bluuebunny/crossref_metadata_2025 huggingface dataset:
Common Symptom, Rare Etiology: A Case Metastatic Cancers of Unknown Primary Origin Presenting with Epistaxis and Gingival Bleeding
Authors: Yalçınkaya Fatma , Uyaroğlu Oğuz Abdullah
Published: May 2021

Introduction
Epistaxis and gingival bleeding are among the most common presentation to the emergency department for patients with thrombocytopenia. Here, we present a case who was admitted to the emergency department with thrombocytopenia and was diagnosed with metastatic cancer of unknown primary
origin.

Case
A 26-year-old male patient was admitted to the emergency department with gingival bleeding and epistaxis. The body temperature was 38.3 °C. Petechial rash, ecchymosis or organomegaly was not detected on physical examination. Laboratory results revealed thrombocytopenia as 31x 10³ (159-388
x 10³/μL). Although hemoglobin and leukocyte counts were normal, no band or precursor cell was observed in the patient's peripheral blood smear. There was no history of weight loss, night sweats, arthritis, malar rash, photosensitivity, contact with ticks, animals, or a COVID-19 patient. Serological tests performed for infections such as HIV, EBV, HCV, Crimean-Congo hemorrhagic fever were negative. Bone marrow biopsy was performed due to the unexplained cytopenia, reported as "signet ring cell metastatic adenocarcinoma". Gastrointestinal system endoscopy was performed to detect primary cancer. A biopsy was taken from the antrum and corpus revealed gastritis. An FDG PET-CT was revealed heterogeneously pathologically increased FDG attitude in all axial and appendicular bones. Despite all the modalities of diagnosis, the origin was not found and the patient was transferred to the oncology department for treatment with a diagnosis of cancer of unknown origin with bone marrow infiltration.

Conclusions
Bone marrow metastases should be kept in mind in patients presenting with thrombocytopenia.
PENERAPAN PEMBELAJARAN KOOPERATIF MODEL NUMBER HEAD TOGETHER UNTUK MENINGKATKAN MOTIVASI DAN HASIL BELAJAR MATA KULIAH BAHASA INGGRIS
Authors: Imron Aly , Mujianto  , Ratnawati Yani
Published: May 2021

Metode belajar mengajar Numbered Heads Together berhubungan dengan banyak siswa untuk memeriksa pemahaman siswa tentang materi ajar. Metode ini memiliki beberapa prosedur yang diterapkan secara eksplisit untuk memberikan waktu yang cukup untuk berpikir, menjawab, dan saling membantu antar anggota dalam kelompok dan diharapkan dalam proses pembelajaran dapat meningkatkan hasil belajar yang lebih baik. Tujuannya adalah untuk mengetahui peningkatan motivasi belajar siswa dan hasil belajar siswa melalui penerapan pembelajaran kooperatif metode Numbered Heads Together pada mata pelajaran bahasa Inggris. Penelitian eksperimental ini menggunakan rancangan Penelitian Tindakan Kelas dengan menerapkan pendekatan kualitatif serta dilaksanakan dalam dua siklus yang meliputi perencanaan, pelaksanaan tindakan, observasi, dan refleksi. Hasil perbandingan siswa antara siklus I dan siklus II signifikan dan meningkat tajam, artinya siklus II cukup baik dilihat dari motivasi belajar siswa yang terdiri dari Minat (57,33%; 88)%, Konsentrasi (62,67%; 92%), perhatian (56%; 85,33%), ketekunan (61,33%; 87,33%). Peningkatan rata-rata sebesar 26% dari siklus pertama ke siklus kedua.
Mechanism of Laccase Induction via Emodin in Trametes versicolor
Authors: Wang Lin , Luo Xuecai , Pan Yu , Zheng Zai , Yin Ruochun , Tian Xiaohe , Zhang Liang
Published: May 2021

Secondary metabolites of traditional Chinese herbs can prominently stimulate the production of laccase from white rot fungi during submerged fermentation. However, the molecular mechanism through which these natural products induce the production of laccase remains unknown. In this study, the Chinese herbal medicine Polygonum cuspidatum was used to induce laccase production in Trametes versicolor, and the best inducer was identified in emodin, even under conditions of 1000-L, large-scale fermentation. Proteomics analysis identified a selection of proteins that were differentially expressed in the presence of emodin, indicating that emodin may affect the expression of laccase genes through three mechanisms: reducing bioenergy productivity, the aryl hydrocarbon receptor (AHR)/xenobiotic response element (XRE) pathway, and the nuclear erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway. Combined with protoplast flow cytometry and fluorescence, it is revealed that emodin might reduce the synthesis of ATP by lowering the mitochondrial membrane potential, leading to the subsequent responses.
Advances in Screening and Development of Therapeutic Aptamers Against Cancer Cells
Authors: Li Zheng , Fu Xuekun , Huang Jie , Zeng Peiyuan , Huang Yuhong , Chen Xinxin , Liang Chao
Published: May 2021

Cancer has become the leading cause of death in recent years. As great advances in medical treatment, emerging therapies of various cancers have been developed. Current treatments include surgery, radiotherapy, chemotherapy, immunotherapy, and targeted therapy. Aptamers are synthetic ssDNA or RNA. They can bind tightly to target molecules due to their unique tertiary structure. It is easy for aptamers to be screened, synthesized, programmed, and chemically modified. Aptamers are emerging targeted drugs that hold great potentials, called therapeutic aptamers. There are few types of therapeutic aptamers that have already been approved by the US Food and Drug Administration (FDA) for disease treatment. Now more and more therapeutic aptamers are in the stage of preclinical research or clinical trials. This review summarized the screening and development of therapeutic aptamers against different types of cancer cells.
Tangential Intrahypothalamic Migration of the Mouse Ventral Premamillary Nucleus and Fgf8 Signaling
Authors: López-González Lara , Alonso Antonia , García-Calero Elena , de Puelles Eduardo , Puelles Luis
Published: May 2021

