bluuebunny/crossref_metadata_2025 huggingface dataset:
Presence of Tumor Necrosis Factor-Alpha in Urine Samples of Patients With Chronic Low Back Pain Undergoing Chiropractic Care: Preliminary Findings From a Prospective Cohort Study
Authors: Gevers-Montoro Carlos , Romero-Santiago Mar , Losapio Lisa , Conesa-Buendía Francisco Miguel , Newell Dave , Álvarez-Galovich Luis , Piché Mathieu , Ortega-De Mues Arantxa
Published: April 2022

Background and aims

Low back pain is the leading cause of years lived with disability worldwide. Chiropractors employ different interventions to treat low back pain, including spinal manipulative therapy, although the mechanisms through which chiropractic care improves low back pain are still unclear. Clinical research and animal models suggest that spinal manipulation might modulate plasma levels of inflammatory cytokines, which have been involved in different stages of low back pain. More specifically, serum levels of Tumor Necrosis Factor-alpha (TNF-α) have been found to be elevated in patients with chronic low back pain. We aimed to investigate whether urine from chronic low back pain patients could be an appropriate medium to measure concentrations of TNF-α and to examine possible changes in its levels associated to chiropractic care.

Methods

Urine samples were collected from 24 patients with chronic low back pain and TNF-α levels were analyzed by ELISA before and after 4–6 weeks of care compared to a reference value obtained from 5 healthy control subjects, by means of a Welch’s t-test. Simultaneously, pain intensity and disability were also evaluated before and after care. Paired t-tests were used to compare mean pre and post urinary concentrations of TNF-α and clinical outcomes.

Results

Significantly higher baseline levels of urinary TNF-α were observed in chronic low back pain patients when compared to our reference value (p < 0.001), which were significantly lower after the period of chiropractic treatment (p = 0.03). Moreover, these changes were accompanied by a significant reduction in pain and disability (both p < 0.001). However, levels of urinary TNF-α were not correlated with pain intensity nor disability.

Conclusion

These results suggest that urine could be a good milieu to assess TNF-α changes, with potential clinical implications for the management of chronic low back pain.
The Association Between Dietary Inflammatory Index and Cognitive Performance in Older Adults Aged 60 Years and Older
Authors: Song Wenlei , Feng Yijun , Gong Zonglin , Tian Changwei
Published: April 2022

Background

Neuroinflammation has been linked to the development of cognitive performance. Epidemiological evidence on dietary inflammatory potential and cognitive performance is scarce. We evaluated the association between dietary inflammatory index (DII) and cognitive performance in older adults.

Methods

This study included adults aged 60 years or older from the 2011–2014 National Health and Nutrition Examination Survey. The DII scores were calculated based on 27 nutritional parameters. Cognitive performance was assessed with four cognitive tests: the Digit Symbol Substitution Test (DSST, n = 2,780), the Consortium to Establish a Registry for Alzheimer’s Disease Word Learning (CERAD-WL, n = 2,859) and Delayed Recall (CERAD-DR, n = 2,857), and the Animal Fluency (AF, n = 2,844) tests. Restricted cubic splines and logistic regression were adopted to assess the associations.

Results

Comparing the highest to lowest tertile of DII scores, the odds ratio (95% CI) of lower cognitive functioning was 1.97 (1.08–3.58) [P-trend = 0.02, per 1 unit increment: 1.17 (1.01–1.38)] on DSST, 1.24 (0.87–1.76) [P-trend = 0.24, per 1 unit increment: 1.09 (0.96–1.23)] on CERAD-WL, 0.93 (0.57–1.51) [P-trend = 0.74, per 1 unit increment: 1.02 (0.87–1.20)] on CERAD-DR, and 1.76 (1.30–2.37) [P-trend < 0.01, per 1 unit increment: 1.17 (1.05–1.29)] on AF. The above-mentioned associations were observed in both men and women. In non-linear dose–response analysis, the association between DII and lower cognitive functioning was not significant at lower DII scores up to 3.0, after which the association was significant and the curve rose steeply.

Conclusion

Higher DII is associated with lower scores on DSST and AF tests in older adults.
Calcifediol During Pregnancy Improves Maternal and Fetal Availability of Vitamin D Compared to Vitamin D3 in Rats and Modifies Fetal Metabolism
Authors: Gázquez Antonio , Sánchez-Campillo María , Barranco Alejandro , Rueda Ricardo , Chan Jia P. , Kuchan Matthew J. , Larqué Elvira
Published: April 2022

The fetus depends on the transplacental transfer of vitamin D. Calcifediol (25-OH-D3) is the vitamin D metabolite that crosses the placenta. Previously, oral 25-OH-D3 improved serum 25-OH-D3 compared to vitamin D3 in non-pregnant subjects, although no studies are available in pregnant women. We evaluated the availability of oral 25-OH-D3 compared to vitamin D3 during pregnancy, as well as, their levels in the fetus and effect on metabolism-related proteins. Twenty female rats per group were fed with 25 μg/kg of diet of vitamin D3 (1,000 UI vitamin D/kg diet) or with 25 μg/kg diet of 25-OH-D3. We analyzed 25-OH-D3 levels in maternal and fetal plasma; protein levels of vitamin D receptor (VDR), fatty acid translocase (FAT), and scavenger-receptor class B type-1 (SR-B1) in both maternal liver and placenta; and protein levels of VDR and Glutamate decarboxylase (GAD67) in fetal brain. 25-OH-D3 doubled the concentration of 25-OH-D3 in both maternal and fetal plasma compared to vitamin D3. In addition, maternal liver VDR, FAT, and SR-BI increased significantly in the 25-OH-D3 group, but no changes were found in the placenta. Interestingly, 25-OH-D3 decreased GAD67 expression in the fetal brain and it also tended to decrease VDR (P = 0.086). In conclusion, 25-OH-D3 provided better vitamin D availability for both mother and fetus when administered during pregnancy compared to vitamin D3. No adverse effects on pregnancy outcomes were observed. The effects of 25-OH-D3 on the expression of VDR and GAD67 in fetal brain require further investigation.
NOL6 Regulates the Proliferation and Apoptosis of Gastric Cancer Cells via Regulating TP53I3, CDK4 and MCM7 Expression
Authors: He Lei , Qian Xiaohan , Ge Pingping , Fan Dong , Ma Xiang , Wu Qiong , Sun Jin , Yang Lihua , Shen Jian , Xu Lijian
Published: April 2022

