bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammatory role of microglia in brain injury caused by subarachnoid hemorrhage
Authors: Wang Xiao-Yi , Wu Fan , Zhan Ren-Ya , Zhou Heng-Jun
Published: December 2022

Early brain injury is a series of pathophysiological changes and direct damage of brain tissue within 72 h after subarachnoid hemorrhage before cerebral vasospasm occurs. Early brain injury is a key factor affecting the prognosis of subarachnoid hemorrhage, and its possible pathological mechanisms include oxidative stress, cell apoptosis, autophagy, and immune inflammation. Microglia are important immune cells of the central nervous system. Microglia play a dual role in protection and injury. Microglia are involved in the occurrence of brain edema, the processes of neuronal apoptosis, and the blood–brain barrier disruption after subarachnoid hemorrhage (SAH) through the signaling pathways mediated by receptors such as Toll-like receptor 4 (TLR4), calcium-sensing receptor (CaSR), and triggering receptor expressed on myeloid cells-1 (TREM-1), which secrete pro-inflammatory cytokines such as interleukins and tumor necrosis factor α. Conversely, they exert their anti-inflammatory and protective effects by expressing substances such as neuroglobin and heme oxygenase-1. This article reviews the latest developments in single-cell transcriptomics for microglia in early brain injury after subarachnoid hemorrhage and its inflammatory role.
Quantitative pupillometry and radiographic markers of intracranial midline shift: A pilot study
Authors: Kim Ivy So Yeon , Balogun Oluwafemi O. , Prescott Brenton R. , Saglam Hanife , Olson DaiWai M. , Speir Kinley , Stutzman Sonja E. , Schneider Nathan , Aguilera Veronica , Lussier Bethany L. , Smirnakis Stelios M. , Dupuis Josée , Mian Asim , Greer David M. , Ong Charlene J.
Published: December 2022

Background

Asymmetric pupil reactivity or size can be early clinical indicators of midbrain compression due to supratentorial ischemic stroke or primary intraparenchymal hemorrhage (IPH). Radiographic midline shift is associated with worse functional outcomes and life-saving interventions. Better understanding of quantitative pupil characteristics would be a non–invasive, safe, and cost-effective way to improve identification of life-threatening mass effect and resource utilization of emergent radiographic imaging. We aimed to better characterize the association between midline shift at various anatomic levels and quantitative pupil characteristics.

Methods

We conducted a multicenter retrospective study of brain CT images within 75 min of a quantitative pupil observation from patients admitted to Neuro-ICUs between 2016 and 2020 with large (>1/3 of the middle cerebral artery territory) acute supratentorial ischemic stroke or primary IPH > 30 mm3. For each image, we measured midline shift at the septum pellucidum (MLS-SP), pineal gland shift (PGS), the ratio of the ipsilateral to contralateral midbrain width (IMW/CMW), and other exploratory markers of radiographic shift/compression. Pupil reactivity was measured using an automated infrared pupillometer (NeurOptics®, Inc.), specifically the proprietary algorithm for Neurological Pupil Index® (NPi). We used rank-normalization and linear mixed-effects models, stratified by diagnosis and hemorrhagic conversion, to test associations of radiographic markers of shift and asymmetric pupil reactivity (Diff NPi), adjusting for age, lesion volume, Glasgow Coma Scale, and osmotic medications.

Results

Of 53 patients with 74 CT images, 26 (49.1%) were female, and median age was 67 years. MLS-SP and PGS were greater in patients with IPH, compared to patients with ischemic stroke (6.2 v. 4.0 mm, 5.6 v. 3.4 mm, respectively). We found no significant associations between pupil reactivity and the radiographic markers of shift when adjusting for confounders. However, we found potentially relevant relationships between MLS-SP and Diff NPi in our IPH cohort (β = 0.11, SE 0.04, P = 0.01), and PGS and Diff NPi in the ischemic stroke cohort (β = 0.16, SE 0.09, P = 0.07).

Conclusion

We found the relationship between midline shift and asymmetric pupil reactivity may differ between IPH and ischemic stroke. Our study may serve as necessary preliminary data to guide further prospective investigation into how clinical manifestations of radiographic midline shift differ by diagnosis and proximity to the midbrain.
A meta-analysis of brain morphometric aberrations in adolescents who experienced childhood trauma
Authors: Tymofiyeva Olga , Hu Rebecca , Kidambi Roma , Nguyen Ca , Max Jeffrey E. , Yang Tony T.
Published: December 2022

Introduction

Childhood trauma is known to have dramatic effects on the risks for developing psychiatric disorders and increased suicidality. We conducted a meta-analysis of whole brain voxel-based morphometry (VBM) correlates of childhood trauma in adolescents exposed to childhood maltreatment (N = 379) and unexposed controls (N = 348).

Methods

Anisotropic effect size-signed differential mapping (AES-SDM) was utilized to synthesize the studies.

Results

We observed increased volume amongst adolescents with a history of childhood trauma in regions that are involved in motor functions and language production: left precentral gyrus, including part of the left inferior frontal gyrus, left fibers of the body of corpus callosum, and left postcentral gyrus. We observed decreased volume amongst adolescents with a history of childhood trauma in regions that are involved in language processing and/or sensory processing: bilateral cerebellum, bilateral middle temporal gyrus, left rostrum of corpus callosum, and bilateral supramarginal gyrus.

