bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Carbohydrate Dietary Approaches for People With Type 2 Diabetes—A Narrative Review
Authors: Wheatley Sean D. , Deakin Trudi A. , Arjomandkhah Nicola C. , Hollinrake Paul B. , Reeves Trudi E.
Published: July 2021

Although carbohydrate restriction is not a new approach for the management of Type 2 diabetes, interest in its safety and efficacy has increased significantly in recent years. The purpose of the current narrative review is to summarise the key relevant research and practical considerations in this area, as well as to explore some of the common concerns expressed in relation to the use of such approaches. There is a strong physiological rationale supporting the role of carbohydrate restriction for the management of Type 2 diabetes, and available evidence suggests that low carbohydrate dietary approaches (LCDs) are as effective as, or superior to, other dietary approaches for its management. Importantly, LCDs appear to be more effective than other dietary approaches for facilitating a reduction in the requirement for certain medications, which leads to their effects on other health markers being underestimated. LCDs have also been demonstrated to be an effective method for achieving remission of Type 2 diabetes for some people. The available evidence does not support concerns that LCDs increase the risk of cardiovascular disease, that such approaches increase the risk of nutrient deficiencies, or that they are more difficult to adhere to than other dietary approaches. A growing number of organisations support the use of LCDs as a suitable choice for individuals with Type 2 diabetes.
Shelf-Life Extension of Refrigerated Turbot (Scophthalmus maximus) by Using Weakly Acidic Electrolyzed Water and Active Coatings Containing Daphnetin Emulsions
Authors: Liu Wenru , Wang Qi , Mei Jun , Xie Jing
Published: July 2021

This research was to investigate the effect of weakly acidic electrolytic water (WAEW) treatments combining with the locust bean gum (LBG) and sodium alginate (SA) active coatings, containing daphnetin emulsions on microbiological, physicochemical, and sensory changes of turbot (Scophthalmus maximus) during refrigerated storage at 4°C for 24 days. Results showed that WAEW, together with LBG-SA coatings containing daphnetin emulsions treatments, could significantly lower the total viable count (TVC), H2S-producing bacteria, pseudomonas spp., and psychrotrophic bacteria counts, and inhibit the productions of off-flavor compounds, including the total volatile basic nitrogen (TVB-N), inosine (HxR), and hypoxanthine (Hx). Furthermore, the treatments also prevented textural deterioration, delayed water migration, and had higher organoleptic evaluation results. Therefore, WAEW, together with LBG-SA coatings, containing daphnetin emulsions treatments, had the potential to improve the quality of turbot during refrigerated storage.
Identification and Validation of a Prognostic Signature for Prostate Cancer Based on Ferroptosis-Related Genes
Authors: Liu Huan , Gao Lei , Xie Tiancheng , Li Jie , Zhai Ting-shuai , Xu Yunfei
Published: July 2021

Ferroptosis, an iron-dependent form of selective cell death, is involved in the development of many cancers. However, ferroptosis related genes (FRGs) in prostate cancer (PCa) are not been well studied. In this study, we collected the mRNA expression profiles and clinical information of PCa patients from TCGA and MSKCC databases. The univariate, LASSO, and multivariate Cox regression analyses were performed to construct a prognostic signature. Seven FRGs, AKR1C3, ALOXE3, ATP5MC3, CARS1, MT1G, PTGS2, and TFRC, were included to establish a risk model, which was validated in the MSKCC dataset. The results showed that the high-risk group was apparently correlated with copy number alteration load, tumor burden mutation, immune cell infiltration, mRNAsi, immunotherapy, and bicalutamide response. Moreover, we found that TFRC overexpression induced the proliferation and invasion of PCa cell lines in vitro. These results demonstrate that this risk model can accurately predict prognosis, suggesting that FRGs are promising prognostic biomarkers and potential drug targets in PCa patients.
Construction of Novel lncRNA–miRNA–mRNA Network Associated With Recurrence and Identification of Immune-Related Potential Regulatory Axis in Hepatocellular Carcinoma
Authors: Zhan Tian , Gao Xiang , Wang Guoguang , Li Fan , Shen Jian , Lu Chen , Xu Lei , Li Yuan , Zhang Jianping
Published: July 2021

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases globally. Despite continuous improvement of treatment methods, high postoperative recurrence rate remains an urgent problem. In order to determine the mechanism underlying recurrence of liver cancer and identify prognostic genes, data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were integrated and analyzed. Differentially expressed genes (DEGs) between HCC tissue and normal liver tissue were identified, and a protein–protein interaction network was constructed to find hub genes. Clinical correlation analysis and disease-free survival (DFS) analysis were performed using the R language and GEPIA to identify relapse-related genes. Correlation analysis was used to identify a potential regulatory axis. Dual-luciferase reporter gene assay was used to confirm the reliability of the long non-coding RNA (lncRNA)–microRNA (miRNA)–mRNA regulatory axis. Immune infiltration analysis was performed using the TIMER database. Correlations between immune gene markers and ASF1B were verified using quantitative real-time polymerase chain reaction (RT-qPCR). In this work, we found that nine lncRNAs and five mRNAs were significantly overexpressed in HCC tissues from patients with recurrence. SNHG3, LINC00205, ASF1B, AURKB, CCNB1, CDKN3, and DTL were also closely related to HCC grade and stage. Survival analysis showed that these seven DEGs were significantly correlated with poor DFS. Correlation analysis identified SNHG3–miR-214-3p–ASF1B as a potential regulatory axis. Dual-luciferase reporter gene assay showed that SNHG3 and ASF1B directly bound to miR-214-3p. ASF1B was negatively regulated by miRNA-214-3p, and overexpression of SNHG3 could inhibit the expression of miRNA-214-3p. In addition, ASF1B was positively correlated with immune infiltration. A reduction in ASF1B could markedly inhibit the expression of CD86, CD8, STAT1, STAT4, CD68, and PD1 in HCC cells. Flow cytometry showed that SNHG3 promoted the PD-1 expression by regulating ASF1B. Meanwhile, elevated ASF1B predicted poor prognosis of HCC patients in subgroups with decreased B cells, CD8+ T cells, or neutrophils, and those with enriched CD4+ T cells. In conclusion, we found that a novel lncRNA SNHG3/miR-214-3p/ASF1B axis could promote the recurrence of HCC by regulating immune infiltration.
Targeting Thymidylate Synthase Enhances the Chemosensitivity of Triple-Negative Breast Cancer Towards 5-FU-Based Combinatorial Therapy
Authors: Haritha Nair Hariprasad , Nawab Akbar , Vijayakurup Vinod , Anto Nikhil Ponnoor , Liju Vijayasteltar B. , Alex Vijai V. , Amrutha Areekkara Nisthul , Aiswarya Sreekumar U. , Swetha Mundanattu , Vinod Balachandran S. , Sundaram Sankar , Guijarro Maria V. , Herlevich Thomas , Krishna Archana , Nestory Nesteena K. , Bava Smitha V. , Sadasivan Chittalakkottu , Zajac-Kaye Maria , Anto Ruby John
Published: July 2021

