bluuebunny/crossref_metadata_2025 huggingface dataset:
The “Local Neighborhood” Effect of Environmental Regulation on Green Innovation Efficiency: Evidence from China
Authors: Lyu Yanwei , Zhang Jinning , Yang Fei , Wu Di
Published: August 2022

Current research has generally concentrated on the motivations of environmental policies on local green innovation while ignoring the effect they may have on green innovation in neighboring places. To obtain a thorough understanding and explanation of the influencing mechanism of environmental regulation (ER) on green innovation efficiency (GIE), the super-slack based measure-data envelopment analysis (Super-SBM-DEA) method was applied to evaluate Chinese provinces’ GIE, a spatial Durbin model was developed to evaluate the effect of ER on GIE from the perspective of the “local neighborhood” effect, and a mediating effect model was built to analyze the transmission mechanism of the neighborhood effect of ER on GIE. The study indicated that China’s regional GIE is high in the east and low in the west, with large spatial variability and significant positive spatial clustering characteristics. The effect of ER on local GIE is “U” shaped, while the influence on green innovation efficiency in neighboring areas is an inverted “U” shape. The influence of environmental regulation on GIE in neighboring areas is mainly achieved through the transfer of local polluting industries to neighboring areas. Based on the results, policy recommendations from the perspectives of choosing environmental regulation tools and transferring polluting industries are made to promote and realize the coordinated development of ER and green innovation.
The Practice of Physical Activity on Psychological, Mental, Physical, and Social Wellbeing for Breast-Cancer Survivors: An Umbrella Review
Authors: Zanghì Marta , Petrigna Luca , Maugeri Grazia , D’Agata Velia , Musumeci Giuseppe
Published: August 2022

(1) Background: The number of breast-cancer patients and survivors is increasing in the last years. Physical activity seems to be a feasible and useful complementary intervention to improve the physical, psychological, and social spheres and decrease some symptoms, especially for survivors. Consequently, the objective of the present umbrella review was to analyze the efficacy of different physical-activity interventions in the physical, mental, and social spheres of breast-cancer survivors. (2) Methods: Systematic reviews and meta-analyses of randomized controlled trials on breast-cancer survivors and physical-activity effects were searched on the electronic databases PubMed, Web of Science, and Scopus till 9 August 2022. The quality of the studies included was evaluated, and the results were narratively analyzed. (3) Results: Physical-activity intervention generally improves the physical, mental, and social spheres of breast-cancer survivors, but the studies included present heterogeneity in the protocols adopted. (4) Conclusions: A well-structured and planned physical-activity intervention is useful for improvements in the physical, mental, and social spheres of breast-cancer survivors, but the studies presented high heterogeneity. Yoga seems to be the most effective physical intervention to complement medical therapy.
A Comparison of Vaping Behavior, Perceptions, and Dependence among Individuals Who Vape Nicotine, Cannabis, or Both
Authors: Saran Savreen K. , Salinas Kalin Z. , Foulds Jonathan , Kaynak Övgϋ , Hoglen Brianna , Houser Kenneth R. , Krebs Nicolle M. , Yingst Jessica M. , Allen Sophia I. , Bordner Candace R. , Hobkirk Andrea L.
Published: August 2022

Background: Electronic delivery systems (e.g., vapes, e-cigarettes) are now popular modes of cannabis and nicotine administration that are often used by the same individuals; however, we still know little about dual nicotine and cannabis vaping. Materials & Methods: An online convenience sample of adult nicotine and/or cannabis vape users residing in the United States completed a 60 min survey on sociodemographic characteristics, cannabis and/or nicotine vape use behaviors and dependence, reasons for vape use, and perceptions of benefits and harms. After data cleaning, we compared dual vs. nicotine-only and cannabis-only vape users with univariate statistics and step-wise hierarchical linear regression analyses. Additionally, we assessed the factor structure, internal consistency, and criterion and convergent validity of the Penn State Cannabis Vaping Dependence Index (PSCVDI). Results: The final sample included 357 dual, 40 cannabis, and 106 nicotine vape users. Compared to nicotine- and cannabis-only vapers, dual vapers started using their nicotine and cannabis vapes at a younger age (p < 0.001), used them for more years (p < 0.001), and were less likely to use their nicotine vape to replace combustible cigarettes (p = 0.047). Dual users vs. single-substance users did not have significantly higher nicotine or cannabis vape dependence scores after controlling for sociodemographic and use behaviors. The PSCVDI showed adequate validity for measuring cannabis vape dependence. Conclusions: This survey is the first to highlight important differences in vape use behaviors and reasons for use between dual vs. cannabis- and nicotine-only vape users.
How Does Manufacturing Agglomeration Affect Green Development? A Spatial and Nonlinear Perspective
Authors: Yuan Huaxi , Zou Longhui , Luo Xiangyong , Feng Yidai
Published: August 2022

