bluuebunny/crossref_metadata_2025 huggingface dataset:
Egg Protein Transferrin-Derived Peptides Irw (Lle-Arg-Trp) and Iqw (Lle-Gln-Trp) Prevent Obesity Mouse Model Induced by a High-Fat Diet via Reducing Lipid Deposition and Reprogramming Gut Microbiota
Authors: Liu Zhuangzhuang , Ding Sujuan , Jiang Hongmei , Fang Jun
Published: September 2022

Egg-derived peptides play important roles in insulin secretion and sensitivity, oxidative stress, and inflammation, suggesting their possible involvement in obesity management. Hence, the aim of this study is to explore the alleviating effects of IRW (lle-Arg-Trp) and IQW (lle-Gln-Trp) on obesity via the mouse model induced by a high-fat diet. The entire experimental period lasted eight weeks. The results demonstrated that IQW prevented weight gain (6.52%), decreased the glucose, low-density lipoprotein (LDL), malonaldehyde, triglycerides, total cholesterol (TC), and leptin levels, and increased the concentration of adiponectin (p < 0.05, n = 8). Although IRW failed to prevent weight gain, it reduced the concentration of glucose, high-density lipoprotein (HDL), LDL, and leptin, and increased the concentration of adiponectin (p < 0.05, n = 8). Moreover, IRW and IQW increased glucose tolerance and insulin resistance based on the results of the intraperitoneal glucose test and insulin tolerance test (p < 0.05, n = 8). The quantitative polymerase chain reaction results revealed that IRW and IQW downregulated the mRNA expression of DGAT1 (Diacylglycerol O-Acyltransferase 1), DGAT2 (Diacylglycerol O-Acyltransferase 2), TNF-α, IL-6, and IL-1β of liver tissue (p < 0.05, n = 8). The results of the 16S ribosomal RNA amplicon sequencing showed that IQW and IRW tended to reduce the relative abundance of Firmicutes and Parabacteroides, and that IRW enhanced the abundance of Bacteroides (p < 0.05, n = 8). Collectively, IRW and IQW supplementation could alleviate the progression of obesity due to the fact that the supplementation reduced lipid deposition, maintained energy balance, and reprogrammed gut microbiota.
Ectopic Expression of Arabidopsis thaliana zDof1.3 in Tomato (Solanum lycopersicum L.) Is Associated with Improved Greenhouse Productivity and Enhanced Carbon and Nitrogen Use
Authors: Luengwilai Kietsuda , Yu Jingwei , Jiménez Randi C. , Thitisaksakul Maysaya , Vega Andrea , Dong Shaoyun , Beckles Diane M.
Published: September 2022

A large collection of transgenic tomato lines, each ectopically expressing a different Arabidopsis thaliana transcription factor, was screened for variants with alterations in leaf starch. Such lines may be affected in carbon partitioning, and in allocation to the sinks. We focused on ‘L4080’, which harbored an A. thaliana zDof (DNA-binding one zinc finger) isoform 1.3 (AtzDof1.3) gene, and which had a 2–4-fold higher starch-to-sucrose ratio in source leaves over the diel (p < 0.05). Our aim was to determine whether there were associated effects on productivity. L4080 plants were altered in nitrogen (N) and carbon (C) metabolism. The N-to-C ratio was higher in six-week-old L4080, and when treated with 1/10 N, L4080 growth was less inhibited compared to the wild-type and this was accompanied by faster root elongation (p < 0.05). The six-week-old L4080 acquired 42% more dry matter at 720 ppm CO2, compared to ambient CO2 (p < 0.05), while the wild-type (WT) remained unchanged. GC-MS-TOF data showed that L4080 source leaves were enriched in amino acids compared to the WT, and at 49 DPA, fruit had 25% greater mass, higher sucrose, and increased yield (25%; p < 0.05) compared to the WT. An Affymetrix cDNA array analysis suggested that only 0.39% of the 9000 cDNAs were altered by 1.5-fold (p < 0.01) in L4080 source leaves. 14C-labeling of fruit disks identified potential differences in 14-DPA fruit metabolism suggesting that post-transcriptional regulation was important. We conclude that AtzDof1.3 and the germplasm derived therefrom, should be investigated for their ‘climate-change adaptive’ potential.
Novel Morpholine-Bearing Quinoline Derivatives as Potential Cholinesterase Inhibitors: The Influence of Amine, Carbon Linkers and Phenylamino Groups
Authors: Liu Cheng , Wang Li-Ning , Liu Yu-Ming
Published: September 2022

A series of novel 4-N-phenylaminoquinoline derivatives containing a morpholine group were designed and synthesized, and their anti-cholinesterase activities and ABTS radical-scavenging activities were tested. Among them, compounds 11a, 11g, 11h, 11j, 11l, and 12a had comparable inhibition activities to reference galantamine in AChE. Especially, compound 11g revealed the most potent inhibition on AChE and BChE with IC50 values of 1.94 ± 0.13 μM and 28.37 ± 1.85 μM, respectively. The kinetic analysis demonstrated that both the compounds 11a and 11g acted as mixed-type AChE inhibitors. A further docking comparison between the 11a- and 12a-AChE complexes agreed with the different inhibitory potency observed in experiments. Besides, compounds 11f and 11l showed excellent ABTS radical-scavenging activities, with IC50 values of 9.07 ± 1.34 μM and 6.05 ± 1.17 μM, respectively, which were superior to the control, Trolox (IC50 = 11.03 ± 0.76 μM). It is worth noting that 3-aminoquinoline derivatives 12a–12d exhibited better drug-like properties.
Phytochemicals with Chemopreventive Activity Obtained from the Thai Medicinal Plant Mammea siamensis (Miq.) T. Anders.: Isolation and Structure Determination of New Prenylcoumarins with Inhibitory Activity against Aromatase
Authors: Luo Fenglin , Manse Yoshiaki , Chaipech Saowanee , Pongpiriyadacha Yutana , Muraoka Osamu , Morikawa Toshio
Published: September 2022

