bluuebunny/crossref_metadata_2025 huggingface dataset:
Preemptive Immunotherapy for Minimal Residual Disease in Patients With t(8;21) Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Fan Shuang , Shen Meng-Zhu , Zhang Xiao-Hui , Xu Lan-Ping , Wang Yu , Yan Chen-Hua , Chen Huan , Chen Yu-Hong , Han Wei , Wang Feng-Rong , Wang Jing-Zhi , Zhao Xiao-Su , Qin Ya-Zhen , Chang Ying-Jun , Liu Kai-Yan , Huang Xiao-Jun , Mo Xiao-Dong
Published: January 2022

In patients with t(8;21) acute myeloid leukemia (AML), recurrent minimal residual disease (MRD) measured by RUNX1-RUNX1T1 transcript levels can predict relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to compare the efficacy of preemptive interferon (IFN)-α therapy and donor lymphocyte infusion (DLI) in patients with t(8;21) AML following allo-HSCT. We also evaluated the appropriate method for patients with different levels of RUNX1-RUNX1T1 transcripts. In this retrospective study, consecutive patients who had high-risk t(8;21) AML and received allo-HSCT were enrolled. The inclusion criteria were as follows: (1) age ≤65 years; (2) regained MRD positive following allo-HSCT. MRD positive was defined as the loss of a ≥4.5-log reduction and/or <4.5-log reduction in the RUNX1-RUNX1T1 transcripts, and high-level, intermediate-level, and low-level MRDs were, respectively, defined as <2.5-log, 2.5−3.5-log, and 3.5−4.5-log reductions in the transcripts compared with the pretreatment baseline level. Patients with positive RUNX1-RUNX1T1 could receive preemptive IFN-α therapy or DLI, which was primarily based on donor availability and the intentions of physicians and patients. The patients received recombinant human IFN-α-2b therapy by subcutaneous injection twice a week every 4 weeks. IFN-α therapy was scheduled for six cycles or until the RUNX1-RUNX1T1 transcripts were negative for at least two consecutive tests. The rates of MRD turning negative for patients with low-level, intermediate-level, and high-level RUNX1-RUNX1T1 receiving IFN-α were 87.5%, 58.1%, and 22.2%, respectively; meanwhile, for patients with intermediate-level and high-level RUNX1-RUNX1T1 receiving DLI, the rates were 50.0% and 14.3%, respectively. For patients with low-level and intermediate-level RUNX1-RUNX1T1, the probability of overall survival at 2 years was higher in the IFN-α group than in the DLI group (87.6% vs. 55.6%; p = 0.003). For patients with high levels of RUNX1-RUNX1T1, the probability of overall survival was comparable between the IFN-α and DLI groups (53.3% vs. 83.3%; p = 0.780). Therefore, patients with low-level and intermediate-level RUNX1-RUNX1T1 could benefit more from preemptive IFN-α therapy compared with DLI. Clinical outcomes were comparable between preemptive IFN-α therapy and DLI in patients with high-level RUNX1-RUNX1T1; however, they should be further improved.
C-Reactive Protein Is an Indicator of the Immunosuppressive Microenvironment Fostered by Myeloid Cells in Hepatocellular Carcinoma
Authors: Wang Yongchun , Li Zhixiong , Huang Zhijie , Yu Xingjuan , Zheng Limin , Xu Jing
Published: January 2022

Background

C-reactive protein (CRP) is a widely used marker of systemic inflammation and predicts poor clinical outcomes in patients with hepatocellular carcinoma (HCC); however, its significance in the local immune response at the tumor site is not clear.

Methods

Serum CRP levels of 329 HCC patients were detected before resection. Paired paraffin-embedded tumor samples were used to quantify immune cell populations, such as CD11b+ myeloid cells, CD68+ macrophages (Mφs), CD15+ neutrophils, CD8+ T cells, and CD206+, CD204+, CD163+ and CD169+ Mφs, by immunohistochemistry. Enrichment scores for 34 types of immune cells based on transcriptome data from 24 HCC samples were calculated by xCell. Overall survival of patients was analyzed using the Kaplan-Meier method.

Results

Serum CRP levels were correlated with liver functions and tumor stages in patients with HCC. The densities of CD68+ tumor-associated macrophages (TAMs) and CD15+ tumor-associated neutrophils (TANs) were significantly higher in patients with elevated serum CRP levels than in those with low CRP levels (both p < 0.0001). Further analysis of TAM subtypes revealed that serum CRP levels were associated with CD204+ and CD163+ Mφ densities (p < 0.0001 and p = 0.0003, respectively). Moreover, transcriptome data showed that CRP expression was associated with the expression of myeloid cell infiltration-related genes in HCC tumors. The combination of serum CRP with TAMs or TANs in both the nontumor and intratumor regions could represent a powerful criterion for predicting patient prognoses.

