bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonthyroidal Illness Syndrome: To Treat or Not to Treat? Have We Answered the Question? A Review of Metanalyses
Authors: Sciacchitano Salvatore , Capalbo Carlo , Napoli Christian , Anibaldi Paolo , Salvati Valentina , De Vitis Claudia , Mancini Rita , Coluzzi Flaminia , Rocco Monica
Published: May 2022

Background and Objective

Nonthyroidal Illness Syndrome (NTIS) occurs in approximately 70% of patients admitted to Intensive Care Units (ICU)s and has been associated with increased risk of death. Whether patients with NTIS should receive treatment with thyroid hormones (TH)s is still debated. Since many interventional randomized clinical trials (IRCT)s were not conclusive, current guidelines do not recommend treatment for these patients. In this review, we analyze the reasons why TH treatment did not furnish convincing results regarding possible beneficial effects in reported IRCTs.

Methods

We performed a review of the metanalyses focused on NTIS in critically ill patients. After a careful selection, we extracted data from four metanalyses, performed in different clinical conditions and diseases. In particular, we analyzed the type of TH supplementation, the route of administration, the dosages and duration of treatment and the outcomes chosen to evaluate the results.

Results

We observed a marked heterogeneity among the IRCTs, in terms of type of TH supplementation, route of administration, dosages and duration of treatment. We also found great variability in the primary outcomes, such as prevention of neurological alterations, reduction of oxygen requirements, restoration of endocrinological and clinical parameters and reduction of mortality.

Conclusions

NTIS is a frequent finding in critical ill patients. Despite several available IRCTs, it is still unclear whether NTIS should be treated or not. New primary endpoints should be identified to adequately validate the efficacy of TH treatment and to obtain a clear answer to the question raised some years ago.
Environmental, Social, and Governance Impact on Energy Sector Default Risk—Long-Term Issuer Credit Ratings Perspective
Authors: Chodnicka-Jaworska Patrycja
Published: May 2022

The aim this study is to analyze the impact of environmental, social, and governance (ESG) measures on energy sector credit ratings. The main hypothesis is as follows: The ESG measures have had a significant impact on energy sector credit ratings during the COVID-19 crisis. The analysis has been conducted by using long-term issuer credit ratings presented by the main credit rating agencies. To verify the hypothesis, quarterly data from financial statements, macroeconomic data, and ESG measures for all companies listed on the stock exchanges from all over the world for the 2000–2021 period were collected. The sector was divided into sub-samples according to the type of sector and the moment of the COVID-19 crisis. It was noticed that a stronger reaction of credit ratings during the COVID-19 crisis on ESG factors, than that before it, was also observed, and confirms the increasing role of ESG measures in the financial market. On the other hand, credit rating agencies take into consideration ESG factors during the first estimation. Later, the mentioned variables lose their importance. This is based on a few reasons. It is still a small sample of entities that publish non-financial statements connected with ESG. Some countries have yet to implement regulations associated with climate risk. The significance of electricity power consumption and CO2 emissions confirms the significance of the mentioned direct or indirect impact of ESG factors. Credit rating agencies are not willing to change credit ratings because usually companies from the energy sector, especially from coal and oil and gas subsectors, are large entities. They sometimes receive financial support from governments. Governments are also stakeholders that create a lower risk of default. In less developed countries, coal is one of the main energy sources, and costs connected with alternative, renewable energy are more expensive. The prepared research also suggests that particular ESG measures have varying significance on credit ratings. Therefore, it can help to analyze and build models by investors. It will not be without significance for estimating the default risk and the cost of the capital. In most cases, the most significant measure is the E factor.
Acoustic Impedance Inversions for Offshore CO2 Storage: South Georgia Embayment, United States
Authors: Almutairi Khaled , Knapp Camelia , Knapp James , Brantley Duke , Terry Darrell
Published: May 2022

This study builds and expands on previous CO2storage resource assessment studies of the southeastern offshore Atlantic margin by providing a detailed evaluation on how rock porosities and permeabilities are distributed across the Upper Cretaceous strata restricted to the South Georgia Embayment (SGE). Using legacy industry two-dimensional seismic reflection and well data, this assessment is the first application of multiple seismic inversion techniques in this area. This workflow provides a reliable and repeatable model-based inversion which gives an improved image to discriminate lithology and predict porosity. The workflow is applicable to future CO2storage resource assessment studies elsewhere. The inversion results indicate that distinct porosity and permeability regimes are present and distributed in the Upper Cretaceous strata within the SGE. The impedance and porosity relationships show well-founded and reliable correlation. These relationships reveal low impedance coincident to the high porosity intervals which are proposed as potential reservoir intervals for CO2storage. In addition, the result shows that the Upper Cretaceous strata have two main potential reservoirs in the lower part. These are overlain by a thick impermeable interval, mostly shale, which has high impedance, low porosity, and low permeability and extends within the SGE. This result is in agreement with a previous study that also proposed two significant storage reservoirs for CO2in the Upper Cretaceous strata. Since porosity distribution is estimated using multiple methods, it follows the trends of seismic signature and structures of the Upper Cretaceous strata. The extracted values of porosity, ranging from 15 to 36%, and permeability, ranging from 1 to 100 mD, are close to the measured values from the well core data at the Upper Cretaceous strata interval.
Assessment of Critical Factors Influencing Consumers’ Acceptance of Wearable Sports Devices During COVID-19 Pandemic Conditions
Authors: He Pengfei , Shang Yunfeng , Ajaz Tahseen , Nureen Naila , Sukstan Wanich
Published: May 2022