Background

The ongoing treatment modalities for breast cancer (BC) primarily rely on the expression status of ER, PR and HER-2 receptors in BC tissues. Our strategy of chemosensitization provides new insights to counter chemoresistance, a major obstacle that limits the benefits of chemotherapy of mammary cancers.

Methods

By utilizing a murine breast cancer model employing NSG mice bearing orthotopic triple-negative breast cancer (TNBC) xenografts, we have evaluated the ability of phytochemical curcumin in chemosensitizing BC to 5-Fluorouracil (5-FU) chemotherapy and the differential modulations of cellular events in response to this strategy, independent of their receptor status.

Results

A significant synergistic antitumor potential was observed in the murine model with a sub-optimal dose treatment of 5-FU plus curcumin, as evaluated by a reduction in the tumor-related parameters. We authenticated the pivotal role of thymidylate synthase (TS) in regulating the 5-FU–curcumin synergism using the TNBC pre-clinical model. Our study also confirmed the pharmacological safety of this chemotherapeutic plus phytoactive combination using acute and chronic toxicity studies in Swiss albino mice. Subsequently, the molecular docking analysis of curcumin binding to TS demonstrated the affinity of curcumin towards the cofactor-binding site of TS, rather than the substrate-binding site, where 5-FU binds. Our concomitant in vivo and in silico evidence substantiates the superior therapeutic index of this combination.

Conclusion

This is the first-ever pre-clinical study portraying TS as the critical target of combinatorial therapy for mammary carcinomas and therefore we recommend its clinical validation, especially in TNBC patients, who currently have limited therapeutic options.
N2E4, a Monoclonal Antibody Targeting Neuropilin-2, Inhibits Tumor Growth and Metastasis in Pancreatic Ductal Adenocarcinoma via Suppressing FAK/Erk/HIF-1α Signaling
Authors: Wang Li , Wang Lanlan , Wang Shengyu , Zhou Zonglang , Liu Zongjunlin , Xu Peilan , Luo Xian , Wu Ting , Luo Fanghong , Yan Jianghua
Published: July 2021

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with extremely limited treatment; the effective targeting strategy stays an urgent unmet need. Neuropilin-2 (NRP2), a multifunctional transmembrane non-tyrosine-kinase glycoprotein, enhances various signal transduction pathways to modulate cancer progression. However, the application value of NRP2 as a therapeutic target in pancreatic cancer is still unclear. Here, we detected the elevated NRP2 was associated with the poor prognosis of pancreas carcinoma. The mouse monoclonal antibody targeting NRP2 (N2E4) that could specifically bind to PDAC cells was developed. Moreover, N2E4 inhibits PDAC proliferation, migration, and invasion in vitro, and repressed growth and metastasis in vivo. Mechanistically, the effect of N2E4 was mainly related to the blocking of interaction between NRP2 with integrinβ1 to inhibit FAK/Erk/HIF-1a/VEGF signaling. Therefore, N2E4 has the potential for targeting therapy of PDAC. This study lays a foundation for the future development of NRP2-based targeted therapy for PDAC.
Clinical Outcomes Among Patients With Metastatic Pancreatic Ductal Adenocarcinoma Treated With Liposomal Irinotecan
Authors: Yu Kenneth H. , Hendifar Andrew E. , Alese Olatunji B. , Draper Amber , Abdelrahim Maen , Burns Ethan , Khan Gazala , Cockrum Paul , Bhak Rachel H. , Nguyen Catherine , DerSarkissian Maral , Duh Mei Sheng , Bahary Nathan
Published: July 2021

Background

The NAPOLI-1 trial demonstrated that liposomal irinotecan in combination with fluorouracil (5-FU) and leucovorin (LV) prolonged survival with a manageable safety profile in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. Real-world data on clinical outcomes associated with liposomal irinotecan in NAPOLI-1-based regimens is needed to further substantiate this.

Methods

This real-world, retrospective chart review study included patients with mPDAC who received NAPOLI-1-based regimens from six academic centers in the United States. Liposomal irinotecan initiation defined the index date. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier methodology.

Results

There were 374 patients evaluated; median age was 68 years, and 51% were female. Among 326 patients with baseline ECOG information, approximately 74% had ECOG score <2. Liposomal irinotecan was administered as a doublet with 5-FU in a NAPOLI-1-based regimen in the first line (1L; 16%), 2L (42%), and 3L+ (42%) of the metastatic setting. For patients treated in 1L, 2L, and 3L+, median [95% confidence interval (CI)] OS was 8.0 [5.1, 11.2], 7.3 [5.3, 8.8], and 4.6 [4.0, 5.7] months, and median [95% CI] PFS was 4.2 [2.2, 6.6], 3.0 [2.6, 3.7], and 2.0 [1.7, 2.2] months, respectively.

