bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution and Controlling Growth Factors of Ooids in Qinghai Lake, Northern Tibet Plateau, China
Authors: Hao Lewei , Tao Huifei , Li Shutong , Ma Xiaofeng , Ji Hongjie , Qiu Junli
Published: February 2022

Ooids are coated carbonate grains, which exist in shallow water marine and lacustrine environments. There is an ongoing debate about whether the origin of ooids is inorganic or organic. Qinghai Lake is the largest inland lake in China, and ooids are seen on the lake shore. This paper focuses on whether environmental energy has an impact on the growth and size of ooids. Through hydrochemical analysis, thin section observation, and scanning electron microscope, the carbonate coats of beach sands from Qinghai Lake were studied. The research shows that the carbonate-coated grain content from the different shores of the lake present variations. The hydrodynamics and particularly the waves seem to control the distribution of carbonate coats in the lake shore, not the hydrochemical condition. In addition, the integrity and thickness of carbonate coats from the shores with a strong hydrodynamic force are high and thick, respectively. The carbonate coats are often observed on medium-grained sands, and the maximum carbonate-coated grain occurred under the strongest waves, indicating that ooids can be produced only when hydrodynamic force and particle size are well matched. Bacteria or extracellular polymeric substances are not observed within the ooid cortices by scanning electron microscopy. So, bacteria may not be a major factor in the formation and growth of ooids, but hydrodynamic forces appear to play a great role in carbonate grain coat distribution, integrity, thickness, and ooid grain size.
Study on Optimization of Infrasound Filtering Method for Coal Sample Failure under Load
Authors: Zhang Jianguo , Wang Man , Jia Bing , Wang Yujie
Published: February 2022

Effective filtering of the infrasound signal generated by coal samples is the basis for realizing the prediction of the infrasound of coal sample damage. Based on the infrasonic signal test of the coal samples during the loading process, a simulation method was used to construct a mixed signal containing noise signals and infrasound signals. Three methods are used to filter the mixed signal, including wavelet filtering, EMD filtering, and EMD-wavelet joint filtering. The filtering effect was compared by correlation coefficient, signal-to-noise ratio, and frequency domain waveform graph. The comparison results showed that the EMD-wavelet joint filtering method had the highest correlation coefficient and signal-to-noise ratio after noise filtering, and the noise signal in the frequency domain waveform diagram was the most thorough. It provides a new method for filtering infrasound signals in the process of coal sample loading, which is greatly significant for improving the accuracy of infrasound prediction of coal sample damage.
Pollen Data as a Temperature Indicator in the Late Holocene: A Review of Results on Regional, Continental and Global Scales
Authors: Rao Zhiguo , Tian Yiping , Guang Kaiyue , Wei Shikai , Guo Haichun , Feng Zixian , Zhao Lin , Li Yunxia
Published: February 2022

The temperature history of the Holocene is intensely debated, with both proxy seasonality effects and climate model sensitivity being proposed as possible reasons for the “Holocene temperature conundrum”. However, possible human impacts on terrestrial proxies are often not adequately considered, especially for the late Holocene. Based on a review of pollen-based and pollen-dominated temperature records on regional, continental and global scales, we propose that pollen may be a poor indicator of temperature change in late Holocene, mainly as a result of the impacts of intensified human activities on terrestrial vegetation. Thus, we suggest that possible human impacts on terrestrial Holocene temperature records should be carefully evaluated; and also that more Holocene temperature records are obtained from areas without significant direct human impacts, or that proxies that are insensitive to human impacts are used for late Holocene climatic reconstruction.
Medium-Range Predictability of Boreal Summer Western North Pacific Subtropical High and Its ENSO Modulation
Authors: Gao Li , Ren Pengfei , Zheng Jiawen
Published: February 2022

In boreal summer, variations of intensity and location of the western North Pacific subtropical high (WNPSH) have significant impacts on weather and climate in East Asia. In this study, the medium-range prediction of WNPSH is comprehensively evaluated with various scores based on reforecast data of the National Centers for Environmental Prediction - Global Ensemble Forecast System, and the predictability source of the WNPSH medium-range forecasting is further analyzed by examining how well the model can reproduce the modulation of El Niño-Southern Oscillation (ENSO) on WNPSH as observed. The results show that this system has a systematic bias in the WNPSH forecasts, mainly manifested by the weak strength and the southeastward shifted position, and such a bias further increases with lead time. Effective prediction skills of WNPSH are 10–11 days for its intensity and area, 7 days for its ridge line, but only 1–3 days for its western boundary ridge point in terms of different scores, respectively, which can be improved through developing a bias correction method of prediction. It is demonstrated that the medium-range predictability of WNPSH is mainly originated from ENSO and its significant lagged effects on WNPSH well revealed in observation can be realistically reproduced by this system within the effective prediction lengths. A strong ENSO modulation of the WNPSH prediction skills has been clearly found in terms of the different indices, which depends on the ENSO’s developing and decaying phases. The intensity and area of WNPSH are usually highly predictable due to the ENSO effect being reproduced by the system well while the location indices of WNPSH have relatively low predictability, which are mainly affected by internal variability and difficultly captured by the model. Predictability analysis of WNPSH as modulated by ENSO shows good potential for medium-range forecasting with high skills.
The Prognosis of ART Is Not Altered in Cystic Fibrosis Women: A Case-Report Study
Authors: Braham Inès , Morisot Adeline , Boukaïdi Samir , Perceval Marie , Durieu Isabelle , Rousset-Jablonski Christine , Hieronimus Sylvie , Leroy Sylvie , Chevalier Nicolas
Published: February 2022

Research Question

Unlike in men, a very limited number of studies were focused on the specificity of ART management of cystic fibrosis (CF) in women. The purpose of this study was to determine the causes of infertility in patients, the appropriate ART treatment, and their prognosis in terms of pregnancy.