Amid rising COVID-19 stringency measures, sedentary behavior has been intensified globally, leading to intense chronic diseases. Due to the potential health benefits associated with digital wearables, there is a dire need to explore the crucial determinants for consumers, which could enhance the usage of sports wearables in addressing health challenges. For this purpose, a novel conceptual framework was developed, and Partial Least Square-Structural Equation Modelling (PLS-SEM) was employed on the primary data of 463 consumers from China. The results revealed a positive association of consumer innovativeness, perceived credibility, perceived ease in using sports wearables, perceived usefulness in using sports wearables, social influence for sports wearables, health benefits, and hedonic motivation for sports wearables during COVID-19 with the adoption intention of sports wearables. The study findings offer valuable policy recommendations to minimize COVID-19 health risks by efficiently monitoring consumers’ health status.
Rice Productivity, Zn Biofortification, and Nutrient-Use Efficiency as Influenced by Zn Fertilization Under Conventional Transplanted Rice and the System of Rice Intensification
Authors: Choudhary Anil K. , Sood Pankaj , Rahi Shakuntla , Yadav D. S. , Thakur O. C. , Siranta K. R. , Dass Anchal , Singh Y. V. , Kumar Adarsh , Vijayakumar S. , Bhupenchandra Ingudam , Dua V. K. , Shivadhar  , Bana R. S. , Pooniya Vijay , Sepat Seema , Kumar Sushil , Rajawat Mahendra Vikram Singh , Rajanna G. A. , Harish M. N. , Varatharajan T. , Kumar Anil , Tyagi Vishal
Published: May 2022

The northwestern Himalayas (NWH) in India have low rice productivity (∼2 t ha−1) and quality due to poor crop and nutrient management in predominantly Zn-deficient soils. Hence, a field experimentation in the NWH compared the conventionally transplanted rice (CTR) and the system of rice intensification(SRI) under three nutrient management practices (NMPs),viz., 1) farmers’ fertilization practice, FYM @ 5 t ha−1+ N:P2O5:K2O @ 50:40:20 kg ha−1(FFP); 2) recommended dose of fertilization, FYM @ 10 t ha−1+ N:P2O5:K2O @ 90:40:40 kg ha−1(RDF); and 3) RDF + Zn fertilization using ZnSO4@ 25 kg ha−1(RDF + Zn). The results revealed that SRI practice harnessed a significantly higher rice yield under different NMPs (6.59–8.69 t ha−1) with ∼1.3–1.4- and ∼3.3–4.3-fold enhancements over the CTR and average rice productivity in NWH, respectively. SRI had the greatest improvement in panicle number hill−1by ∼2.4 folds over the CTR. RDF + Zn had a significantly higher grain (10.7; 7.9%) and straw yield (28.9; 19.7%) over FFP and RDF, respectively, with significant augmentation of Zn biofortification in grains (11.8%) and Zn uptake (23.9%) over the RDF. SRI also enhanced the Zn concentrations in rice grains and straws by ∼4.0 and 2.7% over CTR with respective increases of 36.9 and 25.9% in Zn uptake. The nutrient harvest index and partial factor productivity of applied nutrients (NPK) had a higher magnitude under SRI and RDF + Zn over their respective counterparts, i.e., CTR and RDF. In addition, SRI had higher AE-Zn, CRE-Zn, and PE-Zn to the tune of 119.6, 63.4, and 34%, respectively, over the CTR. Overall, SRI coupled with RDF + Zn in hybrid rice assumes greater significance in enhancing the rice productivity with better Zn-biofortified grains besides higher nutrient use efficiencies to combat widespread malnutrition and acute Zn deficiencies in humans and livestock in the northwestern Himalayas.
How Does Urbanization Affect Citizens’ Pro-Environment Behavior? A Hierarchical Analysis of the Chinese General Social Survey
Authors: Qing Wen , Wang Yibao , Zhang Yanbo , Han Jingwen , Li Cuixi
Published: May 2022

Many studies have focused on the pressure of urbanization on resources and environment, but few have explored the positive effect of urbanization on reducing environmental pressure from the perspective of urbanization affecting pro-environment behavior (PEB). To systematically explore the impact of urbanization with different dimensions on PEB, this study establishes a hierarchical theoretical framework and conducts empirical test based on the data of Chinese General Social Survey (CGSS) and China City Statistical Yearbook (CCSY) as well as a hierarchical linear model (HLM). The results reveal the following: First, urbanization can directly influence PEB and the four dimensions of urbanization (economic, social, spatial and population urbanizations) can influence PEB in different manners. Economic urbanization can positively influence private PEB; social urbanization exerts a slightly positive impact on PEB; spatial urbanization has a notably negative impact on PEB while population urbanization has no significant effect on PEB. Second, Urbanization also indirectly affects PEB by influencing individual characteristic variables. Social and economic urbanizations positively moderate the relationship between social interaction and PEB. The research results illustrate the relationship between urbanization and PEB, and can guide how to promote PEB in the process of urbanization.
Settlement Phenotypes: Social Selection and Immigration in a Common Kestrel Population
Authors: Fargallo Juan Antonio , López-Rull Isabel
Published: May 2022