Conclusions

Patients in a real-world setting treated with NAPOLI-1-based liposomal irinotecan doublet regimens at academic centers were older with poorer performance status compared to trial patients yet had similar outcomes and efficacy. Furthermore, liposomal irinotecan was frequently used in the 3L+ setting where no treatment has been approved and provided clinical benefit.
Postoperative Radiotherapy for Patients With Resectable Stage III-N2 Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Lei Tianyu , Li Jing , Zhong Hao , Zhang Huibo , Jin Yan , Wu Jie , Li Lan , Xu Bin , Song Qibin , Hu Qinyong
Published: July 2021

Purpose

For resectable cases of stage III-N2 non-small cell lung cancer (NSCLC), the best treatment after surgery is still uncertain. The effect of postoperative radiotherapy (PORT) is controversial. Thus, we performed this updated meta-analysis to reassess the data of PORT in stage III-N2 NSCLC patients, to figure out whether these patients can benefit from PORT.

Methods

We conducted searches of the published literature in EMBASE, PubMed, and the Cochrane Library for relevant randomized control trials (RCTs) comparing PORT group with the non-PORT group in NSCLC patients at stage III-N2. These studies allowed the prior chemotherapy in the treatment. We extracted the data from these articles and used the hazard ratios (HRs) and their 95% confidence intervals (CIs) as summary statistics for estimating the effect of PORT on overall survival (OS), disease-free survival (DFS), local-regional recurrence-free survival (LRFS).

Result

The analyses of seven randomized controlled trials (1,318 participants) show no benefit of PORT on survival (HR, 0.87; 95% CI, 0.71 to 1.07; p = 0.18) but a significantly different effect of PORT on DFS (HR, 0.83; 95% CI, 0.71 to 0.97; p = 0.02) and LRFS (HR, 0.64; 95% CI, 0.50 to 0.81; p = 0.0003). There is not enough evidence of a difference in the effect on survival by the utility of chemotherapy along with PORT though subgroup analysis of no chemotherapy group, concurrent chemoradiotherapy and sequential chemoradiotherapy group. Even in trials with 3D-CRT radiation technique, the pooled analysis shows no benefit of PORT on survival in patients with stage III-N2 NSCLC (data is not shown).

Conclusion

Our findings illustrate that in the postoperative treatment for patients with stage III-N2 NSCLC, PORT contributes to a significantly increased DFS and LR and may not associate with an improved OS, indicating a cautious selection.
Down-Regulation of Toll-Like Receptor 5 (TLR5) Increased VEGFR Expression in Triple Negative Breast Cancer (TNBC) Based on Radionuclide Imaging
Authors: Jiang Wen , Han Yeming , Liang Ting , Zhang Chao , Gao Feng , Hou Guihua
Published: July 2021

In this study, GFP-tagged TNBC 4T1 cells with down-regulated TLR5 expression (TLR5− 4T1) and normal TLR5 expression (TLR5+ 4T1) were constructed, respectively. RT-PCR and Western blot studies showed that down-regulation of TLR5 obviously increased the expression of VEGFR in 4T1 cells. Highly stable radio-probes 125I-anti-TLR5 mAb/125I-VEGF/125I-IgG were obtained with labeling rates over 85% and radiochemical purities above 90%. Among these three probes, 125I−anti−TLR5 mAb and 125I-VEGF were used for specifically imaging TNBC, while 125I-IgG was used for comparison. Whole-body phosphorus autoradiography showed clear imaging at 48 h after injection of 125I-anti-TLR5 mAb and 125I-VEGF also provided clear imaging at 24 h. Biodistribution study demonstrated a higher tumor uptake of 125I-anti-TLR5 mAb in TLR5+ group compared with that in TLR5− group (P < 0.05), whereas tumor uptake of 125I-VEGF in TLR5+ group was lower than that in the TLR5− group (P < 0.05). Immunohistochemical staining suggested that the expression of TLR5 was lower, whereas the expression of VEGFR, CD31, and MVD (microvessel density) was higher in TLR5− tumor-bearing mice. In summary, the down-regulation of TLR5 in TNBC promoted the VEGFR expression and angiogenesis, resulting in the proliferation of TNBC cells. TLR5/VEGF might be a better indicator for monitoring the development of TNBC.
Diagnostic Accuracy of SARS-CoV-2 Antigen Detection Test in Children: A Real-Life Study
Authors: Jung Camille , Levy Corinne , Varon Emmanuelle , Biscardi Sandra , Batard Christophe , Wollner Alain , Deberdt Patrice , Sellam Aurélie , Hau Isabelle , Cohen Robert
Published: July 2021

Naso-pharyngeal RT-PCR is the gold standard for the diagnosis of COVID-19, but there is a need for rapid and reliable tests. Some validation studies have used frozen aliquots mainly from adults. The aim of this real-life study was to test the performance of a SARS-CoV-2 rapid antigen test (SC2-RAT) in children. Symptomatic patients aged 0 to 17 years were recruited in the emergency department of the University Hospital of Creteil and in primary care pediatric practices from October 10, 2020 for 7 weeks. Each enrolled child had a SARS-CoV-2 RT-PCR test and a SC2-RAT from two distinct nasopharyngeal swabs. Among the 308 patients (mean [SD] age 4.9 [5.3] years), fever was the main symptom (73.4%), with no difference between COVID-19–negative and –positive groups. The prevalence of COVID-19 was 10.7% (95% CI 7.5–14.7). On the whole cohort, the sensitivity and specificity of the SC2-RAT compared to RT-PCR was 87.9% (95% CI 71.8–96.6) and 98.5% (95% CI 96.3–99.6). Considering samples with cycle threshold >25, the sensibility was lower: 63.6% (95% CI 30.8–89.1) and the specificity 99.6% (95% CI 98.0–100.0). The mean delay to obtain an SC2-RAT result was <15 min but was 3.2 h (SD 5.5) for an RT-PCR result. Contact with a COVID-19–positive person was more frequent for COVID-19–positive than –negative patients (n = 21, 61.6%, vs. n = 64, 24.6%; p < 0.01). In real life, SC2-RAT seems reliable for symptomatic children, allowing to detect contagious children.
A Computational Exploration of the Molecular Network Associated to Neuroinflammation in Alzheimer’s Disease
Authors: El Idrissi Fatima , Gressier Bernard , Devos David , Belarbi Karim
Published: July 2021