The tuberal hypothalamic ventral premamillary nucleus (VPM) described in mammals links olfactory and metabolic cues with mating behavior and is involved in the onset of puberty. We offer here descriptive and experimental evidence on a migratory phase in the development of this structure in mice at E12.5–E13.5. Its cells originate at the retromamillary area (RM) and then migrate tangentially rostralward, eschewing the mamillary body, and crossing the molecularly distinct perimamillary band, until they reach a definitive relatively superficial ventral tuberal location. Corroborating recent transcriptomic studies reporting a variety of adult glutamatergic cell types in the VPM, and different projections in the adult, we found that part of this population heterogeneity emerges already early in development, during tangential migration, in the form of differential gene expression properties of at least 2–3 mixed populations possibly derived from subtly different parts of the RM. These partly distribute differentially in the core and shell parts of the final VPM. Since there is a neighboring acroterminal source of Fgf8, and Fgfr2 is expressed at the early RM, we evaluated a possible influence of Fgf8 signal on VPM development using hypomorphic Fgf8neo/null embryos. These results suggested a trophic role of Fgf8 on RM and all cells migrating tangentially out of this area (VPM and the subthalamic nucleus), leading in hypomorphs to reduced cellularity after E15.5 without alteration of the migrations proper.
Role of RNA N6-Methyladenosine Modification in Male Infertility and Genital System Tumors
Authors: Liu Shuai , Lao Yongfeng , Wang Yanan , Li Rongxin , Fang Xuefeng , Wang Yunchang , Gao Xiaolong , Dong Zhilong
Published: May 2021

Epigenetic alterations, particularly RNA methylation, play a crucial role in many types of disease development and progression. Among them, N6-methyladenosine (m6A) is the most common epigenetic RNA modification, and its important roles are not only related to the occurrence, progression, and aggressiveness of tumors but also affect the progression of many non-tumor diseases. The biological effects of RNA m6A modification are dynamically and reversibly regulated by methyltransferases (writers), demethylases (erasers), and m6A binding proteins (readers). This review summarized the current finding of the RNA m6A modification regulators in male infertility and genital system tumors and discussed the role and potential clinical application of the RNA m6A modification in spermatogenesis and male genital system tumors.
Understanding Reproductive Aging in Wildlife to Improve Animal Conservation and Human Reproductive Health
Authors: Comizzoli Pierre , Ottinger Mary Ann
Published: May 2021

Similar to humans and laboratory animals, reproductive aging is observed in wild species-from small invertebrates to large mammals. Aging issues are also prevalent in rare and endangered species under human care as their life expectancy is longer than in the wild. The objectives of this review are to (1) present conserved as well as distinctive traits of reproductive aging in different wild animal species (2) highlight the value of comparative studies to address aging issues in conservation breeding as well as in human reproductive medicine, and (3) suggest next steps forward in that research area. From social insects to mega-vertebrates, reproductive aging studies as well as observations in the wild or in breeding centers often remain at the physiological or organismal scale (senescence) rather than at the germ cell level. Overall, multiple traits are conserved across very different species (depletion of the ovarian reserve or no decline in testicular functions), but unique features also exist (endless reproductive life or unaltered quality of germ cells). There is a broad consensus about the need to fill research gaps because many cellular and molecular processes during reproductive aging remain undescribed. More research in male aging is particularly needed across all species. Furthermore, studies on reproductive aging of target species in their natural habitat (sentinel species) are crucial to define more accurate reproductive indicators relevant to other species, including humans, sharing the same environment. Wild species can significantly contribute to our general knowledge of a crucial phenomenon and provide new approaches to extend the reproductive lifespan.
EndMT Regulation by Small RNAs in Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress
Authors: Giordo Roberta , Ahmed Yusra M. A. , Allam Hilda , Abusnana Salah , Pappalardo Lucia , Nasrallah Gheyath K. , Mangoni Arduino Aleksander , Pintus Gianfranco
Published: May 2021

Diabetes-associated complications, such as retinopathy, nephropathy, cardiomyopathy, and atherosclerosis, the main consequences of long-term hyperglycemia, often lead to organ dysfunction, disability, and increased mortality. A common denominator of these complications is the myofibroblast-driven excessive deposition of extracellular matrix proteins. Although fibroblast appears to be the primary source of myofibroblasts, other cells, including endothelial cells, can generate myofibroblasts through a process known as endothelial to mesenchymal transition (EndMT). During EndMT, endothelial cells lose their typical phenotype to acquire mesenchymal features, characterized by the development of invasive and migratory abilities as well as the expression of typical mesenchymal products such as α-smooth muscle actin and type I collagen. EndMT is involved in many chronic and fibrotic diseases and appears to be regulated by complex molecular mechanisms and different signaling pathways. Recent evidence suggests that small RNAs, in particular microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are crucial mediators of EndMT. Furthermore, EndMT and miRNAs are both affected by oxidative stress, another key player in the pathophysiology of diabetic fibrotic complications. In this review, we provide an overview of the primary redox signals underpinning the diabetic-associated fibrotic process. Then, we discuss the current knowledge on the role of small RNAs in the regulation of EndMT in diabetic retinopathy, nephropathy, cardiomyopathy, and atherosclerosis and highlight potential links between oxidative stress and the dyad small RNAs-EndMT in driving these pathological states.
Molecular and Nonmolecular Imaging of Macrophages in Atherosclerosis
Authors: Li Zhaoyue , Tang Hao , Tu Yingfeng
Published: May 2021

