bluuebunny/crossref_metadata_2025 huggingface dataset:
Soluble epoxide hydrolase inhibition alleviates chemotherapy induced neuropathic pain
Authors: Takeshita Ashley A. , Hammock Bruce D. , Wagner Karen M.
Published: January 2023

Chemotherapy induced peripheral neuropathy (CIPN) is a particularly pernicious form of neuropathy and the associated pain is the primary dose-limiting factor of life-prolonging chemotherapy treatment. The prevalence of CIPN is high and can last long after treatment has been stopped. Currently, late in the COVID-19 pandemic, there are still increased psychological pressures on cancer patients as well as additional challenges in providing analgesia for them. These include the risks of nonsteroidal anti-inflammatory drug (NSAID) analgesics potentially masking early infection symptoms and the immunosuppression of steroidal and opiate based approaches. Even without these concerns, CIPN is often inadequately treated with few therapies that offer significant pain relief. The experiments we report use soluble epoxide hydrolase inhibitors (sEHI) which relieved this intractable pain in preclinical models. Doses of EC5026, an IND candidate intended to treat neuropathic pain, elicited dose dependent analgesic responses in multiple models including platinum-based, taxane, and vinca alkaloid-based CIPN pain in Sprague Dawley rats. At the same time as a class, the sEHI are known to result in fewer debilitating side effects of other analgesics, likely due to their novel mechanism of action. Overall, the observed dose-dependent analgesia in both male and female rats across multiple models of chemotherapy induced neuropathic pain holds promise as a useful tool when translated to the clinic.
Case Report: Crossing a rugged road in a primary immune regulatory disorder
Authors: Sgrulletti Mayla , Cifaldi Cristina , Di Cesare Silvia , Kroegler Barbara , Del Duca Elisabetta , Ferradini Valentina , Graziani Simona , Bengala Mario , Di Matteo Gigliola , Moschese Viviana
Published: January 2023

Over the last decades, Inborn Errors of Immunity (IEI) characterized by an immune dysregulatory picture, isolated or combined with infections, have been increasingly identified and referred as Primary Immune Regulatory Disorders (PIRD). PIRD diagnosis may be difficult due to heterogeneity of time onset, sequence of clinical manifestations and laboratory abnormalities. Moreover, the dissection of a PIRD vs. a secondary immunodeficiency (SID) might be a real challenge since the same indications for immunosuppressant treatments might represent per se a PIRD clinical expression. Here we report a female patient with a history of recurrent respiratory and urinary tract infections since early infancy and a diagnosis of Rheumatoid Arthritis in adulthood. After poor response to several biologicals she was treated with Rituximab and sent to immunology referral for a severe hypogammaglobulinemia. Clinical and immunological features matched a diagnosis of common variable immunodeficiency and when IgG replacement therapy and antibiotic prophylaxis were added a good infectious control was obtained. Next generation sequencing analysis has revealed a novel heterozygous VUS in the IKBKB gene (c.1465A > G; p.Ser489Gly). Functional analysis has shown a reduced capacity of B lymphocytes and CD4 positive T cells in inducing IκBα degradation, with negative impact on NF-kB pathway. Due to recurrent infections attributed to a common condition in childhood and to an exclusive autoimmunity-centered approach in adulthood, both diagnosis and suitable treatment strategies have suffered a significant delay. To reduce the diagnostic delay, pediatricians, general practitioners and specialists should be aware of IEI and the challenges to differentiate them from SID. Furthermore, genetic characterization and functional analysis may contribute to a personalized approach, in a perspective of targeted or semi-targeted therapy.
The effect of erythropoietin on neonatal hypoxic-ischemic encephalopathy: An updated meta-analysis of randomized control trials
Authors: Pan Jing-Jing , Wu Yue , Liu Yun , Cheng Rui , Chen Xiao-Qing , Yang Yang
Published: January 2023

Objective

Erythropoietin (EPO) seems to have a good application prospect both in experimental models and patients with hypoxic ischaemic encephalopathy (HIE). Data regarding the effect of EPO on death or neurodevelopmental impairment are conflicting.

Methods

A search was conducted by two investigators involved in this research in PubMed, Embase, and Cochrane databases for studies in English, in Wanfang, VIP, and Cnki databases for Chinese studies (all last launched on 2022/08/31). Ultimately, we identified 11 original studies, including the EPO group (n = 636) and the control group (n = 626). Odds ratio (OR) and weighted mean difference were calculated using a random effects or fixed effects model, depending on the data type and heterogeneity of the included studies.

Results

1. The comparison of effectiveness of EPO treatment on HIE: (1) With respect to death, data showed no significant difference between EPO and control groups (OR = 0.97, 95% CI, 0.66–1.43; P = 0.88); Considering the additional effect of mild hypothermia treatment (MHT), no significant difference was found between EPO + MHT/control + MHT groups either (OR = 1.09, 95% CI, 0.69–1.73; P = 0.72); With respect to the interference of different routes of medication administration, Meta-analysis further showed no difference between intravenous EPO/control groups (OR = 1.13, 95% CI, 0.70–1.82; P = 0.62). (2) With respect to cerebral palsy, the analysis showed no significant difference (OR = 0.76, 95% CI, 0.50–1.15; P = 0.20); Considering the effect of MHT and routes of medication administration, data further showed no difference between EPO group and control group (OR = 1.26, 95% CI, 0.73–2.19; P = 0.41). (3) Regarding epilepsy, no significant difference was found (OR = 0.49, 95% CI, 0.20–1.19; P = 0.12). MR abnormality was less common in EPO group (OR = 0.39, 95% CI, 0.19–0.79; P = 0.008). 2. The comparison of possible adverse events of EPO: EPO treatment would not increase the risk of thrombocytopenia, hypotension, and hepatic and kidney injury.