Conclusion

Serum CRP could serve as an indicator of an immunosuppressive TME in HCC, which could be of potential clinical application for treatment strategies targeting the TME.
Prediction of the Mechanisms by Which Quercetin Enhances Cisplatin Action in Cervical Cancer: A Network Pharmacology Study and Experimental Validation
Authors: Ji Huihui , Li Kehan , Xu Wenbin , Li Ruyi , Xie Shangdan , Zhu Xueqiong
Published: January 2022

Yimucao has been used as an herbal medicine to treat gynecological diseases. Common genes of Yimucao active compounds were investigated using network pharmacology. The components and targets of Yimucao were retrieved from the TCMSP database. Cervical cancer targets were collected from GeneCards, TTD, DisGeNET, and KEGG. Cisplatin-related genes were downloaded from GeneWeaver. The protein-protein interaction (PPI) network was created using the STRING database. A drug-bioactive compound-disease-target network was constructed using Cytoscape. GO and KEGG analyses were performed to investigate common targets of quercetin and cisplatin in cervical cancer. We found that quercetin was the highly bioactive compound in Yimucao. The drug-bioactive compound-disease-target network contained 93 nodes and 261 edges. Drug-related key targets were identified, including EGFR, IL6, CASP3, VEGFA, MYC, CCND1, ERBB2, FOS, PPARG, and CASP8. Core targets were primarily related to the response to metal ions, cellular response to xenobiotic stimulus, and transcription factor complex. The KEGG pathway analysis revealed that quercetin and cisplatin may affect cervical cancer through platinum drug resistance and the p53 and HIF-1 pathways. Furthermore, quercetin combined with cisplatin downregulated the expression of EGFR, MYC, CCND1, and ERBB2 proteins and upregulated CASP8 expression in HeLa and SiHa cells. Functionally, quercetin enhanced cisplatin-induced anticancer activity in cervical cancer cells. Our results indicate that quercetin can be used to overcome cisplatin resistance in cervical cancer cells.
Real-World Multicenter Experience in Tumor Debulking Prior to Blinatumomab Administration in Adult Patients With Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia
Authors: Bonifacio Massimiliano , Papayannidis Cristina , Lussana Federico , Fracchiolla Nicola , Annunziata Mario , Sica Simona , Delia Mario , Foà Robin , Pizzolo Giovanni , Chiaretti Sabina
Published: January 2022

Blinatumomab is an immunotherapeutic agent with dual specificity for CD3 and CD19 that is approved for the treatment of relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL). A steroid based pre-treatment is recommended before administering blinatumomab to patients with a high tumor burden to minimize the risk of tumor lysis syndrome, but the optimal debulking regimen and whether it can improve responses remain unclear. The present study retrospectively evaluated real-world outcomes following tumor debulking and blinatumomab infusion in R/R B-ALL adult patients treated at 7 Italian centers. Data were collected from 34 patients. The choice of the cytoreductive therapy was made by the treating clinician on an individual patient basis; regimens included chemotherapy (n=23), steroids (n=7) and tyrosine kinase inhibitors alone or in combination (n=4). The rate of complete responses (CR) and complete minimal residual disease (MRD) responses in CR patients were 67.6% and 81% respectively, after 2 cycles of blinatumomab. Moreover, among patients with a high tumor burden 50% obtained a CR, with 89% of them also achieving a complete MRD response. Favorable responses were also obtained in patients over 50 years of age at treatment initiation. Overall, 7 of 23 patients in CR after blinatumomab underwent hematopoietic stem cell transplantation. The results of this retrospective study highlight the heterogeneity in the use of pre-blinatumomab tumor debulking in real-life clinical practice. Nonetheless, debulking pre-treatment enhanced responses to blinatumomab compared to historic studies, indicating that this strategy may help to improve outcomes for R/R B-ALL patients.
Augmented Reality to Assist Skin Paddle Harvesting in Osteomyocutaneous Fibular Flap Reconstructive Surgery: A Pilot Evaluation on a 3D-Printed Leg Phantom
Authors: Cercenelli Laura , Babini Federico , Badiali Giovanni , Battaglia Salvatore , Tarsitano Achille , Marchetti Claudio , Marcelli Emanuela
Published: January 2022

Background

Augmented Reality (AR) represents an evolution of navigation-assisted surgery, providing surgeons with a virtual aid contextually merged with the real surgical field. We recently reported a case series of AR-assisted fibular flap harvesting for mandibular reconstruction. However, the registration accuracy between the real and the virtual content needs to be systematically evaluated before widely promoting this tool in clinical practice. In this paper, after description of the AR based protocol implemented for both tablet and HoloLens 2 smart glasses, we evaluated in a first test session the achievable registration accuracy with the two display solutions, and in a second test session the success rate in executing the AR-guided skin paddle incision task on a 3D printed leg phantom.

Methods

From a real computed tomography dataset, 3D virtual models of a human leg, including fibula, arteries and skin with planned paddle profile for harvesting, were obtained. All virtual models were imported into Unity software to develop a marker-less AR application suitable to be used both via tablet and via HoloLens 2 headset. The registration accuracy for both solutions was verified on a 3D printed leg phantom obtained from the virtual models, by repeatedly applying the tracking function and computing pose deviations between the AR-projected virtual skin paddle profile and the real one transferred to the phantom via a CAD/CAM cutting guide. The success rate in completing the AR-guided task of skin paddle harvesting was evaluated using CAD/CAM templates positioned on the phantom model surface.

Results

On average, the marker-less AR protocol showed comparable registration errors (ranging within 1-5 mm) for tablet-based and HoloLens-based solution. Registration accuracy seems to be quite sensitive to ambient light conditions. We found a good success rate in completing the AR-guided task within an error margin of 4 mm (97% and 100% for tablet and HoloLens, respectively). All subjects reported greater usability and ergonomics for HoloLens 2 solution.

