bluuebunny/crossref_metadata_2025 huggingface dataset:
Individual‐based morphological brain network organization and its association with autistic symptoms in young children with autism spectrum disorder
Authors: He Changchun , Cortes Jesus M. , Kang Xiaodong , Cao Jing , Chen Heng , Guo Xiaonan , Wang Ruishi , Kong Lingyin , Huang Xinyue , Xiao Jinming , Shan Xiaolong , Feng Rui , Chen Huafu , Duan Xujun
Published: May 2021

Individual‐based morphological brain networks built from T1‐weighted magnetic resonance imaging (MRI) reflect synchronous maturation intensities between anatomical regions at the individual level. Autism spectrum disorder (ASD) is a socio‐cognitive and neurodevelopmental disorder with high neuroanatomical heterogeneity, but the specific patterns of morphological networks in ASD remain largely unexplored at the individual level. In this study, individual‐based morphological networks were constructed by using high‐resolution structural MRI data from 40 young children with ASD (age range: 2–8 years) and 38 age‐, gender‐, and handedness‐matched typically developing children (TDC). Measurements were recorded as threefold. Results showed that compared with TDC, young children with ASD exhibited lower values of small‐worldness (i.e., σ) of individual‐level morphological brain networks, increased morphological connectivity in cortico‐striatum‐thalamic‐cortical (CSTC) circuitry, and decreased morphological connectivity in the cortico‐cortical network. In addition, morphological connectivity abnormalities can predict the severity of social communication deficits in young children with ASD, thus confirming an associational impact at the behavioral level. These findings suggest that the morphological brain network in the autistic developmental brain is inefficient in segregating and distributing information. The results also highlight the crucial role of abnormal morphological connectivity patterns in the socio‐cognitive deficits of ASD and support the possible use of the aberrant developmental patterns of morphological brain networks in revealing new clinically‐relevant biomarkers for ASD.
Hepatic Small Ubiquitin‐Related Modifier (SUMO)–Specific Protease 2 Controls Systemic Metabolism Through SUMOylation‐Dependent Regulation of Liver–Adipose Tissue Crosstalk
Authors: Liu Yang , Dou Xin , Zhou Wei‐yu , Ding Meng , Liu Ling , Du Ruo‐qi , Guo Liang , Qian Shu‐wen , Tang Yan , Yang Qi‐qi , Pan Dong‐ning , Li Xiao‐ying , Lu Yan , Cheng Jin‐ke , Tang Qi‐qun
Published: May 2021

Background and Aims

NAFLD, characterized by aberrant triglyceride accumulation in liver, affects the metabolic remodeling of hepatic and nonhepatic tissues by secreting altered hepatokines. Small ubiquitin‐related modifier (SUMO)–specific protease 2 (SENP2) is responsible for de‐SUMOylation of target protein, with broad effects on cell growth, signal transduction, and developmental processes. However, the role of SENP2 in hepatic metabolism remains unclear.

Approach and Results

We found that SENP2 was the most dramatically increased SENP in the fatty liver and that its level was modulated by fed/fasted conditions. To define the role of hepatic SENP2 in metabolic regulation, we generated liver‐specific SENP2 knockout (Senp2‐LKO) mice. Senp2‐LKO mice exhibited resistance to high‐fat diet–induced hepatic steatosis and obesity. RNA‐sequencing analysis showed that Senp2 deficiency up‐regulated genes involved in fatty acid oxidation and down‐regulated genes in lipogenesis in the liver. Additionally, ablation of hepatic SENP2 activated thermogenesis of adipose tissues. Improved energy homeostasis of both the liver and adipose tissues by SENP2 disruption prompted us to detect the hepatokines, with FGF21 identified as a key factor markedly elevated in Senp2‐LKO mice that maintained metabolic homeostasis. Loss of FGF21 obviously reversed the positive effects of SENP2 deficiency on metabolism. Mechanistically, by screening transcriptional factors of FGF21, peroxisome proliferator–activated receptor alpha (PPARα) was defined as the mediator for SENP2 and FGF21. SENP2 interacted with PPARα and deSUMOylated it, thereby promoting ubiquitylation and subsequent degradation of PPARα, which in turn inhibited FGF21 expression and fatty acid oxidation. Consistently, SENP2 overexpression in liver facilitated development of metabolic disorders.

Conclusions

Our finding demonstrated a key role of hepatic SENP2 in governing metabolic balance by regulating liver–adipose tissue crosstalk, linking the SUMOylation process to metabolic regulation.
Reduction of cycles of bendamustine plus rituximab therapy in the cases with good response for indolent B‐cell lymphomas
Authors: Takezaki Toshiaki , Nakazaki Kumi , Toyama Kazuhiro , Matsuda Kensuke , Kogure Yasunori , Chiba Akira , Nakamura Fumihiko , Honda Akira , Kurokawa Mineo
Published: May 2021

