bluuebunny/crossref_metadata_2025 huggingface dataset:
Crustal velocity structure in the South Yellow Sea revealed by the joint tomographic inversion of reflected and refracted seismic waves
Authors: Ma Fei , Hou Fanghui , Li Tongyu , Wu Zhiqiang , Zhang Jianzhong
Published: January 2023

The crustal velocity structure in the South Yellow Sea (SYS) Basin is crucial for understanding the basin’s geological structure and evolution. OBS (ocean-bottom station) data from the OBS2013 line have been used to determine the crustal velocity structure in the SYS. The velocity model of the upper crust in the northern SYS was determined using first-arrival traveltime tomography. The model showed a higher resolution shallow crustal velocity structure but a lower resolution middle-lower crustal velocity structure. The crustal velocity structure, together with the Moho discontinuity in the SYS Basin, was also constructed using a human–computer interactive traveltime simulation, and the result was highly dependent on the prior knowledge of the operator. In this study, we reconstructed a crustal velocity model in the SYS Basin using a joint tomographic inversion of the traveltime and its gradient data of the reflected and refracted waves picked from the OBS data. The resolution of the inverted velocity structure from shallow-to-deep crust was improved. The results revealed that the massive high-velocity body below the Haiyang Sag of the Jiaolai Basin extends to the Qianliyan Uplift in the SYS; the low-velocity Cretaceous strata directly cover the pre-Sinitic metamorphic rock basement of the Sulu orogenic belt; and the thick Meso-Paleozoic marine strata are retained beneath the Meso–Cenozoic continental strata in the northern depression. The Moho depth in the SYS Basin ranges from 28 to 32 km.
Structural boundary and deep contact relationship between the Yangtze and Cathaysia Blocks from crustal thickness gradients
Authors: Han Rubing , Yang Dinghui , Li Qiusheng , Fu Wei , Zhu Gaohua , Zhang Hongshuang , Chen Hao , Cheng Yongzhi
Published: January 2023

The deep boundary and contact relationship between the Yangtze and Cathaysia Blocks (the major tectonic units of the Southern China Block), as well as the tectonic attributes of the Jiangnan Orogenic Belt, have remained unknown or controversial. Using data recorded by 128 portable broadband stations and 96 permanent stations, we obtained high-resolution images of crustal thickness and Poisson’s ratio in the study area. The influences of crustal anisotropy and inclined interface were eliminated by using the newly proposed receiver function H–κ–c stacking method. We then used a gradient analysis method to obtain crustal thickness gradients at the boundary of the Yangtze and Cathaysia Blocks for the first time. Our results reveal that the crustal thickness varies from >38 km in the Qinling–Dabie Orogenic Belt to <30 km east of the Tanlu Fault and Cathaysia Block. Areas with high Poisson’s ratios (>0.27) are concentrated on the flanks of the deep fault zone and the continental margin of the study area; those with low Poisson’s ratios (<0.23) are concentrated in the Jiangnan Orogenic Belt. Large crustal thickness gradients are found beneath the eastern part of the Jiujiang–Shitai buried fault (>5 km/°). Combined with the velocity structure and discontinuity characteristics at different depths, these findings suggest that the Jiujiang–Shitai fault may constitute a deep tectonic boundary dividing the Yangtze and Cathaysia Blocks on the lithospheric scale. Moreover, our results support that the Cathaysia Block subducted northwest-ward toward the southeastern margin of the Yangtze Block in the Neoproterozoic, and that the Jiujiang–Shitai buried fault and Jiangshan–Shaoxing fault are the deep and shallow crustal contact boundaries of the two Blocks, respectively; that is, the Yangtze Block overlaps the Cathaysia Block.
Spatiotemporal variations and overflow risk analysis of the Salt Lake in the Hoh Xil Region using machine learning methods
Authors: Wang Rui , Guo Lanlan , Chen Bo , Yang Yuting , Zheng Hao , Deng Fang , Liu Jifu
Published: January 2023

Global warming is inducing dramatic changes in fluvial geomorphology and reshaping the hydrological connections between rivers and lakes. The water level and area of the Salt Lake have increased rapidly since the outburst of the Zonag Lake in the Hoh Xil region of the Qinghai–Tibet Plateau in 2011, threatening the downstream infrastructure. However, fewer studies have focused on its spatiotemporal variation and overflow risk over long time series. Here, we used three machine learning algorithms: Classification and Regression Trees (CART), Random Forest (RF), and Support Vector Machine (SVM) to extract the area of the Salt Lake for a long time series, analyzed its spatiotemporal variation from 1973 to 2021, and finally assessed the overflow risk. The Kappa coefficient (KAPPA) and the overall accuracy (OA) were used to evaluate the performance of the models. The results showed that Random Forest performs superior in lake extraction (KAPPA = 0.98, overall accuracy = 0.99), followed by Classification and Regression Trees and Support Vector Machine. normalized difference water index is the relatively important feature variable in both RF and CART. Before the outburst event, the area change of the Salt Lake was consistent with the variation in precipitation; after that, it showed a remarkable area increase (circa 350%) in all orientations, and the main direction was the southeast. Without the construction of the emergency drainage channel, the simulation result indicated that the earliest and latest times of the Salt Lake overflow event are predicted to occur in 2020 and 2031, respectively. The results of this paper not only demonstrate that RF is more suitable for water extraction and help understand the water system reorganization event.
Control mechanism of the migration of heavy metal ions from gangue backfill bodies in mined-out areas
Authors: Zhang Yun , Liu Yongzi , Liu Jia , Zhan Rui , He Wei , Tong Liang , Wan Peifeng , Bai Licheng
Published: January 2023

