bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro and in Silico Analysis of Phytochemicals From Fallopia dentatoalata as Dual Functional Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease
Authors: Wu Yichuang , Su Xiangdong , Lu Jielang , Wu Meifang , Yang Seo Young , Mai Yang , Deng Wenbin , Xue Yongbo
Published: July 2022

Current studies have found that butyrylcholinesterase (BuChE) replaces the biological function of acetylcholinesterase (AChE) in the late stage of Alzheimer’s disease. Species in the genus of Fallopia, rich in polyphenols with diverse chemical structures and significant biological activities, are considered as an important resource for screening natural products to against AD. In this study, thirty-four compounds (1–34) were isolated from Fallopia dentatoalata (Fr. Schm.) Holub, and their inhibitory effects against AChE and BuChE were assessed. Compounds of the phenylpropanoid sucrose ester class emerged as the most promising members of the group, with 31–33 displaying moderate AChE inhibition (IC50 values ranging from 30.6 ± 4.7 to 56.0 ± 2.4 µM) and 30–34 showing potential inhibitory effects against BuChE (IC50 values ranging from 2.7 ± 1.7 to 17.1 ± 3.4 µM). Tacrine was used as a positive control (IC50: 126.7 ± 1.1 in AChE and 5.5 ± 1.7 nM in BuChE). Kinetic analysis highlighted compounds 31 and 32 as non-competitive inhibitors of AChE with Ki values of ∼30.0 and ∼34.4 µM, whilst 30–34 were revealed to competitively inhibit BuChE with Ki values ranging from ∼1.8 to ∼17.5 µM. Molecular binding studies demonstrated that 30–34 bound to the catalytic sites of BuChE with negative binding energies. The strong agreement between both in vitro and in silico studies highlights the phenylpropanoid sucrose esters 30–34 as promising candidates for use in future anti-cholinesterase therapeutics against Alzheimer’s disease.
Natural Compounds: A Hopeful Promise as an Antibiofilm Agent Against Candida Species
Authors: Shariati Aref , Didehdar Mojtaba , Razavi Shabnam , Heidary Mohsen , Soroush Fatemeh , Chegini Zahra
Published: July 2022

The biofilm communities of Candida are resistant to various antifungal treatments. The ability of Candida to form biofilms on abiotic and biotic surfaces is considered one of the most important virulence factors of these fungi. Extracellular DNA and exopolysaccharides can lower the antifungal penetration to the deeper layers of the biofilms, which is a serious concern supported by the emergence of azole-resistant isolates and Candida strains with decreased antifungal susceptibility. Since the biofilms’ resistance to common antifungal drugs has become more widespread in recent years, more investigations should be performed to develop novel, inexpensive, non-toxic, and effective treatment approaches for controlling biofilm-associated infections. Scientists have used various natural compounds for inhibiting and degrading Candida biofilms. Curcumin, cinnamaldehyde, eugenol, carvacrol, thymol, terpinen-4-ol, linalool, geraniol, cineole, saponin, camphor, borneol, camphene, carnosol, citronellol, coumarin, epigallocatechin gallate, eucalyptol, limonene, menthol, piperine, saponin, α-terpineol, β–pinene, and citral are the major natural compounds that have been used widely for the inhibition and destruction of Candida biofilms. These compounds suppress not only fungal adhesion and biofilm formation but also destroy mature biofilm communities of Candida. Additionally, these natural compounds interact with various cellular processes of Candida, such as ABC-transported mediated drug transport, cell cycle progression, mitochondrial activity, and ergosterol, chitin, and glucan biosynthesis. The use of various drug delivery platforms can enhance the antibiofilm efficacy of natural compounds. Therefore, these drug delivery platforms should be considered as potential candidates for coating catheters and other medical material surfaces. A future goal will be to develop natural compounds as antibiofilm agents that can be used to treat infections by multi-drug-resistant Candida biofilms. Since exact interactions of natural compounds and biofilm structures have not been elucidated, further in vitro toxicology and animal experiments are required. In this article, we have discussed various aspects of natural compound usage for inhibition and destruction of Candida biofilms, along with the methods and procedures that have been used for improving the efficacy of these compounds.
Research and Development of Natural Product Tanshinone I: Pharmacology, Total Synthesis, and Structure Modifications
Authors: Huang Xing , Jin Lili , Deng Hao , Wu Dan , Shen Qing-kun , Quan Zhe-shan , Zhang Chang-hao , Guo Hong-Yan
Published: July 2022

Salvia miltiorrhiza (S. miltiorrhiza), which has been used for thousands of years to treat cardiovascular diseases, is a well-known Chinese medicinal plant. The fat-soluble tanshinones in S. miltiorrhiza are important biologically active ingredients including tanshinone I, tanshinone IIA, dihydrotanshinone, and cryptotanshinone. Tanshinone I, a natural diterpenoid quinone compound widely used in traditional Chinese medicine, has a wide range of biological effects including anti-cancer, antioxidant, neuroprotective, and anti-inflammatory activities. To further improve its potency, water solubility, and bioavailability, tanshinone I can be used as a platform for drug discovery to generate high-quality drug candidates with unique targets and enhanced drug properties. Numerous derivatives of tanshinone I have been developed and have contributed to major advances in the identification of new drugs to treat human cancers and other diseases and in the study of related molecular mechanisms. This review focuses on the structural modification, total synthesis, and pharmacology of tanshinone I. We hope that this review will help understanding the research progress in this field and provide constructive suggestions for further research on tanshinone I.
Acetyl-11-Keto-Beta Boswellic Acid (AKBA) Protects Lens Epithelial Cells Against H2O2-Induced Oxidative Injury and Attenuates Cataract Progression by Activating Keap1/Nrf2/HO-1 Signaling
Authors: Yang Tianke , Lin Xiaolei , Li Hongzhe , Zhou Xiyue , Fan Fan , Yang Jianing , Luo Yi , Liu Xin
Published: July 2022