Conclusions

Results revealed that the proposed marker-less AR based protocol may guarantee a registration error within 1-5 mm for assisting skin paddle harvesting in the clinical setting. Optimal lightening conditions and further improvement of marker-less tracking technologies have the potential to increase the efficiency and precision of this AR-assisted reconstructive surgery.
Hypomethylating Agent-Based Combination Therapies to Treat Post-Hematopoietic Stem Cell Transplant Relapse of Acute Myeloid Leukemia
Authors: Ciotti Giulia , Marconi Giovanni , Martinelli Giovanni
Published: January 2022

Allogeneic stem cell transplantation still represents the best curative option for most patients with acute myeloid leukemia, but relapse is still dramatically high. Due to their immunologic activity and safety profile, hypomethylating agents (HMAs) represent an interesting backbone for combination therapies. This review reports mechanism of action, safety, and efficacy data on combination strategies based on HMAs in the setting of post-allogeneic stem cell transplant relapse. Several studies highlighted how HMAs and donor lymphocyte infusion (DLI) combination may be advantageous. The combination strategy of HMA with venetoclax, possibly in association with DLI, is showing excellent results in terms of response rate, including molecular responses. Lenalidomide, despite its well-known high rates of severe graft-versus-host disease in post-transplant settings, is showing an acceptable safety profile in association with HMAs with a competitive response rate. Regarding FLT3 internal tandem duplication (ITD) mutant AML, tyrosine kinase inhibitors and particularly sorafenib have promising results as monotherapy and in combination with HMAs. Conversely, combination strategies with gemtuzumab ozogamicin or immune checkpoint inhibitors did not show competitive response rates and seem to be currently less attractive strategies. Associations with histone deacetylase inhibitors and isocitrate dehydrogenase 1 and 2 (IDH1/2) inhibitors represent new possible strategies that need to be better investigated.
Crosstalk Among YAP, LncRNA, and Tumor-Associated Macrophages in Tumorigenesis Development
Authors: Xu Jing , Liu Xin-Yuan , Zhang Qi , Liu Hua , Zhang Peng , Tian Zi-Bin , Zhang Cui-Ping , Li Xiao-Yu
Published: January 2022

Long non-coding RNAs (ncRNAs), which do not encode proteins, regulate cell proliferation, tumor angiogenesis, and metastasis and are closely associated with the development, progression, and metastasis of many cancers. Tumor-associated macrophages (TAMs) in the tumor microenvironment play an important role in cancer progression. The Hippo signaling pathway regulates cell proliferation and apoptosis, maintains tissue and organ size, and homeostasis of the internal environment of organisms. Abnormal expression of Yes-associated protein (YAP), the Hippo signaling pathway key component, is widely observed in various malignancies. Further, TAM, lncRNA, and YAP are currently valuable targets for cancer immunotherapy. In this review, we have logically summarized recent studies, clarified the close association between the three factors and tumorigenesis, and analyzed the outlook of tumor immunotherapy.
Urine Biomarkers Combined With Ultrasound for the Diagnosis of Obstruction in Pediatric Hydronephrosis
Authors: Kazlauskas Vytis , Bilius Vytautas , Jakutis Virginijus , Komiagiene Renata , Burnyte Birute , Verkauskas Gilvydas
Published: January 2022

Introduction: To establish the efficacy of ultrasound (US) combined with urine biomarkers in differentiating patients who require surgical management from those who do not, avoiding invasive investigations.

Materials and Methods: From February 2019 to February 2021, all pediatric patients who presented with hydronephrosis were selected for the study. All renal units (RU) were evaluated by US, and fresh frozen voided urine samples were collected at the time of inclusion. Hydronephrosis grade was evaluated by the Society for Fetal Urology (SFU) and an alternative grading system (AGS). Patients who had high-grade hydronephrosis on US were referred to renal scan (RS) or intervention, when there was an increase of dilatation in subsequent follow-up images. Fresh frozen urine from the control group with no history of renal diseases and no renal anomalies on US was collected. We compared differences of US parameters combined with urine biomarkers between surgically and non-surgically managed patients and between the groups of patients when they were stratified by different RS findings and analyzed whether urinary biomarkers give any additional value to US. Instead of the anterior–posterior diameter (APD), we used its ratio with mid-parenchymal thickness. The additional efficacy of biomarkers to US was calculated when the US component was derived to a cumulative APD/mid-parenchymal ratio.

Results: Sixty-four patients with hydronephrosis were prospectively included in the study accounting for a total of 81 patient visits and 162 RUs evaluated. A control group of 26 patients was collected. The mean age at inclusion in the hydronephrosis group was 43.7(±45.5) months, and a mean age in a control group was 61.2(±41.3) months. The cumulative APD/mid-parenchymal ratio combined with urinary albumin, β2 microglobulin (β2-M), and urinary neutrophil gelatinase-associated lipocalcin may have a better performance in the prediction of surgical intervention than the cumulative APD/mid-parenchymal ratio alone (p = 0.1). The best performance to detect the increased tissue transit time and obstructive curve on RS was demonstrated by the β2-M creatinine ratio. An increased cumulative APD/mid-parenchymal ratio with biomarkers together had a fairly good sensitivity and specificity for detection of DRF < 40%.

Conclusions: According to our data, the APD/mid-parenchymal ratio alone has good efficacy in prediction of surgery and abnormal RS findings especially when combined with urine biomarkers.
Transient Early Fine Motor Abnormalities in Infants Born to COVID-19 Mothers Are Associated With Placental Hypoxia and Ischemia
Authors: Liu Huan-Yu , Guo Juanjuan , Zeng Chang , Cao Yuming , Ran Ruoxi , Wu Tiancheng , Yang Guifang , Zhao Dongchi , Yang Pu , Yu Xuechen , Zhang Wei , Liu Song-Mei , Zhang Yuanzhen
Published: January 2022

Background: Long-term effects of Coronavirus Disease 2019 (COVID-19) on infants born to infected mothers are not clear. Fine motor skills are crucial for the development of infant emotional regulation, learning ability and social skills.

