bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-Dimensional Fault Model and Activity in the Arc-Shaped Tectonic Belt in the Northeastern Margin of the Tibetan Plateau
Authors: Li Liguo , Li Zhigang , Sun Chuang , Wang Weitao , Dai Xiangming , Zhang Yipeng , Liang Hao , Xu Binbin , Wu Xiancan , Lv Liangwei
Published: May 2022

The arc-shaped tectonic belt, located in the northeastern margin of the Tibetan Plateau, is one of the leading edges of the plateau’s outward growth and uplift expansion, with a large number of active faults and frequent seismic activity. Researchers have carried out numerous studies on active faults in this region, and a wealth of reliable basic data has been accumulated. However, integrating multidisciplinary data to establish a 3D geometrical structure model that is concerned about seismogenic tectonics and can be tested, has become the key to restricting the regional seismic hazard evaluation. Based on a series of published active tectonic research, we analyze in detail the surface and deep coupling relationships of the major active faults in this region and establish three sets of 3D fault structure models, which are built respectively by active fault mapping and dip angles (the V1 model), 7 magnetotelluric profiles and 7 auxiliary profiles (the V2 model), and multi-source data (the V3 model) and continuously close to the real geological facts. From the model perspective, it is suggested that the controversial Haiyuan fault is a crustal-scale left-slip fault and the shape of the Liupanshan fault reflects the absorption of the left-slip component of the Haiyuan fault. Comparing the same fault plane of these three models, we find that the V3 model is more consistent with geological facts, showing that by assisting the multi-source data 3D geological modeling technique we can establish a 3D geological model closest to the real regional structure. Finally, combining the V3 model, the fault segmentation, and the empirical formulas of the moment magnitude-rupture parameters, we segment the faults and calculate the potential moment magnitudes of the major active faults in the study region. The faults with relatively higher seismic hazards are the Liupanshan fault, the southeastern segment of the Xiangshan-Tianjingshan fault, the westernmost segment of the Haiyuan fault, and the West Qinling fault, of which the estimated potential moment magnitudes are generally more than 7.0. Our study provides a referenced 3D geological model for exploring the deep structures of the region, regional geological research, and earthquake disaster prevention.
Origin and Trace of Hydrothermal Calcites in the Hydrocarbon Reservoirs Intruded by Diabase: Evidence From Strontium and Oxygen Isotopic Proxies
Authors: Liu Chao , Xue Rui , Jia Zhiwei , Zhao Xiaodong , Wang Ke , Yang Yong , He Junhao , Liu Ping , Liu Zhigang
Published: May 2022

Thermal contact clastic rocks provide a new potential type of hydrocarbon reservoirs for expanding exploration targets. However, the development mechanism of this type of reservoir remains enigmatic. Authigenic hydrothermal carbonates associated with magmatism exert significant controls over physical properties of the contact reservoirs. Therefore, the origin and trace of hydrothermal carbonates are key issues for reservoir development elucidation of thermal contact reservoirs and need to be further investigated. The current study takes the typical hydrocarbon area of thermal contact metasandstone reservoirs from the Funing Formation, northern Slope of Gaoyou sag, as a case study, aiming to unravel the origin and trace of authigenic hydrothermal calcites developed in thermal contact reservoirs, mainly using strontium and oxygen isotopic geochemistry proxies combined with petrological and mineralogical analyses. Authigenic hydrothermal calcites are distinguished, and their distribution characteristics are examined in thermal contact rocks. Subsequently, the origin and migration trace of the hydrothermal-related calcites are clarified. This study has significant implications for intensive understanding of reservoir development mechanism and reservoir evaluation and prediction of thermal contact clastic rocks.
What Can Professional Scientific Societies Do to Improve Diversity, Equity, and Inclusion: A Case Study of the American Elasmobranch Society
Authors: Shiffman David S. , Arguedas Álvarez Triana , Bangley Charles W. , Boyt Reilly , Côté Isabelle M. , Daly-Engel Toby S. , Davis Alexandra C. D. , Gaskins Leo C. , Graham Jasmin , Graham R. T. , Johri Shaili , Macdonald Catherine C. , Paig-Tran E. W. Misty , Roca Alberto I. , Schwieterman Gail D. , Whitenack Lisa B. , Wiley Tonya R. , Ferry Lara A.
Published: May 2022

Scientific professional societies are reviewing diversity, equity, and inclusion (DEI) practices and policies in response to recent calls for much-needed change. Organizations like scientific professional societies contribute to establishing disciplinary norms, and can influence the diversity of disciplinary workforces in multiple ways through both action and inaction. This paper examines these issues using the American Elasmobranch Society (AES), a medium-sized professional scientific society, as a case study. It consists of three parts: (1) an analysis of the demographics of AES members, leaders, and award winners; (2) an evaluation of a diversity initiative created by the society which includes a survey of program alumni focusing on potential improvements to the program; and (3) a synthesis of recommendations of steps that AES and similarly sized societies can take to better support DEI goals. AES’s membership in recent years is more than half women, but 71.5% of all leadership positions in the Society’s history (including all but two Presidents) have been held by men since the society was founded in 1983. AES’s membership has significantly fewer Black/African-American members than the United States scientific workforce overall, with just 1 member out of over 400 identifying as Black in 2019, and 86.6% of Society leadership positions have been held by white-presenting members. The Society’s diversity initiative has led to some limited professional benefits for awardees, but could benefit from additional resources and support to enact suggested expansions and improvements. We provide a series of actionable recommendations that will make the annual meetings of societies like AES, and the field of chondrichthyan science, safer and more inclusive.
High-Performance Sensorless Operation of Motor-Generator Set With an Improved Torque-Ripple Minimization Strategy
Authors: Hussien Mohamed G. , Salem Elbarbary Zakaria M. , Hassan Abd El-Wahab
Published: May 2022