Bendamusutine plus rituximab (BR) regimen is one of the standard regimens for indolent B‐cell lymphomas, yet the possibility of reduction of cycles of BR therapy without compromising therapeutic effects is not still uncovered. We retrospectively surveyed 57 cases including 40 follicular lymphoma cases who underwent BR regimen in our institute. The overall response (OR) rate and complete response (CR) rate were 86.0% (95% confidential interval (CI), 74.2–93.7) and 54.4% (40.7–67.6), respectively. Five‐year overall survival (OS) and 5‐years progression‐free survival (PFS) were 76.8% and 45.7%, respectively. We then grouped the patients by the number of administered cycles of BR regimen. PFS was significantly longer in 41 cases of the later cessation group (cycle 4–6) than in 16 cases of the earlier cessation group (cycle 1–3) (p = 0.012, 5‐years PFS; 46.8% vs. 35.2%, respectively), and both of OR and CR rate of the former was better than the latter (OR rate; 95.1% vs. 62.5%, p < 0.01, CR rate; 61.4% vs. 31.3%, p = 0.04). Interestingly PFS of twenty‐one (36.8%) cases receiving just 4 cycles was longer than that of 20 cases who received five or 6 cycles (p < 0.01, 5‐years PFS; 71.8% vs. 23.2%, respectively). Focusing on the group of four cycles, the 12 case with CR revealed longer PFS than seven cases with partial response (PR), and median PFS was not reached in CR cases and 16.9 months in the PR cases (p < 0.01). These results suggest that four cycles at least should be administered if possible, and the outcome of the patients who discontinued BR after four cycles was not inferior to that of the cases who received five or six cycles. In conclusion, discontinuation after four cycles may be permissible in some cases with complete response to BR regimen.
Healthcare systems and Covid19: Lessons to be learnt from efficient countries
Authors: Ordu Muhammed , Kirli Akin Hediye , Demir Eren
Published: May 2021

Background

The novel coronavirus is rapidly spreading over the world and puts the health systems of countries under intense pressure. High hospitalization levels due to the pandemic outbreak have caused the intensive care units to work above capacity.

Purpose

A data envelopment analysis (DEA) based modelling approach was developed to evaluate the effectiveness of regions (i.e. city, country or clinical commissioning groups) against the pandemic outbreak. The objective is to enable related authorities better manage the struggle against the outbreak and put in place the emergency action plans immediately.

Methodology/Approach

DEA method was used to measure the efficiency scores of countries. Super efficiency DEA method was also applied to countries based on the level of efficiencies they have achieved. Sixteen countries were selected that have been facing with Covid19 pandemic outbreak for at least 5 consecutive weeks after their 100th confirmed case.

Results

A total of 80 DEA models were developed, that is, 16 DEA models for each week. The percentage of efficient countries decreased dramatically over time, from 43.75% in the first week to 25% in the fifth week. Unlike most European countries, China and South Korea increased their effectiveness after first week of implementing all the necessary measures.

Conclusion

This study sheds light into better understanding the effectiveness of policies adopted by countries and their management strategy in dealing with Covid19 pandemic. Our model will enable political leaders to identify inadequate policies as quickly as possible and learn from their peers for more effective decisions.
The role of chemotherapy in the management of olfactory neuroblastoma: A 40‐year surveillance, epidemiology, and end results registry study
Authors: Brisson Ryan J. , Quinn Thomas J. , Deraniyagala Rohan L.
Published: May 2021

Background

In this retrospective surveillance, epidemiology, and end results (SEER) registry analysis, we investigated the role of chemotherapy (CT) in the treatment of olfactory neuroblastoma (ON), an exceedingly rare sino‐nasal tumor typically treated with surgery and/or radiation therapy (RT).

Methods

We analyzed all patients in the SEER registry diagnosed with a single primary malignancy of ON, a primary tumor site within the nasal cavity or surrounding sinuses, sufficient staging information to derive Kadish staging, and >0 days of survival, ensuring follow‐up data. Receipt of CT in the SEER registry was documented as either Yes or No/Unknown.

Results

Six hundred and thirty‐six patients were identified. One hundred and ninety‐five patients received CT as part of their treatment for ON. Following propensity score matching and inverse probability of treatment weighting, there was inferior overall survival (OS) (HR 1.7, 95% CI: 1.3‐2.2, P = .001) and cancer‐specific survival (CSS) (HR 1.8, 95% CI: 1.3‐2.4, P < .001) for patients who received CT compared to those who were not treated with CT or had unknown CT status. On subgroup analysis, the only patient population that derived benefit from CT were patients who did not receive surgery and were treated with CT and/or RT (HR 0.3, 95% CI: 0.14‐0.61, P < .001).

Conclusions

Based on this retrospective SEER registry analysis, the use of CT in the management of ON is associated with decreased OS. Our analysis suggests that patients who are considered nonsurgical candidates may benefit from the addition of CT.
The Multiscale TROPIcal CatchmentS critical zone observatory M‐TROPICS dataset III: Hydro‐geochemical monitoring of the Mule Hole catchment, south India
Authors: Riotte Jean , Ruiz Laurent , Audry Stéphane , Baud Benjamin , Bedimo Bedimo Jean‐Pierre , Boithias Laurie , Braun Jean‐Jacques , Dupré Bernard , Duprey Jean‐Louis , Faucheux Mikael , Lagane Christelle , Marechal Jean‐Christophe , Moger Hemanth , Mohan Kumar Mandalagiri Subbarayappa , Parate Harshad , Ribolzi Olivier , Rochelle‐Newall Emma , Sriramulu Buvaneshwari , Varma Murari , Sekhar Muddu
Published: May 2021

