29.4%). The prevalence of PTSD was 11.15% [95% confidence interval (CI): 8.56, 13.73] with a cut-off score of 44. Factors such as respiratory symptoms [odds ratio (OR): 3.53; 95% CI: 1.68–7.42], anxiety (OR: 14.64; 95% CI: 7.09–30.21), and sleep difficulty (OR: 2.17; 95% CI: 1.14–4.16) were positively related to PTSD. Those COVID-19 survivors with potential PTSD had significantly lower quality of life than those without (P < 0.05).Conclusion: Our study illustrated that a significant number of COVID-19 survivors were suffering from physical or mental distress to varying degrees at 6 months post-discharge. People with PTSD were more likely to experience persistent respiratory symptoms and sleep difficulty, as well as anxiety and a decreased quality of life. Such survivors require greater attention to their mental health, particularly the PTSD symptoms at the early phase, which may play an important role in the recovery of both the physical and psychological health of COVID-19 survivors.

Abstract Human mesenchymal stem cell (MSC)-derived exosomes (Exos) are a promising therapeutic agent for cell-free regenerative medicine. However, their poor organ-targeting ability and therapeutic efficacy have been found to critically limit their clinical applications. In the present study, we fabricated iron oxide nanoparticle (NP)-labeled exosomes (Exo + NPs) from NP-treated MSCs and evaluated their therapeutic efficacy in a clinically relevant model of skin injury. We found that the Exos could be readily internalized by human umbilical vein endothelial cells (HUVECs), and could significantly promote their proliferation, migration, and angiogenesis both in vitro and in vivo. Moreover, the protein expression of proliferative markers (Cyclin D1 and Cyclin A2), growth factors (VEGFA), and migration-related chemokines (CXCL12) was significantly upregulated after Exo treatment. Unlike the Exos prepared from untreated MSCs, the Exo + NPs contained NPs that acted as a magnet-guided navigation tool. The in vivo systemic injection of Exo + NPs with magnetic guidance significantly increased the number of Exo + NPs that accumulated at the injury site. Furthermore, these accumulated Exo + NPs significantly enhanced endothelial cell proliferation, migration, and angiogenic tubule formation in vivo; moreover, they reduced scar formation and increased CK19, PCNA, and collagen expression in vivo. Collectively, these findings confirm the development of therapeutically efficacious extracellular nanovesicles and demonstrate their feasibility in cutaneous wound repair.

Live Virtual Machine (VM) migration among geographically distributed edge clouds is an important strategy for providing low latency and reliable services for mobile end users. VM migration among edge clouds is more challenging than that in cloud computing, because the network bandwidth among edge clouds is more constrained than the cloud data center networks. In this paper, we study the bandwidth allocation among multiple concurrent live VM migrations in edge clouds. This problem is novel in that existing works aim to reduce the migration time for a single live VM migration among the edge clouds, and also ignores the QoS requirement for the service running on the VM in migration. However, our problem considers multiple VM migration tasks, and aims to maximize the average QoS while meeting the migration time constraint for each VM migration task. We formulate the problem as a Non-Linear Programming (NLP) problem which is also shown to be NP-Hard. We develop a new method to solve this problem. In our approach, we first transfer the problem into a Linear Programming (LP) problem by reducing the solution space. Taking the output from the LP solver as an initial solution, we then develop a heuristic to adjust it in order to find a better one to the original NLP problem. Finally, we design a set of evolutionary algorithms to select the optimal initial solution from the LP solver. Extensive simulations show that our proposed method can achieve good QoS and also has a fast convergence speed.

Today's society has a fundamental need for security and anonymity. Well suited, real-life scenarios such as whistleblower reports, intelligence service operations, and the ability to communicate within oppressive governments, call for such fundamental needs. The contribution and focus of this paper is the study of anonymous communications in the context of Delay Tolerant Networks (DTNs). Current literature achieves anonymity via mechanisms that are built around the onion routing paradigm which, unfortunately, is vulnerable to malicious nodes. Instead, our work introduces a novel message forwarding algorithm that delivers messages, from source to destination, via a random walk process. As such, our protocol does not list the intermediate nodes along the route's path and, therefore, enhances significantly the anonymity of the underlying communications. We propose two different approaches for encrypting the exchanged messages. The first one is based solely on public key cryptosystems and is, thus, suitable for short, SMS-style messaging. The second one is a hybrid solution that combines both public and symmetric key cryptography and is targeted towards large multimedia messages, such as images or video. Through extensive simulation experiments, we show that our proposed anonymous routing protocol achieves high message delivery rates, while using modest computational resources on the mobile devices.

