bluuebunny/crossref_metadata_2025 huggingface dataset:
UPLC-Orbitrap-MS/MS Combined With Biochemical Analysis to Determine the Growth and Development of Mothers and Fetuses in Different Gestation Periods on Tibetan Sow Model
Authors: Zhang Longmiao , Tan Chengquan , Xin Zhongquan , Huang Shuangbo , Ma Junwu , Zhang Meiyu , Shu Gang , Luo Hefeng , Deng Baichuan , Jiang Qingyan , Deng Jinping
Published: March 2022

Pregnancy is a complex and dynamic process, the physiological and metabolite changes of the mother are affected by different pregnancy stages, but little information is available about their changes and potential mechanisms during pregnancy, especially in blood and amniotic fluid. Here, the maternal metabolism rules at different pregnancy stages were investigated by using a Tibetan sow model to analyze the physiological hormones and nutrient metabolism characteristics of maternal serum and amniotic fluid as well as their correlations with each other. Our results showed that amniotic fluid had a decrease (P < 0.05) in the concentrations of glucose, insulin and hepatocyte growth factor as pregnancy progressed, while maternal serum exhibited the highest concentrations of glucose and insulin at 75 days of gestation (P < 0.05), and a significant positive correlation (P < 0.05) between insulin and citric acid. Additionally, T4 and cortisol had the highest levels during late gestation (P < 0.05). Furthermore, metabolomics analysis revealed significant enrichment in the citrate cycle pathway and the phenylalanine/tyrosine/tryptophan biosynthesis pathway (P < 0.05) with the progress of gestation. This study clarified the adaptive changes of glucose, insulin and citric acid in Tibetan sows during pregnancy as well as the influence of aromatic amino acids, hepatocyte growth factor, cortisol and other physiological indicators on fetal growth and development, providing new clues for the normal development of the mother and the fetus, which may become a promising target for improving the well-being of pregnancy.
The Positive Influence of Polyphenols Extracted From Pueraria lobata Root on the Gut Microbiota and Its Antioxidant Capability
Authors: Xu Xiao , Guo Ying , Chen Shaoqin , Ma Wenliang , Xu Xinlei , Hu Shuning , Jin Lifang , Sun Jianqiu , Mao Jian , Shen Chi
Published: March 2022

Pueraria lobata, an edible food and medicinal plant, is a rich source of bioactive components. In this study, a polyphenol-rich extract was isolated from P. lobata. Puerarin was identified, and the high antioxidant bioactivity of the P. lobata extract was evaluated using the methods of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS), and hydroxyl free radical scavenging ratio. Additionally, the IC50 values of DPPH, ABTS, and hydroxyl radical scavenging activities were 50.8, 13.9, and 100.4 μg/ml, respectively. Then, the P. lobata extract was administered to C57Bl/6J mice and confirmed to have a superior effect on enhancing the antioxidant status including improving superoxide dismutase activity, glutathione peroxidase peroxide activity, total antioxidant capacity activity, and malondialdehyde contents in vivo. Furthermore, the P. lobata extract had beneficial and prebiotic effects on the composition and structure of gut microbiota. Results showed that the P. lobata extract significantly increased the abundance of beneficial bacteria, involving Lactobacillaceae and Bacteroidetes, and decreased the abundance of Ruminococcaceae, Prevotellaceae, and Burkholderiaceae. Overall, our results provided a basis for using the P. lobata extract as a promising and potential functional ingredient for the food industry.
Preoperative T and N Restaging of Rectal Cancer After Neoadjuvant Chemoradiotherapy: An Accuracy Comparison Between MSCT and MRI
Authors: Liu Wenjuan , Li Yuyi , Zhang Xue , Li Jia , Sun Jing , Lv Han , Wang Zhenchang
Published: March 2022

Background

It is well established that magnetic resonance imaging (MRI) is better than multi-slice computed tomography (MSCT) for the accurate diagnosis of pretreatment tumor (T) and node (N) staging of rectal cancer. However, the diagnostic value of MRI and MSCT in local restaging of rectal cancer after neoadjuvant chemoradiotherapy (NCRT) is controversial. The aim of this study is to investigate the performance of the two imaging exams in restaging of patients with rectal cancer.

Methods

Patients with rectal cancer from April 2015 to April 2021 were analyzed retrospectively. The inclusion criteria are as follows: 1) diagnosis of rectal cancer through pathology; 2) NCRT had been performed; 3) all patients had undergone both MSCT and MRI examination before the surgery. Exclusion criteria are as follows: 1) incomplete clinical and imaging data; 2) previous history of pelvic surgery. Two radiologists performed T and N staging of patient images. Diagnostic accuracy, consistency analysis, and error restaging distribution of the two imaging exams for T and N restaging of rectal cancer were assessed using postoperative pathological staging as the gold standard.

Results

A total of 62 patients (49 men; mean age: 59 years; age range 29–83 years) were included in the study. The diagnostic accuracy of MSCT and MRI for T restaging was 51.6% (95% CI 39.3%–63.9%) and 41.9% (95% CI 29.6%–54.2%), respectively, and no statistical difference was found between them (p > 0.05). The diagnostic accuracy of MSCT and MRI for N restaging was 56.5% (95% CI 44.2%–68.8%) and 53.2% (95% CI 40.8%–65.6%), respectively, and no statistical difference was found between them (p > 0.05). The consistency analysis showed that T restaging (κ = 0.583, p < 0.001) and N restaging (κ = 0.644, p < 0.001) were similar between MSCT and MRI. There was no significant difference in the distribution of over, accurate, or low staging in T restaging (p > 0.05) and N restaging (p > 0.05) between MSCT and MRI.