This paper aims at minimizing the torque ripples using variable switching frequency technique of PWM (VSFPWM) of the surface-mounted permanent magnet synchronous motor (SPMSM) for a high-performance operation of a motor-generator set. The proposed system was employed to drive the promising brushless doubly-fed reluctance generator (BDFRG) with a sensorless vector-control topology. Validity of the rotor-position/speed estimation critically affects most of the sensorless control strategies. Therefore, a simple estimation method is proposed for the positioning of rotor of the generator. The presented control strategies are confirmed with some of the obtained results to assure its controllability.
Coordinated Management and Control Strategy in the Low-Voltage Distribution Network Based on the Cloud-Edge Collaborative Mechanism
Authors: Gao Jiuguo , Lu Yang , Wu Bin , Zheng Ting , Zhu Yu , Zhang Zhixiang
Published: May 2022

With the gradual increase in the deployment of distributed power sources and electric vehicles, the coordinated dispatch of clean power is of great significance to improve the economics of electricity consumption by prosumers and promote the consumption of renewable energy. On the basis of considering photovoltaic as a shared power resource, a low-voltage distribution network electric vehicle and distributed photovoltaic coordinated management and control strategy was proposed, and a day-ahead dispatch model of photovoltaic and electric vehicles for prosumers was established, which also considered the total cost of electricity consumption and two targets for photovoltaic consumption. The NSGA-2 algorithm is used to solve the model to obtain the Pareto optimal solution set, and the satisfaction evaluation method is used to select the optimal compromise solution. Based on the cloud-edge collaborative mechanism, the aforementioned technologies are deployed in the intelligent perception terminal device to execute downward computing, storage, and resource management strategies of the cloud station. A 24-period simulation calculation was performed on a low-voltage distribution network with 20 households. The results show that the proposed collaborative management and control strategy is beneficial to improve the economic efficiency of users’ electricity consumption and promote the consumption of clean energy.
Geospatial Environmental Influence on Forest Carbon Sequestration Potential of Tropical Forest Growth in Hainan Island, China
Authors: Lin Meizhi , Song Yanni , Lu Di , Qiu Zixuan
Published: May 2022

Tropical forests, although covering only 7% of the world’s land area, have great forest carbon sequestration capacity, accounting for 20% of the world’s forest carbon sink. However, the growth dynamics and forest carbon sink potential of tropical forests remain unclear. Hainan Island is going to be China’s forest carbon trading center. Therefore, accurately assessing the future forest carbon sink potential of Hainan Island’s tropical forest is crucial. In this study, 393 forest permanent sample plots in Hainan Island in 2003, 2008, 2013, and 2018 were selected as the research objects. The dynamic model of tropical forest growth with the geospatial environmental indicators was established based on the measured and most accurate annual diameter at breast height (DBH) growth factors. The DBH growth prediction’s bias ranged from 0.46 to 0.07 cm, RMSE ranged from 1.50 to 5.29 cm, bias% ranged from -2.96 to 0.55%, and RRMSE ranged from 12.18 to 34.30%. In addition, the geospatial environmental indicators of forest growth provide scientific guidance for future ecological protection and land evolution of Hainan Island. Based on DBH–tree height–volume, volume–biomass, and biomass–forest carbon storage relationships, forest carbon sequestration potential could be accurately evaluated by DBH growth. The results show that within the next 30 years, the forest carbon sequestration in Hainan Island will account for 1.8% of the total forest carbon sequestration in China, while the forest area will only account for 0.88% of the total forest area in China. It is roughly estimated that in the next 30 years, the total carbon sink of the tropical forest in Hainan Island will be 83.59 TgC. This study further proves that the annual increase in DBH can accurately assess the forest carbon sink potential of the forest. The forest carbon sink prediction based on the annual increase in DBH can provide data support and theoretical basis for forest carbon sink trading between forest farms and enterprises.
Predicting the Settlement of Mine Waste Dump Using Multi-Source Remote Sensing and a Secondary Consolidation Model
Authors: Tabish Reza , Yang Zefa , Wu Lixin , Xu Zhihua , Cao Zhanpeng , Zheng Kaihui , Zhang Yanqing
Published: May 2022

The settlement (or subsidence) of mine waste dump is likely to cause landslides, thereby imposing threats on the safety of human beings and other local properties. Hence, it is essential to accurately predict the settlement for the early-warning of settlement-induced geohazards. Traditional mechanical methods require in situ mechanical parameters and the geological structure of mine waste dump, narrowing their practical applications. In this paper, we proposed a remote sensing-based method for predicting the settlement of mine waste dump without the requirement for field observations. Firstly, the historical settlement and thickness of mine waste dump were measured by space-borne interferometric synthetic aperture radar (InSAR) and photogrammetry techniques, respectively. Secondly, the temporal evolution of the settlement of mine waste dump was described by a secondary consolidation model. Thirdly, the parameters of the secondary consolidation model were inverted based on the InSAR-measured historical settlements and photogrammetry-estimated thickness. Finally, the evolution trend of the settlement of the mine waste dump was predicted with the secondary consolidation model and its inverted parameters. The proposed method was tested over a mine waste dump in Weijiamao open-pit mine, China. The result shows that the root mean square error of the predicted time-series settlement is about 0.8 cm. The presented method will be beneficial to the assessment and early-warning of the settlement-related geohazards of mine waste dumps over a large area.
The Inflamm-Aging Model Identifies Key Risk Factors in Atherosclerosis
Authors: He Yudan , Chen Yao , Yao Lilin , Wang Junyi , Sha Xianzheng , Wang Yin
Published: May 2022

