bluuebunny/crossref_metadata_2025 huggingface dataset:
MODIFICATION OF MINERAL RAW MATERIAL BY RADIATION PRE-TREATMENT BEFORE PROCESSING: FEATURES AND PROSPECTS
Authors: Rostovtsev Victor I.
Published: October 2021

The earlier case-studies of rebellious lead-zinc ore with grain size of -3 mm at the Chinakal Institute of Mining and Budker Institute of Nuclear Physics, Siberian Branch of the Russian Academy of Sciences provided data on improvement of disintegration selectivity and improved dissociation of useful minerals owing to preliminary treatment by a stream of electrons. The goal of this research is the integrated analysis of the change in the strength of core samples of some rocks, such as limestone, hornfels and granite, after their modification by radiation by a stream of high-energy electrons. It is found that the increase in the absorbed radiation dose results in the change in the strength and deformation properties: ultimate compression strength, modulus of deformation and elasticity modulus. In case of limestone, the ultimate uniaxial compression without radiation treatment is 49.11 MPa and drops to 35.24 MPa at the absorbed dose of 15 kGy. In case of granite, the absorption dose of 10 kGy decreases the ultimate compression strength from 68.33 to 35.08 MPa. The energy input in fracture and crushing is estimated on the equipment designed for uniaxial loading of cores at the Chinakal Institute of Mining. The energy input in fracture and crushing make 78.6 and 7004.2 J/kg for initial granite and 30.6 and 4708.8 J/kg for granite modified by radiation. The size of particle after crushing of treated cores reduces from 10.98 to 8.76 mm. The novelty of this study is the found effect of the range coverage in weakening of minerals with grain sizes to 30-50 mm, including cylindrical granite cores with diameters of 30 mm and lengths of 60 mm (equivalent spherical diameter is 43.2 mm) due to the shock waves generated in minerals during deceleration of electrons in the stream. This effect can be utilized to reduce the energy consumption of the pre-treatment technology and to minimize mineral losses in subsequent processing.
The Research Progress of Electrical Impedance Tomography for Lung Monitoring
Authors: Shi Yan , Yang ZhiGuo , Xie Fei , Ren Shuai , Xu ShaoFeng
Published: October 2021

Medical imaging can intuitively show people the internal structure, morphological information, and organ functions of the organism, which is one of the most important inspection methods in clinical medical diagnosis. Currently used medical imaging methods can only be applied to some diagnostic occasions after qualitative lesions have been generated, and the general imaging technology is usually accompanied by radiation and other conditions. However, electrical impedance tomography has the advantages of being noninvasive and non-radiative. EIT (Electrical Impedance Tomography) is also widely used in the early diagnosis and treatment of some diseases because of these advantages. At present, EIT is relatively mature and more and more image reconstruction algorithms are used to improve imaging resolution. Hardware technology is also developing rapidly, and the accuracy of data collection and processing is continuously improving. In terms of clinical application, EIT has also been used for pathological treatment of lungs, the brain, and the bladder. In the future, EIT has a good application prospect in the medical field, which can meet the needs of real-time, long-term monitoring and early diagnosis. Aiming at the application of EIT in the treatment of lung pathology, this article reviews the research progress of EIT, image reconstruction algorithms, hardware system design, and clinical applications used in the treatment of lung diseases. Through the research and introduction of several core components of EIT technology, it clarifies the characteristics of EIT system complexity and its solutions, provides research ideas for subsequent research, and once again verifies the broad development prospects of EIT technology in the future.
Monitoring Group Activity of Hamsters and Mice as a Novel Tool to Evaluate COVID-19 Progression, Convalescence, and rVSV-ΔG-Spike Vaccination Efficacy
Authors: Melamed Sharon , Politi Boaz , Grauer Ettie , Achdout Hagit , Aftalion Moshe , Gur David , Tamir Hadas , Yahalom-Ronen Yfat , Maimon Shlomy , Yitzhak Efi , Weiss Shay , Rosner Amir , Erez Noam , Yitzhaki Shmuel , Shapira Shmuel C , Paran Nir , Mamroud Emanuelle , Vagima Yaron , Israely Tomer
Published: October 2021

The COVID-19 pandemic initiated a worldwide race toward the development of treatments and vaccines. Small animal models included the Syrian golden hamster and the K18-hACE2 mice infected with SARS-CoV-2 to display a disease state with some aspects of human COVID-19. A group activity of animals in their home cage continuously monitored by the HCMS100 (Home cage Monitoring System 100) was used as a sensitive marker of disease, successfully detecting morbidity symptoms of SARS-CoV-2 infection in hamsters and in K18-hACE2 mice. COVID-19 convalescent hamsters rechallenged with SARS-CoV-2 exhibited minor reduction in group activity compared to naive hamsters. To evaluate the rVSV-ΔG-spike vaccination efficacy against SARS-CoV-2, we used the HCMS100 to monitor the group activity of hamsters in their home cage. A single-dose rVSV-ΔG-spike vaccination of the immunized group showed a faster recovery than the nonimmunized infected hamsters, substantiating the efficacy of rVSV-ΔG-spike vaccine. HCMS100 offers nonintrusive, hands-free monitoring of a number of home cages of hamsters or mice modeling COVID-19.
Expression of Ferroptosis-Related Genes Shapes Tumor Microenvironment and Pharmacological Profile in Gastric Cancer
Authors: Xiao Shilang , Liu Xiaoming , Yuan Lingzhi , Chen Xiao , Wang Fen
Published: October 2021

Background: Ferroptosis is a form of regulated cell death that occurs as a consequence of lethal lipid peroxidation. A wealth of studies has demonstrated that ferroptosis profoundly modulated numerous biological behaviors of tumor. However, its natural functions in gastric cancer (GC) remain to be explored.

