bluuebunny/crossref_metadata_2025 huggingface dataset:
In-vitro Investigation of Polyphenol-Rich Date (Phoenix dactylifera L.) Seed Extract Bioactivity
Authors: Hilary Serene , Kizhakkayil Jaleel , Souka Usama , Al-Meqbaali Fatima , Ibrahim Wissam , Platat Carine
Published: August 2021

Date seeds are a by-product of the date fruit processing industry with minimal human use; however, they are a rich source of polyphenols with a range of potential biological properties. The current study investigates the cytotoxicity of date seed polyphenols against cancer cell lines, its ability to combat hyperglycemia, its antioxidant potential and its anti-adipogenic effect. The present work aimed to establish the usefulness of date seeds in the food industry as a functional ingredient. The anti-tumour activity of DSE was tested in a panel of cell lines such as MCF-7, MDA-MB-231, Hep-G2, Caco-2, and PC-3 by measuring cell viability and cleaved PARP. Lipid accumulation and effect on the differentiation of 3T3-L1 cells (adipocytes) were tested with date seed extract treatments. The influence of date seed polyphenols on glucose uptake was studied in 3T3-L1 cells and C2C12 cells (muscle cells). The antioxidant activity of the polyphenols from date seed products such as date seed extract (DSE), date seed powder (DSP), and date seeds fortified bread (DSB) was tested following in-vitro digestion to study their stability in the gastrointestinal milieu. DSE treatment resulted in significantly reduced viability in MCF-7 and Hep-G2 cells with 48-h treatments. Glucose uptake increased in the adipocytes with DSE treatments; moreover, it inhibited adipocyte differentiation and lipid accumulation. DSE decreased the expression levels of PPAR-γ, C/EBPα, adiponectin and upregulated GLUT-4, and phospho-AMPK. This study also found that date seed samples retained antioxidant activity in the digestive milieu and concludes that the date seed polyphenols remain active in the digestive milieu and exhibit potential anti-hyperglycemic and anti-adipogenic activity.
Consumers' Perceptions of Healthy Food Availability in Online Food Delivery Applications (OFD Apps) and Its Association With Food Choices Among Public University Students in Malaysia
Authors: Eu Elisa Zhen Rong , Sameeha Mohd Jamil
Published: August 2021

This retrospective cross-sectional study was conducted to study consumers' perceptions of healthy food availability in online food delivery applications (OFD apps) among public university students in Malaysia and its association with their food choices. A total of 290 subjects aged 19–29 years old were recruited from 20 public universities in Malaysia via snowball sampling. Data was collected through an online questionnaire which consisted of socio-demographic status, use of OFD apps (most frequently used brand, usage frequency, food choice, and expenditure per transaction), factors affecting food choice in OFD apps, consumers' perceptions of healthy food availability in OFD apps and recommendation for improvements. The most frequently used apps among the subjects was Food Panda (46.6%), however, majority of the subjects in this study (41.4%) rarely used OFD apps. Also, most of the subjects ordered unhealthy food (77.6%) and spent up to RM15–RM19 for each transaction (43.1%). There was no significant difference between the use of OFD apps and gender (p > 0.05). Among the five food choice motives, “price and convenience” motive was the most influencing food choice factor in OFD apps. Majority of the subjects (76.9%) had a negative perception of healthy food availability (variety, price, and quality of healthy food) in OFD apps. No significant association was found between consumers' perceptions of healthy food availability in OFD apps and their food choices made in OFD apps among the subjects in this study (p > 0.05). Also, majority (85.9%) responded they are keen to purchase healthy foods through OFD apps if they are given an option. However, most Malaysian public university students perceived that there were not much variety of healthy food, of good quality and affordable price, available in OFD apps. This finding suggests that the online food environment in Malaysia are perceived as unhealthy. Future studies can explore the online food environment particularly its impact on community health and well-being. Public health professionals and policymakers need to address the online food environment issues as part of the obesogenic food environment in Malaysia especially when OFD is one of the most convenient service in this country.
Prebiotic, Antioxidant, and Immunomodulatory Properties of Acidic Exopolysaccharide From Marine Rhodotorula RY1801
Authors: Wang Zheng , Zhao Yanchen , Jiang Yan , Chu Weihua
Published: August 2021

In this study, an extracellular acidic polysaccharide (EAPS) from marine Rhodotorula sp. RY1801 was extracted, and its biological properties were investigated. EAPS is mainly composed of monosaccharides, including mannose, rhamnose, glucose, galactose, and fucose, had an average molecular weight of 5.902 × 107 Da. The results indicated that EAPS can promote the growth of Lactobacillus acidophilus and L. acidophilus plantarum. EAPS is capable of scavenging both superoxide anion and hydroxyl radicals in vitro. The highest scavenging rate of superoxide anion and hydroxyl radicals is 29 and 84%, respectively. Using in vivo model, we found that the EAPS can expand the lifespan and increase the disease resistance of Caenorhabditis elegans against Klebsiella pneumoniae infection via the DAF-2/DAF-16 pathway. These results suggested that EAPS from marine Rhodotorula sp. RY1801 could promote the growth of beneficial bacteria and can be used as an antioxidant and immunomodulator, which had considerable potential in the food and health industry.
Secondary Structure of Human De Novo Evolved Gene Product NCYM Analyzed by Vacuum-Ultraviolet Circular Dichroism
Authors: Matsuo Tatsuhito , Nakatani Kazuma , Setoguchi Taiki , Matsuo Koichi , Tamada Taro , Suenaga Yusuke
Published: August 2021