Design

We conducted a multicentre analytical case-control study including CF women who were age-matched to non-CF women. We reported the causes of infertility, the ART management type and pregnancy outcomes.

Results

17 cases were compared to 34 controls. There was no significant difference between the groups concerning cause infertility. There was a non-statistically significant trend with a lower antral follicle count in CF compared to controls (19.5 versus 26.8, p=0.08). IUI seemed to be as successful as IVF/ICSI in CF as opposed to controls where the IVF/ICSI was the most effective (in CF group for HCG >100 UI/L: 38.8% vs. 36.8%, p=0.4175). There were more embryos obtained in CF than in controls (3.1 versus 1.6, p=0.02). The number of oocytes and embryos obtained and pregnancy outcomes remained similar between DF508 homozygous group and others CFTR mutations group. The results of ART procedures and pregnancy evolution were not influenced by FEV1.

Conclusion

In absence of any other pathology, IUI may be first option for CF women. If insemination fails, IVF with a low dose of gonadotropins may be more appropriate to prevent the risk of hyperstimulation syndrome. FEV1 and genetic do not seem to be contributing factors in the prognosis of ART.
Low Endogenous LH on the COS Initiation Day of a GnRH-Agonist Regimen Increases the Risk of Early Pregnancy Loss and Adverse ART Outcomes
Authors: Luo Xi , Li Lei , Lin Na , Ma Rui , Li Yonggang , Wu Ze
Published: February 2022

Objective

To assess the impact of serum luteinizing hormone (LH) levels on the day of initiation of controlled ovarian stimulation (COS) after pituitary suppression on early pregnancy loss and assisted reproductive technology (ART) outcomes.

Design

Retrospective cohort study.

Setting

University-affiliated hospital.

Patients

A total of 9540 normogonadotrophic patients were treated with a GnRH agonist for in vitro fertilization (IVF). Based on the serum concentration of LH on the COS initiation day, patients were divided into low (<1 mIU/mL, n=2838), medium (1–1.49 mIU/mL, n=3357), or high (≥1.5 mIU/mL, n=3345) LH groups and received either fresh embryo transfer (ET) or frozen ET (women with high ovarian response, insufficient endometrial thickness, or requesting frozen ET). A total of 6279 cycles were fresh ET (1960, 2222, and 2097 in the low, medium, and high LH groups, respectively).

Intervention(s)

During IVF/ICSI, a GnRH agonist was used to suppress pituitary function in the midluteal phase or follicular phase, and then gonadotropin was used to induce COS.

Main Outcome Measure(s)

The early pregnancy loss rate (ePLR) and live-birth rate (LBR) for fresh ET, as well as the cumulative ePLR and LBR for the entire ovarian stimulation cycle, were compared.

Results

In the fresh ET cycles, the high, medium and low LH groups had an ePLR of 8.6%, 11.9% and 12.5%, respectively, and LBR of 42.1%, 37.9% and 37.5%, respectively. There were no significant differences in terms of clinical pregnancy rate (CPR), late pregnancy loss rate (lPLR), and ectopic pregnancy rate (EPR) among the three LH groups. For the entire ovarian stimulation cycle, the high LH group had a greater number of retrieved oocytes compared with the low and medium LH groups. Among the groups of high, medium and low LH, the cumulative CPR were 72.8%, 69.8% and 68.8%, respectively, and the cumulative LBR were 63.4%, 60.4% and 58.5%, respectively. There were no significant differences in the cumulative ePLR, lPLR, or EPR. After multivariable logistic regression, compared with the high LH group, the adjusted odds ratio of early pregnancy loss in the low and medium LH group were 1.429 (1.065-1.919, P = 0.018) and 1.389 (1.041-1.853, P = 0.026).

Conclusions

After pituitary suppression by a GnRH-agonist during IVF, a low LH level (<1.5 mIU/mL) on the COS initiation day was associated with adverse ART outcomes—including fewer oocytes, higher ePLR and lower LBR in fresh ET—and lower cumulative CPR and LBR in the entire ovarian-stimulation cycle. And LH on the COS initiation day was an independent factor affecting ePLR after multivariate regression.
Research on Energy Management of a Virtual Power Plant Based on the Improved Cooperative Particle Swarm Optimization Algorithm
Authors: Yu Dongmin , Zhao Xuejiao , Wang Yong , Jiang Linru , Liu Huanan
Published: February 2022

Energy management of virtual power plants (VPPs) directly affects operators’ operating profits and is also related to users’ comfort and economy. In order to provide a reasonable scheme for scheduling each unit of the VPP and to improve the operating profits of the VPP, this study focuses on the optimization of VPP energy management under the premise of ensuring the comfort of flexible load users. First, flexible loads are divided into time-shiftable load (TL), power-variable load (PL), and interruptible load (IL), and their accurate power consumption models are established, respectively. Then, aiming at maximizing the operation profits of a VPP operator, an optimization model of VPP energy management considering user comfort is proposed. Finally, the improved cooperative particle swarm optimization (ICPSO) algorithm is applied to solve the proposed VPP energy management optimization model, and the optimal scheduling scheme of VPP energy management is obtained. Taking a VPP in the coastal area of China as an example, results show that the optimization model proposed in this article has the advantages of good economy and higher user comfort. Meanwhile, the ICPSO algorithm has the characteristics of faster optimization speed and higher accuracy when solving the problem with multiple variables.
Decontamination of Mixed Paper and Plastic Municipal Solid Waste Increases Low and High Temperature Conversion Yields
Authors: Brown Rebecca M. , Hoover Amber N. , Klinger Jordan L. , Wahlen Bradley D. , Hartley Damon , Lee Hyeonseok , Thompson Vicki S.
Published: February 2022

