bluuebunny/crossref_metadata_2025 huggingface dataset:
The E3 Ligase PIAS1 Regulates p53 Sumoylation to Control Stress-Induced Apoptosis of Lens Epithelial Cells Through the Proapoptotic Regulator Bax
Authors: Nie Qian , Chen Huimin , Zou Ming , Wang Ling , Hou Min , Xiang Jia-Wen , Luo Zhongwen , Gong Xiao-Dong , Fu Jia-Ling , Wang Yan , Zheng Shu-Yu , Xiao Yuan , Gan Yu-Wen , Gao Qian , Bai Yue-Yue , Wang Jing-Miao , Zhang Lan , Tang Xiang-Cheng , Hu Xuebin , Gong Lili , Liu Yizhi , Li David Wan-Cheng
Published: June 2021

Protein sumoylation is one of the most important post-translational modifications regulating many biological processes (Flotho A & Melchior F. 2013.Ann Rev. Biochem. 82:357–85). Our previous studies have shown that sumoylation plays a fundamental role in regulating lens differentiation (Yan et al., 2010.PNAS, 107(49):21034-9.;Gong et al., 2014.PNAS. 111(15):5574–9). Whether sumoylation is implicated in lens pathogenesis remains elusive. Here, we present evidence to show that the protein inhibitor of activated STAT-1 (PIAS1), a E3 ligase for sumoylation, is implicated in regulating stress-induced lens pathogenesis. During oxidative stress-induced cataractogenesis, expression of PIAS1 is significantly altered at both mRNA and protein levels. Upregulation and overexpression of exogenous PIAS1 significantly enhances stress-induced apoptosis. In contrast, silence of PIAS1 with CRISPR/Cas9 technology attenuates stress-induced apoptosis. Mechanistically, different from other cells, PIAS1 has little effect to activate JNK but upregulates Bax, a major proapoptotic regulator. Moreover, Bax upregulation is derived from the enhanced transcription activity of the upstream transcription factor, p53. As revealed previously in other cells by different laboratories, our data also demonstrate that PIAS1 promotes SUMO1 conjugation of p53 at K386 residue in lens epithelial cells and thus enhances p53 transcription activity to promote Bax upregulation. Silence of Bax expression largely abrogates PIAS1-mediated enhancement of stress-induced apoptosis. Thus, our results demonstrated that PIAS1 promotes oxidative stress-induced apoptosis through positive control of p53, which specifically upregulates expression of the downstream proapoptotic regulator Bax. As a result, PIAS1-promoted apoptosis induced by oxidative stress is implicated in lens pathogenesis.
Recent Advances in Sensing Applications of Molecularly Imprinted Photonic Crystals
Authors: Fan Jing , Qiu Lili , Qiao Yu , Xue Min , Dong Xiao , Meng Zihui
Published: June 2021

Photonic crystals (PhCs) with a brightly colored structure are novel materials and are widely used in chemical and biological sensing. Combining PhCs with molecular imprinting technology (MIT), the molecularly imprinted PhC (MIPC) sensors are fabricated, which can specifically recognize the target molecules. Aside from high sensitivity and selectivity, the MIPC sensors could recognize the naked eye detection because of its optical properties. In this review, an overview of recent advances in sensing applications of MIPC sensors including the responsive mechanisms, application in environmental monitoring, and the application to human health were illustrated. The MIPC sensors all responded to the analytes specifically and also showed high sensitivity in real samples, which provided a method to realize the rapid, convenient, naked eye, and real-time detection. Furthermore, the current limitations and potential future directions of MIPC sensors were also discussed.
Real-Time In Vivo Detection and Monitoring of Bacterial Infection Based on NIR-II Imaging
Authors: Feng Sijia , Li Huizhu , Liu Chang , Chen Mo , Sheng Huaixuan , Huang Mingru , Li Yunxia , Chen Jun , Zhang Jian , Hao Yuefeng , Chen Shiyi
Published: June 2021

Treatment according to the dynamic changes of bacterial load in vivo is critical for preventing progression of bacterial infections. Here, we present a lead sulfide quantum dots (PbS QDs) based second near-infrared (NIR-II) fluorescence imaging strategy for bacteria detection and real-time in vivo monitoring. Four strains of bacteria were labeled with synthesized PbS QDs which showed high bacteria labeling efficiency in vitro. Then bacteria at different concentrations were injected subcutaneously on the back of male nude mice for in vivo imaging. A series of NIR-II images taken at a predetermined time manner demonstrated changing patterns of photoluminescence (PL) intensity of infected sites, dynamically imaging a changing bacterial load in real-time. A detection limit around 102–104 CFU/ml was also achieved in vivo. Furthermore, analysis of pathology of infected sites were performed, which showed high biocompatibility of PbS QDs. Therefore, under the guidance of our developed NIR-II imaging system, real-time detection and spatiotemporal monitoring of bacterial infection in vivo can be achieved, thus facilitating anti-infection treatment under the guidance of the dynamic imaging of bacterial load in future.
Antimicrobial Peptides: A New Hope in Biomedical and Pharmaceutical Fields
Authors: Moretta Antonio , Scieuzo Carmen , Petrone Anna Maria , Salvia Rosanna , Manniello Michele Dario , Franco Antonio , Lucchetti Donatella , Vassallo Antonio , Vogel Heiko , Sgambato Alessandro , Falabella Patrizia
Published: June 2021