In the process of solid backfill mining, the leaching of heavy metal ions from the gangue backfill body in the mined-out area can pose potential risk of polluting water resources in the mine. Accordingly, based on the environment of the gangue backfill body, the migration model of heavy metal ions from the gangue backfill body was established to reveal the pollution mechanism of water resources by the gangue backfill body in the mined-out area. The main factors that affect the migration of heavy metal ions were analyzed, and prevention and control techniques for the leaching and migration of heavy metal ions from gangue backfill bodies were proposed. Research showed that the heavy metal ions in gangue backfill bodies were subjected to the coupled action of seepage, concentration, and stress and then driven by water head pressure and gravitational potential energy to migrate downward along the pore channels in the floor, during which mine water served as the carrier. The migration distance of heavy metal ions increased with time. According to the migration rate, the migration process can be subdivided into three phases: the rapid migration phase (0–50 years), the slow migration phase (50–125 years), and the stable phase (125–200 years). It was concluded that the leaching concentration of heavy metal ions, the particle size of gangue, the permeability of floor strata, and the burial depth of coal seams were the main influencing factors of the migration of heavy metal ions. From the two perspectives of heavy metal ion leaching and migration, prevention and control techniques for the leaching and migration of heavy metal ions from gangue backfill bodies were proposed to protect water resources in mining area. The present study is of great significance to realizing utilization of solid waste in mines and protecting the ecological environment.
Real world effectiveness of subcutaneous semaglutide in type 2 diabetes: A retrospective, cohort study (Sema-MiDiab01)
Authors: Berra Cesare C. , Rossi Maria Chiara , Mirani Marco , Ceccarelli Ceccarelli Daniela , Romano Cristina , Sassi Lorenza , Peretti Elena , Favacchio Giuseppe , Pastore Ida , Folini Laura , Graziano Giusi , Lunati Maria Elena , Solerte Sebastiano Bruno , Fiorina Paolo
Published: January 2023

Introduction

Aim of the present study was to evaluate the real-world impact of once-weekly (OW) subcutaneous semaglutide on different end-points indicative of metabolic control, cardiovascular risk factors, and beta-cell function in type 2 diabetes (T2D).

Methods

This was a retrospective, observational study conducted in 5 diabetes clinics in Italy. Changes in HbA1c, fasting blood glucose (FBG), body weight, blood pressure, lipid profile, renal function, and beta-cell function (HOMA-B) during 12 months were evaluated.

Results

Overall, 594 patients (97% GLP-1RA naïve) were identified (mean age 63.9 ± 9.5 years, 58.7% men, diabetes duration 11.4 ± 8.0 years). After 6 months of treatment with OW semaglutide, HbA1c levels were reduced by 0.90%, FBG by 26 mg/dl, and body weight by 3.43 kg. Systolic blood pressure, total and LDL-cholesterol significantly improved. Benefits were sustained at 12 months. Renal safety was documented. HOMA-B increased from 40.2% to 57.8% after 6 months (p<0.0001).

Discussion

The study highlighted benefits of semaglutide on metabolic control, multiple CV risk factors, and renal safety in the real-world. Semaglutide seems to be an advisable option for preservation of β-cell function and early evidence suggests it might have a role in modifying insulin resistance (HOMA-IR), the pathogenetic basis of prediabetes and T2D.
Benefits of Huang Lian mediated by gut microbiota on HFD/STZ-induced type 2 diabetes mellitus in mice
Authors: Li Dan , Feng Guangli , Li Yue , Pan Han , Luo Pei , Liu Bo , Ding Tao , Wang Xin , Xu Huibo , Zhao Yufeng , Zhang Chenhong
Published: January 2023

Background

Huang Lian (HL), one of the traditional Chinese medicines (TCMs) that contains multiple active components including berberine (BBR), has been used to treat symptoms associated with diabetes for thousands of years. Compared to the monomer of BBR, HL exerts a better glucose-lowering activity and plays different roles in regulating gut microbiota. However, it remains unclear what role the gut microbiota plays in the anti-diabetic activity of HL.

Methods

In this study, a type 2 diabetes mellitus (T2DM) mouse model was induced with a six-week high-fat diet (HFD) and a one-time injection of streptozotocin (STZ, 75 mg/kg). One group of these mice was administrated HL (50 mg/kg) through oral gavage two weeks after HFD feeding commenced and continued for four weeks; the other mice were given distilled water as disease control. Comprehensive analyses of physiological indices related to glycolipid metabolism, gut microbiota, untargeted metabolome, and hepatic genes expression, function prediction by PICRUSt2 were performed to identify potential mechanism.

Results

We found that HL, in addition to decreasing body fat accumulation, effectively improved insulin resistance by stimulating the hepatic insulin-mediated signaling pathway. In comparison with the control group, HL treatment constructed a distinct gut microbiota and bile acid (BA) profile. The HL-treated microbiota was dominated by bacteria belonging to Bacteroides and the Clostridium innocuum group, which were associated with BA metabolism. Based on the correlation analysis, the altered BAs were closely correlated with the improvement of T2DM-related markers.

