bluuebunny/crossref_metadata_2025 huggingface dataset:
Capsaicin Potentiates Anticancer Drug Efficacy Through Autophagy-Mediated Ribophorin II Downregulation and Necroptosis in Oral Squamous Cell Carcinoma Cells
Authors: Huang Yi-Ching , Yuan Tien-Ming , Liu Bang-Hung , Liu Kai-Li , Wung Chiung-Hua , Chuang Show-Mei
Published: September 2021

The ability of capsaicin co-treatment to sensitize cancer cells to anticancer drugs has been widely documented, but the detailed underlying mechanisms remain unknown. In addition, the role of ribophorin II turnover on chemosensitization is still uncertain. Here, we investigated capsaicin-induced sensitization to chemotherapeutic agents in the human oral squamous carcinoma cell lines, HSC-3 and SAS. We found that capsaicin (200 μM) did not induce remarkable apoptotic cell death in these cell lines; instead, it significantly enhanced autophagy with a concomitant decrease of ribophorin II protein. This capsaicin-induced decrease in ribophorin II was intensified by the autophagy inducer, rapamycin, but attenuated by the autophagy inhibitors, ULK1 inhibitor and chloroquine, indicating that the autophagic process was responsible for the capsaicin-induced down-regulation of ribophorin II. Co-administration of capsaicin with conventional anticancer agents did, indeed, sensitize the cancer cells to these agents. In co-treated cells, the induction of apoptosis was significantly reduced and the levels of the necroptosis markers, phospho-MLKL and phospho-RIP3, were increased relative to the levels seen in capsaicin treatment alone. The levels of DNA damage response markers were also diminished by co-treatment. Collectively, our results reveal a novel mechanism by which capsaicin sensitizes oral cancer cells to anticancer drugs through the up-regulation of autophagy and down-regulation of ribophorin II, and further indicate that the induction of necroptosis is a critical factor in the capsaicin-mediated chemosensitization of oral squamous carcinoma cells to conventional anticancer drugs.
Hydrogen Sulfide Prevents Mesenteric Adipose Tissue Damage, Endothelial Dysfunction, and Redox Imbalance From High Fructose Diet-Induced Injury in Aged Rats
Authors: Revenko Oleh , Pavlovskiy Yaroslav , Savytska Maryana , Yashchenko Antonina , Kovalyshyn Vasyl , Chelpanova Ilona , Varyvoda Olena , Zayachkivska Oksana
Published: September 2021

A high fructose diet (HFD) and advanced age are key factors for the gradual loss of physiological integrity of adipose tissue. Endogenous hydrogen sulfide (H2S) has beneficial effects on cytoprotection and redox balance. But its interactive effects on age-related damage of mesenteric vessels and connective and adipose tissues (MA) during HFD which could be the base of the development of effective physiological-based therapeutic strategy are unknown. The aim of study was to investigate age- and HFD-induced mesenteric cellular changes and activities of enzymes in H2S synthesis and to test the effects of sodium hydrosulfide (NaHS) which is considered an H2S donor on them. Adult and aged male rats on a standard diet (SD) or 4-week HFD were exposed to acute water-immersion restraint stress (WIRS) for evaluation of mesenteric subcellular and cellular adaptive responses by electron microscopy. The effects of exogenous NaHS (5.6 mg/kg/day for 9 days) versus vehicle on mesentery changes were investigated. Serum glucose level, thiobarbituric acid reactive substances (TBARS), and activities of cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), thiosulfate-dithiol sulfurtransferase (TST), and sulfite oxidase (SO) were examined by spectrophotometry. In both adult and aged SD groups, treatment with NaHS protected mesenteric cells after WIRS. In both groups, the treatment with NaHS also protected MA mitochondria, microvascular endothelial and sub-endothelial structures, and fibroblasts versus the vehicle-treated group that had signs of damage. HFD increased MA injury and mitochondrial changes in both aged and adult rats. HFD-associated malfunction is characterized by low activities of CSE, CBS, TST, SO, and increased TBARS. Finally, we demonstrated that pretreatment with NaHS inhibited MA and mitochondria alterations in aged rats exposed to HFD and WIRS, lowered TBARS, and enhanced H2S enzyme activities in contrast to the vehicle-treated group. Mitochondrial integrity alterations, endothelial damage, and redox imbalance are key factors for rat mesenteric adipose tissue damage during advanced age. These alterations and MA hypertrophic changes retain the central for HFD-induced damage. Moreover, H2S signaling contributes to MA and mitochondria redox balance that is crucial for advanced age and HFD injury. The future study of H2S donors’ effects on mesenteric cells is fundamental to define novel therapeutic strategies against metabolic changes.
Integrated Proteomics and Metabolomics Link Acne to the Action Mechanisms of Cryptotanshinone Intervention
Authors: Zhu Zhaoming , Chen Tingting , Wang Zhuxian , Xue Yaqi , Wu Wenfeng , Wang Yuan , Du Qunqun , Wu Yufan , Zeng Quanfu , Jiang Cuiping , Shen Chunyan , Liu Li , Zhu Hongxia , Liu Qiang
Published: September 2021