With the aim of searching for phytochemicals with aromatase inhibitory activity, five new prenylcoumarins, mammeasins K (1), L (2), M (3), N (4), and O (5), were isolated from the methanolic extract of Mammea siamensis (Miq.) T. Anders. flowers (fam. Calophyllaceae), originating in Thailand. The stereostructures of 1–5 were elucidated based on their spectroscopic properties. Among the new compounds, 1 (IC50 = 7.6 µM) and 5 (9.1 µM) possessed relatively strong inhibitory activity against aromatase, which is a target of drugs already used in clinical practice for the treatment and prevention of estrogen-dependent breast cancer. The analysis through Lineweaver–Burk plots showed that they competitively inhibit aromatase (1, Ki = 3.4 µM and 5, 2.3 µM). Additionally, the most potent coumarin constituent, mammea B/AB cyclo D (31, Ki = 0.84 µM), had a competitive inhibitory activity equivalent to that of aminoglutethimide (0.84 µM), an aromatase inhibitor used in therapeutics.
Plasma Proteomics Enable Differentiation of Lung Adenocarcinoma from Chronic Obstructive Pulmonary Disease (COPD)
Authors: Bracht Thilo , Kleefisch Daniel , Schork Karin , Witzke Kathrin E. , Chen Weiqiang , Bayer Malte , Hovanec Jan , Johnen Georg , Meier Swetlana , Ko Yon-Dschun , Behrens Thomas , Brüning Thomas , Fassunke Jana , Buettner Reinhard , Uszkoreit Julian , Adamzik Michael , Eisenacher Martin , Sitek Barbara
Published: September 2022

Chronic obstructive pulmonary disease (COPD) is a major risk factor for the development of lung adenocarcinoma (AC). AC often develops on underlying COPD; thus, the differentiation of both entities by biomarker is challenging. Although survival of AC patients strongly depends on early diagnosis, a biomarker panel for AC detection and differentiation from COPD is still missing. Plasma samples from 176 patients with AC with or without underlying COPD, COPD patients, and hospital controls were analyzed using mass-spectrometry-based proteomics. We performed univariate statistics and additionally evaluated machine learning algorithms regarding the differentiation of AC vs. COPD and AC with COPD vs. COPD. Univariate statistics revealed significantly regulated proteins that were significantly regulated between the patient groups. Furthermore, random forest classification yielded the best performance for differentiation of AC vs. COPD (area under the curve (AUC) 0.935) and AC with COPD vs. COPD (AUC 0.916). The most influential proteins were identified by permutation feature importance and compared to those identified by univariate testing. We demonstrate the great potential of machine learning for differentiation of highly similar disease entities and present a panel of biomarker candidates that should be considered for the development of a future biomarker panel.
Drosophila as a Model Organism to Study Basic Mechanisms of Longevity
Authors: Ogienko Anna A. , Omelina Evgeniya S. , Bylino Oleg V. , Batin Mikhail A. , Georgiev Pavel G. , Pindyurin Alexey V.
Published: September 2022

The spatio-temporal regulation of gene expression determines the fate and function of various cells and tissues and, as a consequence, the correct development and functioning of complex organisms. Certain mechanisms of gene activity regulation provide adequate cell responses to changes in environmental factors. Aside from gene expression disorders that lead to various pathologies, alterations of expression of particular genes were shown to significantly decrease or increase the lifespan in a wide range of organisms from yeast to human. Drosophila fruit fly is an ideal model system to explore mechanisms of longevity and aging due to low cost, easy handling and maintenance, large number of progeny per adult, short life cycle and lifespan, relatively low number of paralogous genes, high evolutionary conservation of epigenetic mechanisms and signalling pathways, and availability of a wide range of tools to modulate gene expression in vivo. Here, we focus on the organization of the evolutionarily conserved signaling pathways whose components significantly influence the aging process and on the interconnections of these pathways with gene expression regulation.
Antagonist of Growth Hormone-Releasing Hormone Potentiates the Antitumor Effect of Pemetrexed and Cisplatin in Pleural Mesothelioma
Authors: Gesmundo Iacopo , Pedrolli Francesca , Vitale Nicoletta , Bertoldo Alessia , Orlando Giulia , Banfi Dana , Granato Giuseppina , Kasarla Ramesh , Balzola Federico , Deaglio Silvia , Cai Renzhi , Sha Wei , Papotti Mauro , Ghigo Ezio , Schally Andrew V. , Granata Riccarda
Published: September 2022

Pleural mesothelioma (PM) is an aggressive cancer with poor prognosis and no effective therapies, mainly caused by exposure to asbestos. Antagonists of growth hormone-releasing hormone (GHRH) display strong antitumor effects in many experimental cancers, including lung cancer and mesothelioma. Here, we aimed to determine whether GHRH antagonist MIA-690 potentiates the antitumor effect of cisplatin and pemetrexed in PM. In vitro, MIA-690, in combination with cisplatin and pemetrexed, synergistically reduced cell viability, restrained cell proliferation and enhanced apoptosis, compared with drugs alone. In vivo, the same combination resulted in a strong growth inhibition of MSTO-211H xenografts, decreased tumor cell proliferation and increased apoptosis. Mechanistically, MIA-690, particularly with chemotherapeutic drugs, inhibited proliferative and oncogenic pathways, such as MAPK ERK1/2 and cMyc, and downregulated cyclin D1 and B1 mRNAs. Inflammatory pathways such as NF-kB and STAT3 were also reduced, as well as oxidative, angiogenic and tumorigenic markers (iNOS, COX-2, MMP2, MMP9 and HMGB1) and growth factors (VEGF and IGF-1). Overall, these findings strongly suggest that GHRH antagonists of MIA class, such as MIA-690, could increase the efficacy of standard therapy in PM.
Novel Long-Acting Oxytocin Analog with Increased Efficacy in Reducing Food Intake and Body Weight
Authors: Elfers Clinton T. , Blevins James E. , Salameh Therese S. , Lawson Elizabeth A. , Silva David , Kiselyov Alex , Roth Christian L.
Published: September 2022