Methods: Clinical information of 100 infants born to 98 mothers (COVID-19 n = 31, non-COVID-19 n = 67) were collected. Infants were follow-up up to 9 months post-partum. The placental tissues were examined for SARS-CoV-2 infection, pathological changes, cytokines, and mtDNA content.

Results: Decreased placental oxygen and nutrient transport capacity were found in infected pregnant women. Increased IL-2, IL-6, TNF-α, and IFN-γ were detected in trophoblast cells and maternal blood of COVID-19 placentas. Elevated early fine motor abnormal-ities and increased serum TNI (troponin I) levels at delivery were observed in infants born to mothers with COVID-19. Increased abnormal mitochondria and elevated mtDNA content were found in the placentas from infected mothers. The placental mtDNA content of three infants with abnormal DDST were increased by 4, 7, and 10%, respectively, compared to the mean of the COVID-19 group. The Maternal Vascular Malperfusion (MVM), elevated cytokines and increased placental mtDNA content in mothers with COVID-19 might be associated with transient early fine motor abnormalities in infants. These abnormalities are only temporary, and they could be corrected by daily training.

Conclusions: Babies born to COVID-19 mothers with mild symptoms appeared to have little or no excess long-term risks of abnormal physical and neurobehavioral development as compared with the infants delivered by non-COVID-19 mothers.
Implementation of the Comprehensive Unit-Based Safety Program to Improve Infection Prevention and Control Practices in Four Neonatal Intensive Care Units in Pune, India
Authors: Johnson Julia , Latif Asad , Randive Bharat , Kadam Abhay , Rajput Uday , Kinikar Aarti , Malshe Nandini , Lalwani Sanjay , Parikh Tushar B. , Vaidya Umesh , Malwade Sudhir , Agarkhedkar Sharad , Curless Melanie S. , Coffin Susan E. , Smith Rachel M. , Westercamp Matthew , Colantuoni Elizabeth , Robinson Matthew L. , Mave Vidya , Gupta Amita , Manabe Yukari C. , Milstone Aaron M.
Published: January 2022

Objective: To implement the Comprehensive Unit-based Safety Program (CUSP) in four neonatal intensive care units (NICUs) in Pune, India, to improve infection prevention and control (IPC) practices.

Design: In this quasi-experimental study, we implemented CUSP in four NICUs in Pune, India, to improve IPC practices in three focus areas: hand hygiene, aseptic technique for invasive procedures, and medication and intravenous fluid preparation and administration. Sites received training in CUSP methodology, formed multidisciplinary teams, and selected interventions for each focus area. Process measures included fidelity to CUSP, hand hygiene compliance, and central line insertion checklist completion. Outcome measures included the rate of healthcare-associated bloodstream infection (HA-BSI), all-cause mortality, patient safety culture, and workload.

Results: A total of 144 healthcare workers and administrators completed CUSP training. All sites conducted at least 75% of monthly meetings. Hand hygiene compliance odds increased 6% per month [odds ratio (OR) 1.06 (95% CI 1.03–1.10)]. Providers completed insertion checklists for 68% of neonates with a central line; 83% of checklists were fully completed. All-cause mortality and HA-BSI rate did not change significantly after CUSP implementation. Patient safety culture domains with greatest improvement were management support for patient safety (+7.6%), teamwork within units (+5.3%), and organizational learning—continuous improvement (+4.7%). Overall workload increased from a mean score of 46.28 ± 16.97 at baseline to 65.07 ± 19.05 at follow-up (p < 0.0001).

Conclusion: CUSP implementation increased hand hygiene compliance, successful implementation of a central line insertion checklist, and improvements in safety culture in four Indian NICUs. This multimodal strategy is a promising framework for low- and middle-income country healthcare facilities to reduce HAI risk in neonates.
Targeting Regulatory T Cells for Therapy of Lupus Nephritis
Authors: Venkatadri Rajkumar , Sabapathy Vikram , Dogan Murat , Sharma Rahul
Published: January 2022

Lupus glomerulonephritis (LN) is a complex autoimmune disease characterized by circulating autoantibodies, immune-complex deposition, immune dysregulation and defects in regulatory T cell (Tregs). Treatment options rely on general immunosuppressants and steroids that have serious side effects. Approaches to target immune cells, such as B cells in particular, has had limited success and new approaches are being investigated. Defects in Tregs in the setting of autoimmunity is well known and Treg-replacement strategies are currently being explored. The aim of this minireview is to rekindle interest on Treg-targeting strategies. We discuss the existing evidences for Treg-enhancement strategies using key cytokines interleukin (IL)-2, IL-33 and IL-6 that have shown to provide remission in LN. We also discuss strategies for indirect Treg-modulation for protection from LN.
Effects of Circadian Phase Tailored Light Therapy on Sleep, Mood, and Cognition in Alzheimer’s Disease: Preliminary Findings in a Pivotal Study
Authors: Cremascoli Riccardo , Sparasci Davide , Giusti Gianluca , Cattaldo Stefania , Prina Elisa , Roveta Fausto , Bruno Francesco , Ghezzi Cristina , Cerri Silvia , Picascia Marta , Bernini Sara , Sinforiani Elena , Terzaghi Michele , Priano Lorenzo , Mauro Alessandro , Manni Raffaele
Published: January 2022