The label-free methods of proteomic combined with metabolomics were applied to explore the mechanisms of Cryptotanshinone (CPT) intervention in rats with acne. The model group consisted of rats given oleic acid (MC), then treated with CPT, while control groups did not receive treatment. The skin samples were significantly different between control, model and CPT-treated groups in hierarchical clustering dendrogram. Obvious separations of the skin metabolic profiles from the three groups were found through PCA scoring. In total, 231 and 189 differentially expressed proteins (DEPs) were identified in MC and CPT groups, respectively. By the KEGG analysis, five protein and metabolite pathways were found to be significantly altered. These played important roles in response to oleic acid-induced acne and drug treatment. CPT could negatively regulate glycolysis/gluconeogenesis and histidine metabolisms to decrease keratinocyte differentiation and improve excessive keratinization and cellular barrier function. CPT could down-regulate the IL-17 signaling pathway and regulate the acne-driven immune response of sebum cells. The biosynthesis of unsaturated fatty acids metabolism, glycerophospholipid metabolism and linoleic acid pathways could significantly alter sebum production and control sebaceous gland secretion after CPT treatment. The gap junction was up-regulated after CPT treatment and the skin barrier turned back to normal. Krt 14, Krt 16 and Krt 17 were significantly down-regulated, decreasing keratinization, while inflammatory cell infiltration was improved by down-regulation of Msn, up-regulation of linoleic acid and estrogen pathways after CPT treatment. These results propose action mechanisms for the use of CPT in acne, as a safe and potential new drug.
Natural Small Molecules Targeting NF-κB Signaling in Glioblastoma
Authors: Uddin Md. Sahab , Kabir Md. Tanvir , Mamun Abdullah Al , Sarwar Md. Shahid , Nasrin Fatema , Emran Talha Bin , Alanazi Ibtesam S. , Rauf Abdur , Albadrani Ghadeer M. , Sayed Amany A. , Mousa Shaker A. , Abdel-Daim Mohamed M.
Published: September 2021

Nuclear factor-κB (NF-κB) is a transcription factor that regulates various genes that mediate various cellular activities, including propagation, differentiation, motility, and survival. Abnormal activation of NF-κB is a common incidence in several cancers. Glioblastoma multiforme (GBM) is the most aggressive brain cancer described by high cellular heterogeneity and almost unavoidable relapse following surgery and resistance to traditional therapy. In GBM, NF-κB is abnormally activated by various stimuli. Its function has been associated with different processes, including regulation of cancer cells with stem-like phenotypes, invasion of cancer cells, and radiotherapy resistance identification of mesenchymal cells. Even though multimodal therapeutic approaches such as surgery, radiation therapy, and chemotherapeutic drugs are used for treating GBM, however; the estimated mortality rate for GBM patients is around 1 year. Therefore, it is necessary to find out new therapeutic approaches for treating GBM. Many studies are focusing on therapeutics having less adverse effects owing to the failure of conventional chemotherapy and targeted agents. Several studies of compounds suggested the involvement of NF-κB signaling pathways in the growth and development of a tumor and GBM cell apoptosis. In this review, we highlight the involvement of NF-κB signaling in the molecular understanding of GBM and natural compounds targeting NF-κB signaling.
Integrated Phytochemical Analysis Based on UPLC–MS/MS and Network Pharmacology Approaches to Explore the Effect of Odontites vulgaris Moench on Rheumatoid Arthritis
Authors: Ji Mingyue , Wang Congcong , Yang Tieyi , Meng Xiangxi , Wang Xiaoqin , Li Minhui
Published: September 2021

Odontites vulgaris Moench has the effect of clearing away heat, detoxification, dispelling wind, and clearing dampness. In this study, the potential anti-inflammatory compounds of O. vulgaris were investigated using ultra-high-performance liquid chromatography–mass spectrometry (UPLC–MS/MS) combined with the network pharmacology approach and further confirmed on an LPS-activated RAW 264.7 macrophage model. Monomer compounds were prepared from the active fraction using modern advanced separation and purification methods. UPLC–Q-Exactive HRMS was used to identify the chemical compounds in the active fractions of O. vulgaris. D-mannitol, geniposidic acid, salidroside, shanzhiside methyl ester, eleutheroside B, geniposide, 7,8-dihydroxycoumarin, gardoside methyl ester, arenarioside, vanillic acid, p-hydroxy-cinnamic acid, melampyroside, syringaresinol, tricin, and diosmetin were isolated from O. vulgaris for the first time. A compound database of O. vulgaris was established based on the existing literature to predict the mechanism of O. vulgaris in the treatment of rheumatoid arthritis. The results suggest that the PI3K-Akt pathway mediates O. vulgaris and deserves more attention in the treatment of RA. Finally, the anti-rheumatoid arthritis effects of the four target compounds were validated with the decreased levels of NO, TNF-α, IL-6 and IL-1β in RAW 264.7 macrophage cells treated with LPS. The present study explored the potential targets and signaling pathways of O. vulgaris in the treatment of RA, which may help to illustrate the mechanisms involved in the action of O. vulgaris and may provide a better understanding of the relationship between O. vulgaris and RA. This study provides novel insights into the development of new drugs and utilization of Mongolian traditional Chinese medicine resources.
Dengzhanxixin Injection Ameliorates Cognitive Impairment Through a Neuroprotective Mechanism Based on Mitochondrial Preservation in Patients With Acute Ischemic Stroke
Authors: An Haiting , Tao Wuhai , Liang Ying , Li Peng , Li Min , Zhang Xiaxia , Chen Kewei , Wei Dongfeng , Xie Daojun , Zhang Zhanjun
Published: September 2021

