bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA Splicing: A Versatile Regulatory Mechanism in Pediatric Liver Diseases
Authors: Zhou Jian-Li , Zhao Yu-Zhen , Wang Shan-Shan , Chen Mo-Xian , Zhou Shaoming , Chen Chen
Published: September 2021

With the development of high-throughput sequencing technology, the posttranscriptional mechanism of alternative splicing is becoming better understood. From decades of studies, alternative splicing has been shown to occur in multiple tissues, including the brain, heart, testis, skeletal muscle, and liver. This regulatory mechanism plays an important role in physiological functions in most liver diseases. Currently, due to the absence of symptoms, chronic pediatric liver diseases have a significant impact on public health. Furthermore, the progression of the disease is accelerated in children, leading to severe damage to their liver tissue if no precautions are taken. To this end, this review article summarizes the current knowledge of alternative splicing in pediatric liver diseases, paying special attention to liver damage in the child stage. The discussion of the regulatory role of splicing in liver diseases and its potential as a new therapeutic target is also included.
Increased Levels of Circulating Angiogenic Cells and Signaling Proteins in Older Adults With Cerebral Small Vessel Disease
Authors: Kapoor Arunima , Gaubert Aimée , Marshall Anisa , Meier Irene B. , Yew Belinda , Ho Jean K. , Blanken Anna E. , Dutt Shubir , Sible Isabel J. , Li Yanrong , Jang Jung Yun , Brickman Adam M. , Rodgers Kathleen , Nation Daniel A.
Published: September 2021

Background: Cerebral small vessel disease (SVD) is associated with increased risk of stroke and dementia. Progressive damage to the cerebral microvasculature may also trigger angiogenic processes to promote vessel repair. Elevated levels of circulating endothelial progenitor cells (EPCs) and pro-angiogenic signaling proteins are observed in response to vascular injury. We aimed to examine circulating levels of EPCs and proangiogenic proteins in older adults with evidence of SVD.

Methods: Older adults (ages 55–90) free of dementia or stroke underwent venipuncture and brain magnetic resonance imaging (MRI). Flow cytometry quantified circulating EPCs as the number of cells in the lymphocyte gate positively expressing EPC surface markers (CD34+CD133+CD309+). Plasma was assayed for proangiogenic factors (VEGF-A, VEGF-C, VEGF-D, Tie-2, and Flt-1). Total SVD burden score was determined based on MRI markers, including white matter hyperintensities, cerebral microbleeds and lacunes.

Results: Sixty-four older adults were included. Linear regression revealed that older adults with higher circulating EPC levels exhibited greater total SVD burden [β = 1.0 × 105, 95% CI (0.2, 1.9), p = 0.019], after accounting for age and sex. Similarly, a positive relationship between circulating VEGF-D and total SVD score was observed, controlling for age and sex [β = 0.001, 95% CI (0.000, 0.001), p = 0.048].

Conclusion: These findings suggest that elevated levels of circulating EPCs and VEGF-D correspond with greater cerebral SVD burden in older adults. Additional studies are warranted to determine whether activation of systemic angiogenic growth factors and EPCs represents an early attempt to rescue the vascular endothelium and repair damage in SVD.
The Role of Formyl Peptide Receptors in Neurological Diseases via Regulating Inflammation
Authors: Zhu Jiahui , Li Lingfei , Ding Jiao , Huang Jinyu , Shao Anwen , Tang Bo
Published: September 2021

Formyl peptide receptors (FPRs) are a group of G protein-coupled cell surface receptors that play important roles in host defense and inflammation. Owing to the ubiquitous expression of FPRs throughout different cell types and since they interact with structurally diverse chemotactic agonists, they have a dual function in inflammatory processes, depending on binding with different ligands so that accelerate or inhibit key intracellular kinase-based regulatory pathways. Neuroinflammation is closely associated with the pathogenesis of neurodegenerative diseases, neurogenic tumors and cerebrovascular diseases. From recent studies, it is clear that FPRs are important biomarkers for neurological diseases as they regulate inflammatory responses by monitoring glial activation, accelerating neural differentiation, regulating angiogenesis, and controlling blood brain barrier (BBB) permeability, thereby affecting neurological disease progression. Given the complex mechanisms of neurological diseases and the difficulty of healing, we are eager to find new and effective therapeutic targets. Here, we review recent research about various mechanisms of the effects generated after FPR binding to different ligands, role of FPRs in neuroinflammation as well as the development and prognosis of neurological diseases. We summarize that the FPR family has dual inflammatory functional properties in central nervous system. Emphasizing that FPR2 acts as a key molecule that mediates the active resolution of inflammation, which binds with corresponding receptors to reduce the expression and activation of pro-inflammatory composition, govern the transport of immune cells to inflammatory tissues, and restore the integrity of the BBB. Concurrently, FPR1 is essentially related to angiogenesis, cell proliferation and neurogenesis. Thus, treatment with FPRs-modulation may be effective for neurological diseases.
Evaluation of the Short-Term Music Therapy on Brain Functions of Preterm Infants Using Functional Near-Infrared Spectroscopy
Authors: Ren Haoran , Zou Liangyan , Wang Laishuan , Lu Chunmei , Yuan Yafei , Dai Chenyun , Chen Wei
Published: September 2021