NCYM, a cis-antisense gene of MYCN, encodes a Homininae-specific protein that promotes the aggressiveness of human tumors. Newly evolved genes from non-genic regions are known as de novo genes, and NCYM was the first de novo gene whose oncogenic functions were validated in vivo. Targeting NCYM using drugs is a potential strategy for cancer therapy; however, the NCYM structure must be determined before drug design. In this study, we employed vacuum-ultraviolet circular dichroism to evaluate the secondary structure of NCYM. The SUMO-tagged NCYM and the isolated SUMO tag in both hydrogenated and perdeuterated forms were synthesized and purified in a cell-free in vitro system, and vacuum-ultraviolet circular dichroism spectra were measured. Significant differences between the tagged NCYM and the isolated tag were evident in the wavelength range of 190–240 nm. The circular dichroism spectral data combined with a neural network system enabled to predict the secondary structure of NCYM at the amino acid level. The 129-residue tag consists of α-helices (approximately 14%) and β-strands (approximately 29%), which corresponded to the values calculated from the atomic structure of the tag. The 238-residue tagged NCYM contained approximately 17% α-helices and 27% β-strands. The location of the secondary structure predicted using the neural network revealed that these secondary structures were enriched in the Homininae-specific region of NCYM. Deuteration of NCYM altered the secondary structure at D90 from an α-helix to another structure other than α-helix and β-strand although this change was within the experimental error range. All four nonsynonymous single-nucleotide polymorphisms (SNPs) in human populations were in this region, and the amino acid alteration in SNP N52S enhanced Myc-nick production. The D90N mutation in NCYM promoted NCYM-mediated MYCN stabilization. Our results reveal the secondary structure of NCYM and demonstrated that the Homininae-specific domain of NCYM is responsible for MYCN stabilization.
Molecular Imaging and the PD-L1 Pathway: From Bench to Clinic
Authors: Leung David , Bonacorsi Samuel , Smith Ralph Adam , Weber Wolfgang , Hayes Wendy
Published: August 2021

Programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors target the important molecular interplay between PD-1 and PD-L1, a key pathway contributing to immune evasion in the tumor microenvironment (TME). Long-term clinical benefit has been observed in patients receiving PD-(L)1 inhibitors, alone and in combination with other treatments, across multiple tumor types. PD-L1 expression has been associated with response to immune checkpoint inhibitors, and treatment strategies are often guided by immunohistochemistry-based diagnostic tests assessing expression of PD-L1. However, challenges related to the implementation, interpretation, and clinical utility of PD-L1 diagnostic tests have led to an increasing number of preclinical and clinical studies exploring interrogation of the TME by real-time imaging of PD-(L)1 expression by positron emission tomography (PET). PET imaging utilizes radiolabeled molecules to non-invasively assess PD-(L)1 expression spatially and temporally. Several PD-(L)1 PET tracers have been tested in preclinical and clinical studies, with clinical trials in progress to assess their use in a number of cancer types. This review will showcase the development of PD-(L)1 PET tracers from preclinical studies through to clinical use, and will explore the opportunities in drug development and possible future clinical implementation.
Neoadjuvant Chemotherapy Versus Direct Surgery for Locally Advanced Gastric Cancer With Serosal Invasion (cT4NxM0): A Propensity Score-Matched Analysis
Authors: Xu Wei , Wang Lingquan , Yan Chao , He Changyu , Lu Sheng , Ni Zhentian , Hua Zichen , Zhu Zhenglun , Sah Birendra Kumar , Yang Zhongyin , Zheng Yanan , Feng Runhua , Li Chen , Yao Xuexin , Chen Mingmin , Liu Wentao , Yan Min , Zhu Zhenggang
Published: August 2021

Background

For locally advanced gastric cancer (LAGC) with serosal invasion (cT4NxM0), adjuvant chemotherapy (AC) after D2 gastrectomy is the standard therapy in Asia. However, perioperative chemotherapy (PCT) combined with D2 gastrectomy is mostly suggested in Europe and America. As a part of PCT, the value of neoadjuvant chemotherapy (NAC) is unclear. We investigated whether NAC could further improve survival and other outcomes for these patients.

Methods

Patients with cT4NxM0 gastric cancer who underwent D2 gastrectomy were analyzed. The patients were divided into two groups based on whether they received NAC: the neoadjuvant chemotherapy (NAC) and direct surgery (S) groups. After propensity score matching (1:1 ratio), survival and perioperative outcomes were analyzed between the two groups.

Results

A total of 902 patients met all the eligibility criteria and were enrolled. After propensity score matching, 221 matched pairs of patients were identified. The median overall survival (OS) and disease-free survival (DFS) of all patients were 75.10 and 43.67 months, respectively. The median OS of patients in the NAC and S groups were undefined and 29.80 months, respectively (P<0.0001). The median DFS of patients in the NAC and S groups were undefined and 22.60 months (P<0.0001). There were no significant differences in the radical degrees of operation between the two groups (P=0.07). However, there were significant differences in postoperative hospital stay (P<0.001) and complications (P=0.037) between the two groups.