Despite the importance of tropical ecosystems for climate regulation, biodiversity, water and nutrient cycles, only a few Critical Zone Observatories (CZOs) are located in the tropics. Among these, most are in humid climates, while very few data exist for semi‐arid and sub‐humid climates, due to the difficulty of estimating hydro‐geochemical balances in catchments with ephemeral streams. We contribute to fill this gap by presenting a meteorological and hydro‐geochemical dataset acquired at the Mule Hole catchment (4.1 km2), a pristine dry deciduous forest located in a biosphere reserve in south India. The dataset consists of time series of variables related to (i) meteorology, including rainfall, air temperature, relative humidity, wind speed and direction, and global radiation, (ii) hydrology, including water level and discharge at the catchment outlet, (iii) hydrogeology, including manual (monthly) and/or automated (from 15 min to hourly) groundwater levels in nine piezometers and (iv) geochemistry, including suspended sediment content in the stream and chemical composition of rainfall (event based), groundwater (monthly sampling) and stream water (storm events, 15 min to hourly frequency with an automatic sampler). The time series extend from 2003 to 2019. Measurement errors are minimized by frequent calibration of sensors and quality checks, both in the field and in the laboratory. Despite these precautions, several data gaps exist, due to occasional access restriction to the site and instrument destruction by wildlife. Results show that large seasonal and interannual variations of climatic conditions were reflected in the large variations of stream flow and groundwater recharge, as well as in water chemical composition. Notably, they reveal a long‐term evolution of groundwater storage, suggesting hydrogeological cycles on a decadal scale. This dataset, alone or in combination with other data, has already allowed to better understand water and element cycling in tropical dry forests, and the role of forest diversity on biogeochemical cycles. As tropical ecosystems are underrepresented by Critical Zone Observatories, we expect this data note to be valuable for the global scientific community.
Environmental factors regulating stream nitrate concentrations at baseflow condition in a large region encompassing a climatic gradient
Authors: Makino Soyoka , Tokuchi Naoko , Komai Yukio , Kunimatsu Takao
Published: May 2021

Though high rates of nitrate (NO3−) leaching from forests are undesirable, the factors significantly regulating stream NO3− concentration is not clarified yet. In Japan, not only near metropolitan areas but also the Japan Sea‐side area with heavy snowfall is well known for receiving more than 10 kg‐N ha−1 year−1 of nitrogen (N) deposition. However, NO3− concentration in stream water is relatively low in the Japan Sea‐side area compared with its concentration in other areas. We examined important environmental factors regulating stream NO3− concentrations at baseflow condition in a large region of Japan, the Kinki region (KIN) including a part of Japan Sea‐side (JSK) using Random Forest regression. The amounts of N deposition and precipitation were common regulating factors for stream NO3− concentration at baseflow condition. Random forest showed the significant correlation between the factors related to ecosystem N retention and stream NO3− concentration at baseflow condition, and it suggests that large N deposited during the growing season was incorporated into the ecosystem in the entire KIN. Heavy rain and snow flush N and wash out N accumulated in the surface soil, causing small N accumulation in forests. Also, large precipitation dilute NO3− concentration in baseflows. These things lowered stream NO3− concentration at baseflow condition. Especially in JSK, most of N deposed with the heavy snow flushed out during the snowmelt period. We provided the first statistical confirmation using Random Forest regression that N accumulation and cycling in forest ecosystems were related to NO3− leaching from forests into streams.
Controls on stable isotopic characteristics of water vapour over Thailand
Authors: Laonamsai Jeerapong , Ichiyanagi Kimpei , Patsinghasanee Supapap , Kamdee Kiattipong
Published: May 2021

This study examined the weekly water vapour isotopic composition (δ18Ov) in Thailand. The water vapour was cryogenically collected from eight sites across the country. Two observational samples were collected over one 24‐h period each week (a daytime and a night‐time sample), from September 2013 to September 2014. The primary aim was to investigate the environmental factors influencing water vapour isotopes. The results revealed differences in water vapour isotopic values between day and night samples. Three periods of depleted δ18Ov were associated with large‐scale convective systems in September, December, and May. The statistical relationship between the climate variables and water vapour isotopes indicated that the amount of precipitation and relative humidity were the primary controls on both diurnal and seasonal isotopic variability. The temperature did not affect the δ18Ov, mainly because the atmospheric processes are a function of vertical convection rather than temperature in tropical regions. The water vapour deuterium excess (d‐excess) showed greater variability in 2013 than in 2014. The d‐excess variation reflected the differences in convection occurring in the day and night. In addition, the vapour phase data were combined with the local meteoric water line to identify the local water vapour line and the interaction between the isotopic composition of water vapour and liquid water. The water vapour isotopic patterns paralleled the precipitation isotopes on rainy days because of equilibrium isotopic exchange. Water vapour and precipitation were isotopically similar under low humidity but showed greater differences from each other under wetter conditions. The study results provide insight into water vapour isotopic characteristics in tropical regions and constrain the role of large‐scale atmospheric processes relative to isotopic variability of water vapour in Thailand and nearby countries.
Littoral vegetation predicts mollusc distribution in a network of unconnected small karstic lakes in the Mediterranean zone of Albania
Authors: Lorencová Erika , Bojková Jindřiška , Maršálková Eliška , Horsák Michal
Published: May 2021

Small lakes and ponds in karstic systems have received little attention in terms of mollusc research. Although these systems represent a refuge for lentic biota in most of the Mediterranean, there are virtually no ecological studies from many regions, including Albania. Therefore, we quantitatively studied mollusc assemblages at 58 sampling sites within a compact karstic area of Central Albania and measured a set of potentially important environmental variables. Only nine ubiquitous species, including three non‐native mollusc species, were recorded. Gyraulus albus, Radix auricularia and Physa acuta were the most frequent species. Individual sites hosted notably species‐poor assemblages, ranging between zero and six species, with more than half of the studied sites being unoccupied. Mollusc presence was predicted mainly by fine substrate, depth of soft sediment and high transparency. Despite the importance of calcium for molluscs, more species were recorded at sites with a low calcium concentration. Regression tree analysis explained 40% of the total variation, defining reed cover and lake surface area as the most important variables for mollusc species richness. Based on mollusc species composition, the sites were clustered into four groups, differing mainly in submerged littoral vegetation cover, depth of soft sediment and reed cover. Our results showed that limited development of littoral vegetation and the area of lakes are the major drivers for mollusc species presence and their distribution in the studied network of unconnected karstic lakes.
Transformation of benthic communities in forest lowland streams colonised by Eurasian beaver Castor fiber (L.)
Authors: Wojton Andrzej , Kukuła Krzysztof
Published: May 2021