With the implementation of China’s Green Fence Policy and the following National Sword Policy, there is a need to divert previously accepted waste materials away from the landfill. Mixed plastic and paper wastes that are too contaminated to be economically recycled can be used for conversion into fuels and products. The effect of common contaminants present in waste streams must be determined to make municipal solid waste (MSW) a viable alternative to agricultural feedstocks for conversion. In this study, MSW was sourced from a dual stream materials recovery facility (MRF) in Emmet County, Michigan and characterized via mass balance. The most common contaminants in mixed paper and plastic were quantified and targeted for decontamination when mixed paper was explored for low temperature conversion pathways and plastics for high temperature conversion pathways. Ink, stickies, and plastic contamination were sorted out of the mixed paper stream and did not have an impact on sugar yields during enzymatic hydrolysis (EH). Although no improvement in yield was found, it was noted that copy paper within the mixed paper stream had an elevated pH and higher concentration of fermentation inhibitors, suggesting that intrinsic properties of some paper types may not be ideal for EH and fermentation conversion. Dilute alkaline pretreatment and mechanical refining of mixed paper increased the EH yield of mixed paper, suggesting this previously established process could be used as a decontamination method. “Dirt” and particulates were washed from mixed plastic using either an aqueous detergent or a non-aqueous chemical washing method. Liquid oil yields were increased during microwave assisted fast pyrolysis. All decontamination techniques met the cost target of less than $30/dry ton with plastic decontamination ranging from $18.16 to $24.81/dry ton. Because dilute alkaline pre-treatment and mechanical refining is considered part of the conversion process, the decontamination cost during feedstock preprocessing was considered $0/dry ton.
Investigation of Heavy Metal Accumulation in Vegetables and Health Risk to Humans From Their Consumption
Authors: Gupta Neha , Yadav Krishna Kumar , Kumar Vinit , Prasad Shiv , Cabral-Pinto Marina M. S. , Jeon Byong-Hun , Kumar Sandeep , Abdellattif Magda H. , Alsukaibia Abdulmohsen Khalaf Dhahi
Published: February 2022

Heavy metals contamination of soil and edible parts of vegetables is presently a challenging environmental issue worldwide. The present study determined the accumulated amount of cadmium (Cd), lead (Pb), nickel (Ni), cobalt (Co), zinc (Zn), copper (Cu), and manganese (Mn) in soil, coriander, onion, and tomato collected from agricultural fields of Jhansi city, India. The bio-concentration factor and non-carcinogenic health risks were also assessed to know the vegetables’ accumulation potential of heavy metals from soil and possibility to have non-carcinogenic health risks via an intake of these vegetables. The samples were digested using di-acid solution prior to heavy metals analysis by atomic absorption spectrometric method. The average content of Cd, Pb, Ni, Co, Zn, Cu, and Mn were 2.02, 19.09, 21.56, 9.31, 35.34, 14.96, and 15.21 mg/kg dry weight (dw) in soil, 0.23, 2.12, 0.77, 0.47, 36.65, 5.92, and 21.65 mg/kg dw in coriander, 0.13, 0.66, 0.54, 0.32, 23.94, 6.25, and 20.15 mg/kg dw in onion, 0.14, 0.46, 0.89, 0.22, 16.77, 4.77, and 14.46 mg/kg dw in tomato, respectively. The bio-concentration factor revealed significant accumulation of Zn (1.04) and Mn in coriander (1.42), and in onion (1.32). The target hazard quotient and health risk index signaled that the population consuming these vegetables is risk-free. However, it is recommended that the concentration of heavy metals in the soil and crops of the study area and its related health risks be regularly monitored to avoid significant health risks in the future.
An Optimality-Based Spatial Explicit Ecohydrological Model at Watershed Scale: Model Description and Test in a Semiarid Grassland Ecosystem
Authors: Chen Lajiao , Hu Zhidan , Du Xiaoping , Khan Mohd Yawar Ali , Li Xiaojun , Wen Jie
Published: February 2022

Optimality principles have been applied in ecohydrological modeling to derive optimal vegetation properties and describe co-evolution states of vegetation and water cycle. Unfortunately, most existing optimality-based models only consider vertical vegetation-soil-water interactions on plot scale, without considering the lateral hydrological processes. This work aims to extend the field-scale Vegetation Optimality Model (VOM) to the watershed scale. Lateral flow is incorporated to VOM through a hierarchical strategy, establishing the Distributed Vegetation Optimality Model (DisVOM). The model is tested with long-tem flux measurements in the Walnut Gulch watershed, a United States Agricultural Research Service (US-ARS) experimental watershed in southern Arizona. The results indicate the model performance is acceptable for most of years, especially for the growing season. The seasonal dynamic of ET, soil water, and GPP demonstrate good consistency with observations. The model provides reasonable spatial distribution of ET and GPP, suggesting the model can discriminate the effect of lateral flow on water redistribution, and consequently on root water uptake, as well as carbon assimilation. The model could be a useful tool assessing the impact of climate change and human activities on vegetation and water cycle.
Cost-Benefit Trade-Offs of Aquatic Resource Exploitation in the Context of Hominin Evolution
Authors: de Chevalier Gregorio , Bouret Sébastien , Bardo Ameline , Simmen Bruno , Garcia Cécile , Prat Sandrine
Published: February 2022