The human RECQ4 gene encodes an ATP-dependent DNA helicase that contains a conserved superfamily II helicase domain located at the center of the polypeptide. RECQ4 is one of the five RECQ homologs in human cells, and its helicase domain is flanked by the unique amino and carboxyl termini with sequences distinct from other members of the RECQ helicases. Since the identification of the RECQ4 gene in 1998, multiple RECQ4 mutations have been linked to the pathogenesis of three clinical diseases, which are Rothmund-Thomson syndrome, Baller-Gerold syndrome, and RAPADILINO. Patients with these diseases show various developmental abnormalities. In addition, a subset of RECQ4 mutations are associated with high cancer risks, especially for osteosarcoma and/or lymphoma at early ages. The discovery of clinically relevant RECQ4 mutations leads to intriguing questions: how is the RECQ4 helicase responsible for preventing multiple clinical syndromes? What are the mechanisms by which the RECQ4 disease mutations cause tissue abnormalities and drive cancer formation? Furthermore, RECQ4 is highly overexpressed in many cancer types, raising the question whether RECQ4 acts not only as a tumor suppressor but also an oncogene that can be a potential new therapeutic target. Defining the molecular dysfunctions of different RECQ4 disease mutations is imperative to improving our understanding of the complexity of RECQ4 clinical phenotypes and the dynamic roles of RECQ4 in cancer development and prevention. We will review recent progress in examining the molecular and biochemical properties of the different domains of the RECQ4 protein. We will shed light on how the dynamic roles of RECQ4 in human cells may contribute to the complexity of RECQ4 clinical phenotypes.

Particle size distribution (PSD) is a rich source of information about soil properties, including soil gradation and soil particle size characteristics. This paper compared the PSD prediction ability of three types of mathematical model. We selected nine models that have been proven to accurately predict sample points in previous studies, and we fit 144 pieces of experimental data on 12 texture classes of soil samples from the UNSODA database. We compared the models’ capability for predicting non-sample points, which is important for predicting soil particle size characteristics. Each model’s ability to predict non-sample points of different texture classes of soil was studied using a comprehensive ranking method. The relative differences in the models’ prediction of non-sample points of different texture classes of soil were analyzed using the relative error method. The results showed no considerable correlation between the number of model parameters and the prediction accuracy. For the various texture classes of soil, the Skaggs model and Weipeng model had the highest accuracy in predicting non-sample points, and the Skaggs model had the widest range of application. The Zhongling model and the Weibull model were better in predicting only one texture class of soil, respectively. The Fredlund model, Kolve model, Rosin model, Van Genuchten model and Best model were not as successful as other models. The Weipeng model overestimated the solid particle mass proportion, while the Skaggs model underestimated it when the clay particle content was greater than 20%. Both the Weipeng model and the Skaggs model demonstrated good prediction accuracy when the particle size was within the silt particle size range. The Skaggs model overestimated the particle mass proportion, while the Weipeng model underestimated it when the particle size was within the sand particle size range.

Background: Real-world evidence on the effectiveness of inactivated vaccines against the Delta and Omicron (BA.2.38) variants remains scarce. Methods: A retrospective cohort study was conducted to estimate the adjusted vaccine effectiveness (aVE) of one, two, and three doses of inactivated vaccines in attenuating pneumonia, severe COVID-19, and the duration of viral shedding in Delta and Omicron cases using modified Poisson and linear regression as appropriate. Results: A total of 561 COVID-19 cases were included (59.2% Delta and 40.8% Omicron). In total, 56.4% (184) of Delta and 12.0% (27) of Omicron cases had COVID-19 pneumonia. In the two-dose vaccinated population, 1.4% of Delta and 89.1% of Omicron cases were vaccinated for more than 6 months. In Delta cases, the two-dose aVE was 52% (95% confidence interval, 39–63%) against pneumonia and 61% (15%, 82%) against severe disease. Two-dose vaccination reduced the duration of viral shedding in Delta cases, but not in booster-vaccinated Omicron cases. In Omicron cases, three-dose aVE was 68% (18%, 88%) effective against pneumonia, while two-dose vaccination was insufficient for Omicron. E-values were calculated, and the E-values confirmed the robustness of our findings. Conclusions: In Delta cases, two-dose vaccination within 6 months reduced pneumonia, disease severity, and the duration of viral shedding. Booster vaccination provided a high level of protection against pneumonia with Omicron and should be prioritized.