Music contains substantial contents that humans can perceive and thus has the capability to evoke positive emotions. Even though neonatal intensive care units (NICUs) can provide preterm infants a developmental environment, they still cannot fully simulate the environment in the womb. The reduced maternal care would increase stress levels in premature infants. Fortunately, music intervention has been proved that it can improve the NICU environment, such as stabilize the heart rate and the respiratory rate, reduce the incidence of apnea, and improve feeding. However, the effects of music therapy on the brain development of preterm infants need to be further investigated. In this paper, we evaluated the influence of short-term music therapy on the brain functions of preterm infants measured by functional near-infrared spectroscopy (fNIRS). We began by investigating how premature babies perceive structural information of music by calculating the correlations between music features and fNIRS signals. Then, the influences of short-term music therapy on brain functions were evaluated by comparing the resting-state functional connectivity before and after the short-term music therapy. The results show that distinct brain regions are responsible for processing corresponding musical features, indicating that preterm infants have the capability to process the complex musical content. However, the results of network analysis show that short-term music intervention is insufficient to cause the changes in cerebral functional connectivity. Therefore, long-term music therapy may be required to achieve the deserved effects on brain functional connectivity.
Predictors and Prognosis of Symptomatic Intracranial Hemorrhage in Acute Ischemic Stroke Patients Without Thrombolysis: Analysis of Data From the Chinese Acute Ischemic Stroke Treatment Outcome Registry
Authors: Shen Zhiyuan , Jin Haiqiang , Lu Yuxuan , Sun Wei , Liu Ran , Li Fan , Shu Junlong , Tai Liwen , Li Guozhong , Chen Huisheng , Zhang Guiru , Zhang Lei , Sun Xuwen , Qiu Jinhua , Wei Yan , Sun Weiping , Huang Yining
Published: September 2021

Background and Purpose: There is limited information on symptomatic intracranial hemorrhage (sICH) in stroke patients without thrombolysis. This study aimed to evaluate the risk factors of sICH and the association between sICH and the prognosis at 3 and 12 months in acute ischemic stroke patients without thrombolysis.

Methods: Data originated from the Chinese Acute Ischemic Stroke Treatment Outcome Registry. Univariate analysis and multivariate logistic regression were used to screen the risk factors of sICH. Multivariable logistic regression models were used to assess the association of sICH with poor outcome and all-cause mortality.

Results: Totally, 9,484 patients were included, of which 69 (0.73%) had sICH. Atrial fibrillation (odds ratio [OR], 3.682; 95% confidence interval [CI], 1.945–6.971; p < 0.001), history of tumors (OR, 2.956; 95% CI, 1.115–7.593; p = 0.024), and the National Institutes of Health Stroke Scale (NIHSS) score on admission ([6–15: OR, 2.344; 95% CI, 1.365–4.024; p = 0.002] [>15: OR, 4.731; 95% CI, 1.648–13.583; p = 0.004]) were independently associated with sICH. After adjustment of the confounders, patients with sICH had a higher risk of poor outcome (OR, 1.983; 95% CI, 1.117–3.521; p = 0.018) at 3 months and that of all-cause mortality at 3 (OR, 6.135; 95% CI, 2.328–16.169; p < 0.001) and 12 months (OR, 3.720; 95% CI, 1.513–9.148; p = 0.004).

Conclusion: sICH occurred in 0.73% of acute ischemic stroke patients without thrombolysis and was associated with a worse prognosis at 3 and 12 months. Atrial fibrillation, history of tumors, and NIHSS score at admission were independent risk factors of sICH.
Association Between Dietary Intake of One-Carbon Metabolism-Related Nutrients and Fluorosis in Guizhou, China
Authors: Chen Ting , Tao Na , Yang Sheng , Cao Dafang , Zhao Xun , Wang Donghong , Liu Jun
Published: September 2021

Objective: This study aimed to investigate the associations between dietary one-carbon metabolism-related nutrients (betaine, choline, methionine, folate, vitamin B6, and vitamin B12) and fluorosis among the Chinese population in an area known for coal-burning fluorosis.

Methods: A cross-sectional study was conducted, with 653 fluorosis patients and 241 non-fluorosis participants. Dietary intake was acquired using a validated semi-quantitative 75-item food frequency questionnaire. The risk associations were assessed by unconditional logistical regression.

Results: We observed a significant inverse association between dietary betaine, total choline, methionine, folate, vitamin B6, and choline species and fluorosis. The adjusted OR (95% CI) in the highest quartile of consumption compared with the lowest were 0.59 (0.37–0.94) (P-trend = 0.010) for betaine intake, 0.45 (0.28–0.73) (P-trend = 0.001) for total choline intake, 0.45 (0.28–0.72) (P-trend < 0.001) for methionine intake, 0.39 (0.24–0.63) (P-trend < 0.001) for folate intake, 0.38 (0.24–0.62) (P-trend < 0.001) for vitamin B6 intake, and 0.46 (0.28–0.75) (P-trend = 0.001) for total choline plus betaine intake. Dietary intakes of choline-containing compounds, phosphatidylcholine, free choline, glycerophosphocholine, and phosphocholine were also inversely associated with lower fluorosis (all P-trend < 0.05). No significant associations were observed between dietary vitamin B12 or sphingomyelin and fluorosis.

Conclusion: The present study suggested that the higher dietary intakes of specific one-carbon metabolism-related nutrients, such as betaine, choline, methionine, folate, and vitamin B6, are associated with lower fluorosis prevalence.
Factors Associated With the Discussion of Fertility Preservation in a Cohort of 1,357 Young Breast Cancer Patients Receiving Chemotherapy
Authors: Hours Alice , Toussaint Aullene , De Castelbajac Victoire , Sautter Camille , Borghese Julie , Frank Sophie , Coussy Florence , Laas Enora , Grandal Beatriz , Dumas Elise , Daoud Eric , Guerin Julien , Balezeau Thomas , Feron Jean-Guillaume , Fourchotte Virginie , Kirova Youlia , Lerebours Florence , Pierga Jean-Yves , Guillot Eugénie , Santulli Pietro , Grynberg Michael , Sonigo Charlotte , Reyrat Emmanuel , Soibinet-Oudot Pauline , Reyal Fabien , Hamy Anne-Sophie
Published: September 2021

Purpose

Female breast cancer (BC) patients exposed to gonadotoxic chemotherapy are at risk of future infertility. There is evidence of disparities in the discussion of fertility preservation for these patients. The aim of the study was to identify factors influencing the discussion of fertility preservation (FP).