Background: Atherosclerosis, one of the main threats to human life and health, is driven by abnormal inflammation (i.e., chronic inflammation or oxidative stress) during accelerated aging. Many studies have shown that inflamm-aging exerts a significant impact on the occurrence of atherosclerosis, particularly by inducing an immune homeostasis imbalance. However, the potential mechanism by which inflamm-aging induces atherosclerosis needs to be studied more thoroughly, and there is currently a lack of powerful prediction models.

Methods: First, an improved inflamm-aging prediction model was constructed by integrating aging, inflammation, and disease markers with the help of machine learning methods; then, inflamm-aging scores were calculated. In addition, the causal relationship between aging and disease was identified using Mendelian randomization. A series of risk factors were also identified by causal analysis, sensitivity analysis, and network analysis.

Results: Our results revealed an accelerated inflamm-aging pattern in atherosclerosis and suggested a causal relationship between inflamm-aging and atherosclerosis. Mechanisms involving inflammation, nutritional balance, vascular homeostasis, and oxidative stress were found to be driving factors of atherosclerosis in the context of inflamm-aging.

Conclusion: In summary, we developed a model integrating crucial risk factors in inflamm-aging and atherosclerosis. Our computation pipeline could be used to explore potential mechanisms of related diseases.
The Prognostic Signature and Therapeutic Value of Phagocytic Regulatory Factors in Prostate Adenocarcinoma (PRAD)
Authors: Xin Shiyong , Sun Xianchao , Jin Liang , Li Weiyi , Liu Xiang , Zhou Liqing , Ye Lin
Published: May 2022

There is growing evidence that phagocytosis regulatory factors (PRFs) play important roles in tumor progression, and therefore, identifying and characterizing these factors is crucial for understanding the mechanisms of cellular phagocytosis in tumorigenesis. Our research aimed to comprehensively characterize PRFs in prostate adenocarcinoma (PRAD) and to screen and determine important PRFs in PRAD which may help to inform tumor prognostic and therapeutic signatures based on these key PRFs. Here, we first systematically described the expression of PRFs in PRAD and evaluated their expression patterns and their prognostic value. We then analyzed prognostic phagocytic factors by Cox and Lasso analysis and constructed a phagocytic factor-mediated risk score. We then divided the samples into two groups with significant differences in overall survival (OS) based on the risk score. Then, we performed correlation analysis between the risk score and clinical features, immune infiltration levels, immune characteristics, immune checkpoint expression, IC50 of several classical sensitive drugs, and immunotherapy efficacy. Finally, the Human Protein Atlas (HPA) database was used to determine the protein expression of 18 PRF characteristic genes. The aforementioned results confirmed that multilayer alterations of PRFs were associated with the prognosis of patients with PRAD and the degree of macrophage infiltration. These findings may provide us with potential new therapies for PRAD.
Astrocytes and Microglia in Stress-Induced Neuroinflammation: The African Perspective
Authors: Olude Matthew Ayokunle , Mouihate Abdeslam , Mustapha Oluwaseun Ahmed , Farina Cinthia , Quintana Francisco Javier , Olopade James Olukayode
Published: May 2022

Background:Africa is laden with a youthful population, vast mineral resources and rich fauna. However, decades of unfortunate historical, sociocultural and leadership challenges make the continent a hotspot for poverty, indoor and outdoor pollutants with attendant stress factors such as violence, malnutrition, infectious outbreaks and psychological perturbations. The burden of these stressors initiate neuroinflammatory responses but the pattern and mechanisms of glial activation in these scenarios are yet to be properly elucidated. Africa is therefore most vulnerable to neurological stressors when placed against a backdrop of demographics that favor explosive childbearing, a vast population of unemployed youths making up a projected 42% of global youth population by 2030, repressive sociocultural policies towards women, poor access to healthcare, malnutrition, rapid urbanization, climate change and pollution. Early life stress, whether physical or psychological, induces neuroinflammatory response in developing nervous system and consequently leads to the emergence of mental health problems during adulthood. Brain inflammatory response is driven largely by inflammatory mediators released by glial cells; namely astrocytes and microglia. These inflammatory mediators alter the developmental trajectory of fetal and neonatal brain and results in long-lasting maladaptive behaviors and cognitive deficits. This review seeks to highlight the patterns and mechanisms of stressors such as poverty, developmental stress, environmental pollutions as well as malnutrition stress on astrocytes and microglia in neuroinflammation within the African context.
Abrogation of Notch Signaling in Embryonic TECs Impacts Postnatal mTEC Homeostasis and Thymic Involution
Authors: García-León María Jesús , Mosquera Marta , Cela Carmela , Alcain Juan , Zuklys Saulius , Holländer Georg , Toribio María L.
Published: May 2022