Atherosclerosis is a major cause of ischemic heart disease, and the increasing medical burden associated with atherosclerotic cardiovascular disease has become a major public health concern worldwide. Macrophages play an important role in all stages of the dynamic progress of atherosclerosis, from its initiation and lesion expansion increasing the vulnerability of plaques, to the formation of unstable plaques and clinical manifestations. Early imaging can identify patients at risk of coronary atherosclerotic disease and its complications, enabling preventive measures to be initiated. Recent advances in molecular imaging have involved the noninvasive and semi-quantitative targeted imaging of macrophages and their related molecules in vivo, which can detect atheroma earlier and more accurately than conventional imaging. Multimodal imaging integrates vascular structure, function, and molecular imaging technology to achieve multi-dimensional imaging, which can be used to comprehensively evaluate blood vessels and obtain clinical information based on anatomical structure and molecular level. At the same time, the rapid development of nonmolecular imaging technologies, such as intravascular imaging, which have the unique advantages of having intuitive accuracy and providing rich information to identify macrophage inflammation and inform targeted personalized treatment, has also been seen. In this review, we highlight recent methods and research hotspots in molecular and nonmolecular imaging of macrophages in atherosclerosis that have enormous potential for rapid clinical application.
Medication Name Comprehension of Intelligent Virtual Assistants: A Comparison of Amazon Alexa, Google Assistant, and Apple Siri Between 2019 and 2021
Authors: Palanica Adam , Fossat Yan
Published: May 2021

The current study was a replication and comparison of our previous research which examined the comprehension accuracy of popular intelligent virtual assistants, including Amazon Alexa, Google Assistant, and Apple Siri for recognizing the generic and brand names of the top 50 most dispensed medications in the United States. Using the exact same voice recordings from 2019, audio clips of 46 participants were played back to each device in 2021. Google Assistant achieved the highest comprehension accuracy for both brand medication names (86.0%) and generic medication names (84.3%), followed by Apple Siri (brand names = 78.4%, generic names = 75.0%), and the lowest accuracy by Amazon Alexa (brand names 64.2%, generic names = 66.7%). These findings represent the same trend of results as our previous research, but reveal significant increases of ~10–24% in performance for Amazon Alexa and Apple Siri over the past 2 years. This indicates that the artificial intelligence software algorithms have improved to better recognize the speech characteristics of complex medication names, which has important implications for telemedicine and digital healthcare services.
The QBO Modulation on CO Distribution in the UTLS Over the Asian Monsoon Region During Boreal Summer
Authors: He Xin , Luo Jiali , Xu Xiran , Ren Lu , Tian Hongying , Shang Lin , Xu Pingping
Published: May 2021

Using the Microwave Limb Sounding measurements and the National Center for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) reanalysis product, we have investigated the response of carbon monoxide (CO) mixing ratio within the Asian Summer Monsoon Anticyclone (ASMA) region to the Quasi-Biennial Oscillation (QBO) and the potential dynamical mechanisms behind it. The results showed that the mixing ratio of CO within the ASMA is significantly higher at both 100 hPa and 147 hPa in the east phase of QBO (EQBO) years than in the west phase of QBO (WQBO) years, especially in the eastern part of the ASMA. The CO difference between EQBO and WQBO years is consistent with the interannual variation of the location and strength of the ASMA. Specifically, during the EQBO years, the area of the ASMA reduces to the southeast in the upper troposphere, while the westerly jet on the north side of the anticyclone and the southerly winds on the west side of the anticyclone both strengthen. These variations are associated with tropospheric circulation anomalies. The ascending motions over the Tibetan Plateau (TP) are enhanced during the EQBO years, which are correlated with the relatively high CO at 100 hPa. Consistently, an anomalous cyclonic circulation is found at 500 hPa over the TP when the QBO is on its east phase, which promotes the convergence of air mass and carries CO from the surface to the Upper Troposphere and Lower Stratosphere (UTLS).
Responses of Heat Stress to Temperature and Humidity Changes Due to Anthropogenic Heating and Urban Expansion in South and North China
Authors: Yang Shuai , Li Shuwen , Chen Bin , Xie Zeming , Peng Jing
Published: May 2021

Due to global warming and human activities, heat stress (HS) has become a frequent extreme weather event around the world, especially in megacities. This study aims to quantify the responses of urban HS (UHS) to anthropogenic heat (AH) emission and its antrophogenic sensible heat (ASH)/anthropogenic latent heat (ALH) components and increase in the size of cities in the south and north China for the 2019 summer based on observations and numerical simulations. AH release could aggravate UHS drastically, producing maximal increment in moist entropy (an effective HS metric) above 1 and 2 K over the south and north high-density urban regions mainly through ALH. In contrast, future urban expansion leads to an increase in HS coverage, and it has a larger impact on UHS intensity change (6 and 2 K in south and north China) relative to AH. The city radius of 60 km is a possible threshold to plan to city sprawl. Above that city size, the HS intensity change due to urban expansion tends to slow down in the north and inhibit in the south, and about one-third of the urban regions might be hit by extreme heat stress (EHS), reaching maximal hit ratio. Furthermore, changes in warmest EHS events are more associated with high humidity change responses, irrespective of cities being in the north or south of China, which support the idea that humidity change is the primary driving factor of EHS occurrence. The results of this study serve for effective urban planning and future decision making.
Spontaneous Thyroid Hemorrhage Caused by Langerhans Cell Histiocytosis: A Case Report and Literature Review
Authors: Zhang Jingying , Wang Chengchen , Lin Chuanshuai , Bai Binglong , Ye Mao , Xiang Dapeng , Li Zhiyu
Published: May 2021