Conclusion

This study suggested NAC can further improve prognosis and prevent recurrence in LAGC (cT4NxM0) patients. NAC is feasible and safe for LAGC (cT4NxM0) patients, and does not increase the risk of perioperative surgery.
Elucidating the Role of Serum tRF-31-U5YKFN8DYDZDD as a Novel Diagnostic Biomarker in Gastric Cancer (GC)
Authors: Huang Yuejiao , Zhang Haiyan , Gu Xinliang , Qin Shiyi , Zheng Ming , Shi Xiangrong , Peng Chunlei , Ju Shaoqing
Published: August 2021

Background

Gastric cancer (GC) is one of the malignant tumors with the highest morbidity and mortality in the world. Early diagnosis combined with surgical treatment can significantly improve the prognosis of patients. Therefore, it is urgent to seek higher sensitivity and specificity biomarkers in GC. tRNA-derived small RNAs are a new non-coding small RNA that widely exists in tumor cells and body fluids. In this study, we explore the expression and biological significance of tRNA-derived small RNAs in GC.

Materials and Methods

First of all, we screened the differentially expressed tRNA-derived small RNAs in tumor tissues by high-throughput sequencing. Agarose gel electrophoresis (AGE), Sanger sequencing, and Nuclear and Cytoplasmic RNA Separation Assay were used to screen tRF-31-U5YKFN8DYDZDD as a potential tumor biomarker for the diagnosis of GC. Then, we detected the different expressions of tRF-31-U5YKFN8DYDZDD in 24 pairs of GC and paracancerous tissues, the serum of 111 GC patients at first diagnosis, 89 normal subjects, 48 superficial gastritis patients, and 28 postoperative GC patients by quantitative real-time PCR (qRT-PCR). Finally, we used the receiver operating characteristic (ROC) curve to analyze its diagnostic efficacy.

Results

The expression of tRF-31-U5YKFN8DYDZDD has good stability and easy detection. tRF-31-U5YKFN8DYDZDD was highly expressed in tumor tissue, serum, and cell lines of GC, and the expression was significantly related to TNM stage, depth of tumor invasion, lymph node metastasis, and vascular invasion. The expression of serum tRF-31-U5YKFN8DYDZDD in the GC patients decreased after the operation (P = 0.0003). Combined with ROC curve analysis, tRF-31-U5YKFN8DYDZDD has better detection efficiency than conventional markers.

Conclusions

The expressions of tRF-31-U5YKFN8DYDZDD in the tumor and paracancerous tissues, the serum of GC patients and healthy people, and the serum of GC patients before and after operation were different. tRF-31-U5YKFN8DYDZDD is not only a diagnostic biomarker of GC but also a predictor of poor prognosis.
tRNA-Derived Fragment tRF-Glu-TTC-027 Regulates the Progression of Gastric Carcinoma via MAPK Signaling Pathway
Authors: Xu Weiguo , Zhou Bin , Wang Juan , Tang Li , Hu Qing , Wang Jian , Chen Huanhuan , Zheng Junyu , Yan Feng , Chen Huanqiu
Published: August 2021

Transfer RNA-derived RNA fragments (tRFs) belong to non-coding RNAs (ncRNAs) discovered in most carcinomas. Although some articles have demonstrated the characteristics of tRFs in gastric carcinoma (GC), the underlying mechanisms still need to be elucidated. Meanwhile, it was reported that the MAPK pathway was momentous in GC progression. Thus we focused on investigating whether tRF-Glu-TTC-027 could act as a key role in the progression of GC with the regulation of the MAPK pathway. We collected the data of the tRNA-derived fragments expression profile from six paired clinical GC tissues and corresponding adjacent normal samples in this study. Then we screened tRF-Glu-TTC-027 for analysis by using RT-PCR. We transfected GC cell lines with tRF-Glu-TTC-027 mimics or mimics control. Then the proliferation, migration, and invasion assays were performed to assess the influence of tRF-Glu-TTC-027 on GC cell lines. Fluorescence in situ hybridization assay was conducted to confirm the cell distribution of tRF-Glu-TTC-027. We confirmed the mechanism that tRF-Glu-TTC-027 influenced the MAPK signaling pathway and observed a strong downregulation of tRF-Glu-TTC-027 in clinical GC samples. Overexpression of tRF-Glu-TTC-027 suppressed the malignant activities of GC in vitro and in vivo. MAPK signaling pathway was confirmed to be a target pathway of tRF-Glu-TTC-027 in GC by western blot. This is the first study to show that tRF-Glu-TTC-027 was a new tumor-suppressor and could be a potential object for molecular targeted therapy in GC.
The Effect of Severe Intraventricular Hemorrhage on the Biorhythms of Feeding in Premature Infants
Authors: Gewolb Ira H. , Sobowale Babatunde T. , Vice Frank L. , Patwardhan Abhijit , Solomonia Nino , Reynolds Eric W.
Published: August 2021

Background: Suck-swallow rhythmicity and the integration of breathing into infant feeding are developmentally regulated. Neurological injury and breathing abnormalities can both impact feeding in preterm infants.

Objective: To determine the effects of neurologic injury independent of effects of disordered breathing on feeding biorhythms in premature infants.

Methods: Low-risk preterm infants (LRP), infants with Grade 3–4 Intraventricular Hemorrhage (IVH), those with bronchopulmonary dysplasia (BPD), and those with both BPD and IVH (BPD+IVH) were identified. Forty-seven infants, 32–42 weeks Postmenstrual Age (PMA) were evaluated on one or more occasions (131 studies). Of these, 39 infants (81 studies) were performed at >35 weeks PMA. Coefficient of variation (COV) (=standard deviation of the inter-event (e.g., suck-suck, swallow-breath, etc.) interval divided by the mean of the interval) was used to quantify rhythmic stability.