Beavers are an exception among animals in terms of the scale of environmental transformations they achieve. This study investigated primary environmental factors influencing the occurrence of aquatic invertebrates in lowland streams inhabited by the Eurasian beaver. The study was conducted in two forest streams inhabited by beavers, and in an uninhabited stream. In streams inhabited by beavers, the study covered seven ponds. Sections with flowing water were also analysed downstream and upstream of the ponds. Benthos and water samples were collected at each site. Dissolved oxygen (DO) concentration and saturation were the only physicochemical parameters that indicated decreases in water quality in beaver ponds. The benthic communities of different beaver ponds were similar. The taxa that exerted the greatest influence on the similarity of the invertebrate fauna in the ponds were Oligochaeta and Chironomidae. Ostracods were also abundant in the ponds, whereas they were few in the flowing sections. Mayflies (Cloeon) and caddisflies belonging to the family Phryganeidae were also closely associated with the ponds. Caddisflies (Plectrocnemia and Sericostoma), mayflies (Baetis) and stoneflies (Nemourella and Leuctra) exhibited the highest correlation with DO concentrations, which is typical of flowing sections, and avoided stream fragments dammed by beavers. Bivalvia (Pisidium) were also abundant in each of the streams along the flowing sections. The highest number of taxa and greatest taxonomic diversity was observed in sections flowing below the beaver ponds. The engineering activity of beavers transformed the studied lowland streams, resulting in the development of rheophilic and stagnophilic communities of aquatic invertebrates, in free‐flowing and dammed sections, respectively.
The effect of climate warming on microbial loop function in peat pools and Sphagnum hollows: Mesocosm experiments
Authors: Mieczan Tomasz , Tarkowska‐Kukuryk Monika
Published: May 2021

Climate change models predict a possible increase in air temperature of 2–8°C. This means that global warming will significantly affect the functioning of various types of hydrogenic ecosystems. However, the effect of the temperature increase on microbial loop function in small water bodies associated with peat ecosystems (peat pools and Sphagnum hollows) is still unknown. We used mesocosm experiments (control and treatments with a 2°C, 4°C and 8°C temperature increase) to determine the response of bacterioplankton, flagellates, testate amoebae and ciliates to simulated temperature changes, taking into account seasonal variation in the temperate climate zone. The simulated increase in climate warming increased the species richness of ciliates and the abundance of bacteria, flagellates and ciliates. In contrast, there was a decrease in the species number and abundance of testate amoebae, the top predators in peat ecosystems. The sensitivity of the various microbial groups to temperature was size‐dependent; large‐sized testate amoebae declined under warming. These shifts caused a decrease in the predator–prey mass ratio. An increase in the abundance of top predators promotes increased abundance of ciliates, and thus changes the architecture of the food web. At the same time, we observed the increase in phycoflora biomass thus can cancel the potential negative effects of warming on heterotrophic microbial activity. So, the potential effect of warming on the C budgets of peat pools and hollows is evident. A better understanding of what regulates microbial populations and activity in small reservoirs in peat bogs and unravelling of these fundamental mechanisms are particularly critical to more accurately predict how peat bogs will respond to climate disturbances.
Hydrodynamics drive pelagic communities and food web structure in a tidal environment
Authors: Young Matthew J. , Feyrer Frederick , Stumpner Paul R. , Larwood Veronica , Patton Oliver , Brown Larry R.
Published: May 2021

Hydrodynamic processes can lead to the accumulation and/or dispersal of water column constituents, including sediment, phytoplankton, and particulate detritus. Using a combination of field observations and stable isotope tracing tools, we identified how hydrodynamic processes influenced physical habitat, pelagic communities, and food web structure in a freshwater tidal system. The pelagic habitat of a terminal channel differed spatially, likely aligning with differences in hydrodynamics. Three zones that we classified by exchange with downstream habitat had distinct water quality characteristics, supported different densities of zooplankton and nekton, and exhibited disparate support from benthic and pelagic trophic pathways to pelagic consumers. Hydrodynamically driven zones and their emergent characteristics appeared sensitive to hydrology, as elevated runoff was correlated with a shift in hydrodynamic habitat and organismal distributions. The results of our study highlight the relationship between hydrodynamic processes, biological responses, and climate, and suggest that understanding the physical process can improve understanding of pelagic habitats and communities.
Naringin‐generated ROS promotes mitochondria‐mediated apoptosis in Candida albicans
Authors: Kim Heesu , Lee Dong Gun
Published: May 2021

