bluuebunny/crossref_metadata_2025 huggingface dataset:
Follicular GH and IGF1 Levels Are Associated With Oocyte Cohort Quality: A Pilot Study
Authors: Scheffler Florence , Vandecandelaere Albane , Soyez Marion , Bosquet Dorian , Lefranc Elodie , Copin Henri , Devaux Aviva , Benkhalifa Moncef , Cabry Rosalie , Desailloud Rachel
Published: December 2021

Introduction

Oocyte quality contributes to the development of an optimal embryo and thus a successful pregnancy. The objective of this study was to analyse the association between oocyte cohort quality and the follicular levels of growth hormone (GH), insulin-like growth factor 1 (IGF1), 25-hydroxy vitamin D (25OHD), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4) and antithyroid antibodies, as a function of intracytoplasmic sperm injection (ICSI) outcomes.

Material and methods

We conducted a prospective comparative pilot study from January 2013 to December 2017. 59 ICSI cycles constituted an abnormal oocyte cohort (n=34 cycles, in which more than 50% of oocytes presented at least one morphological abnormality) and a normal oocyte cohort (n=25 cycles, in which 50% or less of the oocytes presented at least one morphological abnormality). GH, IGF1, 25OHD, TSH, fT3, fT4 and antithyroid antibodies were measured in follicular fluid.

Results

The fertilisation rate was lower in the abnormal oocyte cohort (65.5%vs.80%, respectively, p=0.012). Oocytes’ proportion with at least one abnormality was 79.4% in the abnormal oocyte cohort and 29.0% in the normal oocyte cohort. The mean number of morphological abnormalities per oocyte was significantly higher in the abnormal oocyte cohort. The follicular levels of GH (4.98vs.2.75 mIU/L, respectively; p <0.01) and IGF1 (72.1vs.54.2 ng/mL, respectively; p=0.05) were higher in the normal oocyte cohort. There was no association with follicular levels of TSH, fT3, fT4, antithyroid antibodies, or 25OHD.

Conclusion

Oocyte cohort quality appears to be associated with follicular levels of GH and IGF1.
Combined Effects of Warming and Grazing on Rangeland Vegetation on the Qinghai-Tibet Plateau
Authors: Chen Chen , Li Tiejian , Sivakumar Bellie , Sharma Ashish , Albertson John D. , Zhang Li , Wang Guangqian
Published: December 2021

Climate warming has increased grassland productivity on the Qinghai-Tibet Plateau, while intensified grazing has brought increasing direct negative effects. To understand the effects of climate change and make sustainable management decisions, it is crucial to identify the combined effects. Here, we separate the grazing effects with a climate-driven probability model and elaborate scenario comparison, using the Normalized Difference Vegetation Index (NDVI) of the grassland on the Qinghai-Tibet Plateau. We show that grazing has positive effects on NDVI in the beginning and end of the growing season, and negative effects in the middle. Because of the positive effects, studies tend to underestimate and even ignore the grazing pressure under a warming climate. Moreover, the seasonality of grazing effects changes the NDVI-biomass relationship, influencing the assessment of climate change impacts. Therefore, the seasonality of grazing effects should be an important determinant in the response of grassland to warming in sustainability analysis.
Benefits of Short-Duration, High-Stocking Rate Opportunistic Grazing on Arid Rangelands During Favorable Conditions
Authors: Louhaichi Mounir , Gamoun Mouldi , Gouhis Fethi
Published: December 2021

The aim of this study was to assess the impact of short grazing periods with high-stocking density on vegetation during weather conditions favorable to plant growth. Continuous grazing is widely practiced in Tunisian arid rangelands and across most drylands and deserts of the Middle East and North Africa. In the early 1990s, the Tunisian government combined a variety of incentives and restrictions on rangeland grazing practices and initiated a national strategy for rangeland improvement. The strategy emphasizes grazing exclusion for three consecutive years, a practice known locally as gdel. At the end of this period, grazing is allowed with no restrictions or with some guidelines. However, these regulations created discontent among pastoral communities, mainly when local rainfall conditions result in a considerable quantity of green biomass. High stocking-density grazing for a short period would help satisfy pastoralist concerns and achieve the government’s strategic goal. This study was implemented in three arid rangeland types of southern Tunisia that have been under restricted grazing for 2 years. Each area in the study was grazed for short periods in late May (about 7 days) with a flock of 150 head of sheep. Measurements of vegetation cover, forage productivity, density, and species richness were taken before and after grazing. Our results suggest that perennial vegetation is more stable under grazing than annual vegetation. The presence of annual species would enhance rangeland vegetation cover and diversity and at the same time offers an opportunity for livestock to select a high-quality diet rich in protein. Opportunistic grazing, applied to heterogeneous rangelands in late spring and the beginning of the annual temperature increase, encouraged animals to select annual plants due to their higher palatability, higher digestibility, and water content rather than heavily grazing perennial species. Perennial biomass materials that die and do not fall through rapid biological decay tended to decline with increased period of placement, resulting in further oxidation to CO2 which affects photosynthetic performance negatively and may eventually cause plant death. Trampling from high-density stocking enhances the litterfall rates and removes the oxidized plant material. These findings may contribute to strategies for addressing the extreme climatic variations that threaten rangeland and livestock sustainability.
Integrated Bioinformatics Analysis Identifies Heat Shock Factor 2 as a Prognostic Biomarker Associated With Immune Cell Infiltration in Hepatocellular Carcinoma
Authors: Fan Yumei , Hou Jiajie , Liu Xiaopeng , Han Bihui , Meng Yanxiu , Liu Bing , Chen Fei , Shang Yanan , Cao Pengxiu , Tan Ke
Published: December 2021

