bluuebunny/crossref_metadata_2025 huggingface dataset:
CA9-Related Acidic Microenvironment Mediates CD8+ T Cell Related Immunosuppression in Pancreatic Cancer
Authors: Yin Lingdi , Lu Yichao , Cao Cheng , Lu Zipeng , Wei Jishu , Zhu Xiaole , Chen Jianmin , Guo Feng , Tu Min , Xi Chunhua , Zhang Kai , Wu Junli , Gao Wentao , Jiang Kuirong , Miao Yi , Li Qiang , Peng Yunpeng
Published: January 2022

Purpose

This study aims to integrate pancreatic cancer TCGA, GEO, and single-cell RNA-sequencing (scRNA-seq) datasets, and explore the potential prognostic markers and underlying mechanisms of the immune microenvironment of pancreatic cancer through bioinformatics methods, in vitro and in vivo assays.

Methods

Expression data and clinicopathological data of pancreatic cancer TCGA, GEO (GSE131050), single cell sequencing (PAAD_CRA001160) dataset were downloaded. We used R/Bioconductor edgeR for differential expression analysis. ClusterProfiler was utilized to perform GO enrichment analysis on differentially expressed genes. The online software CIBERSORT was used to reanalyze the mRNA expression data of pancreatic cancer. CellRanger, RunPCA, FindNeighbors, FindClusters, RunTSNE and RunUMAP were used to perform preprocessing, cell clustering and expression profile analysis on single-cell sequencing data sets. We analyzed intracellular pH with or without CA9 inhibitor SLC-0111. Indirect co-culture model of human pancreatic cancer cell lines and healthy individual-derived PBMCs were used to determine the effect of CA9-related Acidic Microenvironment on CD8+ T cells.

Results

The CIBERSORT analysis of TCGA pancreatic cancer transcriptome sequencing data showed that among the 22 immune microenvironment components, CD8+ T cell infiltration was significantly correlated with the prognosis of pancreatic cancer patients. The differential expression analysis of the TCGA data grouped by the level of CD8+ T cell infiltration indicates that the expression of carbonic anhydrase 9 (CA9) is the most significant, and the survival analysis suggests that CA9 is associated with the overall survival of pancreatic cancer. TCGA data and GEO data set GSE131050 expression correlation analysis suggests that CA9 and CD8 expression are closely related. Pancreatic cancer single-cell sequencing data set PAAD_CRA001160 analysis results show that CA9 is mainly expressed in pancreatic cancer cell clusters, and the expression of the cancer cell subgroup CA9 in the single-cell data set is correlated with CD8+ T cell infiltration.

Conclusion

Pancreatic cancer cells may inhibit the infiltration of CD8+ T cells through CA9. Further exploration of its related mechanisms can be used to explore the immune escape pathway of pancreatic cancer and provides new perspectives immune targeted therapy.
Treatment Stratification in First-Line Recurrent or Metastatic Head and Neck Cancer, on Behalf of the EORTC Young Investigator Head and Neck Cancer Group
Authors: Klinghammer Konrad , Lorini Luigi , Nevens Daan , Simon Christian , Machiels Jean-Pascal , Bossi Paolo
Published: January 2022

Multiple factors differentially influence treatment decisions in the first line treatment of recurrent/metastatic HNSCC. The EORTC Young investigator group launched a survey among treating physicians to explore the main influencing factors for treatment stratification. The questionnaire was posted as a web-survey link from May to August 2020. Next to defining the factors that mostly influence therapeutic decision the survey was complemented by a clinical case discussion of five patient cases. A total of 118 responses from 19 countries were collected. The key factors identified to guide treatment decision were performance status, PD-L1 Expression, time from last systemic treatment above or below 6 months, and disease burden.

Prospective evaluation of patient characteristics and additional potential predictive biomarkers for novel treatment options remains an important question to stratify personalized treatment for RM HNSCC.
Cancer Genomic Alterations Can Be Potential Biomarkers Predicting Microvascular Invasion and Early Recurrence of Hepatocellular Carcinoma
Authors: Xin Zhaodan , Li Jin , Zhang Haili , Zhou Yi , Song Jiajia , Chen Piaopiao , Bai Ling , Chen Hao , Zhou Juan , Chen Jie , Ying Binwu
Published: January 2022

Background

High recurrence incidence and poor survival after hepatectomy are enormous threats to hepatocellular carcinoma (HCC) patients, which can be caused by microvascular invasion (MVI). However, it is difficult to predict preoperative MVI status. In this study, we focus on cancer genomic alterations to comprehensively explore potential MVI and early recurrence biomarkers and provide clues to the mechanisms of HCC invasion and metastasis.

Methods

Forty-one patients with initially suspected HCC who were undergoing hepatectomy were finally enrolled. High-throughput targeted sequencing was performed on genomic alterations in their preoperative plasma and surgical fresh tumor tissues utilizing the 1,021-gene panel.

Results

HCC patients without MVI had longer RFS than MVI ones (p < 0.0001). The mutant incidence of genes like KEAP1, TP53, HIST1H3D, NFKBIA, PIK3CB, and WRN was higher in both MVI and early-recurrence patients than their counterparts. Besides, the alteration rates of Rap1 and Ras signaling pathways were significantly higher in MVI patients than NMVI ones (p < 0.05), and a similar trend of differences was also found in early-recurrence/non-recurrence comparison. The maximal variant allele frequency (VAF) of circulating tumor DNA (ctDNA) was statistically higher in MVI patients than NMVI ones (0.038 vs. 0.012, p = 0.0048). With the cutoff value of 0.018, ctDNA maximal VAF could potentially predict the presence of MVI with an AUC of 0.85 (95% CI 0.693–0.998, p = 0.0062).