It is shown that the circadian system is affected in patients with Alzheimer’s disease (AD) even at an early stage of the disease and that such dysfunction may be detrimental to sleep, mood, and cognitive functioning. Light is a strong central modulator of the circadian rhythms and is potentially beneficial to mood and cognitive functioning via a direct effect or indirectly via its modulating effects on circadian rhythms. This study focuses on tracking the effect of light therapy on sleep quality, mood, and cognition in AD of mild/moderate severity. We performed a single-blind randomized controlled trial to investigate the effects of a light therapy treatment tailored to the individual circadian phase as measured by dim light melatonin onset (DLMO). Such a treatment induced an objective circadian phase shift consistent with the melatonin phase response curve to light exposure, led to a shortening of the phase angle DLMO-falling asleep time, and was associated with an improvement in subjective sleep quality and cognitive performance.
Functional Expression of Transient Receptor Potential and Piezo1 Channels in Cultured Interstitial Cells of Human-Bladder Lamina Propria
Authors: Zhao MengMeng , Chen Zhenghao , Liu Lei , Ding Ning , Wen Jiliang , Liu Jiaxin , Wang WenZhen , Ge Nan , Zu Shulu , Song Wei , Chen Guoqing , Zhang Xiulin
Published: January 2022

The interstitial cells in bladder lamina propria (LP-ICs) are believed to be involved in sensing/afferent signaling in bladder mucosa. Transient receptor potential (TRP) cation channels act as mechano- or chemo-sensors and may underlie some of the sensing function of bladder LP-ICs. We aimed to investigate the molecular and functional expression of TRP channels implicated in bladder sensory function and Piezo1/Piezo2 channels in cultured LP-ICs of the human bladder. Bladder tissues were obtained from patients undergoing cystectomy. LP-ICs were isolated and cultured, and used for real-time reverse transcription-quantitative polymerase chain reaction, immunocytochemistry, and calcium-imaging experiments. At the mRNA level, TRPA1, TRPV2, and Piezo1 were expressed most abundantly. Immunocytochemical staining showed protein expression of TRPA1, TRPV1, TRPV2, TRPV4, TRPM8, as well as Piezo1 and Piezo2. Calcium imaging using channel agonists/antagonists provided evidence for functional expression of TRPA1, TRPV2, TRPV4, Piezo1, but not of TRPV1 or TRPM8. Activation of these channels with their agonist resulted in release of adenosine triphosphate (ATP) from LP-ICs. Inhibition of TRPV2, TRPV4 and Piezo1 blocked the stretch induced intracellular Ca2+ increase. Whereas inhibition of TRPA1 blocked H2O2 evoked response in LP-ICs. Our results suggest LP-ICs of the bladder can perceive stretch or chemical stimuli via activation of TRPV2, TRPV4, Piezo1 and TRPA1 channels. LP-ICs may work together with urothelial cells for perception and transduction of mechanical or chemical signals in human-bladder mucosa.
Infection of Galleria mellonella (Lepidoptera) Larvae With the Entomopathogenic Fungus Conidiobolus coronatus (Entomophthorales) Induces Apoptosis of Hemocytes and Affects the Concentration of Eicosanoids in the Hemolymph
Authors: Wrońska Anna Katarzyna , Kaczmarek Agata , Kazek Michalina , Boguś Mieczysława Irena
Published: January 2022

Apoptosis and autophagy, the mechanisms of programmed cell death, play critical roles in physiological and pathological processes in both vertebrates and invertebrates. Apoptosis is also known to play an important role in the immune response, particularly in the context of entomopathogenic infection. Of the factors influencing the apoptotic process during infection, two of the lesser known groups are caspases and eicosanoids. The aim of this study was to determine whether infection by the entomopathogenic soil fungus Conidiobolus coronatus is associated with apoptosis and changes in caspase activity in the hemocytes of Galleria mellonella larvae, and to confirm whether fungal infection may affect eicosanoid levels in the host. Larvae were exposed for 24 h to fully grown and sporulating fungus. Hemolymph was collected either immediately after termination of exposure (F24 group) or 24 h later (F48 group). Apoptosis/necrosis tests were performed in hemocytes using fluorescence microscopy and flow cytometry, while ELISA tests were used to measure eicosanoid levels. Apoptosis and necrosis occurred to the same degree in F24, but necrosis predominated in F48. Fungal infection resulted in caspase activation, increased PGE1, PGE2, PGA1, PGF2α, and 8-iso-PGF2α levels and decreased TXB2 levels, but had no effect on TXA2 or 11-dehydro-TXB2 concentrations. In addition, infected larvae demonstrated significantly increased PLA2 activity, known to be involved in eicosanoid biosynthesis. Our findings indicate that fungal infection simultaneously induces apoptosis in insects and stimulates general caspase activity, and this may be correlated with changes in the concentrations of eicosanoids.
Low Salt Delivery Triggers Autocrine Release of Prostaglandin E2 From the Aldosterone-Sensitive Distal Nephron in Familial Hyperkalemic Hypertension Mice
Authors: Zapf Ava M. , Grimm Paul R. , Al-Qusairi Lama , Delpire Eric , Welling Paul A.
Published: January 2022