Notch signaling is crucial for fate specification and maturation of thymus-seeding progenitors along the T-cell lineage. Recent studies have extended the role of Notch signaling to thymic epithelial cells (TECs), showing that Notch regulates TEC progenitor maintenance and emergence of medullary TECs (mTECs) in fetal thymopoiesis. Based on immunohistochemistry studies of spatiotemporal regulation of Notch activation in the postnatal thymus, we show that in vivo Notch activation is not confined to fetal TECs. Rather, Notch signaling, likely mediated through the Notch1 receptor, is induced in postnatal cortical and medullary TECs, and increases significantly with age in the latter, in both humans and mice, suggesting a conserved role for Notch signaling in TEC homeostasis during thymus aging. To investigate the functional impact of Notch activation in postnatal TEC biology, we used a mouse model in which RPBJκ, the transcriptional effector of canonical Notch signaling, is deleted in epithelial cells, including TECs, under the control of the transcription factor Foxn1. Immunohistochemistry and flow cytometry analyses revealed no significant differences in TEC composition in mutant (RPBJκ-KOTEC) and wild-type (WT) littermate mice at early postnatal ages. However, a significant reduction of the medullary region was observed in mutant compared to WT older thymi, which was accompanied by an accelerated decrease of postnatal mTEC numbers. Also, we found that organization and integrity of the postnatal thymic medulla critically depends on activation of the canonical Notch signaling pathway, as abrogation of Notch signaling in TECs led to the disruption of the medullary thymic microenvironment and to an accelerated thymus atrophy. These features paralleled a significant increase in the proportion of intrathymic non-T lineage cells, mostly B cells, and a slight decrease of DP thymocyte numbers compatible with a compromised thymic function in mutant mice. Therefore, impaired Notch signaling induced in embryonic development impacts postnatal TECs and leads to an accelerated mTEC degeneration and a premature thymus involution. Collectively, our data have uncovered a new role for Notch1 signaling in the control of adult mTEC homeostasis, and point toward Notch signaling manipulation as a novel strategy for thymus regeneration and functional recovery from immunosenescence.
Human Pegivirus Type 1: A Common Human Virus That Is Beneficial in Immune-Mediated Disease?
Authors: Stapleton Jack T.
Published: May 2022

Two groups identified a novel human flavivirus in the mid-1990s. One group named the virus hepatitis G virus (HGV) and the other named it GB Virus type C (GBV-C). Sequence analyses found these two isolates to be the same virus, and subsequent studies found that the virus does not cause hepatitis despite sharing genome organization with hepatitis C virus. Although HGV/GBV-C infection is common and may cause persistent infection in humans, the virus does not appear to directly cause any other known disease state. Thus, the virus was renamed “human pegivirus 1” (HPgV-1) for “persistent G” virus. HPgV-1 is found primarily in lymphocytes and not hepatocytes, and several studies found HPgV-1 infection associated with prolonged survival in people living with HIV. Co-infection of human lymphocytes with HPgV-1 and HIV inhibits HIV replication. Although three viral proteins directly inhibit HIV replication in vitro, the major effects of HPgV-1 leading to reduced HIV-related mortality appear to result from a global reduction in immune activation. HPgV-1 specifically interferes with T cell receptor signaling (TCR) by reducing proximal activation of the lymphocyte specific Src kinase LCK. Although TCR signaling is reduced, T cell activation is not abolished and with sufficient stimulus, T cell functions are enabled. Consequently, HPgV-1 is not associated with immune suppression. The HPgV-1 immunomodulatory effects are associated with beneficial outcomes in other diseases including Ebola virus infection and possibly graft-versus-host-disease following stem cell transplantation. Better understanding of HPgV-1 immune escape and mechanisms of inflammation may identify novel therapies for immune-based diseases.
Localization Matters: Epigenetic Regulation of Natural Killer Cells in Different Tissue Microenvironments
Authors: Wiedemann Gabriela M.
Published: May 2022

Natural Killer cells (NK cells) are cytotoxic innate lymphoid cells (ILCs), which play a key role in the early protection against viral infection and cancer. In addition to mounting rapid effector responses, NK cells possess the capacity to generate long-lived memory cells in response to certain stimuli, thus blurring the lines between innate and adaptive immunity and making NK cells an ideal candidate for tumor immunotherapy. NK cell development, activation and memory formation are regulated by epigenetic alterations driven by a complex interplay of external and internal signals. These epigenetic modifications can convey long-lasting functional and phenotypic changes and critically modify their response to stimulation. Here, we review how NK cell functionality and plasticity are regulated at the epigenetic level in different tissue microenvironments and within tumor microenvironments. An in-depth understanding of the epigenetic modifications underlying NK cell functional diversity in different environments is an essential step in the development of NK cell-based cancer therapies.
Kuroshio Intrusion and Its Impact on Swordtip Squid (Uroteuthis edulis) Abundance in the Southern East China Sea
Authors: Cheng Yi-Chen , Jan Sen , Chen Chung-Chi
Published: May 2022