Neuroinflammation, as defined by the presence of classically activated microglia, is thought to play a key role in numerous neurodegenerative disorders such as Alzheimer’s disease. While modulating neuroinflammation could prove beneficial against neurodegeneration, identifying its most relevant biological processes and pharmacological targets remains highly challenging. In the present study, we combined text-mining, functional enrichment and protein-level functional interaction analyses to 1) identify the proteins significantly associated to neuroinflammation in Alzheimer’s disease over the scientific literature, 2) distinguish the key proteins most likely to control the neuroinflammatory processes significantly associated to Alzheimer's disease, 3) identify their regulatory microRNAs among those dysregulated in Alzheimer's disease and 4) assess their pharmacological targetability. 94 proteins were found to be significantly associated to neuroinflammation in Alzheimer’s disease over the scientific literature and IL4, IL10 and IL13 signaling as well as TLR-mediated MyD88- and TRAF6-dependent responses were their most significantly enriched biological processes. IL10, TLR4, IL6, AKT1, CRP, IL4, CXCL8, TNF-alpha, ITGAM, CCL2 and NOS3 were identified as the most potent regulators of the functional interaction network formed by these immune processes. These key proteins were indexed to be regulated by 63 microRNAs dysregulated in Alzheimer's disease, 13 long non-coding RNAs and targetable by 55 small molecules and 8 protein-based therapeutics. In conclusion, our study identifies eleven key proteins with the highest ability to control neuroinflammatory processes significantly associated to Alzheimer’s disease, as well as pharmacological compounds with single or pleiotropic actions acting on them. As such, it may facilitate the prioritization of diagnostic and target-engagement biomarkers as well as the development of effective therapeutic strategies against neuroinflammation in Alzheimer’s disease.
Poloxamer 188 Attenuates Ischemia-Reperfusion-Induced Lung Injury by Maintaining Cell Membrane Integrity and Inhibiting Multiple Signaling Pathways
Authors: Tang Shih-En , Liao Wen-I , Pao Hsin-Ping , Hsu Chin-Wang , Wu Shu-Yu , Huang Kun-Lun , Chu Shi-Jye
Published: July 2021

Background: Poloxamer 188 (P188) possesses anti-inflammatory properties and can help to maintain plasma membrane function. P188 has been reported to exert beneficial effects in the treatment of various disorders. However, the effects of P188 in ischemia/reperfusion (IR)-induced acute lung injury have not been examined.

Methods: We investigated the ability of P188 to attenuate IR-induced acute lung injury in rats and hypoxia/reoxygenation (HR) injury in murine epithelial cells. Isolated perfused rat lungs were exposed to 40 min ischemia followed by 60 min reperfusion to induce IR injury.

Results: IR led to lung edema, increased pulmonary arterial pressure, promoted lung tissue inflammation and oxidative stress, and upregulated the levels of TNF-α, IL-6 and CINC-1, and increased Lactic dehydrogenase (LDH) activity in bronchoalveolar lavage fluid. IR also downregulated the levels of inhibitor of κB (IκB-α), upregulated nuclear factor (NF)-κB (NF-κB), and promoted apoptosis in lung tissues. P188 significantly suppressed all these effects. In vitro, P188 also exerted a similar effect in murine lung epithelial cells exposed to HR. Furthermore, P188 reduced the number of propidium iodide-positive cells, maintained cell membrane integrity, and enhanced cell membrane repair following HR.

Conclusion: We conclude that P188 protects against lung IR injury by suppressing multiple signaling pathways and maintaining cell membrane integrity.
Driving Waveform Optimization by Simulation and Numerical Analysis for Suppressing Oil-Splitting in Electrowetting Displays
Authors: Lai Shufa , Zhong Qinghua , Sun Hailing
Published: July 2021

Electrowetting display (EWD) is a new reflective display device with low power consumption and fast response speed. However, the maximum aperture ratio of EWDs is confined by oil-splitting. In order to suppress oil-splitting, a two-dimensional EWD model with a switch-on and a switch-off process was established in this paper. The process of oil-splitting was obtained by applying different voltage values in this model. Then, the relationship between the oil-splitting process and the waveforms with different slopes was analyzed. Based on this relationship, a driving waveform with a narrow falling ramp, low-voltage maintenance, and a rising ramp was proposed on the basis of square waveform. The proposed narrow falling ramp drove the oil to rupture on one side. The low-voltage maintenance stage drove the oil to shrink with a whole block. The proposed rising ramp was pushed the oil into a corner quickly. The experimental results showed that the oil splitting can be suppressed effectively by applying the proposed driving waveform. The aperture ratio of the proposed driving waveform was 2.9% higher than that of the square waveform with the same voltage.
Decreased Serum Brain-Derived Neurotrophic Factor Concentrations 72 Hours Following Marathon Running
Authors: Roeh Astrid , Holdenrieder Stefan , Schoenfeld Julia , Haeckert Jan , Halle Martin , Falkai Peter , Scherr Johannes , Hasan Alkomiet
Published: July 2021

Background: Physical exercise has been linked to beneficial effects on brain plasticity. One potential key mechanism for this relationship is an exercise-induced increase of brain-derived neurotrophic factor (BDNF). However, the kinetics of BDNF in athletes during training phase, extreme exercise competition, and recovery period have not been investigated so far.