Conclusions

MSCT and MRI have similarly poor performance in the diagnosis of preoperative T and N restaging of rectal cancer after NCRT. Neither of them cannot effectively stage the ypT0-1 of rectal cancer. These findings may be of clinical relevance for planning less imaging exam.
Systematic Characterization of the Clinical Relevance of KPNA4 in Pancreatic Ductal Adenocarcinoma
Authors: Bao Jingpiao , Xu Chaoliang , Li Bin , Wu Zengkai , Shen Jie , Song Pengli , Peng Qi , Hu Guoyong
Published: March 2022

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with poor prognosis. Karyopherin subunit alpha 4 (KPNA4) is a nuclear transport factor and plays tumor-promoting roles in multiple cancers. However, the roles of KPNA4 in PDAC still remain unknown. This study investigated the prognostic value of KPNA4 and its potential functions in PDAC and tumor microenvironment.

Methods

LinkedOmics was utilized to screen genes with survival significance in PDAC. KPNA4 expression was analyzed using multiple datasets and verified in PDAC cells and clinical samples by qRT-PCR and immunohistochemistry. Clinical correlation and survival analyses were conducted to identify the clinical significance and prognostic value of KPNA4 in PDAC patients. Subsequently, KPNA4 was knocked down in PDAC cell lines, and CCK-8, colony formation and wound healing assays were performed to test the functions of KPNA4 in vitro. Immune infiltration analysis was performed to explore the potential roles of KPNA4 in the tumor microenvironment of PDAC. Moreover, functional analyses were conducted to explore the underlying mechanism of KPNA4 in the progression of PDAC.

Results

We found KPNA4 was significantly upregulated in PDAC cells and tissues. KPNA4 expression was associated with tumor progression in PDAC patients. Survival analyses further revealed that KPNA4 could act as an independent predictor of unfavorable survival for PDAC patients. KPNA4 knockdown suppressed the viability, colony formation and migration of PDAC cells. Moreover, KPNA4 was correlated with immunosuppressive cells infiltration and T cell exhaustion in the tumor microenvironment of PDAC. Finally, functional analyses indicated the association of KPNA4 with focal adhesion kinase (FAK) signaling, and KPNA4 silencing significantly decreased the expression of FAK and PD-L1.

Conclusions

This study revealed that KPNA4 is an independent prognostic biomarker for PDAC and plays a tumor-promoting role by facilitating proliferation and migration of cancer cells and participating in immune infiltration, which may be mediated by FAK signaling and PD-L1 expression. These results provide a novel and potential therapeutic target for pancreatic cancer.
BAP1-Related ceRNA (NEAT1/miR-10a-5p/SERPINE1) Promotes Proliferation and Migration of Kidney Cancer Cells
Authors: Liu Rui-ji , Xu Zhi-Peng , Li Shu-Ying , Yu Jun-Jie , Feng Ning-han , Xu Bin , Chen Ming
Published: March 2022

Background

BAP1 is an important tumor suppressor involved in various biological processes and is commonly lost or inactivated in clear-cell renal cell carcinoma (ccRCC). However, the role of the BAP1-deficient tumor competing endogenous RNA (ceRNA) network involved in ccRCC remains unclear. Thus, this study aims to investigate the prognostic BAP1-related ceRNA in ccRCC.

Methods

Raw data was obtained from the TCGA and the differentially expressed genes were screened to establish a BAP1-related ceRNA network. Subsequently, the role of the ceRNA axis was validated using phenotypic experiments. Dual-luciferase reporter assays and fluorescence in situ hybridization (FISH) assays were used to confirm the ceRNA network.

Results

Nuclear enriched abundant transcript 1 (NEAT1) expression was significantly increased in kidney cancer cell lines. NEAT1 knockdown significantly inhibited cell proliferation and migration, which could be reversed by miR-10a-5p inhibitor. Dual-luciferase reporter assay confirmed miR-10a-5p as a common target of NEAT1 and Serine protease inhibitor family E member 1 (SERPINE1). FISH assays revealed the co-localization of NEAT1 and miR-10a-5p in the cytoplasm. Additionally, the methylation level of SERPINE1 in ccRCC was significantly lower than that in normal tissues. Furthermore, SERPINE1 expression was positively correlated with multiple immune cell infiltration levels.

Conclusions

In BAP1-deficient ccRCC, NEAT1 competitively binds to miR-10a-5p, indirectly upregulating SERPINE1 expression to promote kidney cancer cell proliferation. Furthermore, NEAT1/miR-10a-5p/SERPINE1 were found to be independent prognostic factors of ccRCC.
Molecular Biomarker of Drug Resistance Developed From Patient-Derived Organoids Predicts Survival of Colorectal Cancer Patients
Authors: Chen Lifeng , Tian Bo , Liu Wen , Liang Haitao , You Yong , Liu Weizhen
Published: March 2022

