bluuebunny/crossref_metadata_2025 huggingface dataset:
An Enhanced Ubiquitous-Joint Model for a Rock Mass With Conjugate Joints and Its Application on Excavation Simulation of Large Underground Caverns
Authors: Leng Xianlun , Wang Chuan , Sheng Qian , Chen Jian , Li Hailun
Published: September 2021

A conjugate jointed rock mass (CJRM) is a rock mass with two sets of intersecting joints formed from intact rock under shear. Its mechanical properties and excavation-induced hazards of large underground caverns are different from those of common rock masses because of the unique geological origin thereof. To demonstrate numerically the excavation responses of CJRM, the ubiquitous-joint model is enhanced by consideration of the specific mechanical behaviors of the rock mass. In the enhanced model, CJRM is considered as the composite of columns of rock and two sets of weak planes of joints. The local coordinates, failure modes, and failure sequences of the rock columns and joints are redefined based on the composite characteristics of CJRM, and the failure criteria and plastic potential functions are accordingly modified. The enhanced model is verified numerically by triaxial compression tests and then employed to simulate the excavation of large underground caverns of a pumped storage power station in China. Results show that the modification of the local coordinate system, failure modes, and failure sequences made in the enhanced model is suited to the simulation of the mechanical behaviors of CJRM. Compared with the original ubiquitous-joint model, the enhanced model allows better predictions of the distribution of plastic zones and magnitudes of deformations in simulating underground excavations in CJRM and helps to assess the excavation-triggered hazards more accurately.
Association of ANGPTL8 and Resistin With Diabetic Nephropathy in Type 2 Diabetes Mellitus
Authors: Li Mengni , Fan Rongping , Peng Xuemin , Huang Jiaojiao , Zou Huajie , Yu Xuefeng , Yang Yan , Shi Xiaoli , Ma DeLin
Published: September 2021

Background

Previous studies showed altered angiopoietin-like protein-8 (ANGPTL-8) and resistin circulating levels in type 2 diabetes mellitus (T2DM). Whether or not the alteration in ANGPTL-8 and resistin level can be a predictive maker for increased diabetic nephropathy risk remains unclear.

Aim

To Investigate the possible association of ANGPTL-8 and resistin with DN, and whether this association is affected by NAFLD status.

Methods

A total of 278 T2DM patients were enrolled. Serum levels of ANGPTL8, resistin, BMI, blood pressure, duration of diabetes, glycosylated hemoglobin (HbA1c), fasting blood glucose (FPG), hypersensitive C-reactive protein (hs-CRP), lipid profile, liver, and kidney function tests were assessed. The relationship between DN with ANGPTL8 and resistin was analyzed in the unadjusted and multiple-adjusted regression models.

Results

Serum levels of ANGPTL8 and resistin were significantly higher in DN compared with T2DM subjects without DN (respectively; P <0.001), especially in non-NAFLD populations. ANGPTL8 and resistin showed positive correlation with hs-CRP (respectively; P<0.01), and negative correlation with estimated GFR (eGFR) (respectively; P=<0.001) but no significant correlation to HOMA-IR(respectively; P>0.05). Analysis showed ANGPTL8 levels were positively associated with resistin but only in T2DM patients with DN(r=0.1867; P<0.05), and this significant correlation disappeared in T2DM patients without DN. After adjusting for confounding factors, both ANGPTL8(OR=2.095, 95%CI 1.253-3.502 P=0.005) and resistin (OR=2.499, 95%CI 1.484-4.208 P=0.001) were risk factors for DN. Data in non-NAFLD population increased the relationship between ANGPTL8 (OR=2.713, 95% CI 1.494-4.926 P=0.001), resistin (OR=4.248, 95% CI 2.260-7.987 P<0.001)and DN. The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8 and resistin was 0.703, and the specificity was 70.4%. These data were also increased in non-NAFLD population, as the AUC (95%CI) was 0.756, and the specificity was 91.2%.

Conclusion

This study highlights a close association between ANGPTL8, resistin and DN, especially in non-NAFLD populations. These results suggest that ANGPTL-8 and resistin may be risk predictors of DN.
Exploring C-To-G Base Editing in Rice, Tomato, and Poplar
Authors: Sretenovic Simon , Liu Shishi , Li Gen , Cheng Yanhao , Fan Tingting , Xu Yang , Zhou Jianping , Zheng Xuelian , Coleman Gary , Zhang Yong , Qi Yiping
Published: September 2021

As a precise genome editing technology, base editing is broadly used in both basic and applied plant research. Cytosine base editors (CBEs) and adenine base editors (ABEs) represent the two commonly used base editor types that mediate C-to-T and A-to-G base transition changes at the target sites, respectively. To date, no transversion base editors have been described in plants. Here, we assessed three C-to-G base editors (CGBEs) for targeting sequences with SpCas9’s canonical NGG protospacer adjacent motifs (PAMs) as well as three PAM-less SpRY-based CGBEs for targeting sequences with relaxed PAM requirements. The analyses in rice and tomato protoplasts showed that these CGBEs could make C-to-G conversions at the target sites, and they preferentially edited the C6 position in the 20-nucleotide target sequence. C-to-T edits, insertions and deletions (indels) were major byproducts induced by these CGBEs in the protoplast systems. Further assessment of these CGBEs in stably transformed rice and poplar plants revealed the preference for editing of non-GC sites, and C-to-T edits are major byproducts. Successful C-to-G editing in stably transgenic rice plants was achieved by rXRCC1-based CGBEs with monoallelic editing efficiencies up to 38% in T0 lines. The UNG-rAPOBEC1 (R33A)-based CGBE resulted in successful C-to-G editing in polar, with monoallelic editing efficiencies up to 6.25% in T0 lines. Overall, this study revealed that different CGBEs have different preference on preferred editing sequence context, which could be influenced by cell cycles, DNA repair pathways, and plant species.
K-RAS4A: Lead or Supporting Role in Cancer Biology?
Authors: Aran Veronica
Published: September 2021

