bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of Donor-Derived Cell-Free DNA at the Early Phase After Pediatric Kidney Transplantation: A Prospective Cohort Study
Authors: Nie Weijian , Su Xiaojun , Liu Longshan , Li Jun , Fu Qian , Li Xirui , Wu Chenglin , Wang Jiali , Deng Ronghai , Chen E. , Yang Shicong , Li Shujuan , Zhang Huanxi , Wang Changxi
Published: January 2022

Background: Donor-derived cell-free DNA (ddcfDNA) has been suggested as an indicator of allograft injury in adult and pediatric kidney transplantation (KTx). However, the dynamics of ddcfDNA in pediatric KTx have not been investigated. In addition, it has not been demonstrated whether donor-recipient (D/R) size mismatch affect ddcfDNA level.

Methods: Pediatric KTx recipients with a single donor kidney were enrolled and followed up for 1 year. ddcfDNA, calculated as a fraction (%) in the recipient plasma, was examined longitudinally within 3 months post-transplant. D/R size mismatch degree was described as D/R height ratio. The 33rd percentile of D/R height ratio (0.70) was used as the cut-off to divide the patients into low donor-recipient height ratio group (<0.70) and high donor-recipient height ratio group (≥0.70). The dynamics of ddcfDNA were analyzed and the impact factors were explored. Stable ddcfDNA was defined as the first lowest ddcfDNA. ddcfDNA flare-up was defined as a remarkable elevation by a proportion of >30% from stable value with a peak value >1% during elevation.

Results: Twenty-one clinically stable recipients were enrolled. The median D/R height ratio was 0.83 (0.62–0.88). It took a median of 8 days for ddcfDNA to drop from day 1 and reach a stable value of 0.67% (0.46–0.73%). Nevertheless, 61.5% patients presented ddcfDNA>1% at day 30. Besides, 81.0% (17/21) of patients experienced elevated ddcfDNA and 47.6% (10/21) met the standard of ddcfDNA flare-up. Donor-recipient height ratio was an independent risk factor for ddcfDNA flare-up (odds ratio = 0.469 per 0.1, 95% CI 0.237–0.925, p = 0.029) and low donor-recipient height ratio (<0.70) was found to increase the risk of flare-up occurrence (odds ratio = 15.00, 95% CI 1.342–167.638, p = 0.028).

Conclusions: ddcfDNA rebounds in many stable pediatric KTx recipients without rejection. This may be induced by significant D/R size mismatch and may affect its diagnostic performance at the early phase after pediatric KTx in children.
Mobile Genetic Elements Drive Antimicrobial Resistance Gene Spread in Pasteurellaceae Species
Authors: da Silva Giarlã Cunha , Gonçalves Osiel Silva , Rosa Jéssica Nogueira , França Kiara Campos , Bossé Janine Thérèse , Santana Mateus Ferreira , Langford Paul Richard , Bazzolli Denise Mara Soares
Published: January 2022

Mobile genetic elements (MGEs) and antimicrobial resistance (AMR) drive important ecological relationships in microbial communities and pathogen-host interaction. In this study, we investigated the resistome-associated mobilome in 345 publicly available Pasteurellaceae genomes, a large family of Gram-negative bacteria including major human and animal pathogens. We generated a comprehensive dataset of the mobilome integrated into genomes, including 10,820 insertion sequences, 2,939 prophages, and 43 integrative and conjugative elements. Also, we assessed plasmid sequences of Pasteurellaceae. Our findings greatly expand the diversity of MGEs for the family, including a description of novel elements. We discovered that MGEs are comparable and dispersed across species and that they also co-occur in genomes, contributing to the family’s ecology via gene transfer. In addition, we investigated the impact of these elements in the dissemination and shaping of AMR genes. A total of 55 different AMR genes were mapped to 721 locations in the dataset. MGEs are linked with 77.6% of AMR genes discovered, indicating their important involvement in the acquisition and transmission of such genes. This study provides an uncharted view of the Pasteurellaceae by demonstrating the global distribution of resistance genes linked with MGEs.
Functional Interaction Between Drosophila Olfactory Sensory Neurons and Their Support Cells
Authors: Prelic Sinisa , Pal Mahadevan Venkatesh , Venkateswaran Vignesh , Lavista-Llanos Sofia , Hansson Bill S. , Wicher Dieter
Published: January 2022

Insects detect volatile chemicals using antennae, which house a vast variety of olfactory sensory neurons (OSNs) that innervate hair-like structures called sensilla where odor detection takes place. In addition to OSNs, the antenna also hosts various support cell types. These include the triad of trichogen, tormogen, and thecogen support cells that lie adjacent to their respective OSNs. The arrangement of OSN supporting cells occurs stereotypically for all sensilla and is widely conserved in evolution. While insect chemosensory neurons have received considerable attention, little is known about the functional significance of the cells that support them. For instance, it remains unknown whether support cells play an active role in odor detection, or only passively contribute to homeostasis, e.g., by maintaining sensillum lymph composition. To investigate the functional interaction between OSNs and support cells, we used optical and electrophysiological approaches in Drosophila. First, we characterized the distribution of various supporting cells using genetic markers. By means of an ex vivo antennal preparation and genetically-encoded Ca2+ and K+ indicators, we then studied the activation of these auxiliary cells during odor presentation in adult flies. We observed acute responses and distinct differences in Ca2+ and K+ fluxes between support cell types. Finally, we observed alterations in OSN responses upon thecogen cell ablation in mature adults. Upon inducible ablation of thecogen cells, we notice a gain in mechanical responsiveness to mechanical stimulations during single-sensillum recording, but a lack of change to the neuronal resting activity. Taken together, these results demonstrate that support cells play a more active and responsive role during odor processing than previously thought. Our observations thus reveal that support cells functionally interact with OSNs and may be important for the extraordinary ability of insect olfactory systems to dynamically and sensitively discriminate between odors in the turbulent sensory landscape of insect flight.
Cannabinoids in Chronic Pain: Therapeutic Potential Through Microglia Modulation
Authors: van den Hoogen Nynke J. , Harding Erika K. , Davidson Chloé E. D. , Trang Tuan
Published: January 2022