Material and Methods

We analyzed consecutive BC patients treated by chemotherapy at Institut Curie from 2011-2017 and aged 18-43 years at BC diagnosis. The discussion of FP was classified in a binary manner (discussion/no discussion), based on mentions present in the patient’s electronic health record (EHR) before the initiation of chemotherapy. The associations between FP discussion and the characteristics of patients/tumors and healthcare practitioners were investigated by logistic regression analysis.

Results

The median age of the 1357 patients included in the cohort was 38.7 years, and median tumor size was 30.3 mm. The distribution of BC subtypes was as follows: 702 luminal BCs (58%), 241 triple-negative breast cancers (TNBCs) (20%), 193 HER2+/HR+ (16%) and 81 HER2+/HR- (6%). All patients received chemotherapy in a neoadjuvant (n=611, 45%) or adjuvant (n= 744, 55%) setting. A discussion of FP was mentioned for 447 patients (33%). Earlier age at diagnosis (discussion: 34.4 years versus no discussion: 40.5 years), nulliparity (discussion: 62% versus no discussion: 38%), and year of BC diagnosis were the patient characteristics significantly associated with the mention of FP discussion. Surgeons and female physicians were the most likely to mention FP during the consultation before the initiation of chemotherapy (discussion: 22% and 21%, respectively). The likelihood of FP discussion increased significantly over time, from 15% in 2011 to 45% in 2017. After multivariate analysis, FP discussion was significantly associated with younger age, number of children before BC diagnosis, physicians’ gender and physicians’ specialty.

Conclusion

FP discussion rates are low and are influenced by patient and physician characteristics. There is therefore room for improvement in the promotion and systematization of FP discussion.
Crosstalk Between Abnormal TSHR Signaling Activation and PTEN/PI3K in the Dedifferentiation of Thyroid Cancer Cells
Authors: Feng Fang , Han Huiqin , Wu Shuqi , Wang Hui
Published: September 2021

Iodide uptake and the metabolism of thyroid cells are regulated by thyrotropin (TSH)-TSH receptor (TSHR) signaling. Thus, it is necessary to elevate serum TSH levels by T4 withdraw or rTSH administration to facilitate radioiodide (131I) therapy for differentiated thyroid cancer (DTC). However, non-iodide-avid metastases of DTC which is dedifferentiated do not respond to stimulation by high levels of TSH, suggesting abnormal TSH-TSHR signal transduction in cancer cells. In addition, PI3K/AKT/mTOR signaling activation has been shown to be associated with the dedifferentiated phenotype of thyroid cancer, but the mechanism remains elusive. Therefore, in this study, we aimed to explore the role of abnormal TSH-TSHR signaling activation in regulating iodide uptake and cell mobility in thyroid cancer and its relationship with PI3K/AKT/mTOR signaling. We found that in thyroid cancer cells, TSH binds TSHR coupled to the Gα12/13 protein and then activates RhoA through interacting with leukemia associated RhoA guanine exchange factor (LARG). This results in a promigration tumorigenic phenotype independent of canonical TSHR-GαS signaling that regulates the expression of molecules involved in iodine uptake and metabolism. We observed that signaling pathways downstream of Gα12/13 signaling were increased, while that of Gαs signaling was decreased in thyroid cancer cells undergoing dedifferentiation compared to control cells following stimulation with different levels of TSH. PI3K/AKT/mTOR signaling activation enhanced Gα12/13 signaling through increasing LARG levels but also inhibited the expression of molecules downstream of Gαs signaling, including thyroid-specific molecules, and iodide uptake. In summary, our results demonstrate the noncanonical activation of TSH-TSHR signaling and its role in increasing the cell mobility and dedifferentiation of thyroid cancer through crosstalk with PI3K/AKT/mTOR signaling.
Prognostic Value of Serum Osteoprotegerin Level in Patients With Hepatocellular Carcinoma Following Surgical Resection
Authors: Zhang Chihao , Lin Jiayun , Ni Xiaochun , Li Hongjie , Zheng Lei , Zhao Zhifeng , Qi Xiaoliang , Huo Haizhong , Lou Xiaolou , Fan Qiang , Luo Meng
Published: September 2021

Background

Multiple studies have reported that tissue or serum osteoprotegerin (OPG) level is a prognostic factor for patients with cancer. However, little is known about the role of serum OPG in hepatocellular carcinoma (HCC). In this study, we aimed to investigate whether serum OPG concentration has an effect on HCC patients’ prognosis.

Methods

A total of 386 eligible HCC patients undergoing radical hepatectomy were enrolled from Shanghai Ninth People’s Hospital and Zhongshan Hospital between 2010 and 2018. Kaplan-Meier curves, Cox regression model, and the restricted mean survival time (RMST) were used to estimate the association of OPG and HCC patients’ survival outcome. In addition, sensitivity analyses were carried out including subgroup analysis and propensity score matching (PSM).