Acute ischemic stroke (AIS) is a global health burden and cognitive impairment is one of its most serious complication. Adequate interventions for AIS may have the potential to improve cognitive outcomes. In the present study, we selected Erigeron breviscapus (Vaniot) Hand.-Mazz. injection (Dengzhanxixin injection, DZXI), a widely used Chinese herbal injection, in contrast to edaravone as the positive control drug to test its potential to ameliorates neurological and cognitive impairments caused by AIS. We performed a 2-week randomized trial with these two drugs in AIS patients presenting mild to moderate cognitive impairments. Neuropsychological tests and MRI examinations showed that DZXI attenuated the neurological and cognitive impairments of patients and protected the grey matter in specific regions from ischemic damage. Notably, DZXI exerted better effects than edaravone in some neuropsychological tests, probably due to the protective effect of DZXI on grey matter. To explore the therapeutic mechanisms, we carried out an experiment with a middle cerebral artery occlusion rat model. We found that DZXI decreased the infarct volume and increased the survival of neuronal cells in the ischemic penumbra; furthermore, DZXI modulated the mitochondrial respiratory chain process and preserved the mitochondrial structure in the brain tissue. Overall, our data suggested that the administration of DZXI is effective at ameliorating neurological and cognitive impairments in AIS, and the underlying mechanisms are related to the protective effects of DZXI on cerebral neurons and neuronal mitochondria.
Standardized Astragalus Mongholicus Bunge-Curcuma Aromatica Salisb. Extract Efficiently Suppresses Colon Cancer Progression Through Gut Microbiota Modification in CT26-Bearing Mice
Authors: Gu Junfei , Sun Ruolan , Wang Qiaohan , Liu Fuyan , Tang Decai , Chang Xiangwei
Published: September 2021

Altered gut microbiota and a damaged colon mucosal barrier have been implicated in the development of colon cancer. Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (ACE) is a common herbal drug pair that widely used clinically to treat cancer. However, whether the anti-cancer effect of ACE is related to gut microbiota remains unclear yet. We standardized ACE and investigated the effects of ACE on tumour suppression and analyze the related mechanisms on gut microbiota in CT26 colon cancer-bearing mice in the present study. Firstly, four flavonoids (calycosin-7-glucoside, ononin, calycosin, formononetin) and three astragalosides (astragaloside A, astragaloside II, astragaloside I) riched in Astragalus mongholicus Bunge, three curcumins (bisdemethoxycurcumin, demethoxycurcumin, curcumin) and four essential oils (curdione, curzerene, germacrone and β-elemene) from Curcuma aromatica Salisb., in concentrations from 0.08 to 2.07 mg/g, were examined in ACE. Then the results in vivo studies indicated that ACE inhibited solid tumours, liver and spleen metastases of colon cancer while simultaneously reducing pathological tissue damage. Additionally, ACE regulated gut microbiota dysbiosis and the short chain fatty acid content in the gut, repaired intestinal barrier damage. ACE treatment suppressed the overgrowth of conditional pathogenic gut bacteria, including Escherichia-Shigella, Streptococcus and Enterococcus, while the probiotic gut microbiota like Lactobacillus, Roseburia, Prevotellaceae_UCG-001 and Mucispirillum were increased. More interestingly, the content level of SCFAs such as propionic acid and butyric acid was increased after ACE administration, which further mediates intestinal SDF-1/CXCR4 signalling pathway to repair the integrity of the intestinal barrier, decrease Cyclin D1 and C-myc expressions, eventually suppress the tumor the growth and metastasis of colon cancer. To sum up, the present study demonstrated that ACE could efficiently suppress colon cancer progression through gut microbiota modification, which may provide a new explanation of the mechanism of ACE against colon cancer.
Identification of Circular RNAs Circ_0005008 and Circ_0005198 in Plasma as Novel Biomarkers for New-Onset Rheumatoid Arthritis
Authors: Ouyang Qingqing , Liu Chixiang , Lu Xiaoxi , Liang Renge , Zhao Jinjun , Yang Min
Published: September 2021

The progression of autoimmune diseases is affected by the differential expression of circular RNAs (circRNAs). However, in the plasma from rheumatoid arthritis (RA), circRNAs have an uncertain role. Herein, microarray analysis was used to determine the plasma expression profile of circRNAs from new-onset patients with RA and healthy controls (HCs). CircRNA expression was verified using quantitative real-time reverse transcription PCR. The correlation between clinical variables and circRNA expression was assessed using Spearman’s correlation test. The diagnostic value of plasma circRNAs was evaluated using receiver operating characteristic (ROC) curves. Circ_0005008 and circ_0005198 were confirmed to be elevated significantly in plasma samples from new-onset patients with RA compared with those from HCs and from patients with systemic lupus erythematosus. Among these new-onset patients with RA, we found that the levels of circ_0005008 and circ_0005198 correlated positively with the severity of disease, including the rheumatoid factor, C-reactive protein, the erythrocyte sedimentation rate, and the disease activity score in 28 joints (DAS28). However, their expression levels did not correlate with anti-cyclic citrullinated peptide antibodies. Analysis using ROC curves implied that circ_0005008 and circ_0005198 have significant value in the diagnosis of RA. In addition, we found that compared with that in osteoarthritis fibroblast-like synoviocytes (OA-FLSs), circ_0005198 expression was enhanced in RA-FLSs and correlated positively with DAS28. The level of the miRNA target of circ_0005198, miR-4778-3p, was identified as significantly decreased in RA-FLSs, and the expression levels of circ_0005198 and miR-4778-3p correlated significantly and negatively. The results suggested that in new-onset patients with RA, plasma circ_0005008 and circ_0005198 levels are associated with disease activity and represent possible RA biomarkers.
Requirement of Histone Deacetylase 6 for Interleukin-6 Induced Epithelial-Mesenchymal Transition, Proliferation, and Migration of Peritoneal Mesothelial Cells
Authors: Shi Yingfeng , Tao Min , Ni Jun , Tang Lunxian , Liu Feng , Chen Hui , Ma Xiaoyan , Hu Yan , Zhou Xun , Qiu Andong , Zhuang Shougang , Liu Na
Published: September 2021

Aims: Influenced by microenvironment, human peritoneal mesothelial cells (HPMCs) acquired fibrotic phenotype, which was identified as the protagonist for peritoneal fibrosis. In this study, we examined the role of histone deacetylase 6 (HDAC6) for interleukin-6 (IL-6) induced epithelial-mesenchymal transition (EMT), proliferation, and migration of HPMCs.