Discussion

We suggest that these morphometric differences may be reflective of impaired motor development and increased sensory sensitivity and hypervigilance in adolescents with experiences of childhood trauma. Our results differ from meta-analytical findings in adults with history of childhood trauma and may contribute to a better understanding of neural mechanisms of childhood trauma, prediction of neurodevelopmental outcomes, and development of more effective and personalized therapies.
Indigenous yeast can increase the phenolic acid and volatile ester compounds in Petit Manseng wine
Authors: Wang Yanyu , Wang Miao , Li Wenjuan , Wang Xinyuan , Kong Weifu , Huang Weidong , Zhan Jicheng , Xia Guangli , You Yilin
Published: December 2022

Introduction

Indigenous yeasts are generally found in grapes, vineyards, and natural environments. Sequential inoculation and fermentation with non-Saccharomyces cerevisiae yeast (H30) and Saccharomyces cerevisiae (YT13) also improve the flavor of wine.

Methods

This study sequentially inoculated fermented Petit Manseng and natural grape juice with native H30 and YT13 selected from vineyards in Yantai, China.

Results and discussion

The sensory characteristics of Petit Manseng wine were evaluated by detecting the primary organic acids, phenolic acid compounds, and volatile ester compounds. The results showed that the lactic acid content of the natural wine fermented sequentially with H30 and YT13 increased by 490 μg/L compared with the control group, while the ferulic acid content was 1.4 times that of the single-yeast fermentation group. Furthermore, butyrolactone and anthocyanidin propionate were present in the mixed fermentation group, increasing the aroma complexity of Petit Manseng wine and providing high-quality yeast resources that increase the regional characteristics when producing dry white wine.
The prevention and treatment of breast cancer- related lymphedema: A review
Authors: McEvoy Maureen P. , Gomberawalla Ameer , Smith Mark , Boccardo Francesco M. , Holmes Dennis , Djohan Risal , Thiruchelvam Paul , Klimberg Suzanne , Dietz Jill , Feldman Sheldon
Published: December 2022

Background

Breast cancer- related lymphedema (BCRL) affects about 3 to 5 million patients worldwide, with about 20,000 per year in the United States. As breast cancer mortality is declining due to improved diagnostics and treatments, the long-term effects of treatment for BCRL need to be addressed.

Methods

The American Society of Breast Surgeons Lymphatic Surgery Working Group conducted a large review of the literature in order to develop guidelines on BCRL prevention and treatment. This was a comprehensive but not systematic review of the literature. This was inclusive of recent randomized controlled trials, meta-analyses, and reviews evaluating the prevention and treatment of BCRL. There were 25 randomized clinical trials, 13 systemic reviews and meta-analyses, and 87 observational studies included.

Results

The findings of our review are detailed in the paper, with each guideline being analyzed with the most recent data that the group found evidence of to suggest these recommendations.

Conclusions

Prevention and treatment of BCRL involve a multidisciplinary team. Early detection, before clinically apparent, is crucial to prevent irreversible lymphedema. Awareness of risk factors and appropriate practice adjustments to reduce the risk aids are crucial to decrease the progression of lymphedema. The treatment can be costly, time- consuming, and not always effective, and therefore, the overall goal should be prevention.
Predicting of axillary lymph node metastasis in invasive breast cancer using multiparametric MRI dataset based on CNN model
Authors: Zhang Xiaodong , Liu Menghan , Ren Wanqing , Sun Jingxiang , Wang Kesong , Xi Xiaoming , Zhang Guang
Published: December 2022

Purpose

To develop a multiparametric MRI model for predicting axillary lymph node metastasis in invasive breast cancer.

Methods

Clinical data and T2WI, DWI, and DCE-MRI images of 252 patients with invasive breast cancer were retrospectively analyzed and divided into the axillary lymph node metastasis (ALNM) group and non-ALNM group using biopsy results as a reference standard. The regions of interest (ROI) in T2WI, DWI, and DCE-MRI images were segmented using MATLAB software, and the ROI was unified into 224 × 224 sizes, followed by image normalization as input to T2WI, DWI, and DCE-MRI models, all of which were based on ResNet 50 networks. The idea of a weighted voting method in ensemble learning was employed, and then T2WI, DWI, and DCE-MRI models were used as the base models to construct a multiparametric MRI model. The entire dataset was randomly divided into training sets and testing sets (the training set 202 cases, including 78 ALNM, 124 non-ALNM; the testing set 50 cases, including 20 ALNM, 30 non-ALNM). Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of models were calculated. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic performance of each model for axillary lymph node metastasis, and the DeLong test was performed, P< 0.05 statistically significant.

Results

For the assessment of axillary lymph node status in invasive breast cancer on the test set, multiparametric MRI models yielded an AUC of 0.913 (95% CI, 0.799-0.974); T2WI-based model yielded an AUC of 0.908 (95% CI, 0.792-0.971); DWI-based model achieved an AUC of 0.702 (95% CI, 0.556-0.823); and the AUC of the DCE-MRI-based model was 0.572 (95% CI, 0.424-0.711). The improvement in the diagnostic performance of the multiparametric MRI model compared with the DWI and DCE-MRI-based models were significant (P< 0.01 for both). However, the increase was not meaningful compared with the T2WI-based model (P = 0.917).