Oxytocin (OXT) analogues have been designed to overcome the limitation of the short half-life of the native OXT peptide. Here, we tested ASK2131 on obesity related outcomes in diet-induced obese (DIO) Sprague Dawley rats. In vitro function assays were conducted. The effects of daily subcutaneous injections of ASK2131 vs. OXT and pair-feeding were assessed on food intake and body weight in vivo. ASK2131 is a longer-lasting OXT analog with improved pharmacokinetics compared to OXT (T1/2: 2.3 vs. 0.12 h). In chronic 22-day administration, ASK2131 was administered at 50 nmol/kg, while OXT doses were titrated up to 600 nmol/kg because OXT appeared to be less effective at reducing energy intake relative to ASK2131 at equimolar doses. After 22 days, vehicle-treated animals gained 4.5% body weight, OXT rats maintained their body weight, while those treated with ASK2131 declined in weight continuously over the 22-day period, leading to a 6.6 ± 1.3% reduction (mean ± standard error) compared to baseline. Compared to their pair-fed counterparts, ASK2131-treated rats showed a more pronounced reduction in body weight through most of the study. In summary, ASK2131 is a promising OXT-based therapeutic, with extended in vivo stability and improved potency leading to a profound reduction in body weight partly explained by reduced food intake.
Glucogallin Attenuates the LPS-Induced Signaling in Macrophages and Protects Mice against Sepsis
Authors: Singh Rajveer , Chandel Shivani , Ghosh Arijit , Matta Tushar , Gautam Anupam , Bhattacharya Arka , Babu Srivalliputturu Sarath , Sukla Soumi , Nag Debasish , Ravichandiran Velayutham , Roy Syamal , Ghosh Dipanjan
Published: September 2022

The anti-oxidant and anti-inflammatory effect of beta-glucogallin (BGG), a plant-derived natural product, was evaluated in both in vitro and in vivo studies. For the in vitro study, the ability of BGG pre-treatment to quench LPS-induced effects compared to LPS alone in macrophages was investigated. It was found that BGG pre-treatment showed a significant decrease in ROS, NO, superoxide, and pro-inflammatory cytokines (TNF-alpha, IL-4, IL-17, IL-1β, and IL-6) and increased reduced glutathione coupled with the restoration of mitochondrial membrane potential. Gene profiling and further validation by qPCR showed that BGG pre-treatment downregulated the LPS-induced expression of c-Fos, Fas, MMP-9, iNOS, COX-2, MyD88, TRIF, TRAF6, TRAM, c-JUN, and NF-κB. We observed that BGG pre-treatment reduced nuclear translocation of LPS-activated NF-κB and thus reduced the subsequent expressions of NLRP3 and IL-1β, indicating the ability of BGG to inhibit inflammasome formation. Molecular docking studies showed that BGG could bind at the active site of TLR4. Finally, in the LPS-driven sepsis mouse model, we showed that pre-treatment with BGG sustained toxic shock, as evident from their 100% survival. Our study clearly showed the therapeutic potential of BGG in toxic shock syndrome.
Nanoparticles Loaded with Platinum Drugs for Colorectal Cancer Therapy
Authors: Buyana Buhle , Naki Tobeka , Alven Sibusiso , Aderibigbe Blessing Atim
Published: September 2022

Colorectal cancer is a common cancer in both men and women. Numerous studies on the therapeutic effectiveness of nanoparticles against colorectal cancer have been reported. Platinum treatments as well as other medications comprising of nanoparticles have been utilized. Drug resistance restricts the use of platinum medicines, despite their considerable efficacy against a variety of cancers. This review reports clinically licensed platinum medicines (cisplatin, carboplatin, and oxaliplatin) combined with various nanoparticles that have been evaluated for their therapeutic efficacy in the treatment of colorectal cancer, including their mechanism of action, resistance, and limitations.
Organoids: A New Chapter in Sarcoma Diagnosis and Treatment
Authors: Psilopatis Iason , Kokkali Stefania , Palamaris Kostas , Digklia Antonia , Vrettou Kleio , Theocharis Stamatios
Published: September 2022

Sarcomas are malignant tumors of mesenchymal origin that can occur at any age. The rarity of these tumors in combination with the vast number of histological subtypes render the study of sarcomas challenging. Organoids represent complex three-dimensional cell culture systems, deriving from stem cells and preserving the capacity to differentiate into the cell types of their tissue of origin. The aim of the present review is to study the current status of patient-derived organoids, as well as their potential to model tumorigenesis and perform drug screenings for sarcomas. In order to identify relevant studies, a literature review was conducted and we were able to identify 16 studies published between 2019 and 2022. The current manuscript represents the first comprehensive review of the literature focusing on the use of organoids for disease modelling and drug sensitivity testing in diverse sarcoma subtypes.
Structural Characteristics of Polysaccharide GP2a in Gardenia jasminoides and Its Immunomodulatory Effect on Macrophages
Authors: Lin Pingdong , Chen Lifei , Huang Xiaojing , Xiao Fangnan , Fu Lei , Jing Dingding , Wang Jingjing , Zhang Hong , Sun Lifang , Wu Yunkun
Published: September 2022