Purpose

Langerhans cell histiocytosis (LCH) is a rare clonal disorder of Langerhans antigen-presenting cells. However, thyroid LCH involvement is relatively rare. We present the first case of spontaneous thyroid hemorrhage due to LCH progression and discuss the clinical features, diagnosis, and treatments of thyroid LCH in a literature review.

Methods

Clinical data were collected. Previously published articles on thyroid LCH involvement were reviewed to assess the clinical features, diagnosis, and treatments for thyroid LCH.

Results

A 54-year-old female presented with a multi-system LCH, affecting the uterus, liver, pituitary gland, and thyroid gland. Clinical stability was achieved after systemic chemotherapy. After 7 years of regular follow up, the patient complained of a sudden painful neck swelling and progressive dyspnea. Computed Tomography revealed bilateral goiter with hematoma, and the patient was diagnosed with spontaneous thyroid bleeding based on her clinical symptoms and radiological findings. The patient was incubated to relieve airway compromise and partial thyroidectomy was performed for definitive treatment. Pathological evaluation further confirmed the diagnosis of thyroid LCH. The patient recovered well after surgery.

Conclusion

Spontaneous thyroid bleeding due to thyroid LCH progression is extremely rare. Treatments for LCH vary depending on the severity of the disease. We suggest that, for patients with multi-system LCH with thyroid lesion, long-term active surveillance of thyroid hormone concentrations, and thyroid gland volume is required. Physicians should be alert of the potentially life-threatening spontaneous thyroid hemorrhage when aggravated diffuse goiter and hypothyroidism appear. Further investigation is required to establish the guidelines for thyroid LCH treatment.
Associations Between Thyroid Volume and Physical Growth in Pubertal Girls: Thyroid Volume Indexes Need to Be Applied to Thyroid Volume Assessments
Authors: Wang Yingying , Dong Xiaolian , Fu Chaowei , Su Meifang , Jiang Feng , Xu Dongli , Li Rui , Huang Peixin , Wang Na , Chen Yue , Jiang Qingwu
Published: May 2021

Background

Thyroid volume (Tvol) is associated with many factors, but the current reference values for Tvol in children with sufficient iodine intake are inappropriate and need to be updated. Moderate changes in thyroid morphology and accentuated increases in body fat percentage occur during puberty as an adaption of the body and sexual development occurs. This study aimed to evaluate the influences of physical growth on Tvol and propose an easily applicable method for conducting Tvol assessments in pubertal girls with sufficient iodine intake.

Methods

A cohort study was conducted on 481 pubertal girls in East China from 2017 to 2019. B-ultrasound was used to assess Tvol. Multiple linear regression models were used to estimate the associations of Tvol enlargement (dTvol) with changes in height (dH), weight (dW), waist circumference (dW), body mass index (dBMI), and body surface area (dBSA). Thyroid volume indexes (TVIs), including height thyroid volume index (HVI), weight and height thyroid volume index (WHVI), body mass index thyroid index (BMIV), and body surface area thyroid index (BSAV), were calculated to explore an appropriate method for Tvol assessments by Spearman correlation analyses.

Results

Tvol, height, weight, BMI, and BSA increased significantly from baseline to follow-up (P<0.001). The associations between dTvol and physical growth were only observed in the 13 to 14-year-old group. dH, dW,dBMI, and dBSA were positively related to dTvol, with the maximum β of 5.74 (95%CI: 2.54 to 8.94) on dBSA, while dWC was negatively related to dTvol (β= -0.05, 95%CI: -0.08 to -0.03). Both dHVI and dBSAV were not associated with dH, dW, dBMI, or dBSA in both age groups (P>0.05).

Conclusions

Thyroid volume was associated with physical growth in pubertal girls in East China, both age and anthropometric measurements must be comprehensively considered to establish the reference values for Tvol. HVI, and BSAV may be better indicators for Tvol assessments in pubertal girls.
Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers
Authors: Giannetta Elisa , Sesti Franz , Modica Roberta , Grossrubatscher Erika Maria , Guarnotta Valentina , Ragni Alberto , Zanata Isabella , Colao Annamaria , Faggiano Antongiulio
Published: May 2021

Background

Hypercalcemia is a common paraneoplastic syndrome which can occur in up to 10% of patients with advanced neoplasms. Paraneoplastic parathyroid hormone-related protein (PTHrP) represents the most frequent cause of this syndrome. In neuroendocrine neoplasms (NENs) paraneoplastic hypercalcemia is rare.