Methods: We assessed serum BDNF concentrations in 51 marathon runners (23% female, mean age 43 years) in a longitudinal study design over a period of 6 months. Assessments were conducted during the training period before the marathon and after the marathon race during short-term (24 to 72 h) and long-term (3 months) follow-ups. Potential confounders (fitness level, sex, and platelet count) were included in subsequent linear-model analyses.

Results: Linear mixed-model analyses revealed a main effect of time for BDNF concentrations over the study period (F(4,89.389) = 4.296, p = 0.003). Values decreased significantly with the lowest values at 72 h after the marathon compared to baseline (p = 0.025), a finding that was more pronounced in the larger male cohort.

Conclusion: Prolonged exercise induces a significant decrease in serum BDNF concentration 72 h post-exercise. We assume that this observation is mainly driven by regenerative mechanisms and a higher muscular utilization.
The Effects of Acute Aerobic Exercise on Blood Pressure, Arterial Function, and Heart Rate Variability in Men Living With HIV
Authors: Barros Juliana Pereira , de Paula Tainah , Mediano Mauro Felippe Felix , Rangel Marcus Vinicius dos Santos , Monteiro Walace , Cunha Felipe Amorim da , Farinatti Paulo , Borges Juliana Pereira
Published: July 2021

Purpose

This study aims to investigate the effects of acute cycling on blood pressure (BP), arterial function, and heart rate variability (HRV) in men living with HIV (MLHIV) using combined antiretroviral therapy (cART).

Methods

Twelve MLHIV (48.7 ± 9.2 years; 25.2 ± 2.8 kg m–2) and 13 healthy controls (41.2 ± 9.9 years; 26.3 ± 2.9 kg m–2) performed a cycling bout (ES) (intensity: 50% oxygen uptake reserve; duration: time to achieve 150 kcal—MLHIV: 24.1 ± 5.5 vs. controls: 23.1 ± 3.0 min; p = 0.45), and a 20-min non-exercise session (NES).

Results

At rest (p < 0.05), MLHIV presented higher brachial systolic/diastolic BP (SBP/DBP: 123.2 ± 14.2/76.8 ± 6.3 vs. 114.3 ± 5.1/71.6 ± 2.6 mmHg) and central BP (cSBP/cDBP: 108.3 ± 9.3/76.5 ± 6.5 vs. 101.6 ± 4.9/71.3 ± 4.4 mmHg) vs. controls but lower absolute maximal oxygen uptake (2.1 ± 0.5 vs. 2.5 ± 0.3 L min–1) and HRV indices reflecting overall/vagal modulation (SDNN: 24.8 ± 7.1 vs. 42.9 ± 21.3 ms; rMSSD: 20.5 ± 8.5 vs. 38.1 ± 22.8 ms; pNN50: 3.6 ± 4.2 vs. 13.6 ± 11.3%). DBP postexercise lowered in controls vs. MLHIV (∼4 mmHg, p < 0.001; ES: 0.6). Moreover, controls vs. MLHIV had greater reductions (p < 0.05) in augmentation index (−13.6 ± 13.7 vs. −3.1 ± 7.2% min–1; ES: 2.4), and HRV indices up to 5 min (rMSSD: −111.8 ± 32.1 vs. −75.9 ± 22.2 ms min–1; ES: 3.8; pNN50: −76.3 ± 28.3 vs. −19.0 ± 13.7% min–1; ES: 4.4). Within-group (ES vs. NES; p < 0.05) reductions occurred in controls for SBP (∼10 mmHg, 2 h), DBP (∼6 mmHg, 20, 30, and 70 min), cSBP (∼9 mmHg, 30 min), cDBP (∼7 mmHg, 30 and 70 min), augmentation index (∼10%, 30 min), and pNN50 (∼20%; up to 2 h), while in MLHIV only cSBP (∼6 mmHg, 70 min) and cDBP (∼4 mmHg, 30 min) decreased. Similar increases (up to 5 min) in heart rate (∼22 bpm) and decreases in SDNN (∼18 ms) and rMSSD (∼20 ms) occurred in both groups.

Conclusion

MLHIV under cART exhibited attenuated postexercise hypotension vs. healthy controls, which seemed to relate with impairments in vascular function.
Targeting Dermal Fibroblast Subtypes in Antifibrotic Therapy: Surface Marker as a Cellular Identity or a Functional Entity?
Authors: Huang Xin , Khoong Yimin , Han Chengyao , Su Dai , Ma Hao , Gu Shuchen , Li Qingfeng , Zan Tao
Published: July 2021

Fibroblasts are the chief effector cells in fibrotic diseases and have been discovered to be highly heterogeneous. Recently, fibroblast heterogeneity in human skin has been studied extensively and several surface markers for dermal fibroblast subtypes have been identified, holding promise for future antifibrotic therapies. However, it has yet to be confirmed whether surface markers should be looked upon as merely lineage landmarks or as functional entities of fibroblast subtypes, which may further complicate the interpretation of cellular function of these fibroblast subtypes. This review aims to provide an update on current evidence on fibroblast surface markers in fibrotic disorders of skin as well as of other organ systems. Specifically, studies where surface markers were treated as lineage markers and manipulated as functional membrane proteins are both evaluated in parallel, hoping to reveal the underlying mechanism behind the pathogenesis of tissue fibrosis contributed by various fibroblast subtypes from multiple angles, shedding lights on future translational researches.
Self-Reported Onset of Paroxysmal Atrial Fibrillation Is Related to Sleeping Body Position
Authors: Gottlieb Lisa A. , Blanco Lorena Sanchez y , Hocini Mélèze , Dekker Lukas R. C. , Coronel Ruben
Published: July 2021

Background: Because stretch of the atrial myocardium is proarrhythmic for atrial fibrillation (AF) and a left lateral body position increases atrial dimensions in humans, we hypothesized that left lateral recumbence is a frequent AF-triggering body position in AF patients.