Conclusion

These results indicated that the anti-diabetic activity of HL was achieved, at least partly, by regulating the structure of the gut microbiota and the composition of BAs.
Small-signal oscillatory stability of a grid-connected PV power generation farm affected by the increasing number of inverters in daisy-chain connection
Authors: Zhou Yi , Cao Junzheng , Zhao Jing
Published: January 2023

The daisy-chain connection of inverters is one of the basic configurations of the power collecting network in a grid-connected photovoltaic (PV) power generation farm. In this study, the total impact of a cluster of M similar inverters in daisy-chain connection in the PV farm is examined in the following two aspects: 1) aggregated representation of the cluster of inverters is derived for stability study based on the dynamic equivalence. The derivation confirms the rationality of representing the cluster of inverters by an aggregated inverter connected to the external system via an equivalent reactance, which is the maximum eigenvalue of the matrix of daisy-chain connection defined in the article. 2) Analysis is conducted to indicate that the risk of oscillatory instability may be collectively induced by all the inverters in the daisy-chain connection in the cluster. This explains why the increasing number of inverters may imply the possible instability risk of a PV farm. An example of a power system with a grid-connected PV power generation farm is presented in the article to demonstrate and evaluate the analytical conclusion obtained.
Optimal energy flow in integrated heat and electricity system considering multiple dynamics
Authors: Cai Rong , Li Yafei , Qian Kejun
Published: January 2023

Wide promotion of combined heat and power (CHP) units necessitates the combined operation of the power and heating system. However, the dynamics and nonlinearity in integrated heat and electricity systems (IHES) remain an obstacle to efficient and accurate analysis. To handle this issue, this paper constructs an optimal energy flow (OEF) model for the coordinated operation of the IHES considering the multiple dynamics. The dynamic heating system model is formulated as a set of nonlinear partial differential and algebraic equations (PDAE). The dynamic CHP model is formulated as a set of nonlinear differential and algebraic equations (DAEs). Then, the finite difference method (FDM) is adopted to make the dynamics tractable in the OEF. On this basis, a comprehensive OEF model for IHES is proposed. Simulations in two cases verify the effectiveness of the proposed method and highlight the significance of the dynamics in IHES.
Multi-objective optimal dispatching of virtual power plants considering source-load uncertainty in V2G mode
Authors: Ren Lan , Peng Daogang , Wang Danhao , Li Jianfang , Zhao Huirong
Published: January 2023

To solve the risks brought by the uncertainty of renewable energy output and load demand to the virtual power plant dispatch, a multi-objective information gap decision theory (IGDT) dispatching model for virtual power plants considering source-load uncertainty under vehicle-to-grid (V2G) is proposed. With the lowest system operating cost and carbon emission as the optimization objectives, the multi-objective robust optimization model for virtual power plants is constructed based on the uncertainties of wind output, photovoltaic output and load demand guided by the time of use price. The weights of uncertainties quantify the effects of uncertainty factors. The adaptive reference vector based constrained multi-objective evolutionary algorithm is used to solve it. The weight coefficients, evasion coefficients of uncertainties and the penetration rate of electric vehicles are analyzed for the optimal dispatching of the virtual power plant. The algorithm results show that the method can effectively achieve load-side peak shaving and valley filling and has superiority in terms of economy, environmental benefits, robustness and stability.
RNA modification writers pattern in relation to tumor microenvironment and prognosis in prostate cancer
Authors: Cheng Xu , Yi Xuanzi
Published: January 2023

Background: RNA modifications are important in the study of epigenetic regulatory mechanisms in immune responses and tumorigenesis. When RNA writers are mutated or disrupted in expression, the genes associated with the pathways they modify are also disrupted and can activate or repress related pathways, affecting tumorigenesis and progression. However, the potential role of RNA writers in prostate cancer is unclear.

Methods: Based on data from three datasets, we describe 26 RNA writers that mediate gene expression and genetic mutation in prostate cancer and assess their expression patterns in 948 prostate cancer samples. Using principal component analysis algorithms, the RM Score was developed to quantify the RNA modification patterns of specific tumors.

Results: Two different categories were determined by unsupervised clustering methods, and survival analysis showed significant differences in OS prognosis between these two categories. Differentially expressed genes between the different categories were detected and the RNA writers-mediated scoring model RM_Score were constructed based on this. Also, the RM_Score was analyzed in relation to clinical characteristics, immune infiltration level, drug response, and efficacy of chemotherapy and immunotherapy. Those results confirm that multilayer alterations in epitope-modified RNA writers are associated with patient prognosis and with immune cell infiltration characteristics. Finally, we examined differentially expressed mRNA, lncRNA and miRNA between high and low RM_Score groups, based on which a ceRNA regulatory network was constructed.

Conclusion: This work is a comprehensive analysis of modified writers in prostate cancer and identified them to have a role in chemotherapy and immunotherapy.
Modeling C3 glomerulopathies: C3 convertase regulation on an extracellular matrix surface
Authors: Pisarenka Sofiya , Meyer Nicole C. , Xiao Xue , Goodfellow Renee , Nester Carla M. , Zhang Yuzhou , Smith Richard J. H.
Published: January 2023

Introduction

C3 glomerulopathies (C3G) are ultra-rare complement-mediated diseases that lead to end-stage renal disease (ESRD) within 10 years of diagnosis in ~50% of patients. Overactivation of the alternative pathway (AP) of complement in the fluid phase and on the surface of the glomerular endothelial glycomatrix is the underlying cause of C3G. Although there are animal models for C3G that focus on genetic drivers of disease, in vivo studies of the impact of acquired drivers are not yet possible.