Results

Patients were separated into two groups according to the cut-off value of OPG calculated by X-tile. Multivariate Cox analysis showed that patients with high OPG level had worse overall survival (OS) (HR: 1.93; 95% CI: 1.40–2.66, p<0.001) and disease-free survival (DFS) (HR: 1.85; 95% CI: 1.39–2.47, p<0.001) before matching. On average, RMST ratio between high and low OPG turned out to be 0.797 (95% CI: 0.716–0.887, p<0.001). In the matched population, we found that OPG level was negatively associated with OS (HR: 1.85; 95% CI: 1.25–2.74, p=0.002) and DFS (HR: 1.71; 95% CI: 1.20–2.44, p=0.003). In addition, a similar trend was further confirmed by subgroup analyses.

Conclusion

In a word, HCC patients with high OPG level had poorer survival rates compared with HCC patients with low OPG level. This factor could act as a potential prognostic predictor for HCC patients who underwent radical resection in the future.
A Systematic Analysis Identifies Key Regulators Involved in Cell Proliferation and Potential Drugs for the Treatment of Human Lung Adenocarcinoma
Authors: Wang Kai , Zhang Man , Wang Jiao , Sun Pan , Luo Jizhuang , Jin Haizhen , Li Rong , Pan Changqing , Lu Liming
Published: September 2021

Lung adenocarcinoma (LUAD) is one of the most common and malignant cancer types. Abnormal cell proliferation, exemplified by cell cycle and cell division dysregulation, is one of the most prominent hallmarks of cancer and is responsible for recurrence, metastasis, and resistance to cancer therapy. However, LUAD-specific gene regulation and clinical significance remain obscure. Here, by using both tissues and cells from LUAD and normal lung samples, 434 increased and 828 decreased genes of biological significance were detected, including 127 cell cycle-associated genes (95 increased and 32 decreased), 66 cell division-associated genes (56 increased and 10 decreased), and 81 cell proliferation-associated genes (34 increased and 47 decreased). Among them, 12 increased genes (TPX2, CENPF, BUB1, PLK1, KIF2C, AURKB, CDKN3, BUB1B, HMGA2, CDK1, ASPM, and CKS1B) and 2 decreased genes (TACC1 and MYH10) were associated with all the three above processes. Importantly, 2 (CDKN3 and CKS1B) out of the 11 increased genes (except HMGA2) are previously uncharacterized ones in LUAD and can potentially be prognostic markers. Moreover, PLK1 could be a promising therapeutic target for LUAD. Besides, protein–protein interaction network analysis showed that CDK1 and CDC20 were the hub genes, which might play crucial roles in cell proliferation of LUAD. Furthermore, transcriptional regulatory network analysis suggested that the transcription factor E2F1 could be a key regulator in controlling cell proliferation of LUAD via expression modulation of most cell cycle-, cell division-, and cell proliferation-related DEGs. Finally, trichostatin A, hycanthone, vorinostat, and mebeverine were identified as four potential therapeutic agents for LUAD. This work revealed key regulators contributing to cell proliferation in human LUAD and identified four potential therapeutic agents for treatment strategy.
Evaluation of Severity of Illness Scores in the Pediatric ECMO Population
Authors: Pinto Venessa L. , Guffey Danielle , Loftis Laura , Bembea Melania M. , Spinella Philip C. , Hanson Sheila J.
Published: September 2021

Though commonly used for adjustment of risk, severity of illness and mortality risk prediction scores, based on the first 24 h of intensive care unit (ICU) admission, have not been validated in the pediatric extracorporeal membrane oxygenation (ECMO) population. We aimed to determine the association of Pediatric Index of Mortality 2 (PIM2), Pediatric Risk of Mortality Score III (PRISM III) and Pediatric Logistic Organ Dysfunction (PELOD) scores with mortality in pediatric patients on ECMO. This was a retrospective cohort study of children ≤18 years of age included in the Pediatric ECMO Outcomes Registry (PEDECOR) from 2014 to 2018. Logistic regression and Receiver Operating Characteristics (ROC) curves were used to calculate the area under the curve (AUC) to evaluate association of mortality with the scores. Of the 655 cases, 289 (44.1%) did not survive until hospital discharge. AUCs for PIM2, PRISM III, and PELOD predicting mortality were 0.52, 0.52, and 0.51 respectively. PIM2, PRISM III, and PELOD scores are not associated with odds of mortality for pediatric patients receiving ECMO. These scores for a general pediatric ICU population should not be used for prognostication or risk stratification of a select population such as ECMO patients.
Intratracheal Keratinocyte Growth Factor Enhances Surfactant Protein B Expression in Mechanically Ventilated Preterm Pigs
Authors: Krishnan Ramesh , Arrindell Esmond L. , Frank Caminita , Jie Zhang , Buddington Randal K.
Published: September 2021

Bronchopulmonary dysplasia (BPD) is a devastating disease of prematurity that is associated with mechanical ventilation and hyperoxia. We used preterm pigs delivered at gestational day 102 as a translational model for 26–28-week infants to test the hypothesis administering recombinant human keratinocyte growth factor (rhKGF) at initiation of mechanical ventilation will stimulate type II cell proliferation and surfactant production, mitigate ventilator induced lung injury, and reduce epithelial to mesenchymal transition considered as a precursor to BPD. Newborn preterm pigs were intubated and randomized to receive intratracheal rhKGF (20 μg/kg;n= 6) or saline (0.5 ml 0.9% saline; control;n= 6) before initiating 24 h of ventilation followed by extubation to nasal oxygen for 12 h before euthanasia and collection of lungs for histopathology and immunohistochemistry to assess expression of surfactant protein B and markers of epithelial to mesenchymal transition. rhKGF pigs required less oxygen during mechanical ventilation, had higher tidal volumes at similar peak pressures indicative of improved lung compliance, and survival was higher after extubation (83% vs. 16%). rhKGF increased surfactant protein B expression (p< 0.05) and reduced TGF-1β (p< 0.05), that inhibits surfactant production and is a prominent marker for epithelial to mesenchymal transition. Our findings suggest intratracheal administration of rhKGF at initiation of mechanical ventilation enhances surfactant production, reduces ventilator induced lung injury, and attenuates epithelial-mesenchymal transition while improving pulmonary functions. rhKGF is a potential therapeutic strategy to mitigate pulmonary responses of preterm infants that require mechanical ventilation and thereby reduce the incidence and severity of bronchopulmonary dysplasia.
Epidemiology of Adenovirus Pneumonia and Risk Factors for Bronchiolitis Obliterans in Children During an Outbreak in Jilin, China
Authors: Yu Xiuhua , Ma Yucong , Gao Yang , You Hailong
Published: September 2021