Chronic pain is a complex sensory, cognitive, and emotional experience that imposes a great personal, psychological, and socioeconomic burden on patients. An estimated 1.5 billion people worldwide are afflicted with chronic pain, which is often difficult to treat and may be resistant to the potent pain-relieving effects of opioid analgesics. Attention has therefore focused on advancing new pain therapies directed at the cannabinoid system because of its key role in pain modulation. Endocannabinoids and exogenous cannabinoids exert their actions primarily through Gi/o-protein coupled cannabinoid CB1 and CB2 receptors expressed throughout the nervous system. CB1 receptors are found at key nodes along the pain pathway and their activity gates both the sensory and affective components of pain. CB2 receptors are typically expressed at low levels on microglia, astrocytes, and peripheral immune cells. In chronic pain states, there is a marked increase in CB2 expression which modulates the activity of these central and peripheral immune cells with important consequences for the surrounding pain circuitry. Growing evidence indicate that interventions targeting CB1 or CB2 receptors improve pain outcomes in a variety of preclinical pain models. In this mini-review, we will highlight recent advances in understanding how cannabinoids modulate microglia function and its implications for cannabinoid-mediated analgesia, focusing on microglia-neuron interactions within the spinal nociceptive circuitry.
Pathological Targets for Treating Temporal Lobe Epilepsy: Discoveries From Microscale to Macroscale
Authors: You Jing , Huang Haiyan , Chan Clement T. Y. , Li Lin
Published: January 2022

Temporal lobe epilepsy (TLE) is one of the most common and severe types of epilepsy, characterized by intractable, recurrent, and pharmacoresistant seizures. Histopathology of TLE is mostly investigated through observing hippocampal sclerosis (HS) in adults, which provides a robust means to analyze the related histopathological lesions. However, most pathological processes underlying the formation of these lesions remain elusive, as they are difficult to detect and observe. In recent years, significant efforts have been put in elucidating the pathophysiological pathways contributing to TLE epileptogenesis. In this review, we aimed to address the new and unrecognized neuropathological discoveries within the last 5 years, focusing on gene expression (miRNA and DNA methylation), neuronal peptides (neuropeptide Y), cellular metabolism (mitochondria and ion transport), cellular structure (microtubule and extracellular matrix), and tissue-level abnormalities (enlarged amygdala). Herein, we describe a range of biochemical mechanisms and their implication for epileptogenesis. Furthermore, we discuss their potential role as a target for TLE prevention and treatment. This review article summarizes the latest neuropathological discoveries at the molecular, cellular, and tissue levels involving both animal and patient studies, aiming to explore epileptogenesis and highlight new potential targets in the diagnosis and treatment of TLE.
Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy
Authors: Chen Shuang , Xu Da , Fan Liu , Fang Zhi , Wang Xiufeng , Li Man
Published: January 2022

Epilepsy is one of the most common neurological disorders characterized by recurrent seizures. The mechanism of epilepsy remains unclear and previous studies suggest that N-methyl-D-aspartate receptors (NMDARs) play an important role in abnormal discharges, nerve conduction, neuron injury and inflammation, thereby they may participate in epileptogenesis. NMDARs belong to a family of ionotropic glutamate receptors that play essential roles in excitatory neurotransmission and synaptic plasticity in the mammalian CNS. Despite numerous studies focusing on the role of NMDAR in epilepsy, the relationship appeared to be elusive. In this article, we reviewed the regulation of NMDAR and possible mechanisms of NMDAR in epilepsy and in respect of onset, development, and treatment, trying to provide more evidence for future studies.
Case Report: Adult NTRK-Rearranged Spindle Cell Neoplasm: Early Tumor Shrinkage in a Case With Bone and Visceral Metastases Treated With Targeted Therapy
Authors: Recine Federica , De Vita Alessandro , Fausti Valentina , Pieri Federica , Bongiovanni Alberto , Franchini Eugenia , Casadei Roberto , Falasconi Maria Cristina , Oboldi Devil , Matteucci Federica , Pallotti Maria Caterina , Mercatali Laura , Riva Nada , Gurrieri Lorena , Vanni Silvia , Liverani Chiara , Miserocchi Giacomo , Spadazzi Chiara , Cocchi Claudia , Ibrahim Toni
Published: January 2022

Background

NTRK (neurotrophic tyrosine receptor kinase)-rearranged spindle cell neoplasms are a new group of tumors included in the new 5th edition of the World Health Organization (WHO) classification of soft Tissue and Bone Sarcomas. These tumors are characterized by NTRK gene fusions and show a wide spectrum of histologies and clinical behavior. Several targeted therapies have recently been approved for tumors harboring NTRK fusions, including STS.