Developing high-quality manufacturing industries and realizing green transformation are relatively pressing issues in the 21st century. Existing studies only focus on the economic or environmental effects of agglomeration, and the combined effects of manufacturing agglomeration have been neglected. Therefore, by referring to industrial agglomeration theory and constructing a theoretical analytical framework for manufacturing agglomeration and green development, this paper adopts the spatial panel Durbin model and mediating effect model with the panel data from China’s Yangtze River Economic Belt to empirically test the influence and its mechanism of manufacturing agglomeration on green development. The results show that: (1) There are significant temporal and spatial differences in green development in the Yangtze River Economic Belt. Overall, green development has maintained a steady increase on the timeline, but each region shows a hierarchical structure of “multiple peaks-multiple centers”. (2) There is a typical inverted U-shaped relationship between manufacturing agglomeration and green development, and the linear and quadratic coefficients of manufacturing agglomeration are −0.585 and −0.167, respectively. (3) Under the constraints of temporal, spatial, and urban heterogeneity, the impacts of manufacturing agglomeration on green development show significant differences. (4) Manufacturing agglomeration affects green development through three paths: the labor force upgrading effect, industrial structure upgrading effect, and technological innovation effect. The study can provide a theoretical and empirical basis for the green development of developing countries around the world.
Findings and Outcome of Transcatheter Right Ventricular Endomyocardial Biopsy and Hemodynamic Assessment in Children with Suspected Myocarditis or Cardiomyopathy
Authors: Callegari Alessia , Quandt Daniel , Schmitz Achim , Klingel Karin , Balmer Christian , Dave Hitendu , Kretschmar Oliver , Knirsch Walter
Published: August 2022

Objective: The study objective is assessing findings and outcome in children with suspected cardiomyopathy (CMP) or myocarditis undergoing cardiac catheterization with transcatheter right ventricular endomyocardial biopsy (RV-EMB). Methods: All consecutive children undergoing cardiac catheterization with RV-EMB for suspected CMP/myocarditis between 2002–2021 were analysed regarding clinical presentation, cardiac biomarkers, periprocedural management, hemodynamic, histological/immunohistological findings, and outcome. Results: Eighty-five RV-EMBs were performed in 81 patients at a median age of 6.8 (IQR 9.9) years and a bodyweight of 20 (32.2) kg. Histological/immunohistological findings of RV-EMB revealed dilated CMP in 10 (12%), chronic myocarditis in 28 (33%), healing myocarditis in 5 (6%), acute myocarditis in 9 (11%), other heart muscle diseases in 23 (27%) (7 restrictive CMP, 5 hypertrophic CMP, 4 toxic/anthracycline-induced CMP, 4 endocardfibroelastosis, 1 arrhythmogenic right ventricular CMP, 1 laminin CMP, 1 haemangioma), no conclusive histology in 7 (8%), and normal histology in 3 (4%) patients. Median LVEDP was 17 mmHg (IQR 9), LAP 15 mmHg (10), and PVR 1.83 (1.87) Wood Units/m2. There were 3 major complications (3%), all patients recovered without any sequelae. At follow-up (median 1153, IQR 1799 days) 47 (59%) patients were alive, 11 (13%) dead, 15 (18%) underwent cardiac transplantation, and 8 (9%) were lost to follow-up. Death/cardiac transplantation occurred within 3 years from RV-EMB. All patients with an acute myocarditis survived. NT-pro-BNP, echo parameters, and invasive hemodynamics correlate independently with death/cardiac transplant. Conclusion: Hemodynamic invasive data and morphological findings in RV-EMB complete clinical diagnosis in children with suspected CMP/myocarditis and provide important information for further clinical management.
Improving the Treatment Outcome of Naso-Orbito-Ethmoido-Maxillary Fractures Using Virtual Three-Dimensional Anthropometric Data
Authors: Roșu Andrei-Mihail , Șulea Daniela , Bandol Geanina , Cobzeanu Bogdan Mihail , Moisii Liliana , Severin Florentina , Cobzeanu Luiza-Maria , Negru Dragoș , Roșu Oana Cristina , Palade Dragoș Octavian , Costan Victor Vlad , Cobzeanu Mihail Dan
Published: August 2022

Background: Naso-orbito-ethmoido-maxillary (NOEM) fractures are usually the result of a high or moderate intensity impact to the upper midface. These types of fractures are difficult to treat and are frequently misdiagnosed. Craniometric analysis can be of real aid in the treatment of NOEM complex fractures by establishing midfacial proportions. Aim: This study aims to establish the distances between selected anthropometric points and midfacial proportions found in the adult Caucasian population and to determine if any differences exist between genders. Methodology: Measurements between anthropometric points, nasion (N), dacryon (D), infraorbital foramen (IOF), frontomalare orbitale (FMO), rhinion (Rhi) and porion (Po), were made on 3D models obtained using patients’ CT exams. Results: Significant differences were found between genders for the orbital dimensions represented by N–FMO (p = 0.000), N–IOF (p = 0.000), Rhi–FMO (p = 0.000), Rhi–IOF (p = 0.000), nose bridge width N–D (p = 0.001), Rhi–D (p = 0.016), D–D (p = 0.038) and the projection of the nose evaluated by Rhi–Po (p = 0.000), N–Po (p = 0.000), while a t-test showed that there are no significant differences between males and females for the N–Rhi (p = 0.254). Conclusions: The values of these measurements can be utilized during skeletal reconstruction after NOEM fractures, especially for bilateral comminuted fractures where no points of comparison are available.
The Detectability of the Viral RNA in Blood and Cerebrospinal Fluid of Patients with Tick-Borne Encephalitis
Authors: Grygorczuk Sambor , Dunaj-Małyszko Justyna , Czupryna Piotr , Sulik Artur , Toczyłowski Kacper , Siemieniako-Werszko Agnieszka , Żebrowska Agnieszka , Pancewicz Sławomir , Moniuszko-Malinowska Anna
Published: August 2022