While the exploitation of aquatic fauna and flora has been documented in several primate species to date, the evolutionary contexts and mechanisms behind the emergence of this behavior in both human and non-human primates remain largely overlooked. Yet, this issue is particularly important for our understanding of human evolution, as hominins represent not only the primate group with the highest degree of adaptedness to aquatic environments, but also the only group in which true coastal and maritime adaptations have evolved. As such, in the present study we review the available literature on primate foraging strategies related to the exploitation of aquatic resources and their putative associated cognitive operations. We propose that aquatic resource consumption in extant primates can be interpreted as a highly site-specific behavioral expression of a generic adaptive foraging decision-making process, emerging in sites at which the local cost-benefit trade-offs contextually favor aquatic over terrestrial foods. Within this framework, we discuss the potential impacts that the unique intensification of this behavior in hominins may have had on the evolution of the human brain and spatial ecology.
Metabolite Profiling and Transcriptome Analyses Provide Insight Into Phenolic and Flavonoid Biosynthesis in the Nutshell of Macadamia Ternifolia
Authors: Shi Rui , Tao Liang , Tu Xinghao , Zhang Chunsheng , Xiong Zhi , Rami Horowitz Abraham , Asher Jiftah Ben , He Jun , Hu Faguang
Published: February 2022

Macadamia ternifolia is a dynamic oil-producing nut crop in the world. However, the nutshell is frequently considered as a low-quality material. Further, its metabolic profile is still uncharacterized. In order to explore the industrial significance of the nutshell, this study performed metabolic and transcriptomic analyses at various developmental stages of the nutshell. The qualitative and quantitative metabolic data analysis identified 596 metabolic substances including several species of phenolic acids, flavonoids, lipids, organic acids, amino acids and derivatives, nucleotides and derivatives, alkaloids, lignans, coumarins, terpenoids, tannins, and others. However, phenolic acids and flavonoids were predominant, and their abundance levels were significantly altered across various developmental stages of the nutshell. Comparative transcriptome analysis revealed that the expression patterns of phenolic acid and flavonoid pathway related genes were significantly changed during the nutshell growth. In particular, the expression of phenylalanine ammonia-lyase, C4H, 4CL, CHS, CHI, F3H, and FLS had dynamic differences at the various developmental stages of the nutshell. Our integrative metabolomic and transcriptomic analyses identified the key metabolic substances and their abundance levels. We further discussed the regulatory mechanism of phenolic and flavonoid biosynthesis in the nutshell of M. ternifolia. Our results provide new insights into the biological profiles of the nutshell of M. ternifolia and help to elucidate the molecular mechanisms of phenolic and flavonoid biosynthesis in the nutshell of M. ternifolia.
Itaconate and Its Derivatives Repress Early Myogenesis In Vitro and In Vivo
Authors: Oh Tae Seok , Hutchins Damian C. , Mainali Rabina , Goslen Kevin H. , Quinn Matthew A.
Published: February 2022

A Krebs cycle intermediate metabolite, itaconate, has gained attention as a potential antimicrobial and autoimmune disease treatment due to its anti-inflammatory effects. While itaconate and its derivatives pose an attractive therapeutic option for the treatment of inflammatory diseases, the effects outside the immune system still remain limited, particularly in the muscle. Therefore, we endeavored to determine if itaconate signaling impacts muscle differentiation. Utilizing the well-established C2C12 model of in vitro myogenesis, we evaluated the effects of itaconate and its derivatives on transcriptional and protein markers of muscle differentiation as well as mitochondrial function. We found itaconate and the derivatives dimethyl itaconate and 4-octyl itaconate disrupt differentiation media-induced myogenesis. A primary biological effect of itaconate is a succinate dehydrogenase (SDH) inhibitor. We find the SDH inhibitors dimethyl malonate and harzianopyridone phenocopie the anti-myogenic effects of itaconate. Furthermore, we find treatment with exogenous succinate results in blunted myogenesis. Together our data indicate itaconate and its derivatives interfere with in vitro myogenesis, potentially through inhibition of SDH and subsequent succinate accumulation. We also show 4-octyl itaconate suppresses injury-induced MYOG expression in vivo. More importantly, our findings suggest the therapeutic potential of itaconate, and its derivatives could be limited due to deleterious effects on myogenesis.
Supplementation of H7N9 Virus-Like Particle Vaccine With Recombinant Epitope Antigen Confers Full Protection Against Antigenically Divergent H7N9 Virus in Chickens
Authors: Kong Dexin , Chen Taoran , Hu Xiaolong , Lin Shaorong , Gao Yinze , Ju Chunmei , Liao Ming , Fan Huiying
Published: February 2022