Background

Gastric cancer (GC) is a prevalent cancer with high mortality and strong invasiveness, and the entire regulatory networks of GC is still unclear.

Objective

The aim of this study was to explore the specific mechanism of the effect of nucleolar protein 6 (NOL6) on the proliferation and apoptosis of GC cells.

Methods

The human gastric adenocarcinoma cell line HGC-27 and AGS were cultured. qRT-PCR was used to verify the expression level of NOL6 in GC cells; MTT and EdU were used to test cell proliferation; TUNEL staining and Flow cytometry were used to detect cell apoptosis; The downstream genes and pathways following NOL6 knockdown were explored through the microarray assay and ingenuity pathway analysis, and the downstream genes were finally verified by qRT-PCR and Western blotting. The xenograft mice were used to investigate the effect of NOL6 on GC in vivo.

Results

TCGA data analysis showed that NOL6 expression level was higher in GC cells than adjacent normal cells. Over-expression of NOL6 increased proliferation and colony formation, and inhibited the apoptotic rate in AGS and HGC-27 cells, while NOL6 knockdown induced the opposite effects. Through microarray assay and IPA analysis, NOL6-related downstream genes and critical signaling pathways were found. And we verified the relationship between downstream genes and GC. Additionally, NOL6 knockdown could decrease the weight and volume of tumor in the mice.

Conclusion

NOL6 knockdown could inhibit cell proliferation and induce cell apoptosis of GC, suggesting that NOL6 may serve as a potential therapeutic target for treating GC.
Challenges and Opportunities Associated With Platelets in Pancreatic Cancer
Authors: Chen Zhou , Wei Xiaodong , Dong Shi , Han Fangfang , He Ru , Zhou Wence
Published: April 2022

Pancreatic cancer is one of the most common malignant tumors in the digestive system with a poor prognosis. Accordingly, better understanding of the molecular mechanisms and innovative therapies are warranted to improve the prognosis of this patient population. In addition to playing a crucial role in coagulation, platelets reportedly contribute to the growth, invasion and metastasis of various tumors, including pancreatic cancer. This narrative review brings together currently available evidence on the impact of platelets on pancreatic cancer, including the platelet-related molecular mechanisms of cancer promotion, pancreatic cancer fibrosis, immune evasion, drug resistance mechanisms, thrombosis, targeted platelet therapy, combined radiotherapy and chemotherapy treatment, platelet combined with nanotechnology treatment and potential applications of pancreatic cancer organoids. A refined understanding of the role of platelets in pancreatic cancer provides the foothold for identifying new therapeutic targets.
Updated Evaluation of Robotic- and Video-Assisted Thoracoscopic Lobectomy or Segmentectomy for Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Zhang Jianyong , Feng Qingbo , Huang Yanruo , Ouyang Lanwei , Luo Fengming
Published: April 2022

Objectives

Robot-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS) are the two principal minimally invasive surgical approaches for patients with lung cancer. This study aimed at comparing the long-term and short-term outcomes of RATS and VATS for lung cancer.

Methods

A comprehensive search for studies that compared RATS versus VATS for lung cancer published until November 31, 2021, was conducted. Data on perioperative outcomes and oncologic outcomes were subjected to meta-analysis. PubMed, Web of Science, and EMBASE were searched based on a defined search strategy to identify eligible studies before November 2021.

Results

Twenty-six studies comparing 45,733 patients (14,271 and 31,462 patients who underwent RATS and VATS, respectively) were included. The present meta-analysis showed that there were no significant differences in operative time, any complications, tumor size, chest drain duration, R0 resection rate, lymph station, 5-year overall survival, and recurrence rate. However, compared with the VATS group, the RATS group had less blood loss, a lower conversion rate to open, a shorter length of hospital stay, more lymph node dissection, and better 5-year disease-free survival.