Background: Jilin Province, located in northeastern China, recently experienced a human adenovirus (HAdV) epidemic. Few studies involving hospitalized pediatric patients with pneumonia caused by HAdV in our region exist. HAdV pneumonia can lead to severe long-term respiratory sequelae, such as post-infectious bronchiolitis obliterans (PIBO), which has a poor prognosis and greatly influences the quality of life of pediatric patients. However, studies on the risk factors for PIBO are limited.

Objective: To describe the HAdV pneumonia prevalence and determine potential risk factors for PIBO development among hospitalized children in Jilin Province, China.

Methods: The data of 187 children with HAdV pneumonia (10 months−12 years old) admitted to the First Hospital of Jilin University during an outbreak between October 2018 and January 2020 were retrospectively studied. We analyzed the epidemiological characteristics of HAdV pneumonia, focusing on severe HAdV pneumonia (66 cases). The risk factors for BO development were determined by comparing the demographic and clinical data of the BO and non-BO groups.

Results: The largest number of HAdV pneumonia cases occurred in January 2019 (severe n = 18, general n = 21), followed by December 2018 (severe n = 14, general n = 11), June 2019 (general n = 17), July 2019 (general, n = 14), and May 2019 (general, n = 13). In total, 91.98% of the children with HAdV pneumonia were <6 years old (172/187), and 50% of the pediatric patients with severe HAdV pneumonia were <2 years old (33/66). We found that 30.3% of the severe cohort developed BO (20/66), and the strongest independent risk factors for PIBO were persistent wheezing (OR 181.776, 95% CI, 3.385–9,761.543) and acute respiratory failure (OR 51.288, 95% CI, 1.858–1,415.441) during a severe pneumonia episode.

Conclusions: The largest number of HAdV pneumonia cases, especially severe cases, occurred in winter in Northeast China, followed by summer. The majority of children admitted with HAdV pneumonia were <6 years old, and half of severe HAdV pneumonia patients were <2 years old. Children who had persistent wheezing or acute respiratory failure during the acute phase of severe HAdV pneumonia were prone to the development of BO.
Xueshuantong Improves Functions of Lymphatic Ducts and Modulates Inflammatory Responses in Alzheimer’s Disease Mice
Authors: Zheng Rui , Huang Yang-mei , Zhou Qiang
Published: September 2021

Recent studies have revealed significant contributions of lymphatic vessels (LVs) to vital functions of the brain, especially related to clearance of waste from the brain and immune responses in the brain. These studies collectively indicate that enhancing the functions of LVs may improve brain functions during brain aging and in Alzheimer’s disease (AD) where LV functions are impaired. However, it is currently unknown whether this enhancement can be achieved using small molecules. We have previously shown that a widely used Chinese herbal medicine Xueshuantong (XST) significantly improves functions and reduces pathology in AD transgenic mice associated with elevated cerebral blood flow (CBF). Here, we show that XST partially rescues deficits in lymphatic structures, improves clearance of amyloid-β (Aβ) from the brain, and reduces the inflammatory responses in the serum and brains of transgenic AD mice. In addition, we showed that this improvement in the lymphatic system occurs independently of elevated CBF, suggesting independent modulation and limited interaction between blood circulation and lymphatic systems. Moreover, XST treatment leads to a significant increase in GLT-1 level and a significantly lower level of MMP-9 and restores AQP4 polarity in APP/PS1 mice. These results provide the basis for further exploration of XST to enhance or restore LV functions, which may be beneficial to treat neurodegenerative diseases or promote healthy aging.
Combined Administration of Vitamin D3 and Geniposide Is Less Effective than Single Use of Vitamin D3 or Geniposide in the Treatment of Ulcerative Colitis
Authors: Lu Yingyu , Chen Jianqiang , He Xueling , Xu Shuoxi , Chen Yong-er , Gao Jie , Hou Shaozhen
Published: September 2021