The continuous evolution of the H7N9 avian influenza virus suggests a potential outbreak of an H7N9 pandemic. Therefore, to prevent a potential epidemic of the H7N9 influenza virus, it is necessary to develop an effective crossprotective influenza vaccine. In this study, we developed H7N9 virus-like particles (VLPs) containing HA, NA, and M1 proteins derived from H7N9/16876 virus and a helper antigen HMN based on influenza conserved epitopes using a baculovirus expression vector system (BEVS). The results showed that the influenza VLP vaccine induced a strong HI antibody response and provided effective protection comparable with the effects of commercial inactivated H7N9 vaccines against homologous H7N9 virus challenge in chickens. Meanwhile, the H7N9 VLP vaccine induced robust crossreactive HI and neutralizing antibody titers against antigenically divergent H7N9 viruses isolated in wave 5 and conferred on chickens complete clinical protection against heterologous H7N9 virus challenge, significantly inhibiting virus shedding in chickens. Importantly, supplemented vaccination with HMN antigen can enhance Th1 immune responses; virus shedding was completely abolished in the vaccinated chickens. Our study also demonstrated that viral receptor-binding avidity should be taken into consideration in evaluating an H7N9 candidate vaccine. These studies suggested that supplementing influenza VLP vaccine with recombinant epitope antigen will be a promising strategy for the development of broad-spectrum influenza vaccines.
IL-17-Dependent Dysregulated Cutaneous Immune Homeostasis in the Absence of the Wiskott–Aldrich Syndrome Protein
Authors: Herman Katherine E. , Yoshida Takeshi , Hughson Angela , Grier Alex , Gill Steven R. , Beck Lisa A. , Fowell Deborah J.
Published: February 2022

Wiskott–Aldrich Syndrome (WAS) is characterized by recurrent infections, thrombocytopenia, and eczema. Here, we show that WASp-deficient mice on a BALB/c background have dysregulated cutaneous immune homeostasis with increased leukocyte accumulation in the skin, 1 week after birth. Increased cutaneous inflammation was associated with epithelial abnormalities, namely, altered keratinization, abnormal epidermal tight junctional morphology and increased trans-epidermal water loss; consistent with epidermal barrier dysfunction. Immune and physical barrier disruption was accompanied by progressive skin dysbiosis, highlighting the functional significance of the disrupted cutaneous homeostasis. Interestingly, the dysregulated immunity in the skin preceded the systemic elevation in IgE and lymphocytic infiltration of the colonic lamina propria associated with WASp deficiency. Mechanistically, the enhanced immune cell accumulation in the skin was lymphocyte dependent. Elevated levels of both Type 2 (IL-4, IL-5) and Type 17 (IL-17, IL-22, IL-23) cytokines were present in the skin, as well as the ‘itch’ factor IL-31. Unexpectedly, the canonical WAS-associated cytokine IL-4 did not play a role in the immune dysfunction. Instead, IL-17 was critical for skin immune infiltration and elevation of both Type 2 and Type 17 cytokines. Our findings reveal a previously unrecognized IL-17-dependent breakdown in immune homeostasis and cutaneous barrier integrity in the absence of WASp, targeting of which may provide new therapeutic possibilities for the treatment of skin pathologies in WAS patients.
Plasma Exosomes Transfer miR-885-3p Targeting the AKT/NFκB Signaling Pathway to Improve the Sensitivity of Intravenous Glucocorticoid Therapy Against Graves Ophthalmopathy
Authors: Sun Jingxue , Wei Jiaxing , Zhang Yaguang , Li Jingjing , Li Jian , Yan Jiazhuo , Guo Min , Han Jun , Qiao Hong
Published: February 2022

Graves ophthalmopathy (GO), a manifestation of Graves’ disease, is an organ-specific autoimmune disease. Intravenous glucocorticoid therapy (ivGCs) is the first-line treatment for moderate-to-severe and active GO. However, ivGCs is only effective in 70%–80% of GO patients. Insensitive patients who choose 12-week ivGCs not only were delayed in treatment but also took the risk of adverse reactions of glucocorticoids. At present, there is still a lack of effective indicators to predict the therapeutic effect of ivGCs. Therefore, the purpose of this study is to find biomarkers that can determine the sensitivity of ivGCs before the formulation of treatment, and to clarify the mechanism of its regulation of ivGCs sensitivity. This study first characterized the miRNA profiles of plasma exosomes by miRNA sequencing to identify miRNAs differentially expressed between GO patients with significant improvement (SI) and non-significant improvement (NSI) after ivGCs treatment. Subsequently, we analyzed the function of the predicted target genes of differential miRNAs. According to the function of the target genes, we screened 10 differentially expressed miRNAs. An expanded cohort verification showed that compared with NSI patients, mir-885-3p was upregulated and mir-4474-3p and mir-615-3p were downregulated in the exosomes of SI patients. Based on statistical difference and miRNA function, mir-885-3p was selected for follow-up study. The in vitro functional analysis of exosomes mir-885-3p showed that exosomes from SI patients (SI-exo) could transfer mir-885-3p to orbital fibroblasts (OFs), upregulate the GRE luciferase reporter gene plasmid activity and the level of glucocorticoid receptor (GR), downregulate the level of inflammatory factors, and improve the glucocorticoid sensitivity of OFs. Moreover, these effects can be inhibited by the corresponding miR inhibitor. In addition, we found that high levels of mir-885-3p could inhibit the AKT/NFκB signaling pathway, upregulate the GRE plasmid activity and GR level, and downregulate the level of inflammatory factors of OFs. Moreover, the improvement of glucocorticoid sensitivity by mir-885-3p transmitted by SI-exo can also be inhibited by the AKT/NFκB agonist. Finally, through the in vivo experiment of the GO mouse model, we further determined the relationship between exosomes’ mir-885-3p sequence, AKT/NFκB signaling pathway, and glucocorticoid sensitivity. As a conclusion, plasma exosomes deliver mir-885-3p and inhibit the AKT/NFκB signaling pathway to improve the glucocorticoid sensitivity of OFs. Exosome mir-885-3p can be used as a biomarker to determine the sensitivity of ivGCs in GO patients.
New Druggable Targets for Rheumatoid Arthritis Based on Insights From Synovial Biology
Authors: Sandhu Gurvisha , Thelma B. K.
Published: February 2022