Here, we elucidated the structural characteristics of a polysaccharide isolated from Gardenia jasminoides Ellis (labeled as GP2a) and its immunomodulatory activity. GP2a is an acidic polysaccharide with a molecular weight of 44.8 kDa, mostly comprising galacturonic acid. Methylation analysis revealed 4-GalpA (74.8%) to be the major sugar residue in GP2a. Nuclear magnetic resonance analysis indicated that its main chain comprised →4)-α-D-GalpA-6-OMe-(1→4)-α-D-GalpA-(1→ and →4)-α-D-GalpA-6-OMe-(1→2)-α-L-Rhap-(1→, with galactan and arabinans linked to the C-4 position of →2)-α-L-Rhap-(1→ residue as branched chains. Furthermore, GP2a showed no obvious toxicity to macrophages (RAW 264.7) while enhancing cell viability in a dose- and time-dependent manner. Compared with untreated cells, nitric oxide production and secretion of cytokines, such as tumor necrosis factor-α, interferon-γ, interleukin (IL)-1β, IL-6, and granulocyte macrophage colony stimulating factor, in GP2a-treated cells significantly increased after 48 h. At 300 µg/mL GP2a concentration, there was no significant difference in the cytokine levels in GP2a- and lipopolysaccharide-treated cells (the positive control). In summary, GP2a is a pectic polysaccharide with homogalacturonan and rhamnogalacturonan-I structural regions in the main chain. Based on its immunomodulatory effects in vitro, GP2a may have potential uses in functional food and medicine.
Role of Essential Amino Acids in Age-Induced Bone Loss
Authors: Lv Ziquan , Shi Wenbiao , Zhang Qian
Published: September 2022

Age-induced osteoporosis is a global problem. Essential amino acids (EAAs) work as an energy source and a molecular pathway modulator in bone, but their functions have not been systematically reviewed in aging bone. This study aimed to discuss the contribution of EAAs on aging bone from in vitro, in vivo, and human investigations. In aged people with osteoporosis, serum EAAs were detected changing up and down, without a well-established conclusion. The supply of EAAs in aged people either rescued or did not affect bone mineral density (BMD) and bone volume. In most signaling studies, EAAs were proven to increase bone mass. Lysine, threonine, methionine, tryptophan, and isoleucine can increase osteoblast proliferation, activation, and differentiation, and decrease osteoclast activity. Oxidized L-tryptophan promotes bone marrow stem cells (BMSCs) differentiating into osteoblasts. However, the oxidation product of tryptophan called kynurenine increases osteoclast activity, and enhances the differentiation of adipocytes from BMSCs. Taken together, in terms of bone minerals and volume, more views consider EAAs to have a positive effect on aging bone, but the function of EAAs in bone metabolism has not been fully demonstrated and more studies are needed in this area in the future.
Role of Demyelination in the Persistence of Neurological and Mental Impairments after COVID-19
Authors: Khodanovich Marina Y. , Kamaeva Daria A. , Naumova Anna V.
Published: September 2022

Long-term neurological and mental complications of COVID-19, the so-called post-COVID syndrome or long COVID, affect the quality of life. The most persistent manifestations of long COVID include fatigue, anosmia/hyposmia, insomnia, depression/anxiety, and memory/attention deficits. The physiological basis of neurological and psychiatric disorders is still poorly understood. This review summarizes the current knowledge of neurological sequelae in post-COVID patients and discusses brain demyelination as a possible mechanism of these complications with a focus on neuroimaging findings. Numerous reviews, experimental and theoretical studies consider brain demyelination as one of the mechanisms of the central neural system impairment. Several factors might cause demyelination, such as inflammation, direct effect of the virus on oligodendrocytes, and cerebrovascular disorders, inducing myelin damage. There is a contradiction between the solid fundamental basis underlying demyelination as the mechanism of the neurological injuries and relatively little published clinical evidence related to demyelination in COVID-19 patients. The reason for this probably lies in the fact that most clinical studies used conventional MRI techniques, which can detect only large, clearly visible demyelinating lesions. A very limited number of studies use specific methods for myelin quantification detected changes in the white matter tracts 3 and 10 months after the acute phase of COVID-19. Future research applying quantitative MRI assessment of myelin in combination with neurological and psychological studies will help in understanding the mechanisms of post-COVID complications associated with demyelination.
Chronic Exposure to Vinclozolin Induced Fibrosis, Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis in Mice Kidney
Authors: Di Paola Davide , D’Amico Ramona , Genovese Tiziana , Siracusa Rosalba , Cordaro Marika , Crupi Rosalia , Peritore Alessio Filippo , Gugliandolo Enrico , Interdonato Livia , Impellizzeri Daniela , Fusco Roberta , Cuzzocrea Salvatore , Di Paola Rosanna
Published: September 2022

