bluuebunny/crossref_metadata_2025 huggingface dataset:
The Utility of Peripheral Blood Leucocyte Ratios as Biomarkers in Neonatal Sepsis: A Systematic Review and Meta-Analysis
Authors: Zhang Juanjuan , Zeng Jun’an , Zhang Liangjuan , Yu Xiping , Guo Jinzhen , Li Zhankui
Published: July 2022

Background

Early stage diagnosis of neonatal sepsis (NS) remains a major roadblock due to non-specific symptoms and the absence of precise laboratory index tests. The full blood count is a relatively cheap, universal, and rapid diagnostic test.

Method

This study assessed the diagnostic accuracies of immature-to-total neutrophil ratio (ITR), immature-to-mature neutrophil ratio (IMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) used in the diagnosis of NS. Included studies were retrieved by searching four major databases and relevant references, and reviewed based on the inclusion/exclusion criteria. Pooled sensitivities and specificities were calculated, I2 was utilized to test for heterogeneity, and the source was investigated via meta-regression analysis.

Results

Finally, 38 studies passed the eligibility criteria. A total of thirty-one studies (6,221 neonates) included data on the ITR, eight studies (1,230 neonates) included data on the IMR, seven studies (751 neonates) included data on the NLR, and two studies (283 neonates) included data on the PLR. The summary sensitivity estimates with 95% confidence interval (CI) for the ITR, IMR, NLR, and PLR tests were, respectively, 0.74 (95% CI: 0.66–0.80), 0.74 (95% CI: 0.54–0.88), 0.73 (95% CI: 0.68–0.78), and 0.81 (95% CI: 0.55–1.00). The summary specificity values for the ITR, IMR, NLR, and PLR tests were 0.83 (95% CI: 0.77–0.87), 0.89 (95% CI: 0.80–0.94), 0.69 (95% CI: 0.57–0.79), and 0.93 (95% CI: 0.81–1.00), respectively. The area under the summary receiver operating characteristic curves for the ITR, IMR, and NLR tests were 0.85 (95% CI: 0.82–0.88), 0.91 (95% CI: 0.88–0.93), and 0.75 (95% CI: 0.71–0.79). The PLR could not be evaluated because only two studies included pertinent data.

Conclusion

The NLR test might not be sufficiently accurate in precisely diagnosing NS. The ITR and IMR tests alone can improve the accuracy of NS diagnosis, but the marked heterogeneity and the limited number of studies prevented us from reaching any definitive conclusions. Thus, further studies are warranted to validate these findings.

Systematic Review Registration

[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021247850].
Evaluation of the neonatal sequential organ failure assessment and mortality risk in neonates with respiratory distress syndrome: A retrospective cohort study
Authors: Shi Shanshan , Guo Jie , Fu Minqiang , Liao Lihua , Tu Jiabin , Xiong Jialing , Liao Quanwang , Chen Weihua , Chen Kaihong , Liao Ying
Published: July 2022

Background

Respiratory distress syndrome (RDS) is one of the leading causes of neonatal death in the neonatal intensive care unit (NICU). Previous studies have suggested that the development of neonatal RDS may be associated with inflammation and lead to organ dysfunction. The neonatal sequential organ failure assessment (nSOFA) scoring system is an operational definition of organ dysfunction, but whether it can be used to predict mortality in neonates RDS is unknown. The aim of this study was to clarify the performance of the nSOFA score in predicting mortality in patients with neonatal RDS, with the aim of broadening the clinical application of the nSOFA score.

Methods

Neonates with RDS were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. Cox proportional hazards model were used to assess the association between nSOFA score and mortality. Propensity score matched analysis were used to assess the robustness of the analytical results.

Results

In this study of 1,281 patients with RDS of which 57.2% were male, death occurred in 40 cases (3.1%). Patients with high nSOFA scores had a higher mortality rate of 10.7% compared with low nSOFA scores at 0.3%. After adjusting for confounding, multivariate Cox proportional risk analysis showed that an increase in nSOFA score was significantly associated with increased mortality in patients with RDS [adjusted Hazards Ratio (aHR): 1.48, 95% Confidence Interval (CI): 1.32–1.67; p < 0.001]. Similarly, the High nSOFA group was significantly associated with higher mortality in RDS patients (aHR: 19.35, 95% CI: 4.41–84.95; p < 0.001) compared with the low nSOFA group.

Conclusion

The nSOFA score was positively associated with the risk of mortality in cases of neonatal RDS in the NICU, where its use may help clinicians to quickly and accurately identify high risk neonates and implement more aggressive intervention.
Relationship between sleep disorders and attention-deficit–hyperactivity disorder in children
Authors: Yin Huimei , Yang Dong , Yang Lin , Wu Guangsheng
Published: July 2022

Objective

To explore the correlation between sleep disorders and attention-deficit–hyperactivity disorder (ADHD) in children.

Methods

We studied 100 Chinese children (70 boys and 30 girls; mean age, 8.77 ± 2.39 years). Parents completed the Children's Sleep Disturbance Scale (SDSC) and the Swanson Nolan and Pelham Version IV Scale (SNAP-IV) questionnaires. SNAP-IV and SDSC scores were compared in children with and without sleep disorders and ADHD.