Case Series

The present series includes all patients with NENs and paraneoplastic hypercalcemia from four Italian centres: (I) A 40-year-old man was hospitalized for repeated episodes of falls, hyposthenia and drowsiness. Severe hypercalcemia was found. Metastatic pancreatic G2 NEN and PTHrP-related hypercalcemia were diagnosed. The patient started therapy with somatostatin analogs (SSA) and Denosumab. After disease progression peptide receptor radionuclide therapy (PRRT) was started with an objective response associated with PTHrP reduction and normocalcemia. (II) A 45-year-old man was referred for pancreatic G2 NEN. SSA and subsequently everolimus were administered for metastases occurrence. Hypercalcemia occurred and PRRT and Denosumab were started for disease progression with the onset of bone metastases. Despite disease stability after four cycles of PRRT the patient’s performance status worsened until death. (III) A 49-year-old woman was hospitalized for psychic slowdown, confusional state, sensory dullness. A severe hypercalcemia, associated with a pancreatic G1 NEN was diagnosed and treated with haemodialysis, bisphosphonates injections and continuous infusion of calcitonin. 1,25-dihydroxyvitamin D was high, PTHrP was undetectable. After surgery serum calcium levels and 1,25-dihydroxyvitamin D were normalized. (IV) A 69-year-old man was hospitalized after the onset of shortness of breath and dyspnea, asthenia and weight loss. Computed Tomography (CT) and 68Ga DOTATOC Positron Emission Tomography (PET)-CT revealed a left pulmonary nodule. Hypercalcemia and markedly elevated PTHrP levels were detected. The histological examination revealed an atypical carcinoid. After surgery, calcium levels were normalized, PTHrP was significantly reduced with an improvement of general conditions.

Conclusion

In our series, paraneoplastic PTHrP-related hypercalcemia occurred in pancreatic NEN and in one bronchial carcinoid representing the third case in the literature. Our case associated with 1,25-dihydroxyvitamin D secretion represents the fourth case in the literature. PTHrP secretion should be considered in NENs’ patients with hypercalcemia. Acute treatment should be focused on lowering calcium levels, and long-term control can be achieved by tumor cytoreduction inhibiting PTHrP release.
Transient Parameter Analysis of Non-scrammed Local Melting Accidents—A VVER 1000 Case Study
Authors: Salmassian Behzad , Rabiee Ataollah , Nematollahi Mohammad R. , Faghihi Farshad , Pirouzmand Ahmad
Published: May 2021

The first stage of a core degradation—based on the defense-in-depth concept of nuclear power plant (NPP) safety—is prone to fuel melting due to local blockage. The flow blockage accidents with no SCRAM happening can lead to a local fuel-clad failure, consequently affecting the safety of NPP. The present study provides an analysis of Anticipated Transient Without SCRAM (ATWS), which might lead to a condition of burning out. The accidents related to the ATWS scenarios, detailed in the case of VVER-1000/V446 reactor FSAR (Final Safety Analysis Report), include pump failure, local blockage, relative power increase, and a combination of these transients. In this research, first, drawing upon MCNPX 2.7 and COBRA-EN codes, a coupling framework is developed and then validated using an authentic reference point. The obtained results reveal that the reactor SCRAM does not occur while accidents are being investigated as there is a 10% difference in the mass flow rate reduction, a 470 kPa in the channel pressure drop, and a 204°K in the clad temperature, which constitute limitations under most pessimistic scenarios. However, under these conditions, a 70% void fraction over 12 min is observed in certain channels. Hence, burnout and local fuel melting could occur under normal operational and ATWS circumstances. According to uncertainty analyses, the occurrence of the void fraction above zero is locally definite. The transient analysis outputs could be deployed as monitoring system inputs and exploited for identifying weak points in the system.
Integrated Three-Dimensional Carbon Nanopolyhedron/Metal Sulfides: An Efficient Electrocatalyst Toward Oxygen Reduction Reaction
Authors: Yang Yi-Wen , Song Bing-Ye
Published: May 2021

Carbon-based materials hybridized with metal sulfides have gained growing attention as catalytic materials for oxygen reduction reaction (ORR) due to their synergistic effects in terms of richer structural features and higher electrochemical activities. Here, a series of Zn/Co/Fe-based metal-organic frameworks (MOFs) as the precursors, which can be adopted as efficient ORR catalysts, were synthesized through a sulfuration–calcination treatment. The effects of precursor composition, heteroatom doping, and pyrolysis temperature on the structure and electrochemical performance of the catalysts were discussed in detail. It is found that well-grown carbon nanotubes (CNTs) on the surface of graphitic carbon matrix are formed under the synergy effect of trimetallic-based species during pyrolysis. Benefiting from the three-dimensional unique structure with appropriate dopants and high porosity, the catalyst derived from the optimized Zn/Co/Fe-MOFs achieves a half-wave potential of 0.87 V in an alkaline medium for ORR, which is comparable with commercial electrocatalysts. In addition, an outstanding ORR durability of the proposed catalyst in alkaline media was also demonstrated. This work highlights the potential to rationally design and fabricate high-performance ORR catalysts for commercialization.
Techno-Economic Investigation of Using Solar Energy for Heating Swimming Pools in Buildings and Producing Hydrogen: A Case Study
Authors: Almutairi Khalid , Mostafaeipour Ali , Baghaei Negin , Techato Kuaanan , Chowdhury Shahariar , Jahangiri Mehdi , Rezaei Mostafa , Hosseini Dehshiri Seyyed Jalaladdin , Goudarzi Hossein , Issakhov Alibek
Published: May 2021