Naringin is a flavonoid which has a therapeutic effect. However, the details of its antifungal mechanism have not yet been fully elucidated. This study focused on clarifying the relationship between naringin and Candida albicans, to understand its mode of antifungal action. In general, naringin is an antioxidant, but our results indicated that 1 mM naringin generates intracellular superoxide (O2−) and hydroxyl radicals (OH−). Reactive oxygen species (ROS) have a serious impact on Ca2+ signaling and the production of mitochondrial ROS. After exposure to enhanced O2− and OH−, mitochondrial Ca2+ overload and mitochondrial O2− generation were confirmed in C. albicans. It was verified that mitochondrial O2− transforms mitochondrial glutathione (GSH) to oxidized GSH (GSSG), leading to extreme oxidative stress in mitochondria. The previously observed Ca2+ accumulation and oxidative stress resulted in mitochondrial membrane potential (MMP) alteration and increased mitochondrial mass. In succession, cytochrome c release from the mitochondria to the cytosol was detected due to MMP loss. Cytochrome c promotes the initiation of apoptosis, and further experiments were performed to assess the apoptotic hallmarks. Metacaspases activation, chromosomal condensation, DNA fragmentation, and phosphatidylserine exposure were observed, indicating that naringin induces apoptosis in C. albicans. In conclusion, our findings manifested that naringin‐generated O2− and OH− damage the mitochondria and that mitochondrial dysfunction‐mediated apoptosis is novel antifungal mechanism of naringin.
Cross‐domain retinopathy classification with optical coherence tomography images via a novel deep domain adaptation method
Authors: Luo Yuemei , Xu Qing , Hou Yubo , Liu Linbo , Wu Min
Published: May 2021

Deep learning based retinopathy classification with optical coherence tomography (OCT) images has recently attracted great attention. However, existing deep learning methods fail to work well when training and testing datasets are different due to the general issue of domain shift between datasets caused by different collection devices, subjects, imaging parameters, etc. To address this practical and challenging issue, we propose a novel deep domain adaptation (DDA) method to train a model on a labeled dataset and adapt it to an unlabelled dataset (collected under different conditions). It consists of two modules for domain alignment, that is, adversarial learning and entropy minimization. We conduct extensive experiments on three public datasets to evaluate the performance of the proposed method. The results indicate that there are large domain shifts between datasets, resulting a poor performance for conventional deep learning methods. The proposed DDA method can significantly outperform existing methods for retinopathy classification with OCT images. It achieves retinopathy classification accuracies of 0.915, 0.959 and 0.990 under three cross‐domain (cross‐dataset) scenarios. Moreover, it obtains a comparable performance with human experts on a dataset where no labeled data in this dataset have been used to train the proposed DDA method. We have also visualized the learnt features by using the t‐distributed stochastic neighbor embedding (t‐SNE) technique. The results demonstrate that the proposed method can learn discriminative features for retinopathy classification.
Attitudes toward bone health among rural‐dwelling veterans identified as at risk of fracture: a qualitative analysis
Authors: Van Tiem Jennifer M. , Steffen Melissa J.A. , Seaman Aaron T. , Miller Karla , Wardyn Shylo E. , Richards Christopher C. , Solimeo Samantha L.
Published: May 2021

Although much is known about system‐level barriers to prevention and treatment of bone health problems, little is known about patient‐level barriers. The objective of this study was to identify factors limiting engagement in bone health care from the perspective of rural‐dwelling patients with known untreated risk. Over 6 months, 39 patients completed a qualitative interview. Interview questions focused on the patient's experience of care, their decision to not accept care, as well as their knowledge of osteoporosis and the impact it has had on their lives. Participants were well‐informed and could adequately describe osteoporosis and its deleterious effects, and their decision making around accepting or declining a dual‐energy x‐ray absorptiometry (DXA) scan and treatment was both cautious and intentional. Decisions about how to engage in treatment were tempered by expectations for quality of life. Our findings suggest that people hold beliefs about bone health treatment that we can build on. Work to improve care of this population needs to recognize that bone health providers are not adding a behavior of medication taking to patients, they are changing a behavior or belief. Published 2021. This article is a U.S. Government work and is in the public domain in the USA. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Antioxidative effects of silymarin on the reduction of liver complications of fingolimod in patients with relapsing–remitting multiple sclerosis: A clinical trial study
Authors: Ghiasian Masoud , Nafisi Hamid , Ranjbar Akram , Mohammadi Younes , Ataei Sara
Published: May 2021

Multiple sclerosis (MS) is a chronic disease that affects the central nervous system and is characterized by inflammation, demyelination, and degenerative changes. Relapsing–remitting MS (RRMS) is the most common form of MS. Fingolimod (FTY720) is a once‐daily disease‐modifying agent approved to treat RRMS, and it binds to sphingosine 1‐phosphate receptors. Milk thistle (silybum marianum; SM) is an herb generally used to protect the liver with antioxidant and antifibrotic effects. The purpose of this study was to evaluate the effects of silymarin on reducing liver complications of FTY720 in patients with RRMS and decrease the oxidative stress that plays an important role in the pathogenesis of this disease. Forty‐eight patients with RRMS were divided into two groups using random assignment: the placebo and drug‐treated groups. Participants of intervention and control groups took FTY720 with silymarin and placebo without silymarin per day for six months. Findings showed a significant reduction in the level of ALT and AST, reduction of main pathogenic factors in MS containing malondialdehyde, and also a significant rise in total antioxidant capacity, and total thiol groups in the serum of patients treated with silymarin as compared with the placebo group. Our outcomes propose the practical effects of silymarin in multiple sclerosis and reduction of hepatic side effects of fingolimod.
A ten N6‐methyladenosine‐related long non‐coding RNAs signature predicts prognosis of triple‐negative breast cancer
Authors: Wu Jie , Cai Yan , Zhao Gaiping , Li Maolan
Published: May 2021

Background

Patients with triple‐negative breast cancer (TNBC) face a major challenge of the poor prognosis, and N6‐methyladenosine‐(m6A) mediated regulation in cancer has been proposed. Therefore, this study aimed to explore the prognostic roles of m6A‐related long non‐coding RNAs (LncRNAs) in TNBC.