Antibiotics are essential drugs used to treat pathogenic bacteria, but their prolonged use contributes to the development and spread of drug-resistant microorganisms. Antibiotic resistance is a serious challenge and has led to the need for new alternative molecules less prone to bacterial resistance. Antimicrobial peptides (AMPs) have aroused great interest as potential next-generation antibiotics, since they are bioactive small proteins, naturally produced by all living organisms, and representing the first line of defense against fungi, viruses and bacteria. AMPs are commonly classified according to their sources, which are represented by microorganisms, plants and animals, as well as to their secondary structure, their biosynthesis and their mechanism of action. They find application in different fields such as agriculture, food industry and medicine, on which we focused our attention in this review. Particularly, we examined AMP potential applicability in wound healing, skin infections and metabolic syndrome, considering their ability to act as potential Angiotensin-Converting Enzyme I and pancreatic lipase inhibitory peptides as well as antioxidant peptides. Moreover, we argued about the pharmacokinetic and pharmacodynamic approaches to develop new antibiotics, the drug development strategies and the formulation approaches which need to be taken into account in developing clinically suitable AMP applications.
Product Diversification, Adaptive Management, and Climate Change: Farming and Family in the U.S. Corn Belt
Authors: Valliant Julia C. D. , Bruce Analena B. , Houser Matthew , Dickinson Stephanie L. , Farmer James R.
Published: June 2021

A variety of factors shape farmers' views as they face the rising effects of climate change and consider a range of adaptation strategies to build the resilience of their farming systems. We examine a set of related questions to explore farmers' perspectives on risks and potential shifts to their operations: (1) Relative to other environmental factors, how salient of a challenge is climate change and climate-related impacts to farmers? (2) Do farmers intend to adapt to climate impacts generally?, and (3) What factors shape their use of a specific and underexplored adaptive response—farm product diversification? The data come from a survey of 179 operators within a 30-county region of Indiana, Michigan, and Ohio. The region spans various rural-urban gradients. Respondents generally represent smaller operations [median of 80 acres (32 hectares)]. Because our selection methods aimed to over-sample from food-producing farms, 60% of respondents produced some type of food or value-added product, and 40% produced only commodity feedstocks and biofuels. Although the group as a whole indicated only “somewhat” of a concern about changing weather patterns, and half did not anticipate adapting their farming practices to climate change, farmers' responses to a write-in question denoted regional climate effects as challenges to their farms. Analysis of subgroups among the respondents, according to their views of climate change, adaptation, and further diversifying their agricultural products, distinguished farmers' family considerations, and gender. Methods to elicit subgroups included correlation, regression, cluster analysis, and an examination of the many respondents (29%) who indicated uncertainty about adapting practices. Women, who participated in 29% of responses, indicated more concern with changing weather patterns and more openness to adapting farming practices compared to men. Farmers with the most family relationships to consider, and those with the greatest aspirations to employ descendants, were the most receptive to adapting their farming practices. This was the case even when respondents' concern over climate change was low. Results point to the importance of family relationships as a factor in farmers' openness to implementing adaptive and potentially mitigative actions.
Global Data Gaps in Our Knowledge of the Terrestrial Cryosphere
Authors: Pritchard Hamish D.
Published: June 2021

The IPCC Special Report on Oceans and Cryosphere in a Changing Climate identified major gaps in our knowledge of snow and glacier ice in the terrestrial cryosphere. These gaps are limiting our ability to predict the future of the energy and water balance of the Earth's surface, which in turn affect regional climate, biodiversity and biomass, the freezing and thawing of permafrost, the seasonal supply of water for one sixth of the global population, the rate of global sea level rise and the risk of riverine and coastal flooding. Snow and ice are highly susceptible to climate change but although their spatial extents are routinely monitored, the fundamental property of their water content is remarkably poorly observed. Specifically, there is a profound lack of basic but problematic observations of the amount of water supplied by snowfall and of the volume of water stored in glaciers. As a result, the climatological precipitation of the mountain cryosphere is, for example, biassed low by 50–100%, and biases in the volume of glacier ice are unknown but are likely to be large. More and better basic observations of snow and ice water content are urgently needed to constrain climate models of the cryosphere, and this requires a transformation in the capabilities of snow-monitoring and glacier-surveying instruments. I describe new solutions to this long-standing problem that if deployed widely could achieve this transformation.
Acute Mechanical Performance of Magmaris vs. DESolve Bioresorbable Scaffolds in a Real-World Scenario
Authors: Boeder Niklas F. , Dörr Oliver , Koepp Tim , Blachutzik Florian , Achenbach Stephan , Elsässer Albrecht , Hamm Christian W. , Nef Holger M.
Published: June 2021

Background: After the bioresorbable PLLA-based vascular scaffold (Absorb BVS) was taken from the market due to its high adverse event rates, a magnesium-based scaffold (Magmaris) was introduced.

Objective: To compare the acute performance of the sirolimus-eluting magnesium alloy Magmaris scaffold with that of the novolimus-eluting PLLA-based DESolve scaffold in terms of appropriate scaffold deployment using optical coherence tomography (OCT).