Swordtip squid (Uroteuthis edulis) is a primary target species of the commercial fishery in the southern East China Sea (ECS), and they normally migrate to a quasi-permanent upwelling zone (called a cold dome) off northeastern Taiwan for spawning and growth during spring (March–May) and fall (October–December) in a year. We examined the connection of the variability in its standardized annual catch per unit effort (CPUE) during 2009–2017 in regard to the physical processes on the southern shelf of the ECS using temperature and wind observations from an isle north of Taiwan (Peng-jia-yu) as well as satellite sea surface temperature and absolute geostrophic velocity. The annual CPUE is positively correlated with the daily temperature anomaly at Peng-jia-yu in the cold dome in October of the previous year and April of the year. A warmer environment favors the recruitment and consequently the catch of the swordtip squid. During the spawning periods of the 9 years, the warm water carried by the Kuroshio frequently intruded atop the cold dome, which benefited the growth of the larvae and consequently helped maintain a certain value of the standardized annual CPUE. The anomalously low CPUE in 2012 and 2016 is attributed to the blocking of the Kuroshio intrusion due to cold and less salty China Coastal Water atop the cold dome in the spring spawning of 2012 and 2016. Based on the velocity strength in the cold dome and in a specified shelf region together with the daily temperature anomaly at Peng-jia-yu, an occupation intensity factor is used to evaluate the dominance of warm Kuroshio water and cold shelf water in the cold dome, which could help predict annual catches.
Longitudinal Sampling of the Rainbow Trout (Oncorhynchus mykiss) Microbiome Reveals Effects of Dietary Cecropin A and Yersinia ruckeri Infection
Authors: Sibinga Nathaniel A. , Lee Min-Ting , Johnson Elizabeth L. , Selvaraj Vimal , Marquis Hélène
Published: May 2022

The aquaculture industry faces growing pressure to reduce the use of antibiotics for control of bacterial diseases. In this study we tested the effectiveness of dietary cecropin A, an insect-derived antimicrobial peptide, at preventing mortality and reducing incidence of carrier status in rainbow trout (Oncorhynchus mykiss) challenged by immersion with Yersinia ruckeri. Additionally, we conducted longitudinal analyses of microbiome changes to elucidate effects of both cecropin A and bacterial infection. An in vitro experiment indicated that Y. ruckeri is susceptible to cecropin A. However, dietary cecropin A did not improve the survival of fish challenged with Y. ruckeri, nor did it decrease the persistence of Y. ruckeri in the intestine of fish that survived infection. Moreover, levels of intestinal Y. ruckeri as measured by qPCR suggested that cecropin A may have negatively impacted the ability of fish to resist colonization by this bacterial pathogen. Concomitantly with the survival experiments, the microbiomes of challenged and mock-challenged fish were sampled at days 0, 3, 8, and 30. The microbiomes were in general dominated by Mycoplasma sp. at days 0, 3 and 8, independent of diet, and whether fish had been challenged or mock-challenged. At day 30, the microbiomes of mock-challenged fish fed the +cecropin diet were characterized by lower internal (alpha) diversity (p<.01), greater relative abundance of Mycoplasma sp., and a decrease in gram-negative taxa, when compared to the microbiomes of fish fed the control diet. The opposite was observed in the microbiome of challenged fish. Lastly, correlation analysis of amplicon sequence variants (ASVs) revealed a negative correlation between the presence of Y. ruckeri and seven ASVs, including Mycoplasma sp., suggesting possible beneficial effects of these taxa. In addition, six ASVs were positively correlated to Y. ruckeri, including Flavobacterium succinicans – a known opportunistic fish pathogen. In conclusion, this study revealed that dietary cecropin A was bioactive and exerted significant effects on the microbiome but did not improve fish resistance to infection by Y. ruckeri. Based on our observations and other published results, it appears that high relative abundance of Mycoplasma sp. correlates with higher resistance to intestinal colonization by bacterial pathogens.
Electrochemical Studies of LbL Films With Dawson Type Heteropolyanion Glassy Carbon Electrode Sensor Modified for Methyl Parathion Detection
Authors: Ditta Nafeesa Allah , Yaqub Mustansara , Nadeem Sohail , Jamil Sundas , Hassan Sadaf Ul , Iqbal Shahid , Javed Mohsin , Elkaeed Eslam B. , Alshammari Fwzah H. , Alwadai Norah , Alzhrani Rami M. , Awwad Nasser S. , Ibrahium Hala A.
Published: May 2022

Rapid methyl parathion detection was measured using a fabricated glassy carbon electrode (GCE) sensor designed using the layer-by-layer (LBL) method. Multilayer assemblies were developed on the glassy carbon electrode by alternating depositions of anions and cations in which a Dawson Type Polyoxometalate β-K6[(P2W18O62·H2O)]·14H2O (∼P2W18 POM) and polyethyleneimine (PEI) stabilized silver nanoparticles (∼PEI-AgNPs) acted as anions and cations, respectively. The redox behavior of P2W18 POM within LBL assembly was carried out via cyclic voltammetry. This LBL assembly was thoroughly characterized by UV-Visible, FT-IR, XRD, AFM, and SEM techniques. The fabricate GCE sensor was investigated for the electrocatalytic activity to detect methyl parathion. The results clearly showed that the fabricated GCE sensor was successfully synthesized. More interestingly, the current response for detecting methyl parathion was found to be less than 1 ppm, proving that this fabricated GCE sensor may exhibit potential applications in the detection of targeted pesticide.
Efficacy of the Integrative Acupuncture and Moxibustion Treatment in Patients With Major Depressive Disorder: The Study Protocol for a Multicenter, Single-Blinded, Randomized Trial in China
Authors: Zhang Yuan , Liu Yamin , Ning Baile , Yan Luda , Wu Lihua , Zhang Delong , Li Changhong , Ouyang Wenwei , Su Shengyong , Jiang Shuo , Zhang Guangcai , Xu Junfeng , Wang Zhen , Zheng Zhong , Zheng Dong , Chen Shan , Sun Lu , Fu Wenbin
Published: May 2022

Introduction

Antidepressants are the front-line treatments for major depressive disorder (MDD), but remain unsatisfactory in outcome. An increasing number of patients are interested in acupuncture and moxibustion treatment as complementary therapies. This study aims to evaluate the efficacy and safety of integrative acupuncture and moxibustion (iAM) treatment in patients with MDD.