The drug 5-fluorouracil (5-Fu) is the critical composition of colorectal cancer (CRC) treatments. Prognostic and predictive molecular biomarkers for CRC patients (CRCpts) treated with 5-Fu-based chemotherapy can provide assistance for tailoring treatment approach. Here, we established a molecular biomarker of 5-Fu resistance derived from colorectal cancer organoids (CRCOs) for predicting the survival of CRCpts. Forty-one CRCO cultures were generated from 50 CRC tumor tissues after surgery (82%). The following experiments revealed a great diversity in drug sensitivity for 10 μM 5-Fu treatment tested by using organoid size change. Fourteen cases (34.1%) were 5-Fu sensitive and the other 27 (65.9%) were resistant. Then, differentially expressed genes (DEGs) associated with 5-Fu resistance were outputted by transcriptome sequencing. In particular, DEGs were generated in two comparison groups: 1) 5-Fu sensitive and resistant untreated CRCOs; 2) CRCOs before 5-Fu treatment and surviving CRCOs after 5-Fu treatment. Some molecules and most of the pathways that have been reported to be involved in 5-Fu resistance were identified in the current research. By using DEGs correlated with 5-Fu resistance and survival of CRCpts, the gene signature and drug-resistant score model (DRSM) containing five molecules were established in The Cancer Genome Atlas (TCGA)-CRC cohort by least absolute shrinkage and selection operator (LASSO) regression analysis and 5-fold cross-validation. Multivariate analysis revealed that drug-resistant score (DRS) was an independent prognostic factor for overall survival (OS) in CRCpts in TCGA-CRC cohort (P < 0.001). Further validation results from four Gene Expression Omnibus (GEO) cohorts elucidated that the DRSM based on five genes related to 5-Fu chemosensitivity and developed from patient-derived organoids can predict survival of CRCpts. Meanwhile, our model could predict the survival of CRCpts in different subgroups. Besides, the difference of molecular pathways, tumor mutational burden (TMB), immune response-related pathways, immune score, stromal score, and immune cell proportion were dissected between DRS-high and DRS-low patients in TCGA-CRC cohort.
Lung Ultrasound in Pediatric Acute Respiratory Distress Syndrome Received Extracorporeal Membrane Oxygenation: A Prospective Cohort Study
Authors: Zhang Yucai , Wang Chunxia , Wang Fei , Shi Jingyi , Dou Jiaying , Shan Yijun , Sun Ting , Zhou Yiping
Published: March 2022

Objective

The aim of this study was to assess the prognostic value of the lung ultrasound (LUS) score in patients with pediatric acute respiratory distress syndrome (pARDS) who received extracorporeal membrane oxygenation (ECMO).

Methods

A prospective cohort study was conducted in a pediatric intensive care unit (PICU) of a tertiary hospital from January 2016 to June 2021. The severe pARDS patients who received ECMO were enrolled in this study. LUS score was measured at initiation of ECMO (LUS-0 h), then at 24 h (LUS-24 h), 48 h (LUS-48 h), and 72 h (LUS-72 h) during ECMO, and when weaned from ECMO (LUS-wean). The value of LUS scores at the first 3 days of ECMO as a prognostic predictor was analyzed.

Results

Twenty-nine children with severe pARDS who received ECMO were enrolled with a median age of 26 (IQR 9, 79) months. The median duration of ECMO support was 162 (IQR 86, 273) h and the PICU mortality was 31.0% (9/29). The values of LUS-72 h and LUS-wean were significantly lower in survivors than that in non-survivors (both P < 0.001). Daily fluid balance volume during the first 3 days of ECMO support were strongly correlated with LUS score [1st day: r = 0.460, P = 0.014; 2nd day: r = 0.540, P = 0.003; 3rd day: r = 0.589, P = 0.001]. The AUC of LUS-72 h for predicting PICU mortality in these patients was 1.000, and the cutoff value of LUS-72 h was 24 with a sensitivity of 100.0% and a specificity of 100.0%. Furthermore, patients were stratified in two groups of LUS-72 h ≥ 24 and LUS-72 h < 24. Consistently, PICU mortality, length of PICU stay, ratio of shock, vasoactive index score value, and the need for continuous renal replacement therapy were significantly higher in the group of LUS-72 h ≥ 24 than in the group of LUS-72 h < 24 (all P < 0.05).

Conclusion

Lung ultrasound score is a promising tool for predicting the prognosis in patients with ARDS under ECMO support. Moreover, LUS-72 h ≥ 24 is associated with high risk of PICU mortality in patients with pARDS who received ECMO.
Baseline Values of Left Ventricular Systolic Function in Preterm Infants With Septic Shock: A Prospective Observational Study
Authors: Zhong Junjuan , Shuai Chun , Wang Yue , Mo Jing , Ma Dongju , Zhang Jing , Lin Yingyi , Yang Jie , Ye Xiuzhen
Published: March 2022

Background and Aim

Guidelines recommended that cardiac index (CI) of term infants with septic shock should reach the target level of 3.3–6.0L/(min⋅m2). However, there are still no standard values for preterm infants with septic shock. Herein, we investigated the functional echocardiographic baseline values of left ventricular (LV) systolic functional parameters at the onset of septic shock in preterm infants and possible correlations between baseline values and poor outcomes.

Materials and Methods

This was a prospective, observational, and longitudinal single-center study. Eligible infants were monitored for LV systolic functional parameters using functional echocardiography at the onset of septic shock. The primary study outcome was the difference in the baseline value of LV systolic functional parameters in preterm infants with septic shock with different gestational age (GA) and birth weight (BW). The secondary outcome was septic shock-associated death or severe brain injury (including grade 3–4 intraventricular hemorrhage or periventricular leukomalacia).

Results

In total, 43 subjects met the criteria, with a median GA of 321/7 weeks and BW of 1800 grams. No difference was observed in baseline values of LV systolic functional parameters among infants with different GA and BW. Infants were assigned to good and poor outcomes groups based on septic shock-associated death or severe brain injury. Out of 43 infants, 29 (67.4%) had good outcomes vs. 14 (32.6%) with poor outcomes. Stroke index (SI) [18.2 (11.1, 18.9) mL/m2 vs. 23.5 (18.9, 25.8) mL/m2, p = 0.017] and cardiac index (CI)[2.7 (1.6, 3.5) L/(min⋅m2) vs. 3.4 (3.0, 4.8) L/(min⋅m2), p = 0.015] in infants with poor outcomes were significantly lower (P < 0.05). Receiver operating characteristic (ROC) curve analysis showed that the cut-off values of SI and CI for predicting poor outcomes in preterm infants with septic shock were 19.5 mL/m2 (sensitivity, 73.9%; specificity, 81.8%) and 2.9L/(min⋅m2) (sensitivity, 78.3%; specificity, 72.7%), with area under the ROC curve (AUC) value of 0.755 and 0.759, respectively.