Background: The detection rate of viral RNA in tick-borne encephalitis (TBE) is low and variable between studies, and its diagnostic/prognostic potential is not well defined. We attempted to detect RNA of TBE virus (TBEV) in body fluids of TBE patients. Methods: We studied 98 adults and 12 children with TBEV infection, stratified by the disease phase and presentation. EDTA blood and cerebrospinal fluid (CSF) samples were obtained upon hospital admission. RNA was extracted from freshly obtained plasma, concentrated leukocyte-enriched CSF, and whole blood samples, and real time PCR was performed with a Rotor-Gene Q thermocycler. Results: TBEV RNA was detected in (1) plasma of one (of the two studied) adult patients with an abortive infection, (2) plasma of two (of the two studied) adults in the peripheral phase of TBE, and (3) plasma and blood of an adult in the neurologic phase of TBE presenting as meningoencephalomyelitis. No CSF samples were TBEV RNA-positive. Conclusions: The detection of TBEV RNA in blood might be diagnostic in the peripheral phase of TBE. The lack of TBEV RNA in the CSF cellular fraction speaks against TBEV influx into the central nervous system with infiltrating leukocytes and is consistent with a relatively low intrathecal viral burden.
General Construction of Amine via Reduction of N=X (X = C, O, H) Bonds Mediated by Supported Nickel Boride Nanoclusters
Authors: Ke Da , Zhou Shaodong
Published: August 2022

Amines play an important role in synthesizing drugs, pesticides, dyes, etc. Herein, we report on an efficient catalyst for the general construction of amine mediated by nickel boride nanoclusters supported by a TS-1 molecular sieve. Efficient production of amines was achieved via catalytic hydrogenation of N=X (X = C, O, H) bonds. In addition, the catalyst maintains excellent performance upon recycling. Compared with the previous reports, the high activity, simple preparation and reusability of the Ni-B catalyst in this work make it promising for industrial application in the production of amines.
Oxidative Stress in Amyotrophic Lateral Sclerosis: Synergy of Genetic and Environmental Factors
Authors: Motataianu Anca , Serban Georgiana , Barcutean Laura , Balasa Rodica
Published: August 2022

Amyotrophic lateral sclerosis (ALS) is a grievous neurodegenerative disease whose survival is limited to only a few years. In spite of intensive research to discover the underlying mechanisms, the results are fairly inconclusive. Multiple hypotheses have been regarded, including genetic, molecular, and cellular processes. Notably, oxidative stress has been demonstrated to play a crucial role in ALS pathogenesis. In addition to already recognized and exhaustively studied genetic mutations involved in oxidative stress production, exposure to various environmental factors (e.g., electromagnetic fields, solvents, pesticides, heavy metals) has been suggested to enhance oxidative damage. This review aims to describe the main processes influenced by the most frequent genetic mutations and environmental factors concurring in oxidative stress occurrence in ALS and the potential therapeutic molecules capable of diminishing the ALS related pro-oxidative status.
Systematic Analysis and Functional Characterization of R2R3-MYB Genes in Scutellaria baicalensis Georgi
Authors: Wang Wentao , Hu Suying , Zhang Caijuan , Yang Jing , Zhang Tong , Wang Donghao , Cao Xiaoyan , Wang Zhezhi
Published: August 2022

R2R3-MYB transcription factors participate in multiple critical biological processes, particularly as relates to the regulation of secondary metabolites. The dried root of Scutellaria baicalensis Georgi is a traditional Chinese medicine and possesses various bioactive attributes including anti-inflammation, anti-HIV, and anti-COVID-19 properties due to its flavonoids. In the current study, a total of 95 R2R3-MYB genes were identified in S. baicalensis and classified into 34 subgroups, as supported by similar exon–intron structures and conserved motifs. Among them, 93 R2R3-SbMYBs were mapped onto nine chromosomes. Collinear analysis revealed that segmental duplications were primarily responsible for driving the evolution and expansion of the R2R3-SbMYB gene family. Synteny analyses showed that the ortholog numbers of the R2R3-MYB genes between S. baicalensis and other dicotyledons had a higher proportion compared to that which is found from the monocotyledons. RNA-seq data indicated that the expression patterns of R2R3-SbMYBs in different tissues were different. Quantitative reverse transcriptase-PCR (qRT-PCR) analysis showed that 36 R2R3-SbMYBs from different subgroups exhibited specific expression profiles under various conditions, including hormone stimuli treatments (methyl jasmonate and abscisic acid) and abiotic stresses (drought and cold shock treatments). Further investigation revealed that SbMYB18/32/46/60/70/74 localized in the nucleus, and SbMYB18/32/60/70 possessed transcriptional activation activity, implying their potential roles in the regulatory mechanisms of various biological processes. This study provides a comprehensive understanding of the R2R3-SbMYBs gene family and lays the foundation for further investigation of their biological function.
Conformational Changes of α-Crystallin Proteins Induced by Heat Stress
Authors: Chang Yu-Yung , Hsieh Meng-Hsuan , Huang Yen-Chieh , Chen Chun-Jung , Lee Ming-Tao
Published: August 2022