Methods and Analysis

This multicenter, single-blind, 2 × 2 factorial randomized trial will enroll 592 patients with MDD of moderate severity from nine hospitals. All patients will be randomized, in a ratio of 2:2:2:1, through a computerized central randomization system, into four groups (the combined, iAM-only, sertraline-only, and placebo groups). Participants will undergo a 12-week intervention with either 50 mg of sertraline or a placebo once a day and active/sham iAM treatment three times per week. The primary outcome is depression severity, assessed using the Hamilton Depression Scale-17. The secondary outcomes include self-rated depression severity, anxiety, and sleep quality. The primary and secondary outcomes will be measured at weeks 0, 4, 8, 12, and the 8th week posttreatment. Safety will be evaluated through liver and kidney function tests conducted before and after treatment and through monitoring of daily adverse events. An intent-to-treat principle will be followed for the outcome analyses.

Conclusion

This trial will provide sufficient evidence to ascertain whether iAM is effective and safe for treating MDD and provides a suitable combination strategy for treating MDD.

Clinical Trial Registration

[www.chictr.org.cn], identifier [ChiCTR2100042841].
Calpain2 Upregulation Regulates EMT-Mediated Pancreatic Cancer Metastasis via the Wnt/β-Catenin Signaling Pathway
Authors: Peng Xiulan , Yang Rui , Song Jia , Wang Xia , Dong Weiguo
Published: May 2022

Calpains2 (CAPN2) is a calcium-dependent, non-lysosomal cysteine protease that plays critical roles in normal cellular functions and pathological processes, including tumorigenesis, cancer progression, and metastasis. However, the role and underlying regulatory mechanisms of CAPN2 in pancreatic cancer (PC) are still unknown. We found that CAPN2 is highly expressed in PC tissues and associated with poor PC prognosis by using The Cancer Genome Atlas (TCGA) datasets, Gene Expression Omnibus (GEO) datasets, and PC tissue arrays. CAPN2 downregulation significantly inhibited cell proliferation, migration, and invasion and regulated Wnt/β-catenin signaling pathway-mediated epithelial-mesenchymal transition (EMT) in PC cells. Our findings highlight the significance of CAPN2 in tumor regression and, thus, indicate that CAPN2 could be a promising target for PC treatment.
Neurotrophic Keratopathy in Systemic Diseases: A Case Series on Patients Treated With rh-NGF
Authors: Meduri Alessandro , Oliverio Giovanni William , Valastro Antonio , Azzaro Claudia , Camellin Umberto , Franchina Francesco , Inferrera Leandro , Roszkowska Anna , Aragona Pasquale
Published: May 2022

Purpose

To evaluate the prevalence, clinical ocular presentation and corneal healing in moderate and severe neurotrophic keratopathy (NK) caused by systemic diseases and treated with rh-NGF.

Setting

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Ophthalmology Clinic, University of Messina, Italy.

Design

Retrospective observational study of case series.

Materials and Methods

In this retrospective observational study 11 patients (five female and six males) aged from 24 to 88 years (55.4 ± 21.3 years) with moderate and severe NK caused by systemic diseases were enrolled. The VAS questionnaire was dispensed. The ocular examination comprised slit lamp evaluation, ocular surface assessment with Keratograph 5M (Oculus, Germany), corneal sensitivity with Cochet-Bonnet esthesiometer (Lunneaux, France) and corneal thickness measurement with AC-OCT (DRI, Triton, Topcon, Japan). The underlying systemic causes of NK were determined.

Results

The main cause of NK was post-neuroma surgery (36%), followed by diabetes (18%). The remaining causes were rheumatoid arthritis (9%), post-traumatic (9%), post-surgery (9%), atopia (9%), Graves' disease (9%). Seven eyes presented severe grade of NK with corneal ulcer and in four a moderate grade was registered. The rh-NGF (Cenegermin) was administered with a standard protocol one drop six times daily for 8 weeks. The complete healing of all corneal defects was registered at the end of the treatment.