The RAS oncogene is one of the most frequently mutated genes in human cancer, with K-RAS having a leading role in tumorigenesis. K-RAS undergoes alternative splicing, and as a result its transcript generates two gene products K-RAS4A and K-RAS4B, which are affected by the same oncogenic mutations, are highly homologous, and are expressed in a variety of human tissues at different levels. In addition, both isoforms localise to the plasma membrane by distinct targeting motifs. While some evidence suggests nonredundant functions for both splice variants, most work to date has focused on K-RAS4B, or even just K-RAS (i.e., without differentiating between the splice variants). This review aims to address the most relevant evidence published regarding K-RAS4A and to discuss if this “minor” isoform could also play a leading role in cancer, concluding that a significant body of evidence supports a leading role rather than a supporting (or secondary) role for K-RAS4A in cancer biology.
Effect of the Rehabilitation Program, ReStOre, on Serum Biomarkers in a Randomized Control Trial of Esophagogastric Cancer Survivors
Authors: Kennedy Susan A. , Annett Stephanie L. , Dunne Margaret R. , Boland Fiona , O’Neill Linda M. , Guinan Emer M. , Doyle Suzanne L. , Foley Emma K. , Elliott Jessie A. , Murphy Conor F. , Bennett Annemarie E. , Carey Michelle , Hillary Daniel , Robson Tracy , Reynolds John V. , Hussey Juliette , O’Sullivan Jacintha
Published: September 2021

Background

The Rehabilitation Strategies Following Esophagogastric cancer (ReStOre) randomized control trial demonstrated a significant improvement in cardiorespiratory fitness of esophagogastric cancer survivors. This follow-up, exploratory study analyzed the biological effect of exercise intervention on levels of 55 serum proteins, encompassing mediators of angiogenesis, inflammation, and vascular injury, from participants on the ReStOre trial.

Methods

Patients >6 months disease free from esophagogastric cancer were randomized to usual care or the 12-week ReStOre program (exercise training, dietary counselling, and multidisciplinary education). Serum was collected at baseline (T0), post-intervention (T1), and at 3-month follow up (T2). Serum biomarkers were quantified by enzyme-linked immunosorbent assay (ELISA).

Results

Thirty-seven patients participated in this study; 17 in the control arm and 20 in the intervention arm. Exercise intervention resulted in significant alterations in the level of expression of serum IP-10 (mean difference (MD): 38.02 (95% CI: 0.69 to 75.35)), IL-27 (MD: 249.48 (95% CI: 22.43 to 476.53)), and the vascular injury biomarkers, ICAM-1 (MD: 1.05 (95% CI: 1.07 to 1.66)), and VCAM-1 (MD: 1.51 (95% CI: 1.04 to 2.14)) at T1. A significant increase in eotaxin-3 (MD: 2.59 (95% CI: 0.23 to 4.96)), IL-15 (MD: 0.27 (95% CI: 0 to 0.54)) and decrease in bFGF (MD: 1.62 (95% CI: -2.99 to 0.26)) expression was observed between control and intervention cohorts at T2 (p<0.05).

Conclusions

Exercise intervention significantly altered the expression of a number of serum biomarkers in disease-free patients who had prior treatment for esophagogastric cancer.

Impact

Exercise rehabilitation causes a significant biological effect on serum biomarkers in esophagogastric cancer survivors.

Clinical Trial Registration

ClinicalTrials.gov (NCT03314311).
Machine Learning-Based Comparative Analysis of Pan-Cancer and Pan-Normal Tissues Identifies Pan-Cancer Tissue-Enriched circRNAs Related to Cancer Mutations as Potential Exosomal Biomarkers
Authors: Wang Xuezhu , Dong Yucheng , Wu Zilong , Wang Guanqun , Shi Yue , Zheng Yongchang
Published: September 2021

A growing body of evidence has shown that circular RNA (circRNA) is a promising exosomal cancer biomarker candidate. However, global circRNA alterations in cancer and the underlying mechanism, essential for identification of ideal circRNA cancer biomarkers, remain under investigation. We comparatively analyzed the circRNA landscape in pan-cancer and pan-normal tissues. Using co-expression and LASSO regularization analyses, as well as a support vector machine, we analyzed 265 pan-cancer and 319 pan-normal tissues in order to identify the circRNAs with the highest ability to distinguish between pan-cancer and pan-normal tissues. We further studied their expression in plasma exosomes from patients with cancer and their relation with cancer mutations and tumor microenvironment landscape. We discovered that circRNA expression was globally reduced in pan-cancer tissues and plasma exosomes from cancer patients than in pan-normal tissues and plasma exosomes from healthy controls. We identified dynein axonemal heavy chain 14 (DNAH14), the top back-spliced gene exclusive to pan-cancer tissues, as the host gene of three pan-cancer tissue-enriched circRNAs. Among these three circRNAs, chr1_224952669_224968874_+ was significantly elevated in plasma exosomes from hepatocellular carcinoma and colorectal cancer patients. It was also related to the cancer mutation chr1:224952669: G>A, a splice acceptor variant, and was increasingly transcription-driven in cancer tissues. Moreover, pan-cancer tissue-enriched and pan-normal tissue-enriched circRNAs were associated with distinct tumor microenvironment patterns. Our machine learning-based analysis provides insights into the aberrant landscape and biogenesis of circRNAs in cancer and highlights cancer mutation-related and DNAH14-derived circRNA, chr1_224952669_224968874_+, as a potential cancer biomarker.
DNA Damage Response and Repair Gene Alterations Increase Tumor Mutational Burden and Promote Poor Prognosis of Advanced Lung Cancer
Authors: Dai Jiawei , Jiang Minlin , He Kan , Wang Hao , Chen Peixin , Guo Haoyue , Zhao Wencheng , Lu Hui , He Yayi , Zhou Caicun
Published: September 2021