Results: To adjust for PMA, only those infants >35–42 weeks were compared. Suck-suck COV was significantly lower (more rhythmically stable) in the LRP group [COV = 0.274 ± 0.051 (S.D.)] compared to all other groups (BPD = 0.325 ± 0.066; IVH = 0.342 ± 0.072; BPD + IVH = 0.314 ± 0.069; all p < 0.05). Similarly, suck-swallow COV was significantly lower in LRP babies (0.360 ± 0.066) compared to the BPD group (0.475 ± 0.113) and the IVH cohort (0.428 ± 0.075) (p < 0.05). The BPD+IVH group (0.424 ± 0.109), while higher, was not quite statistically significant.

Conclusions: Severe IVH negatively impacts suck-suck and suck-swallow rhythms. The independent effect of neurological injury in the form of IVH on feeding rhythms suggests that quantitative analysis of feeding may reflect and predict neurological sequelae.
Cost-Effectiveness Analysis of Nivolumab Plus Ipilimumab for Advanced Non-Small-Cell Lung Cancer
Authors: Wan Xiaomin , Zeng Xiaohui , Peng Liubao , Peng Ye , Liu Qiao , Yi Lidan , Luo Xia , Deng Qijian , Tan Chongqing
Published: August 2021

Objective: This study evaluated the cost-effectiveness of nivolumab plus ipilimumab vs. chemotherapy in the first-line setting for patients with advanced non-small-cell lung cancer (NSCLC) from the US payer perspective.

Materials and methods: A Markov model wasdeveloped to evaluate the cost and effectiveness of nivolumab plus ipilimumab vs. chemotherapy in the first-line treatment of advanced NSCLC. The survival benefits of nivolumab plus ipilimumab were based on the results of the CheckMate 227 trial. The main endpoints of the model were cost, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER). Univariable and probabilistic sensitivity analyses were conducted to assess model uncertainty. Additonal subgroup analyses were also performed.

Results: nivolumab plus ipilimumab produced a gain of 0.62 QALYs, at a cost of $104238 per QALY. The variables that had the greatest influence on the ICER were body weight and overall survival (OS) hazard ratio (HR). The probability of nivolumab plus ipilimumab being cost-effectiveness compared to chemotherapy is 50.7 and 66.2% when the willingness-to-pay (WTP) value is $ 100,000 and $ 150,000 per QALY. The results of subgroup analyses showed the ICER remained below $150,000/QALY regardless of the PD-L1 expression level.

Conclusions: nivolumab plus ipilimumab was estimated to be cost-effective compared with chemotherapy for patients with advanced NSCLC at a WTP threshold from 100,000/QALY to 150,000/QALY.
MicroRNA-221-3p Suppresses the Microglia Activation and Seizures by Inhibiting of HIF-1α in Valproic Acid-Resistant Epilepsy
Authors: Fu Meng , Zhu Yiqing , Zhang Junqi , Wu Wei , Sun Yunxia , Zhang Xuemei , Tao Jie , Li Zhiping
Published: August 2021

One-third of patients with epilepsy suffer from drug-resistant epilepsy (DRE). Valproic acid (VPA) is a classic anticonvulsant drug, and its resistance is a crucial predictor of DRE, but the pathogenesis remain unknown. Most patients with VPA-resistant epilepsy appear distinct inflammatory response and local hypoxia. Hypoxia-inducible factor (HIF)-1α is an essential effector molecule of hypoxia and inflammation, and may exert therefore a significant effect on the development of VPA-resistant epilepsy. We systematically assess the significance of HIF-1α on children and mice with VPA-resistant epilepsy, and investigated the micro (mi) RNAs that regulate HIF-1α expression. We established models of VPA-sensitive epilepsy and VPA-resistant epilepsy in mice, and confirmed that they had significant differences in epileptic behavior and electroencephalography data. Through proteomics analysis, we identified that HIF-1α was overexpressed in mice with VPA-resistant epilepsy, and regulated the expression of interleukin-1β and tumor necrosis factor-α. Increased expression of HIF-1α led to the increase of microglia and induced their polarization from the M2 phenotype to M1 phenotype, which triggered the release of proinflammatory mediators. Bioinformatics analysis of public databases demonstrated that miR-221-3p was reduced in VPA-resistant epilepsy, and negatively regulated HIF-1α expression. Intervention using miR-221-3p mimics reduced HIF-1α expression markedly and suppressed the activation of microglia and the release of inflammatory mediators, which relieved epileptic seizures of VPA-resistant epilepsy. These observations reveal miR-221-3p/HIF-1α as essential component in pathogenesis of VPA-resistant epilepsy which represent therapeutic antiseizure targets.
Effects of Naringin on Cardiomyocytes From a Rodent Model of Type 2 Diabetes
Authors: Uryash A. , Mijares A. , Flores V. , Adams J. A. , Lopez J. R.
Published: August 2021

