bluuebunny/crossref_metadata_2025 huggingface dataset:
A method for evaluating resource potential and oil mobility in liquid-rich shale plays—An example from upper Devonian Duvernay formation of the Western Canada Sedimentary Basin
Authors: Chen Zhuoheng , Jiang Chunqing , Reyes Julito , Liu Xiaojun , Little Edward
Published: February 2023

This paper discusses methods of assessing oil and gas resources and evaluating their mobility in shale reservoirs using programed pyrolysis data in conjunction with reservoir engineering parameters derived from production data. The hydrocarbon resource is calculated from the measured free hydrocarbon by programed pyrolysis with correction of evaporative loss that occurred during coring, storage and sample preparation. The correction takes account of the loss of light hydrocarbon fluids as a result of phase change during core retrieval to the surface and evaporative loss related to storage and sample preparation. Based on their response to ramping temperature during sample pyrolysis and thermal equilibrium behavior of distinct petroleum products at different thermal maturities, the estimated oil and gas resources are divided into three categories: non-movable, restricted, and movable to characterize the mobility of the petroleum fluids. The mobility classification is compared with oil compositional grouping based on evaporative kinetics of petroleum products in rock samples to examine their affinity. Pyrolysis analysis results from naturally matured samples and production data from different fluid zones in the Duvernay Shale resource play in Western Canada Sedimentary Basin (WCSB) were used to demonstrate the application of the proposed method. While the mobility of petroleum fluids increases with thermal maturation in general, the total movable resource reaches its maximum at the end of oil generation window, then declines as a result of massive loss due to hydrocarbon expulsion towards to gas window where liquids are thermally cracked to gaseous hydrocarbons. Compositional grouping based on evaporative kinetics does not show a complete accordance with mobility grouping, suggesting composition is only one of many factors affecting hydrocarbon fluid flow in shale reservoir. More studies are required to better understand the fundamentals of oil mobility in shale reservoir.
Overburden stress evolution characteristics and prediction of disasters with across-gully mining
Authors: Wang Hongwei , Jiang Baolin , Jiao Jianqiang , Li Yanjun
Published: February 2023

The coal water co-mining of shallow coal seams in the loess gully area of Northern Shaanxi is affected by the coupling effect of overburden rock structure and topography. The development characteristics of mining fracture are complex and can induce mining and environmental disasters. To predict the disaster formation, taking the 113101 working face of the Kunyuan Coal Mine as the engineering background, numerical simulation, physical similarity simulation experiment, and theoretical analysis methods were used to analyze the mining gully of a shallow coal seam in a loess gully area. Based on the dynamic evolution characteristics of stress at different locations, the formation positions, dynamic development, and evolution processes of various fractures were studied; disaster-causing mechanisms were revealed and comprehensive methods were proposed. The results showed that in across-gully mining, the maximum horizontal compressive stress at the bottom of Gully No. 2 was approximately 20.00 MPa, the maximum horizontal tensile stress of the reverse slope section was approximately 1.50 MPa, the width of the F5 fracture of Gully No. 2 was 46.00 cm, and the elevation difference was up to 52.00 cm. The working face across-gully mining formed tensile fractures in most areas, collapsed fractures at the gully bottom, and extruded fractures in the reverse slope section. The fracture at the gully bottom could easily induce water–sand inrush and roof caving and supports crushing. The slope fracture could also induce a gully-induced landslide. According to the mechanisms and distribution areas of fracture disasters, the disaster areas were divided into water–sand inrush areas at the gully bottom, roof caving and supports crushing areas at the gully bottom and at the base of the slope section, and landslide areas at the upper part of the slope section and reverse slope section. Appropriate prevention and control measures were proposed, such as the upstream interception of surface water, slope reinforcement in the middle and upper part of the downhill section, artificial precracking of the roof in the middle and upper part of the downhill section, and grouting reinforcement at the gully bottom and slope toe of the downhill section. These measures were proven to effectively guarantee the safe and efficient mining efficiency of the working face.
Research and application of high-resolution micro-cylindrically focused logging tool
Authors: Xia Jigen , Li Zhiqiang , Ji Yongli , Zhang Hengrong , Li Fangong , Li Junyi , Dong Xingmeng
Published: February 2023

The unknown nature and complexity of non-uniform formations cause new difficulties and challenges to the accurate detection of electrical instruments in shallow formations. The micro-cylindrically focused logging tool (MCFL) can provide three original measurement curves, RB0, RB1, and RB2, with different detection depths, which reflect the flushing zone resistivity, mudcake resistivity, and mudcake thickness. In this study, the finite element method was used to model and analyze the micro-cylindrically focused logging tool tool in a three-dimensional non-uniform medium model. By converting the partial differential equation into a generalized polar problem, the logging response characteristics of the micro-cylindrically focused logging tool tool at different detection depths and ranges, mudcake thicknesses, flush zones, and mudcake resistivity contrasts were investigated. Inverse processing of the micro-cylindrically focused logging tool data using the least-squares method was used to obtain the flush zone resistivity, mudcake resistivity, and mudcake thickness, based on which the micropotential and microgradient curves were synthesized. In addition, a digital focusing method was proposed to improve the focusing accuracy and flexibility of the instrument, enhancing the performance of the micro-cylindrically focused logging tool. The optimized design of the focusing method significantly improved the detection performance of the pole plate. This plays an important role in the evaluation of thin layers and oil-water reservoirs.
Students’ motivation and ownership in a cross-campus and online setting
Authors: Lysne Dag Atle , De Caro-Barek Veruska , Støckert Robin , Røren Kari Anne Flem , Solbjørg Ole Kristen , Nykvist Shaun Sydney
Published: February 2023