Hepatocellular carcinoma (HCC) is one of the most common malignancies and ranks as the second leading cause of cancer-related mortality worldwide. Heat shock factor 2 (HSF2) is a transcription factor that plays a critical role in development, particularly corticogenesis and spermatogenesis. However, studies examining the expression and prognostic value of HSF2 and its association with tumor-infiltrating immune cells in HCC are still rare. In the present study, we found that HSF2 expression was significantly upregulated in HCC tissues compared with normal liver tissues using the TCGA, ICGC, GEO, UALCAN, HCCDB and HPA databases. High HSF2 expression was associated with shorter survival of patients with HCC. Cox regression analyses and nomogram were used to evaluate the association of HSF2 expression with the prognosis of patients with HCC. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and gene set enrichment analysis (GSEA) revealed that HSF2 was associated with various signaling pathways, including the immune response. Notably, HSF2 expression was significantly correlated with the infiltration levels of different immune cells using the TIMER database and CIBERSORT algorithm. HSF2 expression also displayed a significant correlation with multiple immune marker sets in HCC tissues. Knockdown of HSF2 significantly inhibited the proliferation, migration, invasion and colony formation ability of HCC cells. In summary, we explored the clinical significance of HSF2 and provided a therapeutic basis for the early diagnosis, prognostic judgment, and immunotherapy of HCC.
A New HPV score System Predicts the Survival of Patients With Cervical Cancers
Authors: Hu Qunchao , Wang Yani , Zhang Yuchen , Ge Yanjun , Yin Yihua , Zhu Haiyan
Published: December 2021

Persistent high-risk human papillomavirus (hrHPV) infection is confirmed as the major cause of cervical cancer. According to the HPV infection status, cervical cancer could be generalized as following three subgroups: HPV-negative, pure HPV-infection, and HPV-integration. Currently, the impact of HPV status on cervical cancer prognosis remains under dispute. Therefore, we explored the potential correlation between HPV status and the clinical outcome of cervical cancer, by establishing a robust prognostic predicting model based on a cervical cancer cohort using The Cancer Genome Atlas (TCGA) database. We performed an iCluster algorithm incorporating DNA copy number variation, SNP, DNA methylation, mRNA expression, and miRNA expression profile together and classified the cohort into three clusters. According to defined clusters, we established an HPV score system by weighing resultant gene alterations through random forest and COX models. This prediction tool could help to identify cervical cancer prognosis through evaluating individual HPV infection status and subsequent genetic modification, which might provide insights into HPV-related gene driven cervical cancer treatment strategies, yet its predictive power and robustness need to be further verified with independent cohorts.
Comprehensive Analysis of Inhibitor of Apoptosis Protein Expression and Prognostic Significance in Non–Small Cell Lung Cancer
Authors: Liu Jun , Lu Yi , Huang Wenan , He Zhibo
Published: December 2021

Inhibitors of apoptosis proteins (IAPs) have been associated with tumor development and progression by affecting apoptosis through cell death signaling pathways. To date, eight IAPs (BIRC1–8) have been identified in mammalian cells. However, the role of IAPs in non–small cell lung cancer (NSCLC) development and progression has not been explored in depth. In this study, we used public datasets and bioinformatics tools to compare the expression, prognostic significance, and function of IAPs in NSCLC and its subtypes. Expression of IAPs in cancer and normal tissues and at different stages of NSCLC was compared with gene expression profiling interactive analysis, and their prognostic significance was analyzed with the Kaplan–Meier Plotter database. The correlations among IAPs were analyzed with the STRING database and SPSS19.0. Functional annotation of IAPs was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment on the basis of the DAVID tool. Among patients with lung adenocarcinoma (LUAD), the expression level of BIRC5 was higher than that in normal samples, and the expression of BIRC1 and BIRC5 significantly varied in different stages. Moreover, the BIRC1–3 and BIRC5 mRNA levels were associated with overall survival (OS), and the BIRC1–2 and BIRC5–6 mRNA levels were associated with progression-free survival (PFS). Among patients with lung squamous cell carcinoma (LUSC), the expression level of BIRC1 was lower and that of BIRC5 was higher than those in normal tissues, and BIRC5 expression significantly varied in different stages. BIRC1 expression was associated with OS, whereas BIRC2 and BIRC6 expression was associated with PFS. Enrichment analysis showed that most IAPs are associated with ubiquitin- and apoptosis-related pathways. Collectively, this study suggests BIRC5 as a potential diagnostic and staging marker, BIRC1 as a potential marker of OS, and BIRC2 and BIRC6 as potential PFS markers for patients with NSCLC. These highlight new targets for the early detection, treatment, and management of NSCLC.
A Novel Mutation (D395A) in Valosin-Containing Protein Gene Is Associated With Early Onset Frontotemporal Dementia in an Italian Family
Authors: Bruno Francesco , Conidi Maria Elena , Puccio Gianfranco , Frangipane Francesca , Laganà Valentina , Bernardi Livia , Smirne Nicoletta , Mirabelli Maria , Colao Rosanna , Curcio Sabrina , Di Lorenzo Raffaele , Maletta Raffaele , Bruni Amalia Cecilia
Published: December 2021