Methods: Firstly, a total of over 1,000 GC patients from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database were included in our study. Secondly, 32 ferroptosis-related genes were extracted from the ferrDb website. Then, unsupervised clustering was performed to classify patients into three distinct ferroptosis-related clusters. Subsequently, we systematically and comprehensively explored the biological characteristics of each cluster. Finally, we constructed a scoring system, named ferroptosis score, to quantify each cluster and also investigated the predictive therapeutic value of the ferroptosis score for chemotherapy and immunotherapy.

Results: Based on the expressions of 32 ferroptosis-related genes, three distinct ferroptosis-related subtypes with various biological characteristics were determined. Integrated analysis showed that cluster 1 is a microsatellite instability (MSI)-like subtype, cluster 2 is an epithelial–mesenchymal transition (EMT)-like subtype, while cluster 3 tends to be a metabolic-like subtype. Prognostic analysis revealed that patients in cluster 2 had a worse overall survival and relapse-free survival. The distribution of the ferroptosis score was significantly different in clusters and gene clusters. The ferroptosis score could predict the biological characteristics of each cluster, the stromal activity, and progression of tumor. The low ferroptosis score group was characterized by the activation of antigen processing and presentation, DNA damage repair pathways, and metabolic pathways, while the high ferroptosis score group was characterized by stromal activation. In response to anticancer drugs, the ferroptosis score was highly negatively associated with drugs targeting MAPK signaling and PI3K/mTOR signaling, while it was positively correlated with drugs targeting the cell cycle, mitosis, and metabolism. Finally, we also proved that the ferroptosis score could serve as a reliable biomarker to predict response to immunotherapy.

Conclusion: This work revealed that tumor cells and their surrounding microenvironment could be shaped by varying the activation degrees of ferroptosis. Establishing ferroptosis-related subtypes would guide in predicting the biological features of individual tumors and selecting appropriate treatment protocols for patients.
4-Hydroxy-2-Nonenal Promotes Cardiomyocyte Necroptosis via Stabilizing Receptor-Interacting Serine/Threonine-Protein Kinase 1
Authors: Zhai Xiaoxuan , Wang Wenjun , Sun Shukun , Han Yu , Li Jiaxin , Cao Shengchuan , Li Ruochuan , Xu Tonghui , Yuan Qiuhuan , Wang Jiali , Wei Shujian , Chen Yuguo
Published: October 2021

Background: Necroptosis is a vital regulator of myocardial ischemia/reperfusion (MI/R) injury. Meanwhile, 4-hydroxy-2-nonenal (4-HNE) is abundantly increased during MI/R injury. However, whether 4-HNE induces cardiomyocyte necroptosis during MI/R remains unknown.

Methods: To observe the relationship between 4-HNE and necroptosis during MI/R, C57BL/6 mice and aldehyde dehydrogenase 2-transgenic (ALDH2-Tg) mice were both exposed to left anterior descending artery ligation surgery to establish MI/R injury models. For further study, isolated mouse hearts and H9c2 cells were both treated with 4-HNE to elucidate the underlying mechanisms.

Results: Necroptosis and 4-HNE were both upregulated in I/R-injured hearts. Cardiomyocyte necroptosis was significantly decreased in I/R-injured hearts from ALDH2-Tg mice as compared with that of wild-type mice. In vitro studies showed that necroptosis was enhanced by 4-HNE perfusion in a time- and concentration-dependent manner. Knockdown of receptor-interacting serine/threonine-protein kinase 1 (RIP1) using small interfering RNA (siRNA) prevented 4-HNE-induced cardiomyocyte necroptosis, manifesting that RIP1 played a key role in the upregulation of cell necroptosis by 4-HNE. Further studies found that 4-HNE reduced the protein degradation of RIP1 by preventing K48-polyubiquitination of RIP1.

Conclusion: 4-HNE contributes to cardiomyocyte necroptosis by regulating ubiquitin-mediated proteasome degradation of RIP1.
Extracellular Vesicle Proteomes Shed Light on the Evolutionary, Interactive, and Functional Divergence of Their Biogenesis Mechanisms
Authors: Lim Hyobin Julianne , Yoon Haejin , Kim Hyeyeon , Kang Yun-Won , Kim Ji-Eun , Kim Oh Youn , Lee Eun-Young , Twizere Jean-Claude , Rak Janusz , Kim Dae-Kyum
Published: October 2021