Dispersal decisions are affected by the internal state of the individual and the external environment. Immigrants entering a new population are phenotypically different from residents due to selection that mitigate costs of dispersal and facilitate settlement. Sexual and status signaling traits may influence individual’s ability to settle in a population, either by showing a subordinate phenotype thus reducing aggressive interactions, or by signaling a more competitive phenotype, thus gaining local breeding resources, including mates. By comparing immigrants vs. residents in a common kestrel population across 17 years, we evaluated the influence of dispersal on fitness components (laying date, clutch size and number of fledglings) and investigated if sex, age and phenotypic traits (body size, body condition and plumage coloration) involved in movement and social interactions affected settlement. We found that population characteristics affected sexes and age classes differently, as the admission of females and young males into our population had fewer obstacles than the admission of males. In females, immigrant young were larger, had longer wings and tails, showed better body condition, had less gray tails, started breeding earlier, and laid larger clutches than residents. Adult female immigrants also showed better body condition and less gray tails. In males, immigrants had longer tails and higher number of black spots than residents. Summarizing, immigrants are good-quality individuals and, as deduced from their breeding performance, they benefited by signaling subordination, thus reducing the probability of aggressive encounters and facilitating settlement. Our study highlights the role of phenotypic traits related to signaling to study dispersal.
Establishment of a Novel Combined Nomogram for Predicting the Risk of Progression Related to Castration Resistance in Patients With Prostate Cancer
Authors: Li Shuqiang , Shi Lei , Li Fan , Yao Bing , Chang Liansheng , Lu Hongyan , Song Dongkui
Published: May 2022

Background: The emergence of castration resistance is fatal for patients with prostate cancer (PCa); however, there is still a lack of effective means to detect the early progression. In this study, a novel combined nomogram was established to predict the risk of progression related to castration resistance.

Methods: The castration-resistant prostate cancer (CRPC)-related differentially expressed genes (DEGs) were identified by R packages “limma” and “WGCNA” in GSE35988-GPL6480 and GSE70768-GPL10558, respectively. Relationships between DEGs and progression-free interval (PFI) were analyzed using the Kaplan–Meier method in TCGA PCa patients. A multigene signature was built by lasso-penalized Cox regression analysis, and assessed by the receiver operator characteristic (ROC) curve and Kaplan–Meier curve. Finally, the univariate and multivariate Cox regression analyses were used to establish a combined nomogram. The prognostic value of the nomogram was validated by concordance index (C-index), calibration plots, ROC curve, and decision curve analysis (DCA).

Results: 15 CRPC-related DEGs were identified finally, of which 13 genes were significantly associated with PFI and used as the candidate genes for modeling. A two-gene (KIFC2 and BCAS1) signature was built to predict the risk of progression. The ROC curve indicated that 5-year area under curve (AUC) in the training, testing, and whole TCGA dataset was 0.722, 0.739, and 0.731, respectively. Patients with high-risk scores were significantly associated with poorer PFI (p < 0.0001). A novel combined nomogram was successfully established for individualized prediction integrating with T stage, Gleason score, and risk score. While the 1-year, 3-year, and 5-year AUC were 0.76, 0.761, and 0.762, respectively, the good prognostic value of the nomogram was also validated by the C-index (0.734), calibration plots, and DCA.

Conclusion: The combined nomogram can be used to predict the individualized risk of progression related to castration resistance for PCa patients and has been preliminarily verified to have good predictive ability.
Multi-Omic Data Improve Prediction of Personalized Tumor Suppressors and Oncogenes
Authors: Sudhakar Malvika , Rengaswamy Raghunathan , Raman Karthik
Published: May 2022

The progression of tumorigenesis starts with a few mutational and structural driver events in the cell. Various cohort-based computational tools exist to identify driver genes but require multiple samples to identify less frequently mutated driver genes. Many studies use different methods to identify driver mutations/genes from mutations that have no impact on tumor progression; however, a small fraction of patients show no mutational events in any known driver genes. Current unsupervised methods map somatic and expression data onto a network to identify personalized driver genes based on changes in expression. Our method is the first machine learning model to classify genes as tumor suppressor gene (TSG), oncogene (OG), or neutral, thus assigning the functional impact of the gene in the patient. In this study, we develop a multi-omic approach, PIVOT (Personalized Identification of driVer OGs and TSGs), to train on experimentally or computationally validated mutational and structural driver events. Given the lack of any gold standards for the identification of personalized driver genes, we label the data using four strategies and, based on classification metrics, show gene-based labeling strategies perform best. We build different models using SNV, RNA, and multi-omic features to be used based on the data available. Our models trained on multi-omic data improved predictions compared with mutation and expression data, achieving an accuracy ≥0.99 for BRCA, LUAD, and COAD datasets. We show network and expression-based features contribute the most to PIVOT. Our predictions on BRCA, COAD, and LUAD cancer types reveal commonly altered genes such as TP53 and PIK3CA, which are predicted drivers for multiple cancer types. Along with known driver genes, our models also identify new driver genes such as PRKCA, SOX9, and PSMD4. Our multi-omic model labels both CNV and mutations with a more considerable contribution by CNV alterations. While predicting labels for genes mutated in multiple samples, we also label rare driver events occurring in as few as one sample. We also identify genes with dual roles within the same cancer type. Overall, PIVOT labels personalized driver genes as TSGs and OGs and also identified rare driver genes.
Genome-Wide Association Mapping Reveals Novel Putative Gene Candidates Governing Reproductive Stage Heat Stress Tolerance in Rice
Authors: Ravikiran K. T. , Gopala Krishnan S. , Abhijith K. P. , Bollinedi H. , Nagarajan M. , Vinod K. K. , Bhowmick P. K. , Pal Madan , Ellur R. K. , Singh A. K.
Published: May 2022

