bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of a potent anti-PD-L1-CD47 bispecific antibody with a strong therapeutic and safety profile for cancer immunotherapy
Authors: Tang Irene , Schwimmer Lauren , Gu Shenda , Wei Prior Wei , Tran Hieu Van , Chan Allan , McClain Anna , Fraser Christopher C. , Sun Chunyan , Si Meimei , Wang Guijiang , Zhao Yunxia , Zhang Ning , Fu Jiayu , Liu Mengxin , Cao Chuanzeng , Chen Shihao
Published: May 2023

Cell surface molecules PD-L1 and CD47 are potent inhibitors of adaptive and innate anti-cancer immunity. We sought to generate a safe, therapeutic, bispecific antibody specifically targeting, and blocking both PD-L1 and CD47 inhibitory activity. Novel anti-PDL-1 and anti-CD47 antibodies with favorable inhibitory activity, were humanized and constructed into a unique bi-specific antibody intended for clinical use. Previous pre-clinical and clinical studies using anti-CD47 antibodies indicated anemia and thrombocytopenia as potential risks. QL401 is a PD-L1 x CD47 bispecific antibody engineered to reduce effect on red blood cells while retaining potent phagocytic activation of macrophages in vitro and delayed tumor growth in vivo. QL401 comprises three functional components: a PD-L1 binding Fab arm, a CD47 binding scFv arm, and a human IgG4 backbone. The PD-L1 binding arm provides both tumor targeting and blocking of PD-1 for reactivating T cells. The CD47 arm blocks the binding of SIRPα, while the IgG4 Fc retains Fc gamma receptor binding to provide a phagocytic signal. In preclinical efficacy studies, QL401 potently blocked SIRPα to promote phagocytosis of tumor cells with sub-nanomolar potency. In vivo efficacy studies in mouse xenograft tumor models showed QL401 to be comparable or superior to PD-L1 or CD47 monoclonal antibodies alone or in combination. In vitro safety evaluation of QL401 showed significantly reduced binding and phagocytosis of red blood cells, in contrast to CD47 monoclonal antibodies. In addition, QL401 did not induce hemagglutination. In non-human primates, QL401 was well tolerated up to 100 mg/kg without reduction of red blood cells or platelets below the normal range. QL401 is presently in a human phase I safety study.
Sources, supply, and seasonality of total suspended matter and associated organic carbon and total nitrogen in three large Asian rivers—Ganges, Mekong, and Yellow
Authors: Sarkar Siddhartha , Verma Sangeeta , Begum Most Shirina , Park Ji-Hyung , Kumar Sanjeev
Published: May 2023

Asian rivers, covering ∼29% of the global river surface area, account for ∼35% of the global freshwater discharge and transport a disproportionately large flux (∼70%) of total suspended matter to the oceans. With recent anthropogenic and climate-induced changes in the flow regimes, it is challenging to constrain the fluxes and elemental signatures of the suspended organic matter in rivers. This study aimed to understand seasonal changes in the characteristics of total suspended matter (TSM) associated organic carbon (C) and total nitrogen (N) during high and low flow periods in three large Asian rivers (Ganges, Mekong, and Yellow). By measuring organic C and total N contents and their isotopic compositions at multiple locations along the studied rivers, distinct seasonality in the sources of organic matter was observed. Allochthonous sources dominated the organic matter pool during the high flow condition, whereas autochthonous organic matter derived from enhanced phytoplankton production appeared to have dominated during low flow. C/N ratio showed positive correlation with altitude during wet period, which reversed during dry, supporting the transition of sediment dominated high flow riverine system into relatively clear and productive low flow system. Generally, organic matter content in TSM was higher during the low flow with signatures of potential N2 fixation. Temporal analysis based on present and earlier estimates of fluxes and yields of TSM indicated manifold decrease in TSM load and associated C and N fluxes over decades in the three river systems largely attributed to reduction in river discharge. Wastewater dominated locations showed similar C and N contents and isotopic signatures as those of productive river waters during low flow, indicating a possible interference in the interpretation of biogeochemical information.
Spatial and temporal patterns of methane emissions from mountain peatlands in the northern Andes across a disturbance gradient
Authors: Benavides J. C. , Rocha Santiago , Blanco E. A.
Published: May 2023

Methane emitted by wetlands accounts for nearly 30% of the global methane emissions and is expected to double by 2,100. Methane fluxes from peatlands are related to m soil temperature, water table, and vegetation. Disturbances, mostly drainage, are considered to have a more limited impact on CH4 fluxes from peatlands. Here, we studied the temporal and spatial patterns of methane emissions from four peatlands across and elevation and disturbance gradient in the northern Andes. Our research seeks to understand the effects of disturbance legacies and soil temperature, flooding patterns, and vegetation on methane emissions in Andean peatlands. Our results indicated a strong control of CH4 emissions by soil temperature with a stronger effect at intermediate elevations. The removal of peat forming vegetation from the surface had the higher effect on CH4 emissions, increasing methane fluxes by an order of magnitude. Methane fluxes from conserved cushion vascular plants were low, but nearby hollows had relatively high emissions. Our research provides evidence of high methane emissions from degraded peatlands in the tropical Andes. However, the role of climate change and disturbance legacies on methane emissions from tropical Andean peatlands remains unknown affecting our ability to predict future emission patterns and our ability to incorporate climate mitigation strategies.
Prehistoric Hunter-Gatherers in the Philippines—Subsistence strategies, adaptation, and behaviour in maritime environments
Authors: Pawlik Alfred F. , Fuentes Riczar B.
Published: May 2023