Methods: The role of HDAC6 in IL-6-elicited EMT of HPMCs was tested by morphological observation of light microscope, immunoblotting, and immune-fluorescence assay; and the function of HDAC6 in proliferation and migration of HPMCs was examined by CCK-8 assay, wound healing experiment, and immunoblotting.

Results: IL-6 stimulation significantly increased the expression of HDAC6. Treatment with tubastatin A (TA), a highly selective HDAC6 inhibitor, or silencing of HDAC6 with siRNA decreased the expression of HDAC6. Moreover, TA or HDAC6 siRNA suppressed IL-6-induced EMT, as evidenced by decreased expressions of α-SMA, Fibronectin, and collagen I and the preserved expression of E-cadherin in cultured HPMCs. Mechanistically, HDAC6 inhibition suppressed the expression of transforming growth factor β (TGFβ) receptor I (TGFβRI), phosphorylation of Smad3, secretion of connective tissue growth factor (CTGF), and transcription factor Snail. On the other hand, the pharmacological inhibition or genetic target of HDAC6 suppressed HPMCs proliferation, as evidenced by the decreased optical density of CCK-8 and the expressions of PCNA and Cyclin E. The migratory rate of HPMCs also decreased. Mechanistically, HDAC6 inhibition blocked the activation of JAK2 and STAT3.

Conclusion: Our study illustrated that IL-6-induced HDAC6 not only regulated IL-6 itself downstream JAK2/STAT3 signaling but also co-activated the TGF-β/Smad3 signaling, leading to the change of the phenotype and mobility of HPMCs. HDAC6 could be a potential therapeutic target for the prevention and treatment of peritoneal fibrosis.
Gut Microbiota: Novel Therapeutic Target of Ginsenosides for the Treatment of Obesity and Its Complications
Authors: Zhuang Tongxi , Li Wei , Yang Li , Wang Zhengtao , Ding Lili , Zhou Mingmei
Published: September 2021

Obesity, generally characterized by excessive lipid accumulation, is a metabolic threat worldwide due to its rapid growth in global prevalence. Ginsenosides are crucial components derived from natural plants that can confer metabolic benefits for obese patients. Considering the low bioavailability and degradable properties of ginsenosides in vivo, it should be admitted that the mechanism of ginsenosides on anti-obesity contribution is still obscure. Recently, studies have indicated that ginsenoside intervention has beneficial metabolic effects on obesity and its complications because it allows for the correction of gut microbiota dysbiosis and regulates the secretion of related endogenous metabolites. In this review, we summarize the role of gut microbiota in the pathogenetic process of obesity, and explore the mechanism of ginsenosides for ameliorating obesity, which can modulate the composition of gut microbiota by improving the metabolism of intestinal endogenous substances and alleviating the level of inflammation. Ginsenosides are expected to become a promising anti-obesity medical intervention in the foreseeable clinical settings.
Traditional Chinese Medicine is an Alternative Therapeutic Option for Treatment of Pseudomonas aeruginosa Infections
Authors: Pang Zheng , Zhu Qingjun
Published: September 2021

Pseudomonas aeruginosa is an opportunistic pathogen causing life-threatening infections in cystic fibrosis patients and immunocompromised individuals, and it is a leading cause of nosocomial infections associated with significant morbidity and mortality. Treatment of P. aeruginosa infections is challenging due to the antibiotic resistance to most of the conventional antibiotics. Development of alternative therapeutic options is urgently demanded for the patients who have antibiotic-resistant infections. Traditional Chinese medicine (TCM) has a clinical history of thousands of years for prevention and treatment of infectious diseases in China, taking advantages of improving clinical outcomes, producing less side effects, inhibiting pathogen, and modulating host immunity. Recent research has revealed a variety of natural products derived from TCM showing significant antimicrobial effects on antibiotic-resistant strains of P. aeruginosa alone or combined with antibiotics in vitro or in animal models, suggesting that TCM is a promising complementary and alternative therapeutic approach for treatment of chronic P. aeruginosa infections. This review summarizes the recent findings attempting to dissect the mechanisms of TCM combating P. aeruginosa infections and highlights the molecular targets of TCM on P. aeruginosa and host.
Effects of Surface Tension on the Stability of Surface Nanobubbles
Authors: Pan Yongcai , He Bing , Wen Binghai
Published: September 2021