Temperature rise predicted for the future will severely affect rice productivity because the crop is highly sensitive to heat stress at the reproductive stage. Breeding tolerant varieties is an economically viable option to combat heat stress, for which the knowledge of target genomic regions associated with the reproductive stage heat stress tolerance (RSHT) is essential. A set of 192 rice genotypes of diverse origins were evaluated under natural field conditions through staggered sowings for RSHT using two surrogate traits, spikelet fertility and grain yield, which showed significant reduction under heat stress. These genotypes were genotyped using a 50 k SNP array, and the association analysis identified 10 quantitative trait nucleotides (QTNs) for grain yield, of which one QTN (qHTGY8.1) was consistent across the different models used. Only two out of 10 MTAs coincided with the previously reported QTLs, making the remaing eight novel. A total of 22 QTNs were observed for spikelet fertility, among which qHTSF5.1 was consistently found across three models. Of the QTNs identified, seven coincided with previous reports, while the remaining QTNs were new. The genes near the QTNs were found associated with the protein–protein interaction, protein ubiquitination, stress signal transduction, and so forth, qualifying them to be putative for RSHT. An in silico expression analysis revealed the predominant expression of genes identified for spikelet fertility in reproductive organs. Further validation of the biological relevance of QTNs in conferring heat stress tolerance will enable their utilization in improving the reproductive stage heat stress tolerance in rice.
The Spectrum of ACAN Gene Mutations in a Selected Chinese Cohort of Short Stature: Genotype-Phenotype Correlation
Authors: Wu Su , Wang Chunli , Cao Qing , Zhu Ziyang , Liu Qianqi , Gu Xinyan , Zheng Bixia , Zhou Wei , Jia Zhanjun , Gu Wei , Li Xiaonan
Published: May 2022

Objective: Mutations in the ACAN gene have been reported to cause short stature. However, the prevalence estimates of pathogenic ACAN variants in individuals with short stature vary, and the correlation between ACAN genotype and clinical phenotype remain to be evaluated. To determine the prevalence of ACAN variants among Chinese people with short stature and analyze the relationship between genotype and main clinical manifestations of short stature and advanced bone age among patients with ACAN variants.

Methods: We performed next-generation sequencing-based genetic analyses on 442 individuals with short stature. ACAN variants were summarized, previously reported cases were retrospectively analyzed, and an association analysis between genotype and phenotype was conducted.

Result: We identified 15 novel and two recurrent ACAN gene variants in 16 different pedigrees that included index patients with short stature. Among the patients with ACAN variants, 12 of 18 had advanced bone age and 7 of 18 received growth hormone therapy, 5 (71.4%) of whom exhibited variable levels of height standard deviation score improvement. Further analysis showed that patients with ACAN truncating variants had shorter height standard deviation scores (p = 0.0001) and larger bone age–chronological age values (p = 0.0464). Moreover, patients in this Asian population had a smaller mean bone age–chronological age value than those that have been determined in European and American populations (p = 0.0033).

Conclusion: Our data suggest that ACAN mutation is a common cause of short stature in China, especially among patients with a family history of short stature but also among those who were born short for their gestational age without a family history. Patients with truncating variants were shorter in height and had more obvious advanced bone age, and the proportion of patients with advanced bone age was lower in this Asian population than in Europe and America.
Skewed Cellular Distribution and Low Activation of Functional T-Cell Responses in SARS-CoV-2 Non-Seroconvertors
Authors: Kilpeläinen Athina , Jimenez-Moyano Esther , Blanch-Lombarte Oscar , Ouchi Dan , Peña Ruth , Quirant-Sanchez Bibiana , Perez-Caballero Raul , Chamorro Anna , Blanco Ignacio , Martínez-Caceres Eva , Paredes Roger , Mateu Lourdes , Carrillo Jorge , Blanco Julià , Brander Christian , Massanella Marta , Clotet Bonaventura , Prado Julia G.
Published: May 2022

The role of T cells in the control of SARS-CoV-2 infection has been underestimated in favor of neutralizing antibodies. However, cellular immunity is essential for long-term viral control and protection from disease severity. To understand T-cell immunity in the absence of antibody generation we focused on a group of SARS-CoV-2 Non-Seroconvertors (NSC) recovered from infection. We performed an immune comparative analysis of SARS-CoV-2 infected individuals stratified by the absence or presence of seroconversion and disease severity. We report high levels of total naïve and low effector CD8+ T cells in NSC. Moreover, reduced levels of T-cell activation monitored by PD-1 and activation-induced markers were observed in the context of functional SARS-CoV-2 T-cell responses. Longitudinal data indicate the stability of the NSC phenotype over three months of follow-up after infection. Together, these data characterized distinctive immunological traits in NSC including skewed cellular distribution, low activation and functional SARS-CoV-2 T-cell responses. This data highlights the value of T-cell immune monitoring in populations with low seroconversion rates in response to SARS-CoV-2 infection and vaccination.
PD-L1 Inhibits T Cell-Induced Cytokines and Hyaluronan Expression via the CD40-CD40L Pathway in Orbital Fibroblasts From Patients With Thyroid Associated Ophthalmopathy
Authors: Liu Zhibin , Liu Yao , Liu Mingming , Gong Qingjia , Shi Anjie , Li Xiuhong , Bai Xu , Guan Xiaoyue , Hao Bing , Liu Feila , Zhou Xing , Yuan Hongfeng
Published: May 2022