Age-related cataract (ARC) is one of the leading blinding eye diseases worldwide. Chronic oxidative stress and the apoptosis of human lens epithelial cells (HLECs) have been suggested to be the mechanism underlying cataract formation. Acetyl-11-keto-β-boswellic acid (AKBA) is a pentacyclic triterpene with antioxidative and antiapoptotic effects. In this study, we investigated the potential effects of AKBA on oxidative-induced HLECs injury and cataract formation. H2O2 was used to simulate HLECs oxidative injury in vitro, and Na2SeO3 was applied to establish an in vivo cataract model. In our current study, a cell counting kit-8 (CCK-8) assay was performed to evaluate the effects of H2O2 and AKBA on cell viability in vitro. Intracellular reactive oxygen species (ROS) levels were measured with the ROS assay to verify the antioxidant capacity of AKBA. Apoptotic cells were detected and measured by TUNEL staining and flow cytometry, and quantitative real-time (qRT)-PCR and Western blotting were applied to examine the transcription and expression of apoptosis-related proteins. Furthermore, immunofluorescence staining was performed to locate factor-erythroid 2-related factor 2 (Nrf2), and the protein levels of Nrf2, kelch-like ECH-associated protein 1 (Keap1) and heme oxygenase-1 (HO-1) were determined by Western blotting. Finally, we observed the degree of lens opacity and performed hematoxylin-eosin (H&E) staining to assess the protective effect of AKBA on cataract formation in vivo. AKBA increased HLECs viability under H2O2 stimulation, decreased intracellular ROS levels and alleviated the cell apoptosis rate in vitro. AKBA significantly decreased the expression of caspase-3 and Bax and increased the content of Bcl-2. The results of immunofluorescence and immunohistochemical staining proved that the expression and nuclear translocation of Nrf2 were activated with AKBA treatment in vivo and in vitro. Moreover, computational docking results showed that AKBA could bind specifically to the predicted Keap1/Nrf2 binding sites. After AKBA activation, Nrf2 dissociates from the Nrf2/Keap1 complex, translocates into the nucleus, and subsequently promotes HO-1 expression. In addition, AKBA attenuated lens opacity in selenite-induced cataracts. Overall, these findings indicated that AKBA alleviated oxidative injury and cataract formation by activating the Keap1/Nrf2/HO-1 cascade. Therefore, our current study highlights that AKBA may serve as a promising treatment for ARC progression.
Natural Products from Actinobacteria as a Potential Source of New Therapies Against Colorectal Cancer: A Review
Authors: Bahrami Yadollah , Bouk Sasan , Kakaei Elham , Taheri Mohammad
Published: July 2022

Colorectal cancer (CRC) is a common, and deadly disease. Despite the improved knowledge on CRC heterogeneity and advances in the medical sciences, there is still an urgent need to cope with the challenges and side effects of common treatments for the disease. Natural products (NPs) have always been of interest for the development of new medicines. Actinobacteria are known to be prolific producers of a wide range of bioactive NPs, and scientific evidence highlights their important protective role against CRC. This review is a holistic picture on actinobacter-derived cytotoxic compounds against CRC that provides a good perspective for drug development and design in near future. This review also describes the chemical structure of 232 NPs presenting anti-CRC activity with the being majority of quinones, lactones, alkaloids, peptides, and glycosides. The study reveals that most of these NPs are derived from marine actinobacteria followed by terrestrial and endophytic actinobacteria, respectively. They are predominantly produced by Streptomyces, Micromonospors, Saliniospors and Actinomadura, respectively, in which Streptomyces, as the predominant contributor generating over 76% of compounds exclusively. Besides it provides a valuable snapshot of the chemical structure-activity relationship of compounds, highlighting the presence or absence of some specific atoms and chemical units in the structure of compounds can greatly influence their biological activities. To the best of our knowledge, this is the first comprehensive review on natural actinobacterial compounds affecting different types of CRC. Our study reveals that the high diversity of actinobacterial strains and their NPs derivatives, described here provides a new perspective and direction for the production of new anti-CRC drugs and paves the way to innovation for drugs discovery in the future. The knowledge obtain from this review can help us to understand the pivotal application of actinobacteria in future drugs development.
Caryophyllene Oxide Induces Ferritinophagy by Regulating the NCOA4/FTH1/LC3 Pathway in Hepatocellular Carcinoma
Authors: Xiu Zhiru , Zhu Yilong , Han Jicheng , Li Yaru , Yang Xia , Yang Guohua , Song Gaojie , Li Shanzhi , Li Yue , Cheng Cheng , Li Yiquan , Fang Jinbo , Li Xiao , Jin Ningyi
Published: July 2022