Conclusions

RATS is a safe and feasible alternative to VATS for patients with lung cancer.
Diffuse Large B-Cell Lymphoma Promotes Endothelial-to-Mesenchymal Transition via WNT10A/Beta-Catenin/Snail Signaling
Authors: Sun Xianting , Fang Jianchen , Ye Fen , Zhang Shuxian , Huang Honghui , Hou Jian , Wang Ting
Published: April 2022

Diffuse large B-cell lymphoma (DLBCL) is one type of highly heterogeneous lymphoid malignancy with 30%~40% of patients experiencing treatment failure. Novel risk stratification and therapeutic approaches for DLBCL are urgently needed. Endothelial-to-mesenchymal transition (EndMT), which contributes to tumor angiogenesis, metastasis, drug resistance, and cancer-associated fibroblast generation, has been detected in the microenvironment of many types of cancers. However, the existence of EndMT in the hematological malignancies microenvironment remains unknown. Here, we identified the existence of EndMT in DLBCL-associated endothelial cells and the clinical relevance of EndMT markers in DLBCL, which was associated with advanced clinical stage and poor prognosis. In vitro experiments confirmed that DLBCL cells stimulated angiogenesis and EndMT of human umbilical vein endothelial cells (HUVECs). We further unveiled the molecular mechanisms underlying this process. We demonstrated that WNT10A, a WNT family member overexpressed in DLBCL tissues and correlated with clinical features in DLBCL, promoted EndMT through glycogen synthase kinase 3β (GSK3β)/β-catenin/snail signaling. WNT10A inhibited the binding of GSK3β to β-catenin/snail, resulting in β-catenin and snail nuclear accumulation and target gene transcription. Silencing β-catenin and snail respectively attenuated WNT10A-induced angiogenesis and EndMT. The interplay between β-catenin-dependent and snail-dependent signaling was also confirmed in this study. Collectively, these findings identified that WNT10A/GSK3β/β-catenin/snail pathway performed vital roles in DLBCL-induced EndMT and indicated that EndMT markers and WNT10A may serve as novel predictors of clinical outcome.
Reference Values for Wristband Accelerometry Data in Children Aged 6–11 Years of Age
Authors: Lammers Astrid E. , Romanowski Anna Lena , Baumgartner Helmut , Diller Gerhard-Paul , Uebing Anselm
Published: April 2022

Objectives

Wristband activity trackers (accelerometers) could serve as a convenient monitoring tool to continuously quantify physical activity throughout the day. We aim to provide reference values for the use of these devices in healthy children.

Methods

Children were recruited at a local school and provided with activity trackers (Fitbit Charge 2). Pupils were instructed to wear devices during all normal daytime activities over a period of 11–15 days. Demographic data, total number of daily steps and heart rate were recorded. In addition, all children/parents were asked to complete a questionnaire providing information about daily physical routine (mode of transport to school, sporting activities as well as sport club memberships).

Results

Three hundred two children (54.6% boys; median age 8.7 years) participated in this prospective study. Median wearing time of the device was 12.1 h/day. Overall, the median daily total step count was 12,095. Median step counts/day were significantly higher in boys compared to girls (13,015 vs. 11,305 steps/day; p < 0.0001). In addition, step counts were significantly higher during the week, compared to weekend days. The effect of age on daily step count was found to be non-linear: the total daily step count increased from 6 to 8.5 years of age, while older children (aged >8.5 years) had lower step counts compared to the younger children. Significant predictors of the daily step count were male gender (+1,324.9 steps, p = 0.0008), mode of transportation to school (walking, bicycle, scooter: +865.5 steps p = 0.049), active membership in a sports club (+1,324.9 steps/day, p = 0.0008), and number of structured units of physical exercise performed (+336.5/per 45 min, p < 0.0001). Severe obesity was associated with a significant reduction in total daily step count (−3037.7 steps/day, p = 0.015).

Conclusion

Our prospective cohort study of healthy school children provides reference values for wristband accelerometers in normal individuals. In addition, it clarifies the effect of age, body weight and lifestyle on normal daily step counts in school children. This data should be helpful to judge the degree of physical limitation of patients compared to healthy peers.
Safety of Using Traditional Chinese Medicine Injections in Primary Medical Institutions: Based on the Spontaneous Reporting System 2016–2020 in Henan Province, China
Authors: Yan Ziqi , Feng Zhanchun , Jiao Zhiming , Wang Ganyi , Chen Chaoyi , Feng Da
Published: April 2022

Objective: Traditional Chinese medicine (TCM) injection is widely used, but its adverse drug reaction (ADR) may be a serious public health concern in primary medical institutions. This research will explore the safety of TCM injections and provide clinical recommendations at the primary medical institutions.

Method: ADR data were collected by the Henan Adverse Drug Reaction Monitoring Center from 2016 to 2020 were analized Descriptive statistics, chi-square analysis, binary logistic regression, and Mantel-haenszel hierarchical analysis were used to identify the risk factors associated with the rational use of TCM injections in primary medical institutions.

Results: A total of 30,839 cases were collected in this study, 4905 cases (15.90%) were SADRs. Patients using TCM injections in primary medical institutions were more likely to cause SADRs (OR = 1.149, 95% CI: 1.061–1.245). Aged over 60 years (OR = 1.105, 95% CI: 1.007–1.212), non-essential drugs (OR = 1.292, 95% CI: 1.173–1.424), autumn (OR = 1.194, 95% CI: 1.075–1.326) and TCM injections with safflower (OR = 1.402, 95% CI: 1.152–1.706), danshen (OR = 1.456, 95% CI: 1.068–1.984) and medication reasons with chemotherapy (OR = 2.523, 95% CI: 1.182–5.386) and hypertension (OR = 1.495, 95% CI: 1.001–2.233) were more likely to suffer SADR in primary medical institutions.