Thyroid associated ophthalmopathy (TAO), characterized by T cell infiltration and orbital fibroblast activation, is an organ-specific autoimmune disease which is still short of effective and safety therapeutic drugs. The PD-1/PD-L1 pathway has been reported hindering the progression of Graves’ disease to some extent by inhibiting T cell activity, and tumor therapy with a PD-1 inhibitor caused some adverse effects similar to the symptoms of TAO. These findings suggest that the PD-1/PD-L1 pathway may be associated with the pathogenesis of TAO. However, it remains unknown whether the PD-1/PD-L1 pathway is involved in orbital fibroblast activation. Here, we show that orbital fibroblasts from patients with TAO do not express PD-L1. Based on in vitro OF-T cell co-culture system, exogenous PD-L1 weakens T cell-induced orbital fibroblast activation by inhibiting T cell activity, resulting in reduced production of sICAM-1, IL-6, IL-8, and hyaluronan. Additionally, exogenous PD-L1 treatment also inhibits the expression of CD40 and the phosphorylation levels of MAPK and NF-κB pathways in orbital fibroblasts of the OF-T cell co-culture system. Knocking down CD40 with CD40 siRNA or down-regulating the phosphorylation levels of MAPK and NF-κB pathways with SB203580, PD98059, SP600125, and PDTC can both reduce the expression of these cytokines and hyaluronan. Our study demonstrates that the orbital immune tolerance deficiency caused by the lack of PD-L1 in orbital fibroblasts may be one of the causes for the active orbital inflammation in TAO patients, and the utilization of exogenous PD-L1 to reconstruct the orbital immune tolerance microenvironment may be a potential treatment strategy for TAO.
Divergent Characteristics of T-Cell Receptor Repertoire Between Essential Hypertension and Aldosterone-Producing Adenoma
Authors: Chang Che-Mai , Peng Kang-Yung , Chan Chieh-Kai , Lin Yu-Feng , Liao Hung-Wei , Chang Jan-Gowth , Wu Mai-Szu , Wu Vin-Cent , Chang Wei-Chiao
Published: May 2022

Aldosterone-producing adenoma (APA) is a benign adrenal tumor that results in persistent hyperaldosteronism. As one major subtype of primary aldosteronism, APA leads to secondary hypertension that is associated with immune dysregulation. However, how the adaptive immune system, particularly the T-cell population, is altered in APA patients remains largely unknown. Here, we performed TCR sequencing to characterize the TCR repertoire between two age-matched groups of patients: one with APA and the other one with essential hypertension (EH). Strikingly, we found a significant reduction of TCR repertoire diversity in the APA group. Analyses on TCR clustering and antigen annotation further showed that the APA group possessed lower diversity in TCR clonotypes with non-common antigen-specific features, compared with the EH group. In addition, our results indicated that the strength of correlation between generation probabilities and frequencies of TCR clonotypes was significantly higher in the APA group than that in the EH group. Finally, we observed that clinical features, including plasma aldosterone level, aldosterone–renin ratio, and blood sodium level, were positively associated with the strength of correlation between generation and abundance of TCR clonotypes in the APA group. Our findings unveiled the correlation between T-cell immune repertoire and APA, suggesting a critical role of such adrenal adenoma in the T-cell immunity of patients with hypertension.
Topical Simvastatin Improves Lesions of Diffuse Normolipemic Plane Xanthoma by Inhibiting Foam Cell Pyroptosis
Authors: Zha Siyuan , Yu Xia , Wang Xiaoxiao , Gu Yan , Tan Yidong , Lu Ying , Yao Zhirong
Published: May 2022

Xanthoma pathogenesis is speculated to be associated with oxidized low-density lipoprotein (ox-LDL) deposition, although this remains unclear. Most patients with diffuse plane xanthomas present elevated blood lipid levels, and they benefit from treatment with oral lipid-lowering agents. However, there is no available treatment for diffuse normolipemic plane xanthoma (DNPX). In this study, for the first time, we used a topical simvastatin ointment to treat DNPX in three pediatric patients and observed favorable results. Immunofluorescence staining showed that the pyroptotic pathway was significantly attenuated after topical simvastatin application on the skin lesions of the patients. As ox-LDL deposition was observed in the lesions, we used ox-LDL to build a foam cell model in vitro. In the ox-LDL-induced foam cell formation, simvastatin consistently inhibited pyroptotic activation and inflammation in the macrophages. Additionally, the overexpression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) or 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase (HMGCR), the known target of statins, reversed the effects of simvastatin. Moreover, gasdermin D (GSDMD) or HMGCR knockdown inhibited ox-LDL-induced pyroptosis. Furthermore, the immunoprecipitation results confirmed the interaction between NLRP3 and HMGCR, and this interaction was inhibited by simvastatin. In conclusion, we demonstrated that topical application of simvastatin ointment might be a promising treatment for DNPX skin lesions and that this therapeutic effect may be related to pyroptosis inhibition via HMGCR inhibition in foam cells. Moreover, xanthoma pathogenesis might be associated with ox-LDL deposition and inflammation.
The Role of C-Type Lectin Receptor Signaling in the Intestinal Microbiota-Inflammation-Cancer Axis
Authors: Li Muhan , Zhang Runfeng , Li Ji , Li Jingnan
Published: May 2022