α-crystallin is a major structural protein in the eye lenses of vertebrates that is composed of two relative subunits, αA and αB crystallin, which function in maintaining lens transparency. As a member of the small heat-shock protein family (sHsp), α-crystallin exhibits chaperone-like activity to prevent the misfolding or aggregation of critical proteins in the lens, which is associated with cataract disease. In this study, high-purity αA and αB crystallin proteins were expressed from E. coli and purified by affinity and size-exclusion chromatography. The size-exclusion chromatography experiment showed that both αA and αB crystallins exhibited oligomeric complexes in solution. Here, we present the structural characteristics of α-crystallin proteins from low to high temperature by combining circular dichroism (CD) and small-angle X-ray scattering (SAXS). Not only the CD data, but also SAXS data show that α-crystallin proteins exhibit transition behavior on conformation with temperature increasing. Although their protein sequences are highly conserved, the analysis of their thermal stability showed different properties in αA and αB crystallin. In this study, taken together, the data discussed were provided to demonstrate more insights into the chaperone-like activity of α-crystallin proteins.
Transcriptome Analysis and Intraspecific Variation in Spanish Fir (Abies pinsapo Boiss.)
Authors: Ortigosa Francisco , Ávila Concepción , Rubio Lourdes , Álvarez-Garrido Lucía , Carreira José A. , Cañas Rafael A. , Cánovas Francisco M.
Published: August 2022

Spanish fir (Abies pinsapo Boiss.) is an endemic, endangered tree that has been scarcely investigated at the molecular level. In this work, the transcriptome of Spanish fir was assembled, providing a large catalog of expressed genes (22,769), within which a high proportion were full-length transcripts (12,545). This resource is valuable for functional genomics studies and genome annotation in this relict conifer species. Two intraspecific variations of A. pinsapo can be found within its largest population at the Sierra de las Nieves National Park: one with standard green needles and another with bluish-green needles. To elucidate the causes of both phenotypes, we studied different physiological and molecular markers and transcriptome profiles in the needles. “Green” trees showed higher electron transport efficiency and enhanced levels of chlorophyll, protein, and total nitrogen in the needles. In contrast, needles from “bluish” trees exhibited higher contents of carotenoids and cellulose. These results agreed with the differential transcriptomic profiles, suggesting an imbalance in the nitrogen status of “bluish” trees. Additionally, gene expression analyses suggested that these differences could be associated with different epigenomic profiles. Taken together, the reported data provide new transcriptome resources and a better understanding of the natural variation in this tree species, which can help improve guidelines for its conservation and the implementation of adaptive management strategies under climatic change.
Role of Ion Channels in the Chemotransduction and Mechanotransduction in Digestive Function and Feeding Behavior
Authors: Zhu Zhenya , Wu Yuhao , Liu Ziyu , Li Yuezhou , Jiang Mizu
Published: August 2022

The gastrointestinal tract constantly communicates with the environment, receiving and processing a wide range of information. The contents of the gastrointestinal tract and the gastrointestinal tract generate mechanical and chemical signals, which are essential for regulating digestive function and feeding behavior. There are many receptors here that sense intestinal contents, including nutrients, microbes, hormones, and small molecule compounds. In signal transduction, ion channels are indispensable as an essential component that can generate intracellular ionic changes or electrical signals. Ion channels generate electrical activity in numerous neurons and, more importantly, alter the action of non-neurons simply and effectively, and also affect satiety, molecular secretion, intestinal secretion, and motility through mechanisms of peripheral sensation, signaling, and altered cellular function. In this review, we focus on the identity of ion channels in chemosensing and mechanosensing in the gastrointestinal tract.
Synucleinopathy in Amyotrophic Lateral Sclerosis: A Potential Avenue for Antisense Therapeutics?
Authors: Roberts Bradley , Theunissen Frances , Mastaglia Francis L. , Akkari P. Anthony , Flynn Loren L.
Published: August 2022

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease classified as both a neurodegenerative and neuromuscular disorder. With a complex aetiology and no current cure for ALS, broadening the understanding of disease pathology and therapeutic avenues is required to progress with patient care. Alpha-synuclein (αSyn) is a hallmark for disease in neurodegenerative disorders, such as Parkinson’s disease, Lewy body dementia, and multiple system atrophy. A growing body of evidence now suggests that αSyn may also play a pathological role in ALS, with αSyn-positive Lewy bodies co-aggregating alongside known ALS pathogenic proteins, such as SOD1 and TDP-43. This review endeavours to capture the scope of literature regarding the aetiology and development of ALS and its commonalities with “synucleinopathy disorders”. We will discuss the involvement of αSyn in ALS and motor neuron disease pathology, and the current theories and strategies for therapeutics in ALS treatment, as well as those targeting αSyn for synucleinopathies, with a core focus on small molecule RNA technologies.
The Function of N-Myc Downstream-Regulated Gene 2 (NDRG2) as a Negative Regulator in Tumor Cell Metastasis
Authors: Lee Ki Won , Lim Seyeon , Kim Kwang Dong
Published: August 2022

N-myc downstream-regulated gene 2 (NDRG2) is a tumor-suppressor gene that suppresses tumorigenesis and metastasis of tumors and increases sensitivity to anti-cancer drugs. In this review, we summarize information on the clinicopathological characteristics of tumor patients according to NDRG2 expression in various tumor tissues and provide information on the metastasis inhibition-related cell signaling modulation by NDRG2. Loss of NDRG2 expression is a prognostic factor that correlates with TNM grade and tumor metastasis and has an inverse relationship with patient survival in various tumor patients. NDRG2 inhibits cell signaling, such as AKT-, NF-κB-, STAT3-, and TGF-β-mediated signaling, to induce tumor metastasis, and induces activation of GSK-3β which has anti-tumor effects. Although NDRG2 operates as an adaptor protein to mediate the interaction between kinases and phosphatases, which is essential in regulating cell signaling related to tumor metastasis, the molecular mechanism of NDRG2 as an adapter protein does not seem to be fully elucidated. This review aims to assist the research design regarding NDRG2 function as an adaptor protein and suggests NDRG2 as a molecular target to inhibit tumor metastasis and improve the prognosis in tumor patients.
Frontiers in Antimicrobial Biomaterials
Authors: Felgueiras Helena P.
Published: August 2022