Conclusion

The integration of a panel containing specific mutated genes and ctDNA maximal VAF for predicting MVI and early recurrence of HCC may achieve better performance.
A Ferroptosis-Related Genes Model Allows for Prognosis and Treatment Stratification of Clear Cell Renal Cell Carcinoma: A Bioinformatics Analysis and Experimental Verification
Authors: Wu Jiyue , Sun Zejia , Bi Qing , Wang Wei
Published: January 2022

Introduction

Clear cell renal cell carcinoma (ccRCC) is a malignant tumor characterized by poor prognosis and difficult treatment. Ferroptosis is a relatively new form of programmed cell death that involved in cancer development and therapy resistance. Studies have shown that targeted ferroptosis may be a novel option for the treatment of ccRCC, but key genes and their roles between ferroptosis and ccRCC are limited so far. This study aims to develop a ccRCC stratified model based on ferroptosis-related genes to provide a reference for the prognosis prediction and the individualized treatment of ccRCC.

Materials and Methods

The mRNAs expression data of ccRCC and FRGs were obtained from TCGA and FerrDb database, respectively. Through multiple analysis, a 4-FRG based prognostic stratified model was constructed and its predictive performance was validated through various methods. Then, a nomogram based on the model was constructed and ccRCC patients stratified by the model were analyzed for tumor microenvironment, immune infiltration, sensitivity for immune checkpoint inhibitors (ICIs)/traditional anti-tumor therapy and tumor mutation burden (TMB). Functional enrichment analysis was performed to explore potential biological pathways. Finally, we verified our model by RT-qPCR, siRNA transfection, scratch assay and CCK-8 assay.

Results

In this study, the stratified model and a model-based nomogram can accurately predict the prognosis of ccRCC patients in TCGA database. The patients stratified by the model showed different tumor microenvironments, immune infiltration, TMB, resistance to traditional and ICIs therapy, and sensitivity to ferroptosis. Functional enrichment analysis suggested several biological pathways related to the process and prognosis of ccRCC. RT-qPCR confirmed the differential expression of ferroptosis-related genes. Scratch assay and CCK-8 assay indicated the promotion effects of CD44 on the proliferation and migration of ccRCC.

Conclusion

In this study, we established a novel ccRCC stratified model based on FRGs, which can accurately predict the prognosis of ccRCC patients and provide a reference for clinical individualized treatment.
Thymic Polypeptide Fraction Biomodulina T Decreases Exhausted and Terminally Differentiated EMRA T Cells in Advanced Lung Cancer Patients Treated With Platinum-Based Chemotherapy
Authors: Suárez Gisela María , Catalá Mauricio , Peña Yadira , Portela Susana , Añé-Kourí Ana Laura , González Amnely , Lorenzo-Luaces Patricia , Díaz Manuel , Molina María de los A. , Pereira Karla , Hernández Jenysbel de la C. , Ramos Raúl , Reyes Mary Carmen , Ledón Nuris , Mazorra Zaima , Crombet Tania , Lage Agustin , Saavedra Danay
Published: January 2022

Lung cancer is the second cause of cancer related deaths worldwide. Chemotherapy and immunotherapy represent the current standard of care for advanced NSCLC. Platinum-based chemotherapy expands late-differentiated T cell populations. Therefore, immune restoration after chemotherapy to adjuvate the immunotherapeutic potential could be crucial. The aim of this study was to evaluate the effect of Biomodulina T (BT), a thymic polypeptide fraction, on peripheral lymphocytes subpopulations in the context of cancer disease. Additionally, whether these effects might induce a better response to CIMAvax-EGF, an epidermal growth factor (EGF) depleting immunotherapy. Eighteen advanced NSCLC patients were evaluated after being treated with platinum-based chemotherapy. We found that the frequency of terminally differentiated effector T cells re-expressing CD45RA (EMRA) CD4+ (p=0.0031) and CD8+ (p=0.0372) T cells decreased with the administration of BT, whereas CD4+ naive T cells increase in more than 70% of the patients. Remarkably, CD4+ and CD8+ T lymphocytes expressing programmed cell death receptor-1 (PD1) significantly decreased after BT administration (p=0.0005 and p<0.0001, respectively). We also found an enhancement of the anti-EGF antibody response with a large percentage of patients treated with CIMAvax-EGF reaching the good antibody response condition after four vaccine doses. Moreover, the median overall survival of patients treated with CIMAvax-EGF was 16.09 months. In conclusion, our results suggest that the immunorestoration generated by the administration of BT after first-line chemotherapy may induce a better immune response to CIMAvax-EGF that could translate into the clinical benefit of patients diagnosed with advanced NSCLC.
Patterns, Outcomes and Predictors of Pediatric Medical Admissions at Gadarif Hospital in Eastern Sudan
Authors: Ahmed Mohammed Ahmed A. , Musa Imad R. , Mahgoub Hyder M. , Al-Nafeesah Abdullah , Al-Wutayd Osama , Adam Ishag
Published: January 2022

Background

The reduction of childhood mortality is a reliable indicator of a national health system's progress and improvement. Sudan's population is still suffering from communicable diseases, with a considerably higher mortality rate among children. Efforts are therefore needed to reduce mortality and achieve the Millennium Development Goals and Sustainable Development Goals. This study was conducted to determine the morbidity, mortality and outcomes of children admitted to Gadarif Hospital in eastern Sudan.