DNA damage response and repair (DDR) gene alterations increase tumor-infiltrating lymphocytes, genomic instability, and tumor mutational burden (TMB). Whether DDR-related alterations relate to therapeutic response and prognosis in lung cancer lacking oncogenic drivers remains unknown. Pretherapeutic cancer samples of 122 patients [86 non-small cell lung cancer and 36 small cell lung cancer (SCLC)] harboring no EGFR/ALK alterations were collected. Through whole-exome sequencing, we outlined DDR mutational landscape and determined relationships between DDR gene alterations and TMB or intratumoral heterogeneity. Then, we evaluated the impacts of DDR gene alterations on therapeutic response and prognosis and established a DDR-based model for prognosis prediction. In addition, we investigated somatic interactions of DDR genes and immunomodulatory genes, immune expression patterns, immune microenvironment, and immune infiltration characteristics between DDR-deficient and DDR-proficient samples. Samples from cBioportal datasets were utilized for verification. We found that deleterious DDR gene alterations were closely associated with higher TMB than proficient-types (p < 0.001). DDR mechanisms attach great importance to the determination of patients’ prognosis after chemotherapy, and alterations of base excision repair pathway in adenocarcinoma, nucleotide excision repair in squamous carcinoma, and homologous recombination pathway in SCLC tend to associate with worse progression-free survival to first-line chemotherapy (all p < 0.05). A predictive nomogram model was constructed incorporating DDR-related alterations, clinical stage, and smoking status, with the area under curve values of 0.692–0.789 for 1- and 2-year receiver operating characteristic curves in training and testing cohorts. Furthermore, DDR-altered tumors contained enhanced frequencies of alterations in various genes of human leukocyte antigen (HLA) class I pathway including TAP1 and TAP2 than DDR-proficient samples. DDR-deficient types had lower expressions of STING1 (p = 0.01), CD28 (p = 0.020), HLA-DRB6 (p = 0.014) in adenocarcinoma, lower TNFRSF4 (p = 0.017), and TGFB1 expressions (p = 0.033) in squamous carcinoma, and higher CD40 (p = 0.012) and TNFRSF14 expressions (p = 0.022) in SCLC. DDR alteration enhanced activated mast cells in adenocarcinoma (p = 0.044) and M2 macrophage in squamous carcinoma (p = 0.004) than DDR-proficient types. Collectively, DDR gene alterations in lung cancer without oncogenic drivers are positively associated with high TMB. Specific DDR gene alterations tend to associate with worse progression-free survival to initial chemotherapy.
Calmodulin 2 Facilitates Angiogenesis and Metastasis of Gastric Cancer via STAT3/HIF-1A/VEGF-A Mediated Macrophage Polarization
Authors: Mu Ganggang , Zhu Yijie , Dong Zehua , Shi Lang , Deng Yunchao , Li Hongyan
Published: September 2021

Background

Tumor-associated macrophages (TAMs) are indispensable to mediating the connections between cells in the tumor microenvironment. In this study, we intended to research the function and mechanism of Calmodulin2 (CALM2) in gastric cancer (GC)-TAM microenvironment.

Materials and methods

CALM2 expression in GC tissues and GC cells was determined through quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). The correlation between CALM2 level and the survival rate of GC patients was assessed. The CALM2 overexpression or knockdown model was constructed to evaluate its role in GC cell proliferation, migration, and invasion. THP1 cells or HUVECs were co-cultured with the conditioned medium of GC cells. Tubule formation experiment was done to examine the angiogenesis of endothelial cells. The proliferation, migration, and polarization of THP1 cells were measured. A xenograft model was set up in BALB/c male nude mice to study CALM2x’s effects on tumor growth and lung metastasis in vivo. Western Blot (WB) checked the profile of JAK2/STAT3/HIF-1/VEGFA in GC tissues and cells.

Results

In GC tissues and cell lines, CALM2 expression was elevated and positively relevant to the poor prognosis of GC patients. In in-vitro experiments, CALM2 overexpression or knockdown could facilitate or curb the proliferation, migration, invasion, and angiogenesis of HUVECs and M2 polarization of THP1 cells. In in-vivo experiments, CALM2 boosted tumor growth and lung metastasis. Mechanically, CALM2 could arouse the JAK2/STAT3/HIF-1/VEGFA signaling. It was also discovered that JAK2 and HIF-1A inhibition could attenuate the promoting effects of CALM2 on GC, HUVECs cells, and macrophages.