Diabetic cardiomyopathy (DCM) is a primary disease in diabetic patients characterized by diastolic dysfunction leading to heart failure and death. Unfortunately, even tight glycemic control has not been effective in its prevention. We have found aberrant diastolic Ca2+ concentrations ([Ca2+]d), decreased glucose transport, elevated production of reactive oxygen species (ROS), and increased calpain activity in cardiomyocytes from a murine model (db/db) of type 2 diabetes (T2D). Cardiomyocytes from these mice demonstrate significant cell injury, increased levels of tumor necrosis factor-alpha and interleukin-6 and expression of the transcription nuclear factor-κB (NF-κB). Furthermore, decreased cell viability, and reduced expression of Kir6.2, SUR1, and SUR2 subunits of the ATP-sensitive potassium (KATP) channels. Treatment of T2D mice with the citrus fruit flavonoid naringin for 4 weeks protected cardiomyocytes by reducing diastolic Ca2+ overload, improving glucose transport, lowering reactive oxygen species production, and suppressed myocardial inflammation. In addition, naringin reduced calpain activity, decreased cardiac injury, increased cell viability, and restored the protein expression of Kir6.2, SUR1, and SUR2 subunits of the KATP channels. Administration of the KATP channel inhibitor glibenclamide caused a further increase in [Ca2+]d in T2D cardiomyocytes and abolished the naringin effect on [Ca2+]d. Nicorandil, a KATP channel opener, and nitric oxide donor drug mimic the naringin effect on [Ca2+]d in T2D cardiomyocyte; however, it aggravated the hyperglycemia in T2D mice. These data add new insights into the mechanisms underlying the beneficial effects of naringin in T2D cardiomyopathy, thus suggesting a novel approach to treating this cardiovascular complication.
Comprehensive Analysis of Key Genes, Signaling Pathways and miRNAs in Human Knee Osteoarthritis: Based on Bioinformatics
Authors: Chang Liang , Yao Hao , Yao Zhi , Ho Kevin Ki-Wai , Ong Michael Tim-Yun , Dai Bingyang , Tong Wenxue , Xu Jiankun , Qin Ling
Published: August 2021

Background: Osteoarthritis (OA) is one of the main causes of disability in the elderly population, accompanied by a series of underlying pathologic changes, such as cartilage degradation, synovitis, subchondral bone sclerosis, and meniscus injury. The present study aimed to identify key genes, signaling pathways, and miRNAs in knee OA associated with the entire joint components, and to explain the potential mechanisms using computational analysis.

Methods: The differentially expressed genes (DEGs) in cartilage, synovium, subchondral bone, and meniscus were identified using the Gene Expression Omnibus 2R (GEO2R) analysis based on dataset from GSE43923, GSE12021, GSE98918, and GSE51588, respectively and visualized in Volcano Plot. Venn diagram analyses were performed to identify the overlapping DEGs (overlapping DEGs) that expressed in at least two types of tissues mentioned above. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, protein-protein interaction (PPI) analysis, and module analysis were conducted. Furthermore, qRT-PCR was performed to validate above results using our clinical specimens.

Results: As a result, a total of 236 overlapping DEGs were identified, of which 160 were upregulated and 76 were downregulated. Through enrichment analysis and constructing the PPI network and miRNA-mRNA network, knee OA-related key genes, such as HEY1, AHR, VEGFA, MYC, and CXCL12 were identified. Clinical validation by qRT-PCR experiments further supported above computational results. In addition, knee OA-related key miRNAs such as miR-101, miR-181a, miR-29, miR-9, and miR-221, and pathways such as Wnt signaling, HIF-1 signaling, PI3K-Akt signaling, and axon guidance pathways were also identified. Among above identified knee OA-related key genes, pathways and miRNAs, genes such as AHR, HEY1, MYC, GAP43, and PTN, pathways like axon guidance, and miRNAs such as miR-17, miR-21, miR-155, miR-185, and miR-1 are lack of research and worthy for future investigation.

Conclusion: The present informatic study for the first time provides insight to the potential therapeutic targets of knee OA by comprehensively analyzing the overlapping genes differentially expressed in multiple joint components and their relevant signaling pathways and interactive miRNAs.
Clemastine Ameliorates Perioperative Neurocognitive Disorder in Aged Mice Caused by Anesthesia and Surgery
Authors: Wu Wensi , Zhang Xiaojun , Zhou Jiaxin , Yang Hongmei , Chen Junjun , Zhao Le , Zhong Junying , Lin Wei-jye , Wang Zhi
Published: August 2021

Perioperative neurocognitive disorder (PND) leads to progressive deterioration of cognitive function, especially in aged patients. Demyelination is closely associated with cognitive dysfunction. However, the relationship between PND and demyelination remains unclear. Here we showed that demyelination was related to the pathogenesis of PND. Clemastine, an antihistamine with potency in remyelination, was predicted to have a potential therapeutic effect on PND by next-generation sequencing and bioinformatics in our previous study. In the present study, it was given at 10 mg/kg per day for 2 weeks to evaluate the effects on PND in aged mice. We found that clemastine ameliorated PND and reduced the expression levels of inflammatory factors such as tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β). Further investigation suggested clemastine increased the expression of oligodendrocyte transcription factor 2 (OLIG2) and myelin basic protein (MBP) to enhance remyelination by inhibiting the overactivation of the WNT/β-catenin pathway. At the same time, the expression of post-synaptic density protein 95 (PSD95, or DLG4), brain-derived neurotrophic factor (BDNF), synaptosomal-associated protein 25 (SNAP25) and neuronal nuclei (NEUN) were also improved. Our results suggested that clemastine might be a therapy for PND caused by anesthetic and surgical factors in aged patients.
Oscillatory Microrheology, Creep Compliance and Stress Relaxation of Biological Cells Reveal Strong Correlations as Probed by Atomic Force Microscopy
Authors: Flormann D.A.D. , Anton C. , Pohland M.O. , Bautz Y. , Kaub K. , Terriac E. , Schäffer T.E. , Rheinlaender J. , Janshoff A. , Ott A. , Lautenschläger F.
Published: August 2021