Methods and Results: Data from the final OCT pullback of 98 patients were included (19 Magmaris, 79 DESolve) and analyzed at 1-mm intervals. The following indices were calculated: mean and minimal area, residual area stenosis, incomplete strut apposition, tissue prolapse, eccentricity index, symmetry index, strut fracture, and edge dissection. OCT showed a minimum lumen area for Magmaris vs. DESolve of 6.6 ± 1.6 vs. 6.0 ± 1.9 (p = 0.06). Scaffolds with residual area stenosis >20% were predominantly seen in the DESolve group (15.8 vs. 46.8%; p = 0.01). The mean eccentricity index did differ significantly (0.74 ± 0.06 vs. 0.63 ± 0.09; p < 0.001). No fractures were observed for Magmaris scaffolds, but 15.2% were documented for DESolve BRS (p < 0.001). Incomplete scaffold apposition area was significantly higher in the DESolve group (0.01 ± 0.02 vs. 1.05 ± 2.32 mm2; p < 0.001).

Conclusion: This is the first study to compare the acute mechanical performance between Magmaris and DESolve in a real-world setting. The acute mechanical performance of Magmaris BRS seems to be superior to that of DESolve BRS, whereas OCT showed a good acute mechanical performance for both BRS in terms of generally accepted imaging criteria.
Integration of Biobanks in National eHealth Ecosystems Facilitating Long-Term Longitudinal Clinical-Omics Studies and Citizens' Engagement in Research Through eHealthBioR
Authors: Antoniades Athos , Papaioannou Maria , Malatras Apostolos , Papagregoriou Gregory , Müller Heimo , Holub Petr , Deltas Constantinos , Schizas Christos N.
Published: June 2021

Biobanks have long existed to support research activities with BBMRI-ERIC formed as a European research infrastructure supporting the coordination for biobanking with 20 country members and one international organization. Although the benefits of biobanks to the research community are well-established, the direct benefit to citizens is limited to the generic benefit of promoting future research. Furthermore, the advent of General Data Protection Regulation (GDPR) legislation raised a series of challenges for scientific research especially related to biobanking associate activities and longitudinal research studies. Electronic health record (EHR) registries have long existed in healthcare providers. In some countries, even at the national level, these record the state of the health of citizens through time for the purposes of healthcare and data portability between different providers. The potential of EHRs in research is great and has been demonstrated in many projects that have transformed EHR data into retrospective medical history information on participating subjects directly from their physician's collected records; many key challenges, however, remain. In this paper, we present a citizen-centric framework called eHealthBioR, which would enable biobanks to link to EHR systems, thus enabling not just retrospective but also lifelong prospective longitudinal studies of participating citizens. It will also ensure strict adherence to legal and ethical requirements, enabling greater control that encourages participation. Citizens would benefit from the real and direct control of their data and samples, utilizing technology, to empower them to make informed decisions about providing consent and practicing their rights related to the use of their data, as well as by having access to knowledge and data generated from samples they provided to biobanks. This is expected to motivate patient engagement in future research and even leads to participatory design methodologies with citizen/patient-centric designed studies. The development of platforms based on the eHealthBioR framework would need to overcome significant challenges. However, it would shift the burden of addressing these to experts in the field while providing solutions enabling in the long term the lower monetary and time cost of longitudinal studies coupled with the option of lifelong monitoring through EHRs.
A Lacustrine Biomarker Record From Rebun Island Reveals a Warm Summer Climate in Northern Japan During the Early Middle Holocene Due to a Stronger North Pacific High
Authors: Yamamoto Masanobu , Wang Fangxian , Irino Tomohisa , Suzuki Kenta , Yamada Kazuyoshi , Haraguchi Tsuyoshi , Gotanda Katsuya , Yonenobu Hitoshi , Chen Xuan-Yu , Tarasov Pavel
Published: June 2021

The summer climate of northern Japan since the last glacial period has likely been determined by atmospheric and oceanic dynamics, such as changes in the North Pacific High, the position of the westerlies, the Kuroshio Current, the Tsushima Warm Current (TWC), and the East Asian summer monsoon. However, it is unclear which factor has been most important. In this study, we analyzed leaf wax δ13C and δD and glycerol dialkyl glycerol tetraethers (GDGTs) in sediments from Lake Kushu, Rebun Island, northern Japan, and discuss changes in climate over the past 17,000 years. The GDGT-based temperature, the averaged chain length, δ13C and δD of long-chain n-fatty acids indicated that the climate was cold during the Oldest Dryas period ∼16 ka and warm in the early Middle Holocene from ∼9 to 6 ka. This climate change is consistent with the sea surface temperature in the Kuroshio–Oyashio transition, but inconsistent with changes in the TWC in the Sea of Japan. The results imply that the summer climate of northern Japan was controlled mainly by changes in the development of the North Pacific Highviachanges in the position of the westerly jet and East Asian summer monsoon rainfall, whereas the influence of the TWC was limited over a millennial timescale.
Improvement in the Prediction of Summer Precipitation in the North China−Hetao Region Using the Tropospheric Temperature Over the Tibetan Plateau in Spring
Authors: Chen Dan , Nan Sulan , Liu Ge , Zhou Changyan , Shi Renrui , Ao Yinhuan , Li Xiang
Published: June 2021