Conclusion: In general, the number of reported cases of TCM injection was declining over time, but the proportion of SADRs in primary medical institutions increased. In the future, it is necessary to continue to restrict TCM injections at the macro policy level, and vigorously promote the varieties in the essential drug list. At the micro level, it is necessary to intervene in specific populations, specific diseases and specific drugs, first start with them, step by step, and effectively prevent SADR occurrences in primary medical institutions.
Rutaecarpine Attenuates Oxidative Stress-Induced Traumatic Brain Injury and Reduces Secondary Injury via the PGK1/KEAP1/NRF2 Signaling Pathway
Authors: Xu Min , Li Liu , Liu Hua , Lu Wei , Ling Xiaoyang , Gong Mingjie
Published: April 2022

The oxidative stress response caused by traumatic brain injury (TBI) leads to secondary damage in the form of tissue damage and cell death. Nuclear transcription-related factor 2 (NRF2) is a key factor in the body against oxidative stress and has an important role in combating oxidative damage in TBI neurons. In the present study, we investigated whether rutaecarpine could activate the PGK1/KEAP1/NRF2 pathway to antagonize oxidative damage in TBI neurons. We performed controlled cortical impact (CCI) surgery on mice and taken H2O2 treatment on PC12 cells to construct TBI models. The results of western blot showed that the expression of PGK1, KEAP and NRF2 was regulated and accompanied by altered levels of oxidative stress, and the use of rutaecarpine in the TBI model mice significantly improved cognitive dysfunction, increased antioxidant capacity and reduced apoptosis in brain tissue. Similar antioxidant damage results were obtained using rutaecarpine in a PC12 cell model. Furthermore, through the use of the protein synthesis inhibitor CHX and the proteasome synthesis inhibitor MG-132, rutaecarpine was found to promote the expreesions of PGK1 and NRF2 by accelerating PGK1 ubiquitination to reduce PGK1 expression. Therefore, rutaecarpine may be a promising therapeutic agent for the treatment of TBI-related neuro-oxidative damage.
Naringin Interferes Doxorubicin-Induced Myocardial Injury by Promoting the Expression of ECHS1
Authors: Zhao Zirui , Yang Shilei , Deng Yawen , Wang Liang , Zhang Yifen , Feng Zhenyu , Li Han , Chi Zhongchao , Xie Yunpeng , Dong Deshi
Published: April 2022

Doxorubicin (DOX) leads to myocardial cell damage and irreversible heart failure, which limits the clinical application of DOX. Naringin has biological functions of inhibiting inflammation, oxidative stress and apoptosis. Our aim was to investigate whether Naringin could prevent DOX-related cardiotoxicity in mice. Naringin was administered by gavage and mice were intraperitoneally injected with doxorubicin (1 mg/kg/day) for 15 days. H&E, Masson, TUNEL and others experiments were examined. NRVMs and H9C2 cells were treated with Naringin and DOX in vitro. Using IF, ELISA and Western Blot to detect the effect of Naringin and ECHS1 on cells. The results showed that Naringin could prevent DOX related cardiac injury, inhibit cardiac oxidative stress, inflammation and apoptosis in vivo and in vitro. Inhibition of ECHS1 could interfere the effect of Naringin on DOX-induced myocardial injury. Naringin may provide a new cardiac protective tool for preventing the cardiotoxicity of anthracycline drugs.
Inhalation Aromatherapy via Brain-Targeted Nasal Delivery: Natural Volatiles or Essential Oils on Mood Disorders
Authors: Cui Jieqiong , Li Meng , Wei Yuanyuan , Li Huayan , He Xiying , Yang Qi , Li Zhengkun , Duan Jinfeng , Wu Zhao , Chen Qian , Chen Bojun , Li Gang , Ming Xi , Xiong Lei , Qin Dongdong
Published: April 2022

Mood disorders, also often referred to as affective disorders, are a group of psychiatric illnesses that severely impact mood and its related functions. The high medical expenditures have placed a significant financial burden on patients and their families. Aromatherapy is an alternative and complementary treatment that utilizes essential oils (EOs) or volatile oils (VOs) to achieve major therapeutic goals. In general, EOs are volatile chemicals that enter the body primarily through skin absorption and/or nasal inhalation. In addition, they can work through oral administration. Inhalation aromatherapy has shown unique advantages for treating mood disorders, especially depression, anxiety and mental disorders such as sleep disorder, which have been validated over the last decade through clinical and animal studies. Accumulating evidence has shown that EOs or VOs can bypass the blood-brain barrier to target brain tissue through the nasal-brain pathway. Subsequently, they act on the cerebral cortex, thalamus, and limbic system in the brain to improve symptoms of anxiety, depression and improve sleep quality. Here, we review the natural aromatic plants’ volatiles or essential oils used commonly as adjuncts to manage mood disorders and illustrate the mechanisms of inhalation aromatherapy, and mainly summarized the application of transnasal inhalation aromatherapy in depression, anxiety, and sleep disorders. We conclude that aromatherapy does not cause side-effects, which is vastly different from commonly used psychotropic drugs. Inhalation aromatherapy via brain-targeted nasal delivery offers potentially efficacious treatment for mental disorders and merits further study.
Navigating Between Right, Wrong, and Relevant: The Use of Mathematical Modeling in Preclinical Decision Making
Authors: Kondic Anna , Bottino Dean , Harrold John , Kearns Jeffrey D. , Musante CJ , Odinecs Aleksandrs , Ramanujan Saroja , Selimkhanov Jangir , Schoeberl Birgit
Published: April 2022