Conclusion

Multiparametric MRI image analysis based on an ensemble CNN model with deep learning is of practical application and extension for preoperative prediction of axillary lymph node metastasis in invasive breast cancer.
Alterations in cellular metabolisms after TKI therapy for Philadelphia chromosome-positive leukemia in children: A review
Authors: Li Chunmou , Wen Luping , Dong Junchao , Li Lindi , Huang Junbin , Yang Jing , Liang Tianqi , Li Tianwen , Xia Zhigang , Chen Chun
Published: December 2022

Incidence rates of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) are lower but more aggressive in children than in adults due to different biological and host factors. After the clinical application of tyrosine kinase inhibitor (TKI) blocking BCR/ABL kinase activity, the prognosis of children with CML and Ph+ ALL has improved dramatically. Yet, off-target effects and drug tolerance will occur during the TKI treatments, contributing to treatment failure. In addition, compared to adults, children may need a longer course of TKIs therapy, causing detrimental effects on growth and development. In recent years, accumulating evidence indicates that drug resistance and side effects during TKI treatment may result from the cellular metabolism alterations. In this review, we provide a detailed summary of the current knowledge on alterations in metabolic pathways including glucose metabolism, lipid metabolism, amino acid metabolism, and other metabolic processes. In order to obtain better TKI treatment outcomes and avoid side effects, it is essential to understand how the TKIs affect cellular metabolism. Hence, we also discuss the relevance of cellular metabolism in TKIs therapy to provide ideas for better use of TKIs in clinical practice.
Adenocarcinoma arising in an ectopic enterogenous cyst: A rare case report and review of literature
Authors: Du Haina , Xu Dachao , Zhang Shuhui , Zhang Xinliang , Fang Mingzhi , Li Min
Published: December 2022

Enterogenous cyst (EC) is a rare congenital lesion generally located in the central nervous system, such as in the cerebral hemispheres, posterior fossa, or spinal canal. They are usually benign lesions, and malignant transformation is rare. A 42-year-old woman felt an obvious pain in the lump and went to a local hospital for local lumpectomy. After 7 months, she again felt pain in the buttocks and difficulty in urinating and defecation. The computed tomography (CT) scan showed a mass in the pelvis. Sacrococcygeal cyst excision was performed 10 days later, and postoperative pathology showed epidermoid cyst. Shortly after, the patient recovered and was discharged from the hospital; the pain in the buttocks continued to recur. Puncture and drainage were performed five times. Later, the patient went to our hospital for treatment, and pelvic MRI showed multiple abnormal signal shadows in the presacral and sacrococcygeal regions, some of which were considered abscesses, and some were cystic lesions. She underwent tumor resection and was diagnosed with EC with locally moderately differentiated adenocarcinoma. Four months later, the patient’s symptoms of swelling and pain recurred. MRI examination showed multiple high-signal T2 shadows in the anterior sacral and subcutaneous tissues of the buttocks, and enhanced scan showed partial marginal enhancement. After assessment, the patient was given a radiation dose of 60 Gy/25F. ECs in the anterior sacral and soft tissue of the buttocks are very rare, and the case of carcinomatous transformation has never been reported. Therefore, we discussed the clinicopathological features of ectopic ECs and reviewed the literature.
Cost-effectiveness analysis of sintilimab vs. placebo in combination with chemotherapy as first-line therapy for local advanced or metastatic oesophageal squamous cell carcinoma
Authors: Shao Taihang , Zhao Mingye , Tang Wenxi
Published: December 2022

Objective

Results of Orient 15 indicated the health benefits to patients with local advanced or metastatic oesophageal squamous cell carcinoma (OSCC). This study aimed to evaluate the cost-effectiveness of sintilimab plus chemotherapy in treating OSCC from the perspective of Chinese healthcare system.

Methods

A partitioned survival model was constructed to evaluate the cost-effectiveness of sintilimab plus chemotherapy vs. chemotherapy in treating OSCC. Baseline characteristics of patients and key clinical data were extracted from Orient 15. Costs and utilities were collected from published studies and open-access databases. Costs, quality-adjusted life-years (QALYs), life-years gained, and incremental cost-effectiveness ratios (ICER) were chosen as economic outcome indicators. We also performed sensitivity analyses and subgroup analyses to verify the stability of results.

Results

Combination therapy provided additional 0.84 QALYs and 1.46 life-years with an incremental cost of $25,565.48 than chemotherapy, which had an ICER of $30,409.44 per QALY. The probabilistic sensitivity analysis indicated that combination therapy had a 98.8% probability of cost-effectiveness at the willingness-to-pay threshold (WTP) of $38,184 per QALY. Deterministic sensitivity analysis showed that model outcomes were sensitive to the utilities of progression-free survival and progression disease. The subgroup analysis revealed that combination therapy was cost-effective in patients with high expression of PD-L1 and several specific subgroups.