Results

There were significant differences in SDSC scores, Arousal Disorder (AD) scores, and Sleep Breathing Disorder (SBD) scores between children with and without ADHD (P < 0.05). The sleep disorder group had higher SNAP-IV scores than the non-sleep disorder group (P < 0.05). Children with sleep disorders showed higher ADHD symptom values (inattention, hyperactivity/impulsivity, and oppositional defiance) than children without sleep disorders (P < 0.01). There was a moderate correlation between SDSC scores and SNAP-IV scores (r = 0.486, P < 0.05). Using SNAP-IV scores as the dependent variable, multiple linear regression analysis was applied, and a statistically significant effect of AD and Sleep–Wake Transition Disorder (SWTD) scores on SNAP-IV scores was found (P < 0.05). The area under the curve (95% CI) of the SDSC score for predicting sleep disorders with ADHD was 0.714 (0.606, 0.821; P = 0.0005).

Conclusion

Children with ADHD are prone to sleep disorders. The higher the ADHD symptom score, the more sleeping problems. Sleep disorders can also cause or exacerbate ADHD symptoms, and the ADHD symptom score correlates with sleep disorder severity. We can reduce the severity of attention-deficit–hyperactivity in children with ADHD by improving their sleep with behavioral sleep interventions.
Phenotypes of Cornelia de Lange syndrome caused by non-cohesion genes: Novel variants and literature review
Authors: Shangguan Huakun , Chen Ruimin
Published: July 2022

Background

Cornelia de Lange syndrome (CdLS) is a genetic disorder caused by variants in cohesion genes including NIPBL, SMC1A, SMC3, RAD21, and HDAC8. According to the 2018 consensus statement, a patient with clinical scored ≥ 11 points could be diagnosed as CdLS. However, some variants in non-cohesion genes rather than cohesion genes can manifest as phenotypes of CdLS.

Objectives

This study describes six variants of non-cohesion genes (KDM6A, KMT2D, KMT2A ANKRD11, and UBE2A), and assesses the reliability of 11-points scale criteria in the clinical diagnosis of CdLS.

Methods

Whole-exome sequencing (WES) was performed on six patients with features of CdLS. Phenotypic and genotypic spectra of 40 previously reported patients with features of CdLS caused by non-cohesion genes variants and 34 previously reported patients with NIPBL variants were summarized. Clinical score comparison among patients with NIPBL variants versus those with variants in non-cohesin genes was performed.

Results

Variants in non-cohesion genes were found in six patients [KMT2A (n = 2), KMT2D, ANKRD11, KDM6A, and UBE2A]. Of them, four variants (KMT2A c.7789C > T, ANKRD11 c.1757_1776del, KDM6A c.655-1G > A, and UBE2A c.439C > T) were novel. Combining with previously reported cases, 46 patients with phenotypes of CdLS caused by variants in 20 non-cohesion genes are now reported. From this total cohort, the average clinical score of patients in ANKRD11 cohort, SETD5 cohort, and AFF4 cohort was statistically lower than those in NIPBL cohort (8.92 ± 1.77 vs. 12.23 ± 2.58, 7.33 ± 2.52 vs. 12.23 ± 2.58, 5.33 ± 1.53 vs. 12.23 ± 2.58; p < 0.05). The average clinical score of KMT2A cohort, EP300 cohort, and NIPBL cohort had not significantly different from (11 ± 2.19 vs. 12.23 ± 2.58, 10 ± 4.58 vs. 12.23 ± 2.58; p > 0.05).

Conclusion

We described 4 novel variants of non-cohesion genes in six Chinese patients with phenotypes of CdLS. Of note, three genes (KMT2D, KDM6A, and UBE2A) causing features of CdLS have never been reported. The proposed clinical criteria for CdLS needed to be updated and refined, insofar as WES was necessary to confirm the diagnosis of CdLS. Our study expanded the spectra of non-cohesion genetic variations in patients with features of CdLS.
Camostat Mesylate Versus Lopinavir/Ritonavir in Hospitalized Patients With COVID-19—Results From a Randomized, Controlled, Open Label, Platform Trial (ACOVACT)
Authors: Karolyi M. , Pawelka E. , Omid S. , Koenig F. , Kauer V. , Rumpf B. , Hoepler W. , Kuran A. , Laferl H. , Seitz T. , Traugott M. , Rathkolb V. , Mueller M. , Abrahamowicz A. , Schoergenhofer C. , Hecking M. , Assinger A. , Wenisch C. , Zeitlinger M. , Jilma B. , Zoufaly A.
Published: July 2022

Background: To date, no oral antiviral drug has proven to be beneficial in hospitalized patients with COVID-19.

Methods: In this randomized, controlled, open-label, platform trial, we randomly assigned patients ≥18 years hospitalized with COVID-19 pneumonia to receive either camostat mesylate (CM) (considered standard-of-care) or lopinavir/ritonavir (LPV/RTV). The primary endpoint was time to sustained clinical improvement (≥48 h) of at least one point on the 7-category WHO scale. Secondary endpoints included length of stay (LOS), need for mechanical ventilation (MV) or death, and 29-day mortality.

Results: 201 patients were included in the study (101 CM and 100 LPV/RTV) between 20 April 2020 and 14 May 2021. Mean age was 58.7 years, and 67% were male. The median time from symptom onset to randomization was 7 days (IQR 5–9). Patients in the CM group had a significantly shorter time to sustained clinical improvement (HR = 0.67, 95%-CI 0.49–0.90; 9 vs. 11 days, p = 0.008) and demonstrated less progression to MV or death [6/101 (5.9%) vs. 15/100 (15%), p = 0.036] and a shorter LOS (12 vs. 14 days, p = 0.023). A statistically nonsignificant trend toward a lower 29-day mortality in the CM group than the LPV/RTV group [2/101 (2%) vs. 7/100 (7%), p = 0.089] was observed.