Conclusion

CALM2 modulates the JAK2/STAT3/HIF-1/VEGFA axis and bolsters macrophage polarization, thus facilitating GC metastasis and angiogenesis.
Nuclear Mechanisms Involved in Endocrine Resistance
Authors: Dittmer Jürgen
Published: September 2021

Endocrine therapy is a standard treatment offered to patients with ERα (estrogen receptor α)-positive breast cancer. In endocrine therapy, ERα is either directly targeted by anti-estrogens or indirectly by aromatase inhibitors which cause estrogen deficiency. Resistance to these drugs (endocrine resistance) compromises the efficiency of this treatment and requires additional measures. Endocrine resistance is often caused by deregulation of the PI3K/AKT/mTOR pathway and/or cyclin-dependent kinase 4 and 6 activities allowing inhibitors of these factors to be used clinically to counteract endocrine resistance. The nuclear mechanisms involved in endocrine resistance are beginning to emerge. Exploring these mechanisms may reveal additional druggable targets, which could help to further improve patients’ outcome in an endocrine resistance setting. This review intends to summarize our current knowledge on the nuclear mechanisms linked to endocrine resistance.
Spontaneous and Naloxone-Precipitated Withdrawal Behaviors From Chronic Opiates are Accompanied by Changes in N-Oleoylglycine and N-Oleoylalanine Levels in the Brain and Ameliorated by Treatment With These Mediators
Authors: Ayoub Samantha M. , Piscitelli Fabiana , Silvestri Cristoforo , Limebeer Cheryl L. , Rock Erin M. , Smoum Reem , Farag Mathew , de Almeida Hannah , Sullivan Megan T. , Lacroix Sébastien , Boubertakh Besma , Nallabelli Nayudu , Lichtman Aron H , Leri Francesco , Mechoulam Raphael , Di Marzo Vincenzo , Parker Linda A.
Published: September 2021

Rationale: The endocannabinoidome mediators, N-Oleoylglycine (OlGly) and N-Oleoylalanine (OlAla), have been shown to reduce acute naloxone-precipitated morphine withdrawal affective and somatic responses.

Objectives: To determine the role and mechanism of action of OlGly and OlAla in withdrawal responses from chronic exposure to opiates in male Sprague-Dawley rats.

Methods: Opiate withdrawal was produced: 1) spontaneously 24 h following chronic exposure to escalating doses of morphine over 14 days (Experiments 1 and 2) and steady-state exposure to heroin by minipumps for 12 days (Experiment 3), 2) by naloxone injection during steady-state heroin exposure (Experiment 4), 3) by naloxone injection during operant heroin self-administration (Experiment 5).

Results: In Experiment 1, spontaneous morphine withdrawal produced somatic withdrawal reactions. The behavioral withdrawal reactions were accompanied by suppressed endogenous levels of OlGly in the nucleus accumbens, amygdala, and prefrontal cortex, N-Arachidonylglycerol and OlAla in the amygdala, 2-arachidonoylglycerol in the nucleus accumbens, amygdala and interoceptive insular cortex, and by changes in colonic microbiota composition. In Experiment 2, treatment with OlAla, but not OlGly, reduced spontaneous morphine withdrawal responses. In Experiment 3, OlAla attenuated spontaneous steady-state heroin withdrawal responses at both 5 and 20 mg/kg; OlGly only reduced withdrawal responses at the higher dose of 20 mg/kg. Experiment 4 demonstrated that naloxone-precipitated heroin withdrawal from steady-state exposure to heroin (7 mg/kg/day for 12 days) is accompanied by tissue-specific changes in brain or gut endocannabinoidome mediator, including OlGly and OlAla, levels and colonic microbiota composition, and that OlAla (5 mg/kg) attenuated behavioural withdrawal reactions, while also reversing some of the changes in brain and gut endocannabinoidome and gut microbiota induced by naloxone. Experiment 5 demonstrated that although OlAla (5 mg/kg) did not interfere with operant heroin self-administration on its own, it blocked naloxone-precipitated elevation of heroin self-administration behavior.

Conclusion: These results suggest that OlAla and OlGly are two endogenous mediators whose brain concentrations respond to chronic opiate treatment and withdrawal concomitantly with changes in colon microbiota composition, and that OlAla may be more effective than OlGly in suppressing chronic opiate withdrawal responses.
Role of Intra- and Extracellular Lipid Signals in Cancer Stemness and Potential Therapeutic Strategy
Authors: Hu Jianming , Zhang Leyi , Chen Wuzhen , Shen Lesang , Jiang Jingxin , Sun Shanshan , Chen Zhigang
Published: September 2021

Accumulating evidence showed that cancer stem cells (CSCs) play significant roles in cancer initiation, resistance to therapy, recurrence and metastasis. Cancer stem cells possess the ability of self-renewal and can initiate tumor growth and avoid lethal factors through flexible metabolic reprogramming. Abnormal lipid metabolism has been reported to be involved in the cancer stemness and promote the development of cancer. Lipid metabolism includes lipid uptake, lipolysis, fatty acid oxidation, de novo lipogenesis, and lipid desaturation. Abnormal lipid metabolism leads to ferroptosis of CSCs. In this review, we comprehensively summarized the role of intra- and extracellular lipid signals in cancer stemness, and explored the feasibility of using lipid metabolism-related treatment strategies for future cancer.
Loop Diuretics Inhibit Ischemia-Induced Intracellular Ca2+ Overload in Neurons via the Inhibition of Voltage-Gated Ca2+ and Na+ Channels
Authors: Katnik Christopher , Cuevas Javier
Published: September 2021