Archaeological research in the Philippines has produced a timeline of currently over 700,000 years of human occupation. However, while an initial presence of early hominins has been securely established through several radiometric dates between 700 ka to 1 ma from Luzon Island, there is currently little evidence for the presence of hominins after those episodes until c. 67 to 50 ka for Luzon or any of the other Philippine islands. At approximately 40 ka, anatomically modern humans had arrived in the Philippines. Early sites with fossil and/or artifactual evidence are Tabon Cave in Palawan and Bubog 1 in Occidental Mindoro, the latter situated in the Wallacean part of the archipelago. This paper presents an overview of the archaeological research on the prehistory of the Philippines from the Pleistocene until the Late Holocene and the arrival of the first farmers, presumably from Austronesian language groups approximately 4,000 years ago. Research on this topic has significantly intensified over the past 20 years and is providing a variety of evidence for the successful adaptation of those first islanders to maritime environments, the diversity of technological and subsistence strategies, and increasingly complex interrelationships across Island Southeast Asia.
Accuracy assessment of various supervised machine learning algorithms in litho-facies classification from seismic data in the Penobscot field, Scotian Basin
Authors: Narayan Satya , Konka Suresh , Chandra Akash , Abdelrahman Kamal , Andráš Peter , Eldosouky Ahmed M.
Published: May 2023

Litho-facies classification is an essential task in characterizing the complex reservoirs in petroleum exploration and subsequent field development. The lithofacies classification at borehole locations is detailed but lacks in providing larger coverage areas. The acquired 3D seismic data provides global coverage for studying the reservoir facies heterogeneities in the study area. This study applies six supervised machine learning techniques (Random Forest, Support Vector Machine, Artificial Neural Network, Adaptive Boosting, Xtreme Gradient Boosting, and Multilayer Perceptron) to 3D post-stack seismic data to accurately estimate different litho-facies in inter-well regions and compares their performance. Initially, the efficacy of the said models was critically examined via the confusion matrix (accuracy and misclass) and evaluation matrix (precision, recall, F1-score) on the test data. It was found that all the machine learning models performed best in classifying the shale facies (87%–94%) followed by the sand (65%–79%) and carbonate facies (60%–78%) in the Penobscot field, Scotian Basin. On an overall accuracy scale, we found the multilayer perceptron method the best-performing tool, whereas the adaptive boosting method was the least-performing tool in classifying all three litho-facies in the current analysis. While other methods also performed moderately good for the classification of all three litho-facies. The predicted litho-facies using seismic attributes matched well with the log data interpreted facies on the borehole locations. It indicates that the facies estimated in inter-well regions are accurate and reliable. Furthermore, we validated the estimated results with the other seismic attributes to ascertain the accuracy and reliability of the predicted litho-facies between the borehole locations. This study recommends machine learning applications for litho-facies classification to reduce the risk associated with reservoir characterization.
The significance of Anomalocaris and other Radiodonta for understanding paleoecology and evolution during the Cambrian explosion
Authors: Potin Gaëtan J.-M. , Daley Allison C.
Published: May 2023

One of the most widespread and diverse animal groups of the Cambrian Explosion is a clade of stem lineage arthropods known as Radiodonta, which lived exclusively in the early Paleozoic. First reported in 1892 withAnomalocaris canadensis, radiodonts are now one of the best known early animal groups with excellent representation in the fossil record, and are ubiquitous components ofKonservat-Lagerstättenfrom the Cambrian and the Early Ordovician. These large swimmers were characterised by a segmented body bearing laterally-oriented flaps, and a head with a distinct radial oral cone, a pair of large frontal appendages adapted for different feeding modes, compound eyes on stalks, and prominent head carapaces. Radiodonts inform on the paleoecology of early animal communities and the steps involved in euarthropod evolution. Four families within Radiodonta have been established. The raptorial predator families Anomalocarididae and Amplectobeluidae were dominant early in the evolutionary history of Radiodonta, but were later overtaken by the mega-diverse and widespread Hurdiidae, which has a more generalised sediment-sifting predatory mode. Suspension feeding, notably in the families Tamisiocarididae and Hurdiidae, also evolved at least twice in the history of the clade. The well-preserved anatomical features of the radiodont body and head have also provided insights into the evolution of characteristic features of Euarthropoda, such as the biramous limbs, compound eyes, and organisation of the head. With 37 species recovered from all major paleocontinents of the Cambrian and Early Ordovician, Radiodonta provides a unique opportunity for revealing evolutionary patterns during the Cambrian Explosion.
Assessing the impacts of future urban expansion on multiple ecosystem services in the transnational area of Changbai Mountain
Authors: Chen Ruikang , Zhang Da , Nan Ying , Feng Hengdong , Geng Xin
Published: May 2023

Introduction: An assessment of the potential impacts of future urban expansion on multiple ecosystem services (ESs) represents an essential contribution to the sustainable development of the transnational area of Changbai Mountain (TACM). However, the potential ES losses attributed to future urban expansion have been assessed in few studies.