Method

A retrospective study was conducted by reviewing the medical files of pediatric patients who were admitted to Gadarif Hospital between March 1, 2019 and March 31, 2020.

Result

A total of 740 medical files were reviewed. Most, 453 (61.2%) of the admissions were males. The median (interquartile range) age was 3.0 (8.0) years and 433 (58.8%) of the admissions were under 5 years of age. The median (interquartile range) of the length of hospital stay was 9.0 (12.0) days. Visceral leishmaniasis, malnutrition, severe malaria, sickle cell disease, acute watery diarrhea, severe anemia (regardless of its cause), septicemia and acute respiratory infection were the most common causes of admission. The mortality rate was 5.7%, and it was significantly higher in females than males [24/287 (8.4%) vs. 18/453 (4.0%),P= 0.01] and in children under 5 years [36/433 (8.3%) vs. 6/307 (2.0%),P< 0.001]. Malnutrition, visceral leishmaniasis, septicemia and meningitis/encephalitis were the main diseases causing death in the study population. The case fatality rate was not significantly different in malnutrition than in visceral leishmaniasis [9/93 (9.7%) vs. 7/178 (3.9%),P= 0.05].

Conclusion

The main causes of morbidity and mortality for children admitted to Gadarif Pediatric Hospital were communicable diseases. The mortality rate was 5.7%. Females and children under 5 years were the most vulnerable groups for fatality.
Evaluating the Potential Use of Serotonergic Psychedelics in Autism Spectrum Disorder
Authors: Markopoulos Athanasios , Inserra Antonio , De Gregorio Danilo , Gobbi Gabriella
Published: January 2022

Recent clinical and preclinical evidence points towards empathogenic and prosocial effects elicited by psychedelic compounds, notably the serotonin 5-HT2A agonists lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), and their derivatives. These findings suggest a therapeutic potential of psychedelic compounds for some of the behavioural traits associated with autism spectrum disorder (ASD), a neurodevelopmental condition characterized by atypical social behaviour. In this review, we highlight evidence suggesting that psychedelics may potentially ameliorate some of the behavioural atypicalities of ASD, including reduced social behaviour and highly co-occurring anxiety and depression. Next, we discuss dysregulated neurobiological systems in ASD and how they may underlie or potentially limit the therapeutic effects of psychedelics. These phenomena include: 1) synaptic function, 2) serotonergic signaling, 3) prefrontal cortex activity, and 4) thalamocortical signaling. Lastly, we discuss clinical studies from the 1960s and 70s that assessed the use of psychedelics in the treatment of children with ASD. We highlight the positive behavioural outcomes of these studies, including enhanced mood and social behaviour, as well as the adverse effects of these trials, including increases in aggressive behaviour and dissociative and psychotic states. Despite preliminary evidence, further studies are needed to determine whether the benefits of psychedelic treatment in ASD outweigh the risks associated with the use of these compounds in this population, and if the 5-HT2A receptor may represent a target for social-behavioural disorders.
Magnesium-Assisted Cisplatin Inhibits Bladder Cancer Cell Survival by Modulating Wnt/β-Catenin Signaling Pathway
Authors: Li Tianye , Tang Zihan , Li Chunting , Liu Xiaoya , Cheng Linglin , Yang Zhijing , Zhu Xiaojin , Liu Weiwei , Huang Yongye
Published: January 2022

Magnesium, an essential mineral micronutrient, plays a role in the activation of various transporters and enzymes. The present study aimed to investigate the possibility of applying magnesium to enhance the efficacy of cisplatin which is still ranked as one of the major chemotherapeutic drugs for bladder cancer patients. Results showed that the survival rate and colony formation of bladder cancer cells were reduced by combinatorial treatment with cisplatin and magnesium chloride (MgCl2). The proportion of apoptotic cells was also increased in UC3 bladder cancer cells treated with a combination of cisplatin and MgCl2. Most importantly, a marked decrease in nuclear β-catenin was observed in cells that received cisplatin treatment. In addition, the nuclear β-catenin in cisplatin treated cells was further down-regulated by supplementing MgCl2. 6-bromoindirubin-3′-oxime (BIO), an inhibitor of glycogen synthase kinase-3 (GSK-3) that activates the Wnt/β-catenin signaling pathway by modulating β-catenin activity, was thus applied to further exploit the role of this signaling pathway in magnesium aided cancer treatment. The survival rate of bladder cancer cells was decreased by BIO treatment at concentrations of 1.0, 2.5 and 5.0 μM accompanied by increased β-catenin expression. However, the expression of β-catenin in MgCl2-treated cells was lower than in untreated cells under the same BIO concentration. The expression of cleaved caspase-3, cleaved caspase-9 and microtubule-associated protein 1 light chain 3- II (LC3-II) was highest in cells treated with MgCl2 and 5.0 μM BIO among the examined groups. Our findings reveal that magnesium could contribute to cisplatin-based chemotherapy by moderately regulating the Wnt/β-catenin signaling pathway.
Novel Compounds Synergize With Venetoclax to Target KMT2A-Rearranged Pediatric Acute Myeloid Leukemia
Authors: Tregnago Claudia , Benetton Maddalena , Da Ros Ambra , Borella Giulia , Longo Giorgia , Polato Katia , Francescato Samuela , Biffi Alessandra , Pigazzi Martina
Published: January 2022