Conclusions

This meta-analysis showed that EPO treatment is not beneficial for reducing death and improving neurological impairment, though it would not increase the risk of adverse events.
Case Report: Whole genome sequencing identifies CCDC88C as a novel JAK2 fusion partner in pediatric T-cell acute lymphoblastic leukemia
Authors: Krstic Aleksandra , Rezayee Fatemah , Saft Leonie , Hammarsjö Anna , Svenberg Petter , Barbany Gisela
Published: January 2023

In the present report, we applied whole genome sequencing (WGS) to genetically characterize a case of pediatric T-cell acute lymphoblastic leukemia (ALL) refractory to standard therapy. WGS identified a novel JAK2 fusion, with CCDC88C as a partner. CCDC88C encodes a protein part of the Wnt signaling pathway and has previously been described in hematological malignancies as fusion partner to FLT3 and PDGFRB. The novel CCDC88C::JAK2 fusion gene results in a fusion transcript, predicted to produce a hybrid protein, which retains the kinase domain of JAK2 and is expected to respond to JAK2 inhibitors. This report illustrates the potential of WGS in the diagnostic setting of ALL.
Baseline assessment of the WHO/UNICEF/UNFPA maternal and newborn quality-of-care standards around childbirth: Results from an intermediate hospital, northeast Namibia
Authors: Siseho Gloria Mutimbwa , Mathole Thubelihle , Jackson Debra
Published: January 2023

Background

Quality of care around childbirth can reduce above half of the stillbirths and newborn deaths. Northeast Namibia’s neonatal mortality is higher than the national level. Yet, no review exists on the quality of care provided around childbirth. This paper reports on baseline assessment for implementing WHO/UNICEF/UNFPA quality measures around childbirth.

Methods

A mixed-methods research design was used to assess quality of care around childbirth. To obtain good saturation and adequate women opinions, we purposively sampled the only high-volume hospital in northeast Namibia; observed 53 women at admission, of which 19 progressed to deliver on the same day/hours of data collection; and interviewed 20 staff and 100 women who were discharged after delivery. The sampled hospital accounted for half of all deliveries in that region and had a high (27/1,000) neonatal mortality rate above the national (20/1,000) level. We systematically sampled every 22nd delivery until the 259 mother–baby pair was reached. Data were collected using the Every Mother Every Newborn assessment tool, entered, and analyzed using SPSS V.27. Descriptive statistics was used, and results were summarized into tables and graphs.

Results

We reviewed 259 mother–baby pair records. Blood pressure, pulse, and temperature measurements were done in 98% of observed women and 90% of interviewed women at discharge. Above 80% of human and essential physical resources were adequately available. Gaps were identified within the WHO/UNICEF/UNFPA quality standard 1, a quality statement on routine postpartum and postnatal newborn care (1.1c), and also within standards 4, 5, and 6 on provider–client interactions (4.1), information sharing (5.3), and companionship (6.1). Only 45% of staff received in-service training/refresher on postnatal care and breastfeeding. Most mothers were not informed about breastfeeding (52%), postpartum care and hygiene (59%), and family planning (72%). On average, 49% of newborn postnatal care interventions (1.1c) were practiced. Few mothers (0–12%) could mention any newborn danger signs.

Conclusion

This is the first study in Namibia to assess WHO/UNICEF/UNFPA quality-of-care measures around childbirth. Measurement of provider–client interactions and information sharing revealed significant deficiencies in this aspect of care that negatively affected the client’s experience of care. To achieve reductions in neonatal death, improved training in communication skills to educate clients is likely to have a major positive and relatively low-cost impact.
Efficacy and safety of probiotics in Parkinson’s constipation: A systematic review and meta-analysis
Authors: Xie Li , Chen Dongmei , Zhu Xinghui , Cheng Cisong
Published: January 2023

Background: Parkinson’s disease (PD) is the most common neurodegenerative disease closely related to the immune system, among whose prodromes constipation is a representative symptom. Recent Randomized Controlled Trials (RCTs) have proved that probiotics can be used to effectively treat PD constipation, but the results are inconsistent. We performed a meta-analysis to assess the efficacy and safety of probiotic therapy on Parkinson’s constipation.

Methods: Questions about the research focus were constructed based on the Participants, Intervention, Comparison and Outcomes (PICO) Criteria. We searched electronic databases such as PubMed, Web of Science, EMBASE, Scopus, EBSCO, Cochrane and Google Scholar until March 2022 for eligible literatures. Our primary endpoints were stool frequency, stool consistency, the number of laxatives uses, UPDRS-III scores and adverse events.

Results: 12 eligible studies (n = 818 patients) met the inclusion and endpoint criteria. Meta-analysis results showed that constipation symptoms were improved after probiotic treatment, including an increased stool frequency (WMD = 0.94, 95% CI:0.53 to 1.34; OR = 3.22, 95% CI:1.97–5.29), an improved stool consistency (WMD = 1.46, 95% CI:0.54–2.37), a reduced use of laxatives (WMD = −0.72, 95%CI: −1.04 to−0.41), and also a reduced Parkinson’s UPDRS-III score (WMD = −6.58, 95%CI: −12.02 to −1.14); there was no significant difference in total adverse events (OR = 0.82, 95%CI:0.39–1.72).