The existence of surface nanobubbles has already been confirmed by variable detection methods, but the mechanism of their extraordinary stability remains unclear and has aroused widespread research interest in the past 2 decades. Experiments and theoretical analyses have tried to account for these stabilities such as the very long lifetime, very high pressure and very small contact angle. Attractive hydrophobic potential was applied to complement the pinning-oversaturation theory and successfully explain the survival of surface nanobubbles in undersaturation environment by some researchers. However, the survival of nanobubbles on hydrophilic surface still requires sizeable oversaturation. In this paper, we introduce the variable surface tensions, namely Tolman-dependence and state-dependence, and show that they effectively promote the stability of nanobubbles. The decrease in surface tension can lead to larger contact angle and even make the nanobubbles survivable on the highly hydrophilic surface. In Tolman-dependence, the changing rate in the contact angle evolution slows down, which is more obvious when the bubble size is close to the Tolman length. The contact angle is also getting larger in the state-dependence, and the increase of the gas saturation degree is beneficial to the stability of surface nanobubbles. With the gas saturation ratio of 3, the bubbles on the quite hydrophilic surface can also be stable, while grow up on the hydrophobic surface. The variable surface tensions weaken the need of saturation degree for the surface nanobubbles’ stability.
Inhibition of a Novel CLK1-THRAP3-PPARγ Axis Improves Insulin Sensitivity
Authors: Wang Zhenguo , Gao Xiaojing , Li Qingrun , Zhu Hongwen , Zhao Xiangjie , Garcia-Barrio Minerva , Zhang Jifeng , Guo Yanhong , Chen Y. Eugene , Zeng Rong , Wu Jia-Rui , Chang Lin
Published: September 2021

Increasing energy expenditure by promoting “browning” in adipose tissues is a promising strategy to prevent obesity and associated diabetes. To uncover potential targets of cold exposure, which induces energy expenditure, we performed phosphoproteomics profiling in brown adipose tissue of mice housed in mild cold environment at 16°C. We identified CDC2-like kinase 1 (CLK1) as one of the kinases that were significantly downregulated by mild cold exposure. In addition, genetic knockout of CLK1 or chemical inhibition in mice ameliorated diet-induced obesity and insulin resistance at 22°C. Through proteomics, we uncovered thyroid hormone receptor-associated protein 3 (THRAP3) as an interacting partner of CLK1, further confirmed by co-immunoprecipitation assays. We further demonstrated that CLK1 phosphorylates THRAP3 at Ser243, which is required for its regulatory interaction with phosphorylated peroxisome proliferator-activated receptor gamma (PPARγ), resulting in impaired adipose tissue browning and insulin sensitivity. These data suggest that CLK1 plays a critical role in controlling energy expenditure through the CLK1-THRAP3-PPARγ axis.
Metabolic Changes of Hepatocytes in NAFLD
Authors: Lu Qianrang , Tian Xinyao , Wu Hao , Huang Jiacheng , Li Mengxia , Mei Zhibin , Zhou Lin , Xie Haiyang , Zheng Shusen
Published: September 2021

Nonalcoholic fatty liver disease (NAFLD) is often accompanied by systemic metabolic disorders such as hyperglycemia, insulin resistance, and obesity. The relationship between NAFLD and systemic metabolic disorders has been well reviewed before, however, the metabolic changes that occur in hepatocyte itself have not been discussed. In NAFLD, many metabolic pathways have undergone significant changes in hepatocyte, such as enhanced glycolysis, gluconeogenesis, lactate production, tricarboxylic acid (TCA) cycle, and decreased ketone body production, mitochondrial respiration, and adenosine triphosphate (ATP) synthesis, which play a role in compensating or exacerbating disease progression, and there is close and complex interaction existed between these metabolic pathways. Among them, some metabolic pathways can be the potential therapeutic targets for NAFLD. A detailed summary of the metabolic characteristics of hepatocytes in the context of NAFLD helps us better understand the pathogenesis and outcomes of the disease.
Optogenetic Stimulation Using Anion Channelrhodopsin (GtACR1) Facilitates Termination of Reentrant Arrhythmias With Low Light Energy Requirements: A Computational Study
Authors: Ochs Alexander R. , Karathanos Thomas V. , Trayanova Natalia A. , Boyle Patrick M.
Published: September 2021

Optogenetic defibrillation of hearts expressing light-sensitive cation channels (e.g., ChR2) has been proposed as an alternative to conventional electrotherapy. Past modeling work has shown that ChR2 stimulation can depolarize enough myocardium to interrupt arrhythmia, but its efficacy is limited by light attenuation and high energy needs. These shortcomings may be mitigated by using new optogenetic proteins like Guillardia theta Anion Channelrhodopsin (GtACR1), which produces a repolarizing outward current upon illumination. Accordingly, we designed a study to assess the feasibility of GtACR1-based optogenetic arrhythmia termination in human hearts. We conducted electrophysiological simulations in MRI-based atrial or ventricular models (n = 3 each), with pathological remodeling from atrial fibrillation or ischemic cardiomyopathy, respectively. We simulated light sensitization via viral gene delivery of three different opsins (ChR2, red-shifted ChR2, GtACR1) and uniform endocardial illumination at the appropriate wavelengths (blue, red, or green light, respectively). To analyze consistency of arrhythmia termination, we varied pulse timing (three evenly spaced intervals spanning the reentrant cycle) and intensity (atrial: 0.001–1 mW/mm2; ventricular: 0.001–10 mW/mm2). In atrial models, GtACR1 stimulation with 0.005 mW/mm2 green light consistently terminated reentry; this was 10–100x weaker than the threshold levels for ChR2-mediated defibrillation. In ventricular models, defibrillation was observed in 2/3 models for GtACR1 stimulation at 0.005 mW/mm2 (100–200x weaker than ChR2 cases). In the third ventricular model, defibrillation failed in nearly all cases, suggesting that attenuation issues and patient-specific organ/scar geometry may thwart termination in some cases. Across all models, the mechanism of GtACR1-mediated defibrillation was voltage forcing of illuminated tissue toward the modeled channel reversal potential of −40 mV, which made propagation through affected regions impossible. Thus, our findings suggest GtACR1-based optogenetic defibrillation of the human heart may be feasible with ≈2–3 orders of magnitude less energy than ChR2.
Genome-Wide Identification and Analysis of the Phosphoenolpyruvate Carboxylase Gene Family in Suaeda aralocaspica, an Annual Halophyte With Single-Cellular C4 Anatomy
Authors: Cao Jing , Cheng Gang , Wang Lu , Maimaitijiang Tayier , Lan Haiyan
Published: September 2021