Case Presentation

A 26-year-old male with advanced, pretreated NTRK rearranged spindle cell neoplasm and liver, lung and bone metastases was treated with larotrectinib on a continuous 28-day schedule, at a dose of 100 mg twice daily. An 18FDG-PET/CT scan performed after 7 days of treatment showed tumor shrinkage in both visceral and bone lesions. There was no drug-related toxicity. Subsequent evaluations confirmed continued tumor regression in disease sites. The patient is well and continues treatment.

Conclusion

The clinical and radiological response of our patient with an uncommon TPM4 (exon 7)-NTRK1 (exon 12) gene fusion tumor treated with a first-generation TRK inhibitor could contribute to a better understanding of the biology of this new STS entity and help to improve patient management.
Ovarian Biomechanics: From Health to Disease
Authors: Sun Chenchen , Yang Xiaoxu , Wang Tianxiao , Cheng Min , Han Yangyang
Published: January 2022

Biomechanics is a physical phenomenon which mainly related with deformation and movement of life forms. As a mechanical signal, it participates in the growth and development of many tissues and organs, including ovary. Mechanical signals not only participate in multiple processes in the ovary but also play a critical role in ovarian growth and normal physiological functions. Additionally, the involvement of mechanical signals has been found in ovarian cancer and other ovarian diseases, prompting us to focus on the roles of mechanical signals in the process of ovarian health to disease. This review mainly discusses the effects and signal transduction of biomechanics (including elastic force, shear force, compressive stress and tensile stress) in ovarian development as a regulatory signal, as well as in the pathological process of normal ovarian diseases and cancer. This review also aims to provide new research ideas for the further research and treatment of ovarian-related diseases.
A Linear Discriminant Analysis Model Based on the Changes of 7 Proteins in Plasma Predicts Response to Anlotinib Therapy in Advanced Non-Small Cell Lung Cancer Patients
Authors: Xu Fei , Xu Haiyan , Wan Zhiyi , Yang Guangjian , Yang Lu , Wu Xueying , Song Jin , Wang Yan
Published: January 2022

Background

Anlotinib is a multi-targeted tyrosine kinase inhibitor mainly targeting angiogenesis signaling. The predictive marker of anlotinib’s efficacy remains elusive. This study was designed to explore the predictive marker of anlotinib in non-small cell lung cancer (NSCLC).

Methods

We prospectively enrolled 52 advanced NSCLC patients who underwent at least one line of targeted therapy or chemotherapy between August 2018 and March 2020. Patients were divided into durable responders (DR) and non-durable responders (NDR) based on the median progression-free survival (PFS, 176 days). The Olink Immuno-Oncology panel (92 proteins) was used to explore the predictive protein biomarkers in plasma samples before treatment (baseline) and on the first treatment evaluation (paired).

Results

At baseline, the response to anlotinib was not significantly associated with age, gender, smoke history, histology, oligo-metastases, EGFR mutations, and other clinical characteristics. The results of PFS-related protein biomarkers at baseline were all not satisfying. Then we assessed the changes of 92 proteins levels in plasma on the first treatment evaluation. We obtained a Linear discriminant analysis (LDA) model based on 7 proteins, with an accuracy of 100% in the original data and an accuracy of 89.2% in cross validation. The 7 proteins were CD70, MIC-A/B, LAG3, CAIX, PDCD1, MMP12, and PD-L2. Multivariate Cox analysis further showed that the changes of CD70 (HR 25.48; 95% CI, 4.90–132.41, P=0.000) and MIC-A/B (HR 15.04; 95% CI, 3.81–59.36, P=0.000) in plasma were the most significant prognostic factors for PFS.

Conclusion

We reported herein a LDA model based on the changes of 7 proteins levels in plasma before and after treatment, which could predict anlotinib responders among advanced NSCLC patients with an accuracy of 100%. Further studies are warranted to verify the prediction performance of the LDA model.
Imaging the Rewired Metabolism in Lung Cancer in Relation to Immune Therapy
Authors: van Genugten Evelien A. J. , Weijers Jetty A. M. , Heskamp Sandra , Kneilling Manfred , van den Heuvel Michel M. , Piet Berber , Bussink Johan , Hendriks Lizza E. L. , Aarntzen Erik H. J. G.
Published: January 2022

Metabolic reprogramming is recognized as one of the hallmarks of cancer. Alterations in the micro-environmental metabolic characteristics are recognized as important tools for cancer cells to interact with the resident and infiltrating T-cells within this tumor microenvironment. Cancer-induced metabolic changes in the micro-environment also affect treatment outcomes. In particular, immune therapy efficacy might be blunted because of somatic mutation-driven metabolic determinants of lung cancer such as acidity and oxygenation status. Based on these observations, new onco-immunological treatment strategies increasingly include drugs that interfere with metabolic pathways that consequently affect the composition of the lung cancer tumor microenvironment (TME). Positron emission tomography (PET) imaging has developed a wide array of tracers targeting metabolic pathways, originally intended to improve cancer detection and staging. Paralleling the developments in understanding metabolic reprogramming in cancer cells, as well as its effects on stromal, immune, and endothelial cells, a wave of studies with additional imaging tracers has been published. These tracers are yet underexploited in the perspective of immune therapy. In this review, we provide an overview of currently available PET tracers for clinical studies and discuss their potential roles in the development of effective immune therapeutic strategies, with a focus on lung cancer. We report on ongoing efforts that include PET/CT to understand the outcomes of interactions between cancer cells and T-cells in the lung cancer microenvironment, and we identify areas of research which are yet unchartered. Thereby, we aim to provide a starting point for molecular imaging driven studies to understand and exploit metabolic features of lung cancer to optimize immune therapy.
Impact of Postoperative Infectious Complications on Long-Term Outcomes for Patients Undergoing Simultaneous Resection for Colorectal Cancer Liver Metastases: A Propensity Score Matching Analysis
Authors: Chen Qichen , Deng Yiqiao , Chen Jinghua , Zhao Jianjun , Bi Xinyu , Zhou Jianguo , Li Zhiyu , Huang Zhen , Zhang Yefan , Chen Xiao , Zhao Hong , Cai Jianqiang
Published: January 2022

Objective

To investigate the impact of postoperative infectious complications (POI) on the long-term outcomes of patients with colorectal cancer liver metastasis (CRLM) after simultaneous resection of colorectal cancer and liver metastases.