Ferritinophagy is associated with tumor occurrence, development, and therapy effects. Ferritinophagy and ferroptosis are regulated by iron metabolism and are closely connected. LC3 protein is a key protein in autophagy. Following the binding of NCOA4 to FTH1, it links to LC3Ⅱ in lysosomes, a symbol of ferritinophagy. A ferritinophagy’s inducer is likely to open new avenues for anticancer medication research and development. In this study, we discovered that caryophyllene oxide has a substantial inhibitory effect on HCCLM3 and HUH7 cells, by regulating the level of cellular oxidative stress, and the levels of autophagy and iron metabolism in HCCLM3 and HUH7 cells, leading to a ferritinophagy-related phenomenon. Furthermore, the results of T-AOC, DPPH free radical scavenging rate, and hydroxyl radical inhibition indicated that caryophyllene oxide can inhibit cell anti-oxidation. The examination of the ferritinophagy-related process revealed that caryophyllene oxide promotes the production and accumulation of intracellular reactive oxygen species and lipid peroxidation. NCOA4, FTH1, and LC3Ⅱ were found to be targeted regulators of caryophyllene oxide. Caryophyllene oxide regulated NCOA4, LC3 Ⅱ, and FTH1 to promote ferritinophagy. In vivo, we discovered that caryophyllene oxide can lower tumor volume, significantly improve NCOA4 and LC3 protein levels in tumor tissue, and raise Fe2+ and malondialdehyde levels in serum. The compound can also reduce NRF2, GPX4, HO-1, and FTH1 expression levels. The reduction in the expression levels of NRF2, GPX4, HO-1, and FTH1 by caryophyllene oxide also inhibited GSH and hydroxyl radical’s inhibitory capacities in serum, and promoted iron deposition in tumor tissue resulting in the inhibition of tumor growth. In summary, our study revealed that caryophyllene oxide mostly kills liver cancer cells through ferritinophagy-mediated ferroptosis mechanisms. In conclusion, caryophyllene oxide may be used as a ferritinophagy activator in the field of antitumor drug research and development.
Integrated Serum Pharmacochemistry, Metabolomics, and Network Pharmacology to Reveal the Material Basis and Mechanism of Danggui Shaoyao San in the Treatment of Primary Dysmenorrhea
Authors: Xiong Hui , Li Na , Zhao Lanqingqing , Li Zhe , Yu Yongzhou , Cui Xiaoyan , Liu Qi , Zhao Chunying
Published: July 2022

Danggui Shaoyao San (DSS), a well-known formula, has been successfully applied in treating primary dysmenorrhea (PD) in China. However, its material basis and mechanism are still unrevealed. This current research aims to reveal the material basis and mechanism of DSS in treating PD by an integrative approach of serum pharmacochemistry, metabolomics, and network pharmacology. The results showed that DSS markedly relieved the physiological and pathological symptoms of PD as confirmed by the improvement of writhing behavior, inhibition of uterine edema, callback of clinical biochemical indexes, and metabolic profiles. Furthermore, a metabolomic analysis demonstrated that the therapeutic effect of DSS was attributed to the modulation of arachidonic acid metabolism, pentose and glucuronate interconversions, and phenylalanine metabolism. Meanwhile, 23 blood ingredients were identified after the oral administration of DSS. By analyzing the correlation coefficient of the identified biomarkers and blood components, active compounds closely associated with core metabolic pathways were extracted. Taking these active compounds as a basis, network pharmacology prediction was executed. It was found that active components of DSS including alisol B,23-acetate, chlorogenic acid, levistilide A, cianidanol, senkyunolide A, atractylenolide II, and sedanolide, were germane to steroid hormone biosynthesis, arachidonic acid metabolism, sphingolipid signaling pathway, etc. Interestingly, PTGS2 and PTGS1 related to the arachidonic acid metabolism may be pivotal targets of DSS. The current study proved that the integration of serum pharmacochemistry, metabolomics, and network pharmacology, was a powerful approach to investigate the material basis and the molecular mechanisms of DSS, and provided a solid basis for DSS application.
An Interacting Negative Feedback Mechanism in a Coupled Extreme Weather–Humans–Infrastructure System: A Case Study of the 2021 Winter Storm in Texas
Authors: Wu Yaqiao , Yang Saini , Wu Jingyan , Hu Fuyu
Published: July 2022

Extreme weather has long been a threat to human life and critical infrastructures. Previous studies have focused on the reliability and vulnerability of single or interdependent infrastructures under extreme weather threats. However, knowledge of the interactions between coupled real-world complex systems, especially the cascading failure process induced by external shocks, is essential, but the interactions receive less attention. Here, we took the historical winter storm of Texas that occurred in February 2021 as a case study and collected multisource data to explore the interaction between humans and the power system affected by extreme weather. A connectivity-based network was proposed to analyze the connectivity robustness and simulate the cascade of overload failures under random and malicious attacks. Results showed that this network presents higher robustness under random attacks in terms of network connectivity. However, a highly heterogeneous distribution of load was shown in this network, making it particularly vulnerable to attacks and easier to trigger cascading failures. An interacting negative feedback mechanism was discovered in this coupled extreme weather–humans–infrastructure system. Extreme weather events directly caused physical failure in infrastructures, while their impact on individuals stimulated the power demand for heat. An increase in demand further intensified the load on the power network, which induced functional failure in infrastructure systems and finally aggravated the adverse impact on people as end-users in return. This feedback loop inspired us to reconsider the relationship among natural disasters, critical infrastructure, and humans. Furthermore, even under the background of climate change, the impact of extremely cold weather on electric infrastructures is still worthy of attention since the fluctuation of yearly minimum temperature outstood in eastern Texas, where the majority of the population and electric transmission facilities are located. Thus, it is noteworthy to integrate the interaction between systems in the vulnerability assessment of infrastructure systems or the impact prediction of intense external shocks in future research.
Configuration-Induced Directional Nonlinearity Enhancement in Composite Thermal Media
Authors: Wang Jun , Dai Gaole
Published: July 2022