Conclusion: Our analysis suggests that probiotics can be used to improve the constipation and motor symptoms for patients with Parkinson’s constipation, possibly by reducing the inflammatory response and improving gut-brain axis neuron function, whose safety also proved to be good.
Curcumae Rhizoma: A botanical drug against infectious diseases
Authors: Wu Ying-Qi , Tong Tong
Published: January 2023

Curcumae Rhizoma is the dry rhizome coming from Curcuma longa L. which grow widely in tropical south and southwest Asia. It has been used to treat conditions such as dermatoses, infections, stress, and depression. Moreover, in China, Curcumae Rhizoma and its active constituents have been made into different pharmaceutical preparations. Growing evidence suggests that these preparations can exert antioxidant, anti-inflammatory, and anti-cancer effects, which may play crucial roles in the treatment of various diseases, including cancer, infectious-, autoimmune-, neurological-, and cardiovascular diseases, as well as diabetes. The anti-infective effect of Curcumae Rhizoma has become a popular field of research around the world, including for the treatment of COVID-19, influenza virus, hepatitis B virus, human immunodeficiency virus, and human papilloma virus, among others. In this paper, the basic characteristics of Curcumae Rhizoma and its active constituents are briefly introduced, and we also give an overview on their applications and mechanisms in infectious diseases.
Efficacy and safety of concomitant use of proton pump inhibitors with aspirin-clopidogrel dual antiplatelet therapy in coronary heart disease: A systematic review and meta-analysis
Authors: Luo Xiaofeng , Hou Min , He Shuangshuang , Yang Xue , Zhang Pan , Zhao Yingxin , Xing Haiyan
Published: January 2023

Background: Proton pump inhibitors (PPIs) are usually prescribed to prevent gastrointestinal (GI) complications in patients receiving dual antiplatelet therapy (DAPT). This systematic review and meta-analysis aimed to explore the efficacy and safety of the concomitant use of PPIs with aspirin-clopidogrel DAPT in patients with Coronary heart disease (CHD).

Method: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to August 2022 for eligible studies. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the clinical outcomes. Subgroup analysis was conducted according to different PPI subtypes, populations, follow-up times and study types. This study was registered on PROSPERO (CRD42022332195).

Results: A total of 173,508 patients from 18 studies [2 randomized controlled trials (RCTs), 3 post hoc analyses of RCTs, and 13 cohort studies] were included in this study. Pooled data revealed that coadministration of PPIs significantly increased the risk of major adverse cardiovascular events (MACEs) (HR = 1.15, 95% CI = 1.06–1.26, p = .001) and reduced the risk of gastrointestinal (GI) complications (HR = 0.44, 95% CI = 0.30–0.64, p < .0001). Subgroup analysis results showed that the esomeprazole users and patients with coronary stenting in the PPI group were associated with an increased risk of MACEs compared with the non-PPI group. The occurrence of MACEs in PPI users was more common than that in non-PPI users in long-term follow-up (≥12 months) studies and in the observational studies. There was no significant differences in the incidences of net clinical adverse events (NACEs), all-cause mortality, or cardiac death between the two groups.

Conclusion: In patients with CHD, the concomitant use of PPIs with aspirin and clopidogrel was associated with a reduced risk of GI complications but could increase the rates of MACEs (particularly in patients receiving esomeprazole or with coronary stenting). There was no clear evidence of an association between PPI use and NACEs, all-cause mortality, or cardiac death. The results could have been affected by the follow-up time and study type. Further large-scale RCTs with long-term follow-up are needed.
Maternal sevoflurane exposure induces neurotoxicity in offspring rats via the CB1R/CDK5/p-tau pathway
Authors: Wan Yuxiao , Wu Ziyi , Li Xingyue , Zhao Ping
Published: January 2023

Sevoflurane is widely used for maternal anesthesia during pregnancy. Sevoflurane exposure of rats at mid-gestation can cause abnormal development of the central nervous system in their offspring. Sevoflurane is known to increase the expression of cannabinoid 1 receptor (CB1R) in the hippocampus. However, the effect of cannabinoid 1 receptor on fetal and offspring rats after maternal anesthesia is still unclear. At gestational day 14, pregnant rats were subjected to 2-h exposure to 3.5% sevoflurane or air. Rats underwent intraperitoneal injection with saline or rimonabant (1 mg/kg) 30 min prior to sevoflurane or air exposure. cannabinoid 1 receptor, cyclin-dependent kinase 5 (CDK5), p35, p25, tau, and p-tau expression in fetal brains was measured at 6, 12, and 24 h post-sevoflurane/air exposure. Neurobehavioral and Morris water maze tests were performed postnatal days 3–33. The expression of cannabinoid 1 receptor/cyclin-dependent kinase 5/p-tau and histopathological staining of brain tissues in offspring rats was observed. We found that a single exposure to sevoflurane upregulated the activity of cyclin-dependent kinase 5 and the level of p-tau via cannabinoid 1 receptor. This was accompanied by the diminished number of neurons and dendritic spines in hippocampal CA1 regions. Finally, these effects induced lower scores and platform crossing times in behavioral tests. The present study suggests that a single exposure to 3.5% sevoflurane of rats at mid-gestation impairs neurobehavioral abilities and cognitive memory in offspring. cannabinoid 1 receptor is a possible target for the amelioration of postnatal neurobehavioral ability and cognitive memory impairments induced by maternal anesthesia.
The efficacy of ginseng-containing traditional Chinese medicine in patients with acute decompensated heart failure: A systematic review and meta-analysis
Authors: Chen Xiaozhe , Ma Yulong , Li Jianhua , Yao Lei , Gui Mingtai , Lu Bo , Zhou Xunjie , Wang Mingzhu , Fu Deyu
Published: January 2023

Objective: To evaluate the efficacy of ginseng-containing traditional Chinese medicine (TCM) for acute decompensated heart failure (ADHF).