One consequence of ischemic stroke is disruption of intracellular ionic homeostasis. Intracellular overload of both Na+ and Ca2+ has been linked to neuronal death in this pathophysiological state. The etiology of ionic imbalances resulting from stroke-induced ischemia and acidosis includes the dysregulation of multiple plasma membrane transport proteins, such as increased activity of sodium-potassium-chloride cotransporter-1 (NKCC-1). Experiments using NKCC1 antagonists, bumetanide (BMN) and ethacrynic acid (EA), were carried out to determine if inhibition of this cotransporter affects Na+ and Ca2+ overload observed following in vitro ischemia-acidosis. Fluorometric Ca2+ and Na+ measurements were performed using cultured cortical neurons, and measurements of whole-cell membrane currents were used to determine target(s) of BMN and EA, other than the electroneutral NKCC-1. Both BMN and EA depressed ischemia-acidosis induced [Ca2+]i overload without appreciably reducing [Na+]i increases. Voltage-gated Ca2+ channels were inhibited by both BMN and EA with half-maximal inhibitory concentration (IC50) values of 4 and 36 μM, respectively. Similarly, voltage-gated Na+ channels were blocked by BMN and EA with IC50 values of 13 and 30 μM, respectively. However, neither BMN nor EA affected currents mediated by acid-sensing ion channels or ionotropic glutamatergic receptors, both of which are known to produce [Ca2+]i overload following ischemia. Data suggest that loop diuretics effectively inhibit voltage-gated Ca2+ and Na+ channels at clinically relevant concentrations, and block of these channels by these compounds likely contributes to their clinical effects. Importantly, inhibition of these channels, and not NKCC1, by loop diuretics reduces [Ca2+]i overload in neurons during ischemia-acidosis, and thus BMN and EA could potentially be used therapeutically to lessen injury following ischemic stroke.
Streptomyces sp. JCK-6131 Protects Plants Against Bacterial and Fungal Diseases via Two Mechanisms
Authors: Le Khanh Duy , Kim Jeun , Nguyen Hoa Thi , Yu Nan Hee , Park Ae Ran , Lee Chul Won , Kim Jin-Cheol
Published: September 2021

Plant bacterial and fungal diseases cause significant agricultural losses and need to be controlled. Beneficial bacteria are promising candidates for controlling these diseases. In this study, Streptomyces sp. JCK-6131 exhibited broad-spectrum antagonistic activity against various phytopathogenic bacteria and fungi. In vitro assays showed that the fermentation filtrate of JCK-6131 inhibited the growth of bacteria and fungi with minimum concentration inhibitory (MIC) values of 0.31–10% and 0.31–1.25%, respectively. In the in vivo experiments, treatment with JCK-6131 effectively suppressed the development of apple fire blight, tomato bacterial wilt, and cucumber Fusarium wilt in a dose-dependent manner. RP-HPLC and ESI-MS/MS analyses indicated that JCK-6131 can produce several antimicrobial compounds, three of which were identified as streptothricin E acid, streptothricin D, and 12-carbamoyl streptothricin D. In addition, the disease control efficacy of the foliar application of JCK-6131 against tomato bacterial wilt was similar to that of the soil drench application, indicating that JCK-6131 could enhance defense resistance in plants. Molecular studies on tomato plants showed that JCK-6131 treatment induced the expression of the pathogenesis-related (PR) genes PR1, PR3, PR5, and PR12, suggesting the simultaneous activation of the salicylate (SA) and jasmonate (JA) signaling pathways. The transcription levels of PR genes increased earlier and were higher in treated plants than in untreated plants following Ralstonia solanacearum infection. These results indicate that Streptomyces sp. JCK-6131 can effectively control various plant bacterial and fungal diseases via two distinct mechanisms of antibiosis and induced resistance.
Delayed Protein Changes During Seed Germination
Authors: Bai Bing , van der Horst Niels , Cordewener Jan H. , America Antoine H. P. , Nijveen Harm , Bentsink Leónie
Published: September 2021

Over the past decade, ample transcriptome data have been generated at different stages during seed germination; however, far less is known about protein synthesis during this important physiological process. Generally, the correlation between transcript levels and protein abundance is low, which strongly limits the use of transcriptome data to accurately estimate protein expression. Polysomal profiling has emerged as a tool to identify mRNAs that are actively translated. The association of the mRNA to the polysome, also referred to as translatome, provides a proxy for mRNA translation. In this study, the correlation between the changes in total mRNA, polysome-associated mRNA, and protein levels across seed germination was investigated. The direct correlation between polysomal mRNA and protein abundance at a single time-point during seed germination is low. However, once the polysomal mRNA of a time-point is compared to the proteome of the next time-point, the correlation is much higher. 35% of the investigated proteome has delayed changes at the protein level. Genes have been classified based on their delayed protein changes, and specific motifs in these genes have been identified. Moreover, mRNA and protein stability and mRNA length have been found as important predictors for changes in protein abundance. In conclusion, polysome association and/or dissociation predicts future changes in protein abundance in germinating seeds.
Delivering Resources for Augmented Reality by UAVs: a Reinforcement Learning Approach
Authors: Brunori Damiano , Colonnese Stefania , Cuomo Francesca , Flore Giovanna , Iocchi Luca
Published: September 2021

Unmanned aerial vehicles (UAVs) are supposed to be used to provide different services from video surveillance to communication facilities during critical and high-demanding scenarios. Augmented reality streaming services are especially demanding in terms of required throughput, computing resources at the user device, as well as user data collection for advanced applications, for example, location-based or interactive ones. This work is focused on the experimental utilization of a framework adopting reinforcement learning (RL) approaches to define the paths crossed by UAVs in delivering resources for augmented reality services. We develop an OpenAI Gym-based simulator that is tuned and tested to study the behavior of UAVs trained with RL to fly around a given area and serve augmented reality users. We provide abstractions for the environment, the UAVs, the users, and their requests. A reward function is then defined to encompass several quality-of-experience parameters. We train our agents and observe how they behave as a function of the number of UAVs and users at different hours of the day.
A New Constructive Heuristic Driven by Machine Learning for the Traveling Salesman Problem
Authors: Mele Umberto Junior , Gambardella Luca Maria , Montemanni Roberto
Published: September 2021