Nonlinear thermal response enables flexible heat manipulation and management with artificial structures. In particular, intrinsic temperature-dependent parameters of constitutive materials guide the design of self-adaptive thermal metamaterials. However, the geometrical effect in nonlinear composites has not been adequately studied, which may limit the potential multiple functionalities and versatile control. Here, under the effective medium approximation framework, we develop a unified theory for predicting anisotropic nonlinear equivalent thermal conductivities of elliptical inclusions in homogeneous media. By means of the derived results, enhancement of value in nonlinear coefficient can be achieved in a specified direction, based on geometrically anisotropic configurations and temperature-dependent properties. Quantitative relations between directional enhancement and inclusive shape factors are given by analytical theory and verified by numerical simulation. The proposed theoretical methods can be further extended to arbitrary non-circular configurations of complex structures, and the directional nonlinearity enhancement effect will facilitate refined heat control, combined with other nonlinear mechanisms such as spatiotemporal modulation or harmonic generation.
Effects of Branched Fins on Alumina and N-Octadecane Melting Performance Inside Energy Storage System
Authors: Weera Wajaree , Maneengam Apichit , Saeed Abdulkafi Mohammed , Aissa Abderrahmane , Guedri Kamel , Younis Obai , Marzouki Riadh , Asogwa Kanayo K.
Published: July 2022

The importance of Phase change material (PCM) energy storage systems is no longer new in the industry. However, the influence of using branched fins inside the energy storage system on the melting process of alumina nanoparticles and n-octadecane has not been reported in the literature. Consequently, the outcome of a study on the numerical simulation for optimizing the melting performance of a PCM in various tubes, including those with branching fins is presented in this report. Four examples were assessed in relation to a suspension of alumina nanoparticles and n-octadecane paraffin that contains heated fins. A numerical technique based on the Galerkin finite element method (GFEM) was used to solve the dimensionless governing system. The average liquid percentage over the flow zone in question was computed. The primary results indicated that altering the number of heated fins might affect the flow structures, the system’s irreversibility, and the melting process. Case four, with eight heated fins, likewise produces the greatest average liquid fraction values and completes the melting process in 850s. Additionally, when 6% nano-enhanced PCM was used instead of pure PCM, the melting process is accelerated by 28.57 percent.
Signal Peptide Features Determining the Substrate Specificities of Targeting and Translocation Components in Human ER Protein Import
Authors: Lang Sven , Nguyen Duy , Bhadra Pratiti , Jung Martin , Helms Volkhard , Zimmermann Richard
Published: July 2022

In human cells, approximately 30% of all polypeptides enter the secretory pathway at the level of the endoplasmic reticulum (ER). This process involves cleavable amino-terminal signal peptides (SPs) or more or less amino-terminal transmembrane helices (TMHs), which serve as targeting determinants, at the level of the precursor polypeptides and a multitude of cytosolic and ER proteins, which facilitate their ER import. Alone or in combination SPs and TMHs guarantee the initial ER targeting as well as the subsequent membrane integration or translocation. Cytosolic SRP and SR, its receptor in the ER membrane, mediate cotranslational targeting of most nascent precursor polypeptide chains to the polypeptide-conducting Sec61 complex in the ER membrane. Alternatively, fully-synthesized precursor polypeptides and certain nascent precursor polypeptides are targeted to the ER membrane by either the PEX-, SND-, or TRC-pathway. Although these targeting pathways may have overlapping functions, the question arises how relevant this is under cellular conditions and which features of SPs and precursor polypeptides determine preference for a certain pathway. Irrespective of their targeting pathway(s), most precursor polypeptides are integrated into or translocated across the ER membrane via the Sec61 channel. For some precursor polypeptides specific Sec61 interaction partners have to support the gating of the channel to the open state, again raising the question why and when this is the case. Recent progress shed light on the client spectrum and specificities of some auxiliary components, including Sec62/Sec63, TRAM1 protein, and TRAP. To address the question which precursors use a certain pathway or component in intact human cells, i.e., under conditions of fast translation rates and molecular crowding, in the presence of competing precursors, different targeting organelles, and relevant stoichiometries of the involved components, siRNA-mediated depletion of single targeting or transport components in HeLa cells was combined with label-free quantitative proteomics and differential protein abundance analysis. Here, we present a summary of the experimental approach as well as the resulting differential protein abundance analyses and discuss their mechanistic implications in light of the available structural data.
The Effects of Asprosin on Exercise-Intervention in Metabolic Diseases
Authors: Liu Lifei , Liu Yuhao , Huang Mei , Zhang Miao , Zhu Chenyu , Chen Xi , Bennett Samuel , Xu Jiake , Zou Jun
Published: July 2022

