bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of prognosis-related gene features in low-grade glioma based on ssGSEA
Authors: He Yuanzhi , Lin Zhangping , Tan Sanyang
Published: December 2022

Low-grade gliomas (LGG) are commonly seen in clinical practice, and the prognosis is often poor. Therefore, the determination of immune-related risk scores and immune-related targets for predicting prognoses in patients with LGG is crucial. A single-sample gene set enrichment analysis (ssGSEA) was performed on 22 immune gene sets to calculate immune-based prognostic scores. The prognostic value of the 22 immune cells for predicting overall survival (OS) was assessed using the least absolute shrinkage and selection operator (LASSO) and univariate and multivariate Cox analyses. Subsequently, we constructed a validated effector T-cell risk score (TCRS) to identify the immune subtypes and inflammatory immune features of LGG patients. We divided an LGG patient into a high-risk–score group and a low-risk–score group based on the optimal cutoff value. Kaplan–Meier survival curve showed that patients in the low-risk–score group had higher OS. We then identified the differentially expressed genes (DEGs) between the high-risk–score group and low-risk-score group and obtained 799 upregulated genes and 348 downregulated genes. The analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) show that DEGs were mainly concentrated in immune-related processes. In order to further explore the immune-related genes related to prognosis, we constructed a protein–protein interaction (PPI) network using Cytoscape and then identified the 50 most crucial genes. Subsequently, nine DEGs were found to be significantly associated with OS based on univariate and multivariate Cox analyses. It was further confirmed that CD2, SPN, IL18, PTPRC, GZMA, and TLR7 were independent prognostic factors for LGG through batch survival analysis and a nomogram prediction model. In addition, we used an RT-qPCR assay to validate the bioinformatics results. The results showed that CD2, SPN, IL18, PTPRC, GZMA, and TLR7 were highly expressed in LGG. Our study can provide a reference value for the prediction of prognosis in LGG patients and may help in the clinical development of effective therapeutic agents.
Knowledge mapping of alternative splicing of cancer from 2012 to 2021: A bibliometric analysis
Authors: Tian Bo , Bian Yan , Bian De-Jian , Gao Ye , Zhang Xun , Zhou Si-Wei , Zhang Yan-Hui , Pang Ya-Nan , Li Zhao-Shen , Wang Luo-Wei
Published: December 2022

Background

As a processing method of RNA precursors, alternative splicing (AS) is critical to normal cellular activities. Aberrant AS events are associated with cancer development and can be promising targets to treat cancer. However, no detailed and unbiased study describes the current state of AS of cancer research. We aim to measure and recognize the current state and trends of AS cancer research in this study.

Methods

The Web of Science Core Collection was used to acquire the articles. Utilizing three bibliometric tools (CiteSpace, VOSviewer, R-bibliometrix), we were able to measure and recognize the influence and collaboration data of individual articles, journals, and co-citations. Analysis of co-occurrence and burst information helped us identify the trending research areas related to AS of cancer.

Results

From 2012 to 2021, the total number of papers on AS of cancer published in 766 academic journals was 3,507, authored by 20,406 researchers in 405 institutions from 80 countries/regions. Research involving AS of cancer genes was primarily conducted in the United States and China; simultaneously, the Chinese Academy of Sciences, Fudan University, and National Cancer Institute were the institutions with strong research capabilities. Scorilas Andreas is the scholar with the most publications, while the most co-citations were generated by Wang, Eric T. Plos One published the most papers on AS of cancer, while J Biol Chem was the most co-cited academic journal in this field. The results of keyword co-occurrence analysis can be divided into three types: molecular (P53, CD44, androgen receptor, srsf3, esrp1), pathological process (apoptosis, EMT, metastasis, angiogenesis, proliferation), and disease (breast cancer, colorectal cancer, prostate cancer, hepatocellular carcinoma, gastric cancer).

Conclusion

Research on AS of cancer has been increasing in intensity over the past decade. Current AS of cancer studies focused on the hallmarks of AS in cancer and AS signatures including diagnostic and therapeutic targets. Among them, the current trends are splicing factors regulating epithelial–mesenchymal transition and other hallmarks, aberrant splicing events in tumors, and further mechanisms. These might give researchers interested in this field a forward-looking perspective and inform further research.
Nanopore sequencing of clonal IGH rearrangements in cell-free DNA as a biomarker for acute lymphoblastic leukemia
Authors: Sampathi Shilpa , Chernyavskaya Yelena , Haney Meghan G. , Moore L. Henry , Snyder Isabel A. , Cox Anna H. , Fuller Brittany L. , Taylor Tamara J. , Yan Donglin , Badgett Tom C. , Blackburn Jessica S.
Published: December 2022

Background

Acute Lymphoblastic Leukemia (ALL) is the most common pediatric cancer, and patients with relapsed ALL have a poor prognosis. Detection of ALL blasts remaining at the end of treatment, or minimal residual disease (MRD), and spread of ALL into the central nervous system (CNS) have prognostic importance in ALL. Current methods to detect MRD and CNS disease in ALL rely on the presence of ALL blasts in patient samples. Cell-free DNA, or small fragments of DNA released by cancer cells into patient biofluids, has emerged as a robust and sensitive biomarker to assess cancer burden, although cfDNA analysis has not previously been applied to ALL.