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease characterized by chronic inflammation and destruction of multiple small joints which may lead to systemic complications. Altered immunity via pathogenic autoantibodies pre-date clinical symptom development by several years. Incompletely understood range of mechanisms trigger joint-homing, leading to clinically evident articular disease. Advances in therapeutic approaches and understanding pathogenesis have improved prognosis and likely remission. However, partial/non-response to conventional and biologic therapies witnessed in a subset of patients highlights the need for new therapeutics. It is now evident that joint disease chronicity stems from recalcitrant inflammatory synovial environment, majorly maintained by epigenetically and metabolically reprogrammed synoviocytes. Therefore, interference with effector functions of activated cell types seems a rational strategy to reinstate synovial homeostasis and complement existing anti-inflammatory interventions to mitigate chronic RA. Presenting this newer aspect of fibroblast-like synoviocytes and myeloid cells underlying the altered synovial biology in RA and its potential for identification of new druggable targets is attempted in this review. Major leads from i) molecular insights of pathogenic cell types from hypothesis free OMICS approaches; ii) hierarchy of their dysregulated signaling pathways; and iii) knowledge of druggability of molecular nodes in these pathways are highlighted. Development of such synovial biology-directed therapeutics hold promise for an enriched drug repertoire for RA.
The Oxidative Injury of Extracellular Hemoglobin Is Associated With Reactive Oxygen Species Generation of Grass Carp (Ctenopharyngodon idella)
Authors: Qin Zhendong , Yang Minxuan , Lu Zhijie , Babu V. Sarath , Li Yanan , Shi Fei , Zhan Fanbin , Liu Chun , Li Jun , Lin Li
Published: February 2022

Intravascular hemolysis is a fundamental feature of hemorrhagic venereal infection or tissue and releases the endogenous damage-associated molecular pattern hemoglobin (Hb) into the plasma or tissues, which results in systemic inflammation, vasomotor dysfunction, thrombophilia, and proliferative vasculopathy. However, how the cytotoxic Hb affects the tissues of grass carp remains unclear. Here, we established a hemolysis model in grass carp by injecting phenylhydrazine (PHZ). The data revealed that the PHZ-induced hemolysis increased the content of Hb and activated the antioxidant system in plasma. The histopathology analysis data showed that the PHZ-induced hemolysis increased the accumulation of Hb and iron both in the head and middle kidney. The results of quantitative real-time PCR (qRT-PCR) detection suggested that the hemolysis upregulated the expressions of iron metabolism-related genes. In addition, the immunofluorescence and immunohistochemistry data revealed that the hemolysis caused an obvious deposition of collagen fiber, malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) accumulation and increased the content of oxidative-related enzymes such as β-galactosidase (β-GAL), lipid peroxide (LPO), and MDA in both the head and middle kidney. Furthermore, the PHZ-induced hemolysis significantly increased the production of reactive oxygen species (ROS), which resulted in apoptosis and modulated the expressions of cytokine-related genes. Taken together, excess of Hb released from hemolysis caused tissue oxidative damage, which may be associated with ROS and inflammation generation.
TIGIT Signaling Pathway Regulates Natural Killer Cell Function in Chronic Hepatitis B Virus Infection
Authors: Wang Juan , Hou Hongyan , Mao Lie , Wang Feng , Yu Jing , Luo Ying , Lin Qun , Sun Ziyong
Published: February 2022

Background and Objective

Persistent infection of hepatitis B virus (HBV) and liver damage in immune active chronic hepatitis B (CHB) could be partly due to the overreaction of natural killer (NK) cells, including pro-inflammatory cytokine secretion and cytotoxicity. An immunosuppressive receptor, T-cell immunoglobulin and immunoreceptor tyrosine–based inhibitory motif (ITIM) domain (TIGIT) is specifically expressed in NK cells. This study aims to investigate the role of the TIGIT signaling pathway in regulating NK cell functions in patients with CHB.

Method

We comparatively assessed the expression of TIGIT in NK cells of patients with immune active CHB (CHB-IA), carriers of immune control chronic HBV (CHB-IC), and healthy controls (HCs), and then explored mechanisms of the TIGIT signaling pathway in regulating NK cell-mediated liver injury by different molecular assessments.

Result

The expression of TIGIT in NK cells was enhanced in CHB-IC but was reduced in CHB-IA compared with the HC group. In patients with CHB-IA, the expression of TIGIT was inversely correlated with intensity of the liver damage. Moreover, TIGIT-NK cells show higher IFN-γ secretion capability, degranulation activity, and cytotoxicity but lower apoptosis than TIGIT+ NK cells. Blockade of the TIGIT pathway with anti-TIGIT antibody increased NK cell function, while activation of the TIGIT pathway with TIGIT Fc and CD155 Fc chimera protein down-regulated NK cell function.

Conclusion

Our data showed that the TIGIT signaling pathway participates in NK cell impairment, which could be used as a new therapeutic target to protect patients with chronic HBV infection from severe liver injury.
Novel Therapeutic Target(s) for Psoriatic Disease
Authors: Thakur Vishal , Mahajan Rahul
Published: February 2022