Fibrillin is the major constituent of extracellular microfibrils, which are distributed throughout connective tissues. Asprosin is derived from the C-terminal region of the FBN1 gene, which encodes profibrillin that undergoes cleavage by furin protein. In response to fasting with low dietary glucose, asprosin is released as a secreted factor from white adipose tissue, and is transported to the liver for the mediation of glucose release into the blood circulation. Through binding to OLFR734, an olfactory G-protein-coupled receptor in liver cells, asprosin induces a glucogenic effect to regulate glucose homeostasis. Bioinformatics analyses revealed that the FBN1 gene is abundantly expressed in human skeletal muscle-derived mesoangioblasts, osteoblast-like cells, and mesenchymal stem cells, indicating that the musculoskeletal system might play a role in the regulation of asprosin expression. Interestingly, recent studies suggest that asprosin is regulated by exercise. This timely review discusses the role of asprosin in metabolism, its receptor signalling, as well as the exercise regulation of asprosin. Collectively, asprosin may have a vital regulatory effect on the improvement of metabolic disorders such as diabetes mellitus and obesity via exercise.
Growth-Promoting Endophytic Fungus (Stemphylium lycopersici) Ameliorates Salt Stress Tolerance in Maize by Balancing Ionic and Metabolic Status
Authors: Ali Raid , Gul Humaira , Rauf Mamoona , Arif Muhammad , Hamayun Muhammad , Husna  , Khilji Sheza Ayaz , Ud-Din Aziz , Sajid Zahoor Ahmad , Lee In-Jung
Published: July 2022

Climate change is a major cause of the world's food security problems, and soil salinity is a severe hazard for a variety of crops. The exploitation of endophytic fungi that are known to have a positive association with plant roots is preferred for improving plant growth, yield, and overall performance under salt stress. The current study thus rationalized to address how salt stress affected the growth, biochemical properties, antioxidant capacity, endogenous indole-3-acetic acid (IAA), and the ionic status of maize associated with endophytic fungus (Stemphylium lycopersici). According to the findings, salt stress reduced chlorophyll a and b, total chlorophyll, total protein, sugars, lipids, and endogenous IAA levels. Enhanced values of chlorophyll a/b ratio, carotenoids, secondary metabolites (phenol, flavonoids, and tannins), antioxidant enzyme activity (catalase, ascorbate peroxidase), proline, and lipid peroxidation were noticed in maize plants under salt stress. Increased ionic content of Na+, Cl−, Na+/K+, and Na+/Ca2+ ratio, as well as decreased Ca2+, K+, Mg2+, N, and P contents, were also found in salt-stressed maize plants. In comparison to the non-saline medium, endophytic association promoted the antioxidant enzyme activities (798.7 U/g protein; catalase activity, 106 U/g protein; ascorbate peroxidase activity), IAA content (3.47 mg/g FW), and phenolics and flavonoids (88 and 1.68 μg/g FW, respectively), and decreased MDA content (0.016 nmol/g FW), Na+ ion content (18 mg/g dry weight), Cl− ion (16.6 mg/g dry weight), and Na+/K+ (0.78) and Na+/Ca2+ (1.79) ratios, in maize plants under salt stress, whereas Ca2+, K+, Mg2+, N, and P contents were increased in maize plants associated with S. lycopersici under salt stress. Current research exposed the role of S. lycopersici as an effective natural salt stress reducer and maize growth promoter; hence, it can be used as a biofertilizer to ameliorate salt stress tolerance in crops along with better growth performance in saline regions.
Examining the Role of Low Temperature in Satsuma Mandarin Fruit Peel Degreening via Comparative Physiological and Transcriptomic Analysis
Authors: Mitalo Oscar W. , Asiche William O. , Kang Seung W. , Ezura Hiroshi , Akagi Takashi , Kubo Yasutaka , Ushijima Koichiro
Published: July 2022

Peel degreening is the most conspicuous aspect of fruit ripening in many citrus fruits because of its importance for marketability. In this study, peel degreening in response to propylene (an ethylene analog) and at varying storage temperatures was characterized in Satsuma mandarin (Citrus unshiu Marc.) fruit. Propylene treatment triggered rapid peel degreening (within 4–6 days), indicated by an increase in the citrus color index (CCI) and chlorophyll loss. Peel degreening was also observed in fruit at 10°C and 15°C after 28–42 days, with gradual CCI increase and chlorophyll reduction. However, fruit at 5°C, 20°C, and 25°C remained green, and no substantial changes in peel CCI and chlorophyll content were recorded during the 42-day storage duration. The transcriptomes of peels of fruit treated with propylene for 4 days and those stored at varying temperatures for 28 days were then analyzed by RNA-Seq. We identified three categories of differentially expressed genes that were regulated by (i) propylene (and by analogy, ethylene) alone, (ii) low temperature (5°C, 10°C, or 15°C vs. 25°C) alone, and (iii) either propylene or low temperature. Gene-encoding proteins associated with chlorophyll degradation (such as CuSGR1, CuNOL, CuACD2, CuCAB2, and CuLHCB2) and a transcription factor (CuERF114) were differentially expressed by propylene or low temperature. To further examine temperature-induced pathways, we also monitored gene expression during on-tree fruit maturation vs. postharvest. The onset of on-tree peel degreening coincided with autumnal drops in field temperatures, and it was accompanied by differential expression of low temperature-regulated genes. On the contrary, genes that were exclusively regulated by propylene (such as CuCOPT1 and CuPOX-A2) displayed insignificant expression changes during on-tree peel degreening. These findings indicate that low temperatures could be involved in the fruit ripening-related peel degreening independently of ethylene.
Epistasis Activation Contributes Substantially to Heterosis in Temperate by Tropical Maize Hybrids
Authors: Sang Zhiqin , Wang Hui , Yang Yuxin , Zhang Zhanqin , Liu Xiaogang , Li Zhiwei , Xu Yunbi
Published: July 2022