Conclusion: In patients hospitalized for COVID-19, the use of CM was associated with shorter time to clinical improvement, reduced need for MV or death, and shorter LOS than the use of LPV/RTV. Furthermore, research is needed to confirm the efficacy of CM in larger placebo-controlled trials.

Systematic Review Registration: [https://clinicaltrials.gov/ct2/show/NCT04351724, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001302-30/AT], identifier [NCT04351724, EUDRACT-NR: 2020–001302-30].
Worenine Prevents Solar Ultraviolet–Induced Sunburn by Inhibiting JNK2
Authors: Xiao Juanjuan , Lu Hui , Ma Tengfei , Ni Xiaofang , Chang Teding , Liu Man , Li Nijie , Lu Peijiang , Ke Changshu , Tian Qin , Zou Ling , Wang Fei , Wang Wei , Zhang Lu , Yuan Ping , Liu Lin , Zhang Jianmin , Shi Fei , Duan Qiuhong , Zhu Feng
Published: July 2022

Excessive solar ultraviolet (SUV) radiation often causes dermatitis, photoaging, and even skin cancer. In the pathological processes of SUV-induced sunburn, JNK is activated by phosphorylation, and it in turn phosphorylates its downstream transcription factors, such as ATF2 and c-jun. The transcription factors further regulate the expression of pro-inflammatory genes, such as IL-6 and TNF-α, which ultimately leads to dermatitis. Therefore, inhibiting JNK may be a strategy to prevent dermatitis. In this study, we screened for worenine as a potential drug candidate for inhibiting sunburn. We determined that worenine inhibited the JNK-ATF2/c-jun signaling pathway and the secretion of IL-6 and TNF-α in cell culture and in vivo, confirming the role of worenine in inhibiting sunburn. Furthermore, we determined that worenine bound and inhibited JNK2 activity in vitro through the MST, kinase, and in vitro kinase assays. Therefore, worenine might be a promising drug candidate for the prevention and treatment of SUV-induced sunburn.
Treatment of COVID-19 Pneumonia and Acute Respiratory Distress With Ramatroban, a Thromboxane A2 and Prostaglandin D2 Receptor Antagonist: A Four-Patient Case Series Report
Authors: Ogletree Martin L. , Chander Chiang Kate , Kulshrestha Rashmi , Agarwal Aditya , Agarwal Ashutosh , Gupta Ajay
Published: July 2022

Hypoxemia in COVID-19 pneumonia is associated with hospitalization, mechanical ventilation, and mortality. COVID-19 patients exhibit marked increases in fatty acid levels and inflammatory lipid mediators, predominantly arachidonic acid metabolites, notably thromboxane B2>> prostaglandin E2> prostaglandin D2. Thromboxane A2increases pulmonary capillary pressure and microvascular permeability, leading to pulmonary edema, and causes bronchoconstriction contributing to ventilation/perfusion mismatch. Prostaglandin D2-stimulated IL-13 production is associated with respiratory failure, possibly due to hyaluronan accumulation in the lungs. Ramatroban is an orally bioavailable, dual thromboxane A2/TP and prostaglandin D2/DP2 receptor antagonist used in Japan for allergic rhinitis. Four consecutive outpatients with COVID-19 pneumonia treated with ramatroban exhibited rapid relief of dyspnea and hypoxemia within 12–36 h and complete resolution over 5 days, thereby avoiding hospitalization. Therefore, ramatroban as an antivasospastic, broncho-relaxant, antithrombotic, and immunomodulatory agent merits study in randomized clinical trials that might offer hope for a cost-effective pandemic treatment.
Semi-supervised vision transformer with adaptive token sampling for breast cancer classification
Authors: Wang Wei , Jiang Ran , Cui Ning , Li Qian , Yuan Feng , Xiao Zhifeng
Published: July 2022

Various imaging techniques combined with machine learning (ML) models have been used to build computer-aided diagnosis (CAD) systems for breast cancer (BC) detection and classification. The rise of deep learning models in recent years, represented by convolutional neural network (CNN) models, has pushed the accuracy of ML-based CAD systems to a new level that is comparable to human experts. Existing studies have explored the usage of a wide spectrum of CNN models for BC detection, and supervised learning has been the mainstream. In this study, we propose a semi-supervised learning framework based on the Vision Transformer (ViT). The ViT is a model that has been validated to outperform CNN models on numerous classification benchmarks but its application in BC detection has been rare. The proposed method offers a custom semi-supervised learning procedure that unifies both supervised and consistency training to enhance the robustness of the model. In addition, the method uses an adaptive token sampling technique that can strategically sample the most significant tokens from the input image, leading to an effective performance gain. We validate our method on two datasets with ultrasound and histopathology images. Results demonstrate that our method can consistently outperform the CNN baselines for both learning tasks. The code repository of the project is available at https://github.com/FeiYee/Breast-area-TWO.
Connections between metabolism and epigenetics: mechanisms and novel anti-cancer strategy
Authors: Chen Chen , Wang Zehua , Qin Yanru
Published: July 2022