Methods: We performed a questionnaire study of symptomatic paroxysmal AF (episodes of AF < 1 week) patients scheduled for a first AF ablation therapy at Catharina Hospital, Eindhoven, the Netherlands and at University Hospital, Bordeaux, France.

Results: Ninety-four symptomatic paroxysmal AF patients were included [mean age 61 ± 11 years, median AF history of 29(48) months, 31% were females]. Twenty-two percent of patients reported a specific body position as a trigger of their AF symptoms. The triggering body position was left lateral position in 57% of cases, supine position in 33%, right lateral position in 10%, and prone position in 5% (p = 0.003 overall difference in prevalence). Patients with positional AF had a higher body mass index compared to patients without nocturnal/positional AF [28.7(4.2) and 25.4(5.2) kg/m2, respectively, p = 0.025], but otherwise resembled these patients.

Conclusion: Body position, and the left lateral position, in particular, is a common trigger of AF in symptomatic AF patients. Moreover, positional AF is associated with overweight. Understanding of the underlying mechanisms of positional AF can contribute to AF treatment and prevention.
The Effect of Sugarcane Straw Aging in the Field on Cell Wall Composition
Authors: Pagliuso Débora , Grandis Adriana , de Sousa Cristiane Ribeiro , de Souza Amanda Pereira , Driemeier Carlos , Buckeridge Marcos S.
Published: July 2021

Cellulosic ethanol is an alternative for increasing the amount of bioethanol production in the world. In Brazil, sugarcane leads the bioethanol production, and to improve its yield, besides bagasse, sugarcane straw is a possible feedstock. However, the process that leads to cell wall disassembly under field conditions is unknown, and understanding how this happens can improve sugarcane biorefinery and soil quality. In the present work, we aimed at studying how sugarcane straw is degraded in the field after 3, 6, 9, and 12 months. Non-structural and structural carbohydrates, lignin content, ash, and cellulose crystallinity were analyzed. The cell wall composition was determined by cell wall fractionation and determination of monosaccharide composition. Non-structural carbohydrates degraded quickly during the first 3 months in the field. Pectins and lignin remained in the plant waste for up to 12 months, while the hemicelluloses and cellulose decreased 7.4 and 12.4%, respectively. Changes in monosaccharide compositions indicated solubilization of arabinoxylan (xylose and arabinose) and β-glucans (β-1,3 1,4 glucan; after 3 months) followed by degradation of cellulose (after 6 months). Despite cellulose reduction, the xylose:glucose ratio increased, suggesting that glucose is consumed faster than xylose. The degradation and solubilization of the cell wall polysaccharides concomitantly increased the level of compounds related to recalcitrance, which led to a reduction in saccharification and an increase in minerals and ash contents. Cellulose crystallinity changed little, with evidence of silica at the latter stages, indicating mineralization of the material. Our data suggest that for better soil mineralization, sugarcane straw must stay in the field for over 1 year. Alternatively, for bioenergy purposes, straw should be used in less than 3 months.
The Highs and Lows of P Supply in Medical Cannabis: Effects on Cannabinoids, the Ionome, and Morpho-Physiology
Authors: Shiponi Sivan , Bernstein Nirit
Published: July 2021

Environmental conditions, including the availability of mineral nutrients, affect secondary metabolism in plants. Therefore, growing conditions have significant pharmaceutical and economic importance for Cannabis sativa. Phosphorous is an essential macronutrient that affects central biosynthesis pathways. In this study, we evaluated the hypothesis that P uptake, distribution and availability in the plant affect the biosynthesis of cannabinoids. Two genotypes of medical “drug-type” cannabis plants were grown under five P concentrations of 5, 15, 30, 60, and 90 mg L–1 (ppm) in controlled environmental conditions. The results reveal several dose-dependent effects of P nutrition on the cannabinoid profile of both genotypes, as well as on the ionome and plant functional physiology, thus supporting the hypothesis: (i) P concentrations ≤15 mg L–1 were insufficient to support optimal plant function and reduced photosynthesis, transpiration, stomatal conductance and growth; (ii) 30–90 mg L–1 P was within the optimal range for plant development and function, and 30 mg L–1 P was sufficient for producing 80% of the maximum yield; (iii) Ionome: about 80% of the plant P accumulated in the unfertilized inflorescences; (iv) Cannabinoids: P supply higher than 5 mg L–1 reduced Δ9-tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA) concentrations in the inflorescences by up to 25%. Cannabinoid concentrations decreased linearly with increasing yield, consistent with a yield dilution effect, but the total cannabinoid content per plant increased with increasing P supply. These results reveal contrasting trends for effects of P supply on cannabinoid concentrations that were highest under <30 mg L–1 P, vs. inflorescence biomass that was highest under 30–90 mg L–1 P. Thus, the P regime should be adjusted to reflect production goals. The results demonstrate the potential of mineral nutrition to regulate cannabinoid metabolism and optimize pharmacological quality.
Overexpression of Karrikins Receptor Gene Sapium sebiferum KAI2 Promotes the Cold Stress Tolerance via Regulating the Redox Homeostasis in Arabidopsis thaliana
Authors: Shah Faheem Afzal , Ni Jun , Yao Yuanyuan , Hu Hao , Wei Ruyue , Wu Lifang
Published: July 2021