This study focuses on student motivation and ownership of learning in a team-based learning environment that is situated in a cross-campus and online context. Data were collected through semi-structured interviews from 12 students who participated in a joint international Master’s degree in Music, Communication and Technology programme between two large Nordic universities. The aim of the study was to identify factors that were most likely to impact student motivation and ownership in this cross-campus and online setting. Three main themes emerged from the analysis of data relating to student motivation and ownership. These three themes were autonomy, peer learning, and communication and social bonding. The study has the potential to contribute to the continued development of future learning environments, which will be physical as well as virtual, or a mix of those. The findings indicated that there is a need to focus on student tasks that should be flexible and open for student choice, and where peer learning is one of the main learning strategies used to engage students. Additionally, the findings also highlight the importance of having a focus on communication and social bonding in the planning and organisation of cross-campus and online courses in order for universities to succeed and to transform to meet the needs of a very diverse group of current and future students.
A novel TBX19 gene mutation in patients with isolated ACTH deficiency from distinct families with a common geographical origin
Authors: Charnay Théo , Mougel Gregory , Amouroux Cyril , Gueorguieva Iva , Joubert Florence , Pertuit Morgane , Reynaud Rachel , Barlier Anne , Brue Thierry , Saveanu Alexandru
Published: February 2023

Isolated ACTH deficiency (IAD) is a life-threatening condition, particularly in the neonatal period, while a main consequence of undiagnosed isolated ACTH deficiency in survivors is cognitive impairment. TBX19 is involved in the differentiation and proliferation of corticotropic cells and TBX19 mutations are responsible for more than 60% of neonatal cases of IAD. We describe a new variant of the main TBX19 transcript (NM 005149.3, c.840del (p.(Glu280Asp fs*27)), classified as pathogenic, whose pathogenicity is assumed to be due to nonsense mediated decay leading to non-expression of T-box transcription factor TBX19. Moreover we summarize the TBX19 mutations published as individual cases since our last large cohort. Interestingly, this pathogenic variant was identified in four patients from three apparently unrelated families. Two of these families were consanguineous, and after investigations all of three were discovered to have roots in the same mountainous region of northern Morocco, suggesting a founder effect. Early diagnosis, timely treatment (hydrocortisone therapy) and preventive education allowed normal development, growth and quality of life in all patients.
GABA signalling in human pancreatic islets
Authors: Jin Zhe , Korol Sergiy V.
Published: February 2023

The pancreatic islets are essential microorgans controlling the glucose level in the blood. The islets consist of different cell types which communicate with each other by means of auto- and paracrine interactions. One of the communication molecules produced by and released within the islets is γ-aminobutyric acid (GABA), a well-known inhibitor of neuronal excitability in the mammalian nervous system. Interestingly, GABA is also present in the blood in the nanomolar concentration range. Thus, GABA can affect not only islet function per se (e.g. hormone secretion) but also interactions between immune cells and the pancreatic islet cells in physiological conditions and in pathological states (particularly in type 1 diabetes). In the last decade the interest in GABA signalling in islets has increased. The broad research scope ranges from fundamental physiological studies at the molecular and cellular level to pathological implications and clinical trials. The aim of this mini-review is to outline the current status of the islet GABA field mostly in relation to human islets, to identify the gaps in the current knowledge and what clinical implications GABA signalling may have in islets.
Nerve conduction velocity is independently associated with bone mineral density in type 2 diabetes mellitus
Authors: Chen Xiao-jing , Wang Xiao-feng , Pan Zheng-can , Zhang Deng , Zhu Ke-cheng , Jiang Tao , Kong Xiao-ke , Xie Rui , Sun Li-hao , Tao Bei , Liu Jian-min , Zhao Hong-yan
Published: February 2023

Aim

This study investigated the association between nerve conduction velocity (NCV) and bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM).

Methods

This study retrospectively collected medical data of T2DM patients who underwent dual-energy X-ray absorptiometry and nerve conduction study at the Shanghai Ruijin Hospital, Shanghai, China. The primary outcome was the total hip BMD T-score. The main independent variables were motor nerve conduction velocities (MCVs), sensory nerve conduction velocities (SCVs), and composite Z-scores of MCV and SCV. T2DM patients were divided into total hip BMD T-scores < -1 and total hip BMD T-scores ≥ -1 groups. The association between the primary outcome and main independent variables was evaluated by Pearson bivariate correlation and multivariate linear regression.