Solar energy is a free and environmentally friendly supply of power that has negligible impact on the environment, and it has long been used by humans through different methods. However, solar energy technology would use for heating water for buildings as an alternative resource, which would help reduce CO2 reduction and safe environment. A data analysis was performed using the RETScreen software, and the financial outcomes that were calculated using two methods. Clearly, the software is operational with two different methods. Both methods indicate that this project is economically feasible. The aim of this study is to evaluate the utilization of solar energy for household and commercial purposes. The first goal is to explore the technical, economic, and environmental aspects of using evacuated glass tube solar collectors to heat water in an indoor pool in the building, having an area of 50 m2, in the city of Yazd, Iran. The second goal is to evaluate the amount of hydrogen that can be obtained from the installation photovoltaic systems in the province. The results also show that this project will decrease greenhouse gas emissions by 142 ton-CO2 over 20 years of the useful life of a collector, thereby indicating the possible significant role of such collectors in the reduction of greenhouse gas emissions. Furthermore, the findings indicate that installing a single X21-345 photovoltaic system with a performance rate of 20% can result in the production of 2.1 kg of hydrogen annually.
Cell-Mediated Immune Ontogeny Is Affected by Sex but Not Environmental Context in a Long-Lived Primate Species
Authors: Behringer Verena , Deimel Caroline , Stevens Jeroen M. G. , Kreyer Melodie , Lee Sean M. , Hohmann Gottfried , Fruth Barbara , Heistermann Michael
Published: May 2021

Ecoimmunology conceptualizes the role of immunity in shaping life history in a natural context. Within ecoimmunology, macroimmunology is a framework that explains the effects of habitat and spatial differences on variation in immune phenotypes across populations. Within these frameworks, immune ontogeny—the development of the immune system across an individual life span—has received little attention. Here, we investigated how immune ontogeny from birth until adulthood is affected by age, sex, and developmental environment in a long-lived primate species, the bonobo. We found a progressive, significant decline of urinary neopterin levels, a marker for the cell-mediated immune response, from birth until 5 years of age in both sexes. The overall pattern of age-related neopterin changes was sex-specific, with males having higher urinary neopterin levels than females in the first 3 years of life, and females having higher levels than males between 6 and 8 years. Environmental condition (zoo-housed vs. wild) did not influence neopterin levels, nor did age-related changes in neopterin levels differ between environments. Our data suggest that the post-natal development of cell-mediated immune ontogeny is sex-specific but does not show plasticity in response to environmental conditions in this long-lived primate species. This indicates that cell-mediated immune ontogeny in the bonobo follows a stereotypic and maybe a genetically determined pattern that is not affected by environmental differences in pathogen exposure and energy availability, but that sex is an important, yet often overlooked factor shaping patterns of immune ontogeny. Investigating the causes and consequences of variation in immunity throughout life is critical for our understanding of life-history evolution and strategies, mechanisms of sexual selection, and population dynamics with respect to pathogen susceptibility. A general description of sex-specific immune ontogeny as done here is a crucial step in this direction, particularly when it is considered in the context of a species’ ecology and evolutionary history.
Transcriptome-Wide Identification of G-to-A RNA Editing in Chronic Social Defeat Stress Mouse Models
Authors: Tao Ji , Ren Chun-Yan , Wei Zhi-Yuan , Zhang Fuquan , Xu Jinyu , Chen Jian-Huan
Published: May 2021

Emerging evidence suggests that RNA editing is associated with stress, neurological diseases, and psychiatric disorders. However, the role of G-to-A RNA editing in chronic social defeat stress (CSDS) remains unclear. We herein identified G-to-A RNA editing and its changes in the ventral tegmental area (VTA), a key region of the brain reward system, in CSDS mouse models under emotional stress (ES) and physiological stress (PS) conditions. Our results revealed 3812 high-confidence G-to-A editing events. Among them, 56 events were significantly downregulated while 23 significantly upregulated in CSDS compared to controls. Moreover, divergent editing patterns were observed between CSDS mice under ES and PS conditions, with 42 and 21 events significantly upregulated in PS and ES, respectively. Interestingly, differential RNA editing was enriched in genes with multiple editing events. Genes differentially edited in CSDS included those genetically associated with mental or neurodevelopmental disorders, especially mood disorders, such as FAT atypical cadherin 1 and solute carrier family 6 member 1. Notably, changes of G-to-A RNA editing were also implicated in ionotropic glutamate receptors, a group of well-known targets of adenosine-to-inosine RNA editing. Such results demonstrate dynamic G-to-A RNA editing changes in the brain of CSDS mouse models, underlining its role as a potential molecular mechanism of CSDS and stress-related diseases.
Case Report: A Novel Heterozygous ZP3 Deletion Associated With Empty Follicle Syndrome and Abnormal Follicular Development
Authors: Chen Yongzhe , Wang Zesong , Wu Yueren , He Wenbin , Du Juan , Cai Sufen , Gong Fei , Lu Guangxiu , Lin Ge , Dai Can
Published: May 2021

Background: Empty follicle syndrome (EFS) is defined as the complete failure to retrieve oocytes after ovarian stimulation. Although several mutations in ZP1, ZP2, ZP3, and LHCGR have been identified as genetic causes of EFS, its pathogenesis is still not well-understood.

Methods: Whole-exome sequencing (WES) was employed to identify the candidate pathogenic mutations, which were then verified by Sanger sequencing. A study in CHO-K1 cells was performed to analyze the effect of the mutation on protein expression. Additionally, immunohistochemistry (IHC) staining was used to examine follicular development and zona pellucida (ZP) assembly in the ovary of an EFS patient.