Conclusion

In this economic evaluation, sintilimab plus chemotherapy was likely to be cost-effective compared with chemotherapy in the first-line therapy of advanced OSCC from the perspective of Chinese healthcare system. Our findings may provide evidence for clinicians to make optimal decisions in clinical practice and for decision-makers to evaluate the cost-effectiveness of sintilimab.
Optimal predictive probability designs for randomized biomarker-guided oncology trials
Authors: Zabor Emily C. , Kaizer Alexander M. , Pennell Nathan A. , Hobbs Brian P.
Published: December 2022

Introduction

Efforts to develop biomarker-targeted anti-cancer therapies have progressed rapidly in recent years. With efforts to expedite regulatory reviews of promising therapies, several targeted cancer therapies have been granted accelerated approval on the basis of evidence acquired in single-arm phase II clinical trials. And yet, in the absence of randomization, patient prognosis for progression-free survival and overall survival may not have been studied under standard of care chemotherapies for emerging biomarker subpopulations prior to the submission of an accelerated approval application. Historical control rates used to design and evaluate emerging targeted therapies often arise as population averages, lacking specificity to the targeted genetic or immunophenotypic profile. Thus, historical trial results are inherently limited for inferring the potential “comparative efficacy” of novel targeted therapies. Consequently, randomization may be unavoidable in this setting. Innovations in design methodology are needed, however, to enable efficient implementation of randomized trials for agents that target biomarker subpopulations.

Methods

This article proposes three randomized designs for early phase biomarker-guided oncology clinical trials. Each design utilizes the optimal efficiency predictive probability method to monitor multiple biomarker subpopulations for futility. Only designs with type I error between 0.05 and 0.1 and power of at least 0.8 were considered when selecting an optimal efficiency design from among the candidate designs formed by different combinations of posterior and predictive threshold. A simulation study motivated by the results reported in a recent clinical trial studying atezolizumab treatment in patients with locally advanced or metastatic urothelial carcinoma is used to evaluate the operating characteristics of the various designs.

Results

Out of a maximum of 300 total patients, we find that the enrichment design has an average total sample size under the null of 101.0 and a total average sample size under the alternative of 218.0, as compared to 144.8 and 213.8 under the null and alternative, respectively, for the stratified control arm design. The pooled control arm design enrolled a total of 113.2 patients under the null and 159.6 under the alternative, out of a maximum of 200. These average sample sizes that are 23-48% smaller under the alternative and 47-64% smaller under the null, as compared to the realized sample size of 310 patients in the phase II study of atezolizumab.

Discussion

Our findings suggest that potentially smaller phase II trials to those used in practice can be designed using randomization and futility stopping to efficiently obtain more information about both the treatment and control groups prior to phase III study.
Identifying hub genes, key pathways and key immune-related genes in Peyronie’s disease by integrated bioinformatic analysis
Authors: Cui Yuanshan , Chen Lili , Wang Xiaofeng , Yu Luxin , Wu Jitao
Published: December 2022

Scarring diseases, such as Peyronie’s disease (PD), usually lead to disorders in the immune system. Previous studies suggested that the PD process was regulated by immune signaling. However, the pathogenetic mechanism remains incompletely characterized. This article used bioinformatic approaches to identify hub genes, key pathways and key immune-related genes that play essential roles in PD pathogenesis. Two Gene Expression Omnibus (GEO) datasets, GSE126005 and GSE146500, were used to analyse the transcriptional profiling in both PD and normal samples. R software was applied to examine the difference in the expression of hub genes and key immune-related genes. The candidates for hub genes were further validated through protein–protein interactions (PPIs), gene correlation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. In addition, candidate miRNA‒mRNA pairs were functionally assessed. A total of 39 candidate genes were identified, the expression levels of which in PD fibroblast cells were different from those in normal cells (16 showed reduced expression in PD and 21 candidates overexpressed in PD). We found that these genes could interact with each other through PPI analysis. According to the functional enrichment analysis, the candidates may regulate some major biological processes, including cytokine‒cytokine receptor interactions and the JAK-STAT signaling pathway. IL6, IL21R, IFNE, CXCL2, EGF, and ANGPTL5 were identified as key immune-related genes. The findings may help understand the role of immunologic contributors in PD, thus shedding light on the development of more effective strategies to prevent and treat this kind of disease.
Screening of GPCR drugs for repurposing in breast cancer
Authors: Abdulkareem Noor Mazin , Bhat Raksha , Powell Reid T. , Chikermane Soumya , Yande Soham , Trinh Lisa , Abdelnasser Hala Y. , Tabassum Mantasha , Ruiz Alexis , Sobieski Mary , Nguyen Nghi D. , Park Jun Hyoung , Johnson Camille A. , Kaipparettu Benny A. , Bond Richard A. , Johnson Michael , Stephan Clifford , Trivedi Meghana V.
Published: December 2022