As a subset of pattern recognition receptors (PRRs), C-type lectin-like receptors (CLRs) are mainly expressed by myeloid cells as both transmembrane and soluble forms. CLRs recognize not only pathogen associated molecular patterns (PAMPs), but also damage-associated molecular patterns (DAMPs) to promote innate immune responses and affect adaptive immune responses. Upon engagement by PAMPs or DAMPs, CLR signaling initiates various biological activitiesin vivo, such as cytokine secretion and immune cell recruitment. Recently, several CLRs have been implicated as contributory to the pathogenesis of intestinal inflammation, which represents a prominent risk factor for colorectal cancer (CRC). CLRs function as an interface among microbiota, intestinal epithelial barrier and immune system, so we firstly discussed the relationship between dysbiosis caused by microbiota alteration and inflammatory bowel disease (IBD), then focused on the role of CLRs signaling in pathogenesis of IBD (including Mincle, Dectin-3, Dectin-1, DCIR, DC-SIGN, LOX-1 and their downstream CARD9). Given that CLRs mediate intricate inflammatory signals and inflammation plays a significant role in tumorigenesis, we finally highlight the specific effects of CLRs on CRC, especially colitis-associated cancer (CAC), hoping to open new horizons on pathogenesis and therapeutics of IBD and CAC.
Gut Microbiota Dysbiosis Induced by Decreasing Endogenous Melatonin Mediates the Pathogenesis of Alzheimer’s Disease and Obesity
Authors: Zhang Boqi , Chen Tong , Cao Maosheng , Yuan Chenfeng , Reiter Russel J. , Zhao Zijiao , Zhao Yun , Chen Lu , Fan Wenjing , Wang Xin , Zhou Xu , Li Chunjin
Published: May 2022

Lifestyle choices, external environment, aging, and other factors influence the synthesis of melatonin. Although the physiological functions of melatonin have been widely studied in relation to specific organs, the systemic effects of endogenous melatonin reduction has not been reported. This study evaluates the systemic changes and possible pathogenic risks in an endogenous melatonin reduction (EMR) mouse model deficient in the rate limiting enzyme in melatonin production, arylalkylamine N-acetyltransferase (Aanat) gene. Using this model, we identified a new relationship between melatonin, Alzheimer’s disease (AD), and gut microbiota. Systematic changes were evaluated using multi-omics analysis. Fecal microbiota transplantation (FMT) was performed to examine the role of gut microbiota in the pathogenic risks of EMR. EMR mice exhibited a pan-metabolic disorder, with significant transcriptome changes in 11 organs, serum metabolome alterations as well as microbiota dysbiosis. Microbiota dysbiosis was accompanied by increased gut permeability along with gut and systemic inflammation. Correlation analysis revealed that systemic inflammation may be related to the increase of Ruminiclostridium_5 relative abundance. 8-month-old EMR mice had AD-like phenotypes, including Iba-1 activation, A β protein deposition and decreased spatial memory ability. Moreover, EMR mice showed decreased anti stress ability, under high-fat diet, EMR mice had greater body weight and more obvious hepatic steatosis compared with WT group. FMT improved gut permeability, systemic inflammation, and AD-related phenotypes, while reducing obesity in EMR mice. Our findings suggest EMR causes systemic changes mediated by gut microbiota dysbiosis, which may be a pathogenic factor for AD and obesity, we further proved the gut microbiota is a potential target for the prevention and treatment of AD and obesity.
Steps Toward Modelling the Past and Future North Sea Ecosystem With a Focus on Light Climate
Authors: Thewes Daniel , Stanev Emil V. , Zielinski Oliver
Published: May 2022

With ongoing manmade climate change, it is important to understand its impact on regional ecosystems. Furthermore, it is known that the North Sea light climate is subject to ongoing change. The combined effects of climate change and coastal darkening are investigated in this work. We used a three-dimensional ecosystem model, forced with data from a climate model, to project three plausible biogeochemical states for the years 2050–2054, following three representative concentration and shared socioeconomic pathways (RCP2.6-SSP1, RCP4.5-SSP2 and RCP8.5-SSP5). We also performed a historic experiment for the years 1950–1954 and 2000–2004 for comparison. Our results suggest significant reductions of phytoplankton biomass as a consequence of sinking nutrient levels for all future scenarios. Additionally, a modelling study was carried out, in which we raised background SPM levels by 40% to reflect potential changes in the future. This revealed that for RCP2.6-SSP1, the ecosystem is more sensitive to changes in the light climate than for the other scenarios, due to higher nutrient availability.
Effects of Epiphytic Biofilm Activity on the Photosynthetic Activity, pH and Inorganic Carbon Microenvironment of Seagrass Leaves (Zostera marina L.)
Authors: Zhang Qingfeng , Kühl Michael , Brodersen Kasper Elgetti
Published: May 2022