Results

195 female and 415 male patients with T2DM were identified. In male patients with T2DM, bilateral ulnar, median, and tibial MCVs and bilateral sural SCVs were lower in the total hip BMD T-score < -1 group than T-score ≥ -1 group (P < 0.05). Bilateral ulnar, median, and tibial MCVs, and bilateral sural SCVs showed positive correlations with total hip BMD T-score in male patients with T2DM (P < 0.05). Bilateral ulnar and tibial MCVs, bilateral sural SCVs, and composite MCV SCV and MSCV Z-scores were independently and positively associated with total hip BMD T-score in male patients with T2DM, respectively (P < 0.05). NCV did not show significant correlation with the total hip BMD T-score in female patients with T2DM.

Conclusion

NCV showed positive association with total hip BMD in male patients with T2DM. A decline in NCV indicates an elevated risk of low BMD (osteopenia/osteoporosis) in male patients with T2DM.
Toxic effects of per- and polyfluoroalkyl substances on sperm: Epidemiological and experimental evidence
Authors: Sun Zhangbei , Wen Yiqian , Wang Binhui , Deng Shiyi , Zhang Fan , Fu Zhendong , Yuan Yangyang , Zhang Dalei
Published: February 2023

As emerging organic contaminants, per- and polyfluoroalkyl substances (PFASs) have aroused worldwide concern due to their environmental persistence, ubiquitous presence, bioaccumulation, and potential toxicity. It has been demonstrated that PFASs can accumulate in human body and cause multiple adverse health outcomes. Notably, PFASs have been detected in the semen of human, posing a potential hazard to male fecundity. This article reviews the evidence about the toxic effects of exposure to PFASs on male reproduction, focusing on the sperm quality. Epidemiological studies showed that PFASs, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were adversely associated with the semen parameters in humans, including sperm count, morphology and motility. Experimental results also confirmed that PFAS exposure led to testicular and epididymal damage, therefore impairing spermatogenesis and sperm quality. The mechanisms of reproductive toxicity of PFASs may be involved in blood-testosterone barrier destruction, testicular apoptosis, testosterone synthesis disorder, and membrane lipid composition alteration, oxidative stress and Ca2+ influx in sperm. In conclusion, this review highlighted the potential threat of exposure to PFASs to human spermatozoa.
Sex- and age-specific association between outdoor light at night and obesity in Chinese adults: A national cross-sectional study of 98,658 participants from 162 study sites
Authors: Zhang Xiaoyun , Zheng Ruizhi , Xin Zhuojun , Zhao Zhiyun , Li Mian , Wang Tiange , Xu Min , Lu Jieli , Wang Shuangyuan , Lin Hong , Wang Weiqing , Ning Guang , Bi Yufang , Chen Yuhong , Xu Yu
Published: February 2023

Background

Exposure to light at night (LAN) is a potent disruptor of the circadian system. Whether LAN exposure exerts a sex- or age-specific influence on obesity needs investigation.

Objectives

To estimate the sex- and age-specific associations of exposure to outdoor LAN and obesity based on a national and cross-sectional survey.

Methods

The study included a nationally representative sample of 98,658 adults aged ≥ 18 years who had lived in their current residence for ≥ 6 months from 162 study sites across mainland China in 2010. Outdoor LAN exposure was estimated from satellite imaging data. General obesity was defined as body-mass index (BMI) ≥ 28 kg/m2 and central obesity was defined as waist circumference ≥ 90 cm in men and ≥ 85 cm in women. Linear and logistic regression models were used to examine the associations between LAN exposure and prevalent obesity in sex and age categories.

Results

A monotonically increasing association of outdoor LAN with BMI, waist circumference was observed in all sex and age categories, except for adults aged 18-39 years. Significant associations of LAN exposure with prevalent obesity were observed in each sex and age category, especially in men and older people. Per 1-quintile increase in LAN was associated with 14% increased odds of general obesity in men (odds ratio, OR=1.14, 95% confidence interval, CI=1.07-1.23) and 24% in adults aged ≥ 60 years (OR=1.24, 95% CI=1.14-1.35). Per 1-quintile increase in LAN was associated with 19% increased odds of central obesity in men (OR=1.19, 95% CI=1.11-1.26) and 26% in adults aged ≥ 60 years (OR=1.26, 95% CI=1.17-1.35).

Conclusions

Increased chronic outdoor LAN exposure was associated with increased prevalence of obesity in sex- and age- specific Chinese populations. Public health policies on reducing light pollution at night might be considered in obesity prevention.
Simple model of morphometric constraint on carbon burial in boreal lakes
Authors: Cael B. B. , Seekell David A.
Published: February 2023

A geometric theory was developed to explain the empirical relationship between carbon burial and lake shape in boreal lakes. The key feature of this model is an attenuation length scale, analogous to models of marine organic carbon fluxes. This length scale is the ratio of how fast carbon is displaced vertically versus how fast it is respired and engenders a simple model with a single easily constrained free parameter. Lake depths are modeled based on fractal area–volume relationships that reflect the approximate scale invariance of Earth’s topography on idealized lake geometries. Carbon burial is estimated by applying the attenuation length scale to these depths. Using this model, we demonstrate the relationship between the dynamic ratio—a metric of lake morphometry calculated by dividing the square root of surface area by the mean depth—and carbon burial. We use scaling relationships to predict how dynamic ratio, and by extension carbon burial, varies across the lake size spectrum. Our model also provides a basis for generalizing empirical studies to the biome scale. By applying our model to a boreal lake census, we estimate boreal lake carbon burial to be 1.8 ± 0.5 g C/m2/yr or 1.1 ± 0.3 Tg C/yr among all boreal lakes.
Understanding the adsorption of iron oxide nanomaterials in magnetite and bimetallic form for the removal of arsenic from water
Authors: Boruah Himangshu , Tyagi Neha , Gupta Sanjay Kumar , Chabukdhara Mayuri , Malik Tabarak
Published: February 2023