Results: A novel heterozygous deletion in ZP3 (c.565_579del[p.Thr189_Gly193del]) was identified in the EFS patient. It was inherited dominantly and resulted in significant degradation of the ZP3 protein. Oocytes with degenerated cytoplasm and abnormal ZP assembly were observed in follicles up to the secondary stage, and many empty follicle-like structures were present.

Conclusion: We identified a novel ZP3 mutation that expands the mutational spectrum associated with human EFS. We also showed the abnormal follicular development and ZP assembly of the EFS patient with the heterozygous ZP3 mutation, which provides new insights into the pathogenesis of EFS.
Therapeutic Potential of TNFα and IL1β Blockade for CRS/ICANS in CAR-T Therapy via Ameliorating Endothelial Activation
Authors: Chen Yunshuo , Li Ranran , Shang Siqi , Yang Xuejiao , Li Lei , Wang Wenbo , Wang Yueying
Published: May 2021

Severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) strongly hampered the broad clinical applicability of chimeric antigen receptor T cell (CAR-T) therapy. Vascular endothelial activation has been suggested to contribute to the development of CRS and ICANS after CAR-T therapy. However, therapeutic strategies targeting endothelial dysfunction during CAR-T therapy have not been well studied yet. Here, we found that tumor necrosis factor α (TNFα) produced by CAR-T cells upon tumor recognition and interleukin 1β (IL1β) secreted by activated myeloid cells were the main cytokines in inducing endothelial activation. Therefore, we investigated the potential effectiveness of TNFα and IL1β signaling blockade on endothelial activation in CAR-T therapy. The blockade of TNFα and IL1β with adalimumab and anti-IL1β antibody respectively, as well as the application of focal adhesion kinase (FAK) inhibitor, effectively ameliorated endothelial activation induced by CAR-T, tumor cells, and myeloid cells. Moreover, adalimumab and anti-IL1β antibody exerted synergistic effect on the prevention of endothelial activation induced by CAR-T, tumor cells, and myeloid cells. Our results indicate that TNFα and IL1β blockade might have therapeutic potential for the treatment of CAR-T therapy-associated CRS and neurotoxicity.
Contribution of Heptose Metabolites and the cag Pathogenicity Island to the Activation of Monocytes/Macrophages by Helicobacter pylori
Authors: Faass Larissa , Stein Saskia C. , Hauke Martina , Gapp Madeleine , Albanese Manuel , Josenhans Christine
Published: May 2021

The human gastric pathogen Helicobacter pylori activates human epithelial cells by a particular combination of mechanisms, including NOD1 and ALPK1-TIFA activation. These mechanisms are characterized by a strong participation of the bacterial cag pathogenicity island, which forms a type IV secretion system (CagT4SS) that enables the bacteria to transport proteins and diverse bacterial metabolites, including DNA, glycans, and cell wall components, into human host cells. Building on previous findings, we sought to determine the contribution of lipopolysaccharide inner core heptose metabolites (ADP-heptose) in the activation of human phagocytic cells by H. pylori. Using human monocyte/macrophage-like Thp-1 cells and human primary monocytes and macrophages, we were able to determine that a substantial part of early phagocytic cell activation, including NF-κB activation and IL-8 production, by live H. pylori is triggered by bacterial heptose metabolites. This effect was very pronounced in Thp-1 cells exposed to bacterial purified lysates or pure ADP-heptose, in the absence of other bacterial MAMPs, and was significantly reduced upon TIFA knock-down. Pure ADP-heptose on its own was able to strongly activate Thp-1 cells and human primary monocytes/macrophages. Comprehensive transcriptome analysis of Thp-1 cells co-incubated with live H. pylori or pure ADP-heptose confirmed a signature of ADP-heptose-dependent transcript activation in monocyte/macrophages. Bacterial enzyme-treated lysates (ETL) and pure ADP-heptose–dependent activation differentiated monocytes into macrophages of predominantly M1 type. In Thp-1 cells, the active CagT4SS was less required for the heptose-induced proinflammatory response than in epithelial cells, while active heptose biosynthesis or pure ADP-heptose was required and sufficient for their early innate response and NF-κB activation. The present data suggest that early activation and maturation of incoming and resident phagocytic cells (monocytes, macrophages) in the H. pylori–colonized stomach strongly depend on bacterial LPS inner core heptose metabolites, also with a significant contribution of an active CagT4SS.
Dendritic Cells: Versatile Players in Renal Transplantation
Authors: Lin Jinwen , Wang Hongyi , Liu Chenxi , Cheng Ao , Deng Qingwei , Zhu Huijuan , Chen Jianghua
Published: May 2021

Dendritic cells (DCs) induce and regulate adaptive immunity through migrating and maturing in the kidney. In this procedure, they can adopt different phenotypes—rejection-associated DCs promote acute or chronic injury renal grafts while tolerogenic DCs suppress the overwhelmed inflammation preventing damage to renal functionality. All the subsets interact with effector T cells and regulatory T cells (Tregs) stimulated by the ischemia–reperfusion procedure, although the classification corresponding to different effects remains controversial. Thus, in this review, we discuss the origin, maturation, and pathological effects of DCs in the kidney. Then we summarize the roles of divergent DCs in renal transplantation: taking both positive and negative stages in ischemia–reperfusion injury (IRI), switching phenotypes to induce acute or chronic rejection, and orchestrating surface markers for allograft toleranceviaalterations in metabolism. In conclusion, we prospect that multidimensional transcriptomic analysis will revolute researches on renal transplantation by addressing the elusive mononuclear phagocyte classification and providing a holistic view of DC ontogeny and subpopulations.
Dopamine Levels Induced by Substance Abuse Alter Efficacy of Maraviroc and Expression of CCR5 Conformations on Myeloid Cells: Implications for NeuroHIV
Authors: Matt Stephanie M. , Nickoloff-Bybel Emily A. , Rong Yi , Runner Kaitlyn , Johnson Hannah , O’Connor Margaret H. , Haddad Elias K. , Gaskill Peter J.
Published: May 2021