The mechanical properties of cells are important for many biological processes, including wound healing, cancers, and embryogenesis. Currently, our understanding of cell mechanical properties remains incomplete. Different techniques have been used to probe different aspects of the mechanical properties of cells, among them microplate rheology, optical tweezers, micropipette aspiration, and magnetic twisting cytometry. These techniques have given rise to different theoretical descriptions, reaching from simple Kelvin-Voigt or Maxwell models to fractional such as power law models, and their combinations. Atomic force microscopy (AFM) is a flexible technique that enables global and local probing of adherent cells. Here, using an AFM, we indented single retinal pigmented epithelium cells adhering to the bottom of a culture dish. The indentation was performed at two locations: above the nucleus, and towards the periphery of the cell. We applied creep compliance, stress relaxation, and oscillatory rheological tests to wild type and drug modified cells. Considering known fractional and semi-fractional descriptions, we found the extracted parameters to correlate. Moreover, the Young’s modulus as obtained from the initial indentation strongly correlated with all of the parameters from the applied power-law descriptions. Our study shows that the results from different rheological tests are directly comparable. This can be used in the future, for example, to reduce the number of measurements in planned experiments. Apparently, under these experimental conditions, the cells possess a limited number of degrees of freedom as their rheological properties change.
Olfaction-Related Gene Expression in the Antennae of Female Mosquitoes From Common Aedes aegypti Laboratory Strains
Authors: Mitra Soumi , Pinch Matthew , Kandel Yashoda , Li Yiyi , Rodriguez Stacy D. , Hansen Immo A.
Published: August 2021

Adult female mosquitoes rely on olfactory cues like carbon dioxide and other small molecules to find vertebrate hosts to acquire blood. The molecular physiology of the mosquito olfactory system is critical for their host preferences. Many laboratory strains of the yellow fever mosquitoAedes aegyptihave been established since the late 19th century. These strains have been used for most molecular studies in this species. Some earlier comparative studies have identified significant physiological differences between different laboratory strains. In this study, we used a Y-tube olfactometer to determine the attraction of females of seven different strains ofAe. aegyptito a human host: UGAL, Rockefeller, Liverpool, Costa Rica, Puerto Rico, and two odorant receptor co-receptor (Orco) mutants Orco2 and Orco16. We performed RNA-seq using antennae of Rockefeller, Liverpool, Costa Rica, and Puerto Rico females. Our results showed that femaleAedes aegyptifrom the Puerto Rico strain had significantly reduced attraction rates toward human hosts compared to all other strains. RNA-seq analyses of the antenna transcriptomes of Rockefeller, Liverpool, Costa Rica, and Puerto Rico strains revealed distinct differences in gene expression between the four strains, but conservation in gene expression patterns of known human-sensing genes. However, we identified several olfaction-related genes that significantly vary between strains, including receptors with significantly different expression in mosquitoes from the Puerto Rico strain and the other strains.
The Role of Blood Pressure in Carotid Plaque Incidence: Interactions With Body Mass Index, Age, and Sex-Based on a 7-Years Cohort Study
Authors: Liu Jian , Ma Xuehua , Ren Xue-Ling , Xiao Hong , Yan Leyuan , Li Zhuorong , Wang Shengshu
Published: August 2021

Background: Although high blood pressure (BP) is a risk factor for carotid plaque, its long-term prognostic value might be underestimated due to its confounding interactions with BMI, age, and gender. Therefore, we conducted a 7-year prospective cohort study to evaluate the prognostic value of BP for the incidence of carotid plaque.

Methods: The subjects enrolled in 2011 were free of carotid plaque at baseline and were followed up in 2018. Multivariate Cox proportional-hazards models were used to evaluate the association between BP and carotid plaque incidence.

Results: During the follow-up study, the incidence of carotid plaque was 36.5%. The significant positive linear trend showed that subjects with higher BP levels at baseline were more likely to develop carotid plaques at the end. Especially in the female subpopulation, after confounders being adjusted, the carotid plaque was associated with higher BP (adjusted HR 1.52, 95% CI 1.02–2.26), pulse pressure (PP) (adjusted HR 1.15, 95% CI 0.76–1.75), and mean arterial pressure (MAP) (adjusted HR 1.44, 95% CI 1.00–2.08). The adjusted HRs of hypertension, PP, and MAP (HR 27.71, 95% CI 2.27–338.64; HR 14.47, 95% CI 1.53–137.18; HR 9.97, 95% CI 1.29–77.28) were significantly higher after the potential antagonistic interactions between BP categorical indicators and age being adjusted, respectively.

Conclusion: High BP indicators might be associated with higher HRs of carotid plaque after adjusting interactions between BP indicators and BMI, age, and gender, which suggests that the incidence of carotid plaque in female adults with high BP indicators might increase significantly with the increase of age.
Biochar, Compost, and Biochar–Compost Blend Applications Modulate Growth, Photosynthesis, Osmolytes, and Antioxidant System of Medicinal Plant Alpinia zerumbet
Authors: Zulfiqar Faisal , Chen Jianjun , Younis Adnan , Abideen Zainul , Naveed Muhammad , Koyro Hans-Werner , Siddique Kadambot H. M.
Published: August 2021