Arsenic decontamination is a major worldwide concern as prolonged exposure to arsenic (>10 µg L-1) through drinking water causes serious health hazards in human beings. The selection of significant, cost-effective, and affordable processes for arsenic removal is the need of the hour. For the last decades, iron-oxide nanomaterials (either in the magnetite or bimetallic form) based adsorptive process gained attention owing to their high arsenic removal efficiency and high regenerative capacity as well as low yield of harmful by-products. In the current state-of-the-art, a comprehensive literature review was conducted focused on the applicability of iron-based nanomaterials for arsenic removal by considering three main factors: (a) compilation of arsenic removal efficiency, (b) identifying factors that are majorly affecting the process of arsenic adsorption and needs further investigation, and (c) regeneration capacity of adsorbents without affecting the removal process. The results revealed that magnetite and bimetallic nanomaterials are more effective for removing Arsenic (III) and Arsenic (V). Further, magnetite-based nanomaterials could be used up to five to six reuse cycles, whereas this value varied from three to six reuse cycles for bimetallic ones. However, most of the literature was based on laboratory findings using decided protocols and sophisticated instruments. It cannot be replicated under natural aquatic settings in the occurrence of organic contents, fluctuating pH and temperature, and interfering compounds. The primary rationale behind this study is to provide a comparative picture of arsenic removal through different iron-oxide nanomaterials (last twelve yearsof published literature) and insights into future research directions.
The combined effects of VPD and soil moisture on historical maize yield and prediction in China
Authors: Zhao Fujie , Wang Guojie , Li Shijie , Hagan Daniel Fiifi Tawia , Ullah Waheed
Published: February 2023

Understanding the effects of thermal and water stress on maize yield in the context of climate change is crucial to ensure food security in China. However, very few studies looked into the combined effects of heat and water stress on maize yield in China. Here, we utilized historical reanalysis data from ERA5 and four future shared socioeconomic pathway scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5) of the Coupled Model Intercomparison Project 6 (CMIP6) models to predict the maize yield. We used the linear mixed-effects model to quantify the grid cell sensitivity of vapor pressure deficit (VPD) and root-zone soil moisture to maize yield in China during 2010–2016. The results infer that VPD and root-zone soil moisture are excellent representatives of heat and moisture stress. Maize yield is beneficial only when the atmospheric moisture demand and soil moisture are in relative balance. Based on the historical results’ polynomial function for VPD and soil moisture, we predict the maize yield response to soil moisture and VPD in the four SSPs. The results show that considering soil moisture in the future the projected yield estimates reduce the overestimated yield loss by half compared to considering only atmospheric moisture requirements. Maize yield will decrease under representative SSPs due to an increase in temperature (1.5, 2.0, 2.5, 3.0, 3.5, and 4.0°C). This study suggests that both atmospheric moisture demand and supply need to be considered when analyzing the specific influence of climate change on crop yield to secure and assure global food supplies.
Seasonal variations in the gut microbiota of white-headed black langur (Trachypithecus leucocephalus) in a limestone forest in Southwest Guangxi, China
Authors: Chen Yanqiong , Lai Ying , Zheng Jingjin , Liu Zheng , Nong Dengpan , Liang Jipeng , Li Youbang , Huang Zhonghao
Published: February 2023

Investigating gut microbiota is important for understanding the physiological adaptation of animals to food availability changes in fragmented habitats and consequently providing new ideas for the conservation of endangered wild animals. In this study, we explored the gut microbiota of the endangered white-headed black langur (Trachypithecus leucocephalus), which is endemic to the limestone forests of Southwest Guangxi, China, to understand its adaptation strategies to seasonal changes in habitat using 16S rRNA sequencing. Our results revealed significant seasonal variations in the gut microbiota of white-headed black langurs. In particular, the alpha diversity was higher in the rainy season than in the dry season, and the beta diversity was significantly different between the two seasons. At the phylum level, the relative abundance of Firmicutes, Actinobacteriota, and Proteobacteria was higher in the dry season than that in the rainy season, whereas that of Bacteroidetes, Spirochaetota, and Cyanobacteria was significantly higher in the rainy season than that in the dry season. At the family level, Oscillospiraceae and Eggerthellaceae were more abundant in the dry season than in the rainy season, whereas Lachnospiraceae, Ruminococcaceae, and Monoglobaceae were more abundant in the rainy season than in the dry season. These results could have been obtained due to seasonal changes in the diet of langurs in response to food plant phenology. In addition, the neutral community model revealed that the gut microbiota assembly of these langurs was dominated by deterministic processes and was more significantly affected by ecological factors in the dry season than in the rainy season, which could be linked to the higher dependence of these langurs on mature leaves in the dry season. We concluded that the seasonal variations in the gut microbiota of white-headed black langurs occurred in response to food plant phenology in their habitat, highlighting the importance of microbiota in responding to fluctuating ecological factors and adapting to seasonal dietary changes.
Knowledge and attitude of women towards maternity waiting homes and associated factors among women who gave birth in the last twelve months in Dega Damot district, northwest Ethiopia
Authors: Anteneh Tazeb Alemu , Solomon Abayneh Aklilu , Tamiru Animut Tagele , Tibebu Nebiyu Solomon , Abegaz Marta Yimam , Temesgan Wubedle Zelalem , Kebede Azmeraw Ambachew , Aklil Mastewal Belayneh , Mesele Tiruye Tilahun , Tiruye Tiringo Molla
Published: February 2023