Recent systems applying Machine Learning (ML) to solve the Traveling Salesman Problem (TSP) exhibit issues when they try to scale up to real case scenarios with several hundred vertices. The use of Candidate Lists (CLs) has been brought up to cope with the issues. A CL is defined as a subset of all the edges linked to a given vertex such that it contains mainly edges that are believed to be found in the optimal tour. The initialization procedure that identifies a CL for each vertex in the TSP aids the solver by restricting the search space during solution creation. It results in a reduction of the computational burden as well, which is highly recommended when solving large TSPs. So far, ML was engaged to create CLs and values on the elements of these CLs by expressing ML preferences at solution insertion. Although promising, these systems do not restrict what the ML learns and does to create solutions, bringing with them some generalization issues. Therefore, motivated by exploratory and statistical studies of the CL behavior in multiple TSP solutions, in this work, we rethink the usage of ML by purposely employing this system just on a task that avoids well-known ML weaknesses, such as training in presence of frequent outliers and the detection of under-represented events. The task is to confirm inclusion in a solution just for edges that are most likely optimal. The CLs of the edge considered for inclusion are employed as an input of the neural network, and the ML is in charge of distinguishing when such edge is in the optimal solution from when it is not. The proposed approach enables a reasonable generalization and unveils an efficient balance between ML and optimization techniques. Our ML-Constructive heuristic is trained on small instances. Then, it is able to produce solutions—without losing quality—for large problems as well. We compare our method against classic constructive heuristics, showing that the new approach performs well for TSPLIB instances up to 1748 cities. Although ML-Constructive exhibits an expensive constant computation time due to training, we proved that the computational complexity in the worst-case scenario—for the solution construction after training—is O(n2logn2), n being the number of vertices in the TSP instance.
Mechanism and Experiment Study of Non-Contact Ultrasonic Assisted Grinding
Authors: Huang Weiqing , Zhong Qunyou , An Dawei , Yang Chenglong , Zhang Yi
Published: September 2021

Ultrasonic-assisted grinding processing can effectively reduce the surface roughness and enhance the processing efficiency in the processing of hard and brittle materials. However, the most common ultrasonic assisted grinding is a type of contact ultrasonic grinding where the grinding tool directly contacts the workpiece, which means that it is necessary to accurately control the pre-pressure of the grinding tool on the workpiece. The control of pre-pressure will inevitably increase the complexity of the grinding device, and it is easy to wear the workpiece because of improper pre-pressure control. In this paper, a non-contact ultrasonic grinding method is proposed and the machining mechanism of non-contact ultrasonic grinding is revealed. The resonant frequency of the ultrasonic vibration system and vibration amplitude of the grinding tool working face were simulated and experimentally tested, respectively. Then, the experiment of non-contact ultrasonic grinding of a sapphire wafer was carried out. The result showed that non-contact ultrasonic grinding of the sapphire wafer could reduce the surface roughness by 48.6%. Compared with traditional contact grinding of sapphire wafer under certain pre-pressure conditions, the experimental results show that non-contact ultrasonic grinding has better effects in reducing surface roughness, improving processing efficiency, and improving the quality uniformity of the workpiece machining surface.
Controlling Stored Products’ Pests with Plant Secondary Metabolites: A Review
Authors: Nikolaou Polyxeni , Marciniak Paweł , Adamski Zbigniew , Ntalli Nikoletta
Published: September 2021

To date, only a handful of pesticides have been authorized by the European Council for the protection of stored grains. Resistance issues and ecotoxicity concerns necessitate the development of ecofriendly tools in that direction. In this review, we refer to the recent findings on plant extracts and pure plant-derived substances with promising biological activity and the potential to be used as biopesticides for stored products. The main aim of biopesticides is to be effective against target pests, without harming humans and the environment. Many plant species, among those reported herein, are part of the human diet, and are thus not harmful to humans. Edible plant extracts produced with inorganic solvents represent safe candidates for use as repellants, fumigants or contact pesticides. Cinnamon, rosemary, parsley, garlic, oregano and basil are found in products destined for human consumption but also display significant biological activities. Interestingly, cinnamon is one of the most widely tested botanical matrixes, exhibiting the best lethal effects on almost all insect and mite taxa reported herein (Acaroidea, Coleoptera and Lepidoptera), followed by basil and garlic. Prunus persica,Azadirachta indica A. Juss and Carum sp. seem to be very promising too as miticides and/or insecticides, with A. indica already being represented commercially by a plant-derived acaricidal formulation.
Factors Limiting the Development of the Organic Food Sector—Perspective of Processors, Distributors, and Retailers
Authors: Górska-Warsewicz Hanna , Żakowska-Biemans Sylwia , Stangierska Dagmara , Świątkowska Monika , Bobola Agnieszka , Szlachciuk Julita , Czeczotko Maksymilian , Krajewski Karol , Świstak Ewa
Published: September 2021

Our study aimed to explore the factors limiting the development of the organic food sector in Poland from the perspective of processing, distributing, and retailing companies. We used a qualitative approach with in-depth semi-structured interviews with the management board representatives of 17 large- and medium-sized enterprises and the owners of 10 small and medium companies. The potential limiting factors, including legal, economic, technological, and environmental factors, were identified by reviewing the corporate and market reports of processing and retailing companies operating in the Polish organic sector. We used a thematic analysis recommended in the literature to analyze qualitative data. The main factors indicated by the managers were the legal concerns, limitations resulting from a lack of constant supply of organic raw materials, and increased competition on domestic and international markets. In addition, business activities in the Polish organic sector were affected by the instability of the financial situation in terms of financial liquidity, adequate cost, capital structure, and credits. The results of the study may be of value for policymakers to ensure sustainable development of the organic food sector in Poland.
Introgression of QTLs for Drought Tolerance into Farmers’ Preferred Sorghum Varieties
Authors: Mwamahonje Andekelile , Eleblu John Saviour Yaw , Ofori Kwadwo , Feyissa Tileye , Deshpande Santosh , Garcia-Oliveira Ana Luísa , Bohar Rajaguru , Kigoni Milcah , Tongoona Pangirayi
Published: September 2021