Biomaterials can be used as implantable devices or drug delivery platforms, which have significant impacts on the patient’s quality of life [...]
Evaluation of the Therapeutic Potential of Histone Deacetylase 6 Inhibitors for Primary and Metastatic Uveal Melanoma
Authors: Sundaramurthi Husvinee , Giricz Zoltán , Kennedy Breandán N.
Published: August 2022

Patients diagnosed with metastatic uveal melanoma (MUM) have a poor survival prognosis. Unfortunately for this rare disease, there is no known cure and suitable therapeutic options are limited. HDAC6 inhibitors (HDAC6i) are currently in clinical trials for other cancers and show potential beneficial effects against tumor cell survival in vitro and in vivo. In MUM cells, HDAC6i show an anti-proliferative effect in vitro and in preclinical xenograft models. The use of HDAC6 inhibitors as a treatment option for MUM should be explored further. Therefore, this review discusses (1) what is known about HDAC6i in MUM and (2) whether HDAC6 inhibitors offer a potential therapeutic option for MUM.
Drug-Loaded Polymeric Micelles Based on Smart Biocompatible Graft Copolymers with Potential Applications for the Treatment of Glaucoma
Authors: Ozturk Manuela-Ramona (Blanaru) , Popa Marcel , Rata Delia Mihaela , Cadinoiu Anca Niculina , Parfait Frederique , Delaite Christelle , Atanase Leonard Ionut , Solcan Carmen , Daraba Oana Maria
Published: August 2022

Glaucoma is the second leading cause of blindness in the world. Despite the fact that many treatments are currently available for eye diseases, the key issue that arises is the administration of drugs for long periods of time and the increased risk of inflammation, but also the high cost of eye surgery. Consequently, numerous daily administrations are required, which reduce patient compliance, and even in these conditions, the treatment of eye disease is too ineffective. Micellar polymers are core–shell nanoparticles formed by the self-assembly of block or graft copolymers in selective solvents. In the present study, polymeric micelles (PMs) were obtained by dialysis from smart biocompatible poly(ε-caprolactone)-poly(N-vinylcaprolactam-co-N-vinylpyrrolidone) [PCL-g-P(NVCL-co-NVP)] graft copolymers. Two copolymers with different molar masses were studied, and a good correlation was noted between the micellar sizes and the total degree of polymerisation (DPn) of the copolymers. The micelles formed by Cop A [PCL120-g-P(NVCL507-co-NVP128)], with the lowest total DPn, have a Z-average value of 39 nm, whereas the micellar sizes for Cop B [PCL120-g-P(NVCL1253-co-NVP139)] are around 47 nm. These PMs were further used for the encapsulation of two drugs with applications for the treatment of eye diseases. After the encapsulation of Dorzolamide, a slight increase in micellar sizes was noted, whereas the encapsulation of Indomethacin led to a decrease in these sizes. Using dynamic light scattering, it was proved that both free and drug-loaded PMs are stable for 30 days of storage at 4 °C. Moreover, in vitro biological tests demonstrated that the obtained PMs are both haemo- and cytocompatible and thus can be used for further in vivo tests. The designed micellar system proved its ability to release the encapsulated drugs in vitro, and the results obtained were validated by in vivo tests carried out on experimental animals, which proved its high effectiveness in reducing intraocular pressure.
Identification and Characterization of Jasmonic Acid Biosynthetic Genes in Salvia miltiorrhiza Bunge
Authors: Xue Xiaoshan , Li Runqing , Zhang Caijuan , Li Wenna , Li Lin , Hu Suying , Niu Junfeng , Cao Xiaoyan , Wang Donghao , Wang Zhezhi
Published: August 2022

Jasmonic acid (JA) is a vital plant hormone that performs a variety of critical functions for plants. Salvia miltiorrhiza Bunge (S. miltiorrhiza), also known as Danshen, is a renowned traditional Chinese medicinal herb. However, no thorough and systematic analysis of JA biosynthesis genes in S. miltiorrhiza exists. Through genome-wide prediction and molecular cloning, 23 candidate genes related to JA biosynthesis were identified in S. miltiorrhiza. These genes belong to four families that encode lipoxygenase (LOX), allene oxide synthase (AOS), allene oxide cyclase (AOC), and 12-OPDA reductase3 (OPR3). It was discovered that the candidate genes for JA synthesis of S. miltiorrhiza were distinct and conserved, in contrast to related genes in other plants, by evaluating their genetic structures, protein characteristics, and phylogenetic trees. These genes displayed tissue-specific expression patterns concerning to methyl jasmonate (MeJA) and wound tests. Overall, the results of this study provide valuable information for elucidating the JA biosynthesis pathway in S. miltiorrhiza by comprehensive and methodical examination.
Senescence Markers in Peripheral Blood Mononuclear Cells in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease
Authors: Salech Felipe , SanMartín Carol D. , Concha-Cerda Jorge , Romero-Hernández Esteban , Ponce Daniela P. , Liabeuf Gianella , Rogers Nicole K. , Murgas Paola , Bruna Bárbara , More Jamileth , Behrens María I.
Published: August 2022