Methods: Seven databases were included from establishment until 10 July 2022. Pooled data were analyzed with random-effects model. The risk of bias was measured by the risk of bias tool for randomized trials (RoB 2). Modified Jadad scale score was used to assess the quality of including studies. The meta-analysis was performed with RevMan 5.3. Trial sequential analysis was assessed to avoid type I errors. We have registered our protocol in PROSPERO (CRD42021267742).

Results: Twenty-eight articles were included. The results demonstrated that compared with conventional western therapy (WT), ginseng-containing TCM combined with WT further improved clinical efficacy (RR: 1.25, 95% CI: 1.20–1.29, p < 0.00001, I2 = 8%), left ventricular ejection fraction (LVEF) (MD: 5.80, 95% CI: 4.86–6.74, p < 0.00001, I2 = 89%), stroke volume (MD: 13.80, 95% CI: 12.66–14.95, p < 0.00001, I2 = 93%), 6-min walk test (MD: 53.03, 95% CI: 20.76–85.29, p = 0.001, I2 = 97%), decreased 6-month rehospitalization (RR: 0.44, 95% CI: 0.18–1.11, p = 0.08, I2 = 0%), brain natriuretic peptide (MD: 188.12, 95% CI: 248.13 to -128.11, p < 0.00001, I2 = 94%), N-terminal pro-B-type natriuretic peptide (MD = -503.29; 95% CI: 753.18 to -253.40, p < 0.0001, I2 = 89%) and Minnesota living heart failure questionnaire scores (MD: 9.68, 95% CI: 13.67 to -5.70, p < 0.00001, I2 = 83%). The ROB2 assessment and modified Jaded scores showed most studies included were with some concerns.

Conclusion: Compared with WT alone, ginseng-containing TCM is a possible way to benefit ADHF patients. However, limited by the quality of including trials, more high-quality studies are needed to provide reliable evidence.
The mechanism of oxymatrine on atopic dermatitis in mice based on SOCS1/JAK-STAT3 pathway
Authors: Han Xianwei , Ma Tianming , Wang Qiang , Jin Chunlin , Han Yusheng , Liu Guijun , Li Hao
Published: January 2023

Based on the suppressor of cytokine signaling 1 (SOCS1)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway, the mechanism of oxymatrine in the treatment of atopic dermatitis (AD) was preliminarily explored in this study. C57BL/6 mice were induced to establish AD model by smearing carbotriol (MC903) on their back. The AD mice were randomly divided into model group, oxymatrine groups with three dosages (25, 50 and 100 mg/kg), (n = 10). Oxymatrine groups were intragastric administered once daily for 14 days. The same volume of saline was given in the normal control group and model group once daily for 14 days. Subsequently, HE staining was used to observe the pathological changes of skin tissue, ELISA was used to detect the levels of serum inflammatory factors including interleukin-4, 6 and 17 (IL-4, IL-6, and IL-17), tumor necrosis factor-α (TNF-α) and immunoglobulin E (IgE). Immunohistochemistry was used to detect the expression of suppressor of cytokine signaling 1 and CD3 in skin tissue, and Western blotting was used to detect the proteins in suppressor of cytokine signaling 1/JAK-STAT3 pathway. Compared with the normal control group, the pathological damage of mice in the model group, such as skin hyperplasia, edema, congestion and inflammatory infiltration, aggravated increased significantly. And the expression of serum inflammatory factors, CD3 positive expression and JAK-STAT3 pathway protein in the model group were increased (p < .05), and the expression of suppressor of cytokine signaling 1 protein (p < .05) was decreased. Compared with the model group, the above pathological damage of the mice was reduced, and the serum inflammatory factors, JAK-STAT3 pathway protein, and CD3 positive expression were decreased as a dose-dependant manner (p < .05), and the expression of suppressor of cytokine signaling 1 protein was increased as a dose-dependent manner (p < .05). Oxymatrine can improve the skin inflammation symptoms of AD mice by up regulating the expression of suppressor of cytokine signaling 1, inhibiting the activation of JAK-STAT3 pathway and blocking the activation of T lymphocytes.
Deep learning-based hemodynamic prediction of carotid artery stenosis before and after surgical treatments
Authors: Wang Sirui , Wu Dandan , Li Gaoyang , Zhang Zhiyuan , Xiao Weizhong , Li Ruichen , Qiao Aike , Jin Long , Liu Hao
Published: January 2023