Epistasis strongly affects the performance of superior maize hybrids. In this study, a multiple-hybrid population, consisting of three hybrid maize sets with varied interparental divergence, was generated by crossing 28 temperate and 23 tropical inbred lines with diverse genetic backgrounds. We obtained 1,154 tested hybrids. Among these tested hybrids, heterosis increased steadily as the heterotic genetic distance increased. Mid-parent heterosis was significantly higher in the temperate by tropical hybrids than in the temperate by temperate hybrids. Genome-wide prediction and association mapping was performed for grain weight per plant (GWPP) and days to silking (DTS) using 20K high-quality SNPs, showing that epistatic effects played a more prominent role than dominance effects in temperate by tropical maize hybrids. A total of 33 and 420 epistatic QTL were identified for GWPP and DTS, respectively, in the temperate by tropical hybrids. Protein–protein interaction network and gene-set enrichment analyses showed that epistatic genes were involved in protein interactions, which play an important role in photosynthesis, biological transcription pathways, and protein synthesis. We showed that the interaction of many minor-effect genes in the hybrids could activate the transcription activators of epistatic genes, resulting in a cascade of amplified yield heterosis. The multiple-hybrid population design enhanced our understanding of heterosis in maize, providing an insight into the acceleration of hybrid maize breeding by activating epistatic effects.
Features of Activity of the Phenylpropanoid Biosynthesis Pathway in Melanin-Accumulating Barley Grains
Authors: Glagoleva Anastasiia Y. , Vikhorev Alexander V. , Shmakov Nikolay A. , Morozov Sergey V. , Chernyak Elena I. , Vasiliev Gennady V. , Shatskaya Natalia V. , Khlestkina Elena K. , Shoeva Olesya Y.
Published: July 2022

Barley (Hordeum vulgare L.) grain pigmentation is caused by two types of phenolic compounds: anthocyanins (which are flavonoids) give a blue or purple color, and melanins (which are products of enzymatic oxidation and polymerization of phenolic compounds) give a black or brown color. Genes Ant1 and Ant2 determine the synthesis of purple anthocyanins in the grain pericarp, whereas melanins are formed under the control of the Blp1 gene in hulls and pericarp tissues. Unlike anthocyanin synthesis, melanin synthesis is poorly understood. The objective of the current work was to reveal features of the phenylpropanoid biosynthesis pathway functioning in melanin-accumulating barley grains. For this purpose, comparative transcriptomic and metabolomic analyses of three barley near-isogenic lines accumulating anthocyanins, melanins, or both in the grain, were performed. A comparative analysis of mRNA libraries constructed for three stages of spike development (booting, late milk, and early dough) showed transcriptional activation of genes encoding enzymes of the general phenylpropanoid pathway in all the lines regardless of pigmentation; however, as the spike matured, unique transcriptomic patterns associated with melanin and anthocyanin synthesis stood out. Secondary activation of transcription of the genes encoding enzymes of the general phenylpropanoid pathway together with genes of monolignol synthesis was revealed in the line accumulating only melanin. This pattern differs from the one observed in the anthocyanin-accumulating lines, where — together with the genes of general phenylpropanoid and monolignol synthesis pathways — flavonoid biosynthesis genes were found to be upregulated, with earlier activation of these genes in the line accumulating both types of pigments. These transcriptomic shifts may underlie the observed differences in concentrations of phenylpropanoid metabolites analyzed in the grain at a late developmental stage by high-performance liquid chromatography. Both melanin-accumulating lines showed an increased total level of benzoic acids. By contrast, anthocyanin-accumulating lines showed higher concentrations of flavonoids and p-coumaric and ferulic acids. A possible negative effect of melanogenesis on the total flavonoid content and a positive influence on the anthocyanin content were noted in the line accumulating both types of pigments. As a conclusion, redirection of metabolic fluxes in the phenylpropanoid biosynthesis pathway occurs when melanin is synthesized.
Long-Term Mild Heat Causes Post-Mitotic Pollen Abortion Through a Local Effect on Flowers
Authors: Xu Jiemeng , Jansma Stuart Y. , Wolters-Arts Mieke , de Groot Peter F. M. , Jansen Martijn J. , Rieu Ivo
Published: July 2022

Crop reproductive success is significantly challenged by heatwaves, which are increasing in frequency and severity globally. Heat-induced male sterility is mainly due to aborted pollen development, but it is not clear whether this is through direct or systemic effects. Here, long-term mild heat (LTMH) treatment, mimicking a heatwave, was applied locally to tomato flowers or whole plants and followed up by cytological, transcriptomic, and biochemical analyses. By analyzing pollen viability, LTMH was shown to act directly on the flowers and not via effects on other plant tissue. The meiosis to early microspore stage of pollen development was the most sensitive to LTMH and 3 days of exposure around this period was sufficient to significantly reduce pollen viability at the flower anthesis stage. Extensive cytological analysis showed that abnormalities in pollen development could first be observed after pollen mitosis I, while no deviations in tapetum development were observed. Transcriptomic and biochemical analyses suggested that pollen development suffered from tapetal ER stress and that there was a limited role for oxidative stress. Our results provide the first evidence that heat acts directly on flowers to induce pollen sterility, and that the molecular-physiological responses of developing anthers to the LTMH are different from those to severe heat shock.
Plant Evolution History Overwhelms Current Environment Gradients in Affecting Leaf Chlorophyll Across the Tibetan Plateau
Authors: He Yicheng , Li Tingting , Zhang Ruiyang , Wang Jinsong , Zhu Juntao , Li Yang , Chen Xinli , Pan Junxiao , Shen Ying , Wang Furong , Li Jingwen , Tian Dashuan
Published: July 2022

Aims

Leaf chlorophyll (Chl) is a fundamental component and good proxy for plant photosynthesis. However, we know little about the large-scale patterns of leaf Chl and the relative roles of current environment changes vs. plant evolution in driving leaf Chl variations.