Conclusion

There were no differences in baseline LV systolic functional values among preterm infants with septic shock with different GA and BW. However, preterm infants with SI<19.5mL/m2 and/or CI<2.9L/(min⋅m2) at the onset of septic shock were at high risk of having poor outcomes.
Association Between Obesity and Poor Prognosis in Patients Receiving Anlotinib for Advanced Non-Small Cell Lung Cancer
Authors: Xiong Anning , Nie Wei , Cheng Lei , Zhong Hua , Chu Tianqing , Zhong Runbo , Lu Jun , Wang Shuyuan , Xu Jianlin , Shen Yinchen , Pan Feng , Han Baohui , Zhang Xueyan
Published: March 2022

Background: Anlotinib is a novel anti-angiogenesis drug. In non-small cell lung cancer (NSCLC), high body mass index (BMI) was not associated with worse survival in patients treated with bevacizumab compared with those with normal or low BMI. However, it remains unknown whether such an association still exists in NSCLC patients receiving anlotinib therapy. Hence, we conducted this study to investigate whether BMI is associated with clinical outcomes in patients treated with anlotinib for advanced NSCLC.

Methods: Data of 554 patients from the ALTER-0302 and the ALTER-0303 trials were analyzed in this study. The patients were classified into non-obesity (BMI <28 kg/m2) and obesity (BMI ≥28 kg/m2) subgroups. The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). OS was defined as the interval between the first drug administration and death. PFS was defined as the time span from the date of initiating the treatment to the first documented progression or death from any cause, whichever occurred first. ORR included complete response (CR) and partial response (PR).

Results: There were 354 patients (63.9%) who received anlotinib in this study. Restricted cubic spline model showed a U-shaped relation between BMI and the risk of death in the anlotinib group. In a multivariable Cox regression model, a trend of worse overall survival was observed in obese patients who received anlotinib compared with placebo (HR, 2.33; 95% CI, 0.77–7.06; p = 0.136). The interaction between BMI stratification and treatment was significant for OS (P for interaction = 0.038).

Conclusion: Our results revealed a U-shaped relationship between BMI and risk of death in patients receiving anlotinib for advanced NSCLC. More importantly, obesity (BMI ≥28 kg/m2) might be a potential predictor of use of anlotinib in advanced NSCLC.
An m6A-Related lncRNA Signature Predicts the Prognosis of Hepatocellular Carcinoma
Authors: Zhang Zhenyu , Wang Fangkai , Zhang Jianlin , Zhan Wenjing , Zhang Gaosong , Li Chong , Zhang Tongyuan , Yuan Qianqian , Chen Jia , Guo Manyu , Xu Honghai , Yu Feng , Wang Hengyi , Wang Xingyu , Kong Weihao
Published: March 2022

Objective: The purpose of this study was to establish an N6-methylandenosine (m6A)-related long non-coding RNA (lncRNA) signature to predict the prognosis of hepatocellular carcinoma (HCC).

Methods: Pearson correlation analysis was used to identify m6A-related lncRNAs. We then performed univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct an m6A-related lncRNA signature. Based on the cutoff value of the risk score determined by the X-title software, we divided the HCC patients into high -and low-risk groups. A time-dependent ROC curve was used to evaluate the predictive value of the model. Finally, we constructed a nomogram based on the m6A-related lncRNA signature.

Results: ZEB1-AS1, MIR210HG, BACE1-AS, and SNHG3 were identified to comprise an m6A-related lncRNA signature. These four lncRNAs were upregulated in HCC tissues compared to normal tissues. The prognosis of patients with HCC in the low-risk group was significantly longer than that in the high-risk group. The M6A-related lncRNA signature was significantly associated with clinicopathological features and was established as a risk factor for the prognosis of patients with HCC. The nomogram based on the m6A-related lncRNA signature had a good distinguishing ability and consistency.

Conclusion: We identified an m6A-related lncRNA signature and constructed a nomogram model to evaluate the prognosis of patients with HCC.
Ag120-Mediated Inhibition of ASCT2-Dependent Glutamine Transport has an Anti-Tumor Effect on Colorectal Cancer Cells
Authors: Yu Wei , Huang Jianwen , Dong Qichao , Li Wenting , Jiang Lei , Zhang Qian , Sun Li , Yuan Shengtao , He Xu
Published: March 2022

Metabolic reprogramming is considered to be a hallmark of cancer, and increased glutamine metabolism plays an important role in the progression of many tumors, including colorectal cancer (CRC). Targeting of glutamine uptake via the transporter protein ASCT2/SLC1A5 (solute carrier family 1 member 5) is considered to be an effective strategy for the treatment of malignant tumors. Here, we demonstrate that Ag120 (ivosidenib), a mutant isocitrate dehydrogenase 1 (IDH1) inhibitor approved for the treatment of certain cancers, acts as an ASCT2 inhibitor in CRC cells. Ag120 blocked glutamine uptake and metabolism, leading to reduced cell proliferation, elevated autophagy, and increased oxidative stress in CRC cells in vitro and in vivo, potentially via the ERK and mTOR signaling pathways. These effects occurred independently of mutant IDH1 activity and were supported by experiments with ASCT2-depleted or -overexpressing cells. These data identify a novel mechanism of Ag120 anti-tumor activity and support further exploration of ASCT2 inhibitors for cancer therapy.
Identification of Diffracted Vortex Beams at Different Propagation Distances Using Deep Learning
Authors: Lv Heng , Guo Yan , Yang Zi-Xiang , Ding Chunling , Cai Wu-Hao , You Chenglong , Jin Rui-Bo
Published: March 2022