In pediatric acute myeloid leukemia (AML), fusions involving lysine methyltransferase 2A (KMT2A) are considered hallmarks of aggressive AML, for whom the development of targeted specific therapeutic agents to ameliorate classic chemotherapy and obtain a complete eradication of disease is urgent. In this study, we investigated the antiapoptotic proteins in a cohort of 66 pediatric AML patients, finding that 75% of the KMT2A-r are distributed in Q3 + Q4 quartiles of BCL-2 expression, and KMT2A-r have statistically significant high levels of BCL-2, phospho-BCL-2 S70, and MCL-1, indicating a high anti-apoptotic pathway activation. In an attempt to target it, we tested novel drug combinations of venetoclax, a B-cell lymphoma-2 (BCL-2) inhibitor, in KMT2A-MLLT3, for being the most recurrent, and KMT2A-AFDN, for mediating the worst prognosis, rearranged AML cell lines. Our screening revealed that both the bromodomain and extra-terminal domain (BET) inhibitor, I-BET151, and kinase inhibitor, sunitinib, decreased the BCL-2 family protein expression and significantly synergized with venetoclax, enhancing KMT2A-r AML cell line death. Blasts t (6; 11) KMT2A-AFDN rearranged, both from cell lines and primary samples, were shown to be significantly highly responsive to the combination of venetoclax and thioridazine, with the synergy being induced by a dramatic increase of mitochondrial depolarization that triggered blast apoptosis. Finally, the efficacy of novel combined drug treatments was confirmed in KMT2A-r AML cell lines or ex vivo primary KMT2A-r AML samples cultured in a three-dimensional system which mimics the bone marrow niche. Overall, this study identified that, by high-throughput screening, the most KMT2A-selective drugs converged in different but all mitochondrial apoptotic network activation, supporting the use of venetoclax in this AML setting. The novel drug combinations here unveiled provide a rationale for evaluating these combinations in preclinical studies to accelerate the introduction of targeted therapies for the life-threatening KMT2A-AML subgroup of pediatric AML.
Leptin: A Potential Link Between Obstructive Sleep Apnea and Obesity
Authors: Ciriello John , Moreau Jason M. , Caverson Monica M. , Moranis Rebecca
Published: January 2022

Chronic intermittent hypoxia (CIH), a pathophysiological manifestation of obstructive sleep apnea (OSA), is strongly correlated with obesity, as patients with the disease experience weight gain while exhibiting elevated plasma levels of leptin. This study was done to determine whether a relationship may exist between CIH and obesity, and body energy balance and leptin signaling during CIH. Sprague-Dawley rats were exposed to 96 days of CIH or normoxic control conditions, and were assessed for measures of body weight, food and water intake, and food conversion efficiency. At the completion of the study leptin sensitivity, locomotor activity, fat pad mass and plasma leptin levels were determined within each group. Additionally, the hypothalamic arcuate nucleus (ARC) was isolated and assessed for changes in the expression of proteins associated with leptin receptor signaling. CIH animals were found to have reduced locomotor activity and food conversion efficiency. Additionally, the CIH group had increased food and water intake over the study period and had a higher body weight compared to normoxic controls at the end of the study. Basal plasma concentrations of leptin were significantly elevated in CIH exposed animals. To test whether a resistance to leptin may have occurred in the CIH animals due to the elevated plasma levels of leptin, an acute exogenous (ip) leptin (0.04 mg/kg carrier-free recombinant rat leptin) injection was administered to the normoxic and CIH exposed animals. Leptin injections into the normoxic controls reduced their food intake, whereas CIH animals did not alter their food intake compared to vehicle injected CIH animals. Within ARC, CIH animals had reduced protein expression of the short form of the obese (leptin) receptor (isoform OBR100) and showed a trend toward an elevated protein expression of the long form of obese (leptin) receptor (OBRb). In addition, pro-opiomelanocortin (POMC) protein expression was reduced, but increased expression of the phosphorylated extracellular-signal-regulated kinase 1/2 (pERK1/2) and of the suppressor of cytokine signaling 3 (SOCS3) proteins was observed in the CIH group, with little change in phosphorylated signal transducer and activator of transcription 3 (pSTAT3). Taken together, these data suggest that long-term exposure to CIH, as seen in obstructive sleep apnea, may contribute to a state of leptin resistance promoting an increase in body weight.
Assessing Stress Resilience After Smolt Transportation by Waterborne Cortisol and Feeding Behavior in a Commercial Atlantic Salmon (Salmo salar) Grow-Out Recirculating Aquaculture System
Authors: Höglund Erik , Fernandes Paulo , Rojas-Tirado Paula , Rundberget Jan Thomas , Hess-Erga Ole-Kristian
Published: January 2022

Sampling protocols and water quality sensors have been developed to assess fish health and welfare in recirculating aquaculture systems (RASs). Still, the use of fish-based non-invasive welfare indicators, reflecting the physiological state of the fish, is limited in this type of system. Cortisol, the major stress-coping hormone in fish, diffuses through the gills. Consequently, waterborne cortisol is a potential fish-based non-invasive welfare indicator in RAS. However, its use in commercial rearing systems is sparse. In this study, we evaluated water cortisol levels and feeding behavior as welfare indicators of newly inserted smolt in a commercial RAS for harvest size Atlantic salmon. The RAS consisted of two parallel fish rearing raceways, raceways 1 and 2, sharing the same water treatment with common outlets and inlets. The smolts were inserted in raceway 1 while salmon that have been in the system for 6 months or more were kept in raceway 2. The smolt insertion period was 3 days. Samples for water cortisol levels were withdrawn the day before, 1 and 3 days after the smolt insertion period. Smolt insertion resulted in elevated water cortisol concentrations in the entire system, with the highest values in raceway 1, one day after smolt insertion. Estimated cortisol production in newly inserted smolt decreased over time, was similar to what has been reported in salmon adapting to experimental tanks. Feeding behavior indicated that the appetite was not fully resumed in the newly inserted smolts, while the appetite of fish in raceway 2 was unaffected by smolt insertion. These results, obtained in a highly intensive commercial RAS, suggest that waterborne cortisol together with feeding behavior can be used as indicators for adaptive processes associated with stress resilience in farmed fish. Thus, they are promising non-invasive indicators for assessing the impact of potential stressors on fish welfare in this type of rearing system.
Role of Granulosa Cells in the Aging Ovarian Landscape: A Focus on Mitochondrial and Metabolic Function
Authors: Alberico Hannah C. , Woods Dori C.
Published: January 2022