Methods

Clinical information and expression data of TNBC samples were collected from TCGA and GEO databases. Pearson correlation, univariate, and multivariate Cox regression analysis were employed to identify independent prognostic m6A‐related LncRNAs to construct the prognostic score (PS) risk model. Receiver operating characteristic (ROC) curve was used to evaluate the performance of PS risk model. A competing endogenous RNA (ceRNA) network was established for the functional analysis on targeted mRNAs.

Results

We identified 10 independent prognostic m6A‐related LncRNAs (SAMD12‐AS1, BVES‐AS1, LINC00593, MIR205HG, LINC00571, ANKRD10‐IT1, CIRBP‐AS1, SUCLG2‐AS1, BLACAT1, and HOXB‐AS1) and established a PS risk model accordingly. Relevant results suggested that TNBC patients with lower PS had better overall survival status, and ROC curves proved that the PS model had better prognostic abilities with the AUC of 0.997 and 0.864 in TCGA and GSE76250 datasets, respectively. Recurrence and PS model status were defined as independent prognostic factors of TNBC. These ten LncRNAs were all differentially expressed in high‐risk TNBC compared with controls. The ceRNA network revealed the regulatory axes for nine key LncRNAs, and mRNAs in the network were identified to function in pathways of cell communication, signaling transduction and cancer.

Conclusion

Our findings proposed a ten‐m6A‐related LncRNAs as potential biomarkers to predict the prognostic risk of TNBC.
CYLD deficiency causes auditory neuropathy due to reduced neurite outgrowth
Authors: Yang Song , Ma Nan , Wu Xuemei , Ni Hua , Gao Siqi , Sun Lei , Zhou Peng , Tala  , Ran Jie , Zhou Jun , Liu Min , Li Dengwen
Published: May 2021

Background

Auditory neuropathy is a cause of hearing loss that has been studied in a number of animal models. Signal transmission from hair cells to spiral ganglion neurons plays an important role in normal hearing. CYLD is a microtubule‐binding protein, and deubiquitinase involved in the regulation of various cellular processes. In this study, we used Cyld knockout (KO) mice and nerve cell lines to examine whether CYLD is associated with auditory neuropathy.

Methods

Hearing of Cyld KO mice was studied using the TDT RZ6 auditory physiology workstation. The expression and localization of CYLD in mouse cochlea and cell lines were examined by RT‐PCR, immunoblotting, and immunofluorescence. CYLD expression was knocked down in SH‐SY5Y cells by shRNAs and in PC12 and N2A cells by siRNAs. Nerve growth factor and retinoic acid were used to induce neurite outgrowth, and the occurrence and length of neurites were statistically analyzed between knockdown and control groups.

Results

Cyld KO mice had mild hearing impairment. Moreover, CYLD was widely expressed in mouse cochlear tissues and different nerve cell lines. Knocking down CYLD significantly reduced the length and proportion of neurites growing from nerve cells.

Conclusions

The abnormal hearing of Cyld KO mice might be caused by a decrease in the length and number of neurites growing from auditory nerve cells in the cochlea, suggesting that CYLD is a key protein affecting hearing.
PCR array analysis identified hyperproliferation but not autophagy or apoptosis in fibrous epulis
Authors: Jiang Yangyang , Fang Bing , Xu Bin
Published: May 2021

Background

The pathogenesis of fibrous epulis is still quite unclear. Our recent genome‐wide RNA sequencing analysis revealed that in fibrous epulis, RAS‐PI3K‐AKT‐NF‐κB pathway regulates the expression of Bcl‐2 family and IAP family genes, leading to increased proliferation and the inhibition of apoptosis. The PI3K/AKT signaling pathway can promote autophagy in human gingival fibroblasts; therefore, the purpose of the present study was to identify whether autophagy is involved in the pathogenesis of fibrous epulis.

Methods

Differentially expressed genes (DEGs) between fibrous epulis lesions and normal gingival tissues were identified using the PCR array. The expression levels of eighteen autophagy‐related (ATG) family genes, twelve B‐cell lymphoma 2 (Bcl‐2) family genes, and eleven cysteine‐dependent aspartate‐directed protease (caspase) family genes were validated using quantitative real‐time PCR (qRT‐PCR). Autophagy induction was determined by measuring microtubule‐associated protein light chain 3 (LC3) conversion (LC3‐I to LC3‐II) by immunoblot analysis.

Results

The PCR array identified six upregulated genes, whereas no genes were expressed at significantly lower levels. The upregulated genes were BCL2, BCL2L1, CXCR4, HSP90AA1, HSPA8, and IGF1, which all belong to the “regulation of autophagy” group but not the “autophagy machinery components” group. qRT‐PCR verified that the expression levels of BCL2, BCL2L1 (also known as BCL‐XL), and BCL2L2 (also known as BCL‐W) were significantly increased in fibrous epulis. No LC3‐I to LC3‐II conversion was observed.