We investigated the relationship between the spring tropospheric temperature over the Tibetan Plateau (TPT) and summer precipitation in eastern China on an interannual timescale using the monthly mean ERA-Interim reanalysis dataset, the HadISST dataset and the daily mean precipitation dataset for China. We found that there is a significant positive correlation between the spring TPT and summer precipitation in the North China−Hetao region. The relationship is manifested in the context of the East Asia–Pacific pattern teleconnection. In the high spring TPT index years, the geopotential height anomalies over East Asia and the western North Pacific present a negative phase of the East Asia–Pacific pattern teleconnection in the subsequent summer. This circulation pattern is beneficial for the water vapor transport from the western Pacific to inland, which further transport to the North China−Hetao region from the Yangtze River–Yellow rivers region. Anomalous upward motion occurs in the North China–Hetao region, which increases precipitation. The East Asian subtropical westerly jet shifts further north and the South Asian high weakens and shrinks westward. These conditions all favor an increase in precipitation over the North China–Hetao region. The spring TPT plays an important part in the prediction of summer precipitation in the North China−Hetao region. The improvement in the use of the spring TPT to predict summer precipitation in the North China–Hetao region is examined by comparing the prediction equations with and without the prediction factor of the spring TPT on the basis of the sea surface temperatures in key regions. After considering the impact of the spring TPT, the explanatory variance of the prediction equation for precipitation in the North China–Hetao region increases by 17.3%.
Mental Health Stressors in Higher Education Instructors and Students in Mexico During the Emergency Remote Teaching Implementation due to COVID-19
Authors: Zapata-Garibay Rogelio , González-Fagoaga Jesús Eduardo , Asadi-González Ahmed Ali , Martínez-Alvarado Julio Román , Chavez-Baray Silvia M. , Plascencia-López Ismael , González-Fagoaga Clara Judith
Published: June 2021

The COVID 19 pandemic has had a significant impact on the physical and emotional health of the population. In the case of specific populations, such as students and instructors, the change in the teaching-learning model has required both groups to adapt to online learning platforms and modify all academic activities in the context of implementing the emergency remote education model. The relevance of mental health has been continually neglected; however, due to the COVID-19 epidemiological outbreak, the impact of confinement on populations’ mental health has been incorporated into public discussion. In particular, the health emergency’s impact on health workers in the first line of care has been highlighted. The effect of mental health on the lockdown population and those encouraged to work from home, a group in which university professors and students are located, has been emphasized. To understand the changes faced by higher education instructors and students, derived from the implementation of the emergency remote teaching model in the context of the pandemic, we developed a study to investigate the experiences of this sector, with particular emphasis on the mental health stressors associated with their academic activities. We examined indicators related to anxiety, depression, motivation-demotivation, coping, and contextual and family conditions that could generate stress in the teaching-learning process during the emergency remote teaching model. We recruited a sample of 1,040 participants (380 instructors and 660 students) from more than 97 universities and 118 academic programs across the country. As a result, we have found that teachers have faced less difficulty with the teaching-learning model changes and how they deal with confinement. Similarly, this study has identified that women in general, both instructors and students, have more significant signs and symptoms related to mental health conditions, while men, both instructors, and students, resent the lack of socialization in the work and study centers environments.
Sediments and Seashores - A Case Study of Local Citizen Science Contributing to Student Learning and Environmental Citizenship
Authors: Carson Sally , Rock Jenny , Smith Jeffery
Published: June 2021

Citizen science aims to bridge the gap between science and society by engaging people in understanding the process of science. This is needed to foster informed democratic involvement of critical, environmentally informed citizens. Can these aspirations be facilitated by school-based citizen science that offers opportunity to engage scientifically with environmental issues at a scale with local relevance? This is tested through application of Marine Metre Squared (Mm2), a citizen science initiative for long-term monitoring of the New Zealand intertidal zone. Through direct observation and “hands-on” engagement, participants are involved in place-based learning that connects them with nature. Strong interest from teachers and uptake into school programmes has been key to its success in collecting long term biodiversity data. Through facilitated delivery, the project also has the capacity to meet school curriculum goals and develop the environmental science citizenship capabilities of participants. Assessing the use of Mm2 as a citizen science intervention within schools, we found that it affected science learning, skill development and environmental attitudes. Our findings further demonstrate the effect of extended involvement in a citizen science project, the value of a local issue-focused project for student learning outside the classroom, and how school science education can be enriched through citizen science to also grow civic responsibility for the environment (environmental citizenship).
Case Report: Severe Hypocalcemic Episodes Due to Autoimmune Enteropathy
Authors: Halabi Inbal , Barohom Marie Noufi , Peleg Sarit , Trougouboff Phillippe , Elias-Assad Ghadir , Agbaria Rhania , Tenenbaum-Rakover Yardena
Published: June 2021