Extracellular vesicles (EVs) are membranous structures containing bioactive molecules, secreted by most cells into the extracellular environment. EVs are classified by their biogenesis mechanisms into two major subtypes: ectosomes (enriched in large EVs; lEVs), budding directly from the plasma membrane, which is common in both prokaryotes and eukaryotes, and exosomes (enriched in small EVs; sEVs) generated through the multivesicular bodies via the endomembrane system, which is unique to eukaryotes. Even though recent proteomic analyses have identified key proteins associated with EV subtypes, there has been no systematic analysis, thus far, to support the general validity and utility of current EV subtype separation methods, still largely dependent on physical properties, such as vesicular size and sedimentation. Here, we classified human EV proteomic datasets into two main categories based on distinct centrifugation protocols commonly used for isolating sEV or lEV fractions. We found characteristic, evolutionarily conserved profiles of sEV and lEV proteins linked to their respective biogenetic origins. This may suggest that the evolutionary trajectory of vesicular proteins may result in a membership bias toward specific EV subtypes. Protein–protein interaction (PPI) network analysis showed that vesicular proteins formed distinct clusters with proteins in the same EV fraction, providing evidence for the existence of EV subtype-specific protein recruiters. Moreover, we identified functional modules enriched in each fraction, including multivesicular body sorting for sEV, and mitochondria cellular respiration for lEV proteins. Our analysis successfully captured novel features of EVs embedded in heterogeneous proteomics studies and suggests specific protein markers and signatures to be used as quality controllers in the isolation procedure for subtype-enriched EV fractions.
Circular RNA circFNDC3AL Upregulates BCL9 Expression to Promote Chicken Skeletal Muscle Satellite Cells Proliferation and Differentiation by Binding to miR-204
Authors: Wei Yuanhang , Tian Yongtong , Li Xinyan , Amevor Felix Kwame , Shen Xiaoxu , Zhao Jing , Zhao Xiyu , Zhang Xinyi , Huang Wenling , Hu Jihong , Yi Jie , Yan Lei , Zhang Yao , Li Diyan , Ma Menggen , Zhu Qing , Yin Huadong
Published: October 2021

Skeletal muscle is a heterogeneous tissue that is essential for initiating movement and maintaining homeostasis. The genesis of skeletal muscle is an integrative process that lasts from embryonic development to postnatal stages, which is carried out under the modulation of many factors. Recent studies have shown that circular RNAs (circRNAs), a class of non-coding RNAs, are involved in myogenesis. However, more circRNAs and their mechanisms that may regulate skeletal muscle development remain to be explored. Through in-depth analysis of our previous RNA-Seq data, circFNDC3AL was found to be a potentially functional circRNA highly expressed during embryonic development of chicken skeletal muscle. Therefore, in this study, we investigated the effect of circFNDC3AL on skeletal muscle development in chickens and found that circFNDC3AL promoted chicken skeletal muscle satellite cell (SMSC) proliferation and differentiation. To gain a thorough understanding of the exact modulatory mechanisms of circFNDC3AL in chicken skeletal muscle development, we performed target miRNA analysis of circFNDC3AL and found that circFNDC3AL has a binding site for miR-204. Subsequently, we demonstrated that miR-204 inhibited chicken SMSC proliferation and differentiation, which showed the opposite functions of circFNDC3AL. Furthermore, we identified the miR-204 target gene B-cell CLL/lymphoma 9 (BCL9) and validated that miR-204 had an inhibitory effect on BCL9, while the negative effect could be relieved by circFNDC3AL. In addition, we verified that BCL9 performed the same positive functions on chicken SMSC proliferation and differentiation as circFNDC3AL, as opposed to miR-204. In conclusion, our study identified a circRNA circFNDC3AL that upregulates BCL9 expression to promote the proliferation and differentiation of chicken SMSCs by binding to miR-204.
Self-Assembled Materials Incorporating Functional Porphyrins and Carbon Nanoplatforms as Building Blocks for Photovoltaic Energy Applications
Authors: Mao Boyang , Hodges Benjamin , Franklin Craig , Calatayud David G. , Pascu Sofia I.
Published: October 2021

As a primary goal, this review highlights the role of supramolecular interactions in the assembly of new sustainable materials incorporating functional porphyrins and carbon nanoplatforms as building blocks for photovoltaics advancements.
Currently Available Strategies for Target Identification of Bioactive Natural Products
Authors: Li Gen , Peng Xuling , Guo Yajing , Gong Shaoxuan , Cao Shijie , Qiu Feng
Published: October 2021

In recent years, biologically active natural products have gradually become important agents in the field of drug research and development because of their wide availability and variety. However, the target sites of many natural products are yet to be identified, which is a setback in the pharmaceutical industry and has seriously hindered the translation of research findings of these natural products as viable candidates for new drug exploitation. This review systematically describes the commonly used strategies for target identification via the application of probe and non-probe approaches. The merits and demerits of each method were summarized using recent examples, with the goal of comparing currently available methods and selecting the optimum techniques for identifying the targets of bioactive natural products.
De Novo Hepatocellular Carcinoma in Hepatitis C-Related Cirrhosis: Are Advanced Glycation End Products a Key Driver?
Authors: Abdel-Razik Ahmed , Shabana Walaa , El Nakib Ahmed Mohamed , Abdelsalam Mostafa , Abdelwahab Ahmed , Hasan Ahmad S. , Elzehery Rasha , Elhelaly Rania , Fathy Aya Ahmed , Mostafa Sally Abdallah , El-Wakeel Niveen , Moemen Dalia , Eldars Waleed , Yassen Ahmed H.
Published: October 2021

Background and Purpose

The advanced glycation end products (AGEs) have been implicated in different diseases’ pathogenesis, but their role in hepatocellular carcinoma (HCC) is still a matter of debate. This study aims to investigate the association of AGEs with HCC development in patients with hepatitis C-related cirrhosis.

Methods

Only 153 of the 181 non-diabetic patients with cirrhosis were consecutively involved in this pilot cohort prospective study, along with 34 healthy control participants. Demographic characteristics, biochemical parameters, clinical data, and AGEs levels in all subjects at the starting point and every year after that for two years were assessed. Multivariable Cox regression analysis was used to settle variables that could predict HCC development within this period.