Conclusions

The post-neuroma surgery was the most common cause of NK and severe grade was clinically more represented. The rh-NGF proved effective to promote corneal recovery with all defects healed after the treatment.
Phytocannabinoids and Cannabis-Based Products as Alternative Pharmacotherapy in Neurodegenerative Diseases: From Hypothesis to Clinical Practice
Authors: Paes-Colli Yolanda , Aguiar Andrey F. L. , Isaac Alinny Rosendo , Ferreira Bruna K. , Campos Raquel Maria P. , Trindade Priscila Martins Pinheiro , de Melo Reis Ricardo Augusto , Sampaio Luzia S.
Published: May 2022

Historically, Cannabis is one of the first plants to be domesticated and used in medicine, though only in the last years the amount of Cannabis-based products or medicines has increased worldwide. Previous preclinical studies and few published clinical trials have demonstrated the efficacy and safety of Cannabis-based medicines in humans. Indeed, Cannabis-related medicines are used to treat multiple pathological conditions, including neurodegenerative disorders. In clinical practice, Cannabis products have already been introduced to treatment regimens of Alzheimer’s disease, Parkinson’s disease and Multiple Sclerosis’s patients, and the mechanisms of action behind the reported improvement in the clinical outcome and disease progression are associated with their anti-inflammatory, immunosuppressive, antioxidant, and neuroprotective properties, due to the modulation of the endocannabinoid system. In this review, we describe the role played by the endocannabinoid system in the physiopathology of Alzheimer, Parkinson, and Multiple Sclerosis, mainly at the neuroimmunological level. We also discuss the evidence for the correlation between phytocannabinoids and their therapeutic effects in these disorders, thus describing the main clinical studies carried out so far on the therapeutic performance of Cannabis-based medicines.
Transcriptome-Wide N6-Methyladenosine Methylome Alteration in the Rat Spinal Cord After Acute Traumatic Spinal Cord Injury
Authors: Yu Jiangtao , Chen Haihua , Ma Haoli , Zhang Zhongxiang , Zhu Xiaolu , Wang Pengcheng , Liu Ruining , Jin Xiaoqing , Zhao Yan
Published: May 2022

Recent studies showed that RNA N6-methyladenosine (m6A) plays an important role in neurological diseases. We used methylated RNA immunoprecipitation sequencing (MeRIP-Seq) technology to generate the m6A modification map after traumatic spinal cord injury (TSCI). A total of 2,609 differential m6A peaks were identified after TSCI. Our RNA sequencing results after TSCI showed 4,206 genes with significantly altered expression. Cross-link analysis of m6A sequencing results and RNA sequencing results showed that 141 hyper-methylated genes were upregulated, 53 hyper-methylated genes were downregulated, 57 hypo-methylated genes were upregulated, and 197 hypo-methylated genes were downregulated. Among these, the important inflammatory response factor Tlr4 and the important member of the neurotrophin family Ngf were both upregulated and hyper-methylated after TSCI. This study provides that in the future, the epigenetic modifications of the genes could be used as an indicator of TSCI.
Modeling Brain Tumors: A Perspective Overview of in vivo and Organoid Models
Authors: Antonica Francesco , Aiello Giuseppe , Soldano Alessia , Abballe Luana , Miele Evelina , Tiberi Luca
Published: May 2022

Brain tumors are a large and heterogeneous group of neoplasms that affect the central nervous system and include some of the deadliest cancers. Almost all the conventional and new treatments fail to hinder tumoral growth of the most malignant brain tumors. This is due to multiple factors, such as intra-tumor heterogeneity, the microenvironmental properties of the human brain, and the lack of reliable models to test new therapies. Therefore, creating faithful models for each tumor and discovering tailored treatments pose great challenges in the fight against brain cancer. Over the years, different types of models have been generated, and, in this review, we investigated the advantages and disadvantages of the models currently used.
Transcriptional Activation, Deactivation and Rebound Patterns in Cortex, Hippocampus and Amygdala in Response to Ketamine Infusion in Rats
Authors: Kim Jenny J. , Sapio Matthew R. , Vazquez Fernando A. , Maric Dragan , Loydpierson Amelia J. , Ma Wenting , Zarate Carlos A. , Iadarola Michael J. , Mannes Andrew J.
Published: May 2022

Ketamine, an N-methyl-D-aspartate (NMDA)-receptor antagonist, is a recently revitalized treatment for pain and depression, yet its actions at the molecular level remain incompletely defined. In this molecular-pharmacological investigation in the rat, we used short- and longer-term infusions of high dose ketamine to stimulate neuronal transcription processes. We hypothesized that a progressively stronger modulation of neuronal gene networks would occur over time in cortical and limbic pathways. A continuous intravenous administration paradigm for ketamine was developed in rat consisting of short (1 h) and long duration (10 h, and 10 h + 24 h recovery) infusions of anesthetic concentrations to activate or inhibit gene transcription in a pharmacokinetically controlled fashion. Transcription was measured by RNA-Seq in three brain regions: frontal cortex, hippocampus, and amygdala. Cellular level gene localization was performed with multiplex fluorescent in situ hybridization. Induction of a shared transcriptional regulatory network occurred within 1 h in all three brain regions consisting of (a) genes involved in stimulus-transcription factor coupling that are induced during altered synaptic activity (immediate early genes, IEGs, such as c-Fos, 9–12 significant genes per brain region, p < 0.01 per gene) and (b) the Nrf2 oxidative stress-antioxidant response pathway downstream from glutamate signaling (Nuclear Factor Erythroid-Derived 2-Like 2) containing 12–25 increasing genes (p < 0.01) per brain region. By 10 h of infusion, the acute results were further reinforced and consisted of more and stronger gene alterations reflecting a sustained and accentuated ketamine modulation of regional excitation and plasticity. At the cellular level, in situ hybridization localized up-regulation of the plasticity-associated gene Bdnf, and the transcription factors Nr4a1 and Fos, in cortical layers III and V. After 24 h recovery, we observed overshoot of transcriptional processes rather than a smooth return to homeostasis suggesting an oscillation of plasticity occurs during the transition to a new phase of neuronal regulation. These data elucidate critical molecular regulatory actions during and downstream of ketamine administration that may contribute to the unique drug actions of this anesthetic agent. These molecular investigations point to pathways linked to therapeutically useful attributes of ketamine.
Salubrinal Protects Against Cisplatin-Induced Cochlear Hair Cell Endoplasmic Reticulum Stress by Regulating Eukaryotic Translation Initiation Factor 2α Signalling
Authors: Lu Wen , Ni Kun , Li Zhuangzhuang , Xiao Lili , Li Yini , Jiang Yumeng , Zhang Jincheng , Shi Haibo
Published: May 2022