The Orbital angular momentum (OAM) of light is regarded as a valuable resource in quantum technology, especially in quantum communication and quantum sensing and ranging. However, the OAM state of light is susceptible to undesirable experimental conditions such as propagation distance and phase distortions, which hinders the potential for the realistic implementation of relevant technologies. In this article, we exploit an enhanced deep learning neural network to identify different OAM modes of light at multiple propagation distances with phase distortions. Specifically, our trained deep learning neural network can efficiently identify the vortex beam’s topological charge and propagation distance with 97% accuracy. Our technique has important implications for OAM based communication and sensing protocols.
Ultrafast Microfiber Humidity Sensor Based on Three Dimensional Molybdenum Disulfide Network Cladding
Authors: Guo Pan , Cui Danting , Dai Qiaofeng , Cheng Hongdao , Yu Jianhui , Guan Heyuan , Luo Yunhan , Lu Huihui , Xiao Yi , Zhong Yongchun , Zhu Wenguo , Chen Zhe
Published: March 2022

We demonstrate an ultrafast humidity micro-fiber sensor based on molybdenum disulfide (MoS2) cladding with three dimensional network structure. The high surface-to-volume rations and porous mesh structure improve the interaction of between MoS2 and water molecules, further enhancing the performance of the humidity sensor. The results demonstrated that the sensor can perform in a wide relative humidity (RH) range between 10%RH to 90%RH with rapid dynamic behavior (response and recovery time are 0.090 and 0.130 s respectively). The sum of response and recovery time (total time) is 0.220 s, which is the fastest in the reported MoS2-based humidity sensors. The sensitivity of this sensor is up to -1.501 dB/%RH in the RH range (77%RH–90%RH). Such a high performance RH sensor will have a wide range of application potential in chemical processing, various medical diagnostics, and so on.
Protein Kinase C-Mediated Hyperphosphorylation and Lateralization of Connexin 43 Are Involved in Autoimmune Myocarditis-Induced Prolongation of QRS Complex
Authors: Zhong Chunlian , Zhao Huan , Xie Xinwen , Qi Zhi , Li Yumei , Jia Lee , Zhang Jinwei , Lu Yusheng
Published: March 2022

Myocarditis is a serious and potentially life-threatening disease, which leads to cardiac dysfunction and sudden cardiac death. An increasing number of evidence suggests that myocarditis is also a malignant complication of coronavirus pneumonia, associated with heart failure and sudden cardiac death. Prolonged QRS complexes that are related to malignant arrhythmias caused by myocarditis significantly increase the risk of sudden cardiac death in patients. However, the molecular mechanisms are not fully known at present. In this study, we identify protein kinase C (PKC) as a new regulator of the QRS complex. In isolated hearts of normal rats, the PKC agonist, phorbol-12-myristate-13-acetate (PMA), induced prolongation of the QRS complex. Mechanistically, hyperphosphorylation and lateralization of connexin 43 (Cx43) by PKC induced depolymerization and internalization of Cx43 gap junction channels and prolongation of the QRS duration. Conversely, administration of the PKC inhibitor, Ro-32-0432, in experimental autoimmune myocarditis (EAM) rats after the most severe inflammation period still significantly rescued the stability of the Cx43 gap junction and alleviated prolongation of the QRS complex. Ro-32-0432 reduced phosphorylation and blocked translocation of Cx43 in EAM rat heart but did not regulate the mRNA expression level of ventricular ion channels and the other regulatory proteins, which indicates that the inhibition of PKC might have no protective effect on ion channels that generate ventricular action potential in EAM rats. These results suggest that the pharmacological inhibition of PKC ameliorates the prolongation of the QRS complex via suppression of Cx43 hyperphosphorylation, lateralization, and depolymerization of Cx43 gap junction channels in EAM rats, which provides a potential therapeutic strategy for myocarditis-induced arrhythmias.
Regulated Monosyllabic Talk Test vs. Counting Talk Test During Incremental Cardiorespiratory Exercise: Determining the Implications of the Utterance Rate on Exercise Intensity Estimation
Authors: Mahmod Siti Ruzita , Narayanan Leela T. , Abu Hasan Rumaisa , Supriyanto Eko
Published: March 2022

Purpose

When utilizing breathing for speech, the rate and volume of inhalation, as well as the rate of exhalation during the utterance, seem to be largely governed by the speech-controlling system and its requirements with respect to phrasing, loudness, and articulation. However, since the Talk Test represents a non-standardized form of assessment of exercise intensity estimation, this study aimed to compare the utterance rate and the estimated exercise intensity using a newly introduced time-controlled monosyllabic Talk Test (tMTT) versus a self-paced Counting Talk Test (CTT) across incremental exercise stages and examined their associations with the exercise physiological measures.

Methods

Twenty-four participants, 10 males and 14 females (25 ± 4.0 yr; 160 ± 10 cm; 62 ± 14.5 kg) performed two sessions of submaximal cardiorespiratory exercise at incremental heart rate reserve (HRR) stages ranging from 40 to 85% of HRR: one session was performed with a currently available CTT that was affixed to a wall in front of the participants, and the other session was conducted with a tMTT with a 1-s inter-stimulus interval that was displayed from a tablet. In each session, the participants performed six stages of exercise at 40, 50, 60, 70, 80, and 85% HRR on a treadmill and were also asked to rate their perceived exertion based on Borg’s 6 to 20 Rating of Perceived Exertion (RPE) at each exercise stage.