Mitochondria are at the intersection of aging and fertility, with research efforts centered largely on the role that these specialized organelles play in the relatively rapid decline in oocyte quality that occurs as females approach reproductive senescence. In addition to various roles in oocyte maturation, fertilization, and embryogenesis, mitochondria are critical to granulosa cell function. Herein, we provide a review of the literature pertaining to the role of mitochondria in granulosa cell function, with emphasis on how mitochondrial aging in granulosa cells may impact reproduction in female mammals.
Multiscale Modeling of Vascular Remodeling Induced by Wall Shear Stress
Authors: Chen Shiliang , Zhang Hanbing , Hou Qianwen , Zhang Yu , Qiao Aike
Published: January 2022

Objective

Hemodynamics-induced low wall shear stress (WSS) is one of the critical reasons leading to vascular remodeling. However, the coupling effects of WSS and cellular kinetics have not been clearly modeled. The aim of this study was to establish a multiscale modeling approach to reveal the vascular remodeling behavior under the interaction between the macroscale of WSS loading and the microscale of cell evolution.

Methods

Computational fluid dynamics (CFD) method and agent-based model (ABM), which have significantly different characteristics in temporal and spatial scales, were adopted to establish the multiscale model. The CFD method is for the second/organ scale, and the ABM is for the month/cell scale. The CFD method was used to simulate blood flow in a vessel and obtain the WSS in a vessel cross-section. The simulations of the smooth muscle cell (SMC) proliferation/apoptosis and extracellular matrix (ECM) generation/degradation in a vessel cross-section were performed by using ABM. During the simulation of the vascular remodeling procedure, the damage index of the SMC and ECM was defined as deviation from the obtained WSS. The damage index decreased gradually to mimic the recovery of WSS-induced vessel damage.

Results

(1) The significant wall thickening region was consistent with the low WSS region. (2) There was no evident change of wall thickness in the normal WSS region. (3) When the damage index approached to 0, the amount and distribution of SMCs and ECM achieved a stable state, and the vessel reached vascular homeostasis.

Conclusion

The established multiscale model can be used to simulate the vascular remodeling behavior over time under various WSS conditions.
Physical Activity and Cancer Status Among Middle-Aged and Older Chinese: A Population-Based, Cross-Sectional Study
Authors: Zhu Chunsu , Lian Zhiwei , Chen Ying , Wang Jianmin
Published: January 2022

Background

The relative contributions of demographic and lifestyle behaviors to the association between physical activity (PA) and cancer are poorly understood. This study assesses the relationship between PA level and cancer status considering the full activity spectrum within a large and representative Chinese population.

Methods

Data were derived from the Chinese Health and Retirement Longitudinal Study (using four-stage stratified probability-proportional-to-size sampling), including 416 cancer survivors and 14,574 individuals without cancer from 28 provinces in China. Cancer status and sites were self-reported, and PA, other health behaviors (e.g., smoking, drinking) and comorbidities (e.g., hypertension, diabetes) were assessed by a questionnaire. The total PA score was calculated using metabolic equivalent (MET) multipliers. Multivariable logistic regression was used to estimate differences in PA levels between cancer survivors and those without a cancer diagnosis, adjusting for age, sex, and other potential confounding factors.

Results

Cancer survivors (416, 2.8%) were more likely to be women than men (65.4 vs. 34.6%). They were older (age ≥65 years, 43.8 vs. 38.9%) and more likely to be overweight (18.3 vs. 13.3%), be depressed (49.5 vs. 37.6%), have quit smoking (17.8 vs. 14.4%), drink less (17.5 vs. 26.6%), sleep less (65.9 vs. 56.8%) and have more chronic comorbidities (≥2 comorbidities, 26.0 vs. 19.2%) than those without cancer. There was a significant associations between cancer status and participation in vigorous-intensity activity for at least 10 min every week, when compared with the inactivity [odds ratio (OR) = 0.56, 95% CI = 0.39–0.80], while no differences were observed in the moderate and light activity groups. Individuals who spent more than half an hour performing moderate or vigorous intensity activity every day were significantly less likely to report a cancer diagnosis than inactive individuals (moderate OR = 0.64, 95% CI = 0.48–0.86; vigorous OR = 0.50, 95% CI = 0.37–0.68). Participants who spent more than 2 h performing light, moderate or vigorous intensity activity reported fewer cancer cases than their inactive counterparts. In addition, there was an inverse dose-response relationship between the total PA score and cancer status (P–trend < 0.001).