Aberrant activation of with-no-lysine kinase (WNK)-STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) kinase signaling in the distal convoluted tubule (DCT) causes unbridled activation of the thiazide-sensitive sodium chloride cotransporter (NCC), leading to familial hyperkalemic hypertension (FHHt) in humans. Studies in FHHt mice engineered to constitutively activate SPAK specifically in the DCT (CA-SPAK mice) revealed maladaptive remodeling of the aldosterone sensitive distal nephron (ASDN), characterized by decrease in the potassium excretory channel, renal outer medullary potassium (ROMK), and epithelial sodium channel (ENaC), that contributes to the hyperkalemia. The mechanisms by which NCC activation in DCT promotes remodeling of connecting tubule (CNT) are unknown, but paracrine communication and reduced salt delivery to the ASDN have been suspected. Here, we explore the involvement of prostaglandin E2 (PGE2). We found that PGE2 and the terminal PGE2 synthase, mPGES1, are increased in kidney cortex of CA-SPAK mice, compared to control or SPAK KO mice. Hydrochlorothiazide (HCTZ) reduced PGE2 to control levels, indicating increased PGE2 synthesis is dependent on increased NCC activity. Immunolocalization studies revealed mPGES1 is selectively increased in the CNT of CA-SPAK mice, implicating low salt-delivery to ASDN as the trigger. Salt titration studies in an in vitro ASDN cell model, mouse CCD cell (mCCD-CL1), confirmed PGE2 synthesis is activated by low salt, and revealed that response is paralleled by induction of mPGES1 gene expression. Finally, inhibition of the PGE2 receptor, EP1, in CA-SPAK mice partially restored potassium homeostasis as it partially rescued ROMK protein abundance, but not ENaC. Together, these data indicate low sodium delivery to the ASDN activates PGE2 synthesis and this inhibits ROMK through autocrine activation of the EP1 receptor. These findings provide new insights into the mechanism by which activation of sodium transport in the DCT causes remodeling of the ASDN.
Plant Growth-Promoting Rhizobacteria Enhance Defense of Strawberry Plants Against Spider Mites
Authors: Hosseini Afsane , Hosseini Mojtaba , Schausberger Peter
Published: January 2022

Plants mediate interactions between below- and above-ground microbial and animal communities. Microbial communities of the rhizosphere commonly include mutualistic symbionts such as mycorrhizal fungi, rhizobia and free-living plant growth-promoting rhizobacteria (PGPR) that may influence plant growth and/or its defense system against aboveground pathogens and herbivores. Here, we scrutinized the effects of three PGPR, Azotobacter chroococcum, Azospirillum brasilense, and Pseudomonas brassicacearum, on life history and population dynamics of two-spotted spider mites, Tetranychus urticae, feeding on aboveground tissue of strawberry plants, and examined associated plant growth and physiology parameters. Our experiments suggest that these three species of free-living rhizobacteria strengthen the constitutive, and/or induce the direct, anti-herbivore defense system of strawberry plants. All three bacterial species exerted adverse effects on life history and population dynamics of T. urticae and positive effects on flowering and physiology of whole strawberry plants. Spider mites, in each life stage and in total, needed longer time to develop on PGPR-treated plants and had lower immature survival rates than those fed on chemically fertilized and untreated plants. Reduced age-specific fecundity, longer developmental time and lower age-specific survival rates of mites feeding on rhizobacteria treated plants reduced their intrinsic rate of increase as compared to mites feeding on chemically fertilized and control plants. The mean abundance was lower in spider mite populations feeding on PGPR-treated strawberries than in those feeding on chemically fertilized and untreated plants. We argue that the three studied PGPR systemically strengthened and/or induced resistance in above-ground plant parts and enhanced the level of biochemical anti-herbivore defense. This was probably achieved by inducing or upregulating the production of secondary plant metabolites, such as phenolics, flavonoids and anthocyanins, which were previously shown to be involved in induced systemic resistance of strawberry plants. Overall, our study emphasizes that PGPR treatment can be a favorable strawberry plant cultivation measure because providing essential nutrients needed for proper plant growth and at the same time decreasing the life history performance and population growth of the notorious herbivorous pest T. urticae.
Comparative Study of AMMI- and BLUP-Based Simultaneous Selection for Grain Yield and Stability of Finger Millet [Eleusine coracana (L.) Gaertn.] Genotypes
Authors: Anuradha N. , Patro T. S. S. K. , Singamsetti Ashok , Sandhya Rani Y. , Triveni U. , Nirmala Kumari A. , Govanakoppa Nagappa , Lakshmi Pathy T. , Tonapi Vilas A.
Published: January 2022