Inclusion body myopathy (IBM) with Paget’s disease of bone (PDB) and/or frontotemporal dementia (FTD) (IBMPFD) was recently identified as rare autosomal dominant disorder due to mutations in VCP gene. However, VCP mutations have also been documented in patients with amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth type 2 (CMT2) disease, and hereditary spastic paraplegia (HSP), underlining the heterogeneity of the phenotypes due to VCP mutations. In this study, we reported a novel missense heterozygous variant c.1184A > C (p.D395A) in exon 10 of VCP gene identified in three patients (two sisters and one brother) belonging to an Italian family. The patients underwent a detailed clinical evaluation including medical history, neurological examination, and neuropsychological assessment. Brain’s morphologic and functional analysis was also performed. The whole picture was consistent with the criteria of behavioral variant frontotemporal dementia (bvFTD) without IBM and PBD. Our report confirms the high degree of heterogeneity of VCP disease. A VCP analysis should be considered for the genetic screening of familial bvFTD with an early onset also in absence of IBM or PDB signs.
Air Pollution Exposure Impairs Airway Epithelium IFN-β Expression in Pre-School Children
Authors: Bonato Matteo , Gallo Elisa , Turrin Martina , Bazzan Erica , Baraldi Federico , Saetta Marina , Gregori Dario , Papi Alberto , Contoli Marco , Baraldo Simonetta
Published: December 2021

Introduction

Air pollution is a risk factor for respiratory infections and asthma exacerbations. We previously reported impaired Type-I and Type-III interferons (IFN-β/λ) from airway epithelial cells of preschool children with asthma and/or atopy. In this study we analyzed the association between rhinovirus-induced IFN-β/λ epithelial expression and acute exposure to the principal outdoor air pollutants in the same cohort.

Methods

We studied 34 children (17asthmatics/17non-asthmatics) undergoing fiberoptic bronchoscopy for clinical indications. Bronchial epithelial cells were harvested by brushing, cultured and experimentally infected with Rhinovirus Type 16 (RV16). RV16-induced IFN-β and λ expression was measured by quantitative real time PCR, as was RV16vRNA. The association between IFNs and the mean exposure to PM10, SO2 and NO2 in the day preceding bronchoscopy was evaluated using a Generalized Linear Model (GLM) with Gamma distribution.

Results

Acute exposure to PM10 and NO2 was negatively associated to RV16-induced IFNβ mRNA. For each increase of 1ug/m3 of NO2 we found a significative decrease of 2.3x103 IFN-β mRNA copies and for each increase of 1ug/m3 of PM10 a significative decrease of 1x103 IFN-β mRNA copies. No significant associations were detected between IFN-λ mRNA and NO2 nor PM10. Increasing levels of NO2 (but not PM10) were found to be associated to increased RV16 replication.

Conclusions

Short-term exposure to high levels of NO2 and PM10 is associated to a reduced IFN-β expression by the airway epithelium, which may lead to increased viral replication. These findings suggest a potential mechanism underlying the link between air pollution, viral infections and asthma exacerbations.
Proinflammatory Microenvironment During Kingella kingae Infection Modulates Osteoclastogenesis
Authors: Pesce Viglietti Ayelén Ivana , Sviercz Franco Agustín , López Cinthya Alicia Marcela , Freiberger Rosa Nicole , Quarleri Jorge , Delpino María Victoria
Published: December 2021

Kingella kingae is an emerging pathogen that causes septic arthritis, osteomyelitis, and bacteremia in children from 6 to 48 months of age. The presence of bacteria within or near the bone is associated with an inflammatory process that results in osteolysis, but the underlying pathogenic mechanisms involved are largely unknown. To determine the link between K. kingae and bone loss, we have assessed whether infection per se or through the genesis of a pro-inflammatory microenvironment can promote osteoclastogenesis. For that purpose, we examined both the direct effect of K. kingae and the immune-mediated mechanism involved in K. kingae-infected macrophage-induced osteoclastogenesis. Our results indicate that osteoclastogenesis is stimulated by K. kingae infection directly and indirectly by fueling a potent pro-inflammatory response that drives macrophages to undergo functional osteoclasts via TNF-α and IL-1β induction. Such osteoclastogenic capability of K. kingae is counteracted by their outer membrane vesicles (OMV) in a concentration-dependent manner. In conclusion, this model allowed elucidating the interplay between the K. kingae and their OMV to modulate osteoclastogenesis from exposed macrophages, thus contributing to the modulation in joint and bone damage.
Interplay Between Skin Microbiota Dysbiosis and the Host Immune System in Psoriasis: Potential Pathogenesis
Authors: Liang Xiaoqian , Ou Caixin , Zhuang Jiayi , Li Jinsheng , Zhang Fangfei , Zhong Yuanqiu , Chen Yongfeng
Published: December 2021