Hemodynamic prediction of carotid artery stenosis (CAS) is of great clinical significance in the diagnosis, prevention, and treatment prognosis of ischemic strokes. While computational fluid dynamics (CFD) is recognized as a useful tool, it shows a crucial issue that the high computational costs are usually required for real-time simulations of complex blood flows. Given the powerful feature-extraction capabilities, the deep learning (DL) methodology has a high potential to implement the mapping of anatomic geometries and CFD-driven flow fields, which enables accomplishing fast and accurate hemodynamic prediction for clinical applications. Based on a brain/neck CT angiography database of 280 subjects, image based three-dimensional CFD models of CAS were constructed through blood vessel extraction, computational domain meshing and setting of the pulsatile flow boundary conditions; a series of CFD simulations were undertaken. A DL strategy was proposed and accomplished in terms of point cloud datasets and a DL network with dual sampling-analysis channels. This enables multimode mapping to construct the image-based geometries of CAS while predicting CFD-based hemodynamics based on training and testing datasets. The CFD simulation was validated with the mass flow rates at two outlets reasonably agreed with the published results. Comprehensive analysis and error evaluation revealed that the DL strategy enables uncovering the association between transient blood flow characteristics and artery cavity geometric information before and after surgical treatments of CAS. Compared with other methods, our DL-based model trained with more clinical data can reduce the computational cost by 7,200 times, while still demonstrating good accuracy (error<12.5%) and flow visualization in predicting the two hemodynamic parameters. In addition, the DL-based predictions were in good agreement with CFD simulations in terms of mean velocity in the stenotic region for both the preoperative and postoperative datasets. This study points to the capability and significance of the DL-based fast and accurate hemodynamic prediction of preoperative and postoperative CAS. For accomplishing real-time monitoring of surgical treatments, further improvements in the prediction accuracy and flexibility may be conducted by utilizing larger datasets with specific real surgical events such as stent intervention, adopting personalized boundary conditions, and optimizing the DL network.
Effects of cardiac function alterations on the risk of postoperative thrombotic complications in patients receiving endovascular aortic repair
Authors: Sun Xiaoning , Li Siting , He Yuan , Liu Yuxi , Ma Tianxiang , Zeng Rong , Liu Zhili , Chen Yu , Zheng Yuehong , Liu Xiao
Published: January 2023

Introduction: Chronic heart disease (CHD) is a common comorbidity of patients receiving endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAA). The explicit relationship between ventricular systolic function and EVAR complication of thrombotic events is unknown.

Methods: In this study, we proposed a three-dimensional numerical model coupled with the lumped-elements heart model, which is capable of simulating thrombus formation in diverse systolic functions. The relation of cardiac functions and the predicted risk of thrombus formation in the aorta and/or endograft of 4 patients who underwent EVAR was investigated. Relative risks for thrombus formation were identified using machine-learning algorithms.

Results: The computational results demonstrate that thrombus tended to form on the interior side of the aorta arch and iliac branches, and cardiac function can affect blood flow field and affect thrombus formation, which is consistent with the four patients' post-operative imaging follow-up. We also found that RRT, OSI, TAWSS in thrombosis area are lower than whole average. In addition, we found that the thrombus formation has negative correlations with the maximum ventricular contractile force (r = −.281 ± .101) and positive correlations with the minimum ventricular contractile force (r = .238 ± .074), whereas the effect of heart rate (r = −.015 ± .121) on thrombus formation is not significant.

Conclusion: In conclusion, changes in ventricular systolic function may alter the risk of thrombotic events after EVAR repair, which could provide insight into the selection of adjuvant therapy strategies for AAA patients with CHD.
Integrative analysis of microRNAs and mRNAs reveals the regulatory networks of triterpenoid saponin metabolism in Soapberry (Sapindus mukorossi Gaertn.)
Authors: Xu Yuanyuan , Liu Jiming , Ji Xiangqin , Zhao Guochun , Zhao Tianyun , Wang Xin , Wang Lixian , Gao Shilun , Hao Yingying , Gao Yuhan , Gao Yuan , Weng Xuehuang , Jia Liming , Chen Zhong
Published: January 2023

Triterpenoid saponin are important secondary metabolites and bioactive constituents of soapberry (Sapindus mukorossi Gaertn.) and are widely used in medicine and toiletry products. However, little is known about the roles of miRNAs in the regulation of triterpenoid saponin biosynthesis in soapberry. In this study, a total of 3036 miRNAs were identified, of which 1372 miRNAs were differentially expressed at different stages of pericarp development. Important KEGG pathways, such as terpenoid backbone biosynthesis, sesquiterpenoid and triterpenoid biosynthesis, and basal transcription factors were highlighted, as well the roles of some key miRNAs, such as ath-miR5021, han-miR3630-3p, and ppe-miR858, which may play important roles in regulating triterpenoid saponin biosynthesis. In addition, 58 miRNAs might participate in saponin biosynthesis pathways by predicting the targets of those miRNAs to 53 saponin biosynthesis structural genes. And 75 miRNAs were identified to potentially play vital role in saponin accumulation by targeting transcript factor genes, bHLH, bZIP, ERF, MYB, and WRKY, respectively, which are candidate regulatory genes in the pathway of saponin biosynthesis. The results of weighted gene coexpression network analysis (WGCNA) suggested that two saponin-specific miRNA modules and 10 hub miRNAs may participate in saponin biosynthesis. Furthermore, multiple miRNA–mRNA regulatory networks potentially involved in saponin biosynthesis were generated, e.g., ath-miR5021–SmIDI2/SmGPS5/SmbAS1/SmCYP71D-3/SmUGT74G-2, han-miR3630-3p–SmCYP71A-14/SmbHLH54/SmMYB135/SmWRKY32, and ppe-miR858–SmMYB5/SmMYB32. qRT-PCR analysis validated the expression patterns of nine miRNAs and 12 corresponding target genes. This study represents the first comprehensive analysis of miRNAs in soapberry and lays the foundation for further understanding of miRNA-based regulation in triterpenoid saponin biosynthesis.
Low-volume precision spray for plant pest control using profile variable rate spraying and ultrasonic detection
Authors: Nan Yulong , Zhang Huichun , Zheng Jiaqiang , Yang Kunqi , Ge Yufeng
Published: January 2023