Vinclozolin is one of the most used fungicides in the control of fungi in fruits, vegetables, and ornamental plants. The effects of its exposure on different organs have been described, but information regarding its relevance to vinclozolin-induced nephrotoxicity is largely missing. This study focuses on the potential mechanism of vinclozolin-induced nephrotoxicity. CD1 male mice were administered vinclozolin (100 mg/kg) by oral gavage for 28 days. Vinclozolin administration decreased body weight over the treatment period and at the end of the experiment, increased the ratio of kidney weight to body weight and increased serum urea nitrogen and creatinine contents. Vinclozolin also induced histopathological alterations, including tubular dilatation and necrosis and impaired the integrity of the renal-tubular architecture and kidney fibrosis. The analyses conducted showed that vinclozolin administration altered the mRNA levels of mitochondrial function-related proteins (SIRT3, SIRT1, PGC-1α, TFAM, NRF1, VDAC-1, and Cyt c) and oxidative stress (increased lipid peroxidation and decreased total antioxidative capacity, catalase, and superoxide dismutase activities, glutathione levels, and glutathione peroxidase activity) in the kidneys. Furthermore, vinclozolin induced toxicity that altered Nrf2 signalling and the related proteins (HO-1 and NQO-1). Vinclozolin administration also affected both the extrinsic and intrinsic apoptotic pathways, upregulating the expression of proapoptotic factors (Bax, Caspase 3, and FasL) and downregulating antiapoptotic factor (Bcl-2) levels. This study suggests that vinclozolin induced nephrotoxicity by disrupting the transcription of mitochondrial function-related factors, the Nrf2 signalling pathway, and the extrinsic and intrinsic apoptotic pathways.
Genomic Mutations of the STAT5 Transcription Factor Are Associated with Human Cancer and Immune Diseases
Authors: Kim Uijin , Shin Ha Youn
Published: September 2022

Signal transducer and activation of transcription 5 (STAT5) is a key transcription factor that regulates various biological processes in mammalian development. Aberrant regulation of STAT5 has also been causally linked to many diseases, including cancers and immune-related diseases. Although persistent activation of STAT5 due to dysregulation of the signaling cascade has been reported to be associated with the progression of solid tumors and leukemia, various genomic mutations of STAT5 have also been found to cause a wide range of diseases. The present review comprehensively summarizes results of recent studies evaluating the intrinsic function of STAT5 and the link between STAT5 mutations and human diseases. This review also describes the types of disease models useful for investigating the mechanism underlying STAT5-driven disease progression. These findings provide basic knowledge for understanding the regulatory mechanisms of STAT5 and the progression of various diseases resulting from aberrant regulation of STAT5. Moreover, this review may provide insights needed to create optimal disease models that reflect human disease associated STAT5 mutations and to design gene therapies to correct STAT5 mutations.
The Impact of Non-Nodulating Diazotrophic Bacteria in Agriculture: Understanding the Molecular Mechanisms That Benefit Crops
Authors: Thiebaut Flávia , Urquiaga Maria Clara de Oliveira , Rosman Aline Cardozo , da Silva Mirielson Loures , Hemerly Adriana Silva
Published: September 2022

Agriculture is facing increasing challenges with regard to achieving sustainable growth in productivity without negatively impacting the environment. The use of bioinoculants is emerging as a sustainable solution for agriculture, especially bioinoculants based on diazotrophic bacteria. Brazil is at the forefront of studies intended to identify beneficial diazotrophic bacteria, as well as in the molecular characterization of this association on both the bacterial and plant sides. Here we highlight the main advances in molecular studies to understand the benefits brought to plants by diazotrophic bacteria. Different molecular pathways in plants are regulated both genetically and epigenetically, providing better plant performance. Among them, we discuss the involvement of genes related to nitrogen metabolism, cell wall formation, antioxidant metabolism, and regulation of phytohormones that can coordinate plant responses to environmental factors. Another important aspect in this regard is how the plant recognizes the microorganism as beneficial. A better understanding of plant–bacteria–environment interactions can assist in the future formulation of more efficient bioinoculants, which could in turn contribute to more sustainable agriculture practices.
PIKE-A Modulates Mitochondrial Metabolism through Increasing SDHA Expression Mediated by STAT3/FTO Axis
Authors: Sun Mingming , Yan Qi , Qiao Yaya , Zhao Huifang , Wang Yingzhi , Shan Changliang , Zhang Shuai
Published: September 2022

Previous studies have shown that phosphoinositide 3-kinase enhancer-activating Akt (PIKE-A) is involved in the regulation of several biological processes in cancer. In our previous study, we demonstrated a crucial function of PIKE-A in cancer energy metabolism by regulating pentose phosphate pathway (PPP) flux. However, whether PIKE-A regulates energy metabolism through affecting mitochondrial changes are poorly understood. In the present study, we show that PIKE-A promotes mitochondrial membrane potential, leading to increasing proliferation of glioblastoma cell. Mechanistically, PIKE-A affects the expression of respiratory chain complex Ⅱ succinate dehydrogenase A (SDHA), mediated by regulating the axis of STAT3/FTO. Taken together, these results revealed that inhibition of PIKE-A reduced STAT3/FTO/SDHA expression, leading to the suppression of mitochondrial function. Thus, our findings suggest the PIKE-A/STAT3/FTO/SDHA axis as promising anti-cancer treatment targets.
Medicinal Herbs and Their Derived Ingredients Protect against Cognitive Decline in In Vivo Models of Alzheimer’s Disease
Authors: Tsai Yueh-Ting , Kao Shung-Te , Cheng Chin-Yi
Published: September 2022