Methods

Four hundred seventy-nine CRLM patients receiving simultaneous resection between February 2010 and February 2018 at our hospital were enrolled. A 1:3 propensity score matching analysis (PSM) analysis was performed to balance covariates and avoid selection bias. After PSM, 90 patients were distributed to the POI group, and 233 patients were distributed to the no POI group. A log-rank test was performed to compare the progression-free survival (PFS) and overall survival (OS) data. A multivariate Cox regression model was employed to identify prognostic factors influencing OS and PFS. A value of two-sided P<0.05 was considered statistically significant.

Results

Compared to patients in the no POI group, patients in the POI group were more likely to have hepatic portal occlusion (78.9% vs. 66.3%, P=0.021), operation time ≥325 min (61.1% vs. 48.1%, P=0.026), and intraoperative blood loss ≥200 ml (81.1% vs. 67.6%, P=0.012). In multivariate analysis, intraoperative blood loss ≥200 ml (OR = 2.057, 95% CI: 1.165-3.634, P=0.013) was identified as the only independent risk factor for POI. Patients with POI had a worse PFS (P<0.001, median PFS: 7.5 vs. 12.7 months) and a worse OS (P=0.010, median OS: 38.8 vs. 59.0 months) than those without POI. After 1:3 PSM analysis, no differences in clinicopathologic parameters were detected between the POI group and the no POI group. Patients with POI had a worse PFS (P=0.013, median PFS: 7.5 vs. 11.1 months) and a worse OS (P=0.020, median OS: 38.8 vs. 59.0 months) than those without POI. Multivariate analysis showed that POI was an independent predictor for worse PFS (HR=1.410, 95% CI: 1.065-1.869, P=0.017) and worse OS (HR=1.682, 95% CI: 1.113-2.544, P=0.014).

Conclusions

POI can significantly worsen the long-term outcomes of CRLM patients receiving simultaneous resection of colorectal cancer and liver metastases and should be considered to improve postoperative management and make better treatment decisions for these patients.
Intense Acute Swimming Induces Delayed-Onset Muscle Soreness Dependent on Spinal Cord Neuroinflammation
Authors: Borghi Sergio M. , Bussulo Sylvia K. D. , Pinho-Ribeiro Felipe A. , Fattori Victor , Carvalho Thacyana T. , Rasquel-Oliveira Fernanda S. , Zaninelli Tiago H. , Ferraz Camila R. , Casella Antônio M. B. , Cunha Fernando Q. , Cunha Thiago M. , Casagrande Rubia , Verri Waldiceu A.
Published: January 2022

Unaccustomed exercise involving eccentric contractions, high intensity, or long duration are recognized to induce delayed-onset muscle soreness (DOMS). Myocyte damage and inflammation in affected peripheral tissues contribute to sensitize muscle nociceptors leading to muscle pain. However, despite the essential role of the spinal cord in the regulation of pain, spinal cord neuroinflammatory mechanisms in intense swimming-induced DOMS remain to be investigated. We hypothesized that spinal cord neuroinflammation contributes to DOMS. C57BL/6 mice swam for 2 h to induce DOMS, and nociceptive spinal cord mechanisms were evaluated. DOMS triggered the activation of astrocytes and microglia in the spinal cord 24 h after exercise compared to the sham group. DOMS and DOMS-induced spinal cord nuclear factor κB (NFκB) activation were reduced by intrathecal treatments with glial inhibitors (fluorocitrate, α-aminoadipate, and minocycline) and NFκB inhibitor [pyrrolidine dithiocarbamate (PDTC)]. Moreover, DOMS was also reduced by intrathecal treatments targeting C-X3-C motif chemokine ligand 1 (CX3CL1), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β or with recombinant IL-10. In agreement, DOMS induced the mRNA and protein expressions of CX3CR1, TNF-α, IL-1β, IL-10, c-Fos, and oxidative stress in the spinal cord. All these immune and cellular alterations triggered by DOMS were amenable by intrathecal treatments with glial and NFκB inhibitors. These results support a role for spinal cord glial cells, via NFκB, cytokines/chemokines, and oxidative stress, in DOMS. Thus, unveiling neuroinflammatory mechanisms by which unaccustomed exercise induces central sensitization and consequently DOMS.
Determinants of Kidney Function and Accuracy of Kidney Microcysts Detection in Patients Treated With Lithium Salts for Bipolar Disorder
Authors: Tabibzadeh Nahid , Faucon Anne-Laure , Vidal-Petiot Emmanuelle , Serrano Fidéline , Males Lisa , Fernandez Pedro , Khalil Antoine , Rouzet François , Tardivon Coralie , Mazer Nicolas , Dubertret Caroline , Delavest Marine , Marlinge Emeline , Etain Bruno , Bellivier Frank , Vrtovsnik François , Flamant Martin
Published: January 2022

Objectives: Early kidney damage during lithium treatment in bipolar disorder is still hypothetical. We aimed at identifying the determinants of a decreased measured glomerular filtration rate (mGFR) and the accuracy of kidney MRI imaging in its detection.