Phosphoenolpyruvate carboxylase (PEPC) plays pivotal roles in the carbon fixation of photosynthesis and a variety of metabolic and stress pathways. Suaeda aralocaspica belongs to a single-cellular C4 species and carries out a photosynthetic pathway in an unusually elongated chlorenchyma cell, which is expected to have PEPCs with different characteristics. To identify the different isoforms of PEPC genes in S. aralocaspica and comparatively analyze their expression and regulation patterns as well as the biochemical and enzymatic properties in this study, we characterized a bacterial-type PEPC (BTPC; SaPEPC-4) in addition to the two plant-type PEPCs (PTPCs; SaPEPC-1 and SaPEPC-2) using a genome-wide identification. SaPEPC-4 presented a lower expression level in all test combinations with an unknown function; two SaPTPCs showed distinct subcellular localizations and different spatiotemporal expression patterns but positively responded to abiotic stresses. Compared to SaPEPC-2, the expression of SaPEPC-1 specifically in chlorenchyma cell tissues was much more active with the progression of development and under various stresses, particularly sensitive to light, implying the involvement of SaPEPC-1 in a C4 photosynthetic pathway. In contrast, SaPEPC-2 was more like a non-photosynthetic PEPC. The expression trends of two SaPTPCs in response to light, development, and abiotic stresses were also matched with the changes in PEPC activity in vivo (native) or in vitro (recombinant), and the biochemical properties of the two recombinant SaPTPCs were similar in response to various effectors while the catalytic efficiency, substrate affinity, and enzyme activity of SaPEPC-2 were higher than that of SaPEPC-1 in vitro. All the different properties between these two SaPTPCs might be involved in transcriptional (e.g., specific cis-elements), posttranscriptional [e.g., 5′-untranslated region (5′-UTR) secondary structure], or translational (e.g., PEPC phosphorylation/dephosphorylation) regulatory events. The comparative studies on the different isoforms of the PEPC gene family in S. aralocaspica may help to decipher their exact role in C4 photosynthesis, plant growth/development, and stress resistance.
Physiological and Biochemical Response of Wild Olive (Olea europaea Subsp. europaea var. sylvestris) to Salinity
Authors: Tadić Josip , Dumičić Gvozden , Veršić Bratinčević Maja , Vitko Sandra , Radić Brkanac Sandra
Published: September 2021

In the face of climate change, water deficit and increasing soil salinity pose an even greater challenge to olive cultivation in the Mediterranean basin. Due to its tolerance to abiotic stresses, wild olive (Olea europaea subsp. europaea var. sylvestris) presents a good candidate in breeding climate-resilient olive varieties. In this study, the early response of the native Croatian wild olive genotype (WOG) to salinity was evaluated and compared with that of well-known cultivars (cv.) Leccino and Koroneiki. Potted olive plants were exposed either to 150 mM NaCl or 300 mM mannitol for 3 weeks to distinguish between the osmotic and ionic components of salt stress. To determine the impact of the plant age on salinity, 1-, 2-, and 3-year-old WOG plants were used in the study. The growth parameters of both the cultivars and WOG of different ages decreased in response to the mannitol treatment. In contrast to cv. Leccino, the NaCl treatment did not significantly affect the growth of cv. Koroneiki or WOG of any age. The contents of Na+ and Cl− were considerably higher in the salt-treated WOG, regardless of age, compared with the cultivars. However, while both treatments significantly reduced the K+ content of cv. Koroneiki, that nutrient was not significantly affected in either cv. Leccino or WOG. Unlike the cultivars and older WOG, the NaCl treatment caused a significant decline of photosynthetic pigments in the 1-year-old WOG. The cultivars and WOG of different ages experienced a similar drop in the chlorophyll a content under the isotonic mannitol treatment. The absence of lipid peroxidation, modulation of superoxide dismutase, and guaiacol peroxidase activity were noted in all WOG ages under both stressors. These data suggest that WOG resilience to salinity is associated with its large leaf capacity for Na+ and Cl− accumulation, K+ retention, and its adaptable antioxidative mechanisms. The results are promising with regard to obtaining a new olive cultivar with better resilience to soil salinity.
Rhizobial Chemotaxis and Motility Systems at Work in the Soil
Authors: Aroney Samuel T. N. , Poole Philip S. , Sánchez-Cañizares Carmen
Published: September 2021