Alzheimer’s disease (AD) has pathological hallmarks including amyloid beta (Aβ) plaque formation. Currently approved single-target drugs cannot effectively ameliorate AD. Medicinal herbs and their derived ingredients (MHDIs) have multitarget and multichannel properties, engendering exceptional AD treatment outcomes. This review delineates how in in vivo models MHDIs suppress Aβ deposition by downregulating β- and γ-secretase activities; inhibit oxidative stress by enhancing the antioxidant activities and reducing lipid peroxidation; prevent tau hyperphosphorylation by upregulating protein phosphatase 2A expression and downregulating glycogen synthase kinase-3β expression; reduce inflammatory mediators partly by upregulating brain-derived neurotrophic factor/extracellular signal-regulated protein kinase 1/2-mediated signaling and downregulating p38 mitogen-activated protein kinase (p38 MAPK)/c-Jun N-terminal kinase (JNK)-mediated signaling; attenuate synaptic dysfunction by increasing presynaptic protein, postsynaptic protein, and acetylcholine levels and preventing acetylcholinesterase activity; and protect against neuronal apoptosis mainly by upregulating Akt/cyclic AMP response element-binding protein/B-cell lymphoma 2 (Bcl-2)-mediated anti-apoptotic signaling and downregulating p38 MAPK/JNK/Bcl-2-associated x protein (Bax)/caspase-3-, Bax/apoptosis-inducing factor-, C/EBP homologous protein/glucose-regulated protein 78-, and autophagy-mediated apoptotic signaling. Therefore, MHDIs listed in this review protect against Aβ-induced cognitive decline by inhibiting Aβ accumulation, oxidative stress, tau hyperphosphorylation, inflammation, synaptic damage, and neuronal apoptosis in the cortex and hippocampus during the early and late AD phases.
Tracking of Extracellular Vesicles’ Biodistribution: New Methods and Approaches
Authors: Aimaletdinov Alexander M. , Gomzikova Marina O.
Published: September 2022

Extracellular vesicles (EVs) are nanosized lipid bilayer vesicles that are released by almost all cell types. They range in diameter from 30 nm to several micrometres and have the ability to carry biologically active molecules such as proteins, lipids, RNA, and DNA. EVs are natural vectors and play an important role in many physiological and pathological processes. The amount and composition of EVs in human biological fluids serve as biomarkers and are used for diagnosing diseases and monitoring the effectiveness of treatment. EVs are promising for use as therapeutic agents and as natural vectors for drug delivery. However, the successful use of EVs in clinical practice requires an understanding of their biodistribution in an organism. Numerous studies conducted so far on the biodistribution of EVs show that, after intravenous administration, EVs are mostly localized in organs rich in blood vessels and organs associated with the reticuloendothelial system, such as the liver, lungs, spleen, and kidneys. In order to improve resolution, new dyes and labels are being developed and detection methods are being optimized. In this work, we review all available modern methods and approaches used to assess the biodistribution of EVs, as well as discuss their advantages and limitations.
Chronic Exposure to Endocrine Disruptor Vinclozolin Leads to Lung Damage via Nrf2–Nf-kb Pathway Alterations
Authors: D’Amico Ramona , Di Paola Davide , Impellizzeri Daniela , Genovese Tiziana , Fusco Roberta , Peritore Alessio Filippo , Gugliandolo Enrico , Crupi Rosalia , Interdonato Livia , Cuzzocrea Salvatore , Di Paola Rosanna , Siracusa Rosalba , Cordaro Marika
Published: September 2022

Endocrine-disrupting substances (EDS) are common and pervasive in our environment and pose a serious risk to both human and animal health. Endocrine-disrupting compounds (EDCs) have been associated with a variety of detrimental human health effects, including respiratory issues, as a result of their ability to disrupt cell physiology. Vinclozolin ((RS)-3-(3,5-Dichlorophenyl)-5-methyl-5-vinyloxazolidine-2,4-dione) is a common dicarboximide fungicide used to treat plant diseases. Several studies have analyzed the effects of vinclozolin exposure on the reproductive system, but less is known about its effect on other organs such as the lung. Mice were exposed for 28 days to orally administered vinclozolin at a dose of 100 mg/kg. Vinclozolin exposure induced histological alterations and collagen depositions in the lung. Additionally, vinclozolin induced inflammation and oxidative stress that led to lung apoptosis. Our study demonstrates for the first time that the toxicological effects of vinclozolin are not limited to the reproductive system but also involve other organs such as the lung.
A Visual Data Storytelling Framework
Authors: Zhang Yangjinbo , Reynolds Mark , Lugmayr Artur , Damjanov Katarina , Hassan Ghulam Mubashar
Published: September 2022

While the consumption of visual information becomes a daily commodity integrated into our lives, data visualisation is dominated by dashboards and charts. The main contribution of this article is an advanced way to visualise data as a data story. We converged paradigms from digital storytelling, serious games, and data visualisation to turn data into useful insights. The creation, management, and analysis of data have been increasingly given more attention in industry and professional practices. However, the potential of packaging data and analytic results into easily digestible and visually explorable content intended for non-professional audiences has not yet been investigated to its full extent. We contributed towards overcoming the gap between data analytics and data presentation. By integrating a story-like environment and entertainment into data visualisation, we explore the possibilities of efficiently communicating data and insights to general audiences in a casual context. We present this modular approach to customising messages for visual data storytelling from an information and communication perspective, including a test prototype developed to illustrate our data storytelling framework.
Chronological Development of Cardiovascular Disease in Times of COVID-19: A Retrospective Analysis of Hospitalized Diseases of the Circulatory System and COVID-19 Patients of a German University Hospital
Authors: Griewing Sebastian , Gremke Niklas , Kreutz Julian , Schieffer Bernhard , Timmermann Lars , Markus Birgit
Published: September 2022