Spraying chemical pesticides is one of the important means to control plant pest, and the profile variable spraying is an important technology to achieve precise pesticide application. A profiling tracking control method and an improved algorithm based on CMAC-PID (Cerebellar Model Articulation Controller- Potential Induced Degradation) were proposed in the paper. The test results of the sprayer profiling tracking of the tree canopies showed that the profiling control system using the improved algorithm had significantly better dynamic tracking performance, and the overall mean tracking error was reduced by 35.0%, compared with the traditional CMAC-PID. A spray flow calculation method based on tree canopy volume and leaf area density was proposed. Outdoor testing of the profile variable spraying and conventional spraying was carried out. There was no significant difference between the two spraying methods in terms of droplet coverage, VMD (Volume Median Diameter), NMD (Number Median Diameter), spray quality parameter and relative span coefficient, as well as droplet deposition density. The spray coefficient of variation was reduced by 25.9% and 21.9% inside and outside the tree canopy, respectively. The mean value of the ground deposition coverage of the profile variable spraying and the traditional spray was 13.0% and 33.2%, respectively, indicating a significant impact on the ground droplet deposition coverage by the two spraying methods. The spray flow rate of the profile variable spraying could be decreased by 32.1% compared to the conventional spraying. Profile variable spraying would reduce the cost associated with pesticide use and environmental pollution.
Isotopically non-stationary metabolic flux analysis of heterotrophic Arabidopsis thaliana cell cultures
Authors: Smith Edward N. , Ratcliffe R. George , Kruger Nicholas J.
Published: January 2023

Fluxes are the ultimate phenotype of metabolism and their accurate quantification is fundamental to any understanding of metabolic networks. Steady state metabolic flux analysis has been the method of choice for quantifying fluxes in heterotrophic cells, but it is unable to measure fluxes during short-lived metabolic states, such as a transient oxidative load. Isotopically non-stationary metabolic flux analysis (INST-MFA) can be performed over shorter timescales (minutes – hours) and might overcome this limitation. INST-MFA has recently been applied to photosynthesising leaves, but agriculturally important tissues such as roots and storage organs, or plants during the night are heterotrophic. Here we outline the application of INST-MFA to heterotrophic plant cells. Using INST-MFA we were able to identify changes in the fluxes supported by phosphoenolpyruvate carboxylase and malic enzyme under oxidative load, highlighting the potential of INST-MFA to measure fluxes during short-lived metabolic states. We discuss the challenges in applying INST-MFA, and highlight further development required before it can be routinely used to quantify fluxes in heterotrophic plant cells.
Biomass allometric models for Larix rupprechtii based on Kosak’s taper curve equations and nonlinear seemingly unrelated regression
Authors: Wang Dongzhi , Zhang Zhidong , Zhang Dongyan , Huang Xuanrui
Published: January 2023

The diameter at breast height (DBH) is the most important independent variable in biomass allometry models based on metabolic scaling theory (MST) or geometric theory. However, the fixed position DBH can be misleading in its use of universal scaling laws and lead to some deviation for the biomass model. Therefore, it is still an urgent scientific problem to build a high-precision biomass model system. A dataset of 114 trees was destructively sampled to obtain dry biomass components, including stems, branches, and foliage, and taper measurements to explore the applicability of biomass components to allometric scaling laws and develop a new system of additive models with the diameter in relative height (DRH) for each component of a Larch (Larix principis-rupprechtii Mayr) plantation in northern China. The variable exponential taper equations were modelled using nonlinear regression. In addition, applying nonlinear regression and nonlinear seemingly unrelated regression (NSUR) enabled the development of biomass allometric models and the system of additive models with DRH for each component. The results showed that the Kozak’s (II) 2004 variable exponential taper equation could accurately describe the stem shape and diameter in any height of stem. When the diameters in relative height were D0.2, D0.5, and D0.5 for branches, stems, and foliage, respectively, the allometric exponent of the stems and branches was the closest to the scaling relations predicted by the MST, and the allometric exponent of foliage was the most closely related to the scaling relations predicted by geometry theory. Compared with the nonlinear regression, the parameters of biomass components estimated by NSUR were lower, and it was close to the theoretical value and the most precise at forecasting. In the study of biomass process modelling, utilizing the DRH by a variable exponential taper equation can confirm the general biological significance more than the DBH of a fixed position.
Nitrogen assimilation and photorespiration become more efficient under chloride nutrition as a beneficial macronutrient
Authors: Peinado-Torrubia Procopio , Álvarez Rosario , Lucas Marta , Franco-Navarro Juan D. , Durán-Gutiérrez Francisco J. , Colmenero-Flores José M. , Rosales Miguel A.
Published: January 2023

Chloride (Cl−) and nitrate (NO3−) are closely related anions involved in plant growth. Their similar physical and chemical properties make them to interact in cellular processes like electrical balance and osmoregulation. Since both anions share transport mechanisms, Cl− has been considered to antagonize NO3− uptake and accumulation in plants. However, we have recently demonstrated that Cl− provided at beneficial macronutrient levels improves nitrogen (N) use efficiency (NUE). Biochemical mechanisms by which beneficial Cl− nutrition improves NUE in plants are poorly understood. First, we determined that Cl− nutrition at beneficial macronutrient levels did not impair the NO3− uptake efficiency, maintaining similar NO3− content in the root and in the xylem sap. Second, leaf NO3− content was significantly reduced by the treatment of 6 mM Cl− in parallel with an increase in NO3− utilization and NUE. To verify whether Cl− nutrition reduces leaf NO3− accumulation by inducing its assimilation, we analysed the content of N forms and the activity of different enzymes and genes involved in N metabolism. Chloride supply increased transcript accumulation and activity of most enzymes involved in NO3− assimilation into amino acids, along with a greater accumulation of organic N (mostly proteins). A reduced glycine/serine ratio and a greater ammonium accumulation pointed to a higher activity of the photorespiration pathway in leaves of Cl−-treated plants. Chloride, in turn, promoted higher transcript levels of genes encoding enzymes of the photorespiration pathway. Accordingly, microscopy observations suggested strong interactions between different cellular organelles involved in photorespiration. Therefore, in this work we demonstrate for the first time that the greater NO3− utilization and NUE induced by beneficial Cl− nutrition is mainly due to the stimulation of NO3− assimilation and photorespiration, possibly favouring the production of ammonia, reductants and intermediates that optimize C-N re-utilization and plant growth. This work demonstrates new Cl− functions and remarks on its relevance as a potential tool to manipulate NUE in plants.
Differences in the response mechanism of cadmium uptake, transfer, and accumulation of different rice varieties after foliar silicon spraying under cadmium-stressed soil
Authors: Zhao Junyang , Yu Baoshan , Wang Xueli , Chen Lihong , Akhtar Kashif , Tang Shide , Lu Huaming , He Jinhua , Wen Ronghui , He Bing
Published: January 2023