Drug repurposing can overcome both substantial costs and the lengthy process of new drug discovery and development in cancer treatment. Some Food and Drug Administration (FDA)-approved drugs have been found to have the potential to be repurposed as anti-cancer drugs. However, the progress is slow due to only a handful of strategies employed to identify drugs with repurposing potential. In this study, we evaluated GPCR-targeting drugs by high throughput screening (HTS) for their repurposing potential in triple-negative breast cancer (TNBC) and drug-resistant human epidermal growth factor receptor-2-positive (HER2+) breast cancer (BC), due to the dire need to discover novel targets and drugs in these subtypes. We assessed the efficacy and potency of drugs/compounds targeting different GPCRs for the growth rate inhibition in the following models: two TNBC cell lines (MDA-MB-231 and MDA-MB-468) and two HER2+ BC cell lines (BT474 and SKBR3), sensitive or resistant to lapatinib + trastuzumab, an effective combination of HER2-targeting therapies. We identified six drugs/compounds as potential hits, of which 4 were FDA-approved drugs. We focused on β-adrenergic receptor-targeting nebivolol as a candidate, primarily because of the potential role of these receptors in BC and its excellent long-term safety profile. The effects of nebivolol were validated in an independent assay in all the cell line models. The effects of nebivolol were independent of its activation of β3 receptors and nitric oxide production. Nebivolol reduced invasion and migration potentials which also suggests its inhibitory role in metastasis. Analysis of the Surveillance, Epidemiology and End Results (SEER)-Medicare dataset found numerically but not statistically significant reduced risk of all-cause mortality in the nebivolol group. In-depth future analyses, including detailed in vivo studies and real-world data analysis with more patients, are needed to further investigate the potential of nebivolol as a repurposed therapy for BC.
The efficacy and safety of epidural morphine/hydromorphone in the treatment of intractable postherpetic neuralgia: A single-center, double-blinded, randomized controlled, prospective, and non-inferiority study
Authors: Yiping Sun , Jiayi Shen , Guang Hei , Yun Ji , Bingjie Ma , Xuehua Huang , Zhiyuan Yu , Pingchuan Ma , Ke Ma
Published: December 2022

Objective: Postherpetic neuralgia (PHN) is a clinical puzzle, especially in patients who still suffered from moderate and severe pain after standard treatment. This single-center, double-blinded, randomized controlled, prospective, and non-inferiority study observed the safety and effectiveness of the epidural application of morphine or hydromorphone, trying to provide an alternative method for those patients with refractory PHN.

Methods: Eighty PHN patients with a visual analogue scale (VAS) still greater than 50 mm after routine management were randomly divided into two groups according to 1:1, respectively. One group received epidural morphine (EMO group), and the other group received epidural hydromorphone (EHM group). VAS, the number of breakthrough pain, quality of life (QOL), and anxiety/depression assessment (GAD-7 and PHQ-9 scores) were also observed before treatment, at 1, 3, 7, 14, 21, 28, 60, and 90 days after treatment, as well as side effects. Opioid withdrawal symptoms (OWSs) were also measured from 3 to 28 days after treatment.

Results: The EHM group was non-inferior to the EMO group in terms of the VAS decrease relative to baseline (VDRB) after 1-week treatment. The VAS of the two groups on all days after treatment was significantly lower than the corresponding baseline findings (p < 0.05). The breakthrough pain (BTP) decreased significantly after treatment and lasted until 14 days after treatment (p < 0.05). There was no significant difference in BTP between the two groups at each time point (p > 0.05). In terms of the QOL, GAD-7, and PHQ-9 outcomes, those were significantly improved after treatment (p < 0.05), and there was no difference between the two groups (p > 0.05). No significant AE difference across the two groups was observed in this study. Few reports of OWS were found in this trial, and there were no significant differences between the two groups (p > 0.05).

Conclusion: EHM was non-inferior to EMO in terms of the VDRB after 1-week treatment. For patients with VAS still greater than 50 mm after standard treatment, short-term application of EMO or EHM can ameliorate intractable pain, improve the quality of life, and have no obvious side effects. Short-term epidural opioid application will not lead to the appearance of OWS.
Preclinical evaluation of the ROCK1 inhibitor, GSK269962A, in acute myeloid leukemia
Authors: Pan Ting , Wang Sijia , Feng Hao , Xu Jiawen , Zhang Miao , Yao Yao , Xu Kailin , Niu Mingshan
Published: December 2022

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with high mortality that urgently requires new treatments. ROCK1 plays an essential role in regulating growth and survival in AML cells. In this study, we evaluated GSK269962A, a selective ROCK1 inhibitor, in preclinical models of AML. Compared with solid tumors, GSK269962A selectively inhibited cell growth and clonogenicity of AML cells. Furthermore, GSK269962A arrested AML cells in the G2 phase and induced apoptosis by regulating multiple cell cycle- and apoptosis-associated proteins. Strikingly, GSK269962A could eliminate leukemia cells from bone marrow, liver, and spleen in an animal model of AML and significantly prolong mouse survival. Mechanistically, GSK269962A could inhibit the growth of AML by blocking ROCK1/c-Raf/ERK signaling pathway. Notably, a correlation was found between the expression levels of ROCK1 protein and the sensitivity of GSK269962A in AML. These data highlight the potential role of ROCK1 as an attractive target for treating AML, as well as the potential of GSK269962A for use in clinical trials of AML.
Versatile non-Hermitian piezoelectric metamaterial beam with tunable asymmetric reflections
Authors: Wu Zheng , Yi Jianlin , Xia Rongyu , Chen Jianlin , Li Zheng
Published: December 2022