Abstract Background To investigate the prevalence and risk factors of premature thelarche (PT) in girls and gynecomastia (GM) in boys in Southern China. Methods We conducted a cross-sectional study of preschool children across 9 cities in Zhejiang province. A total of 6273 children in the age-group of 2–7 years were recruited from January 2014 to March 2015. Relevant information was collected from mothers through face-to-face interviews. Logistic regression models were used to examine the correlates of PT and GM. Odds ratios (ORs) with 95% confidence intervals (CIs) are reported. Results The prevalence of PT among girls was 4.8% and that of GM among boys was 0.8%. One hundred girls were diagnosed with PT before the age of 2 years; 69 (69.0%) of these girls experienced spontaneous resolution of PT. Twenty-four boys were diagnosed with GM before the age of 2 years; 10 (41.7%) of these experienced spontaneous resolution of GM. Children borne of mothers with early onset of menarche and those belonging to high-income families were at a higher risk of premature breast development. Greater consumption of eggs was associated with premature breast development in early childhood. Conclusions Socioeconomic status of family, early onset of menarche in mother, and consumption of eggs were strongly associated with premature breast development in early childhood.

The 2021 Maduo earthquake occurred in the interior of the Bayan Har block of the Tibetan Plateau. We used space-born radar interferometry to study the coseismic deformation of this earthquake. Sentinel-1 InSAR observations along ascending and descending orbits provide the coseismic deformation. Pixel offset tracking method is used to complement InSAR observations near the rupture zone. The surface trace of the ruptured fault can be clearly mapped by InSAR observations. We constructed a three-dimensional coseismic slip model constrained by interferograms and pixel offset tracking in the form of a geodetic inverse problem. The coseismic slip model demonstrates that: (1) the Maduo earthquake was a left-lateral strike-slip event with moment magnitude of 7.4; (2) the peak slip is approximately 8 m and is located at a depth of 4 km; (3) a ‘shallow slip deficit’ of the Maduo earthquake is observed; (4) the ruptured faults are found to be dipping northward with a high dipping angle (80 degrees). This study has important implications on earthquake hazard evaluation of the Bayan Har block.

Transcription-replication conflicts need to be resolved to minimize genome instability. Here the authors show that SUMO2-conjugated PCNA destabilizes RNAPII from chromatin, enhances replication progression and limits transcription-induced DNA damage at common fragile sites.

The spatial–temporal distribution of the global gravity wave (GW) potential energy (Ep) at the lower stratosphere of 20–35 km is studied using the dry temperature profiles from multi- Global Navigation Satellite System (GNSS) radio occultation (RO) missions, including CHAMP, COSMIC, GRACE, and METOP-A/B/C, during the 14 years from 2007 to 2020, based on which the linear trends of the GW Ep and the responses of GW Ep to solar activity, quasi biennial oscillation (QBO), and El Niño-Southern Oscillation (ENSO) are analyzed using the multivariate linear regression (MLR) method. It is found that the signs and the magnitudes of the trends of GW Ep during each month vary at different altitude ranges and over different latitudes. At 25–35 km of the middle and high latitudes, GW Ep values generally show significant negative trends in almost all months, and the values of the negative trends become smaller in the regions closer to the poles. The distribution of the deseasonalized trends in the monthly zonal-mean GW Ep demonstrates that the GW activities are generally declining from 2007 to 2020 over the globe. The responses of GW Ep to solar activity are found to be mostly positive at 20–35 km over the globe, and the comparison between the distribution pattern of the deseasonalized trends in the GW activities and that of the responses of GWs to solar activity indicates that the sharp decline in solar activity from 2015 to 2017 might contribute to the overall attenuation of gravity wave activity during the 14 years. Significant negative responses of GW Ep to QBO are found at 30–35 km over 30° S–25° N, and the negative responses extend to the mid and high latitudes in the southern hemisphere at 20–30 km. The responses of GW Ep to QBO change to be significantly positive at 20–30 km over 15° S–15° N, which demonstrates that the zonal wind field should be the main factor affecting the GW activities at 20–30 km over the tropics. The responses of GW Ep at 20–35 km to ENSO are found to be positive over 15° S–15° N, while at 30–35 km over 15° N–30° N and at 20–35 km near 50° N, significant negative responses of GW Ep to ENSO exist.