Psoriasis and psoriatic arthritis, together known as psoriatic disease, is highly prevalent chronic relapsing inflammatory disease affecting skin, joints or both and is associated with several comorbidities such as cardiovascular, metabolic, psychiatric, renal disease etc. The etiopathogenesis of psoriasis is complex and mainly driven by aberrant immune response owing to the genetic susceptibility and various environmental factors such as trauma, infections and drugs. Recent advances in understanding molecular and cellular pathways have identified tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), IL-23, IL-22 as major contributors in psoriasis pathogenesis. Advances in the knowledge of pathophysiology, the interaction of autoinflammation and clinical phenotypes have led to the development of highly effective targeted therapeutic agents which include TNF-α, IL-17, IL-23, IL-1 α/β or IL-36 inhibitors or receptor blockers, small molecule drugs like phosphodiesterase-4 inhibitors (apremilast), Janus kinase (JAK) inhibitors, retinoic acid receptor-related orphan receptor γt (RORγt) inhibitors. These novel drugs have promised the potential of improved disease control. In recent years, the transition from biologics to biosimilars especially with TNF-α inhibitors had significant impact on decreasing health care cost and increasing therapeutic options to the patients. However, selection of right treatment for an individual patient still remains challenging. Moreover, interplay between different epigenetic mechanisms such as the DNA methylation, chromatin modifications and noncoding RNA regulation has recently been started to be deciphered. Enzymes inhibitors involved in epigenetic pathways such as DNA methyltransferases and histone deacetylases demonstrated to restore normal epigenetic patterns in clinical settings and have provided the potential as novel therapeutic targets for psoriasis. In this review, we will discuss novel biologic agents and newer therapeutic approaches in treatment of psoriatic disease.
COVI-Prim Longitudinal Survey: Experiences of Primary Care Physicians During the Early Phase of the COVID-19 Pandemic
Authors: Schaffler-Schaden Dagmar , Mergenthal Karola , Avian Alexander , Huter Sebastian , Spary-Kainz Ulrike , Bachler Herbert , Flamm Maria , Siebenhofer Andrea
Published: February 2022

Background

General practitioners (GPs) are the mainstay of primary care and play a critical role in pandemics. During the first wave of the COVID-19 pandemic, this international study aimed to explore changes in the workload of general practitioners, as well as their interactions with patients and colleagues, and their self-confidence and concerns.

Methods

An online survey was conducted among GPs in Austria and Germany. Participants were asked to answer a basic questionnaire and participate in a subsequent longitudinal survey containing closed and open-ended items. All data were pseudonymized.

Results

Overall, 723 general practitioners from Austria and Germany took part in the longitudinal survey over a period of 12 weeks (April 3–July 2, 2020). The majority of GPs had less direct contact with patients at the beginning of the survey (96 vs. 49% at the end of the study period). At first, doctors were mainly concerned with pandemic-related issues and had to care for the patients of GP colleagues that were in quarantine, which meant they had less time for routine work such as screenings and treating chronic diseases. Over the survey period, GPs' self-confidence increased and their concerns about income loss decreased.

Conclusions

Following a difficult initial phase when protective equipment and information were lacking, physicians in primary care adapted quickly to new situations. Experience with telemedicine should help them face future challenges and may help prevent a decline in the delivery of routine health care and care for chronically ill patients.

Registration

Trial registration at the German Clinical Trials Register: DRKS00021231.
Primary Nasal Epithelial Cells as a Surrogate Cell Culture Model for Type-II Alveolar Cells to Study ABCA-3 Deficiency
Authors: Shaw Nicole C. , Kicic Anthony , Fletcher Sue , Wilton Stephen D. , Stick Stephen M. , Schultz André
Published: February 2022

ATP Binding Cassette Subfamily A Member 3 (ABCA-3) is a lipid transporter protein highly expressed in type-II alveolar (AT-II) cells. Mutations in ABCA3 can result in severe respiratory disease in infants and children. To study ABCA-3 deficiency in vitro, primary AT-II cells would be the cell culture of choice although sample accessibility is limited. Our aim was to investigate the suitability of primary nasal epithelial cells, as a surrogate culture model for AT-II cells, to study ABCA-3 deficiency. Expression of ABCA3, and surfactant protein genes, SFTPB and SFTPC, was detected in primary nasal epithelial cells but at a significantly lower level than in AT-II cells. ABCA-3, SP-B, and SP-C were detected by immunofluorescence microscopy in primary nasal epithelial cells. However, SP-B and SP-C were undetectable in primary nasal epithelial cells using western blotting. Structurally imperfect lamellar bodies were observed in primary nasal epithelial cells using transmission electron microscopy. Functional assessment of the ABCA-3 protein demonstrated that higher concentrations of doxorubicin reduced cell viability in ABCA-3 deficient nasal epithelial cells compared to controls in an assay-dependent manner. Our results indicate that there may be a role for primary nasal epithelial cell cultures to model ABCA-3 deficiency in vitro, although additional cell culture models that more effectively recapitulate the AT-II phenotype may be required.
Association Between Red Blood Cell Distribution Width and COVID-19 Severity in Delta Variant SARS-CoV-2 Infection
Authors: Zhang Jianguo , Hu Jianhui , Huang Xing , Fu Shixiang , Ding Daoyin , Tao Zhimin
Published: February 2022

Studies have discovered that wild-type SARS-CoV-2 infections are commonly linked to abnormalities in the hematological profiles of COVID-19 patients, one such abnormality being characterized by elevations in red blood cell distribution width (RDW). Whether this linkage reoccurs in delta variant SARS-CoV-2 infection remains unexamined. Here we compared baseline blood parameters in COVID-19 patients infected by wild type and its delta variant, respectively. Our results here point to that although the delta variant has shown increased virulence, transmissibility, and vaccine escape, it has a minimally negative impact on RDW values that were previously found prognostic for COVID-19 severity.
The Clinical Characteristics and Outcomes of Hemorrhagic Fever With Renal Syndrome in Pregnancy
Authors: Ren Danfeng , Fu Shan , Yan Taotao , Ni Tianzhi , Zhang Ze , Zhang Mengmeng , Zhou Jingwen , Yang Nan , Yang Yuan , He Yingli , Chen Tianyan , Zhao Yingren , Liu Jinfeng
Published: February 2022