Background

Maternal waiting homes have been identified as one strategy to reduce maternal and perinatal mortality by bringing women living in hard-to-reach areas closer to a health facility that provides emergency obstetric care. Even if utilization of maternal waiting homes is repeatedly assessed, there is a scarcity of evidence in Ethiopia regarding women's knowledge and attitude towards maternal waiting homes.

Objective

This study aimed to assess women's knowledge and attitude towards maternity waiting homes and associated factors among women who gave birth in the last twelve months in northwest Ethiopia.

Methods

A community-based cross-sectional study was conducted from January 1st to February 30th, 2021. A total of 872 participants were selected by using a stratified cluster sampling technique. Data were collected by face-to-face interviews using a structured, pretested, and interviewer-administered questionnaire. Data were entered into EPI data version 4.6 and analysis was done through SPSS version 25. The multivariable logistic regression model was fitted and the level of significance was declared at a p-value of ≤0.05.

Result

Women's adequate knowledge and positive attitude towards maternal waiting homes were 67.3% (95% CI: 64–70) and 73% (95% CI: 70–76), respectively. Had antenatal care visit, the shortest distance to reach the nearby health facility, had history of maternal waiting homes utilization, always involved in health care decision, and sometimes involved in health care decisions were significantly associated with women's knowledge regarding maternal waiting homes. Moreover, secondary and above educational level of women, short distance to reach the nearby health facility and had antenatal care visit were significantly associated with women's attitude towards maternity waiting homes.

Conclusion

About two-third of women had adequate knowledge and nearly three-fourth of women had a positive attitude towards maternity waiting homes. It is better to improve the accessibility and utilization of maternal health services Furthermore, it is better to promote women's decision making power and create motivation to have better academic achievement of women.
Identification of a DRB3*011:01-restricted CD4+ T cell response against bovine respiratory syncytial virus fusion protein
Authors: Kaplan Bryan S. , Hofstetter Amelia R. , McGill Jodi L. , Lippolis John D. , Norimine Junzo , Dassanayake Rohana P. , Sacco Randy E.
Published: February 2023

Although Human Respiratory Syncytial Virus (HRSV) is a significant cause of severe respiratory disease with high morbidity and mortality in pediatric and elderly populations worldwide there is no licensed vaccine. Bovine Respiratory Syncytial Virus (BRSV) is a closely related orthopneumovirus with similar genome structure and high homology between structural and nonstructural proteins. Like HRSV in children, BRSV is highly prevalent in dairy and beef calves and known to be involved in the etiology of bovine respiratory disease, in addition to being considered an excellent model for HRSV. Commercial vaccines are currently available for BRSV, though improvements in efficacy are needed. The aims of this study were to identify CD4+ T cell epitopes present in the fusion glycoprotein of BRSV, an immunogenic surface glycoprotein that mediates membrane fusion and a major target of neutralizing antibodies. Overlapping peptides representing three regions of the BRSV F protein were used to stimulate autologous CD4+ T cells in ELISpot assays. T cell activation was observed only in cells from cattle with the DRB3*011:01 allele by peptides from AA249-296 of the BRSV F protein. Antigen presentation studies with C-terminal truncated peptides further defined the minimum peptide recognized by the DRB3*011:01 allele. Computationally predicted peptides presented by artificial antigen presenting cells further confirmed the amino acid sequence of a DRB3*011:01 restricted class II epitope on the BRSV F protein. These studies are the first to identify the minimum peptide length of a BoLA-DRB3 class II-restricted epitope in BRSV F protein.
scRNA-seq reveals aging-related immune cell types and regulators in vaginal wall from elderly women with pelvic organ prolapse
Authors: Miao Yali , Wen Jirui , Wang Ling , Wen Qiao , Cheng Juan , Zhao Zhiwei , Wu Jiang
Published: February 2023

Introduction

In the pathology of pelvic organ prolapse (POP), little is known about the contributing role of pelvic microenvironment. Also, the age-related differences in pelvic microenvironment of POP patients is always ignored. In the present study, we investigated the age-related differences in pelvic microenvironment between Young POP patients and Old POP patients, and the novel cell types and critical regulators which contributes to the age-related differences.