Most studies have shown that foliar silicon (Si) spraying can reduce the risk of rice quality safety caused by cadmium (Cd) contamination. However, it has recently been found that different rice varieties have different responses to Si. Therefore, we selected six rice varieties (YHSM, YXY1179, YXYLS, JLK1377, MXZ2, and YLY900) to compare the differences in the effects of leaf spray on Cd accumulation among different varieties. According to the change in Cd content in brown rice after Si application, the six rice varieties were divided into two types: Si-inhibited varieties (JLY1377, MXZ2, LY900, and YXYLS) and Si-stimulated varieties (WY1179 and YHSM). For Si-inhibited varieties, the Cd content of rice was reduced by 13.5%–65.7% after Si application. At the same time, the Cd content of the root, stem, leaf, panicle, and glume decreased to different degrees, the Cd content of the cell wall component increased by 2.2%–37.6%, the extraction state of Cd with strong mobile activity (ethanol-extracted and deionized water-extracted) was changed to the extraction state of Cd with weak mobile activity (acetic acid-extracted and hydrochloric acid-extracted), and the upward transport coefficient of different parts was reduced. For Si-stimulated varieties, Si application increased the Cd content of rice by 15.7%–24.1%. At the same time, the cell soluble component Cd content significantly increased by 68.4%–252.4% and changed the weakly mobile extraction state Cd to the strong mobile extraction state, increasing the upward transport coefficient of different sites. In conclusion, different rice varieties have different responses to Si. Foliar Si spraying inhibits the upward migration of Cd of Si-inhibited varieties, thereby reducing the Cd content of rice, but it has the opposite effect on Si-stimulated varieties. This result reminds us that we need to consider the difference in the effect of varieties in the implementation of foliar Si spraying in remediation of Cd-contaminated paddy fields.
Detection and counting of pigment glands in cotton leaves using improved U-Net
Authors: She Lixuan , Wang Nan , Xu Yaxuan , Wang Guoning , Shao Limin
Published: January 2023

Gossypol, as an important oil and raw material for feed, is mainly produced by cotton pigment gland, and has a wide range of applications in the fields of pharmaceutics, agriculture and industry. Accurate knowledge of the distribution of pigment gland in cotton leaves is important for estimating gossypol content. However, pigment glands are extremely small and densely distributed, manual counting is laborious and time-consuming, and difficult to count quickly and accurately. It is thus necessary to design a fast and accurate gland counting method. In this paper, the machine vision imaging technology is used to establish an image acquisition platform to obtain cotton leaf images, and a network structure is proposed based on deep learning, named as Interpolation-pooling net, to segment the pigment glands in the cotton leaf images. The network adopts the structure of first interpolation and then pooling, which is more conducive to the extraction of pigment gland features. The accuracy of segmentation of the model in cotton leaf image set is 96.7%, and the mIoU (Mean Intersection over Union), Recall, Precision and F1-score is 0.8181, 0.8004, 0.8004 and 0.8004 respectively. In addition, the number of pigment glands in cotton leaves of three different densities was measured. Compared with manual measurements, the square of the correlation coefficient (R2) of the three density pigment glands reached 0.966, 0.942 and 0.91, respectively. The results show that the proposed semantic segmentation network based on deep learning has good performance in the detection and counting of cotton pigment glands, and has important value for evaluating the gossypol content of different cotton varieties. Compared with the traditional chemical reagent determination method, this method is safer and more economical.
NTR1 is involved in heat stress tolerance through mediating expression regulation and alternative splicing of heat stress genes in Arabidopsis
Authors: He Lei , Wu Qi , Jin Ye , Fan Ye , Shi Huazhong , Wang Yizhong , Yang Wannian
Published: January 2023

As a common adverse environmental factor, heat stress (HS) not only drastically changes the plant transcriptome at the transcription level but also increases alternative splicing (AS), especially intron retention (IR) events. However, the exact mechanisms are not yet well understood. Here, we reported that NTC-related protein 1 (NTR1), which acts as an accessory component for spliceosome disassembly, is necessary for this process. The mutants of NTR1, both the T-DNA insertion and the point mutation identified through ethyl methanesulfonate (EMS) mutagenesis screening, are vulnerable to HS, indicating that NTR1 is essential for plant HS tolerance. At the molecular level, genes of response to heat and response to temperature stimulus are highly enriched among those of heat-induced but less-expressed ntr1 mutants. Moreover, a large portion of HS response (HSR) genes such as heat shock transcription factors (HSFs) and heat shock proteins (HSPs) are less induced by heat treatment, and more AS events, especially IR events, were found in heat-treated ntr1 mutants. Furthermore, HS suppressed the expression of NTR1 and NTR1-associated complex components. Thus, it is very likely that upon HS, the plant reduces the expression of the NTR1-associated complex to fulfill the fast demands for transcription of HSR genes such as HSFs and HSPs, which in turn results in the accumulation of improperly spliced especially IR products and eventually causes harm to plants.
A non-targeted metabolomics analysis identifies wound-induced oxylipins in Physcomitrium patens
Authors: Resemann Hanno Christoph , Feussner Kirstin , Hornung Ellen , Feussner Ivo
Published: January 2023