Analysis of developmental brain networks is fundamentally important for basic developmental neuroscience. In this paper, we focus on the temporally-covarying connection patterns, called meta-networks, and develop a new mathematical model for meta-network decomposition. With the proposed model, we decompose the developmental structural correlation networks of cortical thickness into five meta-networks. Each meta-network exhibits a distinctive spatial connection pattern, and its covarying trajectory highlights the temporal contribution of the meta-network along development. Systematic analysis of the meta-networks and covarying trajectories provides insights into three important aspects of brain network development.

Objective. To evaluate the effects of once-weekly dulaglutide injection and once-daily glimepiride on glucose fluctuation in patients with type 2 diabetes mellitus (T2DM) using the Continuous Glucose Monitoring System (CGMS). Methods. A total of 23 patients with T2DM were randomly assigned into two groups for 26 weeks: the dulaglutide group (n=13) and the glimepiride group (n=10). 72-hour CGMS was applied to all patients: before and after the treatment. General clinical data were collected and measured, such as fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), tumor necrosis factor-α (TNF-α), 8-iso-prostaglandin F2α (8-iso-PGF2α), and interleukin-6 (IL-6). Results. HbA1c of the dulaglutide group was reduced from 8.38±0.93% to 6.68±0.73% after the treatment (P0.05). The Mean Blood Glucose (MBG) of the two groups declined significantly after therapy (P0.05). The percentage time (PT) (>10 mmol/L and 3.9-10 mmol/L) of the two groups was significantly changed after the treatment (P0.05). Conclusion. Once-weekly dulaglutide injection has the same effectiveness as daily glimepiride on lowering blood glucose and decreasing oxidation stress and inflammation and is more effective in controlling glucose fluctuation as compared with glimepiride. This trial is registered with ClinicalTrials.gov NCT01644500.

Aim. To clarify the contributions of fasting glucose (FG) and postprandial glucose (PG) to HbA1c in drug-naïve patients with type 2 diabetes (T2D) and impaired glucose tolerate (IGT)/impaired fasting glucose (IFG). Methods. Continuous glucose monitoring (CGM) was performed in 305 drug-naïve Chinese patients with T2D or IGT/IFG. The incremental area under the curve (AUC) above a glucose value of 6.1 mmol/L or FG glucose levels were calculated to evaluate the contributions of PG or FG to HbA1c values. Results. According to quintiles of HbA1c, T2D patients were divided into five groups (group 1 to 5), and patients with IGT/IFG were assigned into group 0. PG was the predominant contributor in the lower groups with HbA1c 4.9∼6.0% and 6.1∼7.8%. The relative contributions of FG and PG to HbA1c had no significance in the middle groups of HbA1c (7.9∼8.7% and 8.8∼9.5%). FG contributed significantly more than PG in the higher groups of HbA1c (9.6∼10.9% and 11.0∼14.6%). Regression analyses indicate that the contributions of FG and PG were equal (both 50%) when the level of HbA1c was 8.5%. Conclusions. In drug-naïve patients with T2D or IGT/IFG, PG contributed more in patients with HbA1c

Recent advances in MRI have made it easier to collect data for studying human structural and functional connectivity networks. Computational methods can reveal complex spatiotemporal dynamics of the human developing brain. In this paper, we propose a Developmental Meta-network Decomposition (DMD) method to decompose a series of developmental networks into a set of Developmental Meta-networks (DMs), which reveal the underlying changes in connectivity over development. DMD circumvents the limitations of traditional static network decomposition methods by providing a novel exploratory approach to capture the spatiotemporal dynamics of developmental networks. We apply this method to structural correlation networks of cortical thickness across subjects at 3–20 years of age, and identify four DMs that smoothly evolve over three stages, i.e., 3–6, 7–12, and 13–20 years of age. We analyze and highlight the characteristic connections of each DM in relation to brain development.