Methods

Here we present an in vitro model of AP activation and regulation on a glycomatrix surface. We use an extracellular matrix substitute (MaxGel) as a base upon which we reconstitute AP C3 convertase. We validated this method using properdin and Factor H (FH) and then assessed the effects of genetic and acquired drivers of C3G on C3 convertase.

Results

We show that C3 convertase readily forms on MaxGel and that this formation was positively regulated by properdin and negatively regulated by FH. Additionally, Factor B (FB) and FH mutants impaired complement regulation when compared to wild type counterparts. We also show the effects of C3 nephritic factors (C3Nefs) on convertase stability over time and provide evidence for a novel mechanism of C3Nef-mediated C3G pathogenesis.

Discussion

We conclude that this ECM-based model of C3G offers a replicable method by which to evaluate the variable activity of the complement system in C3G, thereby offering an improved understanding of the different factors driving this disease process.
Transient autoantibodies to danger signals
Authors: Shaw Elana R. , Matzinger Polly
Published: January 2023

The Danger Model predicts that there are some molecules that no immune system can ever be fully tolerant of, namely proteins that are only transiently expressed during times of stress, infection, or injury. Among these are the danger/alarm signals themselves. Accordingly, a fleeting autoantibody response to danger signals is expected during times when they are released. Depending on context, these autoantibodies may serve beneficial “housekeeping” functions by removing surplus danger signals from the circulation or, conversely, create an immunodeficiency. Here, we will focus on the Type 1 Interferons as examples of foreseeable targets for a transient autoantibody response, but the principles outlined should hold for other danger-associated molecules as well.
Five genes as diagnostic biomarkers of dermatomyositis and their correlation with immune cell infiltration
Authors: Zhao Xiaohu , Si Shangkun
Published: January 2023

Background

Dermatomyositis (DM) is a rare autoimmune disease characterized by severe muscle dysfunction, and the immune response of the muscles plays an important role in the development of DM. Currently, the diagnosis of DM relies on symptoms, physical examination, and biopsy techniques. Therefore, we used machine learning algorithm to screen key genes, and constructed and verified a diagnostic model composed of 5 key genes. In terms of immunity, The relationship between 5 genes and immune cell infiltration in muscle samples was analyzed. These diagnostic and immune-cell-related genes may contribute to the diagnosis and treatment of DM.

Methods

GSE5370 and GSE128470 datasets were utilised from the Gene Expression Omnibus database as DM test sets. And we also used R software to merge two datasets and to analyze the results of differentially expressed genes (DEGs) and functional correlation analysis. Then, we could detect diagnostic genes adopting least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) analyses. The validity of putative biomarkers was assessed using the GSE1551 dataset, and we confirmed the area under the receiver operating characteristic curve (AUC) values. Finally, CIBERSORT was used to evaluate immune cell infiltration in DM muscles and the correlations between disease-related biomarkers and immune cells.

Results

In this study, a total of 414 DEGs were screened. ISG15, TNFRSF1A, GUSBP11, SERPINB1 and PTMA were identified as potential DM diagnostic biomarkers(AUC > 0.85),and the expressions of 5 genes in DM group were higher than that in healthy group (p < 0.05). Immune cell infiltration analyses indicated that identified DM diagnostic biomarkers may be associated with M1 macrophages, activated NK cells, Tfh cells, resting NK cells and Treg cells.

Conclusion

The study identified that ISG15, TNFRSF1A, GUSBP11, SERPINB1 and PTMA as potential diagnostic biomarkers of DM and these genes were closely correlated with immune cell infiltration.This will contribute to future studies in diagnosis and treatment of DM.
Investigation of the molecular mechanisms which contribute to the survival of the polychaete Platynereis spp. under ocean acidification conditions in the CO2 vent system of Ischia Island (Italy)
Authors: Signorini Silvia Giorgia , Munari Marco , Cannavacciuolo Antonio , Nannini Matteo , Dolfini Diletta , Chiarore Antonia , Farè Fiorenza , Fontana Manuela , Caruso Donatella , Gambi Maria Cristina , Della Torre Camilla
Published: January 2023

The continuous increase of CO2 emissions in the atmosphere due to anthropogenic activities is one of the most important factors that contribute to Climate Change and generates the phenomenon known as Ocean Acidification (OA). Research conducted at the CO2 vents of Castello Aragonese (Ischia, Italy), which represents a natural laboratory for the study of OA, demonstrated that some organisms, such as polychaetes, thrive under acidified conditions through different adaptation mechanisms. Some functional and ecological traits promoting tolerance to acidification in these organisms have been identified, while the molecular and physiological mechanisms underlying acclimatisation or genetic adaptation are still largely unknown. Therefore, in this study we investigated epigenetic traits, as histone acetylation and methylation, in Platynereis spp. individuals coming from the Castello vent, and from a nearby control site, in two different periods of the year (November-June). Untargeted metabolomics analysis was also carried out in specimens from the two sites. We found a different profile of acetylation of H2B histone in the control site compared to the vent as a function of the sampling period. Metabolomic analysis showed clear separation in the pattern of metabolites in polychaetes from the control site with respect to those from the Castello vent. Specifically, a significant reduction of lipid/sterols and nucleosides was measured in polychaetes from the vent. Overall results contribute to better understand the potential metabolic pathways involved in the tolerance to OA.
Toxicological effects of cadmium on deep-sea mussel Gigantidas platifrons revealed by a combined proteomic and metabolomic approach
Authors: Zhou Li , Li Mengna , Zhong Zhaoshan , Chen Hao , Wang Minxiao , Lian Chao , Wang Hao , Zhang Huan , Cao Lei , Li Chaolun
Published: January 2023

Introduction

Marine metal contamination caused by deep-sea mining activities has elicited great concern from both social and scientific communities. Among the various metals deep-sea organisms might encounter, cadmium (Cd) is a widely detected metal that in very small amounts is nonetheless capable of severe toxicity. Yet due to both remoteness and technical challenges, insights into the effects of metal exposure resulting from mining activities upon deep-sea organisms are limited.