The goal of this mini-review is to summarize the collective experience of the authors for how modeling and simulation approaches have been used to inform various decision points from discovery to First-In-Human clinical trials. The article is divided into a high-level overview of the types of problems that are being aided by modeling and simulation approaches, followed by detailed case studies around drug design (Nektar Therapeutics, Genentech), feasibility analysis (Novartis Pharmaceuticals), improvement of preclinical drug design (Pfizer), and preclinical to clinical extrapolation (Merck, Takeda, and Amgen).
Effect of Monoacylglycerol Lipase Inhibition on Intestinal Permeability of Rats With Severe Acute Pancreatitis
Authors: Wang Jing , Xu Hongwei , Chen Tianjie , Xu Changqin , Zhang Xiaohua , Zhao Shulei
Published: April 2022

Background: Endocannabinoid 2-arachidonoylglycerol (2-AG) is an anti-nociceptive lipid that is inactivated through cellular uptake and subsequent catabolism by monoacylglycerol lipase (MAGL). In this study, we investigated the effects of MAGL inhibition on intestinal permeability and explored the possible mechanism.

Methods: A rat model of severe acute pancreatitis (SAP) was established. Rats were divided into three groups according to treatment. We analyzed intestinal permeability to fluorescein isothiocyanate-dextran and the levels of inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and 2-AG. Hematoxylin and eosin staining was used to assess histological tissue changes. In vivo intestinal permeability was evaluated by transmission electron microscopy. We obtained ileum tissues, extracted total RNA, and applied RNA-sequencing. Sequencing data were analyzed by bioinformatics.

Results: Inflammatory factor levels were higher, while 2-AG levels were lower in the SAP group compared with the control group. Administration of JZL184 to rats with SAP increased the levels of 2-AG and lowered the levels of IL-6 and TNF-α. Notably, intestinal permeability was improved by JZL184 as demonstrated by fluorescein isothiocyanate-dextran measurement, hematoxylin and eosin staining, and transmission electron microscopy. RNA-sequencing showed significant transcriptional differences in SAP and JZL184 groups compared with the control group. KEGG analysis showed that the up- or downregulated genes in multiple comparison groups were enriched in two pathways, focal adhesion and PI3K-Akt signaling pathways. Differential alternative splicing (AS) genes, such as Myo9b, Lsp1, and Git2, have major functions in intestinal diseases. A total of 132 RNA-binding proteins (RBPs) were screened by crossing the identified abnormally expressed genes with the reported RBP genes. Among them, HNRNPDL coexpressed the most AS events as the main RBP.

Conclusion: MAGL inhibition improved intestinal mucosal barrier injury in SAP rats and induced a large number of differentially expressed genes and alternative splicing events. HNRNPDL might play an important role in improving intestinal mucosal barrier injury by affecting alternative splicing events.
Ferrostatin-1 Ameliorates Liver Dysfunction via Reducing Iron in Thioacetamide-induced Acute Liver Injury in Mice
Authors: Jiang Hui , Zhang Xinyu , Yang Wanping , Li Meiqi , Wang Guohua , Luo Qianqian
Published: April 2022

Background and Aims: Hepatic iron overload always leads to oxidative stress, which has been found to be involved in the progression of liver disease. However, whether iron disorder is involved in acute liver disease and the further molecular mechanisms remain unclear.

Methods: A mice model of acute liver injury (ALI) was established via intraperitoneal injection of thioacetamide (TAA) (250 mg/kg/day) for 3 consecutive days. Ferrostatin-1 (Fer-1) was administered intraperitoneally (2.5 μM/kg/day) starting 3 days before TAA treatment. Deferoxamine (DFO) was intraperitoneally injected (200 mg/kg/day) with TAA treatment for 3 days. We further observed the effect of Fer-1 on TAA model with high-iron diet feeding. ALI was confirmed using histological examination and liver function activity. Moreover, expressions of iron metabolism and ferroptosis proteins were measured by Western blot analysis.

Results: The study revealed that the iron accumulation and ferroptosis contributed to TAA-induced ALI pathogenesis. TAA induced prominent inflammation and vacuolar degeneration in the liver as well as liver dysfunction. In addition, protein expression of the cystine/glutamate antiporter SLC7A11 (xCT) and glutathione peroxidase 4 (GPX4) was significantly decreased in the liver, while transferrin receptor 1 (TfR1), ferroportin (Fpn) and light chain of ferritin (Ft-L) expression levels were increased after TAA exposure. As the same efficiency as DFO, pre-administration of Fer-1 significantly decreased TAA-induced alterations in the plasma ALT, AST and LDH levels compared with the TAA group. Moreover, both Fer-1 and DFO suppressed TfR1, Fpn and Ft-L protein expression and decreased iron accumulation, but did not affect xCT or GPX4 expression in the liver. Both Fer-1and DFO prevented hepatic ferroptosis by reducing the iron content in the liver. Furthermore, Fer-1 also reduced iron and reversed liver dysfunction under iron overload conditions.

Conclusion: These findings indicate a role of TAA-induced iron accumulation and ferroptosis in the pathogenesis of ALI model. The effect of Fer-1 was consistent with that of DFO, which prevented hepatic ferroptosis by reducing the iron content in the liver. Thus, Fer-1 might be a useful reagent to reverse liver dysfunction and decreasing the iron content of the liver may be a potential therapeutic strategy for ALI.
Targeting Mitochondrial ROS-Mediated Ferroptosis by Quercetin Alleviates High-Fat Diet-Induced Hepatic Lipotoxicity
Authors: Jiang Jin-Jin , Zhang Guo-Fu , Zheng Jia-Yi , Sun Ji-Hu , Ding Shi-Bin
Published: April 2022

Background: The protective effect of quercetin on nonalcoholic fatty liver disease (NAFLD) has been reported, but its mechanism remains poorly understood. Recently, quercetin was reported to be capable of inhibiting ferroptosis, which is a recognized type of regulated cell death. Moreover, hepatic ferroptosis plays an important role in the progression of NAFLD, but experimental evidence is limited. Hence, our study aimed to investigate the effect of quercetin on hepatic ferroptosis in high-fat diet (HFD)-induced NAFLD and further elucidate the underlying molecular mechanism.