Methods: In this study, we evaluated the potential ES losses attributable to urban expansion in the TACM over the period from 2015 to 2050. To achieve this objective, we initially quantified multiple ESs (namely, food production (FP), carbon storage (CS), water retention (WR), and air purification (AP)) based on 1992 data, and subsequently simulated urban expansion from 2015 to 2050 by coupling Shared Socioeconomic Pathways scenarios (SSPs) with the zoned Land Use Scenario Dynamics-urban model. Finally, the potential impacts of future urban expansion on ESs were evaluated on multiple scales.

Results: The results indicated that during the period from 2015 to 2050, the extent of urban land will grow by between 157.59 and 517.77 km2, resulting in FP, CS, WR, and AP losses of 193.76–684.39 thousand tons, 1.47–5.24 million tons, 8.74–30.00 million tons, and 0.34–1.18 thousand tons, respectively.

Discussion: The subregion falling within the Democratic People’s Republic of Korea (DPRK) will experience the most severe future losses of ESs, with losses of FP, CS, WR, and AP being 1.06–3.77-fold, 1.15–3.46-fold, 1.10–3.54-fold, and 1.08–3.21-fold higher, respectively than those that occurred in this subregion the period of 1992–2015. Specifically, the encroachment of new urban land onto cropland and woodland will be the main contributing factor in these future declines in ESs. Furthermore, the reductions in ESs attributable to urban expansion in this subregion will have serious effects on human wellbeing. By 2050, the loss of FP will affect approximately 9.58%–30.00% of the population. Moreover, among the residents of this subregion, the loss of AP will contribute to the need for additional expenditures of 6.63–19.81 million euros on air purification measures. On the basis of these findings, we suggest that effective policies and regulations should be implemented to promote the sustainable development of the TACM.
Authigenic pyrite and gypsum minerals in offshore Zhoushan sediments: morphology, formation, and environmental implications
Authors: Sun Tiantian , Cao Ke , Yin Ping , Jiang Xuejun , Tian Yuan
Published: May 2023

Offshore Zhoushan sediments are a potential area for shallow gas resources in China, where authigenic pyrite is widely distributed. Pyrite content, size distribution, and morphology are influenced by depositional conditions and are sensitive to environmental changes. This study investigated the authigenic pyrites or gypsums of core JC-1 offshore of Zhoushan. Scanning electron microscopy was used to observe the pyrites and identify various aggregations. Changes in lithology, chlorine content, and stable isotope values of organic matter were analyzed to indicate the evolution of ancient marine, floodplain estuary, tidal flat environments, and shallow marine sedimentary facies. The morphology and microcrystalline structure of these types of pyrites can be divided into spherical framboid aggregates, sub-euhedral aggregates, and microcrystalline euhedral pyrites with different sedimentary facies. Gypsum minerals and the coexistence of pyrite and gypsum were found in the enriched authigenic pyrites at the SMTZs. The sources of sulfate formed by authigenic gypsums may originate from overlying seawater and pyrite oxidation, whereas calcium ions may come from the dissolution of carbonate or calcareous shells caused by local environmental acidification. The various aggregations of pyrites observed may be related to SO4-AOM in different environments. The findings suggest that authigenic gypsums form due to local environmental acidification and that the sources of the formed sulfate may be from overlying seawater and pyrite oxidation. This study provides a new perspective for understanding the responses of different sedimentary environments to sea level rise and climate change.
Flexural-slip folding in buckling phases of orogenic belts: Insight into the tectonic evolution of fault splays in the East Iran orogen
Authors: Rashidi Ahmad , Shafieibafti Shahram , Nemati Majid , Ezati Maryam , Gholami Ebrahim , Mousavi Seyed Morteza , Derakhshani Reza
Published: May 2023

Introduction: The East Iran orogen has experienced multiple buckling phases resulting in the formation of strike-slip fault splays. The geometric and kinematic characteristics of these splays are influenced by folding mechanisms. This study focuses on investigating the structural characteristics and tectonic evolution model of the Khousf splay, located in the northern terminus of the Nehbandan right-lateral strike-slip fault system.

Methods: Field visits and geometrical properties from map views were used to analyze the structural features of the Khousf splay. The splay was found to consist of a multi-plunging anticline and syncline, referred to as the Khousf anticline and Khousf syncline, respectively. Flexural slip was identified as a significant mechanism for the formation of these structures. Structural evidence, including parasitic folds, active folds, and strike-slip duplexes, suggested that flexural slip occurred on discrete movement horizons among the rock units.