Recent studies suggest that cellular senescence plays a role in Alzheimer’s Disease (AD) pathogenesis. We hypothesize that cellular senescence markers might be tracked in the peripheral tissues of AD patients. Senescence hallmarks, including altered metabolism, cell-cycle arrest, DNA damage response (DDR) and senescence secretory associated phenotype (SASP), were measured in peripheral blood mononuclear cells (PBMCs) of healthy controls (HC), amnestic mild cognitive impairment (aMCI) and AD patients. Senescence-associated βeta-galactosidase (SA-β-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry, while IL-6 and IL-8 mRNA were analyzed by qPCR, and phosphorylated H2A histone family member X (γH2AX) was analyzed by immunofluorescence. Senescent cells in the brain tissue were determined with lipofuscin staining. An increase in the number of senescent cells was observed in the frontal cortex and hippocampus of advanced AD patients. PBMCs of aMCI patients, but not in AD, showed increased SA-β-Gal compared with HCs. aMCI PBMCs also had increased IL-6 and IL8 mRNA expression and number of cells arrested at G0-G1, which were absent in AD. Instead, AD PBMCs had significantly increased p16 and p53 expression and decreased γH2Ax activity compared with HC. This study reports that several markers of cellular senescence can be measured in PBMCs of aMCI and AD patients.
Lipidomics-Assisted GWAS (lGWAS) Approach for Improving High-Temperature Stress Tolerance of Crops
Authors: Pranneshraj Velumani , Sangha Manjeet Kaur , Djalovic Ivica , Miladinovic Jegor , Djanaguiraman Maduraimuthu
Published: August 2022

High-temperature stress (HT) over crop productivity is an important environmental factor demanding more attention as recent global warming trends are alarming and pose a potential threat to crop production. According to the Sixth IPCC report, future years will have longer warm seasons and frequent heat waves. Thus, the need arises to develop HT-tolerant genotypes that can be used to breed high-yielding crops. Several physiological, biochemical, and molecular alterations are orchestrated in providing HT tolerance to a genotype. One mechanism to counter HT is overcoming high-temperature-induced membrane superfluidity and structural disorganizations. Several HT lipidomic studies on different genotypes have indicated the potential involvement of membrane lipid remodelling in providing HT tolerance. Advances in high-throughput analytical techniques such as tandem mass spectrometry have paved the way for large-scale identification and quantification of the enormously diverse lipid molecules in a single run. Physiological trait-based breeding has been employed so far to identify and select HT tolerant genotypes but has several disadvantages, such as the genotype-phenotype gap affecting the efficiency of identifying the underlying genetic association. Tolerant genotypes maintain a high photosynthetic rate, stable membranes, and membrane-associated mechanisms. In this context, studying the HT-induced membrane lipid remodelling, resultant of several up-/down-regulations of genes and post-translational modifications, will aid in identifying potential lipid biomarkers for HT tolerance/susceptibility. The identified lipid biomarkers (LIPIDOTYPE) can thus be considered an intermediate phenotype, bridging the gap between genotype–phenotype (genotype–LIPIDOTYPE–phenotype). Recent works integrating metabolomics with quantitative genetic studies such as GWAS (mGWAS) have provided close associations between genotype, metabolites, and stress-tolerant phenotypes. This review has been sculpted to provide a potential workflow that combines MS-based lipidomics and the robust GWAS (lipidomics assisted GWAS-lGWAS) to identify membrane lipid remodelling related genes and associations which can be used to develop HS tolerant genotypes with enhanced membrane thermostability (MTS) and heat stable photosynthesis (HP).
KRAS-Mutant Non-Small-Cell Lung Cancer: From Past Efforts to Future Challenges
Authors: Ceddia Serena , Landi Lorenza , Cappuzzo Federico
Published: August 2022

KRAS is the most frequently mutated oncogene identified in human cancers. Despite the numerous efforts to develop effective specific inhibitors against KRAS, this molecule has remained “undruggable” for decades. The development of direct KRAS inhibitors, such as sotorasib, the first FDA-approved drug targeting KRAS G12C, or adagrasib, was made possible with the discovery of a small pocket in the binding switch II region of KRAS G12C. However, a new challenge is represented by the necessity to overcome resistance mechanisms to KRAS inhibitors. Another area to be explored is the potential role of co-mutations in the selection of the treatment strategy, particularly in the setting of immune checkpoint inhibitors. The aim of this review was to analyze the state-of-the-art of KRAS mutations in non-small-cell lung cancer by describing the biological structure of KRAS and exploring the clinical relevance of KRAS as a prognostic and predictive biomarker. We reviewed the different treatment approaches, focusing on the novel therapeutic strategies for the treatment of KRAS-mutant lung cancers.
Advances in Metal-Organic Frameworks MIL-101(Cr)
Authors: Zou Minmin , Dong Ming , Zhao Tian
Published: August 2022