Finger millet, an orphan crop, possesses immense potential in mitigating climate change and could offer threefold security in terms of food, fodder, and nutrition. It is mostly cultivated as a subsistence crop in the marginal areas of plains and hills. Considering the changes in climate inclusive of recurrent weather vagaries witnessed every year, it is crucial to select stable, high-yielding, area-specific, finger millet cultivars. Sixty finger millet varieties released across the country were evaluated over six consecutive rainy seasons from 2011 to 2016 at the Agricultural Research Station, Vizianagaram. The genotype × environment interaction (GEI) was found to be significant in the combined ANOVA. Furthermore, the Additive Main effects and Multiplicative Interaction (AMMI) analysis asserted that genotypes and the GEI effects accounted for approximately 89% of the total variation. Strong positive associations were observed in an estimated set of eleven stability parameters which were chosen to identify stable genotypes. Furthermore, Non-parametric and Parametric Simultaneous Selection indices (NP-SSI and P-SSI) were calculated utilizing AMMI-based stability parameter (ASTAB), modified AMMI stability value (MASV), and Modified AMMI Stability Index (MASI) to identify stable high yielders. Both methods had inherent difficulties in ranking genotypes for SSI. To overcome this, the initial culling [i.e., SSI with culling strategy (C-SSI)] of genotypes was introduced for stability. In the C-SSI method, the top ten genotypes were above-average yielders, while those with below-average yield were observed in NP-SSI and P-SSI methods. Similarly, the estimation of best linear unbiased prediction (BLUP)-based simultaneous selections, such as harmonic mean of genotypic values (HMGV), relative performance of genotypic values (RPGV), and harmonic mean of relative performance of genotypic values (HMRPGV), revealed that none of the top ten entries had below-average yield. The study has proven that C-SSI and BLUP-based methods were equally worthy in the selection of high-yielding genotypes with stable performance. However, the C-SSI approach could be the best method to ensure that genotypes with a considerable amount of stability are selected. The multi-year trial SSI revealed that entries Indaf-9, Sri Chaitanya, PR-202, and A-404; and VL324 and VL146 were ascertained to be the most stable high-yielding genotypes among medium-to-late and early maturity groups, respectively.
Caffeic Acid, an Allelochemical in Artemisia argyi, Inhibits Weed Growth via Suppression of Mitogen-Activated Protein Kinase Signaling Pathway and the Biosynthesis of Gibberellin and Phytoalexin
Authors: Chen Le , Li Jinxin , Zhu Yunyun , Guo Lujuan , Ji Rongsheng , Miao Yuhuan , Guo Lanping , Du Hongzhi , Liu Dahui
Published: January 2022

Artemisia argyi is widely distributed in Asia, and it often becomes the dominant population in the field because of its strong ecological niche competitiveness. Allelochemicals secreted by plants are generally considered an important reason for their dominance in ecological competition. In this study, the allelochemicals in A. argyi were screened by a series of experiments and their mechanisms were explored via transcriptomics. First, the inhibitory effects of A. argyi on Echinochloa crusgalli, Setaria viridis, Portulaca oleracea and Amaranthus retroflexus were evaluated. Then, we carried out a qualitative and quantitative analysis of the chemical composition of the aqueous extract of A. argyi to screen for potential allelochemicals that can inhibit weed growth. Four potential allelochemicals were quantified: neochlorogenic acid (5-CQA), chlorogenic acid (3-CQA), cryptochlorogenic acid (4-CQA), and caffeic acid (CA). Coincidentally, their allelopathic effects on weeds seemed to be identical to their content, in the order CA>4−CQA>5−CQA>3-CQA. These findings suggested that CA might be the main allelopathic compound in the aqueous extract of A. argyi. Subsequently, the allelopathic effect and molecular mechanism of CA on S. viridis leaves were investigated. The physiological results showed that CA significantly induced reactive oxygen species (ROS) production, led to malondialdehyde (MDA) accumulation, and disrupted enzyme activities (POD, SOD, CAT) in S. viridis leaves. Moreover, transcriptome results revealed that CA inhibited S. viridis growth by downregulating multiple genes involved in gibberellin (GA) and phytoalexin biosynthesis and Mitogen-activated protein kinase (MAPK) signaling pathways. In addition, differentially expressed genes (DEGs) related to the biosynthesis and signaling pathways of phytohormones were verified by Quantitative Real-Time PCR (RT-qPCR). Taken together, this study may be the first to identify allelochemicals and explore their molecular mechanism about A. argyi. Importantly, the ecological advantages of A. argyi could be applied to ecological regulation and the development of botanical herbicides.
Girls’ Stuff? Maternal Gender Stereotypes and Their Daughters’ Fear
Authors: Gerdes Antje B. M. , Fraunfelter Laura-Ashley , Braband Melissa , Alpers Georg W.
Published: January 2022

One of the most robust findings in psychopathology is the fact that specific phobias are more prevalent in women than in men. Although there are several theoretical accounts for biological and social contributions to this gender difference, empirical data are surprisingly limited. Interestingly, there is evidence that individuals with stereotypical feminine characteristics are more fearful than those with stereotypical masculine characteristics; this is beyond biological sex. Because gender role stereotypes are reinforced by parental behavior, we aimed to examine the relationship of maternal gender stereotypes and children’s fear. Dyads of 38 mothers and their daughters (between ages 6 and 10) were included. We assessed maternal implicit and explicit gender stereotypes as well as their daughters’ self-reported general fearfulness, specific fear of snakes, and approach behavior toward a living snake. First, mothers’ fear of snakes significantly correlated with their daughters’ fear of snakes. Second, mothers’ gender stereotypes significantly correlated with their daughters’ self-reported fear. Specifically, maternal implicit gender stereotypes were associated with daughters’ fear of snakes and fear ratings in response to the snake. Moreover, in children, self-reported fear correlated with avoidance of the fear-relevant animal. Together, these results provide first evidence for a potential role of parental gender stereotypes in the development and maintenance of fear in their offspring.
Middle School Students From China’s Rice Area Show More Adaptive Creativity but Less Innovative and Boundary-Breaking Creativity
Authors: He Wu-jing , Wong Wan-chi
Published: January 2022