Pregnant women with hemorrhagic fever with renal syndrome (HFRS) are a significant challenge for clinicians. The clinical characteristics of HFRS in pregnant women and its influence on both the pregnant women and fetus have yet to be clarified clearly. To highlight the specific clinical features of HFRS in pregnant women and the outcomes of pregnant women with HFRS and their fetuses, we screened pregnant women with HFRS from inception to May 1st 2021. We also conducted a comparison with non-pregnant women complicated with HFRS. Twenty-seven pregnant women and 87 non-pregnant women with complete electronic medical records were enrolled for final analyses; 55.6% (15/27) and 21.8% (19/87) were diagnosed as critical type in pregnant women and non-pregnant women, respectively. Compared with non-pregnant patients, there was a significantly higher likelihood of critical status in pregnant patients; the risk was significantly higher in late trimester (p <0.001). In addition, hypoalbuminemia and anemia were also evident in pregnant patients (p = 0.04, p <0.001, respectively). Leukocyte count, especially when higher than 15 × 109/L, was significantly correlated with disease severity (p = 0.009). After comprehensive therapy, 26 pregnant patients recovered without sequelae. Five fetal adverse events were reported during hospitalization. All adverse events were observed in mothers with critical types (p = 0.047, X2 = 4.909) and occurred in the later trimester. Collectively, our data show that pregnant woman with HFRS during the third trimester presents a more severe condition, especially those with leukocytosis. However, the majority of those pregnant patients could recover with comprehensive treatment and undergo normal labor.
Pan-Cancer Analysis Identified CD93 as a Valuable Biomarker for Predicting Patient Prognosis and Immunotherapy Response
Authors: Tong Wen , Wang Guangyu , Zhu Liuyang , Bai Yi , Liu Zirong , Yang Long , Wu Hao , Cui Tao , Zhang Yamin
Published: February 2022

Background: The rapid development of immunotherapy has significantly improved patient outcomes in recent years. CD93, a novel biomarker expressed on vascular endothelial cells, is essential for tumor angiogenesis. Recent studies have shown that CD93 is closely related to immune cell infiltration and immunotherapy. However, its role in pan-cancer has not been reported.

Methods: The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), cbioportal, Gene Expression Omnibus (GEO), Tumor Immune Estimation Resource (TIMER2.0), and the Tumor–Immune System Interactions and Drug Bank (TISIDB) databases were used to analyze CD93 in pan-cancers. R software was used for statistical analysis and mapping.

Results: There were significant differences in the expression of CD93 between tumor tissues and adjacent normal tissues in pan-cancer. The high expression of CD93 was associated with poor prognosis and high TNM stage in multiple tumor types. However, a high expression of CD93 was a protective factor in kidney renal clear cell carcinoma (KIRC). In addition, CD93 was closely related to immune cell infiltration in tumor tissues. Moreover, CD93 presented a robust correlation with immune modulators and immunotherapeutic markers [e.g., tumor mutation burden (TMB) and microsatellite instability (MSI)]. The results of gene set enrichment analysis (GSEA) showed that CD93 was correlated with tumor angiogenesis. Importantly, patients with a low expression of CD93 were more sensitive to immunotherapy in urothelial cancer.

Conclusion: CD93, which is involved in various immune responses, controls immune cell infiltration and impacts on the malignant properties of various cancer types. Therefore, CD93 has potential value to be biomarker for determining the prognosis and immune infiltration in multiple cancers.
The Effects of Drugs on Behavior Maintained by Social Contact: Role of Monoamines in Social Reinforcement
Authors: Sharp Jessica L. , Smith Mark A.
Published: February 2022

Drug use is highly concordant among members of adolescent and young adult peer groups. One potential explanation for this observation is that drugs may increase the reinforcing effects of social contact, leading to greater motivation to establish and maintain contact with other members of the peer group. Several classes of drugs, particularly drugs that increase synaptic dopamine, increase the reinforcing effects of contextual stimuli, but the extent to which these drugs enhance the reinforcing effects of social contact is not known. The purpose of this study was to determine the extent to which drugs that increase synaptic dopamine, norepinephrine, and serotonin enhance the positive reinforcing effects of social contact. To this end, male and female Long-Evans rats were pretreated with acute doses of the selective dopamine reuptake inhibitor, WIN-35,428, the selective norepinephrine reuptake inhibitor, atomoxetine, the selective serotonin reuptake inhibitor, fluoxetine, the non-selective monoamine reuptake inhibitor, cocaine, and the non-selective monoamine releasers d-amphetamine and (±)-MDMA. Ten minutes later, the positive reinforcing effects of 30-s access to a same-sex social partner was examined on a progressive ratio schedule of reinforcement. To determine whether the reinforcement-altering effects of these drugs were specific to the social stimulus, the reinforcing effects of a non-social stimulus (30-s access to an athletic sock of similar size and coloring as another rat) was determined in control subjects. WIN-35,428, d-amphetamine, and cocaine, but not atomoxetine, fluoxetine, or MDMA, dose-dependently increased breakpoints maintained by a social partner under conditions in which responding maintained by a non-social stimulus was not affected. These data indicate that increases in extracellular dopamine, but not extracellular norepinephrine or serotonin, increases the positive reinforcing effects of social contact in both male and female rats. These data also provide support for the hypothesis that some drugs with high abuse liability increase the motivation to establish and maintain contact with social peers.