Conclusion

Associations between PA and cancer status were independent of demographics, lifestyle confounders, and comorbidities. Cancer survivors are less physically active than those without cancer.
Effect of Mg-Gluconate on the Osmotic Fragility of Red Blood Cells, Lipid Peroxidation, and Ca2+-ATPase (PMCA) Activity of Placental Homogenates and Red Blood Cell Ghosts From Salt-Loaded Pregnant Rats
Authors: Rojas Deliana , Abad Cilia , Piñero Sandy , Medina Yollyseth , Chiarello Delia I. , Proverbio Fulgencio , Marín Reinaldo
Published: January 2022

Preeclampsia (PE) is a pregnancy-specific syndrome with multisystem involvement which leads to fetal, neonatal, and maternal morbidity and mortality. A model of salt-loaded pregnant rats has been previously studied, sharing several pathological characteristics of preeclamptic women. In this study, it was compared the effects of the treatment with an oral magnesium salt, magnesium gluconate (Mg-gluconate), on the osmotic fragility of red blood cells, lipid peroxidation, and PMCA activity of placental homogenates and red blood cell ghosts in salt-loaded pregnant rats. Mg-gluconate has a higher antioxidant capacity than MgSO4 due to the presence of several hydroxyl groups in the two anions of this salt. Salt-loaded pregnant rats received 1.8% NaCl solution ad libitum as a beverage during the last week of pregnancy. On day 22nd of pregnancy, the rats were euthanized and red blood cells and placenta were obtained. Salt-loaded pregnant rats showed an increased level of lipid peroxidation and a lowered PMCA activity in placental and red blood cell ghosts, as well as an increased osmotic fragility of their red blood cells. The treatment of the salt-loaded pregnant rats with Mg-gluconate avoids the rise in the level of lipid peroxidation and the concomitant lowering of the PMCA activity of their red blood cell membranes, reaching values similar to those from control pregnant rats. Also, this treatment prevents the increase of the osmotic fragility of their red blood cells, keeping values similar to those from control pregnant rats. Mg-gluconate seems to be an important candidate for the replacement of the MgSO4 treatment of preeclamptic women.
Diacylglycerol Kinase ε in Adipose Tissues: A Crosstalk Between Signal Transduction and Energy Metabolism
Authors: Nakano Tomoyuki , Goto Kaoru
Published: January 2022

Diacylglycerol (DG) is unique in lipid metabolism because it serves not only as an intermediate product for triglyceride synthesis, but also as a signaling molecule that activates proteins containing DG-responsive elements, such as protein kinase C. Consequently, DG acts as a hub between energy metabolism and intracellular signaling. Of DG metabolizing pathways, DG kinase (DGK) phosphorylates DG to produce phosphatidic acid, which also serves as a second messenger. Several lines of evidence suggest that DGK is deeply involved in metabolic diseases such as obesity and insulin resistance. Of DGK isozymes, DGKε is simplest in terms of structure, but it is characterized by substrate specificity toward arachidonoyl-DG. Recently, we have reported that DGKε deficiency promotes adipose tissue remodeling in mice during the course of high fat diet (HFD) feeding regimen including obesity, insulin resistance, and beige adipogenesis. DGKε ablation engenders altered expression of other lipid metabolizing enzymes, including adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and diacylglycerol acyltransferase (DGAT). Subcellular localization of DGKε in the endoplasmic reticulum suggests involvement of this isozyme in lipid energy homeostasis. This review presents current findings of DGKε in lipid-orchestrated pathophysiology, especially unique phenotypes of DGKε-knockout mice in the early and late stages of obesogenic conditions.
GIP1 and GIP2 Contribute to the Maintenance of Genome Stability at the Nuclear Periphery
Authors: Singh Gaurav , Batzenschlager Morgane , Tomkova Denisa , Herzog Etienne , Hoffmann Elise , Houlné Guy , Schmit Anne-Catherine , Berr Alexandre , Chabouté Marie-Edith
Published: January 2022

The maintenance of genetic information is important in eukaryotes notably through mechanisms occurring at the nuclear periphery where inner nuclear membrane proteins and nuclear pore-associated components are key factors regulating the DNA damage response (DDR). However, this aspect of DDR regulation is still poorly documented in plants. We addressed here how genomic stability is impaired in the gamma-tubulin complex component 3-interacting protein (gip1gip2) double mutants showing defective nuclear shaping. Using neutral comet assays for DNA double-strand breaks (DSBs) detection, we showed that GIP1 and GIP2 act redundantly to maintain genome stability. At the cellular level, γ-H2AX foci in gip1gip2 were more abundant and heterogeneous in their size compared to wild-type (WT) in root meristematic nuclei, indicative of constitutive DNA damage. This was linked to a constitutive activation of the DDR in the gip1gip2 mutant, with more emphasis on the homologous recombination (HR) repair pathway. In addition, we noticed the presence of numerous RAD51 foci which did not colocalize with γ-H2AX foci. The expression of GIP1-GFP in the double mutant rescued the cellular response to DNA damage, leading to the systematic colocalization of RAD51 and γ-H2AX foci. Interestingly, a significant proportion of RAD51 foci colocalized with GIP1-GFP at the nuclear periphery. Altogether, our data suggest that GIPs may partly contribute to the spatio-temporal recruitment of RAD51 at the nuclear periphery.
AP2/ERF Transcription Factor NbERF-IX-33 Is Involved in the Regulation of Phytoalexin Production for the Resistance of Nicotiana benthamiana to Phytophthora infestans
Authors: Imano Sayaka , Fushimi Mayuka , Camagna Maurizio , Tsuyama-Koike Akiko , Mori Hitoshi , Ashida Akira , Tanaka Aiko , Sato Ikuo , Chiba Sotaro , Kawakita Kazuhito , Ojika Makoto , Takemoto Daigo
Published: January 2022