The present study aimed to conduct a cross-cultural comparison of creative thinking among Chinese middle school students from the rice- and wheat-growing areas in China through the lens ofthe rice theory, which postulates that there are major psychological differences among the individuals in these agricultural regions. Differences in cultural mindsets and creativity between the rice group (n= 336) and the wheat group (n= 347) were identified using the Chinese version of (1) the Auckland Individualism and Collectivism Scale (AICS) and (2) the Test for Creative Thinking–Drawing Production (TCT–DP), respectively. Interesting findings were obtained. The results of latent mean analyses indicate that the rice group showed significantly more collectivism and adaptive creativity than the wheat group but less individualism and innovative and boundary-breaking creativity. However, the two groups showed no significant differences in their overall creative performance, as reflected in the TCT–DP composite score. Moreover, results of hierarchical multiple regression analyses revealed that collectivism was positively related to adaptive creativity but negatively related to innovative and boundary-breaking creativity; however, a reverse pattern was found for individualism. These findings enrich the discourse regarding the rice theory and shed important light on the effect of culture on creativity.
A Case Study on the Impacts of Social Contexts on a Chinese English as a Foreign Language Learner’s L1 and L2 Identities Development
Authors: Xiao Yuehai , Zhao Angel
Published: January 2022

Informed by the poststructuralist theory, this study investigates the case of Ming, a Chinese professor of English, about the impacts of his first language (L1) and second language (L2) learning experience, and the changes of social contexts on his L1 and L2 identities construction. It was found that being a learner of English as a Foreign Language (EFL), Ming’s identities development aligned with the poststructuralist theory, in which it is considered dynamic, fluid and conflicting. Ming negotiated and renegotiated his identities in various social contexts in China and the United States and finally gained acceptance into the L2 academic community. This study not only analyzes Ming’s experience with his language learning and identities, but also unravels that conflicts may be part of the process of identities construction, and encourages learners to be persistent and emotionally resilient, while using certain strategies to retain a stable L1 identity so that they can navigate through the negative encounters during the second language acquisition (SLA) process to sustain the development of their identities and L2 abilities.
Long-Term Influence of Incidental Emotions on the Emotional Judgment of Neutral Faces
Authors: Nudelman Marta F. , Portugal Liana C. L. , Mocaiber Izabela , David Isabel A. , Rodolpho Beatriz S. , Pereira Mirtes G. , Oliveira Leticia de
Published: January 2022

Background:Evidence indicates that the processing of facial stimuli may be influenced by incidental factors, and these influences are particularly powerful when facial expressions are ambiguous, such as neutral faces. However, limited research investigated whether emotional contextual information presented in a preceding and unrelated experiment could be pervasively carried over to another experiment to modulate neutral face processing.

Objective:The present study aims to investigate whether an emotional text presented in a first experiment could generate negative emotion toward neutral faces in a second experiment unrelated to the previous experiment.

Methods:Ninety-nine students (all women) were randomly assigned to read and evaluate a negative text (negative context) or a neutral text (neutral text) in the first experiment. In the subsequent second experiment, the participants performed the following two tasks: (1) an attentional task in which neutral faces were presented as distractors and (2) a task involving the emotional judgment of neutral faces.

Results:The results show that compared to the neutral context, in the negative context, the participants rated more faces as negative. No significant result was found in the attentional task.

Conclusion:Our study demonstrates that incidental emotional information available in a previous experiment can increase participants’ propensity to interpret neutral faces as more negative when emotional information is directly evaluated. Therefore, the present study adds important evidence to the literature suggesting that our behavior and actions are modulated by previous information in an incidental or low perceived way similar to what occurs in everyday life, thereby modulating our judgments and emotions.
Developmental Trend of Subjective Well-Being of Weibo Users During COVID-19: Online Text Analysis Based on Machine Learning Method
Authors: Han Yingying , Pan Wenhao , Li Jinjin , Zhang Ting , Zhang Qiang , Zhang Emily
Published: January 2022

Currently, the coronavirus disease 2019 (COVID-19) pandemic experienced by the international community has increased the usage frequency of borderless, highly personalized social media platforms of all age groups. Analyzing and modeling texts sent through social media online can reveal the characteristics of the psychological dynamic state and living conditions of social media users during the pandemic more extensively and comprehensively. This study selects the Sina Weibo platform, which is highly popular in China and analyzes the subjective well-being (SWB) of Weibo users during the COVID-19 pandemic in combination with the machine learning classification algorithm. The study first invokes the SWB classification model to classify the SWB level of original texts released by 1,322 Weibo active users during the COVID-19 pandemic and then combines the latent growth curve model (LGCM) and the latent growth mixture model (LGMM) to investigate the developmental trend and heterogeneity characteristics of the SWB of Weibo users after the COVID-19 outbreak. The results present a downward trend and then an upward trend of the SWB of Weibo users during the pandemic as a whole. There was a significant correlation between the initial state and the development rate of the SWB after the COVID-19 outbreak (r = 0.36, p < 0.001). LGMM results show that there were two heterogeneous classes of the SWB after the COVID-19 outbreak, and the development rate of the SWB of the two classes was significantly different. The larger class (normal growth group; n = 1,229, 93.7%) showed a slow growth, while the smaller class (high growth group; n = 93, 6.3%) showed a rapid growth. Furthermore, the slope means across the two classes were significantly different (p < 0.001). Therefore, the individuals with a higher growth rate of SWB exhibited stronger adaptability to the changes in their living environments. These results could help to formulate effective interventions on the mental health level of the public after the public health emergency outbreak.