Results

The newly designed tMTT significantly delineated all the six stages of incremental exercise (p ≤ 0.017), while CTT could only delineate exercise stages at 60, 80, and 85% HRR. However, in estimations of exercise intensity, the tMTT demonstrated only moderate associations with HRR and Borg’s RPE, similarly to the CTT.

Conclusion

If the purpose of exercise monitoring is to detect the intensity of light, moderate, and vigorous exercise intensity, the tMTT could be more universally applicable. However, due to its larger variability of speech rate across exercise intensities, the time-regulated approach may alter the speech breathing characteristics of the exercising individuals in other ways that should be investigated in future research.
Gene Editing for Inherited Red Blood Cell Diseases
Authors: Quintana-Bustamante Oscar , Fañanas-Baquero Sara , Dessy-Rodriguez Mercedes , Ojeda-Pérez Isabel , Segovia Jose-Carlos
Published: March 2022

Today gene therapy is a real therapeutic option to address inherited hematological diseases that could be beneficial for thousands of patients worldwide. Currently, gene therapy is used to treat different monogenic hematological pathologies, including several red blood cell diseases such as β-thalassemia, sickle cell disease and pyruvate kinase deficiency. This approach is based on addition gene therapy, which consists of the correction of hematopoietic stem cells (HSCs) using lentiviral vectors, which integrate a corrected version of the altered gene. Lentivirally-corrected HSCs generate healthy cells that compensate for the deficiency caused by genetic mutations. Despite its successful results, this approach lacks both control of the integration of the transgene into the genome and endogenous regulation of the therapeutic gene, both of which are important aspects that might be a cause for concern. To overcome these limitations, gene editing is able to correct the altered gene through more precise and safer approaches. Cheap and easy-to-design gene editing tools, such as the CRISPR/Cas9 system, allow the specific correction of the altered gene without affecting the rest of the genome. Inherited erythroid diseases, such as thalassemia, sickle cell disease and Pyruvate Kinase Deficiency, have been the test bed for these gene editing strategies, and promising results are currently being seen. CRISPR/Cas9 system has been successfully used to manipulate globin regulation to re-activate fetal globin chains in adult red blood cells and to compensate for hemoglobin defects. Knock-in at the mutated locus to express the therapeutic gene under the endogenous gene regulatory region has also been accomplished successfully. Thanks to the lessons learned from previous lentiviral gene therapy research and trials, gene editing for red blood cell diseases is rapidly moving from its proof-of-concept to its first exciting results in the clinic. Indeed, patients suffering from β-thalassemia and sickle cell disease have already been successfully treated with gene editing, which will hopefully inspire the use of gene editing to cure erythroid disorders and many other inherited diseases in the near future.
Multigenerational Exposure to Heat Stress Induces Phenotypic Resilience, and Genetic and Epigenetic Variations in Arabidopsis thaliana Offspring
Authors: Yadav Narendra Singh , Titov Viktor , Ayemere Ivie , Byeon Boseon , Ilnytskyy Yaroslav , Kovalchuk Igor
Published: March 2022

Plants are sedentary organisms that constantly sense changes in their environment and react to various environmental cues. On a short-time scale, plants respond through alterations in their physiology, and on a long-time scale, plants alter their development and pass on the memory of stress to the progeny. The latter is controlled genetically and epigenetically and allows the progeny to be primed for future stress encounters, thus increasing the likelihood of survival. The current study intended to explore the effects of multigenerational heat stress in Arabidopsis thaliana. Twenty-five generations of Arabidopsis thaliana were propagated in the presence of heat stress. The multigenerational stressed lineage F25H exhibited a higher tolerance to heat stress and elevated frequency of homologous recombination, as compared to the parallel control progeny F25C. A comparison of genomic sequences revealed that the F25H lineage had a three-fold higher number of mutations [single nucleotide polymorphisms (SNPs) and insertions and deletions (INDELs)] as compared control lineages, suggesting that heat stress induced genetic variations in the heat-stressed progeny. The F25H stressed progeny showed a 7-fold higher number of non-synonymous mutations than the F25C line. Methylome analysis revealed that the F25H stressed progeny showed a lower global methylation level in the CHH context than the control progeny. The F25H and F25C lineages were different from the parental control lineage F2C by 66,491 and 80,464 differentially methylated positions (DMPs), respectively. F25H stressed progeny displayed higher frequency of methylation changes in the gene body and lower in the body of transposable elements (TEs). Gene Ontology analysis revealed that CG-DMRs were enriched in processes such as response to abiotic and biotic stimulus, cell organizations and biogenesis, and DNA or RNA metabolism. Hierarchical clustering of these epimutations separated the heat stressed and control parental progenies into distinct groups which revealed the non-random nature of epimutations. We observed an overall higher number of epigenetic variations than genetic variations in all comparison groups, indicating that epigenetic variations are more prevalent than genetic variations. The largest difference in epigenetic and genetic variations was observed between control plants comparison (F25C vs. F2C), which clearly indicated that the spontaneous nature of epigenetic variations and heat-inducible nature of genetic variations. Overall, our study showed that progenies derived from multigenerational heat stress displayed a notable adaption in context of phenotypic, genotypic and epigenotypic resilience.
Florivory and Pollination Intersection: Changes in Floral Trait Expression Do Not Discourage Hummingbird Pollination
Authors: Tunes Priscila , Dötterl Stefan , Guimarães Elza
Published: March 2022