MIL-101(Cr) is one of the most well-studied chromium-based metal–organic frameworks, which consists of metal chromium ion and terephthalic acid ligand. It has an ultra-high specific surface area, large pore size, good thermal/chemical/water stability, and contains unsaturated Lewis acid sites in its structure. Due to the physicochemical properties and structural characteristics, MIL-101(Cr) has a wide range of applications in aqueous phase adsorption, gas storage and separation, and catalysis. In this review, the latest synthesis of MIL-101(Cr) and its research progress in adsorption and catalysis are reviewed.
Uromodulin Regulates Murine Aquaporin−2 Activity via Thick Ascending Limb–Collecting Duct Cross−Talk during Water Deprivation
Authors: Takata Tomoaki , Hamada Shintaro , Mae Yukari , Iyama Takuji , Ogihara Ryohei , Seno Misako , Nakamura Kazuomi , Takata Miki , Sugihara Takaaki , Isomoto Hajime
Published: August 2022

Uromodulin, a urinary protein synthesized and secreted from the thick ascending limb (TAL) of the loop of Henle, is associated with hypertension through the activation of sodium reabsorption in the TAL. Uromodulin is a potential target for hypertension treatment via natriuresis. However, its biological function in epithelial cells of the distal nephron segment, particularly the collecting duct, remains unknown. Herein, we examined the regulation of uromodulin production during water deprivation in vivo as well as the effect of uromodulin on the activity of the water channel aquaporin−2 (AQP2) in vitro and in vivo using transgenic mice. Water deprivation upregulated uromodulin production; immunofluorescence experiments revealed uromodulin adhesion on the apical surface of the collecting duct. Furthermore, the activation of AQP2 was attenuated in mice lacking uromodulin. Uromodulin enhanced the phosphorylation and apical trafficking of AQP2 in mouse collecting duct cells treated with the vasopressin analog dDAVP. The uromodulin-induced apical trafficking of AQP2 was attenuated via endocytosis inhibitor treatment, suggesting that uromodulin activates AQP2 through the suppression of endocytosis. This study provides novel insights into the cross−talk between TAL and the collecting duct, and indicates that the modulation of uromodulin is a promising approach for diuresis and hypertension treatment.
Cholesteryl Ester Transfer Protein Inhibition Reduces Major Adverse Cardiovascular Events by Lowering Apolipoprotein B Levels
Authors: Nelson Adam J. , Sniderman Allan D. , Ditmarsch Marc , Dicklin Mary R. , Nicholls Stephen J. , Davidson Michael H. , Kastelein John J. P.
Published: August 2022

Cholesteryl ester transfer protein (CETP) facilitates the exchange of cholesteryl esters and triglycerides (TG) between high-density lipoprotein (HDL) particles and TG-rich, apolipoprotein (apo) B-containing particles. Initially, these compounds were developed to raise plasma HDL cholesterol (HDL-C) levels, a mechanism that was previously thought to lower the risk of atherosclerotic cardiovascular disease (ASCVD). More recently, the focus changed and the use of pharmacologic CETP inhibitors to reduce low-density lipoprotein cholesterol (LDL-C), non-HDL-C and apoB concentrations became supported by several lines of evidence from animal models, observational investigations, randomized controlled trials and Mendelian randomization studies. Furthermore, a cardiovascular outcome trial of anacetrapib demonstrated that CETP inhibition significantly reduced the risk of major coronary events in patients with ASCVD in a manner directly proportional to the substantial reduction in LDL-C and apoB. These data have dramatically shifted the attention on CETP away from raising HDL-C instead to lowering apoB-containing lipoproteins, which is relevant since the newest CETP inhibitor, obicetrapib, reduces LDL-C by up to 51% and apoB by up to 30% when taken in combination with a high-intensity statin. An ongoing cardiovascular outcome trial of obicetrapib in patients with ASCVD is expected to provide further evidence of the ability of CETP inhibitors to reduce major adverse cardiovascular events by lowering apoB. The purpose of the present review is to provide an up-to-date understanding of CETP inhibition and its relationship to ASCVD risk reduction.
Resistance Training Improves Beta Cell Glucose Sensing and Survival in Diabetic Models
Authors: Bronczek Gabriela Alves , Soares Gabriela Moreira , Marmentini Carine , Boschero Antonio Carlos , Costa-Júnior José Maria
Published: August 2022

Resistance training increases insulin secretion and beta cell function in healthy mice. Here, we explored the effects of resistance training on beta cell glucose sensing and survival by using in vitro and in vivo diabetic models. A pancreatic beta cell line (INS-1E), incubated with serum from trained mice, displayed increased insulin secretion, which could be linked with increased expression of glucose transporter 2 (GLUT2) and glucokinase (GCK). When cells were exposed to pro-inflammatory cytokines (in vitro type 1 diabetes), trained serum preserved both insulin secretion and GCK expression, reduced expression of proteins related to apoptotic pathways, and also protected cells from cytokine-induced apoptosis. Using 8-week-old C57BL/6 mice, turned diabetic by multiple low doses of streptozotocin, we observed that resistance training increased muscle mass and fat deposition, reduced fasting and fed glycemia, and improved glucose tolerance. These findings may be explained by the increased fasting and fed insulinemia, along with increased beta cell mass and beta cell number per islet, observed in diabetic-trained mice compared to diabetic sedentary mice. In conclusion, we believe that resistance training stimulates the release of humoral factors which can turn beta cells more resistant to harmful conditions and improve their response to a glucose stimulus.
Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study
Authors: Androutsakos Theodoros , Bakasis Athanasios-Dimitrios , Pouliakis Abraham , Gazouli Maria , Vallilas Christos , Hatzis Gregorios
Published: August 2022