Results

HCC developed in 13 (8.5%) patients. Univariate Cox regression analysis reported that body mass index (P=0.013), homeostatic model assessment-insulin resistance (P=0.006), alpha-fetoprotein (P <0.001), and AGEs levels (P <0.001) were related to HCC development. After adjusting multiple confounders, the multivariable Cox regression model has revealed that AFP and AGEs were the powerful parameters related to the HCC occurrence (all P<0.05). AGEs at a cutoff value of more than 79.6 ng/ml had 100% sensitivity, 96.4% specificity, and 0.999 area under the curve (all P<0.001), using the receiver operating characteristic curve, for prediction of HCC development.

Conclusion

This work suggests that AGEs are associated with an increased incidence of HCC, particularly in cirrhosis, which is encouraging in decreasing the risk of HCC in these patients.
Impact of Bead-Beating Intensity on the Genus- and Species-Level Characterization of the Gut Microbiome Using Amplicon and Complete 16S rRNA Gene Sequencing
Authors: Zhang Bo , Brock Matthew , Arana Carlos , Dende Chaitanya , van Oers Nicolai Stanislas , Hooper Lora V. , Raj Prithvi
Published: October 2021

Bead-beating within a DNA extraction protocol is critical for complete microbial cell lysis and accurate assessment of the abundance and composition of the microbiome. While the impact of bead-beating on the recovery of OTUs at the phylum and class level have been studied, its influence on species-level microbiome recovery is not clear. Recent advances in sequencing technology has allowed species-level resolution of the microbiome using full length 16S rRNA gene sequencing instead of smaller amplicons that only capture a few hypervariable regions of the gene. We sequenced the v3-v4 hypervariable region as well as the full length 16S rRNA gene in mouse and human stool samples and discovered major clusters of gut bacteria that exhibit different levels of sensitivity to bead-beating treatment. Full length 16S rRNA gene sequencing unraveled vast species diversity in the mouse and human gut microbiome and enabled characterization of several unclassified OTUs in amplicon data. Many species of major gut commensals such as Bacteroides, Lactobacillus, Blautia, Clostridium, Escherichia, Roseburia, Helicobacter, and Ruminococcus were identified. Interestingly, v3-v4 amplicon data classified about 50% of Ruminococcus reads as Ruminococcus gnavus species which showed maximum abundance in a 9 min beaten sample. However, the remaining 50% of reads could not be assigned to any species. Full length 16S rRNA gene sequencing data showed that the majority of the unclassified reads were Ruminococcus albus species which unlike R. gnavus showed maximum recovery in the unbeaten sample instead. Furthermore, we found that the Blautia hominis and Streptococcus parasanguinis species were differently sensitive to bead-beating treatment than the rest of the species in these genera. Thus, the present study demonstrates species level variations in sensitivity to bead-beating treatment that could only be resolved with full length 16S rRNA sequencing. This study identifies species of common gut commensals and potential pathogens that require minimum (0-1 min) or extensive (4-9 min) bead-beating for their maximal recovery.
Microbiome Compositions From Infertile Couples Seeking In Vitro Fertilization, Using 16S rRNA Gene Sequencing Methods: Any Correlation to Clinical Outcomes?
Authors: Okwelogu Somadina I. , Ikechebelu Joseph I. , Agbakoba Nneka R. , Anukam Kingsley C.
Published: October 2021

Background

Bacterial infections are usually suspected in infertile couples seeking IVF with no clear understanding of the microbial compositions present in the seminal fluids and vaginal niche of the patients. We used next-generation sequencing technology to correlate microbiota compositions with IVF clinical outcomes.

Methods

Thirty-six couples were recruited to provide seminal fluids and vaginal swabs. Bacterial DNA was extracted, and V4 region of the 16S rRNA was amplified and sequenced in a pair-end configuration on the Illumina MiSeq platform rendering 2 × 150 bp sequences. Microbial taxonomy to species level was generated using the Greengenes database. Linear discriminant analysis (LDA) effect size (LEfSe) was used to identify biologically and statistically significant differences in relative abundance.

Results

Seminal fluid microbiota compositions had lower bacterial concentrations compared with the vagina, but species diversity was significantly higher in seminal fluid samples. Azoospermic subjects had more relative abundance of Mycoplasma and Ureaplasma. In Normospermic semen, Lactobacillus (43.86%) was the most abundant, followed by Gardnerella (25.45%), while the corresponding vaginal samples, Lactobacillus (61.74%) was the most abundant, followed by Prevotella (6.07%) and Gardnerella (5.86%).