Conclusions

The present study reveals that in fibrous epulis, Bcl‐2 and Bcl‐xL coordinately mediate gingival cell escape from apoptosis, leading to uncontrolled proliferation. Moreover, ATG family genes are not activated, and autophagy is not involved in this process.
Single‐cell transcriptomes reveal characteristic features of cell types within the human adrenal microenvironment
Authors: Huang Lin , Liao Jinling , Chen Yang , Zou Chunlin , Zhang Haiying , Yang Xiaobo , Zhang Qinyun , Li Tianyu , Mo Linjian , Zeng Yanyu , Bao Mengying , Zhang Fangxing , Ye Yu , Yang Zhanbin , Cheng Jiwen , Mo Zengnan
Published: May 2021

Various cells within the adrenal microenvironment are important in maintaining the body homeostasis. However, our understanding of adrenal disease pathogenesis is limited by an incomplete molecular characterization of the cell types responsible for the organ's multiple homeostatic functions. We report a cellular landscape of the human adrenal gland using single‐cell RNA sequencing. We reveal characteristic features of cell types within the human adrenal microenvironment and found immune activation of nonimmune cells in the adrenal endothelial cells. We also reveal that abundant immune cells occupied a lot of space in adrenal gland. Additionally, Sex‐related diversity in the adrenocortical cells and different gene expression profiles between the left and right adrenal gland are also observed at single‐cell resolution. Together, at single‐cell resolution, the transcriptomic map presents a comprehensive view of the human adrenal gland, which serves as a fundamental baseline description of this organ and paves a way for the further studies of adrenal diseases.
Modulating stemness of mesenchymal stem cells from exfoliated deciduous and permanent teeth by IL‐17 and bFGF
Authors: Jauković Aleksandra , Kukolj Tamara , Trivanović Drenka , Okić‐Đorđević Ivana , Obradović Hristina , Miletić Maja , Petrović Vanja , Mojsilović Slavko , Bugarski Diana
Published: May 2021

Mesenchymal stem cells (MSCs) have been identified within dental pulp tissues of exfoliated deciduous (SHEDs) and permanent (DPSCs) teeth. Although differences in their proliferative and differentiation properties were revealed, variability in SHEDs and DPSCs responsiveness to growth factors and cytokines have not been studied before. Here, we investigated the influence of interleukin‐17 (IL‐17) and basic fibroblast growth factor (bFGF) on stemness features of SHEDs and DPSCs by analyzing their proliferation, clonogenicity, cell cycle progression, pluripotency markers expression and differentiation after 7‐day treatment. Results indicated that IL‐17 and bFGF differently affected SHEDs and DPSCs proliferation and clonogenicity, since bFGF increased proliferative and clonogenic potential of both cell types, while IL‐17 similarly affected SHEDs, exerting no effects on adult counterparts DPSCs. In addition, both factors stimulated NANOG, OCT4, and SOX2 pluripotency markers expression in SHEDs and DPSCs showing diverse intracellular expression patterns dependent on MSCs type. As for the differentiation capacity, both factors displayed comparable effects on SHEDs and DPSCs, including stimulatory effect of IL‐17 on early osteogenesis in contrast to the strong inhibitory effect showed for bFGF, while having no impact on SHEDs and DPSCs chondrogenesis. Moreover, bFGF combined with IL‐17 reduced CD90 and stimulated CD73 expression on both types of MSCs, whereas each factor induced IL‐6 expression indicating its' role in IL‐17/bFGF‐modulated properties of SHEDs and DPSCs. All these data demonstrated that dental pulp MSCs from primary and permanent teeth exert intrinsic features, providing novel evidence on how IL‐17 and bFGF affect stem cell properties important for regeneration of dental pulp at different ages.
The Light = Healthy Intuition
Authors: Li Yi , Heuvinck Nico , Pandelaere Mario
Published: May 2021

This research documents a “light = healthy” intuition, such that consumers perceive foods that weigh less are healthier than their heavier counterparts with the same serving size. Subsequently, consumers consume a larger quantity of lighter‐weight foods. The intuition is based on a coactivation of two meanings of the word “light”: light in physical weight and light in calorie content. An implicit attitude test finds support for this association between physical weight and food healthiness. ​Subsequently, physically lighter foods are perceived to be healthier because they are assumed to contain fewer calories. In line with the proposed coactivation mechanism, the intuition is bidirectional, where consumers also expect healthier foods to weigh less. Consequently, they discredit health claims issued for heavier foods. Finally, it was found that activating a competing intuition is effective at debiasing the “light = healthy” intuition.
Improvement of d‐lactic acid productivity by introducing Escherichia coli acetyl‐CoA synthesis pathway in engineered Saccharomyces cerevisiae
Authors: Zhong Wei , Yang Maohua , Hao Xuemi , Sharshar Moustafa M , Wang Qinhong , Xing Jianmin
Published: May 2021

BACKGROUND

d‐Lactic acid (d‐LA) is gaining increased attention as it can be applied in the food, pharmaceutical, cosmetic, polylactic acid and textile industries. Acid‐tolerant Saccharomyces cerevisiae is often engineered to produce organic acids. For the pyruvate decarboxylases (PDCs) or alcohol dehydrogenase 1 (ADH1) disrupted strains, the productivity of d‐LA significantly decreases due to the accumulation of acetaldehyde and acetic acid. To overcome the problem, Escherichia coli acetylating acetaldehyde dehydrogenase (A‐ALD) enzyme genes (MHPF and EUTE) (EC 1.2.1.10) were integrated into the d‐LA producing strain YIP‐A15G12 strain (CGMCC2.5803). The function of these genes is to directly convert acetaldehyde into acetyl‐CoA without energy consumption. This strain was integrated with Escherichia coli d‐lactate dehydrogenase and Issatchenkia orientalis glycosylphosphatidylinositol‐anchored protein IoGas1gene and several attenuated key pathway genes, including PDC1, PDC6, ADH1, ADH5, JEN1 (a monocarboxylate transporter), d‐lactate dehydrogenase 1 (DLD1), l‐lactate cytochrome c oxidoreductase (CYB2) and glycerol‐3‐phosphate dehydrogenases (GPD1, GPD2).