Alpinia zerumbet (Zingiberaceae) is a unique ornamental and medicinal plant primarily used in food ingredients and traditional medicine. While organic amendments such as biochar (BC) and compost (Co) have been demonstrated to improve plant productivity, no studies have examined their effects on the growth, physiology, and secondary metabolites of A. zerumbet. This study evaluated the impact of the amendment of BC, Co, or a biochar and compost mixture (BC+Co) on modifying and improving the growth, photosynthesis, antioxidant status, and secondary metabolism of A. zerumbet grown on sandy loam soil. The morpho-physiological and biochemical investigation revealed variation in the response of A. zerumbet to organic amendments. The amendment of BC and BC+Co significantly increased net photosynthetic rates of plants by more than 28%, chlorophyll a and b contents by 92 and 78%, respectively, and carboxylation efficiency by 50% compared with those grown in the sandy loam soil without amendment. Furthermore, the amendment significantly decreased plant oxidative stress, measured as leaf free proline and glycine betaine. Enzymatic antioxidant activity, total phenols, and flavonoids also varied in their response to the organic amendments. In conclusion, this study shows that BC and/or Co amendments are an efficient and sustainable method for improving the metabolite contents and reducing oxidative stress in A. zerumbet.
Mass Production of Virus-Like Particles Using Chloroplast Genetic Engineering for Highly Immunogenic Oral Vaccine Against Fish Disease
Authors: Nakahira Yoichi , Mizuno Kaori , Yamashita Hirofumi , Tsuchikura Minami , Takeuchi Kaoru , Shiina Takashi , Kawakami Hidemasa
Published: August 2021

Nervous necrosis virus (NNV) is the causative agent of viral nervous necrosis (VNN), which is one of the most serious fish diseases leading to mass mortality in a wide range of fish species worldwide. Although a few injectable inactivated vaccines are commercially available, there is a need for more labor-saving, cost-effective, and fish-friendly immunization methods. The use of transgenic plants expressing pathogen-derived recombinant antigens as edible vaccines is an ideal way to meet these requirements. In this study, chloroplast genetic engineering was successfully utilized to overexpress the red-spotted grouper NNV capsid protein (RGNNV-CP). The RGNNV-CP accumulated at high levels in all young, mature, and old senescent leaves of transplastomic tobacco plants (averaging approximately 3 mg/g leaf fresh weight). The RGNNV-CP efficiently self-assembled into virus-like particles (RGNNV-VLPs) in the chloroplast stroma of the transgenic lines, which could be readily observed by in situ transmission electron microscopy. Furthermore, intraperitoneal injection and oral administration of the crudely purified protein extract containing chloroplast-derived RGNNV-VLPs provided the sevenband grouper fish with sufficient protection against RGNNV challenge, and its immunogenicity was comparable to that of a commercial injectable vaccine. These findings indicate that chloroplast-derived VLP vaccines may play a promising role in the prevention of various diseases, not only in fish but also in other animals, including humans.
The Moderation Effects of Comparative Thinking Between Gratitude and Negative Affect During the COVID-19 Outbreak
Authors: Bernabe-Valero Gloria , Blasco-Magraner José Salvador , Aguilar-Moya Remedios , Moret-Tatay Carmen
Published: August 2021

The aim of this research was to examine the moderation effects of comparative thinking (CT) across the relationship between gratitude and affect during the COVID-19 outbreak. To this purpose, multiple regression as well as moderation analyses were carried out. Age and sex were also addressed as variables of interest as described in previous literature. A sample of 306 north Americans was recruited by crowdsourcing platform ProA to obtain a representative sample based on age and gender. The participants filled in a questionnaire based on comparative thinking in relation to the emotional experience experienced before and during the COVID-19 outbreak, positive and negative affect schedule for positive and negative affect, as well as Gratitude Questionnaire - Six Items Form scores for gratitude. The main results of the current study related to the COVID-19 outbreak can be listed as follows: (i) no differences between CT groups in the gratitude trait, but differences in positive and negative affect did occur; (ii) regression models that included age, gratitude, and affect variables predicted negative and positive affects but gender did not reach the statistical level; (iii) two moderation models predicted affect from gratitude, with the CT variable moderating this effect; this moderation effect was also statistically significant in predicting negative affect but it was not statistically significant in predicting positive affect. These results might be of interest for training programs in applied levels and theoretical models of gratitude.
fMRI Neurofeedback-Enhanced Cognitive Reappraisal Training in Depression: A Double-Blind Comparison of Left and Right vlPFC Regulation
Authors: Keller Micha , Zweerings Jana , Klasen Martin , Zvyagintsev Mikhail , Iglesias Jorge , Mendoza Quiñones Raul , Mathiak Klaus
Published: August 2021

Affective disorders are associated with maladaptive emotion regulation strategies. In particular, the left more than the right ventrolateral prefrontal cortex (vlPFC) may insufficiently regulate emotion processing, e.g., in the amygdala. A double-blind cross-over study investigated NF-supported cognitive reappraisal training in major depression (n= 42) and age- and gender-matched controls (n= 39). In a randomized order, participants trained to upregulate either the left or the right vlPFC during cognitive reappraisal of negative images on two separate days. We wanted to confirm regional specific NF effects with improved learning for left compared to right vlPFC (ClinicalTrials.govNCT03183947). Brain responses and connectivity were studied with respect to training progress, gender, and clinical outcomes in a 4-week follow-up. Increase of vlPFC activity was stronger after NF training from the left- than the right-hemispheric ROI. This regional-specific NF effect during cognitive reappraisal was present across patients with depression and controls and supports a central role of the left vlPFC for cognitive reappraisal. Further, the activity in the left target region was associated with increased use of cognitive reappraisal strategies (r= 0.48). In the 4-week follow-up, 75% of patients with depression reported a successful application of learned strategies in everyday life and 55% a clinically meaningful symptom improvement suggesting clinical usability.
Antecedents and Consequences of Smoking Cessation Intention in the Context of the Global COVID-19 Infodemic
Authors: Feng Guangchao Charles , Zhu Shan , Zhao Xinshu
Published: August 2021