Methods: In this cross-sectional cohort study, 217 consecutive lithium-treated patients underwent mGFR and kidney MRI with half-Fourier turbo spin-echo and Single-shot with long echo time sequences.

Results: Median age was 51 [27–62] years, and median lithium treatment duration was 5 [2–14] years. 52% of patients had a stage 2 CKD. In multivariable analysis, the determinants of a lower mGFR were a longer lithium treatment duration (β −0.8 [−1; −0.6] ml/min/1.73 m2 GFR decrease for each year of treatment), a higher age (β −0.4 [−0.6; −0.3] ml/min/1.73 m2 for each year of age, p < 0.001), albuminuria (β −3.97 [−6.6; −1.3], p = 0.003), hypertension (β −6.85 [−12.6; −1.1], p = 0.02) and hypothyroidism (β −7.1 [−11.7; −2.5], p = 0.003). Serum lithium concentration was not associated with mGFR. Renal MRI displayed renal microcyst(s) in 51% of patients, detected as early as 1 year after lithium treatment initiation. mGFR and lithium treatment duration were strongly correlated in patients with microcyst(s) (r = −0.64, p < 0.001), but not in patients with no microcysts (r = −0.24, p = 0.09). The presence of microcysts was associated with the detection of an mGFR <45 ml/min/1.73 m2 (AUC 0.893, p < 0.001, sensitivity 80%, specificity 81% for a cut-off value of five microcysts).

Conclusion: Lithium treatment duration and hypothyroidism strongly impacted mGFR independently of age, especially in patients with microcysts. MRI might help detect early lithium-induced kidney damage and inform preventive strategies.
Dapagliflozin Alleviates Renal Fibrosis by Inhibiting RIP1-RIP3-MLKL-Mediated Necroinflammation in Unilateral Ureteral Obstruction
Authors: Xuan Mei Ying , Piao Shang Guo , Ding Jun , Nan Qi Yan , Piao Mei Hua , Jiang Yu Ji , Zheng Hai Lan , Jin Ji Zhe , Li Can
Published: January 2022

Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, offers renoprotection in diabetes. However, potential for use in nondiabetic kidney disease remains unknown. Herein, we assessed whether dapagliflozin alleviates renal fibrosis by interfering with necroinflammation in a rat model of unilateral ureteral obstruction (UUO) and in vitro. After induction of UUO, rats were administered dapagliflozin daily for seven consecutive days. UUO induced significant renal tubular necrosis and overexpression of RIP1-RIP3-MLKL axis proteins; these coincided with NLRP3 inflammasome activation, and subsequent development of renal fibrosis. Oxidative stress caused by UUO is tightly associated with endoplasmic reticulum stress and mitochondrial dysfunction, leading to apoptotic cell death through Wnt3α/β-catenin/GSK-3β signaling; all of which were abolished by both dapagliflozin and specific RIP inhibitors (necrostatin-1 and GSK872). In H2O2-treated HK-2 cells, dapagliflozin and RIP inhibitors suppressed overexpression of RIP1-RIP3-MLKL proteins and pyroptosis-related cytokines, decreased intracellular reactive oxygen species production and apoptotic cell death, whereas cell viability was improved. Moreover, activated Wnt3α/β-catenin/GSK-3β signaling was inhibited by dapagliflozin and Wnt/β-catenin inhibitor ICG-001. Our findings suggest that dapagliflozin ameliorates renal fibrosis by inhibiting RIP1-RIP3-MLKL-mediated necroinflammation via Wnt3α/β-catenin/GSK-3β signaling in UUO.
First Helicon Plasma Physics and Applications Workshop
Authors: Chang Lei , Boswell Rod , Luo Guangnan
Published: January 2022

The First Helicon Plasma Physics and Applications Workshop was held on September 23−24, 2021, through Zoom Cloud Meeting, instead of in an on-site gathering, due to the COVID-19 pandemic. It was convened by Rod Boswell (IOC) and Guangnan Luo (LOC), and organised by Lei Chang’s group. The workshop attracted 110 registrations and ∼100 online audiences from ∼30 affiliations. There were 33 presentations covering the various fundamental physics of helicon plasma and its applications to space electric propulsion, material processing, and magnetic confinement fusion. This paper highlights the presentations, discussions, and perspectives given in the workshop, serving as reference for the helicon community.
A 3D DEM Model for Air Sparging Technology in the Saturated Granular Soils
Authors: Wu Kai , Li Zan , Liu Zhibin , Liu Songyu
Published: January 2022

This work provides a three-dimensional discrete element simulation (DEM) model to study the air sparging technology. The simulations have taken into account the multi-phases of bubble (gas) - fluid (water) - soil (solid) particles. Bubbles are treated as discrete individual particles, with buoyancy and drag forces applied to bubbles and soil particles. The trajectory of each discrete bubble particle can be tracked using the discrete element model. It is found that the diffusion of the whole bubble is inverted conical though the motion behavior of a single bubble particle is random. Furthermore, the distribution of the radius of influence (ROI) is not uniform. The bubbles become more concentrated as in the center of the inverted cone. The number of bubbles dissipated from the water surface is normally distributed. The DEM simulation is a novel approach to studying air sparging technology that can provide us a deeper insight into bubble migration at the microscopic level.
TmIKKε Is Required to Confer Protection Against Gram-Negative Bacteria, E. coli by the Regulation of Antimicrobial Peptide Production in the Tenebrio molitor Fat Body
Authors: Ko Hye Jin , Patnaik Bharat Bhusan , Park Ki Beom , Kim Chang Eun , Baliarsingh Snigdha , Jang Ho Am , Lee Yong Seok , Han Yeon Soo , Jo Yong Hun
Published: January 2022