Epiphytic biofilms on seagrass leaves can lead to extreme microenvironmental conditions for the encapsulated leaf limiting both its photosynthesis and respiration. Yet, little is known about how the biological activity of the biofilm itself changes the seagrass phyllosphere microenvironment and dynamics. We used microsensors to measure O2 concentrations and pH gradients and calculate fluxes of O2, CO2 and bicarbonate (HCO3−) around seagrass leaves (Z. marina L.) covered with artificial, inactive biofilms and natural epiphytic biofilms. A sterilized seawater-agar matrix was used to make an artificial “inactive” biofilm on seagrass leaves with the same thickness as the natural leaf epiphytic biofilm, which impeded turbulent exchange of gases but did not have microbial activity. We compared the concentration profiles and fluxes of O2 and inorganic carbon of the “active” and “inactive” biofilm to investigate the effect of microbial activity and molecular diffusion in seagrass leaf biofilms. In light, the O2 flux of leaves with inactive biofilm was only 31% of the leaves with active biofilm, indicating that the photosynthesis of the microbial community in the biofilm makes up the majority of O2 production in the leaf microenvironment. During darkness, the O2 concentration profiles and O2 fluxes were almost identical in the “active” and “inactive” biofilms. The pH profiles showed the same trend with an increase in pH of ~1.0 in the “active” biofilms and ~0.3 pH units in the “inactive” biofilms in the light, and both showing a decrease of ~0.3 pH units in darkness compared to the bulk seawater. Our measurements thus demonstrate strong photosynthesis in the epiphyte layer driving phyllosphere basification and inorganic carbon limitation. The calculated CO2 concentration on the leaf surface decreased to 0.09 μmol L-1 in the epiphytic biofilm in the light compared to leaf surface CO2 concentrations of 13.8 μmol L-1 on bare seagrass leaves, and the CO2 influxes were only 3.0% and 5.4% of O2 effluxes for leaves with “active” and “inactive” biofilm, respectively. Calculations also showed that HCO3− influxes in light accounted for 91-97% of the total inorganic carbon influx to the seagrass leaf, although the HCO3− utilization via CO2 concentration mechanisms is energy-consuming. Besides increasing mass transfer impedance, leaf epiphytic biofilm activity thus strongly affects the seagrass leaf microenvironment in the light by inducing higher O2 concentration and pH, increasing CO2 limitation and reducing the leaf photosynthetic efficiency.
Multiple Lenses of N-Isotopes Reveal Active Dissolved Organic Nitrogen Cycling in a Subtropical Estuary and Marginal Sea
Authors: Zhong Xiaosong , Yan Maojun , Xu Wenqi , Yan Zhenwei , Xu Feng , Dong Shuhang , Xin Yu , Shi Xiaoyong
Published: May 2022

Dissolved organic nitrogen (DON) is an important component of the marine nitrogen (N) inventory and plays an essential role in N cycling in global estuaries and marginal seas. Understanding DON cycling is important but challenging. Global estuaries and marginal seas are experiencing significant anthropogenic impacts and have intensive physical/biochemical gradients. Therefore, high-quality DON concentration and N-isotope (δ15N–DON) data are very difficult to obtain. To enrich this knowledge, we take the Changjiang Estuary and the adjacent East China Sea shelf seas as a representative example and analyzed multiple isotopes and the concentrations of nitrate (NO3−), particulate nitrogen (PN), and DON. N isotopes combined with optimum multiparameter analysis proved to be very informative. This integrated analysis discriminates active DON production and consumption from a seemingly conservative distribution pattern of DON. The study area was divided into DON production zones 1 and 2 (P-zone 1 and 2) and DON consumption zones 1 and 2 (C-zone 1 and 2). For P-zone 1, the PN-originated DON elevated the δ15N–DON, while in P-zone 2, the DON excreted by phytoplankton was characterized by low δ15N and lowered δ15N–DON. DON consumption occurred in the NO3− depleted surface waters (C-zone 1) as well as the shelf middle and bottom waters (C-zone 2). This study discovers and consolidates the active and dynamical zoning of DON cycling from the estuary to the offshore marginal sea and establishes a useful means that is of valuable reference to DON cycling studies in global estuaries and marginal seas.
Automatic Mapping and Monitoring of Marine Water Quality Parameters in Hong Kong Using Sentinel-2 Image Time-Series and Google Earth Engine Cloud Computing
Authors: Kwong Ivan H. Y. , Wong Frankie K. K. , Fung Tung
Published: May 2022