Psoriasis is a multifactorial immune-mediated disease. The highly effective and eligible treatment for psoriasis is limited, for its specific pathogenesis is incompletely elucidated. Skin microbiota is a research hotspot in the pathogenesis of immune-mediated inflammatory skin diseases nowadays, and it may have significant involvement in the provocation or exacerbation of psoriasis with broadly applicable prospects. It is postulated that skin microbiota alternation may interplay with innate immunity such as antimicrobial peptides and Toll-like receptors to stimulate T-cell populations, resulting in immune cascade responses and ultimately psoriasis. Achieving a thorough understanding of its underlying pathogenesis is crucial. Herein, we discuss the potential immunopathogenesis of psoriasis from the aspect of skin microbiota in an attempt to yield insights for novel therapeutic and preventive modalities for psoriasis.
CD38 Defines a Subset of B Cells in Rainbow Trout Kidney With High IgM Secreting Capacities
Authors: Martín Diana , Perdiguero Pedro , Morel Esther , Soleto Irene , Herranz-Jusdado J. German , Ramón Luis A. , Abós Beatriz , Wang Tiehui , Díaz-Rosales Patricia , Tafalla Carolina
Published: December 2021

CD38 is a multifunctional molecule that functions both as a transmembrane signaling receptor and as an ectoenzyme with important roles in cell adhesion, calcium regulation and signal transduction. Within the B cell linage, CD38 is expressed in diverse murine B cell subsets, with highest levels in innate B cell subpopulations such as marginal zone (MZ) B cells or B1 cells. In humans, however, CD38 is transiently expressed on early lymphocyte precursors, is lost on mature B cells and is consistently expressed on terminally differentiated plasma cells. In the present work, we have identified two homologues of mammalian CD38 in rainbow trout (Oncorhynchus mykiss), designating them as CD38A and CD38B. Although constitutively transcribed throughout different tissues in homeostasis, both CD38A and CD38B mRNA levels were significantly up-regulated in head kidney (HK) in response to a viral infection. In this organ, after the generation of a specific monoclonal antibody (mAb) against CD38A, the presence of CD38A+populations among IgM+B cells and IgM-leukocytes was investigated by flow cytometry. Interestingly, the percentage of IgM+CD38A+B cells increased in response to anin vitrostimulation with inactivatedAeromonas salmonicida. Finally, we demonstrated that HK IgM+CD38A+B cells had an increased IgM secreting capacity than that of cells lacking CD38A on the cell surface, also showing increased transcription levels of genes associated with B cell differentiation. This study strongly suggests a role for CD38 on the B cell differentiation process in teleosts, and provides us with novel tools to discern between B cell subsets in these species.
The Role of the Tumor Microenvironment and Treatment Strategies in Colorectal Cancer
Authors: Chen Yaping , Zheng Xiao , Wu Changping
Published: December 2021

Colorectal cancer (CRC) has the second highest mortality rate among all cancers worldwide. Surgery, chemotherapy, radiotherapy, molecular targeting and other treatment methods have significantly prolonged the survival of patients with CRC. Recently, the emergence of tumor immunotherapy represented by immune checkpoint inhibitors (ICIs) has brought new immunotherapy options for the treatment of advanced CRC. As the efficacy of ICIs is closely related to the tumor immune microenvironment (TME), it is necessary to clarify the relationship between the immune microenvironment of CRC and the efficacy of immunotherapy to ensure that the appropriate drugs are selected. We herein review the latest research progress in the immune microenvironment and strategies related to immunotherapy for CRC. We hope that this review helps in the selection of appropriate treatment strategies for CRC patients.
Evaluation of the Anti-Aging Effects of a Probiotic Combination Isolated From Centenarians in a SAMP8 Mouse Model
Authors: Fang Xin , Yue Mengyun , Wei Jing , Wang Yun , Hong Daojun , Wang Bo , Zhou Xiaoting , Chen Tingtao
Published: December 2021

Population aging is a prominent global problem in today’s society. However, there are currently no good methods to treat or prevent aging, so anti-aging research has crucial implications. In this research, we screened bacteria from centenarians, and finally selected four probiotics (Lactobacillus fermentum SX-0718, L. casei SX-1107, Bifidobacterium longum SX-1326, and B. animalis SX-0582) to form a probiotic combination. By using the senescence accelerated mouse prone 8 (SAMP8) model, the anti-aging effects of the probiotic combination were evaluated by using behavioural testing, neuroinflammation, intestinal inflammation, and intestinal microbiota. The results showed that probiotic combination improved the impaired spatial memory, motor dysfunction, and decreased exploratory behavior in aging mice. The probiotic combination inhibited Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NFκB)-induced neuroinflammation and up-regulated the expression of Sirt 1 to protect hippocampal neurons. At the same time, the probiotic combination regulated the intestinal microbiota, reduced the relative abundance of Alistipes and Prevotella in SAMP8 mice, inhibited TLR4/NFκB-induced intestinal inflammation, and increased the expression of intestinal permeability related proteins zonula occludens-1 (ZO-1) and Occuldin. The anti-aging effects of the probiotic combination may be through the regulating intestinal microbiota and inhibiting TLR4/NFκB-induced inflammation. This research provides the basis and technical support for the future production and application of the probiotic combination.
An Evaluation of the Impact of Pandemic Driven Lockdown on the Phytoplankton Biomass Over the North Indian Ocean Using Observations and Model
Authors: Seelanki Vivek , Pant Vimlesh
Published: December 2021