The inhibitor of nuclear factor-kappa B (NF-κB) kinase (IKK) is the core regulator of the NF-κB pathway against pathogenic invasion in vertebrates or invertebrates. IKKβ, -ε and -γ have pivotal roles in the Toll and immune deficiency (IMD) pathways. In this study, a homolog of IKKε (TmIKKε) was identified fromTenebrio molitorRNA sequence database and functionally characterized for its role in regulating immune signaling pathways in insects. TheTmIKKεgene is characterized by two exons and one intron comprising an open reading frame (ORF) of 2,196 bp that putatively encodes a polypeptide of 731 amino acid residues.TmIKKε contains a serine/threonine protein kinases catalytic domain. Phylogenetic analysis established the close homology ofTmIKKε toTribolium castaneumIKKε (TcIKKε) and its proximity with other IKK-related kinases. The expression ofTmIKKεmRNA was elevated in the gut, integument, and hemocytes of the last-instar larva and the fat body, Malpighian tubules, and testis of 5-day-old adults.TmIKKεexpression was significantly induced byEscherichia coli,Staphylococcus aureus, andCandida albicanschallenge in whole larvae and tissues, such as hemocytes, gut, and fat body. The knockdown of theTmIKKεmessenger RNA (mRNA) expression significantly reduced the survival of the larvae against microbial challenges. Further, we investigated the induction patterns of 14T. molitorantimicrobial peptides (AMPs) genes inTmIKKεgene-silencing model after microbial challenges. While in hemocytes, the transcriptional regulation of most AMPs was negatively regulated in the gut and fat body tissue ofT. molitor, AMPs, such asTmTenecin 1,TmTenecin 4,TmDefensin,TmColeoptericin A,TmColeoptericin B,TmAttacin 1a, andTmAttacin 2, were positively regulated inTmIKKε-silenced individuals after microbial challenge. Collectively, the results implicateTmIKKεas an important factor in antimicrobial innate immune responses inT. molitor.
Androgenesis-Based Doubled Haploidy: Past, Present, and Future Perspectives
Authors: Hale Brett , Ferrie Alison M. R. , Chellamma Sreekala , Samuel J. Pon , Phillips Gregory C.
Published: January 2022

Androgenesis, which entails cell fate redirection within the microgametophyte, is employed widely for genetic gain in plant breeding programs. Moreover, androgenesis-responsive species provide tractable systems for studying cell cycle regulation, meiotic recombination, and apozygotic embryogenesis within plant cells. Past research on androgenesis has focused on protocol development with emphasis on temperature pretreatments of donor plants or floral buds, and tissue culture optimization because androgenesis has different nutritional requirements than somatic embryogenesis. Protocol development for new species and genotypes within responsive species continues to the present day, but slowly. There is more focus presently on understanding how protocols work in order to extend them to additional genotypes and species. Transcriptomic and epigenetic analyses of induced microspores have revealed some of the cellular and molecular responses required for or associated with androgenesis. For example, microRNAs appear to regulate early microspore responses to external stimuli; trichostatin-A, a histone deacetylase inhibitor, acts as an epigenetic additive; ά-phytosulfokine, a five amino acid sulfated peptide, promotes androgenesis in some species. Additionally, present work on gene transfer and genome editing in microspores suggest that future endeavors will likely incorporate greater precision with the genetic composition of microspores used in doubled haploid breeding, thus likely to realize a greater impact on crop improvement. In this review, we evaluate basic breeding applications of androgenesis, explore the utility of genomics and gene editing technologies for protocol development, and provide considerations to overcome genotype specificity and morphogenic recalcitrance in non-model plant systems.
Genetic Architecture and Candidate Genes for Pubescence Length and Density and Its Relationship With Resistance to Common Cutworm in Soybean
Authors: Li Yawei , Chu Li , Liu Xiaofeng , Zhang Nannan , Xu Yufei , Karikari Benjamin , Wang Yu , Chang Fangguo , Liu Zexinan , Tan Lianmei , Yue Han , Xing Guangnan , Zhao Tuanjie
Published: January 2022

Soybean pubescence plays an important role in insect resistance, drought tolerance, and other stresses. Hence, a deep understanding of the molecular mechanism underlying pubescence is a prerequisite to a deeper understanding of insect resistance and drought tolerance. In the present study, quantitative trait loci (QTL) mapping of pubescence traits was performed using a high-density inter-specific linkage map of one recombinant inbred line (RIL) population, designated NJRINP. It was observed that pubescence length (PL) was negatively correlated with pubescence density (PD). A total of 10 and 9 QTLs distributed on six and five chromosomes were identified with phenotypic variance (PV) of 3.0–9.9% and 0.8–15.8% for PL and PD, respectively, out of which, eight and five were novel. Most decreased PL (8 of 10) and increased PD (8 of 9) alleles were from the wild soybean PI 342618B. Based on gene annotation, Protein ANalysis THrough Evolutionary Relationships and literature search, 21 and 12 candidate genes were identified related to PL and PD, respectively. In addition, Glyma.12G187200 from major QTLs qPL-12-1 and qPD-12-2, was identified as Ps (sparse pubescence) before, having an expression level of fivefold greater in NN 86-4 than in PI 342618B, hence it might be the candidate gene that is conferring both PL and PD. Based on gene expression and cluster analysis, three and four genes were considered as the important candidate genes of PL and PD, respectively. Besides, leaves with short and dense (SD) pubescence, which are similar to the wild soybean pubescence morphology, had the highest resistance to common cutworm (CCW) in soybean. In conclusion, the findings in the present study provide a better understanding of genetic basis and candidate genes information of PL and PD and the relationship with resistance to CCW in soybean.
Defoliation Significantly Suppressed Plant Growth Under Low Light Conditions in Two Leguminosae Species
Authors: Wang Ning , Ji Tianyu , Liu Xiao , Li Qiang , Sairebieli Kulihong , Wu Pan , Song Huijia , Wang Hui , Du Ning , Zheng Peiming , Wang Renqing
Published: January 2022