Cancer cells undergo metabolic adaptations to sustain their growth and proliferation under several stress conditions thereby displaying metabolic plasticity. Epigenetic modification is known to occur at the DNA, histone, and RNA level, which can alter chromatin state. For almost a century, our focus in cancer biology is dominated by oncogenic mutations. Until recently, the connection between metabolism and epigenetics in a reciprocal manner was spotlighted. Explicitly, several metabolites serve as substrates and co-factors of epigenetic enzymes to carry out post-translational modifications of DNA and histone. Genetic mutations in metabolic enzymes facilitate the production of oncometabolites that ultimately impact epigenetics. Numerous evidences also indicate epigenome is sensitive to cancer metabolism. Conversely, epigenetic dysfunction is certified to alter metabolic enzymes leading to tumorigenesis. Further, the bidirectional relationship between epigenetics and metabolism can impact directly and indirectly on immune microenvironment, which might create a new avenue for drug discovery. Here we summarize the effects of metabolism reprogramming on epigenetic modification, and vice versa; and the latest advances in targeting metabolism-epigenetic crosstalk. We also discuss the principles linking cancer metabolism, epigenetics and immunity, and seek optimal immunotherapy-based combinations.
The Cost-Effectiveness of Tislelizumab Plus Chemotherapy for Locally Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer
Authors: Luo Xia , Zhou Zhen , Zeng Xiaohui , Liu Qiao
Published: July 2022

Objective: To investigate the cost-effectiveness of adding Chinese-developed anti-PD-1 antibody tislelizumab to first-line pemetrexed-platinum chemotherapy in (1) a study population of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (nsqNSCLC) and without known sensitizing EGFR mutations or ALK rearrangements and (2) its subgroups from the perspective of Chinese healthcare system.

Material and Methods: Separate Markov models were constructed for the entire study population and its subgroups; 10,000 patients with locally advanced or metastatic nsqNSCLC and without driver gene mutations were simulated in the first-line tislelizumab plus pemetrexed-platinum (TPP) arm and first-line pemetrexed-platinum (PP) arm, respectively. Transition probabilities were extracted from the RATIONALE 304 trial. Public health state utilities and costs were obtained from published literature, public national databases, and local general hospitals. The main outputs were incremental cost-effectiveness ratios (ICERs). The ICERs were compared to a willingness-to-pay threshold of $35,663 per quality-adjusted life-years (QALYs) to determine the cost-effective treatment. Sensitivity analyses were employed to assess the uncertainty in the model.

Results: For the entire patient population, first-line TPP versus PP use increased the effectiveness by 0.99 QALYs and healthcare costs by $28,749, resulting in an ICER of $28,749/QALY that was lower than the prespecified WTP threshold. For patient subgroups, first-line TPP conferred the greatest survival benefit in patients with PD-L1 expression ≥50%, followed by patients with liver metastasis and those who are current or former smokers. Overall, the ICERs for the first-line TPP versus PP ranged from $27,018/QALYs to $33,074/QALYs, which were consistently below the WTP threshold.

Conclusion: For Chinese patients with locally advanced or metastatic nsqNSCLC who had no known sensitizing EGFR mutations or ALK rearrangements, adding the Chinese-developed anti-PD-1 antibody tislelizumab to the first-line pemetrexed-platinum chemotherapy was cost-effective regardless of their baseline characteristics.
The use of traditional Chinese medicines in relieving exercise-induced fatigue
Authors: Liu Yuzhou , Li Congying , Shen Xiaofei , Liu Yue
Published: July 2022

Exercise-induced fatigue is a non-pathological fatigue and indicated by a reduction of muscle performance that is caused by excessive physical activity. It seriously affects the daily lives of people, in particular athletes, military personnel, and manual laborers. In recent years, increasing attention has been paid to improving the adverse effect of exercise-induced fatigue on people’s daily activities. Thus, studies and applications of traditional Chinese medicines (TCMs) in relieving exercise-induced fatigue have become the focus because of their good curative effects with fewer side effects. This review aims to document and summarize the critical and comprehensive information about the biological processes of exercise-induced fatigue, and to know the types of TCMs, their active components, and possible molecular mechanisms in alleviating exercise-induced fatigue. The peripheral and central mechanisms that cause exercise-induced fatigue have been summarized. A total of 47 exercise-induced fatigue relief TCMs have been collected, mostly including the types of visceral function regulation and emotional adjustment TCMs. Polysaccharides, terpenes, flavonoids/polyphenols are demonstrated to be the major bioactive components. The underlying molecular mechanisms are mainly related to the improvement of energy metabolism, elimination of excess metabolites, inhibition of oxidative stress and inflammatory response, regulation of HPA axis and neurotransmitters. Although current results are obtained mostly from animal models, the clinic trials are still insufficient, and a very few TCMs have been reported to possess potential hepatotoxicity. These findings still offer great reference value, and the significant efficacy in relieving exercise-induced fatigue is impossible to ignore. This review is expected to give insights into the research and development of new TCMs-derived drugs and health care products in relieving exercise-induced fatigue.
Optimising Absorption in Luminescent Solar Concentrators constraint by Average Visible Transmission and Color Rendering Index
Authors: de Bruin Thomas A. , van Sark Wilfried G. J. H. M.
Published: July 2022

The luminescent solar concentrator (LSC) as energy harvesting window is an emerging technology in the realm of building integrated photovoltaics. Using recent advancement for assessing the balance between transmitted color quality and potential electricity generation, this paper optimizes theoretical luminophore absorption spectra for the highest power generation possible. The power conversion efficiencies (PCE) are based on coupling of the LSC waveguide to a highly efficient crystalline silicon solar cell. A non-convex optimisation algorithm maximizing absorption is used with constraints for color quality parameters: average visible transmission (AVT) and color rendering index (CRI). An optimal luminophore has been defined using a continuous absorption function with a cut-off and limited absorption in the visible spectrum. Two types of constraints are set: 1) 55% < AVT < 100% and 2) 55% < AVT < 100% and 70 < CRI < 100. The first constraint will ensure sufficient visible light and the second ensures appropriate color rendering. Ray-trace validated results show high power conversion efficiencies ranging from 9.53% to 14.3% for (AVT = 90%, CRI = 98) and (AVT = 55%), respectively. Future studies can use these results to benchmark (tandem) LSCs for specific lighting requirements. Furthermore, the flexibility of the proposed method allows for the adaptation to constraints not used in this paper.
Simulating the Responses of the Magnetosphere–Ionosphere System to the IMF By Reversal
Authors: Gong Fan , Yu Yiqun , Cao Jinbin
Published: July 2022