The unprecedented nationwide lockdown due to the ‘coronavirus disease 2019’ (COVID-19) affected humans and the environment in different ways. It provided an opportunity to examine the effect of reduced transportation and other anthropogenic activities on the environment. In the current study, the impact of lockdown on chlorophyll-a (Chl-a) concentration, an index of primary productivity, over the northern Indian Ocean (IO), is investigated using the observations and a physical-biogeochemical model. The statistics of model validation against observations shows a correlation coefficient of 0.85 (0.89), index of agreement as 0.90 (0.91). Root mean square error of 0.45°C (0.50°C) for sea surface temperature over the Bay of Bengal (BoB) (Arabian Sea, AS) is observed. The model results are analyzed to understand the upper-oceanic physical and biological processes during the lockdown. A comparison of the observed and model-simulated data during the lockdown period (March–June, 2020) and pre-pandemic period (March–June, 2019) shows significant differences in the physical (temperature and salinity) and biogeochemical (Chl-a concentration, nutrient concentration, and dissolved oxygen) parameters over the western AS, western BoB, and regions of Sri Lanka. During the pandemic, the reduced anthropogenic activities lead to a decrease in Chl-a concentration in the coastal regions of western AS and BoB. The enhanced aerosol/dust transport due to stronger westerly winds enhanced phytoplankton biomass in the western Arabian Sea (WAS) in May–June of the pandemic period.
Isobaric Tags for Relative and Absolute Quantitation-Based Proteomics Analysis Provides a New Perspective Into Unsynchronized Growth in Kuruma Shrimp (Marsupenaeus japonicus)
Authors: Zhao Jichen , Liao Minze , Lin Zexu , Huang Yiyi , Zhong Yunqi , Liu Luyao , Chen Guoliang , Ni Zuotao , Sun Chengbo
Published: December 2021

Unsynchronized growth is a common phenomenon in farmed crustaceans. The underlying molecular mechanism of unsynchronized growth of crustaceans is unclear. In this study, a comparative proteomic analysis focusing on growth differences was performed using kuruma shrimp Marsupenaeus japonicus, an economic crustacean species, as the model. The study analyzed kuruma shrimp at fast growth stage and steady growth stage from both fast growth group and slow growth group by an Isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic analysis method. A total of 1,720 proteins, including 12,291 peptides, were identified. Fifty-two and 70 differentially expressed proteins (DEPs) were identified in the fast growth stage and steady growth stage, respectively. Interestingly, 10 DEPs, including 14-3-3-epsilon-like, GPI, GPD1, MHC-1a, and MHC-1b, were presented in both growth stages. In addition, all these 10 DEPs shared the same expression tendency at these two growth stages. The results indicated that these 10 DEPs are potential growth biomarkers of M. japonicus. Proteins associated with faster growth of M. japonicus may promote cell growth and inhibit cell apoptosis through the Hippo signaling pathway. The fast growth group of M. japonicus may also achieve growth superiority by activating multiple related metabolic pathways, including glycolysis, glycerophospholipid metabolism and Citrate cycle. The present study provides a new perspective to explore the molecular mechanism of unsynchronized growth in crustacean species.
Do Differences in Latitudinal Distributions of Species and Organelle Haplotypes Reflect Thermal Reaction Norms Within the Emiliania/Gephyrocapsa Complex?
Authors: von Dassow Peter , Muñoz Farías Paula Valentina , Pinon Sarah , Velasco-Senovilla Esther , Anguita-Salinas Simon
Published: December 2021

The cosmopolitan phytoplankterEmiliania huxleyicontrasts with its closest relatives that are restricted to narrower latitudinal bands, making it interesting for exploring how alternative outcomes in phytoplankton range distributions arise. Mitochondrial and chloroplast haplogroups withinE. huxleyiare shared with their closest relatives: SomeE. huxleyishare organelle haplogroups withGephyrocapsa parvulaandG. ericsoniiwhich inhabit lower latitudes, while otherE. huxleyishare organelle haplogroups withG. muellerae, which inhabit high latitudes. We investigated whether the phylogeny ofE. huxleyiorganelles reflects environmental gradients, focusing on the Southeast Pacific where the different haplogroups and species co-occur. There was a high congruence between mitochondrial and chloroplast haplogroups withinE. huxleyi. Haplogroup II ofE. huxleyiis negatively associated with cooler less saline waters, compared to haplogroup I, both when analyzed globally and across temporal variability at the small special scale of a center of coastal upwelling at 30° S. A new mitochondrial haplogroup Ib detected in coastal Chile was associated with warmer waters. In an experiment focused on inter-species comparisons, laboratory-determined thermal reaction norms were consistent with latitudinal/thermal distributions of species, withG. oceanicaexhibiting warm thermal optima and tolerance andG. muelleraeexhibiting cooler thermal optima and tolerances.Emiliania huxleyihaplogroups I and II tended to exhibit a wider thermal niche compared to the otherGephyrocapsa, but no differences among haplogroups withinE. huxleyiwere found. A second experiment, controlling for local adaptation and time in culture, found a significant difference betweenE. huxleyihaplogroups. The difference between I and II was of the expected sign, but not the difference between I and Ib. The differences were small (≤1°C) compared to differences reported previously withinE. huxleyiby local adaptation and even in-culture evolution. Haplogroup Ib showed a narrower thermal niche. The cosmopolitanism ofE. huxleyimight result from both wide-spread generalist phenotypes and specialist phenotypes, as well as a capacity for local adaptation. Thermal reaction norm differences can well explain the species distributions but poorly explain distributions among mitochondrial haplogroups withinE. huxleyi. Perhaps organelle haplogroup distributions reflect historical rather than selective processes.
Predictive Value of Second-Trimester Maternal Lipid Profiling in Early-Onset Pre-eclampsia: A Prospective Cohort Study and Nomogram
Authors: Li Juan , Lu Juefei , Wang Mengni , Hu Wen , Jin Neng , Li Xingmiao , Zhao Baihui , Luo Qiong
Published: December 2021

Purpose: Maternal lipid profile in second trimester has rarely been investigated in the risk assessment for pre-eclampsia (PE). Since early-onset PE often companied by much worse clinical outcomes, thus, we aimed to evaluate the predictive value of second-trimester maternal lipid profiling for early-onset PE.