Methods

Here, we investigated Cd’s toxicological effects on deep-sea mussels of Gigantidas platifrons exposed to 100 or 1000 g/L of Cd for 7 days; an integrated approach was used that incorporated proteomics and metabolomics along with traditional approaches (metal concentrations, metal subcellular distribution, and anti-oxidative and immune-related biochemical indexes).

Results and Discussion

Results showed that Cd exposure caused significant Cd’s accumulation in mussel gills and redistribution of Cd among subcellular compartments, with cellular debris being the primary binding site. Although anti-oxidative enzymes activities (superoxide dismutase and catalase) were not significantly altered in mussel gills of both exposed groups, the markedly increased level of glutathione S-transferase detected via proteomic technique clearly evinced that deep-sea mussels suffered from oxidative stress under Cd exposure. Besides, altered activities of acid phosphatase and alkaline phosphatase assayed by traditional methods along with the predominant presence of largely altered immune-related proteins detected by proteomic data strongly revealed an immune response of deep-sea mussels elicited by Cd. In addition, results of proteomics combined with those of non-targeted metabolomics demonstrated that Cd could exert toxicity by disrupting cytoskeleton structure, ion homeostasis, and primary metabolisms of energy, lipid, and nucleotide in deep-sea mussels. As demonstrated in this study, proteomics and metabolomics can be used in tandem to provide valuable insights into the molecular mechanisms of deep-sea organisms’ response to Cd exposure and for helping to discover potential biomarkers for application during deep-sea mining assessments.
Responses of Karenia mikimotoi to allelochemical linoleic acid: Growth inhibition, photosynthetic damage, oxidative stress and cell apoptosis
Authors: Wang Renjun , Wang Chao , Liu Xiuxia , Chen Junfeng , Liu Chunchen , Song Yuhao , Ding Ning , Gao Peike
Published: January 2023

Linoleic acid (LA), a potentially algae-inhibiting chemical released by macroalgae, has been shown to hinder the growth of numerous bloom-forming species. The allelopathic effects of LA (varying from 100 μg/L to 900 μg/L) on harmful microalgae K. mikimotoi were examined using population growth dynamics and physiological levels of K. mikimotoi. LA (>500 μg/L) strongly inhibited algal growth with most cells halted at the S and G2 phases and an evident drop in photosynthetic pigments (chlorophyll a (chl a), chlorophyll c (chl c) and carotenoids). Furthermore, chlorophyll fluorescence parameters such as Fv/Fm, PI, ETo/RC showed a declining trend whereas ABS/RC, DIo/RC, TRo/RC showed an increasing trend with increasing LA exposure concentrations. The level of intracellular reactive oxygen species (ROS) was considerably higher, indicating that LA promoted oxidative stress in K. mikimotoi. Excessive ROS promoted apoptosis in K. mikimotoi, which was noted by increased activity of caspase-3, caspase-9, and flow cytometry (FCM) data. Furthermore, N-acetylcysteine (NAC) and N-Acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO) lowered the apoptotic rates of the LA-treated algal cells, indicating that the aforementioned inhibitors delayed K. mikimotoi apoptosis under LA treatment. To summarize, cell cycle arrest of K. mikimotoi is less sensitive to ROS, but the overproduction of ROS generated by LA activated caspase-3 and caspase-9, which further promoted the apoptosis of K. mikimotoi. This research showed that LA might have great potential and application prospects in controlling the outbreak of harmful algae.
Physics-informed machine learning combining experiment and simulation for the design of neodymium-iron-boron permanent magnets with reduced critical-elements content
Authors: Kovacs Alexander , Fischbacher Johann , Oezelt Harald , Kornell Alexander , Ali Qais , Gusenbauer Markus , Yano Masao , Sakuma Noritsugu , Kinoshita Akihito , Shoji Tetsuya , Kato Akira , Hong Yuan , Grenier Stéphane , Devillers Thibaut , Dempsey Nora M. , Fukushima Tetsuya , Akai Hisazumi , Kawashima Naoki , Miyake Takashi , Schrefl Thomas
Published: January 2023