Many flowers are fed on by florivores, but we know little about if and how feeding on flowers affects their visual and chemical advertisement and nectar resource, which could disrupt pollination. Here, we investigated if damages caused by florivores compromise a Neotropical hummingbird pollination system, by modifying the floral advertisements and the nectar resource. We surveyed natural florivory levels and patterns, examined short-term local effects of floral damages caused by the most common florivore, a caterpillar, on floral outline, intra-floral colour pattern and floral scent, as well as on the amount of nectar. Following, we experimentally tested if the most severe florivory pattern affected hummingbird pollination. The feeding activity of the most common florivore did not alter the intra-floral colour pattern, floral scent, and nectar volume, but changed the corolla outline. However, this change did not affect hummingbird pollination. Despite visual floral cues being important for foraging in hummingbirds, our results emphasise that changes in the corolla outline had a neutral effect on pollination, allowing the maintenance of florivore–plant–pollinator systems without detriment to any partner.
A New Series of Strigolactone Analogs Derived From Cinnamic Acids as Germination Inducers for Root Parasitic Plants
Authors: Suzuki Taiki , Kuruma Michio , Seto Yoshiya
Published: March 2022

Root parasitic plants such as Striga and Orobanche cause significant damage on crop production, particularly in sub-Saharan Africa. Their seeds germinate by sensing host root-derived signaling molecules called strigolactones (SLs). SL mimics can be used as suicidal germination inducers for root parasitic plants. Previous attempts to develop such chemicals have revealed that the methylbutenolide ring (D-ring), a common substructure in all the naturally occurring SLs, is critical for SL agonistic activity, suggesting that it should be possible to generate new SL mimics simply by coupling a D-ring with another molecule. Because structural information regarding SLs and their receptor interaction is still limited, such an approach might be an effective strategy to develop new potent SL agonists. Here, we report development of a series of new SL analogs derived from cinnamic acid (CA), the basis of a class of phenylpropanoid natural products that occur widely in plants. CA has an aromatic ring and a double-bond side-chain structure, which are advantageous for preparing structurally diverse derivatives. We prepared SL analogs from cis and trans configuration CA, and found that all the cis-CA-derived SL analogs had stronger activities as seed germination inducers for the root parasitic plants, Orobanche minor and Striga hermonthica, compared with the corresponding trans-CA-derived analogs. Moreover, introduction of a substitution at the C-4 position increased the germination-stimulating activity. We also found that the SL analogs derived from cis-CA were able to interact directly with SL receptor proteins more effectively than the analogs derived from trans-CA. The cis isomer of CA was previously reported to have a growth promoting effect on non-parasitic plants such as Arabidopsis. We found that SL analogs derived from cis-CA also showed growth promoting activity toward Arabidopsis, suggesting that these new SL agonists might be useful not only as suicidal germination inducers for root parasitic weeds, but also as plant growth promoters for the host plants.
The Next Generation of Rice: Inter-Subspecific Indica-Japonica Hybrid Rice
Authors: Zhang Guiquan
Published: March 2022

Rice (Oryza sativa) is an important food crop and has two subspecies, indica and japonica. Since the last century, four generations of rice varieties have been applied to rice production. Semi-dwarf rice, intra-subspecific hybrid rice, and inter-subspecific introgression rice were developed successively by genetic modification based on the first generation of tall rice. Each generation of rice has greater yield potential than the previous generation. Due to the stronger heterosis of indica-japonica hybrids, utilization of the inter-subspecific heterosis has long been of interest. However, indica-japonica hybrid sterility hinders the utilization of heterosis. In the past decades, indica-japonica hybrid sterility has been well understood. It is found that indica-japonica hybrid sterility is mainly controlled by six loci, S5, Sa, Sb, Sc, Sd, and Se. The indica-japonica hybrid sterility can be overcome by developing indica-compatible japonica lines (ICJLs) or wide-compatible indica lines (WCILs) using genes at the loci. With the understanding of the genetic and molecular basis of indica-japonica hybrid sterility and the development of molecular breeding technology, the development of indica-japonica hybrid rice has become possible. Recently, great progress has been made in breeding indica-japonica hybrid rice. Therefore, the indica-japonica hybrid rice will be the next generation of rice. It is expected that the indica-japonica hybrid rice will be widely applied in rice production in the near future.
The Function and Photoregulatory Mechanisms of Cryptochromes From Moso Bamboo (Phyllostachys edulis)
Authors: Chen Ziyin , Li Min , Liu Siyuan , Chen Xiaojie , Zhang Wenxiang , Zhu Qiang , Kohnen Markus V. , Wang Qin
Published: March 2022

Light is one of the most important environmental factors affecting growth and geographic distribution of forestry plants. Moso bamboo is the largest temperate bamboo on earth and an important non-woody forestry species that serves not only important functions in the economy of rural areas but also carbon sequestration in the world. Due to its decades-long reproductive timing, the germplasm of moso bamboo cannot be readily improved by conventional breeding methods, arguing for a greater need to study the gene function and regulatory mechanisms of this species. We systematically studied the photoregulatory mechanisms of the moso bamboo (Phyllostachys edulis) cryptochrome 1, PheCRY1. Our results show that, similar to its Arabidopsis counterpart, the bamboo PheCRY1s are functionally restricted to the blue light inhibition of cell elongation without an apparent activity in promoting floral initiation. We demonstrate that PheCRY1s undergo light-dependent oligomerization that is inhibited by PheBIC1s, and light-dependent phosphorylation that is catalyzed by PhePPKs. We hypothesize that light-induced phosphorylation of PheCRY1s facilitate their degradation, which control availability of the PheCRY1 proteins and photosensitivity of bamboo plants. Our results demonstrate the evolutionary conservation of not only the function but also photoregulatory mechanism of PheCRY1 in this monocot forestry species.
An Apoplastic Effector Pat-1Cm of the Gram-Positive Bacterium Clavibacter michiganensis Acts as Both a Pathogenicity Factor and an Immunity Elicitor in Plants
Authors: Hwang In Sun , Oh Eom-Ji , Song Eunbee , Park In Woong , Lee Yoonyoung , Sohn Kee Hoon , Choi Doil , Oh Chang-Sik
Published: March 2022