In the present work, dry temperature profiles provided by the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) radio occultation (RO) mission and the horizontal wind field provided by the European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis are combined for the first time to retrieve the magnitudes of gravity wave (GW) pseudomomentum flux (PMF). The vertical wave parameters, including Brunt−Väisälä frequencies, potential energy (Ep), and vertical wavelengths, are retrieved from RO temperature profiles. The intrinsic frequencies, which are retrieved from the horizontal wind field of ERA-Interim, are combined with the vertical wave parameters to derive the horizontal wavelengths and magnitudes of the PMF of GWs. The feasibility of this new strategy is validated first by comparing the distributions of GW parameters during June, July, and August (JJA) 2006 derived this way with those derived by previous studies. Then the seasonal and interannual variations of the distributions of GW PMF for three altitude ranges, 20−25 km, 25−30 km, and 30−35 km, over the globe during the seven years from June 2006 to May 2013 are presented. It is shown that the three altitude intervals share similar seasonal and interannual distribution patterns of GW PMF, while the magnitudes of GW PMF decrease with increased height and the hot spots of GW activity are the most discernable at the lowest altitude interval of 20−25 km. The maximums of PMF usually occur at latitudes around 60° in the winter hemispheres, where eastward winds prevail, and the second maximums exist over the subtropics of the summer hemispheres, where deep convection occurs. In addition, the influence of quasi-biennial oscillation (QBO) on both GW PMF and zonal winds is discernible over subtropical regions. The present work complements the GW PMF interannual variation patterns derived based on satellite observations by previous studies in terms of the altitude range, latitude coverage, and time period analyzed.

Amyotrophic lateral sclerosis (ALS) is a devastating, fatal neurological disease that primarily affects spinal cord anterior horn cells and their axons for which there is no treatment. Here we report the use of a recombinant natural human IgM that binds to the surface of neurons and supports neurite extension, rHIgM12, as a therapeutic strategy in murine models of human ALS. A single 200 µg intraperitoneal dose of rHIgM12 increases survival in two independent genetic-based mutant SOD1 mouse strains (SOD1G86R and SOD1G93A) by 8 and 10 days, delays the onset of neurological deficits by 16 days, delays the onset of weight loss by 5 days, and preserves spinal cord axons and anterior horn neurons. Immuno-overlay of thin layer chromatography and surface plasmon resonance show that rHIgM12 binds with high affinity to the complex gangliosides GD1a and GT1b. Addition of rHIgM12 to neurons in culture increases α-tubulin tyrosination levels, suggesting an alteration of microtubule dynamics. We previously reported that a single peripheral dose of rHIgM12 preserved neurological function in a murine model of demyelination with axon loss. Because rHIgM12 improves three different models of neurological disease, we propose that the IgM might act late in the cascade of neuronal stress and/or death by a broad mechanism.

Mitochondrial DNA (mtDNA) encodes proteins that are important for ATP biogenesis. Therefore, changes in mtDNA copy number will have profound consequences on cell survival and proliferation. RECQ4 DNA helicase participates in both nuclear DNA and mtDNA synthesis. However, the mechanism that balances the distribution of RECQ4 in the nucleus and mitochondria is unknown. Here, we show that RECQ4 forms protein complexes with Protein Phosphatase 2A (PP2A), nucleophosmin (NPM), and mitochondrial p32 in different cellular compartments. Critically, the interaction with p32 negatively controls the transport of both RECQ4 and its chromatin-associated replication factor, MCM10, from the nucleus to mitochondria. Amino acids that are deleted in the most common cancer-associated RECQ4 mutation are required for the interaction with p32. Hence, this RECQ4 mutant, which is no longer regulated by p32 and is enriched in the mitochondria, interacts with the mitochondrial replication helicase PEO1 and induces abnormally high levels of mtDNA synthesis.