Methods: C57BL/6J mice were fed either a normal diet (ND), an HFD, or an HFD supplemented with quercetin for 12 weeks. Hepatic lipid peroxidation, steatosis, ferroptosis and iron overload were examined. In vitro, steatotic L-02 cells was used to study the potential mechanism.

Results: We found that the HFD caused lipid peroxidation, lipid accumulation and ferroptosis in the liver, which were rescued by quercetin supplementation. Consistent with the in vivo results, quercetin alleviated lipid droplet accumulation and reduced the levels of lipid reactive oxygen species (ROS) and ferroptosis in steatotic L-02 cells. Using a mitochondrial ROS (MtROS) scavenger (Mito-TEMPO) and ferroptosis specific inhibitor (Fer-1), we found that quercetin remarkably alleviated lipid droplet accumulation and lipid peroxidation by reducing MtROS-mediated ferroptosis in steatotic L-02 cells.

Conclusion: Our data showed that HFD consumption induced lipid accumulation and triggered ferroptosis in liver, ultimately leading to hepatic lipotoxicity, which can be alleviated by quercetin. Findings from this study provide new insight into the mechanism by which quercetin can be used for the prevention and treatment of NAFLD.
Sub-Analysis of CYP-GUIDES Data: Assessing the Prevalence and Impact of Drug-Gene Interactions in an Ethnically Diverse Cohort of Depressed Individuals
Authors: Crutchley Rustin D. , Keuler Nicole
Published: April 2022

Introduction: Minority groups are underrepresented in pharmacogenomics (PGx) research. Recent sub-analysis of CYP-GUIDES showed reduced length of stay (LOS) in depressed patients with CYP2D6 sub-functional status. Our primary objective was to determine whether PGx guided (G) versus standard treatment (S) influenced LOS among different race/ethnic groups. Secondary objectives included prevalence of drug-gene interactions (DGIs) and readmission rates (RAR).

Methods: Retrospective sub-analysis of CYP-GUIDES data comprising CYP2D6 phenotypes was reclassified using standardized CYP2D6 genotype to phenotype recommendations from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group (DPWG). The Mann-Whitney test was used to determine differences in LOS between groups G and S and Kruskal Wallis test to compare LOS among different race/ethnic groups. Logistic regression was used to determine covariates associated with RAR.

Results: This study included 1,459 patients with 67.3% in G group (n = 982). The majority of patients were White (57.5%), followed by Latinos (25.6%) and Blacks (12.3%). Although there were no differences in LOS between G and S groups, Latinos had significant shorter LOS than Whites (p = 0.002). LOS was significantly reduced by 5.6 days in poor metabolizers in group G compared to S (p = 0.002). The proportion of supra functional and ultra-rapid metabolizers (UMs) were 6 and 20.3% using CYP-GUIDES and CPIC/DPWG definitions, respectively. Prevalence of DGIs was 40% with significantly fewer DGIs in Blacks (p < 0.001). Race/ethnicity was significantly associated with RAR (aOR 1.30; p = 0.003).

Conclusion: A greater number of patients were classified as CYP2D6 UMs using CPIC/DPWG definitions as compared to CYP-GUIDES definitions. This finding may have clinical implications for using psychotropics metabolized by CYP2D6.
Chip-Scaled Ka-Band Photonic Linearly Chirped Microwave Waveform Generator
Authors: Brunetti Giuseppe , Armenise Mario N. , Ciminelli Caterina
Published: April 2022

Synthetic aperture radar (SAR) systems employ a Linearly Chirped Microwave Waveform Generator (LCMWG) with large time–bandwidth product (TBWP), to provide a wide range resolution. Photonics has now been recognized as a disruptive approach to achieve high performance at bandwidth of few tens of gigahertz, with light and compact architectures, due to the typical photonics benefits, such as electromagnetic interference immunity, small power consumption, small footprint, and high immunity to vibration/shock and radiation. In this article, we report on the photonic generation of a high-frequency LCMW, with a large TBWP (102–103), using a chip-scaled architecture, based on a frequency-tunable optoelectronic oscillator (OEO) and a recirculating phase modulation loop (RPML). A new configuration of the OEO employing an ultrahigh Q-factor resonator has been conceived to allow the oscillator working in Ka band at 40 GHz or even more, with very low phase noise. Key building block of the RPML is a phase modulator driven by an engineered parabolic split waveform. The ultra-large pulse compression rate (PCR) >> 102, together with large signal purity, was also obtained, making the proposed architecture particularly suitable for SAR systems with large range resolution demand, such as Earth surveillance and monitoring.
Neural Network Model Based on the Tensor Network for Audio Tagging of Domestic Activities
Authors: Yang LiDong , Yue RenBo , Wang Jing , Liu Min
Published: April 2022