The interplanetary magnetic field (IMF) By component can cause asymmetric features in the magnetosphere-ionosphere system and influence the electromagnetic energy input. In this study, we use the Space Weather Modeling Framework (SWMF) to study the transient dynamics after a sudden change in the IMF By component exerts on the magnetosphere system. Simulation results reveal that under northward IMF conditions, an abrupt change of the IMF By from duskward to dawnward induces a dawnward geomagnetic field firstly in the cusp region and then in both the near-Earth and magnetotail regions. The signal of the new y-component of the geomagnetic field in the near-Earth region extends tailward while that in the magnetotail moves Earthward, leading the middle-tail region to react last. We investigate in detail the transitional change of the y-component of the geomagnetic field and compare it to the scenario under southward IMF conditions, and find that the latter case reacts in a much simpler manner and the responses are faster globally.
Optimal Path Planning With Minimum Inspection Teams and Balanced Working Hours For Power Line Inspection
Authors: Hu Zhao-Long , Deng Yuan-Zhang , Peng Hao , Han Jian-Min , Zhu Xiang-Bin , Zhao Dan-Dan , Wang Hui , Zhang Jun
Published: July 2022

Power line inspection plays a significant role in the normal operation of power systems. Although there is much research on power line inspection, the question of how to balance the working hours of each worker and minimize the total working hours, which is related to social fairness and maximization of social benefits, is still challenging. Experience-based assignment methods tend to lead to extremely uneven working hours among the working/inspection teams. Therefore, it is of great significance to establish a theoretical framework that minimizes the number of working teams and the total working hours as well as balances the working hours of inspection teams. Based on two real power lines in Jinhua city, we first provide the theoretical range of the minimum number of inspection teams and also present a fast method to obtain the optimal solution. Second, we propose a transfer-swap algorithm to balance working hours. Combined with an intelligent optimization algorithm, we put forward a theoretical framework to balance the working hours and minimize the total working hours. The results based on the two real power lines verify the effectiveness of the proposed framework. Compared with the algorithm without swap, the total working hours obtained by the transfer-swap algorithm are shorter. In addition, there is an interesting finding: for our transfer-swap algorithm, the trivial greedy algorithm has almost the same optimization results as the simulated annealing algorithm, but the greedy algorithm has an extremely short running time.
Saturated Fatty Acid-Induced Endoplasmic Reticulum Stress and Insulin Resistance Are Prevented by Imoxin in C2C12 Myotubes
Authors: Eo Hyeyoon , Valentine Rudy J
Published: July 2022

In obesity, plasma free fatty acids (FFAs) levels are elevated due to enlarged adipose tissue mass. Saturated fatty acids can induce prolonged ER stress and insulin resistance. Double-stranded RNA-dependent Protein Kinase (PKR) is activated under stress conditions in skeletal muscle. The current study aimed to investigate the effect of imoxin (IMX), a selective PKR inhibitor, on palmitate-induced ER stress and insulin resistance in C2C12 myotubes. Cells were treated with 5 μM imoxin and exposed to 0.5 mM bovine serum albumin (BSA)-conjugated PA for 24 h. A subset of cells was stimulated with 50 nM insulin for the last 15 min. Glucose uptake was monitored and protein levels involved in ER stress and insulin signaling were measured by Western blotting. Palmitate stimulated PKR phosphorylation, which was prevented by imoxin. Moreover, imoxin reduced protein levels of ER stress-related markers including glucose-regulating protein 78 (GRP78), CCAAT-enhancer-binding protein homologous protein (CHOP), activating transcription factor 6 (ATF6) and spliced X-box binding protein 1 (XBP-1s) which were induced by palmitate. Furthermore, imoxin ameliorated palmitate-induced suppression of phospho-insulin receptor beta (p-IRβ) and Akt phosphorylation in myotubes. In addition, imoxin promoted glucose uptake in response to insulin under palmitate exposure. Furthermore, imoxin reduced phospho-c-Jun N-terminal kinase (p-JNK) induced by palmitate treatment. These findings suggest that imoxin may protect against saturated fatty acid-induced ER stress and insulin resistance in skeletal muscle, which are potentially mediated by PKR.
Organic zinc with moderate chelation strength enhances zinc absorption in the small intestine and expression of related transporters in the duodenum of broilers
Authors: Hu Yun , Wang Chuanlong , Wu Wei , Qu Yicheng , Zhang Weiyun , Li Ding , Zhu Ling , Gao Feiyu , Wu Bingxin , Zhang Liyang , Cui Xiaoyan , Li Tingting , Geng Yanqiang , Luo Xugang
Published: July 2022