With the increasing incidence of ulcerative colitis (UC) in China, Chinese medicinal herbs or relatively active compounds are widely applied in treating UC. These medicines may be combined with other therapeutic agents such as vitamin D3. Nevertheless, the efficacy of these combinations for UC is unclear. Geniposide is an active component in many Chinese herbal medicines. It could ameliorate dextran sulfate sodium (DSS)–induced colitis in mice. This study was designed to determine the efficacy and mechanism of the single use and combination of geniposide and vitamin D3 on a mouse model of acute colitis. Data showed that a single administration of geniposide (2 mg/kg) or vitamin D3 (4 IU/day) could significantly improve the symptoms of UC and relieve colon damage. Geniposide and vitamin D could significantly decrease the levels of TNF-α and IL-6 in serum and colon, and increase the level of IL-10 in the colon. However, the combined treatment of geniposide (2 mg/kg) and vitamin D3 (4 IU/day) exerted less beneficial effects on UC in mice, indicating by less improvement of UC symptoms, colon damage, and inflammatory infiltration. The combination only downregulated the level of TNF-α in serum and IL-6 in the colon. Our data further demonstrated that geniposide could inhibit the activation of p38 MAPK and then restrict the vitamin D receptor signaling stimulated by vitamin D3. These results implied that the combination of geniposide and vitamin D3 might not be an ideal combined treatment for acute colitis, and the combination of vitamin D supplementary and geniposide (or herbal medicines rich in geniposide) need more evaluation before being applied to treat UC in clinic.
Selective STAT3 Inhibitor Alantolactone Ameliorates Osteoarthritis via Regulating Chondrocyte Autophagy and Cartilage Homeostasis
Authors: Pei Wenbin , Huang Xiaojian , Ni Bowei , Zhang Rui , Niu Guangyi , You Hongbo
Published: September 2021

Osteoarthritis (OA), which is identified by chronic pain, impacts the quality of life. Cartilage degradation and inflammation are the most relevant aspects involved in its development. Signal transducer and activator of transcription 3(STAT3), a member of the STATs protein family, is associated with inflammation. Alantolactone (ALT), a sesquiterpene lactone compound, can selectively suppress the phosphorylation of STAT3. However, the pharmacological effect of ALT on OA is still imprecise. In this study, IL-1β (10 ng/ml) was applied to cartilage chondrocytes, which were treated with different concentrations of Alantolactone for 24 h. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2(COX2), matrix metalloproteinases (MMPs) and thrombospondin motifs-5 (ADAMTS5) were detected by western blot. Protein expression of Collagen Ⅱ was observed by western blot, safranin O staining and immunofluorescence. Manifestation of autophagy related proteins such as autophagy-related gene-5 (ATG5), P62, LC3Ⅱ/Ⅰ and PI3K/AKT/mTOR-related signaling molecules were measured by western blot and autophagic flux monitored by confocal microscopy. Expression of STAT3 and NF-κB-related signaling molecules were evaluated by western blot and immunofluorescence. In vivo, 2 mg/kg ALT or equal bulk of vehicle was engaged in the destabilization of medial meniscus (DMM) mouse models by intra-articular injection, the degree of cartilage destruction was classified by Safranin O/Fast green staining. Our findings reported that the enhance of inflammatory factors containing iNOS, COX2, MMPs and ADAMTS5 induced by IL-1β could be ameliorated by ALT. Additionally, the diminish of Collagen Ⅱ and autophagy which was stimulated by IL-1β could be alleviated by ALT. Mechanistically, STAT3, NF-κB and PI3K/AKT/mTOR signal pathways might be involved in the effect of ALT on IL-1β-induced mouse chondrocytes. In vivo, ALT protected cartilage in the DMM mouse model. Overall, this study illustrated that ALT attenuated IL-1β-induced inflammatory responses, relieved cartilage degeneration and promoted impaired autophagy via restraining of STAT3 and NF-κB signal pathways, implying its auspicious therapeutical effect for OA.
Pseudospin-dependent Acoustic Topological Insulator by Sonic Crystals With Same Hexagonal Rods
Authors: Jia Ding , Gu Shuai , Jiang Shuai , Ge Yong , Yuan Shou-qi , Sun Hong-xiang
Published: September 2021

We report the experimental and numerical realization of a pseudospin-dependent acoustic topological insulator based on two sonic crystals constructed by the same regular hexagonal rods. Based on the zone folding mechanism, we obtain double Dirac cones with a four-fold deterministic degeneracy in the sonic crystal, and realize a band inversion and topological phase transition by rotating the rods. We observe the topologically protected one-way sound propagation of pseudospin-dependent edge states in a designed topological insulator composed of two selected sonic crystals with different rotation angles of the rods. Furthermore, we experimentally demonstrate the robustness of topological sound propagation against two types of defects, in which the edge states are almost immune to backscattering, and remain pseudospin-dependent characteristics. Our work provides a diverse route for designing tunable topological functional sound devices.
Acceleration of Longitudinal Track and Field Performance Declines in Athletes Who Still Compete at the Age of 100 Years
Authors: Ganse Bergita , Braczynski Anne Kristin , Hoog Antink Christoph , Knobe Matthias , Pohlemann Tim , Degens Hans
Published: September 2021

While physical performance decline rates accelerate after around the age of 70 years, longitudinal athletic performance trends in athletes older than 95 years are unknown. We hypothesized a further accelerated decline in human performance in athletes who still perform at the age of 100 years. To investigate this, longitudinal data of all athletes with results at or over the age of 100 years were collected from the “World Master Rankings” data base spanning 2006–2019 (138 results from 42 athletes; 5 women, 37 men; maximum 105 years) and compared to previously published longitudinal data from 80- to 96-year-old athletes from Sweden (1,134 results from 374 athletes). Regression statistics were used to compare performance decline rates between disciplines and age groups. On average, the individual decline rate of the centenarian group was 2.53 times as steep (100 m: 8.22x; long jump: 0.82x; shot put: 1.61x; discus throw: 1.04x; javelin throw: 0.98x) as that seen in non-centenarians. The steepest increase in decline was found in the 100-m sprint (t-test: p < 0.05, no sign. difference in the other disciplines). The pooled regression statistics of the centenarians are: 100 m: R = 0.57, p = 0.004; long jump: R = 0.90, p < 0.001; shot put: R = 0.65, p < 0.001; discus throw: R = 0.73, p < 0.001; javelin throw: R = 0.68, p < 0.001. This first longitudinal dataset of performance decline rates of athletes who still compete at 100 years and older in five athletics disciplines shows that there is no performance plateau after the age of 90, but rather a further acceleration of the performance decline.
Activation of Yes-Associated Protein/PDZ-Binding Motif Pathway Contributes to Endothelial Dysfunction and Vascular Inflammation in AngiotensinII Hypertension
Authors: Xu Qian , Zhuo Kunping , Cai Ruiping , Su Xiaomin , Zhang Lu , Liu Yueyang , Zhu Lin , Ren Fu , Zhou Ming-Sheng
Published: September 2021