Conclusions

Semen samples with positive IVF were significantly colonized by Lactobacillus jensenii (P=0.002), Faecalibacterium (P=0.042) and significantly less colonized by Proteobacteria, Prevotella, Bacteroides, and lower Firmicutes/Bacteroidetes ratio compared with semen samples with negative IVF. Vaginal samples with positive IVF clinical outcome were significantly colonized by Lactobacillus gasseri, less colonized by Bacteroides and Lactobacillus iners. This study has opened a window of possibility for Lactobacillus replenishments in men and women before IVF treatment.
Fecal Microbiota Transplantation Protects the Intestinal Mucosal Barrier by Reconstructing the Gut Microbiota in a Murine Model of Sepsis
Authors: Gai Xiaowei , Wang Huawei , Li Yaqing , Zhao Haotian , He Cong , Wang Zihui , Zhao Heling
Published: October 2021

The gastrointestinal (GI) tract has long been hypothesized to play an integral role in the pathophysiology of sepsis, and gut microbiota (GM) dysbiosis may be the key factor. Previous studies have shown that the gut flora was significantly altered in critically ill patients. This study aimed to observe what kind of GM dysbiosis is in the early stage of sepsis and whether the application of fecal microbiota transplantation (FMT) can reconstruct the GM of septic mice and restore its protective function on the intestinal mucosal barrier. The study investigated the effect of FMT on gut microbiota, mucosal barrier function, inflammatory response, and survival in a murine model of sepsis established by cecal ligation and puncture (CLP). It is found that FMT can not only reduce morbidity and mortality and restore the abundance and diversity of the gut flora in septic mice, but can also improve the intestinal barrier function by reducing epithelial cell apoptosis, improving the composition of the mucus layer, upregulating the expression of tight junction proteins, and reducing intestinal permeability and the inflammatory response. After FMT, Lachnospiraceae contributed the most to intestinal protection through enhancement of the L-lysine fermentation pathway. FMT offers a microbe-mediated survival advantage in a murine model of sepsis. Therefore, an improved understanding of the connection between microbiota, and systemic illness may yield new therapeutic strategies for patients with sepsis.
Coccidia-Microbiota Interactions and Their Effects on the Host
Authors: Lu Chenyang , Yan Yaqun , Jian Fuchun , Ning Changshen
Published: October 2021

As a common parasitic disease in animals, coccidiosis substantially affects the health of the host, even in the absence of clinical symptoms and intestinal tract colonization. Gut microbiota is an important part of organisms and is closely related to the parasite and host. Parasitic infections often have adverse effects on the host, and their pathogenic effects are related to the parasite species, parasitic site and host-parasite interactions. Coccidia-microbiota-host interactions represent a complex network in which changes in one link may affect the other two factors. Furthermore, coccidia-microbiota interactions are not well understood and require further research. Here, we discuss the mechanisms by which coccidia interact directly or indirectly with the gut microbiota and the effects on the host. Understanding the mechanisms underlying coccidia-microbiota-host interactions is important to identify new probiotic strategies for the prevention and control of coccidiosis.
Diversity of Cardiologic Issues in a Contemporary Cohort of Women With Breast Cancer
Authors: Tini Giacomo , Ameri Pietro , Buzzatti Giulia , Sarocchi Matteo , Murialdo Roberto , Guglielmi Giulia , Arboscello Eleonora , Ballestrero Alberto , Del Mastro Lucia , Spallarossa Paolo , Porto Italo
Published: October 2021

Background: Women with breast cancer (BC) represent a special population particularly exposed to cardiovascular disease (CVD) risk. However, cardiologic assessment in BC is mostly limited to detection of left ventricular dysfunction cardiotoxicity (LVD-CTX) due to anticancer treatments. Our aim was to comprehensively investigate CV profile and events in a contemporary BC cohort.

Methods and Results: Records of BC patients referred for a Cardio-Oncologic evaluation before starting anticancer treatments, between 2016 and 2019, were retrospectively reviewed (n = 508). Information regarding prevalence and control of CV risk factors, and novel CVD diagnoses were extracted. Occurrence of LVD-CTX, CV events other than LVD-CTX and mortality was assessed. Mean age of study population was 64 ± 13 years; 287 patients were scheduled to receive anthracycline and 165 anti-HER2 therapy. Overall, 53% of BC women had ≥2 CV risk factors, and 67% had at least one of arterial hypertension, dyslipidaemia or diabetes mellitus not adequately controlled. Eighteen (4%) patients were diagnosed a previously unknown CVD. Over a mean follow-up of 2.5 ± 1 years, 3% of BC patients developed LVD-CTX, 2% suffered from other CV events and 11% died. CV risk factors were not associated with LVD-CTX, except for family history of CAD. On the contrary, patients with other CV events exhibited a worse CV profile. Those who died more commonly experienced CV events other than LVD-CTX (p = 0.02).

Conclusions: BC women show a suboptimal CV risk profile and are at risk of CV events not limited to LVD-CTX. A baseline Cardio-Oncologic evaluation was instrumental to implement CV prevention and to optimize CV therapies.
Troponin T Elevation After Percutaneous Left Atrial Appendage Occlusion
Authors: Wang Xiaoyan , Chen Xueying , Ye Yong , Peng Juan , Lin Jinyi , Deng Xin , Lin Li , You Jieyun , Wang Xingxu , Zhou Daxin , Chen Qingxing , Ge Junbo
Published: October 2021

Background: Cardiac troponin T (cTNT) has been widely used in detecting cardiac damage. Elevated cTNT level has been reported to be associated with increased mortality in multiple cardiac conditions. It is not uncommon to observe an increased level of cTNT in patients after left atrial appendage occlusion (LAAO). The objective of the study is to study the incidence, significance, and factors associated with cTNT elevation after LAAO.

Methods: We prospectively included patients who underwent LAAO from January 2019 to July 2020 in Fudan Zhongshan Hospital. Patients were divided into those with elevated cTNT after procedure and those with normal postprocedure cTNT. All individuals were followed up for 1 year. The primary outcome is major adverse cardiovascular events, which include myocardial infarction, heart failure, cardiac death, and stroke. The second outcome is periprocedure complication, including chest pain, tachycardia, cardiac tamponade, change of electrocardiograph, and atrial thrombus.