Bacteria navigate their way often as individual cells through their chemical and biological environment in aqueous medium or across solid surfaces. They swim when starved or in response to physical and chemical stimuli. Flagella-driven chemotaxis in bacteria has emerged as a paradigm for both signal transduction and cellular decision-making. By altering motility, bacteria swim toward nutrient-rich environments, movement modulated by their chemotaxis systems with the addition of pili for surface movement. The numbers and types of chemoreceptors reflect the bacterial niche and lifestyle, with those adapted to complex environments having diverse metabolic capabilities, encoding far more chemoreceptors in their genomes. The Alpha-proteobacteria typify the latter case, with soil bacteria such as rhizobia, endosymbionts of legume plants, where motility and chemotaxis are essential for competitive symbiosis initiation, among other processes. This review describes the current knowledge of motility and chemotaxis in six model soil bacteria: Sinorhizobium meliloti, Agrobacterium fabacearum, Rhizobium leguminosarum, Azorhizobium caulinodans, Azospirillum brasilense, and Bradyrhizobium diazoefficiens. Although motility and chemotaxis systems have a conserved core, rhizobia possess several modifications that optimize their movements in soil and root surface environments. The soil provides a unique challenge for microbial mobility, since water pathways through particles are not always continuous, especially in drier conditions. The effectiveness of symbiont inoculants in a field context relies on their mobility and dispersal through the soil, often assisted by water percolation or macroorganism movement or networks. Thus, this review summarizes the factors that make it essential to consider and test rhizobial motility and chemotaxis for any potential inoculant.
Blocking miR530 Improves Rice Resistance, Yield, and Maturity
Authors: Li Yan , Wang Liang-Fang , Bhutto Sadam Hussain , He Xiao-Rong , Yang Xue-Mei , Zhou Xin-Hui , Lin Xiao-Yu , Rajput Aisha Anum , Li Guo-Bang , Zhao Jing-Hao , Zhou Shi-Xin , Ji Yun-Peng , Pu Mei , Wang He , Zhao Zhi-Xue , Huang Yan-Yan , Zhang Ji-Wei , Qin Peng , Fan Jing , Wang Wen-Ming
Published: September 2021

MicroRNAs fine-tune plant growth and resistance against multiple biotic and abiotic stresses. The trade-off between biomass and resistance can penalize crop yield. In this study, we have shown that rice miR530 regulates blast disease resistance, yield, and growth period. While the overexpression of miR530 results in compromised blast disease resistance, reduced grain yield, and late maturity, blocking miR530 using a target mimic (MIM530) leads to enhanced resistance, increased grain yield, and early maturity. Further study revealed that the accumulation of miR530 was decreased in both leaves and panicles along with the increase of age. Such expression patterns were accordant with the enhanced resistance from seedlings to adult plants, and the grain development from panicle formation to fully-filled seeds. Divergence analysis of miR530 precursor with upstream 1,000-bp promoter sequence in 11 rice species revealed that miR530 was diverse in Oryza sativa japonica and O. sativa indica group, which was consistent with the different accumulation of miR530 in japonica accessions and indica accessions. Altogether, our results indicate that miR530 coordinates rice resistance, yield, and maturity, thus providing a potential regulatory module for breeding programs aiming to improve yield and disease resistance.
Chromosome Painting Provides Insights Into the Genome Structure and Evolution of Sugarcane
Authors: Meng Zhuang , Wang Qinnan , Khurshid Haris , Raza Ghulam , Han Jinlei , Wang Baohua , Wang Kai
Published: September 2021

The genus Saccharum is composed of species with high polyploidy and highly varied chromosome numbers, laying a challenge for uncovering its genomic structure and evolution. We developed a chromosome 2 painting (CP2) probe by designing oligonucleotides covering chromosome 2 of Saccharum spontaneum (2n = 8x = 64). Fluorescence in situ hybridization (FISH) using this CP2 probe revealed six types of ploidies from twenty S. spontaneum clones, including 6x, 8x, 10x, 11x, 12x, and 13x clones. The finding of S. spontaneum clones with uneven of ploid suggested that certain S. spontaneum clones come from hybridization. It renews our knowledge that S. spontaneum is derived from autopolyploidization. Combined with a S. spontaneum-specific probe, chromosome 2-derived chromosome or fragments from either S. spontaneum or Saccharum officinarum can be identified in sugarcane modern cultivars. We revealed unexpected high level of interspecific recombination from introgressive S. spontaneum chromosomes (>50.0%) in cultivars ROC22 and ZZ1, indicating frequent chromosome exchange in cultivars. Intriguingly, we observed interspecific recombination recurring among either homoeologous or non-homoeologous chromosomes in sugarcane cultivars. These results demonstrated that chromosome painting FISH is a powerful tool in the genome dissection of sugarcane and provide new insights into the genome structure and evolution of the complex genus Saccharum.
DNA Methylation and RNA-Sequencing Analysis Show Epigenetic Function During Grain Filling in Foxtail Millet (Setaria italica L.)
Authors: Wang Tao , Lu Quanwei , Song Hui , Hu Nan , Wei Yangyang , Li Pengtao , Liu Yuling , Zhao Zilin , Liu Jinrong , Zhang Baohong , Peng Renhai
Published: September 2021