Hepatocellular carcinoma (HCC) is the most common primary liver tumor leading to significant morbidity and mortality; its exact genetic background is largely unrecognized. Toll-like receptor-4 (TLR4) reacts with lipopolysaccharides, molecules found in the outer membrane of Gram-negative bacteria. In damaged liver, TLR4 expression is upregulated, leading to hepatic inflammation and injury. We tried to investigate the role of the two most common single-nucleotide polymorphisms (SNPs) of TLR4 in HCC-genesis. Aged > 18 years old, cirrhotic patients were included in this study. Exclusion criteria were non-HCC tumors and HIV co-infection. TLR4 SNPs association with HCC occurrence was the primary endpoint, and associations with all-cause and liver-related mortality, as well as time durations between diagnosis of cirrhosis and HCC development or death and diagnosis of HCC and death were secondary endpoints. A total of 52 out of 260 included patients had or developed HCC. TLR4 SNPs showed no correlation with primary or secondary endpoints, except for the shorter duration between HCC development and death in patients with TLR4 mutations. Overall, TLR4 SNPs showed no correlation with carcinogenesis or deaths in patients with liver cirrhosis; patients with TLR4 SNPs that developed HCC had lower survival rates, a finding that should be further evaluated.
Mechanical Disturbance of Osteoclasts Induces ATP Release That Leads to Protein Synthesis in Skeletal Muscle through an Akt-mTOR Signaling Pathway
Authors: Morales-Jiménez Camilo , Balanta-Melo Julián , Arias-Calderón Manuel , Hernández Nadia , Gómez-Valenzuela Fernán , Escobar Alejandro , Jaimovich Enrique , Buvinic Sonja
Published: August 2022

Muscle and bone are tightly integrated through mechanical and biochemical signals. Osteoclasts are cells mostly related to pathological bone loss; however, they also start physiological bone remodeling. Therefore, osteoclast signals released during bone remodeling could improve both bone and skeletal muscle mass. Extracellular ATP is an autocrine/paracrine signaling molecule released by bone and muscle cells. Then, in the present work, it was hypothesized that ATP is a paracrine mediator released by osteoclasts and leads to skeletal muscle protein synthesis. RAW264.7-derived osteoclasts were co-cultured in Transwell® chambers with flexor digitorum brevis (FDB) muscle isolated from adult BalbC mice. The osteoclasts at the upper chamber were mechanically stimulated by controlled culture medium perturbation, resulting in a two-fold increase in protein synthesis in FDB muscle at the lower chamber. Osteoclasts released ATP to the extracellular medium in response to mechanical stimulation, proportional to the magnitude of the stimulus and partly dependent on the P2X7 receptor. On the other hand, exogenous ATP promoted Akt phosphorylation (S473) in isolated FDB muscle in a time- and concentration-dependent manner. ATP also induced phosphorylation of proteins downstream Akt: mTOR (S2448), p70S6K (T389) and 4E-BP1 (T37/46). Exogenous ATP increased the protein synthesis rate in FDB muscle 2.2-fold; this effect was blocked by Suramin (general P2X/P2Y antagonist), LY294002 (phosphatidylinositol 3 kinase inhibitor) and Rapamycin (mTOR inhibitor). These blockers, as well as apyrase (ATP metabolizing enzyme), also abolished the induction of FDB protein synthesis evoked by mechanical stimulation of osteoclasts in the co-culture model. Therefore, the present findings suggest that mechanically stimulated osteoclasts release ATP, leading to protein synthesis in isolated FDB muscle, by activating the P2-PI3K-Akt-mTOR pathway. These results open a new area for research and clinical interest in bone-to-muscle crosstalk in adaptive processes related to muscle use/disuse or in musculoskeletal pathologies.
Tumor-Specific Immunoenhancing Effects after Local Cryoablation for Metastatic Bone Tumor in a Mouse Model
Authors: Annen Ryohei , Kato Satoshi , Demura Satoru , Miwa Shinji , Yokka Akira , Shinmura Kazuya , Yokogawa Noriaki , Yonezawa Noritaka , Kobayashi Motoya , Kurokawa Yuki , Gabata Toshifumi , Tsuchiya Hiroyuki
Published: August 2022

We investigated the abscopal effect after cryoablation (CA) on bone metastasis using a mouse model. Breast cancer cells were implanted in the bilateral tibiae of mice. The left tumor was treated locally with CA, and the right abscopal tumor (AT) was left untreated. The mice were divided into four groups based on the combination of CA and intraperitoneal administration of anti-PD-1 antibody (PD) as treatment interventions (Control, CA, PD, and CA + PD). The reduction ratio of the size of AT, the quantitative immune effects at enzyme-linked immunospot (ELISPOT) assay, and the intensity of infiltration of immune-related cells to AT were compared among the groups. CA alone showed a significant immunoenhancing effect on the volume change ratio of AT from day 0 to day 14 (Control-CA: p < 0.05), ELISPOT assay (Control-CA: p < 0.01), and CD4+ cell count in immunostaining (Control-CA: p < 0.05). CA alone showed no significant immunoenhancing effect on CD8+ and Foxp3+ cell counts in immunostaining, but the combination of CA and PD showed a significant immunoenhancing effect (Control-CA + PD: p < 0.01 [CD8, Foxp3]). The results suggested that the abscopal effect associated with the local cryotherapy of metastatic bone tumors was activated by CA and enhanced by its combination with PD.