Due to the serious problem of population aging, monitoring of domestic activities is increasingly important. Audio tagging of domestic activities is very suitable when the visual data are unavailable due to the interference from light and the environment. Aiming at solving this problem, a neural network model based on the tensor network is proposed for audio tagging of domestic activities that is more interpretable than traditional neural networks. The introduction of the tensor network can compress the network parameters and reduce the redundancy of the training model while maintaining a good performance. First, the important features of a Mel spectrogram of the input audio are extracted through the convolutional neural networks (CNNs). Then, they are converted into the high-order space corresponding with the tensor network. The spatial structure information and important features can be further extracted and retained through the matrix product state (MPS). Large patches of the featured data are divided into small local orderless patches when using the tensor network. The final tagging results are obtained through the MPS layers which is just a tensor network structure based on the tensor train decomposition. In order to evaluate the proposed method, the DCASE 2018 challenge task 5 dataset for monitoring domestic activities is selected. The results showed that the average F1-score of the proposed model in the test set of the development dataset and validation dataset reached 87.7 and 85.9%, which are 3.2 and 2.8% higher than the baseline system, respectively. It is verified that the proposed model can perform better and more efficiently for audio tagging of domestic activities.
Distributed Edge-Enhanced Imaging With a Fractional Spiral Phase Filter Using Random Light
Authors: Wang Huahua , Ma Jian , Yang Zhixin , Du Haoran , Kang Xingwang , Su Hengzhi , Gao Lu , Zhang Ze
Published: April 2022

A gradual edge-enhanced ghost imaging method with pseudo-thermal light is proposed in both the theory and experiment. In the experiment, a phase object and fractional spiral phase filter are placed symmetrically in the imaging plane of the pseudo-thermal light source in the distributed test and reference beams of the lensless ghost imaging system. The procedure of gradual edge-enhanced ghost imaging is carried out by modulating the fractional topological charge from 0 to 1. We observe that the brightness of the object edge increases with the increase of the fractional topological charge. It is also found that the intensity distribution is uniform and isotropic when the topological charge is an integer; otherwise, the intensity distribution is not uniform. Theoretical analysis is also provided. The proposed gradual edge-enhanced ghost imaging scenario releases the position limitation in the Fourier plane for the filter of the traditional phase filtering imaging process. The method is believed to have prospective applications in microscopic imaging and biomedical detection.
Accurate Calculation of FFR Based on a Physics-Driven Fluid‐Structure Interaction Model
Authors: Xi Xiaolu , Liu Jincheng , Sun Hao , Xu Ke , Wang Xue , Zhang Liyuan , Du Tianming , Liu Jian , Li Bao
Published: April 2022

Background: The conventional FFRct numerical calculation method uses a model with a multi-scale geometry based upon CFD, and rigid walls. Therefore, important interactions between the elastic vessel wall and blood flow are not routinely considered. Changes in the resistance of coronary microcirculation during hyperaemia are likewise not typically incorporated using a fluid–structure interaction (FSI) algorithm. It is likely that both have resulted in FFRct calculation errors.

Objective: In this study we incorporated both the influence of vascular elasticity and coronary microcirculatory structure on FFR, to improve the accuracy of FFRct calculation. Thus, in this study, a physics-driven 3D–0D coupled model including fluid–structure interaction was established to calculate accurate FFRct values.

Methods: Based upon a novel geometric multi-scale modeling technology, a FSI simulation approach was used. A lumped parameter model (0D) was used as the outlet boundary condition for the 3D FSI coronary artery model to incorporate physiological microcirculation, with bidirectional coupling between the two models.

Results: The accuracy, sensitivity, specificity, and both positive and negative predictive values of FFRDC calculated based upon the coupled 3D–0D model were 86.7, 66.7, 84.6, 66.7, and 91.7%, respectively. Compared to the calculated value using the basic CFD model (MSE = 5.9%, accuracy rate = 80%), the FFRCFD calculated based on the coupled 3D–0D model has a smaller MSE of 1.9%.

Conclusion: The physics-driven coupled 3D–0D model that incorporates fluid–structure interactions not only consider the influence of the elastic vessel wall on blood flow, but also provides reliable microvascular resistance boundary conditions for the 3D FSI model. This allows for a calculation that is based upon conditions that are closer to the physiological environment, and thus improves the accuracy of FFRct calculation. It is likely that more accurate information will provide an enhanced recommendation regarding percutaneous coronary intervention (PCI) in the clinic.
Silicon as a Sustainable Option to Increase Biomass With Less Water by Inducing Carbon:Nitrogen:Phosphorus Stoichiometric Homeostasis in Sugarcane and Energy Cane
Authors: Teixeira Gelza Carliane Marques , de Mello Prado Renato , Rocha Antonio Márcio Souza , de Cássia Piccolo Marisa
Published: April 2022