This study aims at examining the chronological development of hospitalized cardiovascular and COVID-19 patients and comparing the effects on related sub-disciplines and main diagnoses for pre-pandemic (2017–2019) and pandemic (2020–2021) years in the setting of a German university maximum care provider. Data were retrospectively retrieved from the hospital performance controlling system for patient collectives with main diagnosis of diseases of the circulatory system (nCirculatory) and COVID-19 secondary diagnosis (nCOVID-19). The cardiovascular patient collective (nCirculatory = 25,157) depicts a steady state in terms of relative yearly development of patient numbers (+0.4%, 2019–2020, +0.1%, 2020–2021). Chronological assessment points towards monthly decline during lockdowns and phases of high regional incidence of COVID-19 (i.e., 2019–2020: March −10.2%, April −12.4%, December −14.8%). Main diagnoses of congestive heart failure (+16.1% 2019/2020; +19.2% 2019/2021) and acute myocardial infarction show an increase in case numbers over the course of the whole pandemic (+15.4% 2019/2020; +9.4% 2019/2021). The results confirm negative effects on the cardiovascular care situation during the entire pandemic in the setting of a university maximum care provider. A general increase in cardiac disorders and a worrisome turn in case development of acute myocardial infarction emphasize the feared cardiovascular burden of COVID-19.
X-ray Computed Tomography Analysis of Historical Woodwind Instruments of the Late Eighteenth Century
Authors: Tansella Francesca , Vigorelli Luisa , Ricchiardi Gabriele , Re Alessandro , Bonizzoni Letizia , Grassini Sabrina , Staropoli Manuel , Lo Giudice Alessandro
Published: September 2022

In this work, two historical flutes of the late eighteenth century were analysed by means of X-ray computed tomography (CT). The first one is a piccolo flute whose manufacturer is unknown, though some features could suggest an English or American origin. The second musical instrument is a baroque transverse flute, probably produced by Lorenzo Cerino, an Italian instrument maker active in Turin (Italy) in the late eighteenth century. Analyses carried out provided information on manufacturing techniques, materials and conservation state, and are suitable to plan restoration intervention. In particular, through the CT images, it was possible to observe the presence of defects, cracks, fractures and previous restorations, as well as indications of the tools used in the making of the instruments. Particular attention was directed towards extracting metrological information about the objects. In fact, this work is the first step of a study with a final aim of determining an operative protocol to enable the making of precise-sounding copies of ancient instruments starting from CT images, that can be used to plan a virtual restoration, consisting in the creation of digitally restored copies with a 3D printer.
Characterization of a NRPS-like Protein from Pestalotiopsis fici for Aldehyde Generation
Authors: Li Yuanyuan , Wei Peng-Lin , Ran Huomiao , Fan Jie , Yin Wen-Bing
Published: September 2022

Nonribosomal peptide synthetase (NRPS)-like enzymes containing A-T-R domain architecture are also known as carboxylate reductases (CARs) for aldehyde generation. To identify new members of CARs, we established a virtual library containing 84 fungal CARs distributed in seven distinct clades by genome mining and phylogenetic analysis. Nine CARs, including PnlA from Pestalotiopsis fici and eight known CARs, were clustered in clade VI and proposed to catalyze the reduction of nonreducing polyketide synthase (NR-PKS)-derived aryl carboxylic acids. The recombinant protein PnlA was overproduced and purified to apparent homogeneity from Saccharomyces cerevisiae. In vitro enzyme assays of PnlA with 28 different benzoic acid derivatives (1–28) revealed the corresponding aldehyde formation in 14 cases (1–14). Comparison of conversion yields indicated the high preference of PnlA toward 3,5-dimethylorsellinic acid (DMOA, 4) and vanillic acid (10). A specificity-conferring code Q355 in PnlA was postulated by sequence alignment with the known CARs in clade VI. Our study provides an updated virtual library of fungal CAR enzymes and expands the biocatalytic selectivity of CARs.
Nephroprotective Effects of Two Ganoderma Species Methanolic Extracts in an In Vitro Model of Cisplatin Induced Tubulotoxicity
Authors: Sinaeve Sébastien , Husson Cécile , Antoine Marie-Hélène , Welti Stéphane , Stévigny Caroline , Nortier Joëlle
Published: September 2022

Although cisplatin is used as a first-line therapy in many cancers, its nephrotoxicity remains a real problem. Acute kidney injuries induced by cisplatin can cause proximal tubular necrosis, possibly leading to interstitial fibrosis, chronic dysfunction, and finally to a cessation of chemotherapy. There are only a few nephroprotective actions that can help reduce cisplatin nephrotoxicity. This study aims to identify new prophylactic properties with respect to medicinal mushrooms. Among five Ganoderma species, the methanolic extracts of Ganoderma tuberculosum Murill., Ganoderma parvigibbosum Welti & Courtec. (10 µg/mL), and their association (5 + 5 µg/mL) were selected to study respective in vitro effects on human proximal tubular cells (HK-2) intoxicated by cisplatin. Measurements were performed after a pretreatment of 1 h with the extracts before adding cisplatin (20 µM). A viability assay, antioxidant activity, intracytoplasmic β-catenin, calcium, caspase-3, p53, cytochrome C, IL-6, NFκB, membranous KIM-1, and ROS overproduction were studied. Tests showed that both methanolic extracts and their association prevented a loss of viability, apoptosis, and its signaling pathway. G. parvigibbosum and the association prevented an increase in intracytoplasmic β-catenin. G. parvigibbosum prevented ROS overproduction and exhibited scavenger activity. None of the extracts could interfere with pro-inflammatory markers or calcium homeostasis. Our in vitro data demonstrate that these mushroom extracts have interesting nephroprotective properties. Finally, the chemical content was investigated through a phytochemical screening, and the determination of the total phenolic and triterpenoid content. Further studies about the chemical composition need to be conducted.
Deep Meaning in Scenic Assessment: Seeing around the Bend
Authors: Miller Patrick Alan
Published: September 2022