Plant oxylipins are a class of lipid-derived signaling molecules being involved in the regulation of various biotic and abiotic stress responses. A major class of oxylipins are the circular derivatives to which 12-oxo-phytodienoic acid (OPDA) and its metabolite jasmonic acid (JA) belong. While OPDA and its shorter chain homologue dinor-OPDA (dnOPDA) seem to be ubiquitously found in land plants ranging from bryophytes to angiosperms, the occurrence of JA and its derivatives is still under discussion. The bryophyte Physcomitrium patens has received increased scientific interest as a non-vascular plant model organism over the last decade. Therefore, we followed the metabolism upon wounding by metabolite fingerprinting with the aim to identify jasmonates as well as novel oxylipins in P. patens. A non-targeted metabolomics approach was used to reconstruct the metabolic pathways for the synthesis of oxylipins, derived from roughanic, linoleic, α-linolenic, and arachidonic acid in wild type, the oxylipin-deficient mutants of Ppaos1 and Ppaos2, the mutants of Ppdes being deficient in all fatty acids harboring a Δ6-double bond and the C20-fatty acid-deficient mutants of Ppelo. Beside of OPDA, iso-OPDA, dnOPDA, and iso-dnOPDA, three additional C18-compounds and a metabolite being isobaric to JA were identified to accumulate after wounding. These findings can now serve as foundation for future research in determining, which compound(s) will serve as native ligand(s) for the oxylipin-receptor COI1 in P. patens.
Biocontrol of the causal brown patch pathogen Rhizoctonia solani by Bacillus velezensis GH1-13 and development of a bacterial strain specific detection method
Authors: Lee Gahee , Choi Hyeongju , Liu Haifeng , Han Yun-Hyeong , Paul Narayan Chandra , Han Gui Hwan , Kim Hyunsook , Kim Pyoung Il , Seo Sun-Il , Song Jaekyeong , Sang Hyunkyu
Published: January 2023

Brown patch caused by the basidiomycete fungus Rhizoctonia solani is an economically important disease of cool-season turfgrasses. In order to manage the disease, different types of fungicides have been applied, but the negative impact of fungicides on the environment continues to rise. In this study, the beneficial bacteria Bacillus velezensis GH1-13 was characterized as a potential biocontrol agent to manage brown patch disease. The strain GH1-13 strongly inhibited the mycelial growth of turf pathogens including different anastomosis groups of R. solani causing brown patch and large patch. R. solani AG2-2(IIIB) hyphae were morphologically changed, and fungal cell death resulted from exposure to the strain GH1-13. In addition, the compatibility of fungicides with the bacterial strain, and the combined application of fungicide azoxystrobin and the strain in brown patch control on creeping bentgrass indicated that the strain could serve as a biocontrol agent. To develop strain-specific detection method, two unique genes from chromosome and plasmid of GH1-13 were found using pan-genome analysis of 364 Bacillus strains. The unique gene from chromosome was successfully detected using both SYBR Green and TaqMan qPCR methods in bacterial DNA or soil DNA samples. This study suggests that application of GH1-13 offers an environmentally friendly approach via reducing fungicide application rates. Furthermore, the developed pipeline of strain-specific detection method could be a useful tool for detecting and studying the dynamics of specific biocontrol agents.
Outlier analyses and genome-wide association study identify glgC and ERD6-like 4 as candidate genes for foliar water-soluble carbohydrate accumulation in Trifolium repens
Authors: Pearson Sofie M. , Griffiths Andrew G. , Maclean Paul , Larking Anna C. , Hong S. Won , Jauregui Ruy , Miller Poppy , McKenzie Catherine M. , Lockhart Peter J. , Tate Jennifer A. , Ford John L. , Faville Marty J.
Published: January 2023

Increasing water-soluble carbohydrate (WSC) content in white clover is important for improving nutritional quality and reducing environmental impacts from pastoral agriculture. Elucidation of genes responsible for foliar WSC variation would enhance genetic improvement by enabling molecular breeding approaches. The aim of the present study was to identify single nucleotide polymorphisms (SNPs) associated with variation in foliar WSC in white clover. A set of 935 white clover individuals, randomly sampled from five breeding pools selectively bred for divergent (low or high) WSC content, were assessed with 14,743 genotyping-by-sequencing SNPs, using three outlier detection methods: PCAdapt, BayeScan and KGD-FST. These analyses identified 33 SNPs as discriminating between high and low WSC populations and putatively under selection. One SNP was located in the intron of ERD6-like 4, a gene coding for a sugar transporter located on the vacuole membrane. A genome-wide association study using a subset of 605 white clover individuals and 5,757 SNPs, identified a further 12 SNPs, one of which was associated with a starch biosynthesis gene, glucose-1-phosphate adenylyltransferase, glgC. Our results provide insight into genomic regions underlying WSC accumulation in white clover, identify candidate genomic regions for further functional validation studies, and reveal valuable information for marker-assisted or genomic selection in white clover.