In this study, two ionospheric peak parameters (ICPs), NmF2 and hmF2, derived from the global navigation satellite system (GNSS) radio occultation (RO) ionospheric electron density profiles (EDPs) obtained by Feng-Yun 3C (FY-3C) mission are compared with those derived from the observations of the Constellation Observing System for the Meteorology, Ionosphere, and Climate (COSMIC) mission and the measurements from 24 digisonde stations distributed around the world during the year from 2014 to 2017. The FY-3C derived ICPs and the COSMIC-derived ICPs are provided by the National Satellite Meteorological Centre (NSMC) and the COSMIC Data Analysis and Archive Center (CDAAC), respectively. The correlation and bias analyses are carried out in the comparison under the collocation criterion with the time interval of 1 h and the space interval of 3° in latitude and 5° in longitude. When comparing the ICPs derived from the two RO missions, the difference in the azimuth of occultation planes (DAOPs) between the matched pairs is limited to be within 20°. The comparison results are analyzed for different solar activity periods, and solar elevation angle (SEA) is taken for the first time as a factor that represents the comprehensive impacts of latitude zones, seasons, and local time of the observations. The results are shown as follows: (1) Both the COSMIC RO-derived and the digisonde-observed ICPs are in good agreement with the FY-3C RO-derived ones. The correlation coefficient (CC) between the NmF2 and hmF2 derived by COSMIC RO and FY-3C RO is 0.965 and 0.916, respectively, while the correlation coefficient between the NmF2 and hmF2 derived by digisonde and FY-3C RO is 0.924 and 0.832, respectively. The quality of FY-3C RO-derived ICPs are reliable enough for further applications. (2) The CC of NmF2 is, in general, higher than that of hmF2 when comparing FY-3C RO with other observations, and the overall MAB and MRB of FY-3C RO-derived ICPs during the higher solar activity period are higher than the ones during the lower solar activity period. The difference between the two RO missions is much smaller than that one between FY-3C RO and digisonde. (3) For a certain solar activity period, the standard deviations of the absolute bias (SDAB) and the standard deviations of the relative bias (SDRB) of FY-3C RO-derived ICPs compared with digisonde-derived ones generally increases with the increase of SEA, while the SDAB and SDRB of FY-3C RO-derived ICPs both get the minimum values for the AOP interval near to 90°.

Given the great achievements of the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) mission in providing huge amount of GPS radio occultation (RO) data for weather forecasting, climate research, and ionosphere monitoring, further Global Navigation Satellite System (GNSS) RO missions are being followingly planned. Higher spatial and also temporal sampling rates of RO observations, achievable with higher number of GNSS/receiver satellites or optimization of the Low Earth Orbit (LEO) constellation, are being studied by high number of researches. The objective of this study is to design GNSS RO missions which provide multi-GNSS RO events (ROEs) with the optimal performance over the globe. The navigation signals from GPS, GLONASS, BDS, Galileo, and QZSS are exploited and two constellation patterns, the 2D-lattice flower constellation (2D-LFC) and the 3D-lattice flower constellation (3D-LFC), are used to develop the LEO constellations. To be more specific, two evolutionary algorithms, including the genetic algorithm (GA) and the particle swarm optimization (PSO) algorithm, are used for searching the optimal constellation parameters. The fitness function of the evolutionary algorithms takes into account the spatio-temporal sampling rate. The optimal RO constellations are obtained for which consisting of 6–12 LEO satellites. The optimality of the LEO constellations is evaluated in terms of the number of global ROEs observed during 24 h and the coefficient value of variation (COV) representing the uniformity of the point-to-point distributions of ROEs. It is found that for a certain number of LEO satellites, the PSO algorithm generally performs better than the GA, and the optimal 2D-LFC generally outperforms the optimal 3D-LFC with respect to the uniformity of the spatial and temporal distributions of ROEs.

In this study, the relationship between gravity wave (GW) potential energy (Ep) and the tropopause height and temperature over the globe was investigated using COSMIC radio occultation (RO) dry temperature profiles during September 2006 to May 2013. The monthly means of GW Ep with a vertical resolution of 1 km and tropopause parameters were calculated for each 5° × 5° longitude-latitude grid. The correlation coefficients between Ep values at different altitudes and the tropopause height and temperature were calculated accordingly in each grid. It was found that at middle and high latitudes, GW Ep over the altitude range from lapse rate tropopause (LRT) to several km above had a significantly positive/negative correlation with LRT height (LRT-H)/ LRT temperature (LRT-T) and the peak correlation coefficients were determined over the altitudes of 10⁻14 km with distinct zonal distribution characteristics. While in the tropics, the distributions of the statistically significant correlation coefficients between GW Ep and LRT/cold point tropopause (CPT) parameters were dispersive and the peak correlation were are calculated over the altitudes of 14⁻38 km. At middle and high latitudes, the temporal variations of the monthly means and the monthly anomalies of the LRT parameters and GW Ep over the altitude of 13 km showed that LRT-H/LRT-T increases/decreases with the increase of Ep, which indicates that LRT was lifted and became cooler when GWs propagated from the troposphere to the stratosphere. In the tropical regions, statistically significant positive/negative correlations exist between GW Ep over the altitude of 17⁻19 km and LRT-H/LRT-T where deep convections occur and on the other hand, strong correlations exist between convections and the tropopause parameters in most seasons, which indicates that low and cold tropopause appears in deep convection regions. Thus, in the tropics, both deep convections and GWs excited accordingly have impacts on the tropopause structure.