Rare-earth elements like neodymium, terbium and dysprosium are crucial to the performance of permanent magnets used in various green-energy technologies like hybrid or electric cars. To address the supply risk of those elements, we applied machine-learning techniques to design magnetic materials with reduced neodymium content and without terbium and dysprosium. However, the performance of the magnet intended to be used in electric motors should be preserved. We developed machine-learning methods that assist materials design by integrating physical models to bridge the gap between length scales, from atomistic to the micrometer-sized granular microstructure of neodymium-iron-boron permanent magnets. Through data assimilation, we combined data from experiments and simulations to build machine-learning models which we used to optimize the chemical composition and the microstructure of the magnet. We applied techniques that help to understand and interpret the results of machine learning predictions. The variables importance shows how the main design variables influence the magnetic properties. High-throughput measurements on compositionally graded sputtered films are a systematic way to generate data for machine data analysis. Using the machine learning models we show how high-performance, Nd-lean magnets can be realized.
Aerosol delivery through high-flow nasal therapy: Technical issues and clinical benefits
Authors: Calabrese Cecilia , Annunziata Anna , Mariniello Domenica Francesca , Allocca Valentino , Imitazione Pasquale , Cauteruccio Rosa , Simioli Francesca , Fiorentino Giuseppe
Published: January 2023

High-flow nasal cannula (HFNC) therapy is an oxygen delivery method particularly used in patients affected by hypoxemic respiratory failure. In comparison with the conventional “low flow” oxygen delivery systems, it showed several important clinical benefits. The possibility to nebulize drugs via HFNC represents a desirable medical practice because it allows the administration of inhaled drugs, mostly bronchodilators, without the interruption or modification of the concomitant oxygen therapy. HFNC, by itself has shown to exert a small but significant bronchodilator effect and improves muco-ciliary clearance; thus, the nebulization of bronchodilators through the HFNC circuit may potentially increase their pharmacological activity. Several technical issues have been observed which include the type of the nebulizer that should be used, its position within the HFNC circuit, and the optimal gas flow rates to ensure an efficient drug delivery to the lungs both in “quiet” and “distressed” breathing patterns. The aim of this review has been to summarize the scientific evidence coming from “in vitro” studies and to discuss the results of “in vivo” studies performed in adult subjects, mainly affected by obstructive lung diseases. Most studies seem to indicate the vibrating mesh nebulizer as the most efficient type of nebulizer and suggest to place it preferentially upstream from the humidifier chamber. In a quite breathing patterns, the inhaled dose seems to increase with lower flow rates while in a “distressed” breathing pattern, the aerosol delivery is higher when gas flow was set below the patient’s inspiratory flow, with a plateau effect seen when the gas flow reaches approximately 50% of the inspiratory flow. Although several studies have demonstrated that the percentage of the loaded dose nebulized via HFNC reaching the lungs is small, the bronchodilator effect of albuterol seems not to be impaired when compared to the conventional inhaled delivery methods. This is probably attributed to its pharmacological activity. Prospective and well-designed studies in different cohort of patients are needed to standardize and demonstrate the efficacy of the procedure.
Retinal detachments in a patient with minimal change nephrotic syndrome: Case report and review of the literature
Authors: Ye Chunjian , Qiu Miaohua , Zhong Yu , Chen Jiejian
Published: January 2023

Background

To report an unusual case of minimal change nephrotic syndrome with sudden bilateral retinal detachment.

Case presentation

A 54-year-old woman with minimal change nephrotic syndrome presented with sudden-onset visual blurring in both eyes. Optical coherence tomography scans revealed macular schisis and extramacular intraretinal separation. A kidney biopsy confirmed the diagnosis of minimal change disease. Glucocorticoid therapy was quickly started. During remission, her vision was restored, with complete resolution of the subretinal fluid observed on optical coherence tomography.

Conclusions

In minimal change nephrotic syndrome, fluid accumulation in the retina layer may occur, and gravity-induced vitreous traction on the inferior retina may cause retinal detachment. Patients should be advised to avoid large swings of the head and neck, handstands, and other activities that may increase the risk of retinal detachment. The possibility of retinal detachment should be considered when blurred vision occurs.
Advanced age is associated with increased adverse outcomes in patients undergoing middle cerebral artery stenting
Authors: Wang Gong , Liu Juan , He Shengrong , Zhang Xi , Yang Libai , Gao Fei , Guo Yu , Xu Rui
Published: January 2023

Purpose

This study tried to evaluate whether advanced age has an increased incidence of major complications in patients undergoing MCA stenting.

Methods

A total of 348 patients who underwent MCA stenting were reviewed from a prospectively maintained database. Ninety-day ischemic stroke, intracerebral hemorrhage, and death outcomes were compared among the young (≤40 years old), middle (41–60 years old) and old (≥61 years old) groups. Univariate analysis and multivariable logistic regression analysis were used to investigate different variables associated with 90-day major adverse events. Kaplan–Meier analysis was performed to determine long-term outcomes during follow-up.

Results

The incidence of 90-day ischemic stroke was 9.26% in the old group, 2.86% in the middle group, and 0% in the young group (P = 0.024). The incidence of all 90-day major adverse events was 3.33% in patients ≤40 years old, 19.90% in patients 41–60 years old, and 24.07% in patients ≥61 years old, with statistical significance (P = 0.04). Advanced age was associated with increased 90-day ischemic stroke (OR = 1.074, 95% CI: 1.019–1.132, P = 0.007; adjusted OR: 1.071, 95% CI: 1.008–1.138, P = 0.026) and 90-day death (OR = 1.072, 95% CI: 1.012–1.135, P = 0.018; adjusted OR: 1.095, 95% CI: 1.015–1.182, P = 0.018). Meanwhile, advanced age was also associated with decreased long-term survival and ischemic stroke-free survival during follow-up.