Plants recognize molecular patterns unique to a certain group of microbes to induce effective resistance mechanisms. Elicitins are secretory proteins produced by plant pathogenic oomycete genera including Phytophthora and Pythium. Treatment of INF1 (an elicitin produced by P. infestans) induces a series of defense responses in Nicotiana species, including reactive oxygen species (ROS) production, transient induction of ethylene production, hypersensitive cell death and accumulation of the sesquiterpenoid phytoalexin capsidiol. In this study, we analyzed the expression profiles of N. benthamiana genes after INF1 treatment by RNAseq analysis. Based on their expression patterns, N. benthamiana genes were categorized into 20 clusters and 4,761 (8.3%) out of 57,140 genes were assigned to the clusters for INF1-induced genes. All genes encoding enzymes dedicated to capsidiol production, 5-epi-aristolochene (EA) synthase (NbEAS, 10 copies) and EA dehydrogenase (NbEAH, 6 copies), and some genes for ethylene production, such as 1-aminocyclopropane 1-carboxylate (ACC) synthase (NbACS) and ACC oxidase (NbACO), were significantly upregulated by INF1 treatment. Analysis of NbEAS1 and NbEAS4 promoters revealed that AGACGCC (GCC box-like motif) is the essential cis-element required for INF1-induced expression of NbEAS genes. Given that the GCC box is known to be targeted by ERF (ethylene-responsive factor) transcription factors, we created a complete list of N. benthamiana genes encoding AP2/ERF family transcription factors, and identified 45 out of 337 AP2/ERF genes in the clusters for INF1-induced genes. Among INF1-induced NbERF genes, silencing of NbERF-IX-33 compromised resistance against P. infestans and INF1-induced production of capsidiol. Recombinant NbERF-IX-33 protein can bind to the promoter sequence of NbEAS4, suggesting that NbERF-IX-33 is a transcription factor directly regulating the expression of genes for phytoalexin production.
Alkaline Salt Inhibits Seed Germination and Seedling Growth of Canola More Than Neutral Salt
Authors: Wang Weichao , Zhang Fenghua , Sun Lupeng , Yang Lei , Yang Yang , Wang Yajuan , Siddique Kadambot H. M. , Pang Jiayin
Published: January 2022

Salinity is a major constraint to crop growth and productivity, limiting sustainable agriculture production. Planting canola (Brassica napus L.) variety with salinity-alkalinity tolerance as a green manure on the large area of salinity-affected land in Xinjiang could alleviate feed shortage. To investigate the differential effects of neutral and alkaline salt stress on seed germination and seedling growth of canola, we used two salts at varying concentrations, i.e., NaCl (neutral salt at 100, 150, and 200 mM) and Na2CO3 (alkaline salt at 20, 30, and 40 mM). To further explore the effects of Na+ and pH on seed germination, we included combined of NaCl (0, 100, 150, and 200 mM) and pH (7.1, 8.0, 9.0, 10.0, and 11.0). Shoot growth was promoted by low concentrations of NaCl and Na2CO3 but inhibited at high salt concentrations. Given the same Na+ concentration, Na2CO3 inhibited seed germination and seedling growth more than NaCl. The results showed that the main factor affecting seed germination and seedling growth is not pH alone, but the interaction between pH and salt ions. Under NaCl stress, canola increased the absorption of K+, Ca2+, and Mg2+ in roots and K+ in leaves. However, under Na2CO3 stress, canola maintained a high K+ concentration and K+/Na+ ratio in leaves and increased Ca2+ and Mg2+ in roots. Our study showed that alkaline salts inhibit canola seed germination and seedling growth more significantly than neutral salts and salt species, salt concentration, and pH significantly affected on seed germination and seedling growth. However, pH affected seed germination and seedling growth mainly through an interaction with salt ions.
Genome-Wide Identification of Maize Aquaporin and Functional Analysis During Seed Germination and Seedling Establishment
Authors: Su Yingchun , Liu Zhonghao , Sun Jiahui , Wu Chenglai , Li Yan , Zhang Chunqing , Zhao Linmao
Published: January 2022

Water uptake facilitates the initiation of seed germination. It is presumed that aquaporin (AQP)-mediated water inflow contributes to seed germination, but the genetic evidence is still lacking. This study aimed at genome-wide identification of ZmAQPs and further determined the physiological functions. Following a comprehensive search, a total of 41 ZmAQPs were identified according to the latest genome database. Through bioinformatic approaches, the physicochemical characteristics, phylogenetic relationships, and structural features of ZmAQPs were analyzed. The gene expression analysis of 20 high-resolution and multi-tissues samples showed that ZmAQPs had distinct spatiotemporal and tissue-specific expression profiles during seed germination and early seedling development. We then focused on the aquaporin of maize tonoplast intrinsic protein 3 (ZmTIP3), which is specifically expressed in germinating seed. A mutant zmtip3-1 with disruption of the ZmTIP3-1 gene showed shorter shoot and root length, and decreased seedling dry weight compared with the control (W22). The result revealed that ZmTIP3-1 improved the absolute content of seed protein and promoted storage reserves mobilization, suggesting that ZmTIP3 may be a positive regulator of seed vigor. This work provides valuable clues for understanding the function and possible regulatory mechanism of ZmAQPs in seed germination and seedling growth.
Heat Shock-Induced Accumulation of the Glycogen Synthase Kinase 3-Like Kinase BRASSINOSTEROID INSENSITIVE 2 Promotes Early Flowering but Reduces Thermotolerance in Arabidopsis
Authors: Ren Huimin , Wu Xuedan , Zhao Weishuang , Wang Yuetian , Sun Daye , Gao Kang , Tang Wenqiang
Published: January 2022