Results: Analysis of the parasitic folds in the cores and limbs of the Khousf anticline and syncline revealed M, W, Z, and S shapes, with complex slicken-line patterns observed on faults parallel to the beds at the limbs. The analysis results indicated strain partitioning and inclined left- and right-lateral transpressional zones. Shortening estimates obtained from profiles in the Shekarab inclined transpressional zone were approximately 33%, 65%, and 68% for NE-SW, N-S, and NW-SE profiles, respectively. In the Arc area, which is the core of the anticline, shortening estimates from NE-SW and N-S profiles ranged from 14% to 10%. Structural analysis of the folds in this area revealed broad, close, semi-elliptical, and parabolic shapes, suggesting that secondary folds with NW-SE axis directions have been superimposed on the first-generation folds with E-W axis directions in the Khousf refolded splay.

Discussion: The findings of this study highlight the structural characteristics and tectonic evolution model of the Khousf splay in the northern terminus of the Nehbandan right-lateral strike-slip fault system. The results suggest that flexural slip played a crucial role in the formation of the multi-plunging anticline and syncline in the Khousf splay. The presence of parasitic folds and complex slicken-line patterns on faults indicate the complexity of deformation processes. The observed strain partitioning and inclined transpressional zones suggest a complex tectonic history in the study area. The superimposition of secondary folds with different axis directions on first-generation folds adds further complexity to the structural evolution of the Khousf refolded splay. Overall, this study provides new insights into the structural characteristics and tectonic evolution of the Khousf splay in the East Iran orogen.
Micro-seismic events detection and its tectonic implications in Northeastern Hainan Province
Authors: Ma Zeyu , Li Hongyi , Liu Min , Huang Yafen , Zhang Shengzhong , Lv Yuejun
Published: May 2023

In this paper, we combine the U-net-based phase picking method (PhaseNet) with Graphics Processing Unit-Based Match and Locate technology (GPU-M&L) and a deep-learning-based seismic signal de-noising method (DeepDenoiser) as a workflow for automatically extracting micro-seismic information from continuous raw seismic data. PhaseNet is first used to detect missed seismic phases by scanning through the 5-year continuous waveform data recorded at five broad-band stations in Hainan province. Then Rapid Earthquake Association and Location method (REAL), VELEST program (1-D inversion of velocities and hypocenter locating) and HypoDD (a double-difference locating method) are applied to associate seismic phases with events and to locate, respectively. This initially established catalogue can be served as the template for the following match-filter work. We choose events with a high signal-to-noise ratio (SNR) as templates and apply GPU-M&L to detect more small earthquakes which are difficult to pick by routine methods due to the low SNR. Then, a deep learning-based noise reduction technique named DeepDenoiser is applied to extract seismic signal from noise to provide a better picking of arrival time and then to improve the relocation effects. Finally, we use HypoDD to relocate these events with P- and S- wave arrival times picked by PhaseNet. Compared with the five events listed in the China Earthquake Networks Center routine catalogue, in this study, we detect and locate 977 earthquakes by following the above procedure. Our relocation results illustrate quite a complex distribution pattern of events due to the complicated fault system in the northeastern part of Hainan Province.
Research on evaluation model of rock failure integrity under complex geological conditions in karst area
Authors: Jianbo Ma , Zhongqi Wang , En Yang , Menghua Liu
Published: May 2023

Blasting lumpiness prediction is one of the most important research contents in engineering blasting. Although the traditional KUZ-RAM model is widely used, it often overestimates the size of blasting. Therefore, the KUZ-RAM model was updated or corrected in this paper by simplifying the difficult problem of statistical burst fragmentation in LS-DYNA. Based on the theory of area measurement method, the fitting mechanism of machine learning is used to study the lumpiness of simulation results. The updated KUZ-RAM model adds a coefficient of 0.623 to the original equation of average lumpiness xm. The linear coefficient R2 between the predicted results and the field blasting results increases from −1.99 to 0.97, which significantly improves the prediction of blasting lumpiness.
Basic characteristics and environmental impact of iron ore tailings
Authors: Wang Changlong , Jing Jianlin , Qi Yang , Zhou Yongxiang , Zhang Kaifan , Zheng Yongchao , Zhai Yuxin , Liu Feng
Published: May 2023

Introduction: In our study, various test methods were adopted to explore the mineralogical characteristics, grindability, particle morphology, particle size distribution, and environmental leaching toxicity of iron ore tailings (lOTs).

Methods: The methods include petrographic analysis, X-ray diffraction (XRD), scanning electronic microscopy (SEM), synchronous thermal analyzer (DSC-TGA), electron probe X-ray microanalyser (EPMA), and synthetic precipitation leaching Procedure (SPLP).

Results: The results show that the used IOTs contained 14.54% iron which was mainly stored in magnetite and pyrite. The content of iron silicate accounted for 11.82% of the total iron content. Most of it existed in silicate minerals, including grunerite and hornblende. A small amount of iron was contained in biotite, chlorite and augite. Besides, the grindability of lOTs was much better than that of granulated blast furnace slag (GBFS). After grinding for 140 min, the mass fraction of lOTs particles with the particle size less than 5 um was 44.19%. These particles could be used to fill in the voids in the cement-powder-packed structure. lOTs also contained a large number of submicron and nanoscale particles.