Locations

The east to west grassland transect of the Tibetan Plateau.

Methods

We performed a grassland transect over 1,600 km across the Tibetan Plateau, measuring leaf Chl among 677 site-species.

Results

Leaf Chl showed a significantly spatial pattern across the grasslands in the Tibetan Plateau, decreasing with latitude but increasing with longitude. Along with environmental gradient, leaf Chl decreased with photosynthetically active radiation (PAR), but increased with water availability and soil nitrogen availability. Furthermore, leaf Chl also showed significant differences among functional groups (C4 > C3 species; legumes < non-legume species), but no difference between annual and perennial species. However, we surprisingly found that plant evolution played a dominant role in shaping leaf Chl variations when comparing the sum and individual effects of all the environmental factors above. Moreover, we revealed that leaf Chl non-linearly decreased with plant evolutionary divergence time. This well-matches the non-linearly increasing trend in PAR or decreasing trend in temperature during the geological time-scale uplift of the Tibetan Plateau.

Main Conclusion

This study highlights the dominant role of plant evolution in determining leaf Chl variations across the Tibetan Plateau. Given the fundamental role of Chl for photosynthesis, these results provide new insights into reconsidering photosynthesis capacity in alpine plants and the carbon cycle in an evolutionary view.
FIGNL1 Inhibits Non-homologous Chromosome Association and Crossover Formation
Authors: Yang Shuying , Zhang Chao , Cao Yiwei , Du Guijie , Tang Ding , Li Yafei , Shen Yi , Yu Hengxiu , Cheng Zhukuan
Published: July 2022

Meiotic crossovers (COs) not only generate genetic diversity but also ensure the accuracy of homologous chromosome segregation. Here, we identified FIGNL1 as a new inhibitor for extra crossover formation in rice. The fignl1 mutant displays abnormal interactions between non-homologous chromosomes at diakinesis, and chromosome bridges and fragmentation at subsequent stages of meiosis, but shows normal homologous chromosome pairing and synapsis during early prophase I. FIGNL1 participates in homologous chromosome recombination and functions downstream of DMC1. Mutation of FIGNL1 increases the number of bivalents in zip4 mutants, but does not change the number of HEI10 foci, indicating that FIGNL1 functions in limiting class II CO formation. FIGNL1 interacts with MEICA1, and colocalizes with MEICA1 in a dynamic pattern as punctate foci located between two linear homologous chromosomes. The localization of FIGNL1 depends on ZEP1-mediated assembly of the synaptonemal complex. Based on these results, we propose that FIGNL1 inhibits non-homologous chromosome interaction and CO formation during rice meiosis.
Recent Advancements and Development in Nano-Enabled Agriculture for Improving Abiotic Stress Tolerance in Plants
Authors: Manzoor Natasha , Ali Liaqat , Ahmed Temoor , Noman Muhammad , Adrees Muhammad , Shahid Muhammad Shafiq , Ogunyemi Solabomi Olaitan , Radwan Khlode S. A. , Wang Gang , Zaki Haitham E. M.
Published: July 2022

Abiotic stresses, such as heavy metals (HMs), drought, salinity and water logging, are the foremost limiting factors that adversely affect the plant growth and crop productivity worldwide. The plants respond to such stresses by activating a series of intricate mechanisms that subsequently alter the morpho-physiological and biochemical processes. Over the past few decades, abiotic stresses in plants have been managed through marker-assisted breeding, conventional breeding, and genetic engineering approaches. With technological advancement, efficient strategies are required to cope with the harmful effects of abiotic environmental constraints to develop sustainable agriculture systems of crop production. Recently, nanotechnology has emerged as an attractive area of study with potential applications in the agricultural science, including mitigating the impacts of climate change, increasing nutrient utilization efficiency and abiotic stress management. Nanoparticles (NPs), as nanofertilizers, have gained significant attention due to their high surface area to volume ratio, eco-friendly nature, low cost, unique physicochemical properties, and improved plant productivity. Several studies have revealed the potential role of NPs in abiotic stress management. This review aims to emphasize the role of NPs in managing abiotic stresses and growth promotion to develop a cost-effective and environment friendly strategy for the future agricultural sustainability.
Cognitive Writing Process Characteristics in Alzheimer’s Disease
Authors: Meulemans Catherine , Leijten Mariëlle , Van Waes Luuk , Engelborghs Sebastiaan , De Maeyer Sven
Published: July 2022

In this article, we explore if the observation of writing behavior can assist in the screening and follow-up of mild cognitive impairment (MCI) and mild dementia due to Alzheimer’s disease (AD). To this end, we examined the extent to which overall writing process measures and pausing behavior during writing differed between 15 cognitively impaired patients and 15 age- and gender-matched healthy controls. Participants completed two typed picture description tasks that were registered with Inputlog, a keystroke logging program that captures keyboard activity during text production. The following variables were analyzed with mixed-effects models: time on task; number of characters, pauses and Pause-bursts per minute; proportion of pause time; duration of Pause-bursts; and pause time between words. For pause time between words, also the effect of pauses preceding specific word categories was analyzed. Results showed a main effect of group on all variables. In addition, for pause time between words a main effect of part-of-speech was found as well. Results indicate that writing process analysis can possibly serve as a supplementary tool for the screening and follow-up of AD.
A Large-Scale Prospective Study on Functional Ability and Mortality Following Stroke Based on HRS Data Set: Implications for Rehabilitation
Authors: Zhu Hansheng
Published: July 2022