Brassinosteroids (BRs) are essential plant growth- and development-regulating phytohormones. When applied exogenously, BRs ameliorate heat shock (HS)-induced cell damage and enhance plant thermotolerance; however, the molecular mechanism by which BRs regulate plant thermotolerance is unknown. In this study, by analyzing the thermotolerance of a series of BR signaling mutants and plants that overexpressed different BR signaling components, we obtained comprehensive data showing that BRASSINOSTEROID INSENSITIVE 2 (BIN2) plays a major role in mediating the crosstalk between BR signaling and plant HS responses. By RNA-Seq, 608 HS- and BIN2-regulated genes were identified. An analysis of the 1-kb promoter sequences of these genes showed enrichment of an abscisic acid (ABA) INSENSITIVE 5 (ABI5)-binding cis-element. Physiological studies showed that thermotolerance was reduced in bin2-1 mutant and ABI5-OX plants but increased in the abi5 mutant, and that the abi5 mutation could recover the thermotolerance of bin2-1 plants to a wild-type level, suggesting that ABI5 functions downstream of BIN2 in regulating plant thermotolerance. Further, HS treatment increased the cellular abundance of BIN2. Both bin2-1 mutant and BIN2-OX plants showed early flowering, while the BIN2 loss-of-function mutant bin2-3 bil1 bil2 flowered late. Given these findings, we propose that under HS conditions plants increase BIN2 activity to promote early flowering and ensure species survival; however, this reduces the thermotolerance and survivability of individual plants partially by activating ABI5.
Do Different Types of Intelligence and Its Implicit Theories Vary Based on Gender and Grade Level?
Authors: Ayoub Alaa Eldin A. , Aljughaiman Abdullah M. , Alabbasi Ahmed M. Abdulla , Abo Hamza Eid G.
Published: January 2022

The current study investigated correlations among gifted students’ academic performance; emotional, social, analytical, creative, and practical intelligence; and their implicit theories of intelligence. Furthermore, it studied the effect of gender and grade on these variables. The participants included 174 gifted fifth (41.4%) and sixth (58.6%) grade students, comprising 53.4% male and 46.6% female. The following analytical, creative, and practical intelligence tests were administered: Aurora Battery, the emotional intelligence scale, the implicit theories of intelligence scale, and an assessment scale of students’ performances. The results revealed significant correlations among academic performance, kinds of intelligence, and implicit theories of intelligence. There were no significant differences between the male and female students in these measures. There were, however, significant differences between the fifth and sixth grade students, with the sixth-grade students showing higher levels of all kinds of intelligence, except emotional intelligence. Moreover, the results indicated that the intelligence measures were non-significantly affected by either gender or gender–grade interaction. Overall, our results showed that most types of intelligence are related to giftedness, and that there were no gender differences among gifted students on measures of intelligence.
Multicultural Psychological Empowerment Scale for Saudi Women
Authors: Moubarak Hanaa Faize A. , Afthanorhan Asyraf , Alrasheedi Eisa Sneitan N.
Published: January 2022

The current study aimed to construct a multicultural psychological empowerment scale for Saudi women depending on the four dimensions of psychological empowerment, namely, meaningfulness, impact, self-efficacy, and self-determination. It was applied to a sample (N = 1,080) of Saudi women from various age categories, different social, educational, and employment status, and geographical regions. Pooled confirmatory factor analysis was using to determine the reliability and validity of the scale. As a result, the reliability and validity of the entire model were satisfied. Specifically, the composite reliability values fell in the range between 0.804 and 0.883. Meanwhile, the convergent validity was achieved as these values produced from each construct were higher than the acceptable limit of 0.50. Also, the construct validity of fitness indexes (e.g., comparative fit index, incremental fit index, Tucker–Lewis Index, root mean square error of approximation, and chi-square over degree of freedom) was achieved. In its final form, multicultural psychological empowerment scale for Saudi Women included (26) phrases distributed over its four dimensions. The study suggested systematic measurements of psychological empowerment for Saudi women from different categories, targeted with therapeutic, preventative and developmental visions, plans, and programs to determine the extent of their psychological empowerment.
Post-traumatic Stress and Growth Among the Children and Adolescents in the Aftermath of COVID-19
Authors: Bhushan Braj , Basu Sabnam , Ganai Umer Jon
Published: January 2022

The coronavirus disease 2019 (COVID-19) pandemic has enkindled many mental health problems across the globe. Prominent among them is the prevalence of post-traumatic stress (PTS) with hosts of its precipitating factors being present in the surrounding. With India witnessing severe impact of the second wave of COVID-19, marked by a large number of hospitalizations, deaths, unemployment, imposition of lockdowns, etc., its repercussions on children and adolescents demand particular attention. This study aims to examine the direct and the indirect exposure of COVID-19-related experiences on children and adolescents and its subsequent relationship with PTS and post-traumatic growth (PTG). The direct exposure was operationalized in terms of death or hospitalization in the family, while the indirect exposure was gauged in terms of exposure to media reports of the COVID situation. Data from 412 children and adolescents aged 9–20 years, collected online, revealed 68.9% of them with PTS. Interestingly, 39.8% of those reporting PTS were also experiencing PTG. Arousal appeared to be the most frequently reported characteristics of trauma. The multivariate analysis of variance (MANOVA) endorses significant difference between those with direct and indirect exposures to hospitalization. Those with direct exposure to hospitalization reported higher PTS. The indirect exposure of COVID-19-related news through electronic media was also significantly associated with higher PTS. Exposure through print media did not lead to significant difference in PTS, but those reading only magazines reported significantly higher PTG than not reading magazines. The findings are analyzed in the light of unfolding of events during the second wave of COVID-19 in India.