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare monogenic disorder, associated with endocrine deficiencies and non-endocrine involvement. Gastrointestinal (GI) manifestations appear in approximately 25% of patients and are the presenting symptom in about 10% of them. Limited awareness among pediatricians of autoimmune enteropathy (AIE) caused by destruction of the gut endocrine cells in APECED patients delays diagnosis and appropriate therapy. We describe an 18-year-old female presenting at the age of 6.10 years with hypoparathyroidism, oral candidiasis and vitiligo. The clinical diagnosis of APECED was confirmed by sequencing the autoimmune regulator-encoding (AIRE) gene. Several characteristics of the disease—Hashimoto’s thyroiditis, Addison’s disease, diabetes mellitus type 1 and primary ovarian insufficiency—developed over the years. She had recurrent episodes of severe intractable hypocalcemia. Extensive GI investigations for possible malabsorption, including laboratory analyses, imaging and endoscopy with biopsies were unremarkable. Revision of the biopsies and chromogranin A (CgA) immunostaining demonstrated complete loss of enteroendocrine cells in the duodenum and small intestine, confirming the diagnosis of AIE. Management of hypocalcemia was challenging. Only intravenous calcitriol maintained calcium in the normal range. Between hypocalcemic episodes, the proband maintained normal calcium levels, suggesting a fluctuating disease course. Repeated intestinal biopsy revealed positive intestinal CgA immunostaining. The attribution of severe hypocalcemic episodes to AIE emphasizes the need for increased awareness of this unique presentation of APECED. The fluctuating disease course and repeated intestinal biopsy showing positive CgA immunostaining support a reversible effect of GI involvement. CgA immunostaining is indicated in patients with APECED for whom all other investigations have failed to reveal an explanation for the malabsorption.
Free Thyroxine Levels are Associated with Cold Induced Thermogenesis in Healthy Euthyroid Individuals
Authors: Maushart Claudia Irene , Senn Jaël Rut , Loeliger Rahel Catherina , Kraenzlin Marius E. , Müller Julian , Becker Anton S. , Balaz Miroslav , Wolfrum Christian , Burger Irene A. , Betz Matthias Johannes
Published: June 2021

Thyroid hormone (TH) is an important regulator of mammalian metabolism and facilitates cold induced thermogenesis (CIT) in brown adipose tissue (BAT). Profound hypothyroidism or hyperthyroidism lead to alterations in BAT function and CIT. In euthyroid humans the inter-individual variation of thyroid hormones is relatively large. Therefore, we investigated whether levels of free thyroxine (T4) or free triiodothyronine (T3) are positively associated with CIT in euthyroid individuals. We performed an observational study in 79 healthy, euthyroid volunteers (mean age 25.6 years, mean BMI 23.0 kg · m-2). Resting energy expenditure (REE) was measured by indirect calorimetry during warm conditions (EEwarm) and after a mild cold stimulus of two hours (EEcold). CIT was calculated as the difference between EEcold and EEwarm. BAT activity was assessed by 18F-FDG-PET after a mild cold stimulus in a subset of 26 participants. EEcold and CIT were significantly related to levels of free T4 (R2 = 0.11, p=0.0025 and R2 = 0.13, p=0.0011, respectively) but not to free T3 and TSH. Cold induced BAT activity was also associated with levels of free T4 (R2 = 0.21, p=0.018). CIT was approximately fourfold higher in participants in the highest tertile of free T4 as compared to the lowest tertile. Additionally, free T4 was weakly, albeit significantly associated with outdoor temperature seven days prior to the respective study visit (R2 = 0.06, p=0.037). These finding suggests that variations in thyroid hormone levels within the euthyroid range are related to the capability to adapt to cool temperatures and affect energy balance.
Adrenocortical Carcinoma Steroid Profiles: In Silico Pan-Cancer Analysis of TCGA Data Uncovers Immunotherapy Targets for Potential Improved Outcomes
Authors: Muzzi João C. D. , Magno Jessica M. , Cardoso Milena A. , de Moura Juliana , Castro Mauro A. A. , Figueiredo Bonald C.
Published: June 2021

Despite progress in understanding the biology of adrenocortical carcinoma (ACC), treatment options have not dramatically changed in the last three decades, nor have we learned how to avoid some of its long-term side effects. Our goal was to improve the understanding of immune pathways that may include druggable targets to enhance immune responses of patients with ACC, focusing on immune evasion and the activation of immune cells against ACC. Our strategy was aimed at improving insight regarding gene expression without steroid interference. Using approaches based on high and low steroid phenotypes (HSP and LSP, respectively), we characterized immune pathways using The Cancer Genome Atlas (TCGA) ACC cohort data. Although previous studies have suggested that patients with ACC receive minimal benefit from immunotherapy, high expression of immune modulators was noted in patients with LSP, suggesting the activation of these biomarkers may be an important adjuvant therapy target after clearance of excess glucocorticoids. In addition, patients with LSP ACC had higher immune cell infiltration than patients with HSP ACC and other cancer subtypes. Our findings can be summarized as follows (1): we confirmed and improved the definition of two immune response pathways to ACC (HSP and LSP) based on in silico transcriptome analysis (2), we demonstrated the steroid profile should be considered, otherwise analyses of ACC immune characteristics can generate confounding results (3), among the overexpressed immunotherapy targets, we demonstrated that LSP was rich in PDCD1LG2 (PD-L2) and both HSP and LSP overexpressed CD276 (B7-H3), which was associated with resistance to anti-PD1 therapy and may have accounted for the modest results of previous clinical trials, and (4) identification of patients with LSP or HSP ACC can be used to help determine whether immunotherapy should be used. In conclusion, we highlighted the differences between LSP and HSP, drawing attention to potential therapeutic targets (CD276, PDCD1, and PDCD1LG2). Treatments to reduce immune evasion, as well as the use of other natural and pharmacological immune activators, should include prior pharmacological inhibition of steroidogenesis. Attempts to combine these with tumor cell proliferation inhibitors, if they do not affect cells of the immune system, may produce interesting results.
Does Exist a Differential Impact of Degarelix Versus LHRH Agonists on Cardiovascular Safety? Evidences From Randomized and Real-World Studies
Authors: Sciarra Alessandro , Busetto Gian Maria , Salciccia Stefano , Del Giudice Francesco , Maggi Martina , Crocetto Felice , Ferro Matteo , De Berardinis Ettore , Scarpa Roberto Mario , Porpiglia Francesco , Carmignani Luca , Damiano Rocco , Artibani Walter , Carrieri Giuseppe
Published: June 2021