Discussion: With great strength and environmental friendliness, the composite cementitious material (CCM) prepared from lOTs can be well applied to the building material field and environmental remediation.
Acoustic emission precursor information of rock failure under true triaxial loading and unloading conditions
Authors: Liu Sijie , Zheng Haijun , Chen Guoqing , Hu Yitao , Meng Kai
Published: May 2023

Rock failure generally leads to serious consequences, and it is significant to obtain the precursor information prior to failure using associated techniques. Acoustic emission (AE) is one of the indispensable methods for disaster warning of hard and brittle rock. Acoustic emission detection technology can effectively monitor real-time information about changes in the rock interior and predict the process of rock damage failure. To probe the relationship among the AE precursor information of red sandstone under different intermediate principal stresses, an experimental study was conducted by us to examine the alterations in AE parameters during the failure of red sandstone under both loading and unloading circumstances. The study shows that the ringing count rate and absolute energy versus time curves are divided into four stages, namely, quiet, frequent, sudden increase and decline periods. The cumulative count curve is also divided into four phases: pre-unloading period, post-unloading period, sharp increase period, and decrease period. With the rise of the intermediate principal stress, the ringing count rate and energy exhibited during the frequent period of AE demonstrate a consistent increase, with a larger increase in the maximum value and a smaller increase in the average value. In addition, the peak value of AE signals during failure also increases accordingly. The occurrence moment and clarity of the frequent period determine the reliability and priority of the information related to the rock’s failure precursor; moreover, the reliability and priority of the AE precursor information will increase with the increase of the intermediate principal stress. After comparison, it is found that the AE precursor information occurs prior to the thermal infrared precursor information.
Cry me a Pele’s tear: new insights on the internal structures of Pele’s tears
Authors: Moyer Scott , Sahagian Dork
Published: May 2023

In this paper we present novel observations of internal structures of Pele’s tears and spheres revealed from SEM studies of particles formed within Kilauean lava fountains. Partially weathered Pele’s tears from eruption episodes in 1969 include a crust, or rind, of material that is smooth on the external surface. However, once this crust is peeled away, it reveals a sub-crustal surface within the tear that is morphologically complex. This surface is characterized by a network of ridges and valleys that warp around radial structures with pores at their centers. The ridges and valleys are interpreted to represent the differential cooling and shrinkage of the external surface of the spheres and tears relative to the interior upon exiting the lava fountain and chilling in ambient air. The radial structures are interpreted to be formed as result of chemical zonation within the cooling at locations where a vesicle contacts the external crust. An additional feature is observed on the underside of crust that is peeled off each tear. This surface has a roughly polygonal network of tubes that surround pores at the center of many of the polygons. The tubes are hollow and some contain solid material within, possibly the remains of the crushed top of the tube where the SEM can peer inside. The origin of this tube network is a puzzle remaining to be solved.
Reimagining informal STEM learning opportunities to foster STEM identity development in underserved learners
Authors: Çolakoğlu Jasmin , Steegh Anneke , Parchmann Ilka
Published: May 2023

Informal science, technology, engineering, and mathematics (STEM) learning opportunities offer great potential to position learners as insiders to STEM and to foster their positive STEM identity development. Despite their goal to create equal insights and access to STEM learning for all, however, these informal STEM learning opportunities often fail to reach underserved students, hindering their STEM identity development and perpetuating inequity. To address this issue, out-of-school programs need to be designed with underserved students in mind, and concepts, as well as practical approaches that foster STEM identity development, need to be identified. In this article, we review 13 peer-reviewed publications that investigate informal STEM learning opportunities for underserved learners at a young age. We synthesize concepts such as competence, performance, recognition, supportive relationships, sense of belonging, agency, interest, and attitudes that influence underserved learners’ STEM identity development, and corresponding practical approaches such as personal relationships, role models, authentic settings, hands-on-activities, and non-stereotypical structures fostering agency. We also discuss theoretical frameworks for underserved learners’ STEM identity development. We suggest that recognition, a sense of belonging, supportive relationships, and agency play important roles in fostering STEM identity development in underserved students. The paper concludes with recommendations to change traditional patterns in informal and formal STEM education to empower underserved students to construct their own STEM identity as agentic individuals.
Targeting the gut microbiota and its metabolites for type 2 diabetes mellitus
Authors: Wu Jiaqiang , Yang Kangping , Fan Hancheng , Wei Meilin , Xiong Qin
Published: May 2023

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia and insulin resistance. The incidence of T2DM is increasing globally, and a growing body of evidence suggests that gut microbiota dysbiosis may contribute to the development of this disease. Gut microbiota-derived metabolites, including bile acids, lipopolysaccharide, trimethylamine-N-oxide, tryptophan and indole derivatives, and short-chain fatty acids, have been shown to be involved in the pathogenesis of T2DM, playing a key role in the host-microbe crosstalk. This review aims to summarize the molecular links between gut microbiota-derived metabolites and the pathogenesis of T2DM. Additionally, we review the potential therapy and treatments for T2DM using probiotics, prebiotics, fecal microbiota transplantation and other methods to modulate gut microbiota and its metabolites. Clinical trials investigating the role of gut microbiota and its metabolites have been critically discussed. This review highlights that targeting the gut microbiota and its metabolites could be a potential therapeutic strategy for the prevention and treatment of T2DM.
Regulation of enteroendocrine cell respiration by the microbial metabolite hydrogen sulfide
Authors: Larraufie Pierre , Haroun Kenza , Fleury Carla , Andriamihaja Mireille , Blachier François
Published: May 2023