Results: A total of 190 patients were enrolled. Of the patients, 85.3% had elevated cTNT after LAAO, while 14.7% of them did not. Exposure time, dosage of contrast, types of devices, shapes, and sizes of LAA could contribute to elevated postprocedure cTNT. We found that patients with a Watchman device were more likely to have elevated postprocedure cTNT than those with a Lambre device (89.2 vs. 76.7%, p = 0.029). LAAO shapes were associated with cTNT levels in patients with a Watchman device, while the diameter of the outer disc and LAA depth mattered for the Lambre device. There was no significant difference in the primary and second outcome between the two groups (p-value: 0.619, 0.674).

Conclusion: LAAO was found to be commonly accompanied with cTNT elevation, which might not to be related to the complications and adverse cardiac outcomes within 1 year of follow-up. Moreover, eGFR at baseline, exposure time, dosage of contrast, types of LAAO device, and LAA morphology could contribute to cTNT elevation.
Hydrological Evolution of a Lake Recharged by Groundwater in the Badain Jaran Desert Over the Past 140 years
Authors: Jiang Gaolei , Wang Nai’ang , Mao Xin , Zhao Hua , Liu Linjing , Shen Jianmei , Nie Zhenlong , Wang Zhe
Published: October 2021

Understanding the evolution of lakes in arid areas is very important for water resource management. Previous studies have mainly focused on lakes with runoff recharge, while the evolution of groundwater recharge lakes in hyper-arid areas is still less known. In this study, an 86 cm-long sediment core was extracted from Sayinwusu Lake, one of groundwater-recharge lakes in the southeastern Badain Jaran Desert, Northwest China. 210Pb and 137Cs dating, total organic carbon (TOC) and total nitrogen (TN) contents, and mineral content analysis were used to reconstruct the lake evolution over the past 140 years. The evolution of Sayinwusu Lake since 1880 can be divided into two periods. In the first period from 1880 to 1950, the TOC and TN contents were low, and the minerals consisted of all detrital minerals, which indicate that the lake’s primary productivity and salinity were low. During the second period from 1950 to 2018, the contents of TOC, TN, and carbonate minerals increased rapidly at the beginning of the 1950s, indicating that the lake’s primary productivity and salinity increased. Comprehensive analysis of regional climate data suggests that the increase in evaporation caused by rising temperature is an important factor affecting lake evolution in the desert. Although precipitation has increased in the arid region of Northwest China in recent decades with increasing temperature, the enhancement of the evaporation effect is much greater. As a record from groundwater recharge lakes in deserts, our study provides new insight into projecting future lake changes in hyper-arid areas.
Spatio-Temporal Evolution of Intermediate-Depth Seismicity Beneath the Himalayas: Implications for Metamorphism and Tectonics
Authors: Michailos Konstantinos , Carpenter N. Seth , Hetényi György
Published: October 2021

Intermediate-depth earthquakes (>40 km) have been observed beneath the central Himalayas over decades, with little known about their nature and characteristics. Here, we apply a state-of-the-art systematic processing routine, starting from continuous waveform data, to obtain the most comprehensive high-quality earthquake catalog with a focus on the intermediate-depth seismicity beneath the central Himalayas. We construct a catalog containing 414 robust earthquake locations with depths ranging from 40 to 110 km spanning from late 2001 till mid-2003. We calculate earthquake magnitudes in a consistent way and obtain values ranging between ML0.8 and 4.5 with a magnitude of completeness of Mc2.4. This information allows us to study the spatiotemporal characteristics of the seismicity in great detail. Earthquakes mainly take place in a cluster, consisting of two linear segments at ca. 35° azimuth difference, situated beneath the high Himalayas in NE Nepal and adjacent S. Tibet. Seismicity there does not feature any mainshock-aftershock patterns but presents a few sequences with potential seismicity migration rates compatible with linear or diffusive migration. This result, along with previous studies in the lower Indian crust, allows interpreting these events as related to metamorphic reactions involving dehydration processes. However, given the geodynamic context, a tectonic interpretation with a dextral basement fault zone propagating beneath the Himalaya and continuing as a westward propagating tear fault would also be possible. This represents a continuous fault zone from the deep crust in S. Tibet, across the Himalaya along the Dhubri-Chungthang fault zone (DCFZ) to the Shillong plateau, which could be an inherited tectonic feature.
Investigation on Thermal Characteristics of the Oil-Circulating Hydraulic Energy Storage System for Hybrid Mining Trucks
Authors: Yi Tong , Ma Fei , Jin Chun , Hong Jichao , Liu Yanbo
Published: October 2021

The improved hydraulic energy storage system (IHESS) is a novel compact hydraulic ESS with only 10% of oil and 64.78% of installation space of the regular ones. However, its novel circulating structure and lightweight material result in poor heat dissipation. The thermodynamic and heat transfer model of IHESS with an oil-circulating layout is proposed. Based on the mining trucks’ dynamic model, thermal characteristics of IHESSs with different parameters under the actual and simplified working conditions are studied and the factors causing overheating are analyzed. Finally, a feasible thermal design is put forward, and its efficiency is analyzed. The simulation shows that more accumulators and higher recovery power lead to higher system temperature and vice versa. Under the standard simplified working condition at 40°C ambient temperature, the highest oil temperature reached is 93.13°C. About 90% of the generated heat is converted into the internal energy of nitrogen and oil. On this basis, by adopting an energy-saving passive cooling system with a cooling power of 6.68 kW, the highest temperature of the oil drops to 52.79°C and 28% of the generated heat is released through the cooling system.
An Inductor Current Sensorless Control Strategy Based on Modified VSG Method for Single-Phase Microgrid Application With Seamless Transfer Capability
Authors: Zhang Zhi , Wu Junkai , Zheng Liupeng , Xie Di , Tang Xiao
Published: October 2021