Conclusion

Our data indicated that MCA stenting in elderly patients is associated with a high risk of adverse events and should be cautiously considered.
Photophobia and migraine outcome during treatment with galcanezumab
Authors: Schiano di Cola Francesca , Ceccardi Giulia , Bolchini Marco , Caratozzolo Salvatore , Liberini Paolo , Padovani Alessandro , Rao Renata
Published: January 2023

Background

Calcitonin gene-related peptide (CGRP) plays a pivotal role in migraine physiology, not only regarding migraine pain but also associated symptoms such as photophobia. The aim of the present study was to assess monoclonal antibodies targeting CGRP efficacy not only in terms of headache and migraine frequency and disability but also in reducing ictal photophobia.

Material and methods

This is a retrospective observational study, conducted at the Headache Center–ASST Spedali Civili Brescia. All patients in monthly treatment with galcanezumab with at least a 6-month follow-up in September 2022 with reported severe photophobia during migraine attacks were included. Data regarding headache frequency, analgesics consumption, and migraine disability were collected quarterly. Moreover, patients were asked the following information regarding photophobia: (1) whether they noticed an improvement in photophobia during migraine attacks since galcanezumab introduction; (2) the degree of photophobia improvement (low, moderate, and high); and (3) timing photophobia improvement.

Results

Forty-seven patients were enrolled in the present study as they met the inclusion criteria. Seventeen patients had a diagnosis of high-frequency episodic migraine and 30 of chronic migraine. From baseline to T3 and T6, a significant improvement in terms of headache days (19.2 ± 7.6 vs. 8.6 ± 6.8 vs. 7.7 ± 5.7; p < 0.0001), migraine days (10.4 ± 6.7 vs. 2.9 ± 4.3 vs. 3.6 ± 2.8; p < 0.0001), analgesics consumption (25.1 ± 28.2 vs. 7.6 ± 7.5 vs. 7.6 ± 8.1; p < 0.0001), MIDAS score (82.1 ± 48.4 vs. 21.6 ± 17.6 vs. 18.1 ± 20.5; p < 0.0001), and HIT-6 score (66.2 ± 6.2 vs. 57.2 ± 8.6 vs. 56.6 ± 7.6; p < 0.0001) was found. Thirty-two patients (68.1%) reported a significant improvement in ictal photophobia, with over half of the patients reporting it within the first month of treatment. Photophobia improvement was more frequent in patients with episodic migraine (p = 0.02) and triptans responders (p = 0.03).

Conclusions

The present study confirms previous reports regarding galcanezumab efficacy beyond migraine frequency. In particular, over 60% of patients, in our cohort, documented a significant improvement also in reducing ictal photophobia. This improvement was, in most patients, moderate to high, and within the first 6 months of treatment, regardless of the clinical response on migraine frequency.
Study of brain network alternations in non-lesional epilepsy patients by BOLD-fMRI
Authors: Li Zhisen , Hou Xiaoxia , Lu Yanli , Zhao Huimin , Wang Meixia , Xu Bo , Shi Qianru , Gui Qian , Wu Guanhui , Shen Mingqiang , Zhu Wei , Xu Qinrong , Dong Xiaofeng , Cheng Qingzhang , Zhang Jibin , Feng Hongxuan
Published: January 2023

Objective

To investigate the changes of brain network in epilepsy patients without intracranial lesions under resting conditions.

Methods

Twenty-six non-lesional epileptic patients and 42 normal controls were enrolled for BOLD-fMRI examination. The differences in brain network topological characteristics and functional network connectivity between the epilepsy group and the healthy controls were compared using graph theory analysis and independent component analysis.

Results

The area under the curve for local efficiency was significantly lower in the epilepsy patients compared with healthy controls, while there were no differences in global indicators. Patients with epilepsy had higher functional connectivity in 4 connected components than healthy controls (orbital superior frontal gyrus and medial superior frontal gyrus, medial superior frontal gyrus and angular gyrus, superior parietal gyrus and paracentral lobule, lingual gyrus, and thalamus). In addition, functional connectivity was enhanced in the default mode network, frontoparietal network, dorsal attention network, sensorimotor network, and auditory network in the epilepsy group.

Conclusion

The topological characteristics and functional connectivity of brain networks are changed in in non-lesional epilepsy patients. Abnormal functional connectivity may suggest reduced brain efficiency in epilepsy patients and also may be a compensatory response to brain function early at earlier stages of the disease.
Proof of lung muscarinic receptor occupancy by tiotropium: Translational Positron Emission Tomography studies in non-human primates and humans
Authors: Cselényi Zsolt , Jucaite Aurelija , Ewing Pär , Stenkrona Per , Kristensson Cecilia , Johnström Peter , Schou Magnus , Bolin Martin , Halldin Christer , Larsson Bengt , Grime Ken , Eriksson Ulf G , Farde Lars
Published: January 2023

Introduction

Molecular imaging has not been used to support the development of drugs for the treatment of pulmonary disorders. The aim of the present translational study was to advance quantitative pulmonary PET imaging by demonstrating occupancy of the reference asthma drug tiotropium at muscarinic acetylcholine receptors (mAChR).

Methods

PET imaging was performed using the muscarinic radioligand [11C]VC-002. The key methodological step involved estimating muscarinic receptor binding while disentangling it from the background of non-specific binding. The relationship between tiotropium exposure and receptor occupancy (RO) was assessed in non-human primates (NHPs) after intravenous injection of tiotropium doses at a broad dose interval (0.03–1 µg/kg). The feasibility of measuring RO in the human lung was then confirmed in seven healthy human subjects after inhalation of a single therapeutic dose of tiotropium (18 µg).