Endocrine functions of the gut are supported by a scattered population of cells, the enteroendocrine cells (EECs). EECs sense their environment to secrete hormones in a regulated manner. Distal EECs are in contact with various microbial compounds including hydrogen sulfide (H2S) which modulate cell respiration with potential consequences on EEC physiology. However, the effect of H2S on gut hormone secretion remains discussed and the importance of the modulation of cell metabolism on EEC functions remains to be deciphered. The aim of this project was to characterize the metabolic response of EECs to H2S and the consequences on GLP-1 secretion. We used cell line models of EECs to assess their capacity to metabolize H2S at low concentration and the associated modulation of cell respiration. We confirmed that like what is observed in colonocytes, colonic EEC model, NCI-h716 cell line rapidly metabolizes H2S at low concentrations, resulting in transient increased respiration. Higher concentrations of H2S inhibited this respiration, with the concentration threshold for inhibition depending on cell density. However, increased or inhibited oxidative respiration had little effect on acute GLP-1 secretion. Overall, we present here a first study showing the EEC capacity to detoxify low concentrations of H2S and used this model to acutely address the importance of cell respiration on secretory activity.
The clinical and genetic features in patients coexisting primary breast and thyroid cancers
Authors: Fu Jingyao , He Miao , Wu Qiong , Zhang Xiangkai , Qi Xin , Shen Keyu , Wang Xiaochun , Zhang Guang
Published: May 2023

Background

We attempted to examine the clinical characteristics in patients with breast cancer (BC) and thyroid cancer (TC); explore the potential mechanisms of tumorigenesis and progression.

Methods

Using the Surveillance, Epidemiology, and End Result Program-9 (SEER-9) database, a retrospective study (1975-2017) was conducted on patients with BC and TC. We identified the common differentially expressed genes involved in BC and TC using the Gene Expression Omnibus database (GEO). Immunohistochemical staining (IHC) was performed to verify the expression of the hit gene in patients with co-occurrence of BC and TC. Using The Cancer Genome Atlas (TCGA) database, the relationship between gene expression and clinicopathological characters was determined. Gene set enrichment analysis (GSEA) was used to identify the pathways enriched in BC and TC.

Results

BC patients had a higher predisposition to develop TC (standardized incidence ratio, SIR: 1.29) and vice-versa (SIR: 1.12). Most of these patients were differentiated thyroid carcinoma (DTC) and hormone receptor (HR) - positive BC. The mRNA expression of COMP (Cartilage oligomeric matrix protein) was significantly overexpressed in BC and TC by analyzing the GEO database. The protein expression of COMP was increased in both BC and TC tissues obtained from the same patients validated by IHC. COMP was correlated with worse OS in BC (stage II-IV) and TC; it was the independent factor for prognosis of BC. GSEA indicated that the estrogen response and epithelial-mesenchymal transition (EMT) pathways were significantly enriched in both TC- and BC- COMP overexpressed groups.

Conclusion

The co-occurrence risk of BC and TC in the same individual is higher than in the general population. Overexpression of COMP could promote oncogenesis and progression in patients with BC and TC through estrogen signaling and EMT pathways.
Interrelations between clinical-psychological features and bone mineral density changes in post-menopausal women undergoing anti-osteoporotic treatment: a two-year follow-up
Authors: Martino Gabriella , Bellone Federica , Vicario Carmelo Mario , Gaudio Agostino , Corica Francesco , Squadrito Giovanni , Lund-Jacobsen Trine , Schwarz Peter , Lo Coco Gianluca , Morabito Nunziata , Catalano Antonino
Published: May 2023

Introduction

Psychological features have been bidirectionally associated with osteoporosis, but it is still unclear whether patient’s anxiety fluctuations during the anti-osteoporotic treatment can have an impact on bone mineral density (BMD) variation. The aim of this study was to investigate the interrelations between psychological distress features, such as anxiety, depression, health-related QoL (HRQoL) and bone health in women receiving anti-osteoporotic treatment.

Methods

192 post-menopausal osteoporotic women were treated with alendronate or risedronate according to the standard procedure. The levels of anxiety, depression, and perceived HRQoL, along with BMD, were assessed at baseline and at a 2-year follow-up.

Results

At the end of the study, the patients showed a statistically significant increase of both psychic and somatic anxiety (p<0.0001) and exhibited a worsening of depressive symptoms (p<0.0001), whereas HRQoL showed no change. BMD improved and no incident fractures occurred. BMD variation (ΔBMD) at lumbar spine was significantly associated with anxiety levels (r=0.23, p=0.021). Multiple regression analysis showed that both patients’ worsening anxiety levels (β = -0.1283, SE=0.06142, p=0.04) and their treatment adherence (β=0.09, SE=0.02, p=0.0006) were independently associated with ΔBMD.