Methods

Single-cell transcriptomic analyses were used to detect the changes in cell composition and gene expression from the pelvic microenvironment of control group (<60 years), Young POP group (<60 years) and Old POP group (>60 years). Then, immunohistochemistry and immunofluorescence were used to verify the novel cell types and critical regulators in the pelvic microenvironment. Furthermore, histopathological alteration and mechanical property alteration in POP with different ages were revealed by vaginal tissue histology and biomechanical testing.

Results

The up-regulated biological process in Old women with POP is mainly related to chronic inflammation, while the up-regulated biological process in Young women with POP is mainly related to extracellular matrix metabolism. Meantime, CSF3+ endothelial cells and FOLR2+ macrophages were found to play a central role in inducing pelvic chronic inflammation. Furthermore, the collagen fiber and mechanical property of POP patients decreased with aging.

Conclusions

Taken together, this work provides a valuable resource for deciphering the aging-related immune cell types and the critical regulators in pelvic microenvironment. With better understanding of normal and abnormal events in this pelvic microenvironment, we provided rationales of personalized medicine for POP patients with different ages.
Therapeutic effects of mesenchymal stem cells and their derivatives in common skin inflammatory diseases: Atopic dermatitis and psoriasis
Authors: Yang Jie , Xiao Minglu , Ma Kui , Li Hongyu , Ran Mingzi , Yang Shuxu , Yang Yuguang , Fu Xiaobing , Yang Siming
Published: February 2023

Chronic skin inflammatory diseases including atopic dermatitis (AD) and psoriasis have been considered uncontrolled inflammatory responses, which have usually troubled patients around the world. Moreover, the recent method to treat AD and psoriasis has been based on the inhibition, not regulation, of the abnormal inflammatory response, which can induce a number of side effects and drug resistance in long-term treatment. Mesenchymal stem/stromal cells (MSCs) and their derivatives have been widely used in immune diseases based on their regeneration, differentiation, and immunomodulation with few adverse effects, which makes MSCs a promising treatment for chronic skin inflammatory diseases. As a result, in this review, we aim to systematically discuss the therapeutic effects of various resources of MSCs, the application of preconditioning MSCs and engineering extracellular vesicles (EVs) in AD and psoriasis, and the clinical evaluation of the administration of MSCs and their derivatives, which can provide a comprehensive vision for the application of MSCs and their derivatives in future research and clinical treatment.
Identification of copper death-associated molecular clusters and immunological profiles in rheumatoid arthritis
Authors: Zhou Yu , Li Xin , Ng Liqi , Zhao Qing , Guo Wentao , Hu Jinhua , Zhong Jinghong , Su Wenlong , Liu Chaozong , Su Songchuan
Published: February 2023

Objective

An analysis of the relationship between rheumatoid arthritis (RA) and copper death-related genes (CRG) was explored based on the GEO dataset.

Methods

Based on the differential gene expression profiles in the GSE93272 dataset, their relationship to CRG and immune signature were analysed. Using 232 RA samples, molecular clusters with CRG were delineated and analysed for expression and immune infiltration. Genes specific to the CRGcluster were identified by the WGCNA algorithm. Four machine learning models were then built and validated after selecting the optimal model to obtain the significant predicted genes, and validated by constructing RA rat models.

Results

The location of the 13 CRGs on the chromosome was determined and, except for GCSH. LIPT1, FDX1, DLD, DBT, LIAS and ATP7A were expressed at significantly higher levels in RA samples than in non-RA, and DLST was significantly lower. RA samples were significantly expressed in immune cells such as B cells memory and differentially expressed genes such as LIPT1 were also strongly associated with the presence of immune infiltration. Two copper death-related molecular clusters were identified in RA samples. A higher level of immune infiltration and expression of CRGcluster C2 was found in the RA population. There were 314 crossover genes between the 2 molecular clusters, which were further divided into two molecular clusters. A significant difference in immune infiltration and expression levels was found between the two. Based on the five genes obtained from the RF model (AUC = 0.843), the Nomogram model, calibration curve and DCA also demonstrated their accuracy in predicting RA subtypes. The expression levels of the five genes were significantly higher in RA samples than in non-RA, and the ROC curves demonstrated their better predictive effect. Identification of predictive genes by RA animal model experiments was also confirmed.

Conclusion

This study provides some insight into the correlation between rheumatoid arthritis and copper mortality, as well as a predictive model that is expected to support the development of targeted treatment options in the future.
The melanoma tumor glyco-code impacts human dendritic cells’ functionality and dictates clinical outcomes
Authors: Sosa Cuevas Eleonora , Roubinet Benoît , Mouret Stephane , Thépaut Michel , de Fraipont Florence , Charles Julie , Fieschi Franck , Landemarre Ludovic , Chaperot Laurence , Aspord Caroline
Published: February 2023