Our previous study demonstrated that the absorption of zinc (Zn) from the organic Zn proteinate with moderate chelation strength was significantly higher than that of Zn from the inorganic Zn sulfate in the in situ ligated duodenal segment of broilers, but the underlying mechanisms are unknown. The present study aimed to determine the effect of organic Zn with moderate chelation strength and inorganic Zn on the Zn absorption in the small intestine and the expression of related transporters in the duodenum of broilers. The Zn-deficient broilers (13 days old) were fed with the Zn-unsupplemented basal diets (control) containing 25.72 and 25.64 mg Zn/kg by analysis or the basal diets supplemented with 60 mg Zn/kg as the Zn sulfate or the Zn proteinate with moderate chelation strength (Zn-Prot M) for 26 days. The results showed that the plasma Zn contents from the hepatic portal vein of broilers at 28 days and 39 days of age were increased (p < 0.05) by Zn addition and greater (p < 0.05) in the Zn-Prot M than in the Zn sulfate. On d 28, Zn addition upregulated (p < 0.05) mRNA expression of zinc transporter 1 (ZnT1), Zrt-irt-like protein 5 (ZIP5), y + L-type amino transporter 2 (y + LAT2) and b0,+-type amino acid transporter (rBAT), zinc transporter 4 (ZnT4) protein expression, and zinc transporter 9 (ZnT9) mRNA and protein expression in the duodenum. Moreover, ZnT9 mRNA expression, ZnT4, ZIP5, and rBAT protein expression, zinc transporter 7 (ZnT7), and y + LAT2 mRNA and protein expression in the duodenum of broilers on 28 days were higher (p < 0.05) in the Zn-Prot M than in the Zn sulfate. On d 39, supplemental Zn increased (p < 0.05) peptide-transporter 1 (PepT1) mRNA expression and y + LAT2 protein expression, while the mRNA expression of ZnT7 and Zrt-irt-like protein 3 (ZIP3) were higher (p < 0.05) for the Zn-Prot M than for the Zn sulfate in the duodenum. It was concluded that the Zn-Prot M enhanced the Zn absorption in the small intestine partially via upregulating the expression of ZnT4, ZnT7, ZnT9, ZIP3, ZIP5, y + LAT2, and rBAT in the duodenum of broilers.
Kinetically Consistent Data Assimilation for Plant PET Sparse Time Activity Curve Signals
Authors: D'Ascenzo Nicola , Xie Qingguo , Antonecchia Emanuele , Ciardiello Mariachiara , Pagnani Giancarlo , Pisante Michele
Published: July 2022

Time activity curve (TAC) signal processing in plant positron emission tomography (PET) is a frontier nuclear science technique to bring out the quantitative fluid dynamic (FD) flow parameters of the plant vascular system and generate knowledge on crops and their sustainable management, facing the accelerating global climate change. The sparse space-time sampling of the TAC signal impairs the extraction of the FD variables, which can be determined only as averaged values with existing techniques. A data-driven approach based on a reliable FD model has never been formulated. A novel sparse data assimilation digital signal processing method is proposed, with the unique capability of a direct computation of the dynamic evolution of noise correlations between estimated and measured variables, by taking into explicit account the numerical diffusion due to the sparse sampling. The sequential time-stepping procedure estimates the spatial profile of the velocity, the diffusion coefficient and the compartmental exchange rates along the plant stem from the TAC signals. To illustrate the performance of the method, we report an example of the measurement of transport mechanisms in zucchini sprouts.
The mungbean VrP locus encoding MYB90, an R2R3-type MYB protein, regulates anthocyanin biosynthesis
Authors: Lin Yun , Laosatit Kularb , Liu Jinyang , Chen Jingbing , Yuan Xingxing , Somta Prakit , Chen Xin
Published: July 2022

Anthocyanins are water-soluble pigments present in several tissues/parts of plants. The pigments provide color and are wildly known for health benefits for human, insect attraction for plant pollination, and stress resistance in plants. Anthocyanin content variations in mungbean [Vigna radiata (L.) Wilczek] were first noticed a long time ago, but the genetic mechanism controlling the anthocyanins in mungbean remains unknown. An F2 population derived from the cross between purple-hypocotyl (V2709) and green-hypocotyl (Sulv1) mungbeans was used to map the VrP locus controlling purple hypocotyl. The VrP locus was mapped to a 78.9-kb region on chromosome 4. Sequence comparison and gene expression analysis identified an R2R3-MYB gene VrMYB90 as the candidate gene for the VrP locus. Haplotype analysis using 124 mungbean accessions suggested that 10 single nucleotide polymorphisms (SNPs) in exon 3 may lead to an abolished expression of VrMYB90 and an absence of anthocyanin accumulation in the hypocotyl of Sulv1 and KPS2. The overexpression of VrMYB90 in mungbean hairy root, tobacco leaf, and Arabidopsis resulted in anthocyanin accumulation (purple color). Gene expression analysis demonstrated that VrMYB90 regulated anthocyanin accumulation in the hypocotyl, stem, petiole, and flowers, and the expression was sensitive to light. VrMYB90 protein may upregulate VrDFR encoding dihydroflavonol 4-reductase at the late biosynthesis step of anthocyanins in mungbeans. These results suggest that VrMYB90 is the dominator in the spatiotemporal regulation of anthocyanin biosynthesis. Our results provide insight into the biosynthesis mechanism of anthocyanin and a theoretical basis for breeding mungbeans.
Identification of candidate genes and clarification of the maintenance of the green pericarp of weedy rice grains
Authors: Han Zhenyun , Li Fei , Qiao Weihua , Nong Baoxuan , Cheng Yunlian , Zhang Lifang , Huang Jingfen , Wang Yanyan , Lou Danjing , Ge Jinyue , Xing Meng , Fan Weiya , Nie Yamin , Guo Wenlong , Wang Shizhuang , Liu Ziran , Li Danting , Zheng Xiaoming , Yang Qingwen
Published: July 2022