Objective

Cisplatin is a broad-spectrum anti-tumour drug commonly used in clinical practice. However, its ototoxicity greatly limits its clinical application, and no effective method is available to prevent this effect. Endoplasmic reticulum stress (ERS) is reportedly involved in cisplatin ototoxicity, but the exact mechanism remains unclear. Therefore, this study aimed to investigate the role of eukaryotic translation initiation factor 2α (eIF2α) signalling and its dephosphorylation inhibitor salubrinal in cisplatin ototoxicity.

Methods

We evaluated whether salubrinal could protect against cisplatin-induced damage in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and mouse cochlear explants. By knocking down eIF2α, we elucidated the vital role of eIF2α in cisplatin-induced damage in HEI-OC1 cells. Whole-mount immunofluorescent staining and confocal microscopy of mouse cochlear explants and HEI-OC1 cells were performed to analyse cisplatin-induced damage in cochlear hair cells and the auditory cell line.

Results

Data suggested salubrinal attenuated cisplatin-induced hair cell injury by inhibiting apoptosis. In addition, salubrinal significantly reduced ERS levels in hair cells via eIF2α signalling, while eIF2α knockdown inhibited the protective effect of salubrinal.

Significance

Salubrinal and eIF2α signalling play a role in protecting against cisplatin-induced ototoxicity, and pharmacological inhibition of eIF2α-mediated ERS is a potential treatment for cisplatin-induced damage in the cochlea and HEI-OC1 cells.
Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA
Authors: Ran Qijie , Xu Dehong , Wang Qi , Wang Dongsheng
Published: May 2022

Multiple myeloma has a long course, with no obvious symptoms in the early stages. However, advanced stages are characterized by injury to the bone system and represent a severe threat to human health. The results of the present work indicate that the hypermethylation of miR-23 promoter mediates the aberrant expression of uPA/PLAU (urokinase plasminogen activator, uPA) in multiple myeloma cells. miR-23, a microRNA that potentially targets uPA’s 3’UTR, was predicted by the online tool miRDB. The endogenous expressions of uPA and miR-23 are related to disease severity in human patients, and the expression of miR-23 is negatively related to uPA expression. The hypermethylation of the promoter region of miR-23 is a promising mechanism to explain the low level of miR-23 or aberrant uPA expression associated with disease severity. Overexpression of miR-23 inhibited the expression of uPA by targeting the 3’UTR of uPA, not only in MM cell lines, but also in patient-derived cell lines. Overexpression of miR-23 also inhibited in vitro and in vivo invasion of MM cells in a nude mouse model. The results therefore extend our knowledge about uPA in MM and may assist in the development of more effective therapeutic strategies for MM treatment.
Evaluation of Galanin Expression in Colorectal Cancer: An Immunohistochemical and Transcriptomic Study
Authors: Talaat Iman M. , Yakout Nada M. , Soliman Ahmed S.A. , Venkatachalam Thenmozhi , Vinod Arya , Eldohaji Leen , Nair Vidhya , Hareedy Amal , Kandil Alaa , Abdel-Rahman Wael M. , Hamoudi Rifat , Saber-Ayad Maha
Published: May 2022

Colorectal cancer (CRC) represents around 10% of all cancers, with an increasing incidence in the younger age group. The gut is considered a unique organ with its distinctive neuronal supply. The neuropeptide, human galanin, is widely distributed in the colon and expressed in many cancers, including the CRC. The current study aimed to explore the role of galanin at different stages of CRC. Eighty-one CRC cases (TNM stages I – IV) were recruited, and formalin-fixed paraffin-embedded samples were analyzed for the expression of galanin and galanin receptor 1 (GALR1) by immunohistochemistry (IHC). Galanin intensity was significantly lower in stage IV (n= 6) in comparison to other stages (p= 0.037 using the Mann-Whitney U test). Whole transcriptomics analysis using NGS was performed for selected samples based on the galanin expression by IHC [early (n=5) with high galanin expression and late (n=6) with low galanin expression]. Five differentially regulated pathways (using Absolute GSEA) were identified as drivers for tumor progression and associated with higher galanin expression, namely, cell cycle, cell division, autophagy, transcriptional regulation of TP53, and immune system process. The top shared genes among the upregulated pathways are AURKA, BIRC5, CCNA1, CCNA2, CDC25C, CDK2, CDK6, EREG, LIG3, PIN1, TGFB1, TPX2. The results were validated using real-time PCR carried out on four cell lines [two primaries (HCT116 and HT29) and two metastatic (LoVo and SK-Co-1)]. The current study shows galanin as a potential negative biomarker. Galanin downregulation is correlated with advanced CRC staging and linked to cell cycle and division, autophagy, transcriptional regulation of TP53 and immune system response.