KARRIKINS INSENSITIVE2(KAI2) is the receptor gene for karrikins, recently found to be involved in seed germination, hypocotyl development, and the alleviation of salinity and osmotic stresses. Nevertheless, whetherKAI2could regulate cold tolerance remains elusive. In the present study, we identified thatArabidopsismutants ofKAI2had a high mortality rate, while overexpression of, a bioenergy plant,Sapium sebiferum KAI2(SsKAI2) significantly recovered the plants after cold stress. The results showed that theSsKAI2overexpression lines (OEs) had significantly increased levels of proline, total soluble sugars, and total soluble protein. Meanwhile,SsKAI2OEs had a much higher expression of cold-stress-acclimation-relate genes, such asCold Shock ProteinsandC-REPEAT BINDING FACTORSunder cold stress. Moreover, the results showed thatSsKAI2OEs were hypersensitive to abscisic acid (ABA), and ABA signaling genes were w significantly affected inSsKAI2OEs under cold stress, suggesting a potential interaction betweenSsKAI2and ABA downstream signaling. InSsKAI2OEs, the electrolyte leakage, hydrogen peroxide, and malondialdehyde contents were reduced under cold stress inArabidopsis.SsKAI2OEs enhanced the anti-oxidants like ascorbate peroxidase, catalase, peroxidase, superoxide dismutase, and total glutathione level under cold stress. Conclusively, these results provide novel insights into the understanding of karrikins role in the regulation of cold stress adaptation.
Production of Organic Acids by Arbuscular Mycorrhizal Fungi and Their Contribution in the Mobilization of Phosphorus Bound to Iron Oxides
Authors: Andrino Alberto , Guggenberger Georg , Kernchen Sarmite , Mikutta Robert , Sauheitl Leopold , Boy Jens
Published: July 2021

Most plants living in tropical acid soils depend on the arbuscular mycorrhizal (AM) symbiosis for mobilizing low-accessible phosphorus (P), due to its strong bonding by iron (Fe) oxides. The roots release low-molecular-weight organic acids (LMWOAs) as a mechanism to increase soil P availability by ligand exchange or dissolution. However, little is known on the LMWOA production by AM fungi (AMF), since most studies conducted on AM plants do not discriminate on the LMWOA origin. This study aimed to determine whether AMF release significant amounts of LMWOAs to liberate P bound to Fe oxides, which is otherwise unavailable for the plant. Solanum lycopersicum L. plants mycorrhized with Rhizophagus irregularis were placed in a bicompartmental mesocosm, with P sources only accessible by AMF. Fingerprinting of LMWOAs in compartments containing free and goethite-bound orthophosphate (OP or GOE-OP) and phytic acid (PA or GOE-PA) was done. To assess P mobilization via AM symbiosis, P content, photosynthesis, and the degree of mycorrhization were determined in the plant; whereas, AM hyphae abundance was determined using lipid biomarkers. The results showing a higher shoot P content, along with a lower N:P ratio and a higher photosynthetic capacity, may be indicative of a higher photosynthetic P-use efficiency, when AM plants mobilized P from less-accessible sources. The presence of mono-, di-, and tricarboxylic LMWOAs in compartments containing OP or GOE-OP and phytic acid (PA or GOE-PA) points toward the occurrence of reductive dissolution and ligand exchange/dissolution reactions. Furthermore, hyphae grown in goethite loaded with OP and PA exhibited an increased content of unsaturated lipids, pointing to an increased membrane fluidity in order to maintain optimal hyphal functionality and facilitate the incorporation of P. Our results underpin the centrality of AM symbiosis in soil biogeochemical processes, by highlighting the ability of the AMF and accompanying microbiota in releasing significant amounts of LMWOAs to mobilize P bound to Fe oxides.
Genetic Dissection of Grain Yield of Maize and Yield-Related Traits Through Association Mapping and Genomic Prediction
Authors: Ma Juan , Cao Yanyong
Published: July 2021

High yield is the primary objective of maize breeding. Genomic dissection of grain yield and yield-related traits contribute to understanding the yield formation and improving the yield of maize. In this study, two genome-wide association study (GWAS) methods and genomic prediction were made on an association panel of 309 inbred lines. GWAS analyses revealed 22 significant trait–marker associations for grain yield per plant (GYP) and yield-related traits. Genomic prediction analyses showed that reproducing kernel Hilbert space (RKHS) outperformed the other four models based on GWAS-derived markers for GYP, ear weight, kernel number per ear and row, ear length, and ear diameter, whereas genomic best linear unbiased prediction (GBLUP) showed a slight superiority over other modes in most subsets of the trait-associated marker (TAM) for thousand kernel weight and kernel row number. The prediction accuracy could be improved when significant single-nucleotide polymorphisms were fitted as the fixed effects. Integrating information on population structure into the fixed model did not improve the prediction performance. For GYP, the prediction accuracy of TAMs derived from fixed and random model Circulating Probability Unification (FarmCPU) was comparable to that of the compressed mixed linear model (CMLM). For yield-related traits, CMLM-derived markers provided better accuracies than FarmCPU-derived markers in most scenarios. Compared with all markers, TAMs could effectively improve the prediction accuracies for GYP and yield-related traits. For eight traits, moderate- and high-prediction accuracies were achieved using TAMs. Taken together, genomic prediction incorporating prior information detected by GWAS could be a promising strategy to improve the grain yield of maize.
Integrating Genome-Wide Association Analysis With Transcriptome Sequencing to Identify Candidate Genes Related to Blooming Time in Prunus mume
Authors: Zhang Man , Yang Qingqing , Yuan Xi , Yan Xiaolan , Wang Jia , Cheng Tangren , Zhang Qixiang
Published: July 2021