Discussion

The findings of the current follow-up study suggest that BMD in post-menopausal women undergoing anti-osteoporotic treatment was predicted by treatment adherence and anxiety change over time.
The effects of sucrose and arsenic on muscular insulin signaling pathways differ between the gastrocnemius and quadriceps muscles
Authors: Pánico Pablo , Velasco Myrian , Salazar Ana María , Ostrosky-Wegman Patricia , Hiriart Marcia
Published: May 2023

Introduction

Insulin resistance in muscle can originate from a sedentary lifestyle, hypercaloric diets, or exposure to endocrine-disrupting pollutants such as arsenic. In skeletal muscle, insulin stimulates glucose uptake by translocating GLUT4 to the sarcolemma. This study aimed to evaluate the alterations induced by sucrose and arsenic exposure in vivo on the pathways involved in insulinstimulated GLUT4 translocation in the quadriceps and gastrocnemius muscles.

Methods

Male Wistar rats were treated with 20% sucrose (S), 50 ppm sodium arsenite (A), or both (A+S) in drinking water for 8 weeks. We conducted an intraperitoneal insulin tolerance (ITT) test on the seventh week of treatment. The quadriceps and gastrocnemius muscles were obtained after overnight fasting or 30 min after intraperitoneal insulin injection. We assessed changes in GLUT4 translocation to the sarcolemma by cell fractionation and abundance of the proteins involved in GLUT4 translocation by Western blot.

Results

Male rats consuming S and A+S gained more weight than control and Atreated animals. Rats consuming S, A, and A+S developed insulin resistance assessed through ITT. Neither treatments nor insulin stimulation in the quadriceps produced changes in GLUT4 levels in the sarcolemma and Akt phosphorylation. Conversely, A and A+S decreased protein expression of Tether containing UBX domain for GLUT4 (TUG), and A alone increased calpain-10 expression. All treatments reduced this muscle’s protein levels of VAMP2. Conversely, S and A treatment increased basal GLUT4 levels in the sarcolemma of the gastrocnemius, while all treatments inhibited insulin-induced GLUT4 translocation. These effects correlated with lower basal levels of TUG and impaired insulin-stimulated TUG proteolysis. Moreover, animals treated with S had reduced calpain-10 protein levels in this muscle, while A and A+S inhibited insulin-induced Akt phosphorylation.

Conclusion

Arsenic and sucrose induce systemic insulin resistance due to defects in GLUT4 translocation induced by insulin. These defects depend on which muscle is being analyzed, in the quadriceps there were defects in GLUT4 retention and docking while in the gastrocnemius the Akt pathway was impacted by arsenic and the proteolytic pathway was impaired by arsenic and sucrose.
Cellular dynamics of distinct skeletal cells and the development of osteosarcoma
Authors: Otani Shohei , Ohnuma Mizuho , Ito Kosei , Matsushita Yuki
Published: May 2023

Bone contributes to the maintenance of vital biological activities. At the cellular level, multiple types of skeletal cells, including skeletal stem and progenitor cells (SSPCs), osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, orchestrate skeletal events such as development, aging, regeneration, and tumorigenesis. Osteosarcoma (OS) is a primary malignant tumor and the main form of bone cancer. Although it has been proposed that the cellular origins of OS are in osteogenesis-related skeletal lineage cells with cancer suppressor gene mutations, its origins have not yet been fully elucidated because of a poor understanding of whole skeletal cell diversity and dynamics. Over the past decade, the advent and development of single-cell RNA sequencing analyses and mouse lineage-tracing approaches have revealed the diversity of skeletal stem and its lineage cells. Skeletal stem cells (SSCs) in the bone marrow endoskeletal region have now been found to efficiently generate OS and to be robust cells of origin under p53 deletion conditions. The identification of SSCs may lead to a more limited redefinition of bone marrow mesenchymal stem/stromal cells (BM-MSCs), and this population has been thought to contain cells from which OS originates. In this mini-review, we discuss the cellular diversity and dynamics of multiple skeletal cell types and the origin of OS in the native in vivo environment in mice. We also discuss future challenges in the study of skeletal cells and OS.
Senescence: a double-edged sword in beta-cell health and failure?
Authors: Varghese Sneha S. , Dhawan Sangeeta
Published: May 2023

Cellular senescence is a complex process marked by permanent cell-cycle arrest in response to a variety of stressors, and acts as a safeguard against the proliferation of damaged cells. Senescence is not only a key process underlying aging and development of many diseases, but has also been shown to play a vital role in embryogenesis as well as tissue regeneration and repair. In context of the pancreatic beta-cells, that are essential for maintaining glucose homeostasis, replicative senescence is responsible for the age-related decline in regenerative capacity. Stress induced premature senescence is also a key early event underlying beta-cell failure in both type 1 and type 2 diabetes. Targeting senescence has therefore emerged as a promising therapeutic avenue for diabetes. However, the molecular mechanisms that mediate the induction of beta-cell senescence in response to various stressors remain unclear. Nor do we know if senescence plays any role during beta-cell growth and development. In this perspective, we discuss the significance of senescence in beta-cell homeostasis and pathology and highlight emerging directions in this area that warrant our attention.
Available power estimation of wind farms based on deep spatio-temporal neural networks
Authors: Liu Yu , Huang Kunpeng , Liu Jincheng , Zhang Pei , Liu Zhao
Published: May 2023