Methods

We present a simple and rapid workflow based on NanoporeMinION sequencing of PCR amplified B cell-specific rearrangement of the (IGH) locus in cfDNA from B-ALL patient samples. A cohort of 5 pediatric B-ALL patient samples was chosen for the study based on the MRD and CNS disease status.

Results

Quantitation of IGH-variable sequences in cfDNA allowed us to detect clonal heterogeneity and track the response of individual B-ALL clones throughout treatment. cfDNA was detected in patient biofluids with clinical diagnoses of MRD and CNS disease, and leukemic clones could be detected even when diagnostic cell-count thresholds for MRD were not met. These data suggest that cfDNA assays may be useful in detecting the presence of ALL in the patient, even when blasts are not physically present in the biofluid sample.

Conclusions

The Nanopore IGH detection workflow to monitor cell-free DNA is a simple, rapid, and inexpensive assay that may ultimately serve as a valuable complement to traditional clinical diagnostic approaches for ALL.
Construction of an immune-related ceRNA network in cervical cancer based on HPV E6 splicing
Authors: Jiang Senwei , Zhou Yun , Ye Minjuan , Li Xiaomao , Zhang Lan , Yang Yuebo
Published: December 2022

Background

Cervical cancer is one of the leading causes of cancer-related deaths worldwide. The unspliced human papillomavirus (HPV) E6 plays an important role in tumor progression and immune regulation. Improved immunotherapy implementation might benefit from a better knowledge of HPV E6 splicing-related immune gene expressions and immunocyte infiltration in cervical cancer. This study aimed to identify the potential therapeutic and prognostic roles of unspliced/spliced E6 ratio (E6 ratio) in cervical cancer.

Methods

Data from the TCGA were used to analyze the E6 condition and clinical information. Nomogram and K-M analysis were used to analyze assess the prognostic significance, IOBR was used to investigate immunological infiltrates. Functions and pathway enrichment analysis of DEGs were investigated through GO analysis and KEGG pathway analysis, respectively. A core module was taken from the competitive endogenous RNA (ceRNA) network and used to build a lncRNA-miRNA-mRNA network. QT-qPCR was used to detect the expression of genes. CCK-8, colony formation, wound healing and migration assays were used to detect cell functions.

Results

Our study found that HPV E6 ratio had significantly correlation with overall survival. In cervical cancer, a high E6 ratio was adversely linked with infiltrating levels of aDC, M1 macrophages, monocytes, NKT, and Tgd. High E6 ratio phenotypes were shown to be implicated in immune response regulation, cell adhesion, and Wnt signaling pathways, according to functional enrichment analysis. Subsequently, we constructed an immune-related ceRNA network based on E6 splicing in cervical cancer, including three lncRNA (LINC00943, LIFR-AS1, DANT2, and RASSF8-AS1), four miRNA (miR-205-5p, miR-181d-5p, miR-222-3p, and miR-221-3p), and seven mRNA (FGFR1, PRLR, CXCL2, ISG20, ISG15, SDC1, and NR2F2). Among them, CXCL2, SDC1, and miR-221-3p were associated with survival and immune cell infiltration.

Conclusions

These data imply that a high E6 ratio in cervical cancer contributes to the immune-related ceRNA network, resulting in a low amount of infiltrating effector immune cells and tumor growth. As a result, the E6 ratio might be employed as a biomarker in cervical cancer to determine prognosis and treatment success.
Heightened cocaine-seeking in male rats associates with a distinct transcriptomic profile in the medial prefrontal cortex
Authors: Merritt Christina R. , Smith Ashley E. , Khanipov Kamil , Golovko George , Dineley Kelly T. , Anastasio Noelle C. , Cunningham Kathryn A.
Published: December 2022

Drug overdose deaths involving cocaine have skyrocketed, an outcome attributable in part to the lack of FDA-approved medications for the treatment of cocaine use disorder (CUD), highlighting the need to identify new pharmacotherapeutic targets. Vulnerability to cocaine-associated environmental contexts and stimuli serves as a risk factor for relapse in CUD recovery, with individual differences evident in the motivational aspects of these cues. The medial prefrontal cortex (mPFC) provides top-down control of striatal circuitry to regulate the incentive-motivational properties of cocaine-associated stimuli. Clinical and preclinical studies have identified genetic variations that impact the degree of executive restraint over drug-motivated behaviors, and we designed the present study to employ next-generation sequencing to identify specific genes associated with heightened cue-evoked cocaine-seeking in the mPFC of male, outbred rats. Rats were trained to stably self-administer cocaine, and baseline cue-reinforced cocaine-seeking was established. Rats were phenotyped as either high cue (HC) or low cue (LC) responders based upon lever pressing for previously associated cocaine cues and allowed 10 days of abstinence in their home cages prior to mPFC collection for RNA-sequencing. The expression of 309 genes in the mPFC was significantly different in HC vs. LC rats. Functional gene enrichment analyses identified ten biological processes that were overrepresented in the mPFC of HC vs. LC rats. The present study identifies distinctions in mPFC mRNA transcripts that characterizes individual differences in relapse-like behavior and provides prioritized candidates for future pharmacotherapeutics aimed to help maintain abstinence in CUD. In particular the Htr2c gene, which encodes the serotonin 5-HT2C receptor (5-HT2CR), is expressed to a lower extent in HC rats, relative to LC rats. These findings build on a plethora of previous studies that also point to the 5-HT2CR as an attractive target for the treatment of CUD.
Yao medicine Amydrium hainanense suppresses hepatic fibrosis by repressing hepatic stellate cell activation via STAT3 signaling
Authors: Wu Bingmin , Huang Lan , Wang Yange , Zeng Lishan , Lin Ying , Li Jingyan , Wang Shaogui , Zhang Guifang , An Lin
Published: December 2022

Ethnopharmacological relevance: Hepatic fibrosis (HF) occurs in response to chronic liver injury and may easily develop into irreversible liver cirrhosis or even liver cancer. Amydrium hainanense water extract (AHWE) is a water-soluble component extracted from the Yao medicine Amydrium hainanense (H.Li, Y.Shiao & S.L.Tseng) H.Li, which is commonly used for treating inflammatory diseases in folk. Previous evidence suggested that AHWE significantly inhibited hepatic stellate cell activation. However, little is known regarding the therapeutic effect of AHWE in HF and its underlying action mechanism.

Objective: Investigation of the therapeutic effect of AHWE in HF and its underlying mechanism.

Methods: The therapeutic effect of AHWE was tested in vivo using an HF mouse model via an intraperitoneal injection of carbon tetrachloride (CCl4). Histological evaluation of liver injury and fibrosis were tested by H&E staining and Masson’s trichrome staining. Serum levels of ALT, AST, collagen type I (Col I), and hydroxyproline (HYP) were measured. The mRNA expression of liver fibrotic and inflammatory genes were tested, and the protein levels of alpha smooth muscle actin (α-SMA) and signal transducers and activators of transcription 3 (STAT3) were analyzed. The in vitro experiments were conducted using HSC-T6 and RAW264.7 cell lines.

Results: Treatment with AHWE significantly reversed histopathological liver damage and liver function abnormalities in CCl4 mouse model. Also, the serum levels of ALT, AST, Col I, and HYP in CCl4-induced HF mice were improved in AHWE treatment. Further, AHWE showed a remarkable inhibitory effect on the expression of fibrosis markers (Acta2, Col1a1, and Col3a1) and inflammatory factors (Stat3, Tnfa, Il6, and Il1b) induced by CCl4. The results of in vitro experiments were consistent with those obtained in vivo. In addition, it is shown that STAT3 signaling was involved in the anti-fibrotic effects of AHWE as evidenced by STAT3 overexpression.

Conclusion: The present study proposed a novel ethnomedicine for HF and suggested the underlying role of STAT3 signaling pathway regulation in this anti-fibrotic effect of the proposed medicine. These findings would serve as solid scientific evidence in support of the development of AHWE as a novel alternative or complementary therapy for HF prevention and treatment.
Characterization of the acetylation of cyclooxygenase-isozymes and targeted lipidomics of eicosanoids in serum and colon cancer cells by the new aspirin formulation IP1867B versus aspirin in vitro
Authors: Hofling Ulrika , Tacconelli Stefania , Contursi Annalisa , Bruno Annalisa , Mucci Matteo , Ballerini Patrizia , Cohen Simon , Patrignani Paola
Published: December 2022

Background: Aspirin(acetylsalicylic acid, ASA) is recommended for the secondary prevention of atherothrombotic events and has shown anticancer effects. The current enteric-coated drug formulation may reduce aspirin bioavailability. Liquid formulations could improve aspirin pharmacokinetics and pharmacodynamics. IP1867B is a liquid-aspirin formulation that combines three ingredients, ASA/triacetin/saccharin.

Methods: ASA and IP1867B(L-ASA) were assessed in human serum(obtained by allowing to clot human whole blood at 37 °C for 1h), washed platelets, and colonic adenocarcinoma HCA7 cells on eicosanoid generation and COX-isozyme acetylation at Serine529 and 516 by LC-MS/MS.

Results: In serum, ASA and L-ASA acted by selectively affecting COX-1-derived eicosanoids, including thromboxane(TX)B2. L-ASA was more potent in inhibiting serum TXB2, a known biomarker of aspirin antiplatelet effect, than ASA. However, ASA and L-ASA were equipotent to acetylate COX-1 in washed platelets and COX-2 in HCA7 cells. In HCA7 cells, ASA and L-ASA acted by inhibiting prostaglandin(PG)E2(the most abundant prostanoid) and TXB2 biosynthesis. In the presence of a high arachidonic acid concentration(100 μM), 15R-hydroxyeicosatetraenoic acid(HETE) was generated at baseline by cancer cell COX-2 and was only slightly enhanced by supratherapeutic concentrations of ASA(1 mM). In whole blood and HCA7 cells treated with ASA or L-ASA, 15-epi-lipoxin(LX)A4 were undetectable.

Conclusion: IP1867B was more potent in affecting serum TXB2 generation than ASA. The relevance of this finding deserves evaluation in vivo in humans. In cancer cells, ASA and IP1867B acted by inhibiting PGE2 and TXB2 generation via the acetylation of COX-2. ASA and IP867B at clinically relevant concentrations did not substantially induce the biosynthesis of 15R-HETE and 15-epi-LXA4.
Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma
Authors: Zhou Zheng , Zhou Yusong , Liu Dongbo , Yang Qingping , Tang Mengjie , Liu Wei
Published: December 2022

Hepatocellular carcinoma (HCC) is one of the world’s malignant tumors with high morbidity and mortality. Cuproptosis is a novel form of cell death. However, the prognostic evaluation and immune relevance of cuproptosis-related genes (CRGs) in HCC are largely unknown. In our study, we constructed a prognostic model of CRGs in HCC and performed immune infiltration, functional analysis, immune checkpoint and drug sensitivity analysis. Systematically elaborated the prognostic and immune correlation of CRGs in HCC. The results showed that 15 CRGs were up-regulated or down-regulated in HCC, and the mutation frequency of CRGs reached 10.33% in HCC, with CDKN2A having the highest mutation frequency. These 19 CRGs were mainly involved in the mitochondrion, immune response and metabolic pathways. Five selected genes (CDKN2A, DLAT, DLST, GLS, PDHA1) were involved in constructing a prognostic CRGs model that enables the overall survival in HCC patients to be predicted with moderate to high accuracy. Prognostic CRGs, especially CDKN2A, the independent factor of HCC prognosis, may be closely associated with immune-cell infiltration, tumor mutation burden (TMB), microsatellite instability(MSI), and immune checkpoints. CD274, CTLA4, LAG3, PDCD1, PDCD1LG2 and SIGLEC15 may be identified as potential therapeutic targets and CD274 correlated highly with prognostic genes. Quantitative Real-Time PCR (qRT-PCR) and immunohistochemical were performed to validate the mRNA and protein expression levels of CDKN2A in adjacent normal tissues and HCC tissues, and the results were consistent with gene difference analysis. In conclusion, CRGs, especially CDKN2A, may serve as potential prognostic predictors in HCC patients and provide novel insights into cancer therapy.
A novel deep learning segmentation model for organoid-based drug screening
Authors: Wang Xiaowen , Wu Chunyue , Zhang Shudi , Yu Pengfei , Li Lu , Guo Chunming , Li Rui
Published: December 2022

Organoids are self-organized three-dimensional in vitro cell cultures derived from stem cells. They can recapitulate organ development, tissue regeneration, and disease progression and, hence, have broad applications in drug discovery. However, the lack of effective graphic algorithms for organoid growth analysis has slowed the development of organoid-based drug screening. In this study, we take advantage of a bladder cancer organoid system and develop a deep learning model, the res-double dynamic conv attention U-Net (RDAU-Net) model, to improve the efficiency and accuracy of organoid-based drug screenings. In this RDAU-Net model, the dynamic convolution and attention modules are integrated. The feature-extracting capability of the encoder and the utilization of multi-scale information are substantially enhanced, and the semantic gap caused by skip connections has been filled, which substantially improved its anti-interference ability. A total of 200 images of bladder cancer organoids on culture days 1, 3, 5, and 7, with or without drug treatment, were employed for training and testing. Compared with the other variations of the U-Net model, the segmentation indicators, such as Intersection over Union and dice similarity coefficient, in the RDAU-Net model have been improved. In addition, this algorithm effectively prevented false identification and missing identification, while maintaining a smooth edge contour of segmentation results. In summary, we proposed a novel method based on a deep learning model which could significantly improve the efficiency and accuracy of high-throughput drug screening and evaluation using organoids.
Efficacy and safety of traditional Chinese medicine external washing in the treatment of postoperative wound of diabetes complicated with anal fistula: Study protocol of a randomized, double-blind, placebo-controlled, multi-center clinical trial
Authors: Kang Jian , Liu Ya , Peng Sihan , Tang Xiao , Liu Lu , Xie Ziyan , He Yuchi , Zhang Xiyu
Published: December 2022

Introduction: Anal fistula is one of the commonest ailments seen by anorectal surgeons as surgery is currently the preferred treatment for it. Diabetes mellitus is a risk factor that can lead to slow wound healing after anal fistula surgery. Because of the large postoperative wound surface of anal fistula, patients with diabetes can have an increased probability of wound infection, which makes it hard to heal. There is an extensive clinical experience for wound healing in traditional Chinese medicine (TCM). The Jiedu Shengji decoction (JSD) is a widely used external washing decoction in clinical practice. However, the current evidence on it is still insufficient. Therefore, we report this carefully designed clinical trial to assess the efficacy and safety of JSD in the treatment of postoperative wounds in diabetic patients with anal fistula.

Methods and analysis: This study was designed to be a randomized, double-blind, placebo-controlled, multi-center clinical trial. There were 60 eligible participants who were randomized at a 1:1 ratio to the intervention and placebo groups. Both groups received the same standard treatment. The intervention group was given external washing decoction of TCM (JSD), while the placebo group was given the placebo made of excipients and flavoring agents. The main outcome measures include wound healing, distribution of wound pathogens, levels of inflammatory mediators, and blood glucose. The secondary outcome measures included lipids, the quality of the life evaluation scale (Short-Form Health Survey 36). Assessments were performed before the start of the study, at 1st, 2nd, 3rd, and 4th weeks after the intervention, and at 8th, 12th, and 16th follow-up weeks.

Discussion: The clinical study we proposed will be the first randomized, double-blind, placebo-controlled, multi-center clinical trial study to assess the efficacy and safety of TCM external washing (JSD) in the treatment of postoperative wounds in diabetic patients with anal fistula.

Ethics and dissemination: The Medical Ethics Committee of Hospital of Chengdu University of Traditional Chinese Medicine has reviewed this study protocol and gave its approval and consent on 17 March, 2022 (Ethical Review Number: 2022KL-018).
Analytical results of the k-core pruning process on multiplex networks
Authors: Wu Rui-Jie , Kong Yi-Xiu , Zhang Yi-Cheng , Shi Gui-Yuan
Published: December 2022

Multiplex networks are generally considered as networks that have the same set of vertices but different types of edges. Multiplex networks are especially useful when describing systems with several kinds of interactions. In this paper, we study the analytical solution of the k-core pruning process on multiplex networks. k-Core decomposition is a widely used method to find the dense core of the network. Previously, the Non-Backtracking Expansion Branch (NBEB) has been found to be able to easily derive the exact analytical results in the k-core pruning process. Here, we further extend this method to solve the k-core pruning process on multiplex networks by designing a variation of the method called the Multicolor Non-Backtracking Expansion Branch (MNEB). Our results show that, given any uncorrelated multiplex network, the Multicolor Non-Backtracking Expansion Branch can offer the exact solution for each intermediate state of the pruning process.
The ethics of diversity, equity, inclusion, and justice in the earth system sciences
Authors: Burt Melissa A. , Haacker Rebecca , Montaño Patricia , Vara Marissa , Sloan Valerie
Published: December 2022

Institutions’ motivations for pursuing diversity, equity, inclusion and justice (DEIJ) often center on the benefits to the organization, an argument known as the business case for diversity in which diverse teams are more creative, set high bars for research, and produce ideas that are more innovative than those produced by homogeneous groups. As the sole motivation for DEIJ efforts, the business case is flawed and does not address the harmful workplaces many marginalized scholars encounter. Institutions can make more progress towards diversifying the STEM workforce by acknowledging the ethical responsibilities for doing so and transitioning to an equity-centered approach. Emphasizing personal motivations to actively engage in DEIJ work resonates with individuals more, rather than engaging with DEIJ to benefit an institution’s goals. Two recent studies support this argument. The first is an alumni survey and focus groups of postdoctoral fellows in the Advanced Studies Program at the National Center for Atmospheric Research to explore alumni efforts and motivations for engaging in DEIJ work. The second study surveyed attitudes towards DEIJ efforts among STEM graduate students at Colorado State University who took a course on social responsibility in science. Both studies show the motivations for scientists to support and get involved in these efforts and indicate that the business case is misaligned with the motivations of students and professionals in STEM. Understanding the attitudes and motivations that individuals have for DEIJ in STEM presents an opportunity for how institutions can best learn from and support these motivations for systemic change.
Exaggerated blood pressure response to static exercise in hindlimb ischemia-reperfusion
Authors: Qin Lu , Li Jianhua
Published: December 2022

Peripheral artery disease (PAD) reduces the blood flow supply in the affected limbs as one of the significant cardiovascular concerns. Revascularization surgery in the femoral artery plays a central role in treating PAD. Exercise is also a rehabilitation strategy suggested for PAD patients to improve vascular functions. However, the effects of limb ischemia-reperfusion (IR), one of the most predominant complications in revascularization surgery, on exercise-induced arterial blood pressure (BP) response are poorly understood. In the present study, we determined 1) the blood flow status in the hindlimb muscles of rats (plantar muscle, red and white portions of gastrocnemius) with different time points of the hindlimb IR; and 2) the BP response to static muscle contraction in rats at different time points after the blood flow reperfusion procedure. Results of this study indicated that, compared with the Sham group, the blood flow in the hindlimb muscles evaluated by Evans blue concentration was significantly reduced at 6 h of femoral artery occlusion (FAO 6 h) (vs. sham control, p < 0.05). The decreased blood flow was gradually recovered after the blood flow reperfusion for 18 (IR 18 h), 66 (IR 66 h), and 114 (IR 114 h) hours (p < 0.05 vs. FAO 6 h for all IR groups). The response of mean arterial pressure was 20 ± 4 mmHg in Sham rats (n = 7); 32 ± 10 mmHg in IR 18 h rats (n = 10); 27 ± 7 mmHg in IR 66 h rats (n = 13); 26 ± 4 mmHg in IR 114 h rats (n = 9) (p < 0.05 vs. Sham for all groups). No significant difference was observed in the peak-developed tension during muscle contraction among all the groups (p > 0.05). In conclusion, static exercise-induced BP response is exaggerated following IR. Whereas the BP response is not statistically significant but tends to decrease with a prolonged IR time, the exaggerated BP response remains through time points from post-IR 18 h–114 h.
Evolution of casein kinase 1 and functional analysis of new doubletime mutants in Drosophila
Authors: Thakkar Nirav , Giesecke Astrid , Bazalova Olga , Martinek Jan , Smykal Vlastimil , Stanewsky Ralf , Dolezel David
Published: December 2022

Circadian clocks are timing devices that rhythmically adjust organism’s behavior, physiology, and metabolism to the 24-h day-night cycle. Eukaryotic circadian clocks rely on several interlocked transcription-translation feedback loops, where protein stability is the key part of the delay between transcription and the appearance of the mature proteins within the feedback loops. In bilaterian animals, including mammals and insects, the circadian clock depends on a homologous set of proteins. Despite mostly conserved clock components among the fruit fly Drosophila and mammals, several lineage-specific differences exist. Here we have systematically explored the evolution and sequence variability of insect DBT proteins and their vertebrate homologs casein kinase 1 delta (CKIδ) and epsilon (CKIε), dated the origin and separation of CKIδ from CKIε, and identified at least three additional independent duplications of the CKIδ/ε gene in Petromyzon, Danio, and Xenopus. We determined conserved regions in DBT specific to Diptera, and functionally tested a subset of those in D. melanogaster. Replacement of Lysine K224 with acidic residues strongly impacts the free-running period even in heterozygous flies, whereas homozygous mutants are not viable. K224D mutants have a temperature compensation defect with longer free-running periods at higher temperatures, which is exactly the opposite trend of what was reported for corresponding mammalian mutants. All DBTs of dipteran insects contain the NKRQK motif at positions 220–224. The occurrence of this motif perfectly correlates with the presence of BRIDE OF DOUBLETIME, BDBT, in Diptera. BDBT is a non-canonical FK506-binding protein that physically interacts with Drosophila DBT. The phylogeny of FK506-binding proteins suggests that BDBT is either absent or highly modified in non-dipteran insects. In addition to in silico analysis of DBT/CKIδ/ε evolution and diversity, we have identified four novel casein kinase 1 genes specific to the Drosophila genus.
Post-pollination sepal longevity of female flower co-regulated by energy-associated multiple pathways in dioecious spinach
Authors: Ma Xiaokai , Fatima Mahpara , Li Jing , Zhou Ping , Zaynab Madiha , Ming Ray
Published: December 2022

Reproductive growth is a bioenergetic process with high energy consumption. Pollination induces female flower longevity in spinach by accelerating sepal retention and development. Cellular bioenergetics involved in cellular growth is at the foundation of all developmental activities. By contrast, how pollination alter the sepal cells bioenergetics to support energy requirement and anabolic biomass accumulation for development is less well understood. To investigate pollination-induced energy-associated pathway changes in sepal tissues after pollination, we utilized RNA-sequencing to identify transcripts that were differentially expressed between unpollinated (UNP) and pollinated flower sepals at 12, 48, and 96HAP. In total, over 6756 non-redundant DEGs were identified followed by pairwise comparisons (i.e. UNP vs 12HAP, UNP vs 48HAP, and UNP vs 96HAP). KEGG enrichment showed that the central carbon metabolic pathway was significantly activated after pollination and governed by pivotal energy-associated regulation pathways such as glycolysis, the citric acid cycle, oxidative phosphorylation, photosynthesis, and pentose phosphate pathways. Co-expression networks confirmed the synergistically regulation interactions among these pathways. Gene expression changes in these pathways were not observed after fertilization at 12HAP, but started after fertilization at 48HAP, and significant changes in gene expression occurred at 96HAP when there is considerable sepal development. These results were also supported by qPCR validation. Our results suggest that multiple energy-associated pathways may play a pivotal regulatory role in post-pollination sepal longevity for developing the seed coat, and proposed an energy pathway model regulating sepal retention in spinach.
Genome-wide analysis of the Tritipyrum WRKY gene family and the response of TtWRKY256 in salt-tolerance
Authors: Li Kuiyin , Liu Xiaojuan , He Fang , Chen Songshu , Zhou Guangyi , Wang Yuhai , Li Luhua , Zhang Suqin , Ren Mingjian , Yuan Yuanyuan
Published: December 2022

Introduction

The transcription factor WRKY is widespread in the plant kingdom and plays a crucial role in diverse abiotic stress responses in plant species. Tritipyrum, an octoploid derived from an intergeneric cross between Triticum aestivum (AABBDD) and Thinopyrum elongatum (EE), is a valuable germplasm resource for introducing superior traits of Th. elongatum into T. aestivum. The recent release of the complete genome sequences of T. aestivum and Th. elongatum enabled us to investigate the organization and expression profiling of Tritipyrum WRKY genes across the entire genome.

Results

In this study, 346 WRKY genes, from TtWRKY1 to TtWRKY346, were identified in Tritipyrum. The phylogenetic analysis grouped these genes into three subfamilies (I-III), and members of the same subfamilies shared a conserved motif composition. The 346 TtWRKY genes were dispersed unevenly across 28 chromosomes, with 218 duplicates. Analysis of synteny suggests that the WRKY gene family may have a common ancestor. Expression profiles derived from transcriptome data and qPCR demonstrated that 54 TtWRKY genes exhibited relatively high levels of expression across various salt stresses and recovery treatments. Tel1E01T143800 (TtWRKY256) is extremely sensitive to salt stress and is on the same evolutionary branch as the salt-tolerant A. thaliana genes AtWRKY25 and AtWRKY33. From 'Y1805', the novel AtWRKY25 was cloned. The Pearson correlation analysis identified 181 genes that were positively correlated (R>0.9) with the expression of TtWRKY256, and these genes were mainly enriched in metabolic processes, cellular processes, response to stimulus, biological regulation, and regulation of biological. Subcellular localization and qRT-PCR analysis revealed that TtWRKY256 was located in the nucleus and was highly expressed in roots, stems, and leaves under salt stress.

Discussion

The above results suggest that TtWRKY256 may be associated with salt stress tolerance in plants and may be a valuable alien gene for improving salt tolerance in wheat.
Identification of a major QTL, Parth6.1 associated with parthenocarpic fruit development in slicing cucumber genotype, Pusa Parthenocarpic Cucumber-6
Authors: Devi Shilpa , Sharma Parva Kumar , Behera Tusar Kanti , Jaiswal Sarika , Boopalakrishnan G. , Kumari Khushboo , Mandal Neha Kumari , Iquebal Mir Asif , Gopala Krishnan S. , Bharti  , Ghosal Chandrika , Munshi Anilabha Das , Dey Shyam Sundar
Published: December 2022

Parthenocarpy is an extremely important trait that revolutionized the worldwide cultivation of cucumber under protected conditions. Pusa Parthenocarpic Cucumber-6 (PPC-6) is one of the important commercially cultivated varieties under protected conditions in India. Understanding the genetics of parthenocarpy, molecular mapping and the development of molecular markers closely associated with the trait will facilitate the introgression of parthenocarpic traits into non-conventional germplasm and elite varieties. The F1, F2and back-crosses progenies with a non-parthenocarpic genotype, Pusa Uday indicated a single incomplete dominant gene controlling parthenocarpy in PPC-6. QTL-seq comprising of the early parthenocarpy and non-parthenocarpic bulks along with the parental lines identified two major genomic regions, one each in chromosome 3 and chromosome 6 spanning over a region of 2.7 Mb and 7.8 Mb, respectively. Conventional mapping using F2:3population also identified two QTLs,Parth6.1andParth6.2in chromosome 6 which indicated the presence of a major effect QTL in chromosome 6 determining parthenocarpy in PPC-6. The flanking markers, SSR01148 and SSR 01012 forParth6.1locus and SSR10476 and SSR 19174 forParth6.2locus were identified and can be used for introgression of parthenocarpy through the marker-assisted back-crossing programme. Functional annotation of the QTL-region identified two major genes,Csa_6G396640andCsa_6G405890designated as probable indole-3-pyruvate monooxygenase YUCCA11 and Auxin response factor 16, respectively associated with auxin biosynthesis as potential candidate genes.Csa_6G396640showed only one insertion at position 2179 in the non-parthenocarpic parent. In the case ofCsa_6G405890, more variations were observed between the two parents in the form of SNPs and InDels. The study provides insight about genomic regions, closely associated markers and possible candidate genes associated with parthenocarpy in PPC-6 which will be instrumental for functional genomics study and better understanding of parthenocarpy in cucumber.
Transcriptomics-based analysis of genes related to lead stress and their expression in the roots of Pogonatherum crinitum
Authors: Zhu Chenlu , Yu Junbao , Cao Shuyi , Wu Xinyi , Meng Weicai , Hou Xiaolong
Published: December 2022

Revealing plants’ tolerance and transport genes to heavy metal stress play an important role in exploring the potential of phytoremediation. Taking the heavy metal lead (Pb) hyperaccumulator plant Pogonatherum crinitum (Thunb.) Kunth as the research object, a hydroponic simulation stress experiment was set up to determine the physiological indicators such as antioxidant enzymes and non-enzymatic antioxidants in the roots of P. crinitum under different Pb concentrations (0, 300, 500, 1000, 2000 mg·L-1). RNA-Seq was performed, the Unigenes obtained by transcriptome sequencing were enriched and annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and the differential expression genes (DEGs) of root were screened and verified by quantitative real-time polymerase chain reaction (qRT-PCR). The results are as follows: with the increase of Pb concentration, superoxide dismutase (SOD), catalase (CAT), and ascorbic acid (AsA) content increased. Peroxidase (POD), malondialdehyde (MDA), and ascorbic acid–glutathione (AsA-GSH) cycles showed low promotion with high inhibition. A total of 38.21 Gb of bases were obtained by transcriptome sequencing, and the base quality of each sample reached Q20 and Q30, accounting for 90%, making the sequencing results reliable. Combined with transcriptome sequencing, functional annotation, and qRT-PCR validation results, 17 root Pb-tolerant genes of P. crinitum were screened out, which were related to antioxidation, transportation, and transcription functions. Moreover, qRT-PCR verification results under different Pb stress concentrations were consistent with the transcriptome sequencing results and changes in physiological indicators. In brief, the root of P. crinitum can adapt to the Pb stress environment by up-regulating the expression of related genes to regulate the physiological characteristics.
Transgenic tobacco plant overexpressing ginkgo dihydroflavonol 4-reductase gene GbDFR6 exhibits multiple developmental defects
Authors: Ni Jun , Zhang Ning , Zhan Yang , Ding Kexin , Qi Peng , Wang Xuejun , Ding Wona , Xu Maojun
Published: December 2022

Dihydroflavonol Q 4-reductase (DFR), a key enzyme in the flavonoid biosynthetic pathway in plants, significantly influences plant survival. However, the roles of DFR in the regulation of plant development are largely unknown. In the present study, phenotypes of transgenic tobacco plants overexpressing the Ginkgo biloba DFR gene, GbDFR6, were investigated. Transgenic tobacco seedlings exhibited relatively low fresh weights, long primary roots, decreased lateral root numbers, and impaired root gravitropic responses when compared to wild-type tobacco plants. Adult transgenic tobacco plants exhibited a considerably high percentage of wrinkled leaves when compared to the wild-type tobacco plants. In addition to the auxin-related phenotypic changes, transgenic tobacco plants exhibited delayed flowering phenotypes under short-day conditions. Gene expression analysis revealed that the delayed flowering in transgenic tobacco plants was caused by the low expression levels of NtFT4. Finally, variations in anthocyanin and flavonoid contents in transgenic tobacco plants were evaluated. The results revealed that the levels of most anthocyanins identified in transgenic tobacco leaves increased. Specifically, cyanidin-3,5-O-diglucoside content increased by 9.8-fold in transgenic tobacco plants when compared to the wild-type tobacco plants. Pelargonidin-3-O-(coumaryl)-glucoside was only detected in transgenic tobacco plants. Regarding flavonoid compounds, one flavonoid compound (epicatechin gallate) was upregulated, whereas seven flavonoid compounds (Tamarixetin-3-O-rutinoside; Sexangularetin-3-O-glucoside-7-O-rhamnoside; Kaempferol-3-O-neohesperidoside; Engeletin; 2’-Hydoxy,5-methoxyGenistein-O-rhamnosyl-glucoside; Diosmetin; Hispidulin) were downregulated in both transgenic tobacco leaves and roots. The results indicate novel and multiple roles of GbDFR6 in ginkgo and provide a valuable method to produce a late flowering tobacco variety in tobacco industry.
Combining physical and virtual worlds for motor-cognitive training interventions: Position paper with guidelines on technology classification in movement-related research
Authors: Šlosar Luka , Voelcker-Rehage Claudia , Paravlić Armin H. , Abazovic Ensar , de Bruin Eling D. , Marusic Uros
Published: December 2022

Efficient movements require intact motor and cognitive function. There is a growing literature on motor-cognitive interventions to improve the overall quality of life of healthy or diseased older people. For such interventions, novel technological advances are crucial not only in terms of motivation but also to improve the user experience in a multi-stimuli world, usually offered as a mixture of real and virtual environments. This article provides a classification system for movement-related research dealing with motor-cognitive interventions performed in different extents of a virtual environment. The classification is divided into three categories: (a) type of digital device with the associated degree of immersiveness provided; (b) presence or absence of a human-computer interaction; and (c) activity engagement during training, defined by activity >1.5 Metabolic Equivalent of task. Since virtual reality (VR) often categorizes different technologies under the same term, we propose a taxonomy of digital devices ranging from computer monitors and projectors to head-mounted VR technology. All immersive technologies that have developed rapidly in recent years are grouped under the umbrella term Extended Reality (XR). These include augmented reality (AR), mixed reality (MR), and VR, as well as all technologies that have yet to be developed. This technology has potential not only for gaming and entertainment, but also for research, motor-cognitive training programs, rehabilitation, telemedicine, etc. This position paper provides definitions, recommendations, and guidelines for future movement-related interventions based on digital devices, human-computer interactions, and physical engagement to use terms more consistently and contribute to a clearer understanding of their implications.
More income, less depression? Revisiting the nonlinear and heterogeneous relationship between income and mental health
Authors: Li Chao , Ning Guangjie , Wang Lin , Chen Feier
Published: December 2022

This paper uses a large-scale nationally representative dataset to examine the nonlinear effect of income on mental health. To investigate their causal relationship, the exogenous impact of automation on income is utilized as the instrument variable (IV). In addition, to explore their nonlinear relationship, both income and its quadratic term are included in regressions. It is found that the impact of income on mental health is U-shaped rather than linear. The turning point (7.698) of this nonlinear relation is near the midpoint of the income interval ([0, 16.113]). This suggests that depression declines as income increases at the lower-income level. However, beyond middle income, further increases in income take pronounced mental health costs, leading to a positive relationship between the two factors. We further exclude the possibility of more complex nonlinear relationships by testing higher order terms of income. In addition, robustness checks, using other instrument variables and mental health indicators, different IV models and placebo analysis, all support above conclusions. Heterogeneity analysis demonstrates that males, older workers, ethnic minorities and those with lower health and socioeconomic status experience higher levels of depression. Highly educated and urban residents suffer from greater mental disorders after the turning point. Religious believers and Communist Party of China members are mentally healthier at lower income levels, meaning that religious and political beliefs moderate the relationship between income and mental health.
“Double awareness”—adolescents and young adults coping with an uncertain or poor cancer prognosis: A qualitative study
Authors: Burgers Vivian W. G. , van den Bent Martin J. , Rietjens Judith A. C. , Roos Daniëlle C. , Dickhout Annemiek , Franssen Suzanne A. , Noordoek Marloes J. , van der Graaf Winette T. A. , Husson Olga
Published: December 2022

Introduction

Adolescents and young adults with an uncertain or poor cancer prognosis (UPCP) are confronted with ongoing and unique age-specific challenges, which forms an enormous burden. To date, little is known about the way AYAs living with a UPCP cope with their situation. Therefore, this study explores how AYAs with a UPCP cope with the daily challenges of their disease.

Method

We conducted semi-structured in-depth interviews among AYAs with a UPCP. Patients of the three AYA subgroups were interviewed (traditional survivors, new survivors, low-grade glioma survivors), since we expected different coping strategies among these subgroups. Interviews were analyzed using elements of the Grounded Theory by Corbin and Strauss. AYA patients were actively involved as research partners.

Results

In total 46 AYAs with UPCP participated, they were on average 33.4 years old (age range 23–44) and most of them were woman (63%). Most common tumor types were low-grade gliomas (16), sarcomas (7), breast cancers (6) and lung cancers (6). We identified seven coping strategies in order to reduce the suffering from the experienced challenges: (1) minimizing impact of cancer, (2) taking and seeking control, (3) coming to terms, (4) being positive, (5) seeking and receiving support, (6) carpe diem and (7) being consciously alive.

Conclusion

This study found seven coping strategies around the concept of ‘double awareness’ and showcases that AYAs are able to actively cope with their disease but prefer to actively choose life over illness. The findings call for CALM therapy and informal AYA support meetings to support this group to cope well with their disease.