Continuous monitoring of coastal water qualities is critical for water resource management and marine ecosystem sustainability. While remote sensing data such as Sentinel-2 satellite imagery routinely provide high-resolution observations for time-series analysis, the cloud-based Google Earth Engine (GEE) platform supports simple image retrieval and large-scale processing. Using coastal waters of Hong Kong as the study area, this study utilized GEE to (i) query and pre-process all Sentinel-2 observations that coincided with in situ measurements; (ii) extract the spectra to develop empirical models for water quality parameters using artificial neural networks; and (iii) visualize the results using spatial distribution maps, time-series charts and an online application. The modeling workflow was applied to 22 water quality parameters and the results suggested the potential to predict the levels of several nutrients and inorganic constituents. In-depth analyses were conducted for chlorophyll-a, suspended solids and turbidity which produced high correlations between the predicted and observed values when validated with an independent dataset. The selected input variables followed spectral characteristics of the optical constituents. The results were considered more robust compared to previous works in the same region due to the automatic extraction of all available images and larger number of observations from different years and months. Besides visualizing long-term spatial and temporal variabilities through distribution maps and time-series charts, potential anomalies in the monitoring period including algal bloom could also be captured using the models developed from historical data. An online application was created to allow novice users to explore and analyze water quality trends with a simple web interface. The integrated use of remotely-sensed images, in situ measurements and cloud computing can offer new opportunities for implementing effective monitoring programs and understanding water quality dynamics. Although the obtained levels of accuracies were below the desired standard, the end-to-end cloud computing workflow demonstrated in this study should be further investigated considering the cost and computational efficiency for timely information delivery.
A Novel Automatic Water Autosampler Operated From UAVs for Determining Dissolved Trace Elements
Authors: Sparaventi Erica , Rodríguez-Romero Araceli , Navarro Gabriel , Tovar-Sánchez Antonio
Published: May 2022

Monitoring water systems under extreme conditions or in remote areas poses a risk to scientists and staff involved, and can also result in disturbances to the local flora and fauna. In order to overcome these limitations, new techniques are being developed with the aim to gain more insight into how geochemical pathways of trace elements regulate the functioning of the ocean. Here, we present the first trace metals and inorganic nutrients concentrations measured in dissolved (<0.22 µm) surface water samples collected in the Antarctic by using an Automatic Water Autosampler (AWA) system onboard an unmanned aerial vehicle (UAV). The AWA system has been used to chemically quantify the composition of the water masses (lake and coastal water) of Deception Island (South Shetland Islands, Antarctica), with, for example, Pb values ranging from 0.01 to 0.25 nM in seawater and 1.20 to 2.11 nM in lake water. The results demonstrate the effectiveness of the AWA system in environmental studies that require the sampling of trace metals and nutrients without sample contamination.
Optimization of Lapping and Polishing of Steel Samples for Nanoindentation Based on SVM-GA
Authors: Cheng Zhichao , Wei Qianfeng , Wen Donghui
Published: May 2022

The nanoindentation test is extensively used to obtain the mechanics performance of different kinds of materials. In this study, the general process in the lapping and polishing of Q235 steel samples for nanoindentation has been analyzed by considering the pressure (P), rotation speed of the lapping and polishing plate (rp), flow rate of abrasive slurry (Qa), and the processing time (t). It is found from the lapping experiments with a full factorial design that the optimized processing parameters are rp of 200 r/min, P of 30 N, and t of 4 min considered in this study by considering the material removal rate and subsurface damage. The central composite design method has been used to design the polishing experiments, and the support vector machine (SVM) method has been used to deal with these experimental results, and it is found that the developed SVM model can accurately predict the surface roughness under different processing parameters. Then, based on the SVM model, the genetic algorithm (GA) method is used to obtain the optimized processing parameters in the polishing process, and it is found from the SVM-GA study that the optimized processing parameters in the lapping process are rp of 108 r/min, P of 33 N, Qa of 20 ml/min, and t of 3 min. Finally, a set of nanoindentation tests have been conducted to evaluate the lapping and polishing performance, and it is found that the surface integrity has been significantly improved after the optimization of the lapping and polishing parameters by using the SVM-GA method considered in this study.
Radial Seismic Metamaterials Based on Layering Theory: Broadband Shielding of Ultra-Low Frequency Seismic Surface Waves
Authors: Liu Haixia , Li Lixia , Jia Qi , Jiang Sanhe , Li Pengguo , Zhang Xicheng
Published: May 2022

In this paper, a novel radial seismic metamaterial (LRSM) based on layering theory is proposed. Compared with traditional seismic metamaterials, the structure of LRSM is a periodic array of multi-layer rings distributed along the radial direction. By using the finite element method, the dispersion relationship and displacement vector field of LRSM with different layers are studied, and the influence of structural geometric parameters and circumferential continuity on the band gap characteristics of LRSM is discussed. The frequency domain analysis of finite periodic structure and the three-dimensional transient wave propagation analysis are carried out. The results show that the LRSM has ultra-low frequency broadband characteristics, which is produced by the coupling between the local resonance of the LRSM and the surface wave mode. Comparing three LRSMs with different layers, the initial frequency and bandwidth do not change monotonically with the increase of the number of layers. There is an optimal bandgap characteristic in two layers, and the relative bandwidth can reach 83.9%. The increase of the number causes the change of the structural stiffness, which is caused by the change of the local resonance strength. The position and width of the band gap in the LRSM are very sensitive to the height of the structure. The increase of the height of the LRSM can move the first band gap to the low frequency, and the total bandwidth increases, which is mainly caused by the increase of the equivalent mass of the system with the increase of the height of the structure. Further, it is verified that LRSM can effectively attenuate seismic surface waves of 0.1–20 Hz, and its maximum amplitude attenuation can exceed 85%. The novel periodic structure proposed in this paper can provide new options for the fields of earthquake and low-frequency vibration reduction.