The weedy rice (Oryza sativa f. spontanea) pericarp has diverse colors (e.g., purple, red, light-red, and white). However, research on pericarp colors has focused on red and purple, but not green. Unlike many other common weedy rice resources, LM8 has a green pericarp at maturity. In this study, the coloration of the LM8 pericarp was evaluated at the cellular and genetic levels. First, an examination of their ultrastructure indicated that LM8 chloroplasts were normal regarding plastid development and they contained many plastoglobules from the early immature stage to maturity. Analyses of transcriptome profiles and differentially expressed genes revealed that most chlorophyll (Chl) degradation-related genes in LM8 were expressed at lower levels than Chl a/b cycle-related genes in mature pericarps, suggesting that the green LM8 pericarp was associated with inhibited Chl degradation in intact chloroplasts. Second, the F2 generation derived from a cross between LM8 (green pericarp) and SLG (white pericarp) had a pericarp color segregation ratio of 9:3:4 (green:brown:white). The bulked segregant analysis of the F2 populations resulted in the identification of 12 known genes in the chromosome 3 and 4 hotspot regions as candidate genes related to Chl metabolism in the rice pericarp. The RNA-seq and sqRT-PCR assays indicated that the expression of the Chl a/b cycle-related structural gene DVR (encoding divinyl reductase) was sharply up-regulated. Moreover, genes encoding magnesium-chelatase subunit D and the light-harvesting Chl a/b-binding protein were transcriptionally active in the fully ripened dry pericarp. Regarding the ethylene signal transduction pathway, the CTR (encoding an ethylene-responsive protein kinase) and ERF (encoding an ethylene-responsive factor) genes expression profiles were determined. The findings of this study highlight the regulatory roles of Chl biosynthesis- and degradation-related genes influencing Chl accumulation during the maturation of the LM8 pericarp.
Development of Rice Variety With Durable and Broad-Spectrum Resistance to Blast Disease Through Marker-Assisted Introduction of Pigm Gene
Authors: Feng Zhiming , Li Mingyou , Xu Zhiwen , Gao Peng , Wu Yunyu , Wu Keting , Zhao Jianhua , Wang Xiaoqiu , Wang Jianan , Li Mengchen , Hu Keming , Chen Hongqi , Deng Yiwen , Li Aihong , Chen Zongxiang , Zuo Shimin
Published: July 2022

Rice blast, caused by Magnaporthe oryzae (M. oryzae), is one of the most destructive diseases threatening rice production worldwide. Development of resistant cultivars using broad-spectrum resistance (R) genes with high breeding value is the most effective and economical approach to control this disease. In this study, the breeding potential of Pigm gene in geng/japonica rice breeding practice in Jiangsu province was comprehensively evaluated. Through backcross and marker-assisted selection (MAS), Pigm was introduced into two geng rice cultivars (Wuyungeng 32/WYG32 and Huageng 8/HG8). In each genetic background, five advanced backcross lines with Pigm (ABLs) and the same genotypes as the respective recurrent parent in the other 13 known R gene loci were developed. Compared with the corresponding recurrent parent, all these ABLs exhibited stronger resistance in seedling inoculation assay using 184 isolates collected from rice growing regions of the lower region of the Yangtze River. With respect to panicle blast resistance, all ABLs reached a high resistance level to blast disease in tests conducted in three consecutive years with the inoculation of seven mixed conidial suspensions collected from different regions of Jiangsu province. In natural field nursery assays, the ABLs showed significantly higher resistance than the recurrent parents. No common change on importantly morphological traits and yield-associated components was found among the ABLs, demonstrating the introduction of Pigm had no tightly linked undesirable effect on rice economically important traits and its associated grain weight reduction effect could be probably offset by others grain weight genes or at least in the background of the aforementioned two varieties. Notably, one rice line with Pigm, designated as Yangnonggeng 3091, had been authorized as a new variety in Jiangsu province in 2021, showing excellent performance on both grain yield and quality, as well as the blast resistance. Together, these results suggest that the Pigm gene has a high breeding value in developing rice varieties with durable and broad-spectrum resistance to blast disease.
Whole-genome resequencing identified QTLs, candidate genes and Kompetitive Allele-Specific PCR markers associated with the large fruit of Atlantic Giant (Cucurbita maxima)
Authors: Pan Liu , Wang Min , Yang Yating , Chen Chen , Dai Haibo , Zhang Zhiping , Hua Bing , Miao Minmin
Published: July 2022

Atlantic Giant (AG) pumpkin (Cucurbita maxima) produces the world’s largest fruit. Elucidating the molecular mechanism of AG fruit formation is of scientific and practical importance. In this research, genome-wide resequencing of an F2 population produced by a cross between AG and its small-fruit ancestor Hubbard was used to identify quantitative trait loci (QTLs) and candidate genes. Transgressive segregation of fruit size-related traits was observed in the F2 population, suggesting that fruit size was a quantitative trait controlled by multiple genes. A genetic map with an average physical distance of 154 kb per marker was constructed, and 13 QTLs related to fruit size were identified using bin-map construction. RNA sequencing analysis revealed that pathways associated with assimilate accumulation into the fruit, including carbohydrate metabolism, were significantly enriched in differentially expressed genes. According to the predicted impact of mutation on the biological function of certain proteins, 13 genes were selected as candidate genes associated with fruit size, among which two phytohormone-related genes, CmaCh17G011340 (a flavin-containing monooxygenase) and CmaCh04G029660 (a leucine-rich repeat protein kinase) were chosen for further investigation. Finally, one insertion-deletion (inDel) and three single nucleotide polymorphisms (SNPs) were successfully transformed to Kompetitive Allele-Specific PCR (KASP) markers. The novel QTLs and candidate genes identified provide insights into the genetic mechanism of large fruit formation of AG, and the genetic map and tightly linked KASP markers developed in this study can be employed for marker-assisted breeding to alter fruit size of C. maxima.
Three strategies of transgenic manipulation for crop improvement
Authors: Yu Haoqiang , Yang Qingqing , Fu Fengling , Li Wanchen
Published: July 2022