Non-Hermitian systems have been widely utilized to achieve specific functions for manipulating abnormal wave motion, such as asymmetric mode switching, unidirectional zero reflection (UZR), and unidirectional perfect absorption (UPA). In this paper, a novel non-Hermitian piezoelectric metamaterial beam is proposed to realize the tunable UZR of flexural waves. The unit cell of this non-Hermitian metamaterial beam consists of a host beam and two pairs of piezoelectric patches shunting different resistor–inductor circuits. Based on the flexural wave theory, the transfer matrix method is introduced to analyze the influence of electrical boundary conditions on the UZR and further clarify the relationship between the UZR and the exceptional point. The exceptional point depends only on the dissipative circuit, and it has no need for the balanced gain and loss like parity–time symmetric metamaterial. Furthermore, the UZR for the desired frequency is realized by applying a genetic algorithm, and its effectivity is experimentally validated. In addition, the non-Hermitian metamaterial beam is designed to realize the UPA of flexural waves. Results indicate that the proposed metamaterial beam is versatile and can achieve tunable manipulations of asymmetric wave propagations and has widely promising applications in many fields, such as non-destructive testing, enhanced sensing, wave isolation and vibration attenuation.
The role of tetradecane in the identification of host plants by the mirid bugs Apolygus lucorum and Adelphocoris suturalis and potential application in pest management
Authors: Yin Haichen , Li Wenjing , Xu Min , Xu Dong , Wan Peng
Published: December 2022

The mirid bugs Apolygus lucorum and Adelphocoris suturalis are considered serious pests of many crops in China, the host plant recognition of these pests remains unclear. The current study investigated the vital odor cues of two mirid bugs and evaluated the role of olfactory recognition in host recognition. The GC-EAD response of mirid bugs to volatiles of their host plant Phaseolus vulgaris was tested. Tetradecane, 2-propyl-1-pentanol, and dodecanal elicited strong EAG responses by mirid bugs and were tested with field experiments. The results indicated tetradecane was significantly more attractive than other attractants, yielding 30.33 ± 2.19 mirid bugs trapped during 7 days. The selected response rates to tetradecane were above 60%, which was most attractive to female A. lucorum at 1.5 mg/ml. Among seven tetradecane derivatives, tetradecane and tetradecanoic acid were the most potent attractants to A. lucorum and A. suturalis. Tetradecane was present in the volatiles of 10 common hosts, and their difference in relative content was significant. The presence of tetradecane seemed relevant to the olfactory response intensity of two mirid bugs towards the different host plants. The artificial supplement of tetradecane increased the attractive effect of host plants. These results suggested that tetradecane plays a vital role in the olfactory selection by two mirid bugs, and it can be made into field baits as a novel ecological strategy to manage these pests with widely reported pesticide resistance. However, results suggested host recognition is not entirely dependent on odor cues. We demonstrated that A. suturalis and A. lucorum adults have similar olfactory recognition mechanisms to their hosts in long-distance host selection. While, the differences in host plant selection between the two pests should occur in close range due to differences in gustatory or tactile sensory organs of A. lucorum and A. suturalis.
Characterization and diagnostic value of the gut microbial composition in patients with minimal change disease
Authors: Zhang Yiding , Zhou Yukun , Cui Wen , Wang Zhihui , Wang Xuemei , Wu Feng , Wang Peipei , Wang Ting , Yu Wei , Wang Li , Shang Jin , Zhao Zhanzheng
Published: December 2022

Background: Minimal change disease (MCD) is one of the most common causes of primary nephrotic syndrome with high morbidity. This study aimed to explore the typical alterations of gut microbiota in MCD and establish a non-invasive classifier using key gut microbiome. We also aimed to evaluate the therapeutic efficiency of gut microbiota intervention in MCD through animal experiments.

Methods: A total of 222 stool samples were collected from MCD patients and healthy controls at the First Affiliated Hospital of Zhengzhou University and Shandong Provincial Hospital for 16S rRNA sequencing. Optimum operational taxonomic units (OTUs) were obtained for constructing a diagnostic model. MCD rat models were established using doxorubicin hydrochloride for exploring the therapeutic efficiency of gut microbial intervention through fecal microbiota transplantation (FMT).

Results: The α-diversity of gut microbiota decreased in MCD patients when compared with healthy controls. The relative abundance of bacterial species also changed significantly. We constructed a diagnostic model based on eight optimal OTUs and it achieved efficiency of 97.81% in discovery cohort. The high efficiency of diagnostic model was also validated in the patients with different disease states and cross-regional cohorts. The treatment partially recovered the gut microbial dysbiosis in patients with MCD. In animal experiments, likewise, the gut microbiota changed sharply in MCD rats. However, gut microbial interventions did not reduce urinary protein or pathological kidney damage.

Conclusion: Gut Microbiota shifts sharply in both patients and rats with MCD. Typical microbial changes can be used as biomarkers for MCD diagnosis. The gut microbiota compositions in patients with MCD tended to normalize after treatment. However, the intervention of gut microbiota seems to have no therapeutic effect on MCD.
Phenotypic analysis of Longya-10 × pale flax hybrid progeny and identification of candidate genes regulating prostrate/erect growth in flax plants
Authors: Qi Yanni , Wang Limin , Li Wenjuan , Xie Yaping , Zhao Wei , Dang Zhao , Li Wen , Zhao Lirong , Zhang Jianping
Published: December 2022