Results

There was an evident effect of tiotropium on [11C]VC-002 binding to mAChRs in lungs in both NHPs and humans. In NHPs, RO was 11 to 78% and increased in a dose dependent manner. Non-displaceable binding in NHPs was about 10% of total binding. In humans, RO was 6%–65%, and non-displaceable binding was about 20% of total binding at baseline.

Discussion

The results demonstrate that [11C]VC-002 binds specifically to mAChRs in the lungs enabling the assessment of RO following administration of muscarinic antagonist drugs. Furthermore, the methodology has potential not only for dose finding and comparison of drug formulations in future applied studies, but also for evaluating changes in lung receptor distribution during disease or in response to therapy.

Clinical Trial Registration

ClinicalTrials.gov, identifier: NCT03097380.
Study on the preparation process of quinoa anti-hypertensive peptide and its stability
Authors: Fan Xing , Ma Xuemei , Maimaitiyiming Ruxianguli , Aihaiti Aihemaitijiang , Yang Jiangyong , Li Xianai , Wang Xiaoyun , Pang Guangxian , Liu Xiaolu , Qiu Chenggong , Abra Redili , Wang Liang
Published: January 2023

Quinoa seeds are a food resource rich in protein, vitamins, minerals, and other functional components such as polyphenols, polysaccharides, and saponins. The seeds have become favored by modern consumers due to being gluten-free and featuring a high protein content. This study focused on the preparation of quinoa peptides by short-time enzymatic-assisted fermentation. Quinoa flour (QF) was mixed with water in a certain ratio before being enzymatically digested with 0.5% amylase and 0.1% lipase for 6 h. Then, 16 bacterial taxa were used for fermentation, respectively. The peptide content in the resulting fermentation broths were determined by the biuret method. The dominant taxon was then identified and the peptide content, amino acid distribution, and molecular weight distribution of the prepared quinoa peptides were analyzed. Further, the temperature, pH, metal ions, organic solvents, ion concentration, and anti-enzyme stability of the quinoa anti-hypertensive peptides of different molecular weights after fermentation with the dominant taxon were investigated. Finally, the inhibitory activity of fermented quinoa peptides on bacteria was studied. The results show that the peptide content of the fermentation broth reached 58.72 ± 1.3% at 40 h of fermentation with Lactobacillus paracasei and the molecular weights of the hydrolyzed quinoa peptides were mainly distributed below 2 kDa by polyacrylamide gel. The Angiotensin Converting Enzyme (ACE) inhibition and peptide retention of the 0–3 kDa quinoa peptides were screened to be high and stable. At the same time, the inhibitory activity of quinoa peptide after fermentation on E. coli was obvious. This study provides a theoretical basis for further research on quinoa peptide and its application in industrial production, and also lays a foundation for the later application of polypeptides in new food and chemical products.
The treatment of acute promyelocytic leukemia in 2023: Paradigm, advances, and future directions
Authors: Iyer Sunil Girish , Elias Laila , Stanchina Michele , Watts Justin
Published: January 2023

The transformation of acute promyelocytic leukemia (APL) from an often fatal to highly curable cancer with long-term survival exceeding 90% is one of the greatest and most inspiring successes in oncology. A deeper understanding of the pathogenesis of APL heralded the introduction of highly effective therapies targeting the mutant protein that drives the disease, leading to the chemotherapy-free approach to cure almost all patients. In this review, we discuss the paradigm of treatment of APL in 2023, reinforce the high risk of early death without prompt initiation of treatment at first clinical suspicion, and dedicate a special focus to novel agents and future directions to improve cure rates and quality of life in patients affected by APL.
Comparative genomic analysis of esophageal squamous cell carcinoma among different geographic regions
Authors: Zhang Ruixiang , Li Canjun , Wan Zhiyi , Qin Jianjun , Li Yong , Wang Zhen , Zheng Qingfeng , Kang Xiaozheng , Chen Xiankai , Li Yun , He Jie , Li Yin
Published: January 2023

Introduction

Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence, survival, and risk factors. Although the genomic characteristics of ESCC have been extensively characterized, the genomic differences between different geographic regions remain unclear.

Methods

In this study, we sequenced 111 patients with ESCC from northern (NC) and southern (SC) China, combined their data with those of 1081 cases from previous reports, and performed a comparative analysis among different regions. In total, 644 ESCC cases were collected from six geographic regions (NC, SC, Xinjiang, China [XJC], Japan [JP], Vietnam [VN], and Europe & America [EA]) as the discovery cohort. Validation cohort 1 included 437 patients with ESCC from the NC region. Validation cohort 2 included 54 and 57 patients from the NC and SC regions, respectively.

Results

Patients with ESCC in different regions had different genomic characteristics, including DNA signatures, tumor mutation burdens, significantly mutated genes (SMGs), altered signaling pathways, and genes associated with clinical features. Based on both the DNA mutation signature and the mutation profile of the most common genes, the NC and SC groups were clustered close together, followed by the JP, XJC, EA, and VN groups. Compared to patients with ESCC from SC, SMGs, including KMT2D, FAT1, and NOTCH1 were more frequently identified in patients with ESCC from NC. Furthermore, some genes (TDG and DNAH8) correlated with overall survival in completely opposite ways in patients with ESCC from different geographical regions.

Conclusions

Our study provides insights into genomic differences in ESCC among different regions. These differences may be related to differences in environmental carcinogens, incidence, and survival.