Yes-associated protein (YAP) and its associated coactivator of PDZ-binding motif (TAZ) are co-transcriptional regulators and down effectors of the Hippo signaling pathway. Recent studies have shown that the Hippo/YAP signaling pathway may play a role in mediating vascular homeostasis. This study investigated the role of YAP/TAZ in endothelial dysfunction and vascular inflammation in angiotensin (Ang)II hypertensive mice. The infusion of AngII (1.1 mg/kg/day by mini-pump) for 3 weeks induced the activation of YAP/TAZ, manifested by decreased cytosolic phosphor-YAP and phosphor-TAZ, and increased YAP/TAZ nuclear translocation, which were prevented by YAP/TAZ inhibitor verteporfin. AngII significantly increased systolic blood pressure (SBP), macrophage infiltration, and expressions of proinflammatory cytokines, and impaired endothelial function in the aorta of the mice. Treatment with verteporfin improved endothelial function and reduced vascular inflammation with a mild reduction in SBP. AngII also induced YAP/TAZ activation in human umbilical vein endothelial cells in vitro, which were prevented by LB-100, an inhibitor of protein phosphatase 2A (PP2A, a major dephosphorylase). Treatment with LB-100 reversed AngII-induced proinflammatory cytokine expression and impairment of phosphor-eNOS expression in vitro. Our results suggest that AngII induces YAP/TAZ activation via PP2A-dependent dephosphorylation, which may contribute to the impairment of endothelial function and the induction of vascular inflammation in hypertension. YAP/TAZ may be a new target for hypertensive vascular injury.
Boswellia serrata Extract Containing 30% 3-Acetyl-11-Keto-Boswellic Acid Attenuates Inflammatory Mediators and Preserves Extracellular Matrix in Collagen-Induced Arthritis
Authors: Majeed Muhammed , Nagabhushanam Kalyanam , Lawrence Lincy , Nallathambi Rameshprabu , Thiyagarajan Varadharajan , Mundkur Lakshmi
Published: September 2021

Boswellia serrata extracts have been traditionally employed for the treatment of inflammatory diseases. In the present study, we have evaluated the mechanism of activity of Boswellin Super® FJ (BSE), a standardized extract of B. serrata containing not less than 30% 3-acetyl-11-keto-β-boswellic acid along with other β-boswellic acids. The in vitro anti-inflammatory activities were carried out in RAW 264.7 macrophages or human peripheral blood mononuclear cells stimulated with bacterial lipopolysaccharides (LPS) and treated with 1.25-5μg/ml BSE. The anti-arthritic activity of the extract was evaluated in a rat model of collagen-induced arthritis. BSE at 40 and 80mg/kg and celecoxib 10mg/kg were orally dosed for 21days. BSE showed significant (p<0.05) inhibition of inflammation (TNF-α, IL-6, nitric oxide, and COX-2 secretion) and downregulates the mRNA levels of TNF-α, IL-6, IL1-β, and inducible nitric oxide synthase in macrophages. BSE treatment reduced the levels of phosphorylated-NF-κB (P65), suggesting an anti-inflammatory activity mediated by blocking this key signal transduction pathway. In addition, BSE showed inhibition (p<0.05) of collagenase, elastase, hyaluronidase enzymes, and a reduction in reactive oxygen species and matrix-degrading proteins in RAW 264.7 macrophages stimulated with LPS. BSE treatment significantly (p<0.05) reduced the arthritic index, paw volume, and joint inflammation comparable to celecoxib in collagen-induced arthritis (CIA) in rats. The circulating anti-collagen antibodies were reduced in BSE and celecoxib-treated animals as compared to the CIA. In confirmation with in vitro data, BSE showed a significant (p<0.05) dose-dependent effect on C-reactive protein, prostaglandin E2, and erythrocyte sedimentation rate, which is widely used as a blood marker of inflammation. Further, BSE treatment suppressed the cartilage oligomeric matrix protein and significantly enhanced the hyaluronan levels in synovial fluid. As observed by collagen staining in joints, the loss of matrix proteins was lower in BSE-treated animals, suggesting that BSE could preserve the extracellular matrix in RA. The extract showed inhibition of collagenase enzyme activity in vitro, further strengthening this hypothesis. BSE treatment was found to be safe, and rats displayed no abnormal behavior or activities. The results suggest that Boswellin Super® mediates its activity by preserving matrix proteins, reducing pro-inflammatory mediators, and oxidative stress.
Sex Differences and Regulatory Actions of Estrogen in Cardiovascular System
Authors: Ueda Kazutaka , Fukuma Nobuaki , Adachi Yusuke , Numata Genri , Tokiwa Hiroyuki , Toyoda Masayuki , Otani Akira , Hashimoto Masaki , Liu Pang-Yen , Takimoto Eiki
Published: September 2021