This paper proposes an inductor current sensorless control strategy based on modified virtual synchronous generator (VSG) method for single-phase inverter-interfaced microgrid application. Firstly, the outer power loop with Q-U integral term is presented for output reactive power enhancement, and an inner voltage regulation loop based on luenberger state observer is proposed to reduce the inductor current sensor. Meanwhile, in order to improve the response speed of the observer, the luenberger observer is designed based on the optimal pole assignment method. Secondly, a seamless switching strategy based on the modified VSG method is proposed, which can realize the seamless transition between the island mode and grid-connected mode. Finally, a single-phase 3kW VSG prototype is built, and the effectiveness and correctness of the proposed control strategy is verified by the simulation and experimental results.
Common Statin Intolerance Variants in ABCB1 and LILRB5 Show Synergistic Effects on Statin Response: An Observational Study Using Electronic Health Records
Authors: Melhem Alaa’ Lutfi , Chourasia Mehul Kumar , Bigossi Margherita , Maroteau Cyrielle , Taylor Alasdair , Pola Roberto , Dawed Adem Y. , Tornio Aleksi , Palmer Colin N. A. , Siddiqui Moneeza K.
Published: October 2021

Background: Statin intolerance impacts approximately 10% of statin users, with side effects ranging from mild myalgia to extreme intolerance resulting in myopathy and rhabdomyolysis. Statin intolerance results in poor adherence to therapy and can impact statin efficacy. Many genetic variants are associated with statin intolerance. The effect of these variants on statin efficacy has not been systematically explored.

Methods: Using longitudinal electronic health records and genetic biobank data from Tayside, Scotland, we examined the effect of seven genetic variants with previously reported associations with simvastatin or atorvastatin intolerance on the outcome of statin response. Statin response was measured by the reduction achieved when comparing pre- and post-statin non-high-density lipoprotein-cholesterol (non-HDL-C). Post-treatment statin response was limited to non-HDL-C measured within 6months of therapy initiation. Univariate and multivariable linear regression models were used to assess the main and adjusted effect of the variants on statin efficacy.

Results: Around 9,401 statin users met study inclusion criteria, of whom 8,843 were first prescribed simvastatin or atorvastatin. The average difference in post-treatment compared to pre-treatment non-HDL-cholesterol was 1.45 (±1.04) mmol/L. In adjusted analyses, only two variants, one in the gene ATP-binding cassette transporter B1 (ABCB1; rs1045642), and one in leukocyte immunoglobulin like receptor B5 (LILRB5; rs12975366), were associated with statin efficacy. In ABCB1, homozygous carriers of the C allele at rs1045642 had 0.06mmol/L better absolute reduction in non-HDL-cholesterol than carriers of the T allele (95% CI: 0.01, 0.1). In LILRB5 (rs12975366), carriers of the C allele had 0.04mmol/L better absolute reduction compared to those homozygous for the T allele (95% CI: 0.004, 0.08). When combined into a two-variant risk score, individuals with both the rs1045642-CC genotype and the rs12975366-TC or CC genotype had a 0.11mmol/L greater absolute reduction in non-HDL-cholesterol compared to those with rs1045642-TC or TT genotype and the rs12975366-TT genotype (95% CI: 0.05, 0.16; p<0.001).

Conclusion: We report two genetic variants for statin adverse drug reactions (ADRs) that are associated with statin efficacy. While the ABCB1 variant has been shown to have an association with statin pharmacokinetics, no similar evidence for LILRB5 has been reported. These findings highlight the value of genetic testing to deliver precision therapeutics to statin users.
Differential Methylation and Transcriptome Integration Analysis Identified Differential Methylation Annotation Genes and Functional Research Related to Hair Follicle Development in Sheep
Authors: Tian Yuezhen , Yang Xuemei , Du Jianwen , Zeng Weidan , Wu Weiwei , Di Jiang , Huang Xixia , Tian Kechuan
Published: October 2021

Hair follicle growth and development are a complex and long-term physiological process, which is regulated by a variety of physical factors and signal pathways. Increasing the understanding of the epigenetic regulation and function of candidate genes related to hair follicle development will help to better understand the molecular regulatory mechanisms of hair follicle development. In this study, the methylated DNA immunoprecipitation sequencing (MeDIP-seq) was used to obtain the genome-wide methylation map of the hair follicular development of Super Merino sheep in six stages (fetal skin tissue at 65d, 85d, 105d, 135d, 7d, and 30d after birth). Combined with the results of previous RNA-sequencing, 65 genes were screened out that were both differential methylation and differential expression, including EDN1, LAMC2, NR1D1, RORB, MyOZ3, and WNT2 gene. Differential methylation genes were enriched in Wnt, TNF, TGF-beta, and other signaling pathways related to hair follicle development. The bisulfite sequencing PCR results and MeDIP-seq were basically consistent, indicating that the sequencing results were accurate. As a key gene in the Wnt signaling pathway, both differential methylation and expression gene identified by MeDIP-seq and RNA-seq, further exploration of the function of WNT2 gene revealed that the DNA methylation of exon 5 (CpG11 site) promoted the expression of WNT2 gene. The overexpression vector of lentivirus pLEX-MCS-WNT2 was constructed, and WNT2 gene effectively promoted the proliferation of sheep skin fibroblasts. The results showed that WNT2 gene could promote the growth and development of skin and hair follicles. The results of this study will provide a theoretical basis for further research on sheep hair follicle development and gene regulation mechanisms.
Revisiting Secondary Information Related to Pharmacogenetic Testing
Authors: Haga Susanne B.
Published: October 2021