A growing body of scientific studies has been published to inform responses to the ongoing coronavirus pandemic, and some have claimed that cigarette smoking has a beneficial or mixed effect on the prevention and treatment of COVID-19. The presentation of such findings, unfortunately, has created an infodemic. This study integrated the theory of planned behavior and the health belief model and incorporated findings on addiction from the medical literature to predict cessation intention and support for tobacco control measures in the context of the COVID-19 infodemic. The study found that cessation intention partially mediated the effect of perceived severity and fully mediated the effects of perceived benefits, self-efficacy, and addiction on support for control measures. In addition, a positively-valenced message of the effect of smoking on the prevention and treatment of COVID-19 vs. a mixedly-valenced message was significant in predicting cessation intention, and the positively-valenced message of smoking indirectly predicted support for tobacco control measures. Perceived susceptibility, barriers, and subjective norms, however, exerted neither direct nor indirect effects on the two outcome variables.
Improved Understanding of Industrial Process Relationships Through Conditional Path Modelling With Process PLS
Authors: Offermans Tim , Hendriks Lynn , van Kollenburg Geert H. , Szymańska Ewa , Buydens Lutgarde M. C. , Jansen Jeroen J.
Published: August 2021

Understanding how different units of an industrial production plant are operationally related is key to improving production quality and sustainability. Data science has proven indispensable in obtaining such understanding from vast amounts of historical process data. Path modelling is a valuable statistical tool to obtain such information from historical production data. Investigating how relationships within a process are affected by multiple production conditions and their interactions can however provide an even deeper understanding of the plant’s daily operation. We therefore propose conditional path modelling as an approach to obtain such improved understanding, demonstrated for a milk protein powder production plant. For this plant we studied how the relationships between different production units and steps are dependent on factors like production line, different seasons and product quality range. We show how the interaction of such factors can be quantified and interpreted in context of daily plant operation. This analysis revealed an augmented insight into the process that can be readily placed in the context of the plant’s structure and behavior. Such insights can be vital to identify and improve upon shortcomings in current plant-wide monitoring and control routines.
Reducing Urban Flood Risk Through Building- and Lot-Scale Flood Mitigation Approaches: Challenges and Opportunities
Authors: Sandink Dan , Binns Andrew D.
Published: August 2021

Urban flooding events are a significant driver of disaster loss, resulting in insured and uninsured losses, property damage, and negative impacts on residents and communities in Canada and internationally. The risk of flooding in urban environments is affected by watershed characteristics, environmental conditions, and the presence and condition of flood management and mitigation technologies. Several building- and lot-scale (or private-side) flood mitigation options are available to better protect properties from the risk of flooding, including backwater valves and foundation drainage systems to reduce the risks of sewer surcharge and infiltration flooding into basements, respectively. The overall success of private-side approaches to reduce the risk of flooding into buildings is reliant upon consistent installation procedures, building code interpretation and enforcement, public engagement, and maintenance. Current research into private-side approaches is presenting many opportunities and solutions for improved flood protection against water-related disasters at home. A greater understanding of the performance of private-side technologies under complex site-specific conditions can help to appoint flood prevention strategies better suited to individual home characteristics. This review paper explores the inter-related factors that affect the risk of basement flooding and explores the challenges and opportunities associated with the adoption and success of private-side flood mitigation approaches. Developing a greater understanding of basement flood vulnerability at the lot-scale will assist in identifying and prioritizing private-side strategies for homeowners to adopt and reduce the risk of flooding based on site-specific conditions affecting flood vulnerability. Continued efforts to evaluate and identify flood risk factors and the performance of private-side strategies are needed to better manage urban flooding events.
Positive Relationship Between Precompetitive Sympathetic Predominance and Competitive Performance in Elite Extreme Sports Athletes
Authors: Matsumura Seiji , Watanabe Ken , Saijo Naoki , Ooishi Yuuki , Kimura Toshitaka , Kashino Makio
Published: August 2021

Elite athletes achieve superior performance under high pressure in competitive situations. Although it is known that such situations affect the precompetitive activity of their autonomic nervous system (ANS), the relationship between precompetitive ANS activity and performance remains controversial. Especially in extreme sports, it has been shown that cardiac sympathetic tone occurs in athletes before competition attempts. However, the relationship between precompetitive sympathetic tone and performance is unclear. To investigate this relationship in extreme sports, we organized a freestyle snowboard jumping competition and examined competitors' physiological states and performance during this event. The electrocardiograms (ECGs) of 20 elite snowboarders were measured 10 min before each jump in different competitive situations: practice, qualifying, and final sessions. The mean heart rate (HR), the low-frequency to high-frequency component ratio (LF/HF ratio), the logarithm of the HF (lnHF) component of the frequency-domain of the heart rate variability (HRV), the ratio of the standard deviation of all R–R intervals to the root mean square of successive differences of R–R intervals (SDNN/rMSSD ratio), and the rMSSD of the time-domain of the HRV were calculated from the ECG data. The results showed a significant increase in the mean HR as well as significant decreases in the lnHF component and rMSSD of the HRV as the sessions progressed. Interestingly, the mean HR, LF/HF ratio and SDNN/rMSSD ratio of the HRV showed significant positive correlations with competitive scores, and the lnHF component and rMSSD of the HRV showed significant negative correlations with the scores. Our results indicate that precompetitive ANS activity becomes predominantly sympathetic in elite extreme athletes, such as freestyle snowboarders, when the competition intensifies, and that this sympathetic predominance is positively related to competitive performance.