Great progress has been made in the understanding of the pathophysiology of cardiovascular diseases (CVDs), and this has improved the prevention and prognosis of CVDs. However, while sex differences in CVDs have been well documented and studied for decades, their full extent remains unclear. Results of the latest clinical studies provide strong evidence of sex differences in the efficacy of drug treatment for heart failure, thereby possibly providing new mechanistic insights into sex differences in CVDs. In this review, we discuss the significance of sex differences, as rediscovered by recent studies, in the pathogenesis of CVDs. First, we provide an overview of the results of clinical trials to date regarding sex differences and hormone replacement therapy. Then, we discuss the role of sex differences in the maintenance and disruption of cardiovascular tissue homeostasis.
Composition and Protein Precipitation Capacity of Condensed Tannins in Purple Prairie Clover (Dalea purpurea Vent.)
Authors: Huang Qianqian , Hu Tianming , Xu Zhongjun , Jin Long , McAllister Tim A. , Acharya Surya , Zeller Wayne E. , Mueller-Harvey Irene , Wang Yuxi
Published: September 2021

This study aimed to determine the concentration and composition of condensed tannins (CT) in different tissues of purple prairie clover (PPC; Dalea purpurea Vent.) at different maturities and to determine their protein-precipitating capacity. The compositions of CT were elucidated after thiolysis with benzyl mercaptan followed by high-performance liquid-chromatography (HPLC) and 1H–13C heteronuclear single quantum coherence (HSQC) NMR spectroscopy. The results indicated that PPC flowering heads contained the highest CT concentration. Purple prairie clover CT consisted mainly of epicatechin (EC) and epigallocatechin (EGC) subunits. CT in the leaves were composed of more EC and less EGC than CT in stems and flowering heads at both the early flowering (EF) and late flowering (LF) head stages. The mean degree of polymerization was the highest for CT in stems and increased with maturity. CT isolated from PPC leaves at the early flowering head stage exhibited the greatest biological activity in terms of protein precipitation. Overall, the CT in PPC were predominantly procyanidins and the concentration and composition varied among the plant tissues and with maturity.
Extensively Current Activity of Transposable Elements in Natural Rice Accessions Revealed by Singleton Insertions
Authors: Liu Zhen , Zhao Han , Yan Yan , Wei Ming-Xiao , Zheng Yun-Chao , Yue Er-Kui , Alam Mohammad Shah , Smartt Kwesi Odel , Duan Ming-Hua , Xu Jian-Hong
Published: September 2021

Active transposable elements (TEs) have drawn more attention as they continue to create new insertions and contribute to genetic diversity of the genome. However, only a few have been discovered in rice up to now, and their activities are mostly induced by artificial treatments (e.g., tissue culture, hybridization etc.) rather than under normal growth conditions. To systematically survey the current activity of TEs in natural rice accessions and identify rice accessions carrying highly active TEs, the transposon insertion polymorphisms (TIPs) profile was used to identify singleton insertions, which were unique to a single accession and represented the new insertion of TEs in the genome. As a result, 10,924 high-confidence singletons from 251 TE families were obtained, covering all investigated TE types. The number of singletons varied substantially among different superfamilies/families, perhaps reflecting distinct current activity. Particularly, eight TE families maintained potentially higher activity in 3,000 natural rice accessions. Sixty percent of rice accessions were detected to contain singletons, indicating the extensive activity of TEs in natural rice accessions. Thirty-five TE families exhibited potentially high activity in at least one rice accession, and the majority of them showed variable activity among different rice groups/subgroups. These naturally active TEs would be ideal candidates for elucidating the molecular mechanisms underlying the transposition and activation of TEs, as well as investigating the interactions between TEs and the host genome.
Efficacy of Entrepreneurs' Psychological Capital on the Performance of New Ventures in the Development of Regional Economy in the Greater Bay Area
Authors: Chen Hongbo , Tao Yitao
Published: September 2021

The study aims to analyze the relationship between the psychological capital and enterprise performance of the entrepreneurs and provide direction for the optimization of regional economic development and talent introduction mechanism. First, the theoretical basis is established from regional economic development, innovative talent introduction, and individual psychological capital theory, according to which the questionnaire survey is designed, and four dimensions of self-efficacy (C), wish (W), toughness (T), and optimism (O) are selected to set the questions on psychological capital and innovation performance. Then, following statistical analysis, the characteristics of the new ventures are revealed. Finally, based on the empirical research model, the hypotheses are put forward based on psychological capital and its four subdimensions, and the relationship between the efficacy of the psychological capital and the performance of new ventures of the entrepreneurs is revealed through regression analysis. The results show that the proportion of the computer and education industry in the new ventures reaches 67.7%, and the proportion of enterprises with 1–5 entrepreneurial years reaches 78%. Meanwhile, the proportion of first-time entrepreneurship is 60.5%, and the proportion of entrepreneurs motivated by their ideal reaches 35.8%. The new entrepreneurs have a good grasp of the market situation, and the overall operation condition is stable. Most of them originate from micro and small enterprises (MSE). Psychological capital has a great influence on individual entrepreneurship. The empirical results show that the psychological capital of entrepreneurs has a positive effect on the performance of new ventures. Except for the subdimension of O, the other three subdimensions (C, T, and W) of psychological capital have a positive effect on the performance of new ventures, and psychological capital as a whole has the greatest impact. The results provide a reference for the relationship between the performance improvement of new ventures and regional economic development.
Finger-Counting and Numerical Structure
Authors: Overmann Karenleigh A.
Published: September 2021

Number systems differ cross-culturally in characteristics like how high counting extends and which number is used as a productive base. Some of this variability can be linked to the way the hand is used in counting. The linkage shows that devices like the hand used as external representations of number have the potential to influence numerical structure and organization, as well as aspects of numerical language. These matters suggest that cross-cultural variability may be, at least in part, a matter of whether devices are used in counting, which ones are used, and how they are used.