Sorghum is a major staple food crop for the people in semi-arid areas of Africa and Asia. Post-flowering drought is a global constraint of sorghum production. The study aimed to improve stay-green (STG) characteristics of farmer-preferred sorghum varieties in Tanzania using marker-assisted backcrossing. A total of 752 individuals representing five BC2F1 populations and their parents were genotyped using previously reported KASP markers linked with STG 3A and STG 3B quantitative trait loci (QTL). In the BC2F1 populations, the maximum number of individuals with heterozygous alleles were observed in S35*Pato background (37) whereas only seven individuals derived from the B35*Wahi parents’ background contained heterozygous alleles. Of the 30 single nucleotide polymorphism (SNP) markers, favourable alleles were observed at 18 loci in BC2F1 populations. In the BC2F1 generation, the highest (0.127 kg/panicle) grain yield was observed in the B35*NACO Mtama 1 background population. The genotypic analysis revealed the presence of favourable alleles in homozygous conditions at markers loci associated with STG 3A and STG 3B QTLs in BC2F3 populations, suggesting successful introgression of STG QTLs from the donor parents to the recurrent parents. Across water irrigation regimes, the highest (0.068 kg/panicle) mean grain weight was observed in the genotype NA316C. Therefore, our study demonstrated the utility of marker-assisted backcrossing for drought tolerance improvement of locally adapted sorghum varieties in Africa.
Early Detection of Mold-Contaminated Peanuts Using Machine Learning and Deep Features Based on Optical Coherence Tomography
Authors: Manhando Edwin , Zhou Yang , Wang Fenglin
Published: September 2021

Fungal infection is a pre-harvest and post-harvest crisis for farmers of peanuts. In environments with temperatures around 28 °C to 30 °C or relative humidity of approximately 90%, mold-contaminated peanuts have a considerable likelihood to be infected with Aflatoxins. Aflatoxins are known to be highly carcinogenic, posing danger to humans and livestock. In this work, we proposed a new approach for detection of mold-contaminated peanuts at an early stage. The approach employs the optical coherence tomography (OCT) imaging technique and an error-correcting output code (ECOC) based Support Vector Machine (SVM) trained on features extracted using a pre-trained Deep Convolutional Neural Network (DCNN). To this end, mold-contaminated and uncontaminated peanuts were scanned to create a data set of OCT images used for training and evaluation of the ECOC-SVM model. Results showed that the proposed approach is capable of detecting mold-contaminated peanuts with respective accuracies of approximately 85% and 96% after incubation periods of 48 and 96 h.
The Resurrection of Mabrokan: Production of Multiple Cloned Offspring from Decade-Old Vitrified Tissue Collected from a Deceased Champion Show Camel
Authors: Hossein Mohammad Shamim , Yu Xianfeng , Son Young-Bum , Jeong Yeon-Ik , Jeong Yeon-Woo , Choi Eun-Ji , Tinson Alex H. , Singh Kuhad Kuldip , Singh Rajesh , Noura Al Shamsi , Hwang Woo-Suk
Published: September 2021

Somatic cell nuclear transfer (SCNT) provides a unique opportunity to reproduce animals with superior genetics. Viable cell lines are usually established from tissues collected by biopsy from living animals in the SCNT program. In the present study, tissues were collected and preserved from a suddenly deceased champion camel. We established cell lines from these decade-old tissues and used them as nuclear donors. After 42 h of in vitro maturation, 68.00 ± 2.40% of oocytes reached the metaphase II (M II) stage while 87.31 ± 2.57% in vivo collected oocytes were matured at collection (p < 0.05). We observed a higher blastocyst formation rate when in vivo matured oocytes (43.45 ± 2.07%) were used compared to in vitro matured oocytes (21.52 ± 1.74%). The live birth rate was 6.45% vs. 16.67% for in vitro and in vivo matured oocytes, respectively. Microsatellite analysis of 13 camel loci revealed that all the SCNT-derived offspring were identical to each other and with their somatic cell donor. The present study succeeded in the resurrection of 11 healthy offspring from the decade-old vitrified tissues of a single somatic cell donor individual using both in vitro and in vivo matured oocytes.
Exogenous Enzymes Influenced Eimeria-Induced Changes in Cecal Fermentation Profile and Gene Expression of Nutrient Transporters in Broiler Chickens
Authors: Lin Yang , Olukosi Oluyinka A.
Published: September 2021

Two 21-day experiments were conducted to investigate the effects of exogenous enzymes on growth performance, tight junctions, and nutrient transporters, jejunal oligosaccharides and cecal short-chain fatty acids (SCFA) of broiler chickens challenged with mixed Eimeria. Two different basal diets: high fiber-adequate protein (HFAP; Expt. 1) or low fiber-low protein (LFLP; Expt. 2) were used in the two experiments. In each experiment, birds were allocated to four treatments in a 2 × 2 factorial arrangement (with or without protease and xylanase combination; with or without Eimeria challenge). In Expt. 1, with HFAP diets, Eimeria upregulated (p < 0.05) the expression of claudin-1, but downregulated (p < 0.05) glucose transporters GLUT2/GLUT5. On the contrary, enzymes downregulated (p < 0.05) claudin-1 and alleviated the Eimeria-depressed GLUT2/GLUT5 expression. In both experiments, Eimeria decreased (p < 0.05) cecal saccharolytic SCFA and increased (p < 0.05) cecal branched-chain fatty acids. The challenge × enzyme interaction (p < 0.05) showed that enzymes reversed the Eimeria effects on fermentation pattern shift. In conclusion, Eimeria altered tight junctions and nutrient transporters expression promoted cecal proteolytic fermentation and inhibited saccharolytic fermentation. Exogenous enzymes showed the potential of alleviating the Eimeria-induced intestinal gene expression changes and reversing the unfavorable cecal fermentation pattern.
7S,15R-Dihydroxy-16S,17S-Epoxy-Docosapentaenoic Acid, a Novel DHA Epoxy Derivative, Inhibits Colorectal Cancer Stemness through Repolarization of Tumor-Associated Macrophage Functions and the ROS/STAT3 Signaling Pathway
Authors: Wang Lifang , Choi Hack Sun , Su Yan , Lee Binna , Song Jae Jun , Jang Yong-Suk , Seo Jeong-Woo
Published: September 2021