According to the WHO, 15 million people worldwide suffer a stroke annually. Of these, 5 million die and another 5 million are left permanently disabled. Patients endure the impacts of strokes during their rehabilitation and afterward, placing economical and emotional burdens on family and community. Using data from the Health and Retirement Study (HRS) of the USA, the research performed a large-scale prospective analysis to examine how demographics, socioeconomic factors, cognition, emotion, and physical activity predict functional impairment and mortality. Multiple regression was employed to identify statistically significant variables that predict longitudinal Activities of Daily Life (ADLs). The least absolute shrinkage and selection operator (LASSO) logistic regression, a supervised machine learning approach, was deliberately chosen to obtain the subset of predictors that provide the best possible classification for the dependent variable. The LASSO regression produced a model with a fair mean Area Under the Curve (AUC) of 0.75 in predicting the risk of the patient's mortality. My findings also uncovered the important roles of BMI, mobility, muscle strength, memory, mental status, and socioeconomic status play in the long-term ADLs and survival of patients with stroke.
The Impact of Baseline Mindfulness Scores on Mindfulness-Based Intervention Outcomes: Toward Personalized Mental Health Interventions
Authors: Vergara Rodrigo C. , Baquedano Constanza , Lorca-Ponce Enrique , Steinebach Christoph , Langer Álvaro I.
Published: July 2022

A growing body of evidence has portrayed mindfulness as a useful tool for dealing with a broad range of psychological problems and disorders. This has created the impression that mindfulness-based interventions (MBIs) can be used to treat nearly all psychological difficulties, in all cases. Nonetheless, little research has been done on how individual differences may contribute to intervention outcomes. The goal of this study was to evaluate the role of baseline mindfulness on participants’ outcomes by examining three prior Randomized Controlled Trials that addressed the impact of MBIs on mental health and mindfulness measures. The participants were 164 people, aged between 12 and 45, from both clinical and non-clinical samples. Our findings indicate that at least two thirds of the change produced by these interventions in terms of mindfulness scores can be predicted by the baseline scores of the same variables. We also found that many trajectories are not only strongly influenced by the initial status of the participants, but also by the intervention performed, as attested to by the significant interactions found. These results stress the need to continue doing research in a way that considers the diversity of participants’ trajectories, increasing the room for intervention improvements aligned with a more personalized health care model.
Enhancing Chinese EFL Teachers’ Work Engagement: The Role of Self and Collective Efficacy
Authors: Ge Liping
Published: July 2022

Teachers’ work engagement is considered an essential component in instruction. Accordingly, the emphasis should be over physical and mental predictors of this construct. In this line, this study investigates the relationship between Chinese English as a Foreign Language (EFL) teachers’ individual self-efficacy, collective efficacy, and work engagement. To this end, 300 Chinese instructors (males = 96, females = 204) from different colleges and universities participated in this study. The questionnaires were distributed among teachers with different educational levels and experiences. Linear multiple regression was used as a measure for data analysis. The findings showed the significant correlations between teachers’ work engagement, self-efficacy, and collective efficacy. Comparing the predictability power, teachers’ self-efficacy (B= 0.57) proved to have a higher index compared to their index of collective efficacy competence (B= 0.22). This study concluded that self-efficacious teachers and teachers who believe in collective efficacy are more engaged in the EFL contexts. Moreover, the study has some pedagogical implications and suggestions for different teacher educators, administrators, and advisors.
Moral Injury in Trauma-Exposed, Treatment-Seeking Police Officers and Military Veterans: Latent Class Analysis
Authors: Mensink Beijka , van Schagen Annette , van der Aa Niels , ter Heide F. Jackie June
Published: July 2022

Exposure to morally injurious events may have a severe, prolonged negative impact on psychosocial functioning, known as moral injury (MI). Research into the prevalence of MI has mostly focused on event exposure rather than on psychosocial impact. Also, the relationship between MI and post-traumatic stress disorder (PTSD) remains a matter of interest. The aim of this study was to identify MI and PTSD symptom profiles among trauma-exposed, treatment-seeking police officers and military veterans, and to explore demographic and clinical differences between symptom profiles. Latent class and multinomial regression analyses were conducted in a sample of 1,703 participants, using the Clinician-Administered PTSD Scale for DSM-5 and the Brief Symptom Inventory. Four classes of participants were identified, labeled as aMIclass (n= 192; 11.27%), aMI-PTSDclass (n= 565; 33.18%), aPTSDclass (n= 644; 37.82%), and aNeither MI-nor PTSDclass (n= 302; 17.73%), resulting in 44.45% (n= 757) of participants who met an MI symptom profile with or without PTSD. There were significant differences between the classes in terms of gender as well as PTSD and comorbid psychopathology symptom severity, the latter of which was highest in the MI-PTSD class. In conclusion, a substantial subgroup of trauma-exposed, treatment-seeking police officers and military veterans could be classified as suffering from MI. Routinely screening for MI in treatment-seeking police officers and military veterans is recommended, and interventions aimed at relieving MI in these populations may be indicated.