Prunus mumeis one of the most important woody perennials for edible and ornamental use. Despite a substantial variation in the flowering phenology among theP. mumegermplasm resources, the genetic control for flowering time remains to be elucidated. In this study, we examined five blooming time-related traits of 235P. mumelandraces for 2 years. Based on the phenotypic data, we performed genome-wide association studies, which included a combination of marker- and gene-based association tests, and identified 1,445 candidate genes that are consistently linked with flowering time across multiple years. Furthermore, we assessed the global transcriptome change of floral buds from the twoP. mumecultivars exhibiting contrasting bloom dates and detected 617 associated genes that were differentially expressed during the flowering process. By integrating a co-expression network analysis, we screened out 191 gene candidates of conserved transcriptional pattern during blooming across cultivars. Finally, we validated the temporal expression profiles of these candidates and highlighted their putative roles in regulating floral bud break and blooming time inP. mume. Our findings are important to expand the understanding of flowering time control in woody perennials and will boost the molecular breeding of novel varieties inP. mume.
FERONIA Confers Resistance to Photooxidative Stress in Arabidopsis
Authors: Shin Seung Yong , Park Ji-Sun , Park Hye-Bin , Moon Ki-Beom , Kim Hyun-Soon , Jeon Jae-Heung , Cho Hye Sun , Lee Hyo-Jun
Published: July 2021

Plants absorb light energy required for photosynthesis, but excess light can damage plant cells. To protect themselves, plants have developed diverse signaling pathways which are activated under high-intensity light. Plant photoprotection mechanisms have been mainly investigated under conditions of extremely high amount of light; thus, it is largely unknown how plants manage photooxidative damage under moderate light intensities. In the present study, we found that FERONIA (FER) is a key protein that confers resistance to photooxidative stress in plants under moderate light intensity. FER-deficient mutants were highly susceptible to increasing light intensity and exhibited photobleaching even under moderately elevated light intensity (ML). Light-induced expression of stress genes was largely diminished by the fer-4 mutation. In addition, excitation pressure on Photosystem II was significantly increased in fer-4 mutants under ML. Consistently, reactive oxygen species, particularly singlet oxygen, accumulated in fer-4 mutants grown under ML. FER protein abundance was found to be elevated after exposure to ML, which is indirectly affected by the ubiquitin-proteasome pathway. Altogether, our findings showed that plants require FER-mediated photoprotection to maintain their photosystems even under moderate light intensity.
Cross-Cultural Comparison of How Mind-Body Practice Affects Emotional Intelligence, Cognitive Well-Being, and Mental Well-Being
Authors: Walter Ofra , Shenaar-Golan Vered , Routray Surekha
Published: July 2021

The study tested cross-cultural differences between Israeli and Indian participants in the outcomes of mind-body practice (MBP) on emotional intelligence (EI), cognitive well-being, and mental well-being, as well as the predictive role of gender and MBP on cognitive and mental well-being. It drew on a sample of 699 Indian and Israeli participants (ages 18–65) from urban settings and used questionnaires to measure cognitive well-being, demographics, EI, and mental well-being. EI was assessed using the Self Report Emotional Intelligence (SREIT); cognitive well-being was assessed using the Personal Well-being Index; mental well-being was assessed using the Warwick-Edinburgh Mental Well-being Scale (WEMWBS). The effect of demographic variables was tested using the two-sampleT-test or the Chi-square test. The associations between EI, mental, and cognitive subscales were evaluated using the Pearson correlation coefficient and linear regression with stepwise selection. Results indicated MBP affected EI in both cultures, but Indian participants showed higher EI, and Israeli participants showed lower EI. Israelis also reported higher mental well-being. Future research should examine EI as ability (we examined it as a trait) thus contributing to a better understanding of the similarities and differences between trait and ability EI in different cultures. Future work should also probe gender differences.
Compilation and Application of the Scale of Sustainable Knowledge Sharing Willingness in Virtual Academic Community During the Times of the Coronavirus Pandemic (COVID-19)
Authors: Chen Huaruo , Liu Fei , Wen Ya , Ling Ling , Gu Xueying
Published: July 2021

With the outbreak of COVID-19, many offline academic activities have been turned online, and virtual academic communities have been further emphasized. Based on this situation, this study took the Eagly and Chaiken’s Heuristic-System Model of Persuasion and the general rules of behavioral decision as a theoretical basis, established a theoretical model of sustainable knowledge sharing willingness in virtual academic communities. Firstly, this study developed the scale of willingness to share sustainable knowledge based on the heuristic system model of persuasion. After analyzing the data of 62 participants, the scale was revised. Secondly, 256 valid data were collected from China, the United States, Singapore, and Indonesia. Finally, the conceptual model and theoretical hypothesis were tested based on the data. The results show that knowledge sharing satisfaction is affected by heuristic factors (knowledge sharing quantity, knowledge source credibility) and system factors (knowledge sharing quality, knowledge sharing usefulness), and has a significant positive correlation with sustainable knowledge sharing willingness.
Job Insecurity, Work-Related Flow, and Financial Anxiety in the Midst of COVID-19 Pandemic and Economic Downturn
Authors: Basyouni Sawzan Sadaqa , El Keshky Mogeda El Sayed
Published: July 2021

During the COVID-19 pandemic, every domain of industry has experienced a severe economic downturn with concomitant stress throughout the economy. Employees working in government and private sectors are experiencing different psychological problems. The current study was conducted to investigate the role of work-related flow in the relationship of job insecurity with financial anxiety in the employees working in private and government sectors of Saudi Arabia. The sample comprised 1,195 employees, 886 females, and 309 males. The participants' ages ranged from 25 to 60 years. The Financial Anxiety Scale, Work-Related Flow Inventory, and Qualitative Job Insecurity Measures were found valid and reliable. Structural equation modeling was applied to test the associations. As hypothesized, the results indicated that job insecurity was positively related to financial anxiety, work-related flow was negatively associated with financial anxiety, and work-related flow mediated the relationship between job insecurity and financial anxiety. All these associations were significant regardless of gender, age, marital status, sector of employment, income, self-rated health, and COVID-19 infection status. Further research is needed to understand the impact of job insecurity on financial anxiety in-depth through the paths of work-related flow, especially in the midst of COVID-19.