Subversion of immunity is a hallmark of cancer development. Dendritic cells (DCs) are strategic immune cells triggering anti-tumor immune responses, but tumor cells exploit their versatility to subvert their functions. Tumor cells harbor unusual glycosylation patterns, which can be sensed through glycan-binding receptors (lectins) expressed by immune cells that are crucial for DCs to shape and orientate antitumor immunity. Yet, the global tumor glyco-code and its impact on immunity has not been explored in melanoma. To decrypt the potential link between aberrant glycosylation patterns and immune evasion in melanoma, we investigated the melanoma tumor glyco-code through the GLYcoPROFILE™ methodology (lectin arrays), and depicted its impact on patients’ clinical outcome and DC subsets’ functionality. Specific glycan patterns correlated with clinical outcome of melanoma patients, GlcNAc, NeuAc, TF-Ag and Fuc motifs being associated with poor outcome, whereas Man and Glc residues elicited better survival. Strikingly, tumor cells differentially impacting cytokine production by DCs harbored distinct glyco-profiles. GlcNAc exhibited a negative influence on cDC2s, whereas Fuc and Gal displayed inhibitory impacts on cDC1s and pDCs. We further identified potential booster glycans for cDC1s and pDCs. Targeting specific glycans on melanoma tumor cells restored DCs’ functionality. The tumor glyco-code was also linked to the nature of the immune infiltrate. This study unveils the impact of melanoma glycan patterns on immunity, and paves the way for innovative therapeutic options. Glycans/lectins interactions arise as promising immune checkpoints to rescue DCs from tumor’ hijacking to reshape antitumor immunity and inhibit immunosuppressive circuits triggered by aberrant tumor glycosylation.
Identification of a novel senescence-associated signature to predict biochemical recurrence and immune microenvironment for prostate cancer
Authors: Han Chenglin , Deng Yuxuan , Yang Bin , Hu Peng , Hu Bintao , Wang Tao , Liu Jihong , Xia Qidong , Liu Xiaming
Published: February 2023

Background

Prostate cancer (PCa) is an age-associated malignancy with high morbidity and mortality rate, posing a severe threat to public health. Cellular senescence, a specialized cell cycle arrest form, results in the secretion of various inflammatory mediators. In recent studies, senescence has shown an essential role in tumorigenesis and tumor development, yet the extensive effects of senescence in PCa have not been systematically investigated. Here, we aimed to develop a feasible senescence-associated prognosis model for early identification and appropriate management in patients with PCa.

Method

The RNA sequence results and clinical information available from The Cancer Genome Atlas (TCGA) and a list of experimentally validated senescence-related genes (SRGs) from the CellAge database were first obtained. Then, a senescence-risk signature related with prognosis was constructed using univariate Cox and LASSO regression analysis. We calculated the risk score of each patient and divided them into high-risk and low-risk groups in terms of the median value. Furthermore, two datasets (GSE70770 and GSE46602) were used to assess the effects of the risk model. A nomogram was built by integrating the risk score and clinical characteristics, which was further verified using ROC curves and calibrations. Finally, we compared the differences in the tumor microenvironment (TME) landscape, drug susceptibility, and the functional enrichment among the different risk groups.

Results

We established a unique prognostic signature in PCa patients based on eight SRGs, including CENPA, ADCK5, FOXM1, TFAP4, MAPK, LGALS3, BAG3, and NOX4, and validated well prognosis-predictive power in independent datasets. The risk model was associated with age and TNM staging, and the calibration chart presented a high consistency in nomogram prediction. Additionally, the prognostic signature could serve as an independent prediction factor due to its high accuracy. Notably, we found that the risk score was positively associated with tumor mutation burden (TMB) and immune checkpoint, whereas negatively correlated with tumor immune dysfunction and exclusion (TIDE), suggesting that these patients with risk scores were more sensitive to immunotherapy. Drug susceptibility analysis revealed differences in the responses to general drugs (docetaxel, cyclophosphamide, 5-Fluorouracil, cisplatin, paclitaxel, and vincristine) were yielded between the two risk groups.

Conclusion

Identifying the SRG-score signature may become a promising method for predicting the prognosis of patients with PCa and tailoring appropriate treatment strategies.
Comparative study on antibacterial characteristics of the multiple liver expressed antimicrobial peptides (LEAPs) in teleost fish
Authors: Liu Xun , Hu Ya-Zhen , Pan Yi-Ru , Liu Jia , Jiang You-Bo , Zhang Yong-An , Zhang Xu-Jie
Published: February 2023

Antimicrobial peptides are important components of the host innate immune system, forming the first line of defense against infectious microorganisms. Among them, liver-expressed antimicrobial peptides (LEAPs) are a family of antimicrobial peptides that widely exist in vertebrates. LEAPs include two types, named LEAP-1 and LEAP-2, and many teleost fish have two or more LEAP-2s. In this study, LEAP-2C from rainbow trout and grass carp were discovered, both of which are composed of 3 exons and 2 introns. The antibacterial functions of the multiple LEAPs were systematically compared in rainbow trout and grass carp. The gene expression pattern revealed that rainbow trout and grass carp LEAP-1, LEAP-2A, LEAP-2B and/or LEAP-2C were differentially expressed in various tissues/organs, mainly in liver. After bacterial infection, the expression levels of LEAP-1, LEAP-2A, LEAP-2B and/or LEAP-2C in the liver and gut of rainbow trout and grass carp increased to varying degrees. Moreover, the antibacterial assay and bacterial membrane permeability assay showed that rainbow trout and grass carp LEAP-1, LEAP-2A, LEAP-2B and LEAP-2C all have antibacterial activities against a variety of Gram-positive and Gram-negative bacteria with varying levels through membrane rupture. Furthermore, cell transfection assay showed that only rainbow trout LEAP-1, but not LEAP-2, can lead to the internalization of ferroportin, the only iron exporter on cell surface, indicating that only LEAP-1 possess iron metabolism regulation activity in teleost fish. Taken together, this study systematically compared the antibacterial function of LEAPs in teleost fish and the results suggest that multiple LEAPs can enhance the immunity of teleost fish through different expression patterns and different antibacterial activities to various bacteria.
The adverse effects of 17β-estradiol immersion during gonadal differentiation on ovarian development of female Takifugu rubripes
Authors: Hu Peng , Liu Shufang , Liu Xinfu , Liu Haijin , Liu Shengcong , Zhuang Zhimeng
Published: February 2023