The main systemic therapy for the management of hormone-sensitive prostate cancer (PC) is androgen deprivation therapy (ADT), with the use of long-acting luteinizing hormone releasing-hormone (LHRH) agonists considered the main form of ADT used in clinical practice to obtain castration in PC. The concomitant administration of antiandrogens for the first weeks could reduce the incidence of clinical effects related to the testosterone flare-up in the first injection of LHRH. On the contrary, Gonadotropin Rh (GnRH) antagonists produce a rapid decrease of testosterone levels without the initial flare-up, with degarelix commonly used in clinical practice to induce castration in PC patients. Even if no long-term data are reported in terms of survival to define a superiority of GnRH or LHRH, for oncological efficacy and PC control, data from randomized clinical trials and from real-life experiences, suggest a difference in cardiovascular risk of patients starting ADT. The age-related decline in testosterone levels may represent a factor connected to the increase of cardiovascular disease risk, however, the role of ADT in increasing CV events remains controversial. For these reasons, the aim of the paper is to synthesize the difference in cardiovascular risk between LHRH and degarelix in patients undergoing ADT. A difference in cardiovascular risk could be indeed an important parameter in the evaluation of these two forms of castration therapy. The Randomized trials analyzed in this paper sustain a possible protective role for degarelix versus LHRH agonists in reducing the rate of new CV events and interventions in the short-term period. On the contrary, real-word data are contradictory in different national experiences and are strongly conditioned by huge differences between the LHRH agonists group and the degarelix group.
Study on Dispersion of Carbon Dioxide over the Shrubbery Region
Authors: Huiru Wang , Zhanping You , Fan Mo , Bin Liu , Peng Han
Published: June 2021

In the carbon capture and storage (CCS) infrastructure, the risk of a high-pressure buried pipeline rupture possibly leads to catastrophic accidents due to the release of tremendous amounts of carbon dioxide (CO2). Therefore, a comprehensive understanding of the effects of CO2 dispersion pattern after release from CCS facilities is essential to allow the appropriate safety precautions to be taken. Due to variations in topography above the pipeline, the pattern of CO2 dispersion tends to be affected by the real terrain features, such as trees and hills. However, in most previous studies, the dynamic impact of trees on the wind field was often approximated to linear treatment or even ignored. In this article, a computational fluid dynamics (CFD) model was proposed to predict CO2 dispersion over shrubbery areas. The shrubs were regarded as a kind of porous media, and the model was validated against the results from experiment. It was found that shrubbery affected the flow field near the ground, enhancing the lateral dispersion of CO2. Compared with that of the shrub-free terrain, the coverage area of the three shrub terrains at 60 s increased by 8.1 times, 6.7 times, and 9.1 times, respectively. The influence of shrub height and porosity on CO2 dispersion is nonlinear. This research provides reliable data for the risk assessment of CCS.
Characteristics and Mechanism of Pb2+ Adsorption From Aqueous Solution Onto Biochar Derived From Microalgae and Chitosan-Modified Microalgae
Authors: Liu Weigang , Li Kelin , Hu Xi , Hu Xinjiang , Zhang Ruibin , Li Qi
Published: June 2021

With increasing aquatic heavy metal pollution and eutrophication, using algae to prepare novel adsorbent materials for remediating heavy metal pollution has recently attracted research attention worldwide. However, microalgae biochar exhibits poor adsorption capacity in certain conditions, and little is known regarding microalgae biochar modification using chitosan. Chitosan has been previously used to directly modify microalgae biochar; however, in this study, chitosan is used to modify algae powder used to prepare biochar. Therefore, in this study, chitosan was used as a microalgae biochar modifier to enhance its applicability and adsorption capacity. Accordingly, two new types of microalgae biochars, chitosan-biochar (CTS-BC) and biochar-chitosan (BC-CTS), were developed as an adsorbent material using Clostridium and adding chitosan as a modifier at different stages of its preparation. These developed microalgae biochars were characterized using Brunauer–Emmett–Teller surface area,X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and scanning electron microscopy. The adsorption processes of these biochars can be well described by a pseudo-second-order kinetic model. Pb2+ was dominantly adsorbed by microalgal biochar through chemisorption. Following chitosan modification, several mino, cyano, and aromatic ring groups were attached onto the surface of the microalgal biochar. The Pb2+ adsorption capacity of the chitosan-modified biochar was better than that of the unmodified biochar. The maximum Pb2+ adsorption capacity of CTS-BC under acidic conditions (pH = 5) was 9.41 mg g−1, whereas that of BC-CTS under alkaline conditions (pH = 9) was 9.94 mg g−1, both were higher than that of unmodified microalgae biochar under similar conditions. CTS-BC and BC-CTS possessed excellent stability and reusability for Pb(II) adsorption, the adsorption efficiency still remained above 50% even after three cycles. This study demonstrated that adsorbent materials having a stronger heavy-metal adsorption capacity can be prepared by adding chitosan during different stages of the microalgae biochar preparation process.
Dual Effects of Synoptic Weather Patterns and Urbanization on Summer Diurnal Temperature Range in an Urban Agglomeration of East China
Authors: Guo Min , Zhang Minxuan , Wang Hong , Wang Linlin , Liu Shuhong , Zong Lian , Zhang Yanhao , Li Yubin
Published: June 2021