Colorectal cancer is a highly malignant cancer that is inherently resistant to many chemotherapeutic drugs owing to the complicated tumor-supportive microenvironment (TME). Tumor-associated macrophages (TAM) are known to mediate colorectal cancer metastasis and relapse and are therefore a promising therapeutic target. In the current study, we first confirmed the anti-inflammatory effect of 7S,15R-dihydroxy-16S,17S-epoxy-docosapentaenoic acid (diHEP-DPA), a novel DHA dihydroxy derivative synthesized in our previous work. We found that diHEP-DPA significantly reduced lipopolysaccharide (LPS)-induced inflammatory cytokines secretion of THP1 macrophages, IL-6, and TNF-α. As expected, diHEP-DPA also modulated TAM polarization, as evidenced by decreased gene and protein expression of the TAM markers, CD206, CD163, VEGF, and TGF-β1. During the polarization process, diHEP-DPA treatment decreased the concentration of TGF-β1, IL-1β, IL-6, and TNF-α in culture supernatants via inhibiting the NF-κB pathway. Moreover, diHEP-DPA blocked immunosuppression by reducing the expression of SIRPα in TAMs and CD47 in colorectal cancer cells. Knowing that an inflammatory TME largely serves to support epithelial-mesenchymal transition (EMT) and cancer stemness, we tested whether diHEP-DPA acted through polarization of TAMs to regulate these processes. The intraperitoneally injected diHEP-DPA inhibited tumor growth when administered alone or in combination with 5-fluorouracil (5-FU) chemotherapy in vivo. We further found that diHEP-DPA effectively reversed TAM-conditioned medium (TCCM)-induced EMT and enhanced colorectal cancer stemness, as evidenced by its inhibition of colorectal cancer cell migration, invasion and expression of EMT markers, as well as cancer cell tumorspheres formation, without damaging colorectal cancer cells. DiHEP-DPA reduced the population of aldehyde dehydrogenase (ALDH)-positive cells and expression of colorectal stemness marker proteins (CD133, CD44, and Sox2) by modulating TAM polarization. Additionally, diHEP-DPA directly inhibited cancer stemness by inducing the production of reactive oxygen species (ROS), which, in turn, reduced the phosphorylation of nuclear signal transducer and activator of transcription 3 (STAT3). These data collectively suggest that diHEP-DPA has the potential for development as an anticancer agent against colorectal cancer.
Stereospecific Epoxidation of Limonene Catalyzed by Peroxygenase from Oat Seeds
Authors: Biondi Daniela Maria , Sanfilippo Claudia , Patti Angela
Published: September 2021

Limonene is one of the most abundant naturally occurring cyclic monoterpenes and has recently emerged as a sustainable alternative to petroleum-based solvents as well as a chemical platform for the production of value-added compounds. The biocatalytic epoxidation of both enantiomers of limonene was carried out in the presence of a peroxygenase-containing preparation from oat (Avena sativa) flour. Different reaction profiles were observed depending on the starting enantiomer of limonene, but in both cases the 1,2-monoepoxide was obtained as the main product with excellent diastereoselectivity. Trans-1,2-monoepoxide and cis-1,2-monoepoxide were isolated from the reaction of (R)-limonene and (S)-limonene, respectively, and the reactions were scaled-up to 0.17 M substrate concentration. The process is valuable for operational simplicity, lack of toxic metal catalysts, and cost-effectiveness of the enzymatic source. Pure stereoisomers of 1,2-monoepoxides of limonene constitute a useful starting material for biorenewable polymers, but can be also converted into other chiral derivatives by epoxide ring opening with nucleophiles. As a proof of concept, a tandem protocol for the preparation of enantiopure (1S,2S,4R)-1,2-diol from (R)-limonene and (1R,2R,4S)-1,2-diol from (S)-limonene was developed.
Nrf2 and Heme Oxygenase-1 Involvement in Atherosclerosis Related Oxidative Stress
Authors: Alonso-Piñeiro Jose Angel , Gonzalez-Rovira Almudena , Sánchez-Gomar Ismael , Moreno Juan Antonio , Durán-Ruiz Ma Carmen
Published: September 2021

Atherosclerosis remains the underlying process responsible for cardiovascular diseases and the high mortality rates associated. This chronic inflammatory disease progresses with the formation of occlusive atherosclerotic plaques over the inner walls of vascular vessels, with oxidative stress being an important element of this pathology. Oxidation of low-density lipoproteins (ox-LDL) induces endothelial dysfunction, foam cell activation, and inflammatory response, resulting in the formation of fatty streaks in the atherosclerotic wall. With this in mind, different approaches aim to reduce oxidative damage as a strategy to tackle the progression of atherosclerosis. Special attention has been paid in recent years to the transcription factor Nrf2 and its downstream-regulated protein heme oxygenase-1 (HO-1), both known to provide protection against atherosclerotic injury. In the current review, we summarize the involvement of oxidative stress in atherosclerosis, focusing on the role that these antioxidant molecules exert, as well as the potential therapeutic strategies applied to enhance their antioxidant and antiatherogenic properties.