With the development of advanced digital infrastructure in new wind power plants in China, the individual wind-turbine level data are available to power operators and can potentially provide more accurate available wind power estimations. In this paper, considering the state of the wind turbine and the loss in the station, a four-layer spatio-temporal neural network is proposed to compute the available power of wind farms. Specifically, the long short-term memory (LSTM) network is built for each wind turbine to extract the time-series correlations in historical data. In addition, the graph convolution network (GCN) is employed to extract the spatial relationship between neighboring wind turbines based on the topology and patterns of historical data. The case studies are performed using actual data from a wind farm in northern China. The study results indicate that the computation error using the proposed model is lower than that using the conventional physics-based methods and is also lower than that using other artificial intelligence methods.
A novel large-scale EV charging scheduling algorithm considering V2G and reactive power management based on ADMM
Authors: Zhang Chen , Sheinberg Rachel , Narayana Gowda Shashank , Sherman Michael , Ahmadian Amirhossein , Gadh Rajit
Published: May 2023

Electric vehicle aggregators (EVAs) that utilize vehicle-to-grid (V2G) technologies can function as both controllable loads and virtual power plants, providing key energy management services to the distribution system operator (DSO). EVAs can also balance the grid’s reactive power as a virtual static VAR compensator (SVC) and provide voltage stability by utilizing advanced electric vehicle (EV) chargers that are capable of four-quadrant operations to provide reactive power management. Finally, managed charging can benefit EVAs themselves by minimizing power factor penalties in their electricity bills. In this paper, we propose a novel EV charging scheduling algorithm based on a hierarchical distributed optimization framework that minimizes peak load and provides reactive power compensation for the DSO by collaboration with EVAs that manage both the active and the reactive charging and discharging power of participating EVs. Utilizing the alternative direction method of multipliers (ADMM), the proposed distributed optimization approach scales well with increased EV charging infrastructure by balancing active and reactive power while decreasing computational burden. In our proposed hierarchical approach, each EVA schedules the active and reactive EV charging and discharging power for 1) reactive power compensation in order to minimize power factor penalty and electricity cost accrued by the EVA, 2) satisfaction of each EV’s energy demand at minimal charging cost, and 3) peak shaving and load management for the DSO. When compared with an uncoordinated charging model, the efficacy of this proposed model is successfully demonstrated through a 300% decreased peak EV load for the DSO, 28% lower electricity costs for EV users, and 98.55% smaller power factor penalty, along with 17.58% lower overall electricity costs, for EVAs. The performance of our approach is validated in a case study with 50 EVs at multiple EVAs in an IEEE 13-bus test case and compared the results with uncoordinated EV charging.
A protection scheme based on impedance for LV and MV lines in microgrids with high-impedance fault detection capability
Authors: Nobakhti Seyyed Mohammad , Ketabi Abbas
Published: May 2023

Microgrid properties including bidirectional power flow in feeders, fault level decrease in the islanded mode, and intermittent nature of distributed generators (DGs) result in the malfunctioning of microgrid conventional protection schemes. In the present article, a protection scheme based on impedance is suggested for fault detection in LV and MV overhead and cable distribution lines in both grid-connected and islanded modes. To determine a fault detection index, new suggested equivalent circuits for doubly fed lines are applied. Relay location data and magnitude of positive sequence voltage of the other end of the line are used. It is simulated by PSCAD and MATLAB software in order to evaluate its performance and approve its validity. This scheme can detect even high-impedance faults in both grid connected and islanded modes in LV and MV overhead and cable distribution lines. In addition, it is robust against load and generation uncertainty and network reconfigurations. Low sampling rate and minimum data exchange are among the advantages of the proposed scheme.
Impact of microannulus on the efficiency of heat transfer in the bottomhole
Authors: Santos Livio , Dahi Taleghani Arash
Published: May 2023

To ensure feasible power generation from closed-loop geothermal wells, deeper wells are required to reach higher temperature zones. However, weak bonding between cement and casing or cement and formation may allow formation of a small gap (known as microannulus), which could have a negative effect on the heat extraction rate and consequently compromises the entire investment. Previous projects have reported that the output temperatures were significantly lower than the expected values, and the cause is believed to be cement debonding. This study aims to develop a reliable simulation model to demonstrate the impact of microannulus in closed-loop geothermal systems. Multi-physics finite element analysis is used to construct models with and without microannulus. The microannulus is modeled based on real cement evaluation logs, with gaps varying between a few micrometers to few millimeters. In extreme cases, the presence of microannulus is found to decrease the geothermal power by more than 35%. Furthermore, the possibility of heat loss containment is investigated by a sensitivity study of wellbore parameters. These sensitivity analyses demonstrate that cement and geothermal fluids with higher thermal conductivity can improve but cannot compensate the presence of microannuli. The results also highlight the importance of proper cementing design to ensure wellbore integrity and avoid geothermal power loss.