Many of today’s scenic assessment tools were developed initially to preserve the visual quality of public lands and to mitigate the negative visual impacts of large-scale landscape alterations, such as timber harvesting, mineral extraction, and renewable energy production. However, we are beginning to see more interest today in preserving scenic views on non-public lands. This essay makes a case for additional scenic assessment tools that reveal deep meaning in the landscape. Deep meaning is different than the immediately visible attributes of the landscape. It includes things that come to mind when looking at the landscape and are shared by people familiar with that landscape. Understanding the concept of deep meaning can be difficult. The author describes how deep meaning in the landscape was first revealed to him. Two non-landscape examples are then used to demonstrate different aspects of deep meaning. First, the rocks in a rock garden show the personal nature and attachment of deep meaning. Second, the wording on two wine bottle labels illustrates the distinction between surface meaning and deep meaning. Poetry is then examined as a means of conveying deeper landscape meaning. Lastly, four different landscape contents categories that are used in the proposed Virginia Scenic Viewshed Program demonstrate how deep meaning content can be used in the scenic viewshed assessment. The conclusion is that deep meaning would be a valuable addition to the scenic assessment of non-public land viewsheds, particularly if the assessment process involves the public.
The Impact of Development Zones on Economic Growth in Less Developed Regions: Evidence from Guangxi, China
Authors: Xu Lanzhuang , Xue Hu , Wu Qianrong
Published: September 2022

The development zone is an important institutional form of industrial spatial organization in China’s economic transformation and is an essential growth pole of urban economic development. Based on the county-level panel data of Guangxi from 2005 to 2017, this study contributes to the discussion by exploring the effects of development zones on economic development in developed regions. Additionally, this study further attempts to illustrate the character of the agglomeration effect built on development zones and try to reveal the significant influence factors of the effect of development zones on the economy. Through the progressive difference-in-difference (DID) model approach, empirical results reveal that the development zone has a negative effect on the local economy within three years after its establishment, and the “development zone fever” significantly reduces the potential for regional economic growth. With the decrease in the established frequency of development zones, the effect of the development zone on economic growth becomes positive. However, this promoting effect is unsustainable because the agglomeration effect of development zones is mainly caused by the “clusters of enterprises”. Certain industrial agglomeration and technological capabilities are essential prerequisites for development zones to promote economic growth, while the negative impact appears in a highly competitive environment caused by excessive government intervention. Therefore, the key to maintaining the sustainability of development zones’ competition is to strengthen the assessment standard of survival of the fittest for enterprises, and promote the agglomeration of high-end industries by improving the selection effect of development zones. These findings have great potential in policy making and can be used as a resource by policymakers to promote the sustainable development of less developed regions.
Development of Hybrid Intelligent Models for Prediction Machining Performance Measure in End Milling of Ti6Al4V Alloy with PVD Coated Tool under Dry Cutting Conditions
Authors: Al-Zubaidi Salah , A.Ghani Jaharah , Che Haron Che Hassan , Mohammed M. N. , Jameel Al-Tamimi Adnan Naji , M.Sarhan Samaher , Salleh Mohd Shukor , Abdulrazaq M. , Abdullah Oday I.
Published: September 2022

Ti6Al4V alloy is widely used in aerospace and medical applications. It is classified as a difficult to machine material due to its low thermal conductivity and high chemical reactivity. In this study, hybrid intelligent models have been developed to predict surface roughness when end milling Ti6Al4V alloy with a Physical Vapor Deposition PVD coated tool under dry cutting conditions. Back propagation neural network (BPNN) has been hybridized with two heuristic optimization techniques, namely: gravitational search algorithm (GSA) and genetic algorithm (GA). Taguchi method was used with an L27 orthogonal array to generate 27 experiment runs. Design expert software was used to do analysis of variances (ANOVA). The experimental data were divided randomly into three subsets for training, validation, and testing the developed hybrid intelligent model. ANOVA results revealed that feed rate is highly affected by the surface roughness followed by the depth of cut. One-way ANOVA, including a Post-Hoc test, was used to evaluate the performance of three developed models. The hybrid model of Artificial Neural Network-Gravitational Search Algorithm (ANN-GSA) has outperformed Artificial Neural Network (ANN) and Artificial Neural Network-Genetic Algorithm (ANN-GA) models. ANN-GSA achieved minimum testing mean square error of 7.41 × 10−13 and a maximum R-value of 1. Further, its convergence speed was faster than ANN-GA. GSA proved its ability to improve the performance of BPNN, which suffers from local minima problems.
Methyl 5-Imino-2-methyl-1,10a-dihydro-5H-chromeno[2,3-b]pyridine-3-carboxylate
Authors: Pinto Joana , Silva Artur M. S. , Silva Vera L. M.
Published: September 2022

Multicomponent reactions are valuable synthetic tools to deliver highly functionalized motifs starting from simple building blocks in only one step and in an atom-economical way. Herein we disclose the structure of a new and unexpected compound, the methyl 5-imino-2-methyl-1,10a-dihydro-5H-chromeno[2,3-b]pyridine-3-carboxylate, which was formed in the ohmic-heating-assisted multicomponent Hantzsch reaction of 3-formylchromone with methyl acetoacetate and ammonium acetate, in aqueous medium, in the presence of tetrabutylammonium bromide as phase transfer catalyst. The title compound was isolated with no need of chromatographic separation and was analyzed by nuclear magnetic resonance (1H and 13C-NMR, HSQC and HMBC) spectroscopy, mass spectrometry (MS) and high-resolution mass spectrometry (HRMS). Its formation as the main reaction product was observed when the reaction was performed using ohmic heating, which may lead to some speculations about the possible existence of specific effects of ohmic heating in the reactivity pathway because of the passage of an alternating electric current of high frequency within the reaction media, opening new opportunities for further investigations of the potential of this thermal processing method in organic synthesis and reactivity optimization.