RESULTS

The strain expressions of the A‐ALD enzymes effectively complemented the attenuated acetaldehyde dehydrogenase (ALD) acetyl‐CoA synthetase (ACS) pathway and significantly improved the levels of acetyl‐CoA and the productivity of d‐LA. Finally, the resulting strainYIP‐m‐ald6 (CGMCC2.5826) produced 86.9 g L–1 d‐LA with a yield of 0.77 g g–1 glucose and a volumetric productivity of 1.77 g L–1 h–1 at pH 3.58 under fed‐batch fermentation conditions.

CONCLUSION

Introducing the E. coli acetyl‐CoA synthesis pathway into the yeast strain can significantly enhance the growth of the strain and improve the d‐LA productivity, as a benefit for d‐LA production in industry. © 2021 Society of Chemical Industry (SCI).
Recovery of roseoflavin from a recombinant Streptomyces davaonensis strain by using biphasic aqueous systems
Authors: Ibarra‐Herrera Celeste C , Meza‐Dorantes Aranza , Mora‐Lugo Rodrigo , González‐Valdez José , Mack Matthias , Mata‐Gómez Marco A
Published: May 2021

BACKGROUND

Roseoflavin (RoS) is a naturally occurring red color riboflavin analog compound, produced mainly by Streptomyces davaonensis, with a rising profile owing to its antibacterial potential. However, there is a lack of strategies for its downstream processing and the existing ones are limited to chromatographic techniques involving harmful reagents. The use of aqueous two‐phase systems (ATPS), a liquid–liquid extraction method, is explored in this work as an alternative strategy to recover and purify RoS from S. davaonensis cultures.

RESULTS

Polymer‐phosphate, alcohol‐phosphate and ionic liquid (IL)‐phosphate systems that varied in composition were tested, where polyethylene glycol (PEG), ethanol (EtOH) and 1‐ethyl‐3‐methylimidazolium acetate ([C2mim] [OAC]) represent the top phases, and phosphate the bottom phase. The partition behavior of either RoS alone or with contaminants was evaluated. In both cases, RoS showed a preference for top phase in all the systems tested. When cell‐free cultures were added to the systems, IL‐salt (13% and 30% w/w), EtOH‐phosphate [50% tie‐line length (TLL)] and PEG8000‐phosphate (35% w/w TLL) systems presented the highest RoS recovery (>95%), but separation of RoS and contaminants was not accomplished. The systems that demonstrated separation of RoS and contaminants were the PEG3350‐ and PEG8000‐salt systems, both with a 15% w/w TLL, as RoS and contaminants partitioned to top and bottom phases, respectively.

CONCLUSION

This is the first attempt at using ATPS to recover RoS from S. davaonensis cultures. It has been proven that RoS can be recovered directly from S. davaonensis cultures using biphasic systems. This strategy may represent a greener alternative to chromatographic techniques. © 2021 Society of Chemical Industry (SCI).
Poly (L‐lactic acid) nanofibrous scaffolds support the proliferation and neural differentiation of mouse neural stem and progenitor cells
Authors: Miri Vahideh , Asadi Asadollah , Sagha Mohsen , Najafzadeh Nowruz , Golmohammadi Mohammad Ghasem
Published: May 2021

Background

The distribution and growth of cells on nanofibrous scaffolds seem to be an indispensable precondition in cell tissue engineering. The potential use of biomaterial scaffolds in neural stem cell therapy is increasingly attracting attention.

Aim

In this study, we produced porous nanofibrous scaffolds fabricated from random poly‐L‐lactic acid (PLLA) to support neurogenic differentiation of neural stem and progenitor cells (NSPCs), isolated from the subventricular zone (SVZ) of the adult mouse brain.

Methods

The viability and proliferation of the NSPCs on the nanofibrous PLLA scaffold were also tested by nuclear staining with 4, 6‐diamidino‐2‐phenylindole dihydrochloride (DAPI), 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyl tetrazolium bromide (MTT) assay and scanning electron microscopy (SEM). To investigate the differentiation potential of NSPCs on the scaffolds, the cells were treated with a neurogenic differentiation medium, and immunostaining was done to detect neuronal and glial cells after 14 and 21 days of cultivation. Furthermore, the morphology of differentiated cells on the scaffold was examined using SEM.

Results

The DAPI staining revealed the proliferation of NSPCs onto the surface of the nanofibrous PLLA scaffold. DAPI‐positive cells were counted on days 2 and 5 after cultivation. The mean number of cells in each microscopic field was significantly (p < .05) increased (51 ± 19 on day 2 compared to 77 ± 25 cells on day 5). The results showed that the cell viability on PLLA scaffolds significantly increased compared to control groups. Moreover, cell viability was significantly increased 5 days after culturing (262.3 ± 50.2) as compared to 2 days culture in Vitro (174.2 ± 28.3, p < .05). Scanning electron micrographs also showed that the NSPCs adhered and differentiated on PLLA scaffolds. We found that the neural cell markers, microtubule‐associated protein 2 (MAP2) and glial ﬁbrillary acidic protein (GFAP), were expressed in NSPCs seeded on random PLLA scaffolds after 21 days of cultivation.

Conclusion

These results suggest that the PLLA nano‐scaffolds, due to their biocompatible property, are an appropriate structure for the proliferation, differentiation, and normal growth of NSPCs.