Heterologous expression of exogenous genes, overexpression of endogenous genes, and suppressed expression of undesirable genes are the three strategies of transgenic manipulation for crop improvement. Up to 2020, most (227) of the singular transgenic events (265) of crops approved for commercial release worldwide have been developed by the first strategy. Thirty-eight of them have been transformed by synthetic sequences transcribing antisense or double-stranded RNAs and three by mutated copies for suppressed expression of undesirable genes (the third strategy). By the first and the third strategies, hundreds of transgenic events and thousands of varieties with significant improvement of resistance to herbicides and pesticides, as well as nutritional quality, have been developed and approved for commercial release. Their application has significantly decreased the use of synthetic pesticides and the cost of crop production and increased the yield of crops and the benefits to farmers. However, almost all the events overexpressing endogenous genes remain at the testing stage, except one for fertility restoration and another for pyramiding herbicide tolerance. The novel functions conferred by the heterologously expressing exogenous genes under the control of constitutive promoters are usually absent in the recipient crops themselves or perform in different pathways. However, the endogenous proteins encoded by the overexpressing endogenous genes are regulated in complex networks with functionally redundant and replaceable pathways and are difficult to confer the desirable phenotypes significantly. It is concluded that heterologous expression of exogenous genes and suppressed expression by RNA interference and clustered regularly interspaced short palindromic repeats-cas (CRISPR/Cas) of undesirable genes are superior to the overexpression of endogenous genes for transgenic improvement of crops.
SlMYC2 mediates stomatal movement in response to drought stress by repressing SlCHS1 expression
Authors: Xu Bing-Qin , Wang Jing-Jing , Peng Yi , Huang Huang , Sun Lu-Lu , Yang Rui , Suo Lin-Na , Wang Shao-Hui , Zhao Wen-Chao
Published: July 2022

Drought stress limits plant development and reproduction. Multiple mechanisms in plants are activated to respond to stress. The MYC2 transcription factor is a core regulator of the jasmonate (JA) pathway and plays a vital role in the crosstalk between abscisic acid (ABA) and JA. In this study, we found that SlMYC2 responded to drought stress and regulated stomatal aperture in tomato (Solanum lycopersicum). Overexpression of SlMYC2 repressed SlCHS1 expression and decreased the flavonol content, increased the reactive oxygen species (ROS) content in guard cells and promoted the accumulation of JA and ABA in leaves. Additionally, silencing the SlCHS1 gene produced a phenotype that was similar to that of the MYC2-overexpressing (MYC2-OE) strain, especially in terms of stomatal dynamics and ROS levels. Finally, we confirmed that SlMYC2 directly repressed the expression of SlCHS1. Our study revealed that SlMYC2 drove stomatal closure by modulating the accumulation of flavonol and the JA and ABA contents, helping us decipher the mechanism of stomatal movement under drought stress.
Evaluating the Efficacy of Gum Arabic-Zinc Oxide Nanoparticles Composite Coating on Shelf-Life Extension of Mandarins (cv. Kinnow)
Authors: Nxumalo Kwanele Andy , Fawole Olaniyi Amos , Oluwafemi Oluwatobi Samuel
Published: July 2022

Restricted postharvest application of synthetic fungicides in maintaining the quality of citrus fruits has led to a search for alternative postharvest treatments. This study evaluated the efficacy of gum arabic (GA) enriched with green synthesized zinc oxide nanoparticles (ZnO-NPs) in maintaining the postharvest quality of mandarin (cv. Kinnow). ZnO-NPs were synthesized usingBidens pilosaleaf extract and incorporated into GA (2% w/v) at 0, 0.25, 0.5, and 1% to form composite coatings: GA, GA + ZnO-NP 0.25%, GA + ZnO-NP 0.5% and GA + ZnO-NP 1%, respectively. Fruit were dipped for 3 min in the respective coatings, with untreated fruit used as control. Fruit were air-dried, packed in commercial cartons, and stored at 5 ± 1°C and 90 ± 5% relative humidity (RH) for 40 days and observed at 10 days intervals, plus 5 days at 20 ± 5°C and 65 ± 5% RH to determine the incidence of physiological disorders. GA + ZnO-NP showed promise as an alternative postharvest treatment for controlling postharvest physiological disorders associated with ‘Kinnow’ mandarin. For instance, GA + ZnO-NP 0.5% markedly minimized weight loss (9.2%), electrolyte leakage (43.8%) and chilling injury incidence (5.4%) compared to control (weight loss; 33.3%, electrolyte leakage; 90.3% and chilling injury incidence; 41.5%) at the end of the storage. GA + ZnO-NP 1% significantly alleviated rind pitting, with 13.2% incidence compared to 45.2% rind pitting incidence in the control fruit. This was due to significantly higher phytochemical and antioxidant capacity and reduced antioxidant enzyme degradation in coated fruit than in control. In conclusion, gum arabic coating enriched with ZnO-NPs at concentrations between 0.5 and 1% is recommended as a viable option to maintain the quality of ‘Kinnow’ mandarin fruit during cold storage.