Seedlings in regenerating layer are frequently attacked by herbivorous insects, while the combined effects of defoliation and shading are not fully understood. In the present study, two Leguminosae species (Robinia pseudoacacia and Amorpha fruticosa) were selected to study their responses to combined light and defoliation treatments. In a greenhouse experiment, light treatments (L+, 88% vs L−, 8% full sunlight) and defoliation treatments (CK, without defoliation vs DE, defoliation 50% of the upper crown) were applied at the same time. The seedlings’ physiological and growth traits were determined at 1, 10, 30, and 70 days after the combined treatment. Our results showed that the effects of defoliation on growth and carbon allocation under high light treatments in both species were mainly concentrated in the early stage (days 1–10). R. pseudoacacia can achieve growth recovery within 10 days after defoliation, while A. fruticosa needs 30 days. Seedlings increased SLA and total chlorophyll concentration to improve light capture efficiency under low light treatments in both species, at the expense of reduced leaf thickness and leaf lignin concentration. The negative effects of defoliation treatment on plant growth and non-structural carbohydrates (NSCs) concentration in low light treatment were significantly higher than that in high light treatment after recovery for 70 days in R. pseudoacacia, suggesting sufficient production of carbohydrate would be crucial for seedling growth after defoliation. Plant growth was more sensitive to defoliation and low light stress than photosynthesis, resulting in NSCs accumulating during the early period of treatment. These results illustrated that although seedlings could adjust their resource allocation strategy and carbon dynamics in response to combined defoliation and light treatments, individuals grown in low light conditions will be more suppressed by defoliation. Our results indicate that we should pay more attention to understory seedlings’ regeneration under the pressure of herbivorous insects.
Water Use Characteristics of Weeds: A Global Review, Best Practices, and Future Directions
Authors: Singh Mandeep , Kukal Meetpal Singh , Irmak Suat , Jhala Amit J.
Published: January 2022

Weeds usually penalize crop yields by competing for resources, such as water, light, nutrients, and space. Most of the studies on the crop-weed competition domain are limited to assessing crop-yield losses due to weed pressure and other crop-weed interactions, overlooking the significant uptake of soil-water by weeds that exacerbates global water constraints and threatens the productivity and profitability. The objective of this review was to synthesize globally available quantitative data on weed water use (WU) sourced from 23 peer-reviewed publications (filtered from 233 publications via a multi-step protocol of inclusion criteria) with experimental investigations across space (3 continents), time (1927–2018), weed species (27 broadleaf and 7 grasses) and characteristics, cropping systems (5), soil types (ranging from coarse-textured sand to fine-textured clay soils), determination techniques, experimental factors (environment, management, resource availability, and competition), and aridity regimes (ranging from semi-arid to humid climate). Distributions of weed WU data reported via eight different metrics were assessed for variability and mean WU. A lack of the best experimental and reporting practices in weed WU research was identified that undermined the robustness, transferability, and application of the WU data. Mandatory protocols and the best practices typically followed in the agricultural water management research were described and recommended for weed scientists to avoid pitfalls in quantifying and presenting weed WU. A model of mixed plant community evapotranspiration (ET) was adapted to model weed-crop-soil system evaporation and transpiration in a crop canopy infested with multiple (n) weed species. Finally, potential cross-disciplinary questions across the domains of crop science, weed science, agricultural water management, irrigation science and engineering, and environmental changes were proposed to direct and prioritize future research efforts in the crop-weed-water arena.
Instability and Uncertainty Are Critical for Psychotherapy: How the Therapeutic Alliance Opens Us Up
Authors: Connolly Patrick
Published: January 2022

Tschacher and Haken have recently applied a systems-based approach to modeling psychotherapy process in terms of potentially beneficial tendencies toward deterministic as well as chaotic forms of change in the client’s behavioral, cognitive and affective experience during the course of therapy. A chaotic change process refers to a greater exploration of the states that a client can be in, and it may have a potential positive role to play in their development. A distinction is made between on the one hand, specific instances of instability which are due to techniques employed by the therapist, and on the other, a more general instability which is due to the therapeutic relationship, and a key, necessary result of a successful therapeutic alliance. Drawing on Friston’s systems-based model of free energy minimization and predictive coding, it is proposed here that the increase in the instability of a client’s functioning due to therapy can be conceptualized as a reduction in the precisions (certainty) with which the client’s prior beliefs about themselves and their world, are held. It is shown how a good therapeutic alliance (characterized by successful interpersonal synchrony of the sort described by Friston and Frith) results in the emergence of a new hierarchical level in the client’s generative model of themselves and their relationship with the world. The emergence of this new level of functioning permits the reduction of the precisions of the client’s priors, which allows the client to ‘open up’: to experience thoughts, emotions and experiences they did not have before. It is proposed that this process is a necessary precursor to change due to psychotherapy. A good consilience can be found between this approach to understanding the role of the therapeutic alliance, and the role of epistemic trust in psychotherapy as described by Fonagy and Allison. It is suggested that beneficial forms of instability in clients are an underappreciated influence on psychotherapy process, and thoughts about the implications, as well as situations in which instability may not be beneficial (or potentially harmful) for therapy, are considered.
Computer-Based Assessment: Dual-Task Outperforms Large-Screen Cancellation Task in Detecting Contralesional Omissions
Authors: Villarreal Sanna , Linnavuo Matti , Sepponen Raimo , Vuori Outi , Bonato Mario , Jokinen Hanna , Hietanen Marja
Published: January 2022