Flax is a dual-purpose crop that is important for oil and fiber production. The growth habit is one of the crucial targets of selection during flax domestication. Wild hybridization between cultivated flax and wild flax can produce superior germplasms for flax breeding and facilitate the study of the genetic mechanism underlying agronomically important traits. In this study, we used pale flax, Linum grandiflorum, and L. perenne to pollinate Longya-10. Only pale flax interspecific hybrids were obtained, and the trait analysis of the F1 and F2 generations showed that the traits analyzed in this study exhibited disparate genetic characteristics. In the F1 generation, only one trait, i.e., the number of capsules per plant (140) showed significant heterosis, while the characteristics of other traits were closely associated with those of the parents or a decline in hybrid phenotypes. The traits of the F2 generation were widely separated, and the variation coefficient ranged from 9.96% to 146.15%. The quantitative trait locus underlying growth habit was preliminarily found to be situated on chromosome 2 through Bulked-segregant analysis sequencing. Then linkage mapping analysis was performed to fine-map GH2.1 to a 23.5-kb interval containing 4 genes. Among them, L.us.o.m.scaffold22.109 and L.us.o.m.scaffold22.112 contained nonsynonymous SNPs with Δindex=1. Combined with the qRT-PCR results, the two genes might be possible candidate genes for GH2.1. This study will contribute to the development of important germplasms for flax breeding, which would facilitate the elucidation of the genetic mechanisms regulating the growth habit and development of an ideal architecture for the flax plant.
Volatile organic compounds shape belowground plant–fungi interactions
Authors: Duc Nguyen Hong , Vo Ha T. N. , van Doan Cong , Hamow Kamirán Áron , Le Khac Hoang , Posta Katalin
Published: December 2022

Volatile organic compounds (VOCs), a bouquet of chemical compounds released by all life forms, play essential roles in trophic interactions. VOCs can facilitate a large number of interactions with different organisms belowground. VOCs-regulated plant-plant or plant-insect interaction both below and aboveground has been reported extensively. Nevertheless, there is little information about the role of VOCs derived from soilborne pathogenic fungi and beneficial fungi, particularly mycorrhizae, in influencing plant performance. In this review, we show how plant VOCs regulate plant-soilborne pathogenic fungi and beneficial fungi (mycorrhizae) interactions. How fungal VOCs mediate plant–soilborne pathogenic and beneficial fungi interactions are presented and the most common methods to collect and analyze belowground volatiles are evaluated. Furthermore, we suggest a promising method for future research on belowground VOCs.
A non-destructive coconut fruit and seed traits extraction method based on Micro-CT and deeplabV3+ model
Authors: Yu Lejun , Liu Lingbo , Yang Wanneng , Wu Dan , Wang Jinhu , He Qiang , Chen ZhouShuai , Liu Qian
Published: December 2022

With the completion of the coconut gene map and the gradual improvement of related molecular biology tools, molecular marker-assisted breeding of coconut has become the next focus of coconut breeding, and accurate coconut phenotypic traits measurement will provide technical support for screening and identifying the correspondence between genotype and phenotype. A Micro-CT system was developed to measure coconut fruits and seeds automatically and nondestructively to acquire the 3D model and phenotyping traits. A deeplabv3+ model with an Xception backbone was used to segment the sectional image of coconut fruits and seeds automatically. Compared with the structural-light system measurement, the mean absolute percentage error of the fruit volume and surface area measurements by the Micro-CT system was 1.87% and 2.24%, respectively, and the squares of the correlation coefficients were 0.977 and 0.964, respectively. In addition, compared with the manual measurements, the mean absolute percentage error of the automatic copra weight and total biomass measurements was 8.85% and 25.19%, respectively, and the adjusted squares of the correlation coefficients were 0.922 and 0.721, respectively. The Micro-CT system can nondestructively obtain up to 21 agronomic traits and 57 digital traits precisely.
NtbHLH49, a jasmonate-regulated transcription factor, negatively regulates tobacco responses to Phytophthora nicotianae
Authors: Wang Wenjing , Zhang Jianhui , Cao Yi , Yang Xingyou , Wang Fenglong , Yang Jinguang , Wang Xiaoqiang
Published: December 2022

Tobacco black shank caused by Phytophthora nicotianae is a devastating disease that causes huge losses to tobacco production across the world. Investigating the regulatory mechanism of tobacco resistance to P. nicotianae is of great importance for tobacco resistance breeding. The jasmonate (JA) signaling pathway plays a pivotal role in modulating plant pathogen resistance, but the mechanism underlying JA-mediated tobacco resistance to P. nicotianae remains largely unclear. This work explored the P. nicotianae responses of common tobacco cultivar TN90 using plants with RNAi-mediated silencing of NtCOI1 (encoding the perception protein of JA signal), and identified genes involved in this process by comparative transcriptome analyses. Interestingly, the majority of the differentially expressed bHLH transcription factor genes, whose homologs are correlated with JA-signaling, encode AtBPE-like regulators and were up-regulated in NtCOI1-RI plants, implying a negative role in regulating tobacco response to P. nicotianae. A subsequent study on NtbHLH49, a member of this group, showed that it’s negatively regulated by JA treatment or P. nicotianae infection, and its protein was localized to the nucleus. Furthermore, overexpression of NtbHLH49 decreased tobacco resistance to P. nicotianae, while knockdown of its expression increased the resistance. Manipulation of NtbHLH49 expression also altered the expression of a set of pathogen resistance genes. This study identified a set of genes correlated with JA-mediated tobacco response to P. nicotianae, and revealed the function of AtBPE-like regulator NtbHLH49 in regulating tobacco resistance to this pathogen, providing insights into the JA-mediated tobacco responses to P. nicotianae.
Water use strategies of Ferula bungeana on mega-dunes in the Badain Jaran Desert
Authors: Qin Jie , Si Jianhua , Jia Bing , Zhao Chunyan , Zhou Dongmeng , He Xiaohui , Wang Chunlin , Zhu Xinglin
Published: December 2022