Methods: A prospective cohort study was conducted to measure the second-trimester maternal lipid profile of pregnant women from January to December 2019. The pairwise association between maternal lipid profile and PE onset or pregnancy termination time was quantified. Multiple logistic regression was preformed to define risk factors for early-onset PE, and a nomogram for early-onset PE was developed. The net benefit of our model was evaluated by calibration curve and decision curve analyses.

Results: We enrolled 5,908 pregnant women and they were divided into healthy (n = 5,789), late-onset PE (n = 64), and early-onset PE (n = 55) groups. Total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c) were elevated in patients with PE, while high-density lipoprotein cholesterol (HDL-c) was decreased in patients with PE. TC, TG, and LDL-c were negatively correlated with PE onset time or gestational week at delivery. Receiver operating characteristic curves (ROC) defined the cutoff values of TG and HDL-c, and the final regression model included five statistically significant risk predictors for early-onset PE (maternal age of ≥35 years, multipara, pre-pregnancy body mass index (BMI) ≥25 kg/m2, second trimester TG ≥ 2.59 mmol/L and second trimester HDL-c ≤ 2.03 mmol/L. The nomogram had an excellent diagnostic performance (area under the curve = 0.912, sensitivity = 92.7%, and specificity = 76%) and was further validated with good calibration and positive net benefits in a decision curve analysis.

Conclusions: An abnormally increased TG concentration and a decreased HDL-c concentration might serve as predictors of early-onset PE. Whether blood lipid-lowering measures can improve severe PE prognosis require further clarification.
Impaired Dendritic Cell Homing in COVID-19
Authors: Borcherding Lukas , Teksen Alime Sema , Grosser Bianca , Schaller Tina , Hirschbühl Klaus , Claus Rainer , Spring Oliver , Wittmann Michael , Römmele Christoph , Sipos Éva , Märkl Bruno
Published: December 2021

The high mortality of COVID-19 is mostly attributed to acute respiratory distress syndrome (ARDS), whose histopathological correlate is diffuse alveolar damage (DAD). Furthermore, severe COVID-19 is often accompanied by a cytokine storm and a disrupted response of the adaptive immune system. Studies aiming to depict this dysregulation have mostly investigated the peripheral cell count as well as the functionality of immune cells. We investigated the impact of SARS-CoV-2 on antigen-presenting cells using multiplexed immunofluorescence. Similar to MERS-CoV and SARS-CoV, SARS-CoV-2 appears to be impairing the maturation of dendritic cells (DCs). DC maturation involves a switch in surface antigen expression, which enables the cells' homing to lymph nodes and the subsequent activation of T-cells. As quantitative descriptions of the local inflammatory infiltrate are still scarce, we compared the cell population of professional antigen-presenting cells (APC) in the lungs of COVID-19 autopsy cases in different stages of DAD. We found an increased count of myeloid dendritic cells (mDCs) in later stages. Interestingly, mDCs also showed no significant upregulation of maturation markers in DAD-specimens with high viral load. Accumulation of immature mDCs, which are unable to home to lymph nodes, ultimately results in an inadequate T-cell response.
Social Isolation Is Associated With Rapid Kidney Function Decline and the Development of Chronic Kidney Diseases in Middle-Aged and Elderly Adults: Findings From the China Health and Retirement Longitudinal Study (CHARLS)
Authors: Zhou Weiran , Li Yang , Ning Yichun , Gong Shaomin , Song Nana , Zhu Bowen , Wang Jialin , Zhao Shuan , Shi Yiqin , Ding Xiaoqiang
Published: December 2021

Background: There is limited evidence on the relationship between social isolation and renal outcomes. To address this gap, this study estimated the prospective relationship of social isolation with rapid kidney function decline and the development of chronic kidney disease (CKD) in middle-aged and elderly Chinese with normal kidney function.

Methods: We analyzed data from 3,031 participants aged ≥ 45 years with baseline estimated glomerular filtration rates (eGFR) ≥ 60 ml/min/1.73 m2. All data were obtained from the 2011 and 2015 waves of the Chinese Longitudinal Study of Health and Retirement (CHARLS). eGFR was estimated based on a combination of serum creatinine and cystatin C. The primary outcome was rapid decline in renal function, as defined by an eGFR decrease of > 5 ml/min/1.73 m2 per year, while the secondary outcome was the development of CKD, as defined by an eGFR decrease to a level < 60 ml/min/1.73 m2.

Results: During the follow-up of 4 years, 258 (8.5%) participants experienced a rapid decline in renal function, while 87 (2.9%) developed CKD. In the fully adjusted model, high social isolation was significantly related to an increased risk of experiencing a rapid decline in renal function (OR 1.805, 95% CI 1.310–2.487) and CKD onset (OR 1.842, 95% CI 1.084–3.129). Among the five components of social isolation, being unmarried, not participating in social activities, and living alone independently predicted declined renal function.