Objective: Traditionally, asymmetric spatial processing (i.e., hemispatial neglect) has been assessed with paper-and-pencil tasks, but growing evidence indicates that computer-based methods are a more sensitive assessment modality. It is not known, however, whether simply converting well-established paper-and-pencil methods into a digital format is the best option. The aim of the present study was to compare sensitivity in detecting contralesional omissions of two different computer-based methods: a “digitally converted” cancellation task was compared with a computer-based Visual and Auditory dual-tasking approach, which has already proved to be very sensitive.

Methods: Participants included 40 patients with chronic unilateral stroke in either the right hemisphere (RH patients, N = 20) or the left hemisphere (LH patients, N = 20) and 20 age-matched healthy controls. The cancellation task was implemented on a very large format (173 cm × 277 cm) or in a smaller (A4) paper-and-pencil version. The computer-based dual-tasks were implemented on a 15′′ monitor and required the detection of unilateral and bilateral briefly presented lateralized targets.

Results: Neither version of the cancellation task was able to show spatial bias in RH patients. In contrast, in the Visual dual-task RH patients missed significantly more left-sided targets than controls in both unilateral and bilateral trials. They also missed significantly more left-sided than right-sided targets only in the bilateral trials of the Auditory dual-task.

Conclusion: The dual-task setting outperforms the cancellation task approach even when the latter is implemented on a (large) screen. Attentionally demanding methods are useful for revealing mild forms of contralesional visuospatial deficits.
Eminence of Leader Humility for Follower Creativity During COVID-19: The Role of Self-Efficacy and Proactive Personality
Authors: Asghar Farwa , Mahmood Shahid , Iqbal Khan Kanwal , Gohar Qureshi Madeeha , Fakhri Mahendra
Published: January 2022

The purpose of this study is to understand how leader humility effectively stimulates follower creativity in the workplace during the coronavirus disease 2019 (COVID-19) scenario. Relying on social cognitive and social information processing theories, this study investigates how leader humility cultivates follower self-efficacy and follower creativity. Furthermore, it explores an intervening mechanism of follower self-efficacy and examines a moderating role of leader proactive personality. The hypothesized model is empirically tested by collecting the data from 405 employees and 87 managers working in the banking sector of Pakistan. The results indicate that leader humility is positively related to follower self-efficacy and follower creativity, which improve the organization’s innovation climate and an environment for social sustainability. Follower self-efficacy is also significantly related to follower creativity. The mediation analysis shows that follower self-efficacy mediates the relationship between leader humility and follower creativity. Additionally, leader proactive personality moderates the relation between follower self-efficacy and follower creativity. This study highlights the importance of leader humility for creativity and extends the literature by explaining the role of self-efficacy. Furthermore, the findings may assist the policymakers in how a humble leader heightens employee creativity and social sustainability in COVID-19.
Teacher's Emotional Display Affects Students' Perceptions of Teacher's Competence, Feelings, and Productivity in Online Small-Group Discussions
Authors: Cheng Xuejiao , Xie Han , Hong Jianzhong , Bao Guanghua , Liu Zhiqiang
Published: January 2022

Teacher's emotions have been shown to be highly important in the quality and effectiveness of teaching and learning. There is a recognized need to examine the essential role of teacher's emotions in students' academic achievement. However, the influence of teacher's displays of emotions on students' outcomes in small-group interaction activities, especially in the online environment, has received little attention in prior research. The aim of the present study was to explore the relationship between teacher's different emotional displays and students' perceptions of the teacher's competence, as well as students' collaborative feelings and productivity in online small-group discussions. Using a three-level between-subjects design, 74 participants were randomly divided into four-member groups comprising a teacher and three other participants. All the groups were asked to discuss an open-ended realistic problem using online software, during which the teacher's display of emotions varied (positive vs. negative vs. neutral). The participants' self-reported questionnaire data (perception of the teacher's competence, students' feeling of pleasure, collaborative satisfaction, and willingness to continue collaborating) and productivity (number of effective ideas expressed within a given time) were measured to compare the participants who were exposed to different emotional displays. As expected, the results showed that the participants who received the teacher's positive emotional display reported that they experienced higher levels of pleasure during the task. However, in contrast to our expectations, those under the negative emotional display condition showed a significantly higher level of productivity in the group task. In addition, compared to emotional display, the participants' perceptions of the teacher's competence were rated significantly higher under the neutral condition, and they reported higher levels of collaborative satisfaction and greater willingness to continue collaborating with their group. The findings have the potential benefit of informing educational practice on whether teachers should display their emotions in a small-group discussion or how they should display emotions following adjustment for the relative aim of the teaching activities.