Previous studies on the impact of urbanization on the diurnal temperature range (DTR) have mainly concentrated on the intra-seasonal and interannual–decadal scales, while relatively fewer studies have considered synoptic scales. In particular, the modulation of DTR by different synoptic weather patterns (SWPs) is not yet fully understood. Taking the urban agglomeration of the Yangtze River Delta region (YRDUA) in eastern China as an example, and by using random forest machine learning and objective weather classification methods, this paper analyzes the characteristics of DTR and its urban–rural differences (DTRU–R) in summer from 2013 to 2016, based on surface meteorological observations, satellite remote sensing, and reanalysis data. Ultimately, the influences of urbanization-related factors and different large-scale SWPs on DTR and DTRU–R are explored. Results show that YRDUA is controlled by four SWPs in the 850-hPa geopotential height field in summer, and the DTRs in three sub-regions are significantly different under the four SWPs, indicating that they play a role in regulating the DTR in YRDUA. In terms of the average DTR for each SWP, the southern sub-region of the YRDUA is the highest, followed by the northern sub-region, and the middle sub-region is the lowest, which is most significantly affected by high-level urbanization and high anthropogenic heat emission. The DTRU–R is negative and differs under the four different SWPs with variation in sunshine and rainfall. The difference in anthropogenic heat flux between urban and rural areas is one of the potentially important urbanization-related drivers for DTRU–R. Our findings help towards furthering our understanding of the response of DTR in urban agglomerations to different SWPs via the modulation of local meteorological conditions.
Identifying Hypoxia Characteristics to Stratify Prognosis and Assess the Tumor Immune Microenvironment in Renal Cell Carcinoma
Authors: Zhang Zhenan , Li Qinhan , Wang Feng , Ma Binglei , Meng Yisen , Zhang Qian
Published: June 2021

Background: Renal cell carcinoma (RCC) is a common malignant tumor worldwide, and immune checkpoint inhibitors are a new therapeutic option for metastatic RCC. Infiltrating immune cells in the tumor microenvironment (TME) play a critical part in RCC biology, which is important for tumor therapy and prediction. Hypoxia is a common condition that occurs in the TME and may lead to RCC immunosuppression and immune escape. This study was conducted to analyze the extent of the hypoxia immune microenvironment in the TME of RCC and develop a hypoxia-related risk model for predicting the prognosis of patients with RCC.

Methods: The gene expression profiles of 526 patients with RCC were downloaded from The Cancer Genome Atlas database. Combined with the hallmark-hypoxia gene dataset downloaded from Gene Set Enrichment Analysis, prognosis-related hypoxia genes were selected by survival analysis. A protein–protein interaction network and functional enrichment analysis were performed. A hypoxia-related risk model predicting the prognosis of patients with RCC was established using the least absolute shrinkage and selection operator. Data of 91 cases downloaded from the International Cancer Genome Consortium (ICGC) database were used for validation. CIBERSORT was applied to analyze the fractions of 22 immune cell types in the TME of RCC between low- and high-risk groups. The expression profiles of immunomodulators and immunosuppressive cytokines were also analyzed.

Results: Ninety-three genes were significantly associated with poor overall survival of patients with RCC and were mainly involved in 10 pathways. Using the established hypoxia-related risk model, the receiver operating characteristic curves showed an accuracy of 76.1% (95% CI: 0.719–0.804), and Cox proportional hazards regression analysis revealed that the model was an independent predictor of the prognosis of patients with RCC [hazard ratio (HR) = 2.884; 95% CI: 2.090–3.979] (p < 0.001). Using the ICGC database, we verified that the low-risk score group had a better overall survival outcome than the high-risk group. Additionally, dividing the hypoxia risk score into high-risk and low-risk groups could predict the immune microenvironment of RCC.