Conclusions: Social isolation is significantly associated with the risk of rapid eGFR decline and CKD onset in middle-aged and older adults with normal kidney function in China.
Heteroresistance to Amikacin in Carbapenem-Resistant Klebsiella pneumoniae Strains
Authors: Zhang Feiyang , Li Qin , Bai Jiawei , Ding Manlin , Yan Xiangjin , Wang Guangxi , Zhu Baoli , Zhou Yingshun
Published: December 2021

Heteroresistance can lead to treatment failure and is difficult to detect by the methods currently employed by clinical laboratories. The aim of this study was to investigate the prevalence of the amikacin-heteroresistant Klebsiella pneumoniae strains and explore potential amikacin heteroresistance mechanism through whole-genome sequencing (WGS) and quantitative reverse-transcription PCR (qRT-PCR). In this study, 13 isolates (8.39%) were considered as amikacin-heteroresistant K. pneumoniae strains among a total of 155 K. pneumoniae strains. The majority of the heterogeneous phenotypes (11/13, 84.61%) was unstable and the minimal inhibitory concentrations (MICs) fully or partially reverted back to the level of susceptibility of the parental isolate. The frequency of heteroresistant subpopulation ranged from 2.94×10−7 to 5.59×10−6. Whole-genome sequencing and single-nucleotide variants (SNVs) analysis showed that there were different nucleotide and resultant amino acid alterations among an amikacin-heteroresistant strain S38 and the resistant subpopulation S38L in several genes. Quantitative reverse-transcription PCR analysis revealed that the increased expression of aminoglycoside resistance genes detected in amikacin-heteroresistant K. pneumoniae strains might be associated with amikacin heteroresistance. The findings raise concerns for the emergence of amikacin-heteroresistant K. pneumoniae strains and the use of amikacin as therapy for the treatment of multidrug-resistant K. pneumoniae strains.
Nano-La2O3 Induces Honeybee (Apis mellifera) Death and Enriches for Pathogens in Honeybee Gut Bacterial Communities
Authors: Liu Yong-Jun , Jing Zhongwang , Bai Xue-Ting , Diao Qing-Yun , Wang Jichen , Wu Yan-Yan , Zhao Qing , Xia Tian , Xing Baoshan , Holden Patricia A. , Ge Yuan
Published: December 2021

Honeybees (Apis mellifera) can be exposedvianumerous potential pathways to ambient nanoparticles (NPs), including rare earth oxide (REO) NPs that are increasingly used and released into the environment. Gut microorganisms are pivotal in mediating honeybee health, but how REO NPs may affect honeybee health and gut microbiota remains poorly understood. To address this knowledge gap, honeybees were fed pollen and sucrose syrup containing 0, 1, 10, 100, and 1000mgkg−1of nano-La2O3for 12days. Nano-La2O3exerted detrimental effects on honeybee physiology, as reflected by dose-dependent adverse effects of nano-La2O3on survival, pollen consumption, and body weight (p<0.05). Nano-La2O3caused the dysbiosis of honeybee gut bacterial communities, as evidenced by the change of gut bacterial community composition, the enrichment of pathogenicSerratiaandFrischella, and the alteration of digestion-related taxaBombella(p<0.05). There were significant correlations between honeybee physiological parameters and the relative abundances of pathogenicSerratiaandFrischella(p<0.05), underscoring linkages between honeybee health and gut bacterial communities. Taken together, this study demonstrates that nano-La2O3can cause detrimental effects on honeybee health, potentially by disordering gut bacterial communities. This study thus reveals a previously overlooked effect of nano-La2O3on the ecologically and economically important honeybee speciesApis mellifera.
The Fungal Communities and Flavor Profiles in Different Types of High-Temperature Daqu as Revealed by High-Throughput Sequencing and Electronic Senses
Authors: Cai Wenchao , Xue Yu’ang , Wang Yurong , Wang Wenping , Shu Na , Zhao Huijun , Tang Fengxian , Yang Xinquan , Guo Zhuang , Shan Chunhui
Published: December 2021

Polymicrobial co-fermentation is among the distinct character of high-temperature Daqu. However, fungal communities in the three types of high-temperature Daqu, namely, white high-temperature Daqu, black high-temperature Daqu, and yellow high-temperature Daqu, are yet to be characterized. In this study, the fungal diversity, taste, and aroma profiles in the three types of high-temperature Daqu were investigated by Illumina MiSeq high-throughput sequencing, electronic tongue, and electronic nose, respectively. Ascomycota and Basidiomycota were detected as the absolute dominant fungal phylum in all types of high-temperature Daqu samples, whereas Thermomyces, Thermoascus, Aspergillus, Rasamsonia, Byssochlamys, and Trichomonascus were identified as the dominant fungal genera. The fungal communities of the three types of high-temperature Daqu differed significantly (p < 0.05), and Thermomyces, Thermoascus, and Monascus could serve as the biomarkers in white high-temperature Daqu, black high-temperature Daqu, and yellow high-temperature Daqu, respectively. The three types of high-temperature Daqu had an extremely significant difference (p < 0.01) in flavor: white high-temperature Daqu was characterized by sourness, bitterness, astringency, richness, methane, alcohols, ketones, nitrogen oxides, and sulfur organic compounds; black high-temperature Daqu was characterized by aftertaste-A, aftertaste-B, methane-aliph, hydrogen, and aromatic compounds; and yellow high-temperature Daqu was characterized by saltiness, umami, methane, alcohols, ketones, nitrogen oxides, and sulfur organic compounds. The fungal communities in the three types of high-temperature Daqu were significantly correlated with taste but not with aroma, and the aroma of high-temperature Daqu was mainly influenced by the dominant fungal genera including Trichomonascus, Aspergillus, Thermoascus, and Thermomyces. The result of the present study enriched and refined our knowledge of high-temperature Daqu, which had positive implications for the development of traditional brewing technique.
Screening and Identification of Lujo Virus Entry Inhibitors From an Food and Drug Administration-Approved Drugs Library
Authors: Cao Junyuan , Dong Siqi , Liu Yang , Zhou Minmin , Guo Jiao , Jia Xiaoying , Zhang Yueli , Hou Yuxia , Tian Ming , Xiao Gengfu , Wang Wei
Published: December 2021