Although statin therapy is a cornerstone of current low density lipoprotein (LDL)-lowering strategies, there is a need for additional therapies to incrementally lower plasma LDL cholesterol. In this study, we investigated the effect of several methylenedioxyphenol derivatives in regulating LDL cholesterol through induction of LDL receptor (LDLR). INV-403, a modified methylenedioxyphenol derivative, increased LDLR mRNA and protein expression in HepG2 cells in a dose- and time-dependent fashion. These effects were apparent even under conditions of HMG-CoA reductase inhibition. Electrophoresis migration shift assays demonstrated that INV-403 activates SREBP2 but not SREBP1c, with immunoblot analysis showing an increased expression of the mature form of SREBP2. Knockdown of SREBP2 reduced the effect of INV-403 on LDLR expression. The activation of SREBP2 by INV-403 is partly mediated by Akt/GSK3β pathways through inhibition of phosphorylation-dependent degradation by ubiquitin-proteosome pathway. Treatment of C57Bl/6j mice with INV-403 for two weeks increased hepatic SREBP2 levels (mature form) and upregulated LDLR with concomitant lowering of plasma LDL levels. Transient expression of a LDLR promoter-reporter construct, a SRE-mutant LDLR promoter construct, and a SRE-only construct in HepG2 cells revealed an effect predominantly through a SRE-dependent mechanism. INV-403 lowered plasma LDL cholesterol levels through LDLR upregulation. These results indicate a role for small molecule approaches other than statins for lowering LDL cholesterol.

Harmful algal blooms have become a great challenge to global aquatic ecosystems over the past decades. Given their low toxicity, high selectivity, and environment-friendly properties, the use of natural products and their analogues as algicides has proven to be particularly efficient. In the present study, algicidal activity of naturally occurring bacillamides A–C, alkaloid (1), and neobacillamide A, as well as their synthetic analogues were investigated intensively. Bioassay results showed that, relative to natural bacillamide alkaloids, aniline-derived analogue (10d) exhibited higher algicidal potential against three freshwater harmful algae Mycrocyctis aeruginosa, Scenedesmus obliquus, and Chlorella pyrenoidosa, suggesting that it could be used as a promising lead compound to develop novel algicide for controlling harmful algal blooms.

Exercise training offers cardioprotection against ischemia and reperfusion (I/R) injury. However, few essential signals have been identified to underscore the protection from injury. In the present study, we hypothesized that exercise-induced acceleration of myocardial tissue oxygenation recovery contributes to this protection. C57BL/6 mice (4 weeks old) were trained on treadmills for 45 min/day at a treading rate of 15 m/min for 8 weeks. At the end of 8-week exercise training, mice underwent 30-min left anterior descending coronary artery occlusion followed by 60-min or 24-h reperfusion. Electron paramagnetic resonance oximetry was performed to measure myocardial tissue oxygenation. Western immunoblotting analyses, gene transfection, and myography were examined. The oximetry study demonstrated that exercise markedly shortened myocardial tissue oxygenation recovery time following reperfusion. Exercise training up-regulated Kir6.1 protein expression (a subunit of ATP-sensitive K(+)channel on vascular smooth muscle cells, VSMC sarc-K(ATP)) and protected the heart from I/R injury. In vivo gene transfer of dominant negative Kir6.1AAA prolonged the recovery time and enlarged infarct size. In addition, transfection of Kir6.1AAA increased the stiffness and reduced the relaxation capacity in the vasculature. Together, our study demonstrated that exercise training up-regulated Kir6.1, improved tissue oxygenation recovery, and protected the heart against I/R injury. This exercise-induced cardioprotective mechanism may provide a potential therapeutic intervention targeting VSMC sarc-K(ATP) channels and reperfusion recovery.