Grain filling is a crucial process for crop yield and quality. Certain studies already gained insight into the molecular mechanism of grain filling. However, it is unclear whether epigenetic modifications are associated with grain filling in foxtail millet. Global DNA methylation and transcriptome analysis were conducted in foxtail millet spikelets during different stages to interpret the epigenetic effects of the grain filling process. The study employed the whole-genome bisulfite deep sequencing and advanced bioinformatics to sequence and identify all DNA methylation during foxtail millet grain filling; the DNA methylation-mediated gene expression profiles and their involved gene network and biological pathway were systematically studied. One context of DNA methylation, namely, CHH methylation, was accounted for the largest percentage, and it was gradually increased during grain filling. Among all developmental stages, the methylation levels were lowest at T2, followed by T4, which mainly occurred in CHG. The distribution of differentially methylated regions (DMR) was varied in the different genetic regions for three contexts. In addition, gene expression was negatively associated with DNA methylation. Evaluation of the interconnection of the DNA methylome and transcriptome identified some stage-specific differentially expressed genes associated with the DMR at different stages compared with the T1 developmental stage, indicating the potential function of epigenetics on the expression regulation of genes related to the specific pathway at different stages of grain development. The results demonstrated that the dynamic change of DNA methylation plays a crucial function in gene regulation, revealing the potential function of epigenetics in grain development in foxtail millet.
Three Is a Crowd? Podemos, Ciudadanos, and Vox: The End of Bipartisanship in Spain
Authors: Rama José , Cordero Guillermo , Zagórski Piotr
Published: September 2021

The traditional Spanish imperfect bipartisanship and the alternation in power that emerged in the early 80s between the center-left PSOE and the conservative PP have shifted towards a multiparty system after the emergence of three new parties. At first, as a result of the economic and political representation crises, Podemos (We Can) emerged at the 2014 European Parliament elections. This left-wing populist party managed to grow rapidly among the dissatisfied voters, reaching the third electoral position in the 2015 general elections. In the same contest, the liberal center party Ciudadanos (Citizens) became the fourth political force boosted, among other reasons, by notorious corruption scandals involving high-rank PP’s officials and the process of secession in Catalonia. Finally, driven by the same secession process and thanks to the removal from the office of PP’s Prime Minister after a motion of no confidence, the support for the populist radical right Vox also experienced a boost, winning 15 percent of the seats in Parliament in the general elections of November 2019. In this research, we describe the contexts which facilitated the irruptions of these new parties, analyze their impact on the Spanish party system, and study their current voters’ profiles.
A Study on Green Advertising Effectiveness in the Perspective of Image Proximity
Authors: Sheng Guanghua , Xia Qing , Yue Beibei , Li Yuqi
Published: September 2021

Based on the construal level theory (CLT), this study discusses the effects of congruence between image proximity and product type on advertising attitude and product attitude from the perspective of spatial distance and investigates the mediating role of mental imagery. Data are collected using two laboratory experiments and one online experiment. A two-way ANOVA is used to test the interaction between image proximity and product type, and a bootstrap analysis is used to test the mediating role of mental imagery. The result shows that: (1) For search products, compared with full-length shots, the close-up shots of environmental information can enable consumers to generate more positive advertising attitude and product attitude. For experience products, the full-length shots of environmental information can enable consumers to generate more positive advertising attitude and product attitude than the close-up shots. (2) The congruence effect of image proximity and product type has an impact on advertising attitude and product attitude through mental imagery. This research uses different kinds of image proximity to express environmental information about green products and tries to interpret the effectiveness of green advertisements from a new perspective.
Effects of Video Task With a High-Level Exercise Illustration on Knee Movements in Male Volleyball Spike Jump
Authors: Liu Xiangyu , Huang Huiming , Li Xiaohan , Li Jianshe , Shi Huijuan , Wang Aiwen
Published: September 2021

Hazardous knee biomechanics, such as excessive knee affordance link with injuries in volleyball spike jumps (SPJs) and can be reconfigured by the enhancement of internal focus. The study aimed to explore the effects of video tasks illustrating a high-level SPJ on knee movement in the volleyball SPJ with 15 elite male volleyball athletes. This study investigated the knee movements in sagittal, coronal, and transverse planes before and after the video task in SPJ using one-dimensional statistical parametric mapping (SPM 1D) and discrete statistics. The SPM 1D indicated a larger knee flexion angle (31.17–73.19%,t= 2.611, andp= 0.012), increased knee flexion moment (19.72–21.38%,t= 0.029, andp= 0.029), and increased knee adduction angular velocity (49.07–62.64%,t= 3.148, andp= 0.004) after video task; alternatively, smaller knee external rotation angular velocity (45.85–49.96%,t= 5.199, andp= 0.017) and vertical ground reaction (vGRF) (3.13–5.94%,t= 4.096, andp= 0.014; 19.83–21.97%,t= 4.096, andp= 0.024) were found after the task. With discrete value statistics, the video task increased the peak of knee flexion angle while decreased the peak of extension moment, flexion moment, abduction moment, external moment, the first peak vGRF, and related loading rate.

Conclusions: The results indicate that knee biomechanics in volleyball SPJ positively influenced by the video task. The task has the athletes control the knee movements more actively and improves the original hazardous movement strategies. Therefore, the video task presumably can abate the occurrence of knee injuries in volleyball SPJ. Further validation especially in the exercise effect is needed in the future.
Multiple Sources of Surprisal Affect Illusory Vowel Epenthesis
Authors: Whang James
Published: September 2021

Illusory epenthesis is a phenomenon in which listeners report hearing a vowel between a phonotactically illegal consonant cluster, even in the complete absence of vocalic cues. The present study uses Japanese as a test case and investigates the respective roles of three mechanisms that have been claimed to drive the choice of epenthetic vowel—phonetic minimality, phonotactic predictability, and phonological alternations—and propose that they share the same rational goal of searching for the vowel that minimally alters the original speech signal. Additionally, crucial assumptions regarding phonological knowledge held by previous studies are tested in a series of corpus analyses using the Corpus of Spontaneous Japanese. Results show that all three mechanisms can only partially account for epenthesis patterns observed in language users, and the study concludes by discussing possible ways in which the mechanisms might be integrated.