Lujo virus (LUJV) belongs to the Old World (OW) genus Mammarenavirus (family Arenaviridae). It is categorized as a biosafety level (BSL) 4 agent. Currently, there are no U.S. Food and Drug Administration (FDA)-approved drugs or vaccines specifically for LUJV or other pathogenic OW mammarenaviruses. Here, a high-throughput screening of an FDA-approved drug library was conducted using pseudotype viruses bearing LUJV envelope glycoprotein (GPC) to identify inhibitors of LUJV entry. Three hit compounds, trametinib, manidipine, and lercanidipine, were identified as LUJV entry inhibitors in the micromolar range. Mechanistic studies revealed that trametinib inhibited LUJV GPC-mediated membrane fusion by targeting C410 [located in the transmembrane (TM) domain], while manidipine and lercanidipine inhibited LUJV entry by acting as calcium channel blockers. Meanwhile, all three hits extended their antiviral spectra to the entry of other pathogenic mammarenaviruses. Furthermore, all three could inhibit the authentic prototype mammarenavirus, lymphocytic choriomeningitis virus (LCMV), and could prevent infection at the micromolar level. This study shows that trametinib, manidipine, and lercanidipine are candidates for LUJV therapy and highlights the critical role of calcium in LUJV infection. The presented findings reinforce the notion that the key residue(s) located in the TM domain of GPC provide an entry-targeted platform for designing mammarenavirus inhibitors.
Electrodeposited Platinum Iridium Enables Microstimulation With Carbon Fiber Electrodes
Authors: della Valle Elena , Koo Beomseo , Patel Paras R. , Whitsitt Quentin , Purcell Erin K. , Chestek Cynthia A. , Weiland James D.
Published: December 2021

Ultrasmall microelectrode arrays have the potential to improve the spatial resolution of microstimulation. Carbon fiber (CF) microelectrodes with cross-sections of less than 8 μm have been demonstrated to penetrate cortical tissue and evoke minimal scarring in chronic implant tests. In this study, we investigate the stability and performance of neural stimulation electrodes comprised of electrodeposited platinum-iridium (PtIr) on carbon fibers. We conducted pulse testing and characterized charge injection in vitro and recorded voltage transients in vitro and in vivo. Standard electrochemical measurements (impedance spectroscopy and cyclic voltammetry) and visual inspection (scanning electron microscopy) were used to assess changes due to pulsing. Similar to other studies, the application of pulses caused a decrease in impedance and a reduction in voltage transients, but analysis of the impedance data suggests that these changes are due to surface modification and not permanent changes to the electrode. Comparison of scanning electron microscope images before and after pulse testing confirmed electrode stability.
Mutual Skill Learning and Adaptability to Others via Haptic Interaction
Authors: Saracbasi Ozge Ozlem , Harwin William , Kondo Toshiyuki , Hayashi Yoshikatsu
Published: December 2021

When learning a new skill through an unknown environment, should we practice alone, or together with another beginner, or learn from the expert? It is normally helpful to have an expert guiding through unknown environmental dynamics. The guidance from the expert is fundamentally based on mutual interactions. From the perspective of the beginner, one needs to face dual unknown dynamics of the environment and motor coordination of the expert. In a cooperative visuo-haptic motor task, we asked novice participants to bring a virtual mass onto the specified target location under an unknown external force field. The task was completed by an individual or with an expert or another novice. In addition to evaluation of the motor performance, we evaluated the adaptability of the novice participants to a new partner while attempting to achieve a common goal together. The experiment was set in five phases; baseline for skill transfer and adaptability, learning and evaluation for adaptability and skill transfer respectively. The performance of the participants was characterized by using the time to target, effort index, and length of the trajectory. Experimental results suggested that (1) peer-to-peer interactions among paired beginners enhanced the motor learning most, (2) individuals practicing on their own (learning as a single) showed better motor learning than practicing under the expert's guidance, and (3) regarding the adaptability, peer-to-peer interactions induced higher adaptability to a new partner than the novice-to-expert interactions while attempting to achieve a common goal together. Thus, we conclude that the peer-to-peer interactions under a collaborative task can realize the best motor learning of the motor skills through the new environmental dynamics, and adaptability to others in order to achieve a goal together. We suggest that the peer-to-peer learning can induce both adaptability to others and learning of motor skills through the unknown environmental dynamics under mutual interactions. On the other hand, during the peer-to-peer interactions, the novice can learn how to coordinate motion with his/her partner (even though one is a new partner), and thus, is able to learn the motor skills through new environmental dynamics.