bluuebunny/crossref_metadata_2025 huggingface dataset:
Review of Gastroretentive Drug Delivery System (GRDDS)
Authors: Annisa Viviane
Published: May 2021

Penghantaran obat oral memiliki keterbatasan terkait dengan absorpsi pada saluran pencernaan yang tidak sempurna. Absorpsi yang tidak sempurna ini dapat mempengaruhi tercapainya dosis terapi. Hal ini dipengaruhi oleh lambung karena adanya faktor Gastro Residence Time (GRT). Untuk meningkatkan absorpsi obat pada lambung, maka memerlukan sistem penghantaran obat yang dapat memperlama GRT. Salah satu penghantaran obat yang dapat memperlama GRT adalah Gastroretentive Drug Delivery System (GRDDS). Pengembangan GRDDS memiliki banyak keuntungan, seperti meningkatkan bioavailabilitas obat, meningkatkan kelarutan obat yang kurang larut dalam pH tinggi, dapat mengontrol level terapi sehingga mengurangi terjadinya fluktuasi, serta dapat memperpanjang waktu paruh sehingga frekuensi pemberian obat dapat dikurangi. Faktor yang dapat mempengaruhi formulasi GRDDS adalah faktor farmasetika, fisiologis, dan kondisi pasien. Terdapat beberapa sistem dalam formulasi GRDDS, seperti sistem floating, bioadesif, densitas tinggi, superporos, expandable, raft forming, dan magnetik. