bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Cortical Stimulation to Probe the Ictogenicity of the Epileptogenic Nodes in Temporal Lobe Epilepsy
Authors: Irannejad Auriana , Chaitanya Ganne , Toth Emilia , Pizarro Diana , Pati Sandipan
Published: January 2022

Accurate mapping of the seizure onset zone (SOZ) is critical to the success of epilepsy surgery outcomes. Epileptogenicity index (EI) is a statistical method that delineates hyperexcitable brain regions involved in the generation and early propagation of seizures. However, EI can overestimate the SOZ for particular electrographic seizure onset patterns. Therefore, using direct cortical stimulation (DCS) as a probing tool to identify seizure generators, we systematically evaluated the causality of the high EI nodes (>0.3) in replicating the patient's habitual seizures. Specifically, we assessed the diagnostic yield of high EI nodes, i.e., the proportion of high EI nodes that evoked habitual seizures. A retrospective single-center study that included post-stereo encephalography (SEEG) confirmed TLE patients (n = 37) that had all high EI nodes stimulated, intending to induce a seizure. We evaluated the nodal responses (true and false responder rate) to stimulation and correlated with electrographic seizure onset patterns (hypersynchronous-HYP and low amplitude fast activity patterns-LAFA) and clinically defined SOZ. The ictogenicity (i.e., the propensity to induce the patient's habitual seizure) of a high EI node was only 44.5%. The LAFA onset pattern had a significantly higher response rate to DCS (i.e., higher evoked seizures). The concordance of an evoked habitual seizure with a clinically defined SOZ with good outcomes was over 50% (p = 0.0025). These results support targeted mapping of SOZ in LAFA onset patterns by performing DCS in high EI nodes to distinguish seizure generators (true responders) from hyperexcitable nodes that may be involved in early propagation.
Diagnostic Developments in Differentiating Unresponsive Wakefulness Syndrome and the Minimally Conscious State
Authors: Porcaro Camillo , Nemirovsky Idan Efim , Riganello Francesco , Mansour Zahra , Cerasa Antonio , Tonin Paolo , Stojanoski Bobby , Soddu Andrea
Published: January 2022

When treating patients with a disorder of consciousness (DOC), it is essential to obtain an accurate diagnosis as soon as possible to generate individualized treatment programs. However, accurately diagnosing patients with DOCs is challenging and prone to errors when differentiating patients in a Vegetative State/Unresponsive Wakefulness Syndrome (VS/UWS) from those in a Minimally Conscious State (MCS). Upwards of ~40% of patients with a DOC can be misdiagnosed when specifically designed behavioral scales are not employed or improperly administered. To improve diagnostic accuracy for these patients, several important neuroimaging and electrophysiological technologies have been proposed. These include Positron Emission Tomography (PET), functional Magnetic Resonance Imaging (fMRI), Electroencephalography (EEG), and Transcranial Magnetic Stimulation (TMS). Here, we review the different ways in which these techniques can improve diagnostic differentiation between VS/UWS and MCS patients. We do so by referring to studies that were conducted within the last 10 years, which were extracted from the PubMed database. In total, 55 studies met our criteria (clinical diagnoses of VS/UWS from MCS as made by PET, fMRI, EEG and TMS- EEG tools) and were included in this review. By summarizing the promising results achieved in understanding and diagnosing these conditions, we aim to emphasize the need for more such tools to be incorporated in standard clinical practice, as well as the importance of data sharing to incentivize the community to meet these goals.
Stabilometric Correlates of Motor and Motor Imagery Expertise
Authors: Di Rienzo Franck , Joassy Pierric , Ferreira Dias Kanthack Thiago , Moncel François , Mercier Quentin , Collet Christian , Guillot Aymeric
Published: January 2022

Motor Imagery (MI) reproduces cognitive operations associated with the actual motor preparation and execution. Postural recordings during MI reflect somatic motor commands targeting peripheral effectors involved in balance control. However, how these relate to the actual motor expertise and may vary along with the MI modality remains debated. In the present experiment, two groups of expert and non-expert gymnasts underwent stabilometric assessments while performing physically and mentally a balance skill. We implemented psychometric measures of MI ability, while stabilometric variables were calculated from the center of pressure (COP) oscillations. Psychometric evaluations revealed greater MI ability in experts, specifically for the visual modality. Experts exhibited reduced surface COP oscillations in the antero-posterior axis compared to non-experts during the balance skill (14.90%, 95% CI 34.48–4.68, p < 0.05). Experts further exhibited reduced length of COP displacement in the antero-posterior axis and as a function of the displacement area during visual and kinesthetic MI compared to the control condition (20.51%, 95% CI 0.99–40.03 and 21.85%, 95% CI 2.33–41.37, respectively, both p < 0.05). Predictive relationships were found between the stabilometric correlates of visual MI and physical practice of the balance skill, as well as between the stabilometric correlates of kinesthetic MI and the training experience in experts. Present results provide original stabilometric insights into the relationships between MI and expertise level. While data support the incomplete inhibition of postural commands during MI, whether postural responses during MI of various modalities mirror the level of motor expertise remains unclear.
MED10 Drives the Oncogenicity and Refractory Phenotype of Bladder Urothelial Carcinoma Through the Upregulation of hsa-miR-590
Authors: Wu Chia-Chang , Wang Yuan-Hung , Hu Su-Wei , Wu Wen-Ling , Yeh Chi-Tai , Bamodu Oluwaseun Adebayo
Published: January 2022

Background

Dysfunctional transcription machinery with associated dysregulated transcription characterizes many malignancies. Components of the mediator complex, a principal modulator of transcription, are increasingly implicated in cancer. The mediator complex subunit 10 (MED10), a vital kinase module of the mediator, plays a critical role in bladder physiology and pathology. However, its role in the oncogenicity, metastasis, and disease recurrence in bladder cancer (BLCA) remains unclear.

Objective

Thus, we investigated the role of dysregulated or aberrantly expressed MED10 in the enhanced onco-aggression, disease progression, and recurrence of bladder urothelial carcinoma (UC), as well as the underlying molecular mechanism.

Methods

Using an array of multi-omics big data analyses of clinicopathological data, in vitro expression profiling and functional assays, and immunocytochemical staining, we assessed the probable roles of MED10 in the progression and prognosis of BLCA/UC.

Results

Our bioinformatics-aided gene expression profiling showed that MED10 is aberrantly expressed in patients with BLCA, is associated with high-grade disease, is positively correlated with tumor stage, and confers significant survival disadvantage. Reanalyzing the TCGA BLCA cohort (n = 454), we showed that aberrantly expressed MED10 expression is associated with metastatic and recurrent disease, disease progression, immune suppression, and therapy failure. Interestingly, we demonstrated that MED10 interacts with and is co-expressed with the microRNA, hsa-miR-590, and that CRISPR-mediated knockout of MED10 elicits the downregulation of miR-590 preferentially in metastatic UC cells, compared to their primary tumor peers. More so, silencing MED10 in SW1738 and JMSU1 UC cell lines significantly attenuates their cell proliferation, migration, invasion, clonogenicity, and tumorsphere formation (primary and secondary), with the associated downregulation of BCL-xL, MKI67, VIM, SNAI1, OCT4, and LIN28A but upregulated BAX protein expression. In addition, we showed that high MED10 expression is a non-inferior biomarker of urothelial recurrence compared with markers of cancer stemness; however, MED10 is a better biomarker of local recurrence than any of the stemness markers.

Conclusion

These data provide preclinical evidence that dysregulated MED10/MIR590 signaling drives onco-aggression, disease progression, and recurrence of bladder UC and that this oncogenic signal is therapeutically actionable for repressing the metastatic/recurrent phenotypes, enhancing therapy response, and shutting down stemness-driven disease progression and relapse in patients with BLCA/UC.
Knockdown of NAA25 Suppresses Breast Cancer Progression by Regulating Apoptosis and Cell Cycle
Authors: Xu Jingkai , Li Zhi , Zuo Xianbo , Li Guozheng , Zhang Xuejun , Zhang Bo , Cui Yong
Published: January 2022

NAA25 gene variants were reported as risk factors for type 1 diabetes, rheumatoid arthritis and acute arterial stroke. But it’s unknown whether it could contribute to breast cancer. We identified rs11066150 in lncHSAT164, which contributes to breast cancer, in our earlier genome-wide long non-coding RNA association study on Han Chinese women. However, rs11066150 A/G variant is also located in NAA25 intron. Based on the public database, such as TCGA and Curtis dataset, NAA25 gene is highly expressed in breast cancer tissues and this result has also been proved in our samples and cell lines through RT-qPCR and western blot analysis. To better understand the function of NAA25 in breast cancer, we knocked down the expression of NAA25 in breast cancer cell lines, FACS was used to detect cell apoptosis and cell cycle and colony formation assay was used to detect cell proliferation. We found that NAA25-deficient cells could increase cell apoptosis, delay G2/M phase cell and decrease cell clone formation. RNA sequencing was then applied to analyze the molecular profiles of NAA25−deficient cells, and compared to the control group, NAA25 knockdown could activate apoptosis-related pathways, reduce the activation of tumor-associated signaling pathways and decrease immune response-associated pathways. Additionally, RT-qPCR was employed to validate these results. Taken together, our results revealed that NAA25 was highly expressed in breast cancer, and NAA25 knockdown might serve as a therapeutic target in breast cancer.
Real-Time Elastography: A Web-Based Nomogram Improves the Preoperative Prediction of Central Lymph Node Metastasis in cN0 PTC
Authors: Huang Chunwang , Yan Wenxiao , Zhang Shumei , Wu Yanping , Guo Hantao , Liang Kunming , Xia Wuzheng , Cong Shuzhen
Published: January 2022

Background

Given the difficulty of accurately determining the central lymph node metastasis (CLNM) status of patients with clinically node-negative (cN0) papillary thyroid carcinoma (PTC) before surgery, this study aims to combine real-time elastography (RTE) and conventional ultrasound (US) features with clinical features. The information is combined to construct and verify the nomogram to foresee the risk of CLNM in patients with cN0 PTC and to develop a network-based nomogram.

Methods

From January 2018 to February 2020, 1,157 consecutive cases of cN0 PTC after thyroidectomy and central compartment neck dissection were retrospectively analyzed. The patients were indiscriminately allocated (2:1) to a training cohort (771 patients) and validation cohort (386 patients). Multivariate logistic regression analysis of US characteristics and clinical information in the training cohort was performed to screen for CLNM risk predictors. RTE data were included to construct prediction model 1 but were excluded when constructing model 2. DeLong’s test was used to select a forecast model with better receiver operator characteristic curve performance to establish a web-based nomogram. The clinical applicability, discrimination, and calibration of the preferable prediction model were assessed.

Results

Multivariate regression analysis showed that age, sex, tumor size, bilateral tumors, the number of tumor contacting surfaces, chronic lymphocytic thyroiditis, and RTE were risk predictors of CLNM in cN0 PTC patients, which constituted prediction model 1. Model 2 included the first six risk predictors. Comparison of the areas under the curves of the two models showed that model 1 had better prediction performance (training set 0.798 vs. 0.733, validation set 0.792 vs. 0.715, p < 0.001) and good discrimination and calibration. RTE contributed significantly to the performance of the prediction model. Decision curve analysis showed that patients could obtain good net benefits with the application of model 1.

Conclusion

A noninvasive web-based nomogram combining US characteristics and clinical risk factors was developed in the research. RTE could improve the prediction accuracy of the model. The dynamic nomogram has good performance in predicting the probability of CLNM in cN0 PTC patients.
HIPK3 Inhibition by Exosomal hsa-miR-101-3p Is Related to Metabolic Reprogramming in Colorectal Cancer
Authors: Tao Lihuiping , Xu Changliang , Shen Weixing , Tan Jiani , Li Liu , Fan Minmin , Sun Dongdong , Lai Yueyang , Cheng Haibo
Published: January 2022

Background

Exosomes are extracellular vesicles secreted by most cells to deliver functional cargoes to recipient cells. MicroRNAs (miRNAs) constitute a significant part of exosomal contents. The ease of diffusion of exosomes renders them speedy and highly efficient vehicles to deliver functional molecules. Cancer cells secrete more exosomes than normal cells. Reports have showed that exosomal miRNAs of cancer cells facilitate cancer progression. Yet the complexity of cancer dictates that many more functional exosomal miRNAs remain to be discovered.

Methods

In this study, we analyzed miRNA expression profiles of tissue and plasma exosome samples collected from 10 colorectal cancer (CRC) patients and 10 healthy individuals. We focused on hsa-miR-101-3p (101-3p), a profoundly up-regulated miRNA enriched in plasma exosomes of patients bearing CRC. We performed target analysis of 101-3p and pursued functional studies of this microRNA in two colorectal cancer cell lines, namely HCT116 and SW480.

Results

Our results indicated that inhibiting 101-3p slowed cell growth and retarded cell migration in vivo in two colorectal cancer cell lines. Target analysis showed that Homeodomain-interacting protein kinase (HIPK3) is a target of miR-101-3p. HCT116 and SW480 cells stably overexpressing HIPK3 showed increased level of phosphorylated FADD, as well as retarded cell growth, migration, and increased sensitivity to 5-FU. In-depth analysis revealed increased mitochondrial membrane potential upon HIPK3 overexpression along with increased production of reactive oxygen species, number of mitochondria, and expression of respiratory complexes. Measurements of glycolytic parameters and enzymes revealed decreased level of glycolysis upon HIPK3 overexpression in these two cell lines. Xenograft model further confirmed a profoundly improved potency of the synergistic treatment combining both 5-FU and 101-3p inhibitor compared to 5-FU alone.

Conclusion

This study unraveled an oncogenic nature of the exosomal 101-3p and suggested a relationship between the 101-3p-HIPK3 axis and metabolic homeostasis in colorectal cancer. Expression level of 101-3p is positively correlated with glycolytic capacity in CRC and therefore 101-3p itself is an oncomiR. Combining 101-3p inhibitor with chemotherapeutic agents is an effective strategy against CRC.
Decreased Expression of ACADSB Predicts Poor Prognosis in Clear Cell Renal Cell Carcinoma
Authors: Liu Xianhui , Zhang Weiyu , Wang Huanrui , Zhu Lin , Xu Kexin
Published: January 2022

Background

Previous reports have shown that short/branched chain acyl-CoA dehydrogenase (ACADSB) plays an important role in glioma, but its role in clear cell renal carcinoma (ccRCC) has not been reported.

Methods

The TIMER and UALCAN databases were used for pan-cancer analysis. RNA sequencing and microarray data of patients with ccRCC were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus database. The differential expression of ACADSB in ccRCC and normal kidney tissues was tested. Correlations between ACADSB expression and clinicopathological parameters were assessed using the Wilcoxon test. The influences of ACADSB expression and clinicopathological parameters on overall survival were assessed using Cox proportional hazards models. Gene set enrichment analysis (GSEA) was performed to explore the associated gene sets enriched in different ACADSB expression phenotypes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on genes with similar expression patterns to ACADSB. Correlations between ACADSB and ferroptosis-related genes were assessed using Spearman’s correlation analysis.

Results

Pan-cancer analysis revealed that ACADSB is down-regulated in multiple cancers, and decreased expression of ACADSB correlates with poor prognosis in certain types of cancer. Differential expression analyses revealed that ACADSB was down-regulated in ccRCC, indicating that ACADSB expression could be a single significant parameter to discriminate between normal and tumor tissues. Clinical association analysis indicated that decreased ACADSB expression was associated with high tumor stage and grade. The Cox regression model indicated that low ACADSB expression was an independent risk factor for the overall survival of patients with ccRCC. GSEA showed that 10 gene sets, including fatty acid (FA) metabolism, were differentially enriched in the ACADSB high expression phenotype. GO and KEGG pathway enrichment analysis revealed that ACADSB-related genes were significantly enriched in categories related to FA metabolism, branched-chain amino acid (BCAA) metabolism, and iron regulation. Spearman’s correlation analysis suggested that the expression of ACADSB was positively correlated with the expression of ferroptosis driver genes.

Conclusions

ACADSB showed good diagnostic and prognostic abilities for ccRCC. The downregulation of ACADSB might promote tumorigenesis and tumor progression by inhibiting FA catabolism, BCAA catabolism, and ferroptosis in ccRCC.
FAM21C Promotes Hepatocellular Carcinoma Invasion and Metastasis by Driving Actin Cytoskeleton Remodeling via Inhibiting Capping Ability of CAPZA1
Authors: Lu Yao , Huang Deng , Wang Baolin , Zheng Bowen , Liu Jialong , Song Juxian , Zheng Shuguo
Published: January 2022

Hepatocellular carcinoma (HCC) is characterized by a high incidence of metastasis. The dynamic remodeling of the actin cytoskeleton plays an important role in the invasion and migration of HCC cells. In previous studies, we found that CAPZA1, a capping protein, can promote EMT of HCC cells by regulating the remodeling of the actin filament (F-actin) cytoskeleton, thus promoting the invasion and migration of HCC cells. In this study, we found that FAM21C may have a regulatory effect on CAPZA1, and we conducted an in-depth study on its potential regulatory mechanism. First, we found that FAM21C is highly expressed in HCC tissues and its high expression could promote the malignant progression of HCC. Meanwhile, the high expression of FAM21C promoted the invasion and migration of HCC cells in vitro and in vivo. Further, FAM21C interacted with CAPZA1, and their binding inhibited the capping capacity of CAPZA1, thus promoting the invasion and migration of HCC cells. This effect of FAM21C was abolished by mutating the CP-interacting (CPI) domain, the CAPZA1 binding site on FAM21C. In conclusion, high expression of FAM21C in HCC tissues can promote malignant progression of HCC and its potential mechanism involves FAM21C inhibition of CAPZA1 capping capacity by binding to CAPZA1, which drives F-actin cytoskeleton remodeling, and thus promotes invasion and migration of HCC cells.
Long Non-Coding RNA CD27-AS1-208 Facilitates Melanoma Progression by Activating STAT3 Pathway
Authors: Ma Jingjing , Shi Qiong , Guo Sen , Xu Peng , Yi Xiuli , Yang Yuqi , Zhang Weigang , Liu Yu , Liu Lin , Yue Qiao , Zhao Tao , Gao Tianwen , Guo Weinan , Li Chunying
Published: January 2022

Melanoma is the most lethal skin cancer that originates from epidermal melanocytes. Recently, long non-coding RNAs (lncRNAs) are emerging as critical regulators of cancer pathogenesis and potential therapeutic targets. However, the expression profile of lncRNAs and their role in melanoma progression have not been thoroughly investigated. Herein, we firstly obtained the expression profile of lncRNAs in primary melanomas using microarray analysis and unveiled the differentially-expressed lncRNAs compared with nevus. Subsequently, a series of bioinformatics analysis showed the great involvement of dysregulated lncRNAs in melanoma biology and immune response. Further, we identified lncRNA CD27-AS1-208 as a novel nuclear-localized factor with prominent facilitative role in melanoma cell proliferation, invasion and migration. Mechanistically, CD27-AS1-208 could directly interact with STAT3 and contribute to melanoma progression in a STAT3-dependent manner. Ultimately, the role of CD27-AS1-208 in melanoma progression in vivo was also investigated. Collectively, the present study offers us a new horizon to better understand the role of lncRNAs in melanoma pathogenesis and demonstrates that CD27-AS1-208 up-regulation contributes to melanoma progression by activating STAT3 pathway. Targeting CD27-AS1-208 in melanoma cells can be exploited as a potential therapeutic approach that needs forward validation in clinical trials in the future.
“Double-Hit” Chronic Lymphocytic Leukemia, Involving the TP53 and MYC Genes
Authors: Nguyen-Khac Florence
Published: January 2022

Although the 17p deletion [del(17p)] is rare in cases of treatment-naive chronic lymphocytic leukemia (CLL), its frequency is higher in refractory/relapsed CLL – particularly in patients undergoing chemo(immuno)therapy. TP53 disruption (deletion and/or mutation) is the strongest prognostic factor for refractoriness to chemotherapy; the use of Bruton tyrosine kinase inhibitors and BCL2 inhibitors is then indicated. Rare cases of CLL can also harbor translocation or gain of the MYC oncogene. “Double-hit CLL” (with del(17p) and MYC gain) is associated with a very poor prognosis. The prognostic impact of TP53 disruption with MYC aberrations in patients receiving targeted therapies must now be evaluated.
Combination of Anlotinib and Celecoxib for the Treatment of Abdominal Desmoid Tumor: A Case Report and Literature Review
Authors: Wang Jianzheng , Li Hongle , Wang Hui , Li Qingli , Bai Xuanye , Lv Huifang , Nie Caiyun , Chen Beibei , Xu Weifeng , Tu Shuiping , Chen Xiaobing
Published: January 2022

Desmoid tumor is a rare disease, which is histologically characterized by local invasion, monoclonality, and fibroblast proliferation; and clinically characterized by a variable and often unpredictable course. The treatment of desmoid tumor is mainly surgical resection, but the recurrence rate is high. In recent years, a variety of treatment methods, including endocrine therapy, surgery, radiotherapy, chemotherapy, non-steroidal anti-inflammatory drugs, targeted drugs, interferon and more, have been used and achieved certain curative effects. In addition, in view of the inertia characteristics of desmoid tumor, observation is also a first-line scheme recommended by multiple guidelines. In the past, the research progress of targeted therapy for desmoid tumor is relatively slow and the curative effect is limited. Thus, targeted therapy is usually used as a remedial treatment after the failure of other conventional treatment methods. However, in recent years, with the rapid progress in the basic research of targeted therapy, some new targeted drugs are increasingly used for the clinical treatment of desmoid tumor and have achieved good results. Herein, we described a patient with aggressive fibromatosis in the abdominal cavity. Following a combined treatment using anlotinib and celecoxib, the patient achieved a partial response with mild toxicity. Simultaneously, the patient’s pain symptoms completely disappeared. This case indicates that the combination of anlotinib and NSAIDs could be an effective treatment for desmoid tumor.
Assessing the Utility of an Outpatient Exercise Program for Children With Cystic Fibrosis: A Quality Improvement Project
Authors: Adair Dionne , Hider Ahmad , Filbrun Amy G. , Tapley Chris , Bouma Sandra , Iwanicki Courtney , Nasr Samya Z.
Published: January 2022

Children with cystic fibrosis (CF) (cwCF) suffer from inadequate weight gain, failure to thrive, and muscle weakness. The latter may be secondary to disuse atrophy (muscle wasting or reduction in muscle size associated with reduced physical activity and inflammation). Handgrip strength (HGS) is a reliable surrogate for muscle strength and lean body mass. Data from our CF center have shown an association between low HGS and forced expiratory volume in 1 s (FEV1) in cwCF. High-intensity interval training (HIIT) improves physical strength. Therefore, we devised a project to assess implementing a HIIT exercise program in the home setting, in order to improve physical strength in cwCF with HGS ≤ 50th percentile. Patients were instructed to complete 3–5 sessions of HIIT exercises per week. Wilcoxon matched-pairs signed-rank tests were used to compare HGS, FEV1, and body mass index (BMI) percentile at baseline and at a follow-up clinic visit. Follow-up was limited due to the COVID pandemic. Adherence to the HIIT regimen was poor. A total of twenty-nine cwCF participated in the program. However, a total of 13 individuals reported some form of moderate activity at follow-up and therefore constituted our final study population. There was a statistically significant increase in absolute grip strength (AGS) and FEV1 for these individuals. Even though the home HIIT protocol was not followed, the project demonstrated that moderate physical activity in cwCF can lead to significant improvement in HGS and overall physical strength.
Safety Evaluation of Natural Drugs in Chronic Skeletal Disorders: A Literature Review of Clinical Trials in the Past 20 years
Authors: Zhou Dongyang , Zhang Hao , Xue Xu , Tao Yali , Wang Sicheng , Ren Xiaoxiang , Su Jiacan
Published: January 2022

Chronic skeletal disorders (CSDs), including degenerative diseases such as osteoporosis (OP) and autoimmune disorders, have become a leading cause of disability in an ageing society, with natural drugs being indispensable therapeutic options. The clinical safety evaluation (CSE) of natural drugs in CSDs has been given priority and has been intensively studied. To provide fundamental evidence for the clinical application of natural drugs in the elderly population, clinical studies of natural drugs in CSDs included in this review were selected from CNKI, Web of Science, PubMed, Science Direct and Google Scholar since 2001. Seventeen randomized controlled trials (RCTs) met our inclusion criteria: four articles were on OP, seven on osteoarthritis (OA), four on rheumatoid arthritis (RA) and two on gout. Common natural drugs used for the treatment of OP include Epimedium brevicornu Maxim [Berberidaceae], Dipsacus asper Wall ex DC [Caprifoliaceae] root, and Phalaenopsis cornu-cervi (Breda) Blume & Rchb. f[ Orchidaceae], which have been linked to several mild adverse reactions, such as skin rash, gastric dysfunction, abnormal urine, constipation and irritability. The safety of Hedera helix L [Araliaceae] extract, Boswellia serrata Roxb [Burseraceae] extract and extract from perna canaliculus was evaluated in OA and upper abdominal pain, and unstable movements were obsrerved as major side effects. Adverse events, including pneumonia, vomiting, diarrhoea and upper respiratory tract infection, were reported when RA was treated with Tripterygium wilfordii, Hook. F [Celastraceae][TwHF] polyglycosides and quercetin (Capsella bursa-pastoris (L.) Medik [Brassicaceae]). The present review aimed to summarize the CSE results of natural drugs in CSDs and could provide evidence-based information for clinicians.
Transcriptomic and Lipidomic Profiles in Nasal Polyps of Glucocorticoid Responders and Non-Responders: Before and After Treatment
Authors: Zhu Zhenzhen , Wang Weiqing , Zha Yang , Wang Xiaowei , Wang Lei , Han Jinbo , Zhang Jianmin , Lv Wei
Published: January 2022

Background:The pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and mechanisms underlying different responses to systemic glucocorticoids (GC) remain unclear. The major aim of this study was to explore the transcriptomic and oxidative lipidomic signatures and the effects of GC in patients with different clinical responses.

Methods:Nasal polyp biopsies were obtained before and after 14-day oral GC treatment from 16 patients with CRSwNP, and normal nasal mucosa specimens were collected from 12 control subjects. RNA sequencing and oxidative lipidomics were performed, and differential gene expression analysis was conducted in the Responder and Non-responder groups at baseline and after treatment.

Results:In the Responder group, GC significantly improved clinical symptoms and reduced tissue eosinophil infiltration. Meanwhile, GC led to a pronounced transcriptomic reversion with robust suppression of inflammatory responses and abnormal metabolism of extracellular matrix, as well as restoration of cilia function. However, non-responders were mainly characterized by epithelial hyperplasia and keratinization, with much less transcriptomic improvement after GC treatment. Higher expression of type 2 inflammatory molecules (CCL13, IGHE, CCL18, CCL23, CCR3,andCLC) with lower levels ofLACRT, PPDPFL, DES, C6, MUC5B,andSCGB3A1were related to a stronger clinical response to GC. Besides decreased prostaglandins and increased leukotrienes, increased dysregulation in other oxylipid mediators derived from polyunsaturated fatty acids was determined in nasal polyps, which was ameliorated by GC treatment.

Conclusion:Systemic GC exert anti-inflammatory effects, improve tissue remodeling, restore cilia function, and ameliorate dysregulation of oxylipid mediator pathway in CRSwNP. GC-responders exhibited different transcriptomic signatures from non-responders.
Fluorescence Record Diagnostics of 3D Rough-Surface Landscapes With Nano-Scale Inhomogeneities
Authors: Angelsky O. V. , Bekshaev A. Y. , Zenkova C. Yu. , Ivansky D. I. , Zheng J. , Tkachuk V. M.
Published: January 2022

The paper proposes a new approach that enables the structure analysis and reconstruction of a rough surface where the height of inhomogeneities (from the depression to the upper point) varies within the spread about 20 nm. For the surface diagnostics, carbon nanoparticles are used, which serve as sensitive probes of the local surface height. A single nanoparticle can be positioned at a desirable point of the studied surface with the help of an optical tweezer employing the He-Ne laser radiation. Then the particle is illuminated by the strongly focused exciting beam of 405 nm wavelength, with the waist plane precisely fixed at a certain distance from the surface base plane. The particle’s luminescence response (in the yellow-green spectral range) strongly depends on the distance between the exciting beam waist and the particle, thus indicating the local height of the surface. After scanning the surface area and the consecutive interpolation, the surface “vertical” landscape can be reconstructed with a high accuracy: the numerical simulation shows that the RMS surface roughness is restored with an accuracy of 6.9% while the landscape itself is reconstructed with the mean error 7.7%.
Simulation of Deformation Process Failure of Jointed Rock Masses Based on the Numerical Manifold Method
Authors: Lin Xing-Chao , Zhang Qiang , Jin Jiufeng , Chen Guangming , Li Jin-Hang
Published: January 2022

On the basis of the numerical manifold method, this work introduces the concept of stress intensity factor at the crack tip in fracture mechanics and proposes the utilisation of artificial joint technology to ensure the accuracy of joint geometric dimensions in the element generation of the numerical manifold method. The contour integral method is used to solve the stress intensity factor at the joint tip, and the failure criterion and direction of crack propagation at the joint tip are determined. Element reconstruction and crack tracking are implemented in crack propagation, and a simulation programme of the entire process of deformation, failure, propagation and coalescence of jointed rock masses is developed. The rationality of the proposed method is verified by performing the typical uniaxial compression test and direct shear test.
Mycorrhizal Switching and the Role of Fungal Abundance in Seed Germination in a Fully Mycoheterotrophic Orchid, Gastrodia confusoides
Authors: Li Yuan-Yuan , Boeraeve Margaux , Cho Yu-Hsiu , Jacquemyn Hans , Lee Yung-I
Published: January 2022

Mycorrhizal associations are essential for orchid germination and seedling establishment, and thus may constrain the distribution and abundance of orchids under natural conditions. Previous studies have shown that germination and seedling establishment in several orchids often decline with increasing distance from adult plants, resulting in non-random spatial patterns of seedling establishment. In contrast, individuals of the fully mycoheterotrophic orchidGastrodia confusoidesoften tend to have random aboveground spatial patterns of distribution within bamboo forests. SinceG. confusoidesis parasitic on litter-decaying fungi, its random spatial patterns of distribution may be due to highly scattered patterns of litter-decaying fungi within bamboo forests. To test this hypothesis, we first identified the main mycorrhizal fungi associating with developing seeds and adult plants at a bamboo forest site in Taiwan using Miseq high-throughput DNA sequencing. Next, we combined seed germination experiments with quantitative PCR (qPCR) analyses to investigate to what extent the abundance of mycorrhizal fungi affected spatial patterns of seed germination. Our results show that seed germination and subsequent growth to an adult stage inG. confusoidesrequired a distinct switch in mycorrhizal partners, in which protocorms associated with a singleMycenaOTU, while adults mainly associated with an OTU from the genusGymnopus. A strong, positive relationship was observed between germination andMycenaabundance in the litter, but not between germination andGymnopusabundance. Fungal abundance was not significantly related to the distance from the adult plants, and consequently germination was also not significantly related to the distance from adult plants. Our results provide the first evidence that the abundance of litter-decaying fungi varies randomly within the bamboo forest and independently fromG. confusoidesadults.
Select and Sequence of a Segregating Sugar Beet Population Provides Genomic Perspective of Host Resistance to Seedling Rhizoctonia solani Infection
Authors: Galewski Paul , Funk Andrew , McGrath J. Mitchell
Published: January 2022

Understanding the genetic basis of polygenic traits is a major challenge in agricultural species, especially in non-model systems. Select and sequence (SnS) experiments carried out within existing breeding programs provide a means to simultaneously identify the genomic background of a trait while improving the mean phenotype for a population. Using pooled whole genome sequencing (WGS) of selected and unselected bulks derived from a synthetic outcrossing sugar beet population EL57 (PI 663212), which segregates for seedling rhizoctonia resistance, we identified a putative genomic background involved in conditioning a resistance phenotype. Population genomic parameters were estimated to measure fixation (He), genome divergence (FST), and allele frequency changes between bulks (DeltaAF). We report on the genome wide patterns of variation resulting from selection and highlight specific genomic features associated with resistance. Expected heterozygosity (He) showed an increased level of fixation in the resistant bulk, indicating a greater selection pressure was applied. In total, 1,311 biallelic loci were detected as significant FST outliers (p < 0.01) in comparisons between the resistant and susceptible bulks. These loci were detected in 206 regions along the chromosomes and contained 275 genes. We estimated changes in allele frequency between bulks resulting from selection for resistance by leveraging the allele frequencies of an unselected bulk. DeltaAF was a more stringent test of selection and recovered 186 significant loci, representing 32 genes, all of which were also detected using FST. Estimates of population genetic parameters and statistical significance were visualized with respect to the EL10.2 physical map and produced a candidate gene list that was enriched for function in cell wall metabolism and plant disease resistance, including pathogen perception, signal transduction, and pathogen response. Specific variation associated with these genes was also reported and represents genetic markers for validation and prediction of resistance to Rhizoctonia. Select and sequence experiments offer a means to characterize the genetic base of sugar beet, inform selection within breeding programs, and prioritize candidate variation for functional studies.
Soybean Yield Preharvest Prediction Based on Bean Pods and Leaves Image Recognition Using Deep Learning Neural Network Combined With GRNN
Authors: Lu Wei , Du Rongting , Niu Pengshuai , Xing Guangnan , Luo Hui , Deng Yiming , Shu Lei
Published: January 2022

Soybean yield is a highly complex trait determined by multiple factors such as genotype, environment, and their interactions. The earlier the prediction during the growing season the better. Accurate soybean yield prediction is important for germplasm innovation and planting environment factor improvement. But until now, soybean yield has been determined by weight measurement manually after soybean plant harvest which is time-consuming, has high cost and low precision. This paper proposed a soybean yield in-field prediction method based on bean pods and leaves image recognition using a deep learning algorithm combined with a generalized regression neural network (GRNN). A faster region-convolutional neural network (Faster R-CNN), feature pyramid network (FPN), single shot multibox detector (SSD), and You Only Look Once (YOLOv3) were employed for bean pods recognition in which recognition precision and speed were 86.2, 89.8, 80.1, 87.4%, and 13 frames per second (FPS), 7 FPS, 24 FPS, and 39 FPS, respectively. Therefore, YOLOv3 was selected considering both recognition precision and speed. For enhancing detection performance, YOLOv3 was improved by changing IoU loss function, using the anchor frame clustering algorithm, and utilizing the partial neural network structure with which recognition precision increased to 90.3%. In order to improve soybean yield prediction precision, leaves were identified and counted, moreover, pods were further classified as single, double, treble, four, and five seeds types by improved YOLOv3 because each type seed weight varies. In addition, soybean seed number prediction models of each soybean planter were built using PLSR, BP, and GRNN with the input of different type pod numbers and leaf numbers with which prediction results were 96.24, 96.97, and 97.5%, respectively. Finally, the soybean yield of each planter was obtained by accumulating the weight of all soybean pod types and the average accuracy was up to 97.43%. The results show that it is feasible to predict the soybean yield of plants in situ with high precision by fusing the number of leaves and different type soybean pods recognized by a deep neural network combined with GRNN which can speed up germplasm innovation and planting environmental factor optimization.
Transcriptome and Proteomics Analysis of Wheat Seedling Roots Reveals That Increasing NH4+/NO3– Ratio Induced Root Lignification and Reduced Nitrogen Utilization
Authors: Yang Dongqing , Zhao Jihao , Bi Chen , Li Liuyin , Wang Zhenlin
Published: January 2022

Wheat growth and nitrogen (N) uptake gradually decrease in response to high NH4+/NO3–ratio. However, the mechanisms underlying the response of wheat seedling roots to changes in NH4+/NO3–ratio remain unclear. In this study, we investigated wheat growth, transcriptome, and proteome profiles of roots in response to increasing NH4+/NO3–ratios (Na: 100/0; Nr1: 75/25, Nr2: 50/50, Nr3: 25/75, and Nn: 0/100). High NH4+/NO3–ratio significantly reduced leaf relative chlorophyll content, Fv/Fm, and ΦII values. Both total root length and specific root length decreased with increasing NH4+/NO3–ratios. Moreover, the rise in NH4+/NO3–ratio significantly promoted O2–production. Furthermore, transcriptome sequencing and tandem mass tag-based quantitative proteome analyses identified 14,376 differentially expressed genes (DEGs) and 1,819 differentially expressed proteins (DEPs). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that glutathione metabolism and phenylpropanoid biosynthesis were the main two shared enriched pathways across ratio comparisons. Upregulated DEGs and DEPs involving glutathione S-transferases may contribute to the prevention of oxidative stress. An increment in the NH4+/NO3–ratio induced the expression of genes and proteins involved in lignin biosynthesis, which increased root lignin content. Additionally, phylogenetic tree analysis showed that both A0A3B6NPP6 and A0A3B6LM09 belong to the cinnamyl-alcohol dehydrogenase subfamily. Fifteen downregulated DEGs were identified as high-affinity nitrate transporters or nitrate transporters. UpregulatedTraesCS3D02G344800andTraesCS3A02G350800were involved in ammonium transport. Downregulated A0A3B6Q9B3 is involved in nitrate transport, whereas A0A3B6PQS3 is a ferredoxin-nitrite reductase. This may explain why an increase in the NH4+/NO3–ratio significantly reduced root NO3–-N content but increased NH4+-N content. Overall, these results demonstrated that increasing the NH4+/NO3–ratio at the seedling stage induced the accumulation of reactive oxygen species, which in turn enhanced root glutathione metabolism and lignification, thereby resulting in increased root oxidative tolerance at the cost of reducing nitrate transport and utilization, which reduced leaf photosynthetic capacity and, ultimately, plant biomass accumulation.
The Rice Abscisic Acid-Responsive RING Finger E3 Ligase OsRF1 Targets OsPP2C09 for Degradation and Confers Drought and Salinity Tolerance in Rice
Authors: Kim Suyeon , Park Seong-Im , Kwon Hyeokjin , Cho Mi Hyeon , Kim Beom-Gi , Chung Joo Hee , Nam Myung Hee , Song Ji Sun , Kim Kyung-Hwan , Yoon In Sun
Published: January 2022

Drought and salinity are major important factors that restrain growth and productivity of rice. In plants, many really interesting new gene (RING) finger proteins have been reported to enhance drought and salt tolerance. However, their mode of action and interacting substrates are largely unknown. Here, we identified a new small RING-H2 type E3 ligase OsRF1, which is involved in the ABA and stress responses of rice. OsRF1 transcripts were highly induced by ABA, salt, or drought treatment. Upregulation of OsRF1 in transgenic rice conferred drought and salt tolerance and increased endogenous ABA levels. Consistent with this, faster transcriptional activation of key ABA biosynthetic genes, ZEP, NCED3, and ABA4, was observed in OsRF1-OE plants compared with wild type in response to drought stress. Yeast two-hybrid assay, BiFC, and co-immunoprecipitation analysis identified clade A PP2C proteins as direct interacting partners with OsRF1. In vitro ubiquitination assay indicated that OsRF1 exhibited E3 ligase activity, and that it targeted OsPP2C09 protein for ubiquitination and degradation. Cell-free degradation assay further showed that the OsPP2C09 protein is more rapidly degraded by ABA in the OsRF1-OE rice than in the wild type. The combined results suggested that OsRF1 is a positive player of stress responses by modulating protein stability of clade A PP2C proteins, negative regulators of ABA signaling.
Shade Avoidance 3 Mediates Crosstalk Between Shade and Nitrogen in Arabidopsis Leaf Development
Authors: Yang Xin-Yue , Zhang Zhong-Wei , Fu Yu-Fan , Feng Ling-Yang , Li Meng-Xia , Kang Qi , Wang Chang-Quan , Yuan Ming , Chen Yang-Er , Tao Qi , Lan Ting , Tang Xiao-Yan , Chen Guang-Deng , Zeng Jian , Yuan Shu
Published: January 2022

After nitrogen treatments, plant leaves become narrower and thicker, and the chlorophyll content increases. However, the molecular mechanisms behind these regulations remain unknown. Here, we found that the changes in leaf width and thickness were largely compromised in the shade avoidance 3 (sav3) mutant. The SAV3 gene encodes an amino-transferase in the auxin biosynthesis pathway. Thus, the crosstalk between shade and nitrogen in Arabidopsis leaf development was investigated. Both hypocotyl elongation and leaf expansion promoted by the shade treatment were reduced by the high-N treatment; high-N-induced leaf narrowing and thickening were reduced by the shade treatment; and all of these developmental changes were largely compromised in the sav3 mutant. Shade treatment promoted SAV3 expression, while high-N treatment repressed SAV3 expression, which then increased or decreased auxin accumulation in cotyledons/leaves, respectively. SAV3 also regulates chlorophyll accumulation and nitrogen assimilation and thus may function as a master switch responsive to multiple environmental stimuli.
Efficient Genome Editing in Setaria italica Using CRISPR/Cas9 and Base Editors
Authors: Liang Zhen , Wu Yuqing , Ma Lingling , Guo Yingjie , Ran Yidong
Published: January 2022

The genome editing toolbox based on CRISPR/Cas9 has brought revolutionary changes to agricultural and plant scientific research. With the development of stable genetic transformation protocols, a highly efficient genome editing system for foxtail millet (Setaria italica) is required. In the present study, we use the CRISPR/Cas9 single- and multi-gene knockout system to target the SiFMBP, SiDof4, SiBADH2, SiGBSS1, and SiIPK1 genes in the foxtail millet protoplasts to screen out highly efficient targeted sgRNAs. Then, we recovered homozygous mutant plants with most of the targeted genes through an Agrobacterium-mediated genetic transformation of foxtail millet. The mutagenesis frequency in the T0 generation was as high as 100%, and it was passed stably on to the next generation. After screening these targeted edited events, we did not detect off-target mutations at potential sites. Based on this system, we have achieved base editing successfully using two base editors (CBE and ABE) to target the SiALS and SiACC genes of foxtail millet. By utilizing CBE to target the SiALS gene, we created a homozygous herbicide-tolerant mutant plant. The current system could enhance the analysis of functional genomics and genetic improvement of foxtail millet.
Differences in School Performance Between Only Children and Non-only Children: Evidence From China
Authors: Jia Chaochao , Yang Zhaoxi , Xin Tao , Li Youfa , Wang Yehui , Yang Tao
Published: January 2022

This study aimed to investigate the features of only child status related to physical health, mathematics achievement, and school feelings and expectations from a different perspective. A representative sample of 91,619 Grade 4 students with an average age of 10.4 ± 0.7, among which 28,631 were only children, were assessed. We used propensity score matching (PSM) and the average treatment effects on the treatment to analyze data. The treatment was the only child of a family. The results indicated that only children have better academic achievement and school feelings (only for urban only child girls), while non-only children have better physical status and anaerobic fitness (AF). In addition, gender and rural vs. urban areas differences were also explored. The adverse situation for rural only boys is emphasized for families, researchers, and governments to focus on. Some suggestions are given under the Two- and Three-Child Policy.