Incidental or secondary findings have been a major part of the discussion of genomic medicine research and clinical applications. For pharmacogenetic (PGx) testing, secondary findings arise due to the pleiotropic effects of pharmacogenes, often related to their endogenous functions. Unlike the guidelines that have been developed for whole exome or genome sequencing applications for management of secondary findings (though slightly different from PGx testing in that these refer to detection of variants in multiple genes, some with clinical significance and actionability), no corresponding guidelines have been developed for PGx clinical laboratories. Nonetheless, patient and provider education will remain key components of any PGx testing program to minimize adverse responses related to secondary findings.
IL-27 Derived From Macrophages Facilitates IL-15 Production and T Cell Maintenance Following Allergic Hypersensitivity Responses
Authors: Suwanpradid Jutamas , Lee Min Jin , Hoang Peter , Kwock Jeffery , Floyd Lauren P. , Smith Jeffrey S. , Yin Zhinan , Atwater Amber R. , Rajagopal Sudarshan , Kedl Ross M. , Corcoran David L. , Zhang Jennifer Y. , MacLeod Amanda S.
Published: October 2021

Crosstalk between T cells, dendritic cells, and macrophages in temporal leukocyte clusters within barrier tissues provides a new concept for T cell activation in the skin. Activated T cells from these leukocyte clusters play critical roles in the efferent phase of allergic contact hypersensitivity (CHS). However, the cytokines driving maintenance and survival of pathogenic T cells during and following CHS remain mostly unknown. Upon epicutaneous allergen challenge, we here report that macrophages produce IL-27 which then induces IL-15 production from epidermal keratinocytes and dermal myeloid cells within leukocyte clusters. In agreement with the known role of IL-15 as a T cell survival factor and growth cytokine, this signaling axis enhances BCL2 and survival of skin T cells. Genetic depletion or pharmacological blockade of IL-27 in CHS mice leads to abrogated epidermal IL-15 production resulting in a decrease in BCL2 expression in T cells and a decline in dermal CD8+ T cells and T cell cluster numbers. These findings suggest that the IL-27 pathway is an important cytokine for regulating cutaneous T cell immunity.
Regulatory T Cells in Chronic Heart Failure
Authors: Lu Yuzhi , Xia Ni , Cheng Xiang
Published: October 2021

Heart failure is a global problem with high hospitalization and mortality rates. Inflammation and immune dysfunction are involved in this disease. Owing to their unique function, regulatory T cells (Tregs) have reacquired attention recently. They participate in immunoregulation and tissue repair in the pathophysiology of heart failure. Tregs are beneficial in heart by suppressing excessive inflammatory responses and promoting stable scar formation in the early stage of heart injury. However, in chronic heart failure, the phenotypes and functions of Tregs changed. They transformed into an antiangiogenic and profibrotic cell type. In this review, we summarized the functions of Tregs in the development of chronic heart failure first. Then, we focused on the interactions between Tregs and their target cells. The target cells of Tregs include immune cells (such as monocytes/macrophages, dendritic cells, T cells, and B cells) and parenchymal cells (such as cardiomyocytes, fibroblasts, and endothelial cells). Next-generation sequencing and gene editing technology make immunotherapy of heart failure possible. So, prospective therapeutic approaches based on Tregs in chronic heart failure had also been evaluated.
Reactive Oxygen Species in Macrophages: Sources and Targets
Authors: Canton Marcella , Sánchez-Rodríguez Ricardo , Spera Iolanda , Venegas Francisca C. , Favia Maria , Viola Antonella , Castegna Alessandra
Published: October 2021

Reactive oxygen species (ROS) are fundamental for macrophages to eliminate invasive microorganisms. However, as observed in nonphagocytic cells, ROS play essential roles in processes that are different from pathogen killing, as signal transduction, differentiation, and gene expression. The different outcomes of these events are likely to depend on the specific subcellular site of ROS formation, as well as the duration and extent of ROS production. While excessive accumulation of ROS has long been appreciated for its detrimental effects, there is now a deeper understanding of their roles as signaling molecules. This could explain the failure of the “all or none” pharmacologic approach with global antioxidants to treat several diseases. NADPH oxidase is the first source of ROS that has been identified in macrophages. However, growing evidence highlights mitochondria as a crucial site of ROS formation in these cells, mainly due to electron leakage of the respiratory chain or to enzymes, such as monoamine oxidases. Their role in redox signaling, together with their exact site of formation is only partially elucidated. Hence, it is essential to identify the specific intracellular sources of ROS and how they influence cellular processes in both physiological and pathological conditions to develop therapies targeting oxidative signaling networks. In this review, we will focus on the different sites of ROS formation in macrophages and how they impact on metabolic processes and inflammatory signaling, highlighting the role of mitochondrial as compared to non-mitochondrial ROS sources.