Climate change has prolonged periods of water deficit in sugarcane and energy cane crops. This condition induces an imbalance of the carbon (C): nitrogen (N): phosphorus (P) stoichiometric homeostasis, impairing accumulated nutrients from being converted into biomass. Silicon (Si) supplementation can mitigate the damage caused by water deficit in plants by improving the C:N:P balance, increasing C, N, and P use efficiencies and the biomass conversion, and reducing climate change effects on crops. This study assesses the beneficial effects of Si applied through fertigation associated with foliar spraying on the alleviation of damage caused by severe water deficit in sugarcane and energy cane for intermediate and long periods. In addition, the effects in maintenance of nutritional homeostasis we assessed and C, N, and P use efficiencies on sugarcane and energy cane under those conditions were increased. Four experiments were conducted during the first growth cycle of each species. The effect of fertigation associated with Si foliar spraying was evaluated by applying Si only during the seedling formation phase in sugarcane and energy cane grown under severe water deficit for 60 days after transplanting (intermediate period). Then, the effect of Si applied during seedling formation and supplemented after transplanting was evaluated in sugarcane and energy cane grown under severe water deficit for 160 days after transplanting (long period). The Si supply decreased C contents, modified the C:N:P ratio, and increased C, N, and P use efficiencies in plants of both species under water deficit at the intermediate and long periods after transplanting. The effects of applying Si through fertigation associated with foliar spraying during seedling formation mitigated the damage caused by severe water deficit in the intermediate period, which was mainly observed in sugarcane. When supplemented with Si after transplanting, the mitigating effects occurred in both species under severe long period water deficit. Therefore, the Si supply through fertigation associated with foliar spraying is a viable alternative to provide Si to the plant. It also comes with beneficial effects that partially reverse the damage to nutritional homeostasis and increase nutritional efficiency in plants under severe water deficit.
Phytoene Synthase: The Key Rate-Limiting Enzyme of Carotenoid Biosynthesis in Plants
Authors: Zhou Xuesong , Rao Sombir , Wrightstone Emalee , Sun Tianhu , Lui Andy Cheuk Woon , Welsch Ralf , Li Li
Published: April 2022

Phytoene synthase (PSY) catalyzes the first committed step in the carotenoid biosynthesis pathway and is a major rate-limiting enzyme of carotenogenesis. PSY is highly regulated by various regulators and factors to modulate carotenoid biosynthesis in response to diverse developmental and environmental cues. Because of its critical role in controlling the total amount of synthesized carotenoids, PSY has been extensively investigated and engineered in plant species. However, much remains to be learned on its multifaceted regulatory control and its catalytic efficiency for carotenoid enrichment in crops. Here, we present current knowledge on the basic biology, the functional evolution, the dynamic regulation, and the metabolic engineering of PSY. We also discuss the open questions and gaps to stimulate additional research on this most studied gene/enzyme in the carotenogenic pathway.
How to Measure the Safety Cognition Capability of Urban Residents? An Assessment Framework Based on Cognitive Progression Theory
Authors: Xiong Yachao , Zhang Changli , Qi Hui , Zhang Rui , Zhang Yanbo
Published: April 2022

The salience of social risks and the incidence of various crises in China have induced widespread concerns among urban residents. Encountering frequent risks places higher demands on the cognition of urban residents. The concept of safety cognition capability is defined within the context of urban residents' daily life, and measurement instruments are developed and tested to lay the foundation for grasping the current safety cognition capability of urban residents and conducting further research. In this study, the five-dimensional structure of urban residents' safety cognition capability (URSCC) was proposed by using the grounded theory method to sort out the interview transcript of interviews with 30 urban residents, and a 38-item URSCC scale was designed and used for surveys conducted in China. The results show that the scale can be used as a valid tool to measure the URSCC, and it can help city managers to better understand the safety needs of residents, as well as monitor the effectiveness of policy implementation.
Research on the Influencing Factors of Problem-Driven Children’s Deep Learning
Authors: Zhang Xiao-Hong , Li Chun-Yan
Published: April 2022

Deep learning is widely used in the fields of information technology and education innovation but there are few studies for young children in the preschool stage. Therefore, we aimed to explore factors that affect children’s learning ability through collecting relevant information from teachers in the kindergarten. Literature review, interview, and questionnaire survey methods were used to determine the influencing factors of deep learning. There were five dimensions for these factors: the level of difficulty of academic, communication skills, level of active collaboration, level of in-depth processing, and reflection level evaluation. Reliability and validity tests were used to analyze the data from questionnaires. In total, 100 valid questionnaires were collected. The Cronbach coefficients for academic challenge, communication, active cooperation, deep processing, and reflective evaluation were 0.801, 0.689, 0.770, 0.758, and 0.665, respectively. Principal component analysis revealed that there were three main factors that affect children’s learning depth: the level of deep processing (maximum KMO: 0.908), the level of reflective evaluation (maximum KMO: 0.542), and the active level of collaboration (maximum KMO: 0.410). In conclusion, there were several factors affecting deep learning in children and further studies are warranted to promote the development of this field.
Effects of Age and Expertise on Mental Representation of the Throwing Movement Among 6- to 16-Year-Olds
Authors: Gromeier Michael , Schack Thomas , Koester Dirk
Published: April 2022

The aim of this article was to assess the development of mental representation of the overhead throwing movement as a function of age and expertise. The mental representational structure of the overhead throwing movement was measured using the Structural Dimensional Analysis-Motoric (SDA-M) method that reflects the organization of basic action concepts (BACs). BACs are fundamental building blocks of mental representations, which comprise functional, sensory, spatiotemporal, and biomechanical characteristics of a movement (Schack, 2010). In this study, novices and handball athletes (N= 199) each were grouped according to the level of development in motor ontogenesis (in childhood, pubescence, and adolescents). Male and female handball athletes played in the highest leagues of their age groups. As a result, novices of all age groups showed the same unstructured mental representation. Athletes in the earliest age band resemble all novices’ groups and showed similar unstructured mental representation, whereas athletes within pubescence and adolescents showed functionally well-structured representations, which were similar to the structure of the reference group (N= 8). These results are consistent with a previous investigation of related quantitative and qualitative performance parameters of the overhead throwing movement (Gromeier et al., 2017). Without an increased training, neither the throwing performance nor the associated mental representation is unlikely to improve further by itself or automatically.