Despite widespread use of antiretroviral therapy (ART), HIV remains a major public health issue. Even with effective ART many infected individuals still suffer from the constellation of neurological symptoms now known as neuroHIV. These symptoms can be exacerbated by substance abuse, a common comorbidity among HIV-infected individuals. The mechanism(s) by which different types of drugs impact neuroHIV remains unclear, but all drugs of abuse increase central nervous system (CNS) dopamine and elevated dopamine increases HIV infection and inflammation in human myeloid cells including macrophages and microglia, the primary targets for HIV in the brain. Thus, drug-induced increases in CNS dopamine may be a common mechanism by which distinct addictive substances alter neuroHIV. Myeloid cells are generally infected by HIV strains that use the chemokine receptor CCR5 as a co-receptor, and our data indicate that in a subset of individuals, drug-induced levels of dopamine could interfere with the effectiveness of the CCR5 inhibitor Maraviroc. CCR5 can adopt distinct conformations that differentially regulate the efficiency of HIV entry and subsequent replication and using qPCR, flow cytometry, Western blotting and high content fluorescent imaging, we show that dopamine alters the expression of specific CCR5 conformations of CCR5 on the surface of human macrophages. These changes are not affected by association with lipid rafts, but do correlate with dopamine receptor gene expression levels, specifically higher levels of D1-like dopamine receptors. These data also demonstrate that dopamine increases HIV replication and alters CCR5 conformations in human microglia similarly to macrophages. These data support the importance of dopamine in the development of neuroHIV and indicate that dopamine signaling pathways should be examined as a target in antiretroviral therapies specifically tailored to HIV-infected drug abusers. Further, these studies show the potential immunomodulatory role of dopamine, suggesting changes in this neurotransmitter may also affect the progression of other diseases.
Tryptophan Catabolites in Bipolar Disorder: A Meta-Analysis
Authors: Hebbrecht Kaat , Skorobogatov Katrien , Giltay Erik J. , Coppens Violette , De Picker Livia , Morrens Manuel
Published: May 2021

Objective

Tryptophan catabolites (TRYCATs) are implicated in the pathophysiology of mood disorders by mediating immune-inflammation and neurodegenerative processes. We performed a meta-analysis of TRYCAT levels in bipolar disorder (BD) patients compared to healthy controls.

Methods

A systematic literature search in seven electronic databases (PubMed, Embase, Web of Science, Cochrane, Emcare, PsycINFO, Academic Search Premier) was conducted on TRYCAT levels in cerebrospinal fluid or peripheral blood according to the PRISMA statement. A minimum of three studies per TRYCAT was required for inclusion. Standardized mean differences (SMD) were computed using random effect models. Subgroup analyses were performed for BD patients in a different mood state (depressed, manic). The methodological quality of the studies was rated using the modified Newcastle-Ottawa Quality assessment Scale.

Results

Twenty-one eligible studies were identified. Peripheral levels of tryptophan (SMD = -0.44; p < 0.001), kynurenine (SMD = - 0.3; p = 0.001) and kynurenic acid (SMD = -.45; p = < 0.001) were lower in BD patients versus healthy controls. In the only three eligible studies investigating TRP in cerebrospinal fluid, tryptophan was not significantly different between BD and healthy controls. The methodological quality of the studies was moderate. Subgroup analyses revealed no significant difference in TRP and KYN values between manic and depressed BD patients, but these results were based on a limited number of studies.

Conclusion

The TRYCAT pathway appears to be downregulated in BD patients. There is a need for more and high-quality studies of peripheral and central TRYCAT levels, preferably using longitudinal designs.
Missing in the Middle: A Review of Equatorially Disjunct Marine Taxa
Authors: Ludt William B.
Published: May 2021

Disjunct distributions of flora and fauna have intrigued biogeographers for centuries and have been central to debates over the roles that dispersal and vicariance have in speciation and evolutionary biology. One of the most notable disjunct distributions is when a single species or closely related taxa are present in temperate or polar regions of both hemispheres, but absent near the equator. Generally referred to as an anti-tropical distribution, this pattern is prevalent in marine taxa, occurring across the Tree of Life from single-celled bacteria and radiolarians, to algae, many invertebrates, fishes and marine mammals. The abundance of different species that exhibit this distribution pattern has led to a large number of theories on how it is formed and maintained. Here, seven central hypotheses that recur throughout the literature regarding the mechanisms responsible for this pattern are described and discussed in light of both historic and contemporary data. Recent advances in paleoclimate modeling and phylogenetic approaches have revealed that three of these hypotheses lack support. However, these data also highlight that a single driver of anti-tropicality is unlikely and that multiple mechanisms are responsible for this observed distribution pattern. The importance of using a multifaceted approach in future studies that incorporates phylogenetic, physiological, life history and ecological data is discussed, as there is a gap in our knowledge regarding adult and larval behavior, as well as thermal tolerances of many anti-tropical species. While recent studies have helped reveal some commonalities between anti-tropical groups, only by using an integrative approach will we be able to more fully understand which mechanisms are most prevalent in driving this pattern across the oceans.