Conclusions: We demonstrated that a hypoxia-related risk model can be used to predict the outcomes of patients with RCC and reflect the immune microenvironment of RCC, which may help improve the overall clinical response to immune checkpoint inhibitors.
Novel Hypoxia-Related Gene Signature for Risk Stratification and Prognosis in Hepatocellular Carcinoma
Authors: Li Quanxiao , Jin Limin , Jin Meng
Published: June 2021

Hepatocellular carcinoma (HCC) is the most common form of liver cancer with limited therapeutic options and low survival rate. The hypoxic microenvironment plays a vital role in progression, metabolism, and prognosis of malignancies. Therefore, this study aims to develop and validate a hypoxia gene signature for risk stratification and prognosis prediction of HCC patients. The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases were used as a training cohort, and one Gene Expression Omnibus database (GSE14520) was served as an external validation cohort. Our results showed that eight hypoxia-related genes (HRGs) were identified by the least absolute shrinkage and selection operator analysis to develop the hypoxia gene signature and demarcated HCC patients into the high- and low-risk groups. In TCGA, ICGC, and GSE14520 datasets, patients in the high-risk group had worse overall survival outcomes than those in the low-risk group (all log-rank P < 0.001). Besides, the risk score derived from the hypoxia gene signature could serve as an independent prognostic factor for HCC patients in the three independent datasets. Finally, a nomogram including the gene signature and tumor-node-metastasis stage was constructed to serve clinical practice. In the present study, a novel hypoxia signature risk model could reflect individual risk classification and provide therapeutic targets for patients with HCC. The prognostic nomogram may help predict individualized survival.
Polymerase Gamma Mitochondrial DNA Depletion Syndrome Initially Presenting as Disproportionate Respiratory Distress in a Moderately Premature Neonate: A Case Report
Authors: Franklin Andrew D. , Chaudhari Bimal P. , Koboldt Daniel C. , Machut Kerri Z.
Published: June 2021

A 32-week premature infant presented with respiratory failure, later progressing to pulmonary hypertension (PH), liver failure, lactic acidosis, and encephalopathy. Using exome sequencing, this patient was diagnosed with a rare Polymerase Gamma (POLG)-related mitochondrial DNA (mtDNA) depletion syndrome. This case demonstrates that expanding the differential to uncommon diagnoses is important for complex infants, even in premature neonates whose condition may be explained partially by their gestational age (GA). It also shows that patients with complex neonatal diseases with significant family history may benefit from exome sequencing for diagnosis.
Correlations Between the Characteristics of Alternative Splicing Events, Prognosis, and the Immune Microenvironment in Breast Cancer
Authors: Deng Youyuan , Zhao Hongjun , Ye Lifen , Hu Zhiya , Fang Kun , Wang Jianguo
Published: June 2021

Objective

Alternative splicing (AS) is the mechanism by which a few genes encode numerous proteins, and it redefines the concept of gene expression regulation. Recent studies showed that dysregulation of AS was an important cause of tumorigenesis and microenvironment formation. Therefore, we performed a systematic analysis to examine the role of AS in breast cancer (Breast Cancer, BrCa) progression.

Methods

The present study included 993 BrCa patients from The Cancer Genome Atlas (TCGA) database in the genome-wide analysis of AS events. We used differential and prognostic analyses and found differentially expressed alternative splicing (DEAS) events and independent prognostic factors related to patients’ overall survival (OS) and disease-free survival (DFS). We divided the patients into two groups based on these AS events and analyzed their clinical features, molecular subtyping and immune characteristics. We also constructed a splicing factor (SF) regulation network for key AS events and verified the existence of AS events in tissue samples using real-time quantitative PCR.

Results

A total of 678 AS events were identified as differentially expressed, of which 13 and 10 AS events were independent prognostic factors of patients’ OS and DFS, respectively. Unsupervised clustering analysis based on these prognostic factors indicated that the Cluster 1 group had a better prognosis and more immune cell infiltration. SFs were significantly related to the expression of AS events, and AA-RPS21 was significantly upregulated in tumors.

Conclusion

Alternative splicing expands the mechanism of breast cancer progression from a new perspective. Notably, alternative splicing may affect the patient’s prognosis by affecting the infiltration of immune cells. Our research provides important guidance for subsequent studies of AS in breast cancer.
The Role of Renal Macrophage, AIM, and TGF-β1 Expression in Renal Fibrosis Progression in IgAN Patients
Authors: Yang Min , Liu Jia Wei , Zhang Yu Ting , Wu Gang
Published: June 2021

Objective

To analyze the expression of macrophages, AIM, TGF-β1 in the kidney of IgAN patients, and to explore the role of macrophages, AIM, TGF-β1 in the progression of renal fibrosis in IgAN patients.

Methods

The paraffin specimens of renal tissue from 40 IgAN patients were selected as the observation group. At the same time, paraffin specimens of normal renal tissue from 11 patients treated by nephrectomy were selected as the normal control group. We observed the distribution of macrophages, the expression of AIM and TGF-β1 by immunohistochemical staining and/or immunofluorescence.

Result

The number of M0, M1, M2 macrophages could be found increased in IgAN patients. M0 macrophages are mainly polarized towards M2 macrophages. The expression of AIM and TGF-β1 were significantly higher in IgAN patients than in NC. M2 macrophage, AIM and TGF-β1 were positively correlated with serum creatinine and 24-hour proteinuria, but negatively correlated with eGFR. M2 macrophages, AIM, TGF-β1 were positively correlated with fibrotic area.

Conclusion

M2 macrophages, AIM and TGF-β1 play important roles in the process of IgAN fibrosis, and the three influence each other.