In desert ecosystems, ephemeral plants have developed specialized water use strategies in response to long-term natural water stress. To examine the water use strategies of desert ephemeral plants under natural extreme drought conditions, we investigated the water absorption sources, water potential, hydraulic conductivity, and water use efficiency of Ferula bungeana at different elevations on the slopes of mega-dunes in the Badain Jaran Desert, Inner Mongolia, during a period of extreme drought. We found that the water utilized by F. bungeana was mostly absorbed from the 0–60 cm soil layers (80.47 ± 4.28%). With progression of the growing season, the source of water changed from the 0–30 cm soil layer to the 30-60 cm layer. The water potentials of the leaves, stems, and roots of F. bungeana were found to be characterized by clear diurnal and monthly variation, which were restricted by water availability and the hydraulic conductivity of different parts of the plant. The root hydraulic conductivity of F. bungeana was found to be considerably greater than that of the canopy, both of which showed significant diurnal and monthly variation. The water use efficiency of F. bungeana under extreme drought conditions was relatively high, particularly during the early and late stages of the growing season. Variations in water availability led to the regulation of water uptake and an adjustment of internal water conduction, which modified plant water use efficiency. These observations tend to indicate that the water use strategies of F. bungeana are mainly associated with the growth stage of plants, whereas the distribution pattern of plants on mega-dunes appeared to have comparatively little influence. Our findings on the water use of ephemeral plants highlight the adaptive mechanisms of these plants in desert habitats and provide a theoretical basis for selecting plants suitable for the restoration and reconstruction of desert ecosystems.
Effect of mindfulness on online impulse buying: Moderated mediation model of problematic internet use and emotional intelligence
Authors: Vihari Nitin Simha , Sinha Nishit Kumar , Tyagi Akansha , Mittal Saurabh
Published: December 2022

Introduction

Online impulse buying behavior is an unplanned urge to buy a product or service in an online setting and it has several negative consequences for customers, such as guilt and financial distress, and e-commerce firms, such as higher returns and customer complaints. Evidently, it is important to examine the various psychological processes which may assist in a better understanding, therefore addressing the high prevalence of online impulse buying. This study builds upon self-regulation theory to explore how mindfulness influences online impulse buying, and examines problematic internet use as a mediator in the relationship between mindfulness and online impulse buying. Further, this study investigates how emotional intelligence as a moderator plays the role of a suppressant on the adverse impact of problematic Internet use which fuels online impulse buying.

Method

A total of 598 individuals working with various servicebased industries responded to the questionnaire. Multiple regression and moderated mediation analysis was used using SPSS and AMOS for analyzing the data.

Result

Problematic internet use mediates the relationship between mindfulness and online impulse buying behavior. Emotional intelligence negatively moderates the relationship between problematic internet use and online impulse buying behavior.

Discussion

This study findings outlined the inverse relationship of mindfulness & online impulse buying, along with the mediating effect of problematic internet use between mindfulness and online impulse buying. Further, this study showed how emotional intelligence played an important role as a moderator by suppressing the adverse impact of problematic Internet use and preventing online impulse buying. The study offers implications to online marketers in regulating the unplanned purchase process—while minimizing uninhibited buying behavior that leads to regret, and the subsequent intention to return products. Further, social and theoretical implications are discussed.
Does CEO tenure moderate the link between corporate social responsibility and business performance in small- and medium-sized enterprises?
Authors: Lee Sae-Mi , Sinha Paresha N. , Bae Jee-Eun , Lee Yong-Ki
Published: December 2022

This study investigates the effect of CSR activities on business performance of small- and medium-sized enterprises (SMEs) in South Korea setting. Based on upper echelons theory and stakeholder theory, the study further examines CEO tenure as a potential moderator between CSR activities and business performance. The study considers four dimensions of CSR (economic, legal, ethical, and philanthropic) and two types of business performance (financial and non-financial). To test the moderating effect of CEO tenure, we divided the sample into two groups: companies with short-term tenured CEOs and long-term tenured CEOs. The data were collected from 443 CEOs of SMEs in South Korea. We used a multi-group analysis with SmartPLS 4. The study finds that CEO tenure moderates the relationship between dimensions of CSR and business performance. More specifically, the study finds that CEOs in early-stage tenure focus on philanthropic activities to drive financial performance, while their counterparts focus on economic/legal dimension. CEOs, regardless of the length of tenure, consider the philanthropic dimension helpful for improving both financial and non-financial performance. This study expands prior research by examining the relationship between CSR and business performance in SMEs, considering the impact of the CEO tenure. The findings of this study make contributions to the literature by demonstrating that CEO tenure is an important factor in linking CSR to business performance. This research also adds evidence to the CSR literature that economic and legal dimensions are considered mandatory responsibilities, and CEOs of SMEs view them as interconnected. For practical implications, this study identifies different predictors of financial performance for companies with short-term vs. long-term CEO tenure. Short-term CEOs focus on philanthropy to improve financial performance, and both long- and short-term CEOs believe that philanthropy affects the company’s financial and non-financial performance.