Clavibacter michiganensis, a Gram-positive plant-pathogenic bacterium, utilizes apoplastic effectors for disease development in host plants. Here, we determine the roles of Pat-1Cm (a putative serine protease) in pathogenicity and plant immunity. Pat-1Cm was found to be a genuine secreted protein, and the secreted mature form did not carry the first 33 amino acids predicted to be a signal peptide (SP). The pat-1Cm mutant impaired to cause wilting, but still caused canker symptom in tomato. Moreover, this mutant failed to trigger the hypersensitive response (HR) in a nonhost Nicotiana tabacum. Among orthologs and paralogs of pat-1Cm, only chp-7Cs from Clavibacter sepedonicus, a potato pathogen, successfully complemented pat-1Cm function in pathogenicity in tomato, whereas all failed to complement pat-1Cm function in HR induction in N. tabacum. Based on the structural prediction, Pat-1Cm carried a catalytic triad for putative serine protease, and alanine substitution of any amino acids in the triad abolished both pathogenicity and HR-inducing activities of Pat-1Cm in C. michiganensis. Ectopic expression of pat-1Cm with an SP from tobacco secreted protein triggered HR in N. tabacum, but not in tomato, whereas a catalytic triad mutant failed to induce HR. Inoculation of the pat-1Cm mutant mixed with the mutant of another apoplastic effector CelA (cellulase) caused severe wilting in tomato, indicating that these two apoplastic effectors can functionally cooperate in pathogenicity. Overall, these results indicate that Pat-1Cm is a distinct secreted protein carrying a functional catalytic triad for serine protease and this enzymatic activity might be critical for both pathogenicity and HR-eliciting activities of Pat-1Cm in plants.
Can Identity Buffer Against the Detrimental Effects of Threat? The Case of the Qatar Blockade
Authors: Amin Azzam , Van Assche Jasper , Abdelrahman Mohamed , McCashin Darragh , Al-Adwan Duaa , Hasan Youssef
Published: March 2022

In 2017, the blockade of Qatar Gulf states caused a plethora of effects on the country. This paper sought to examine the resulting threat effects of this blockade in terms of lowered self-esteem and well-being, and the potential buffering effects of an overarching identity. Using self-report questionnaire data from Qatari secondary school students (N = 1,410), multiple moderated mediation models investigated the predictive effects of youngsters’ perceived threat, via self-esteem, on their well-being, and the mitigating roles herein of, respectively, national, Gulf region, and Arab identity. Perceived threat was indeed related to lower well-being via lower self-esteem, and this relationship was equally strong for those low and high in social identity. In terms of the three facets of identity, the overarching Gulf identity seems the most predictive, and it even (marginally significantly) buffers the negative relationship between threat and reduced self-esteem.
Innovation to Immune: Empirical Evidence From COVID-19 Focused Enterprise Surveys
Authors: Khan Karamat , Liu Sheng , Xiong Baowei , Zhang Leihao , Li Chuntao
Published: March 2022

The recent COVID-19 crisis caught many by surprise. Yet some firms were better prepared to weather the downturn than others. Using a comprehensive data set that observes over 15,000 firms in 27 countries, including several developing countries, shortly before and after the pandemic, we document that pre-crisis innovation affected firm’s survival odds and performance thereafter. The results show that innovative firms are less likely to close and perform better than non-innovators during the pandemic crisis. Innovative firms are also more optimistic about the future than non-innovators. Our results further indicate that firm’s adaptability mediates the relationship between innovation and survival outcomes. The study finding shows that innovative firms are more likely to introduce new products, remote work arrangements, increase delivery, pivoting, and online activities than non-innovators during the pandemic crisis.
Longitudinal Relationship Between Bullying Victimization and Depression Among Left-Behind Children: Roles of Negative Thoughts and Self-Compassion
Authors: Yan Ru , Xie Ruibo , Jiang Min , Li Jiayi , Lin Xiuyun , Ding Wan
Published: March 2022

Background

Left-behind children (LBC) in China have aroused widespread concern in society and the academic field because they have a high risk of psychological problems. For left-behind children, depression is the most serious problem. Bullying victimization has been evidenced as one of the most common causes of children’s depression. However, less is known about its longitudinal association and the process for how bullying victimization influences depression among left-behind children. Thus, the presentation aims to explore the mechanisms underlying by considering the roles of left-behind children’s negative thoughts and self-compassion.

Methods

The 3-wave longitudinal data were collected from a sample of 605 aged 8–11 from central China. We used the Olweus bully and victimization questionnaire, the children’s automatic thoughts scale, the depression scale, and the self-compassion scale.

Results

Bullying victimization positively predicted the depression level of left-behind children. Negative thoughts and self-compassion mediate the relationship between bullying victimization and depression. In the mechanism of bullying victimization on depression exists gender differences among left-behind children.

Conclusion

The present study suggested the association between bullying victimization and left-behind children’s depression and revealed the internal mechanism of negative thoughts and self-compassion. These findings provide a new perspective for left-behind children’s mental health education and intervention.