Estrogen exposure during early-life stages has been found to delay ovarian development in female fish, even after a long-term depuration period. However, the mechanisms underlying the disordered ovarian development remain unclear. In this study, the larvae of tiger puffer Takifugu rubripes were exposed to 0 (control) and 10 μg/L 17β-estradiol (E2) from 20 to 90 days post-hatch (dph) and maintained in clear seawater until 180 dph. Genetic females collected at 90 and 180 dph were identified by analyzing a sex-associated SNP. Then, the ovarian structure, gonadosomatic index (GSI), the maximum follicle area and the mRNA levels of genes involving in cell cycle (ckd2, ckd4, cdk6, ccna2, ccnd2, cdkn1b and cdkn2c), meiosis initiation (sycp3, rec8, spo11, and dmc1), follicle formatiaon (bmp2, hnrnpk, hmp15, gdf9, nobox and figla) and apoptosis (bax and bcl-2) were analyzed between control and E2-exposed females. The results show that, no structure difference in ovaries was observed between control and E2-treated females at 90 dph, but the primary growth follicles in E2-treated females were observed to be fewer in number than control at 180 dph. Both ovarian weight and GSI of E2-treated females were significant lower than the control at 90 and 180 dph, while there was no significant different in the maximum follicle area between control and E2-treated females at neither 90 or 180 dph. Additionally, the E2 exposure suppressed the expression of sycp3, rec8, spo11, dmc1, bmp2, hnrnpk and bcl-2 at 90 dph, but the mRNA levels of those genes in E2-treated females showed no significant different with the control at 180 dph. The reduced mRNA levels of sycp3, rec8, spo11 and dmc1 might result in disrupted meiosis, and suppression the expression of bmp2 and hnrnpk affected follicle formation. Then, abnormal meiosis initiation and follicle formation might further promote apoptosis as indicated by the decrease in mRNA levels of bcl-2, which ultimately contributed to less number of follicles and low GSI value in E2-treated females.
Swiss Sepsis National Action Plan: A coordinated national action plan to stop sepsis-related preventable deaths and to improve the support of people affected by sepsis in Switzerland
Authors: Schlapbach Luregn J. , Zimmermann Elisa A. , Meylan Sylvain , Stocker Martin , Suter Peter M. , Jakob Stephan M. , National Action Plan Working Group on behalf of the Swiss Sepsis
Published: February 2023

Background

Sepsis is a devastating disease which causes yearly over 10 million deaths worldwide. In 2017, the World Health Organization (WHO) issued a resolution prompting member states to improve the prevention, recognition, and management of sepsis. The 2021 European Sepsis Report revealed that—contrary to other European countries—Switzerland had not yet actioned the sepsis resolution.

Methods

A panel of experts convened at a policy workshop to address how to improve awareness, prevention, and treatment of sepsis in Switzerland. Goal of the workshop was to formulate a set of consensus recommendations toward creating a Swiss Sepsis National Action Plan (SSNAP). In a first part, stakeholders presented existing international sepsis quality improvement programs and national health programs relevant for sepsis. Thereafter, the participants were allocated into three working groups to identify opportunities, barriers, and solutions on (i) prevention and awareness, (ii) early detection and treatment, and (iii) support for sepsis survivors. Finally, the entire panel summarized the findings from the working groups and identified priorities and strategies for the SSNAP. All discussions during the workshop were transcribed into the present document. All workshop participants and key experts reviewed the document.

Results

The panel formulated 14 recommendations to address sepsis in Switzerland. These focused on four domains, including (i) raising awareness in the community, (ii) improving healthcare workforce training on sepsis recognition and sepsis management; (iii) establishing standards for rapid detection, treatment and follow-up in sepsis patients across all age groups; and (iv) promoting sepsis research with particular focus on diagnostic and interventional trials.

Conclusion

There is urgency to tackle sepsis. Switzerland has a unique opportunity to leverage from lessons learnt during the COVID-19 pandemic to address sepsis as the major infection-related threat to society. This report details consensus recommendations, the rationale thereof, and key discussion points made by the stakeholders on the workshop day. The report presents a coordinated national action plan to prevent, measure, and sustainably reduce the personal, financial and societal burden, death and disability arising from sepsis in Switzerland.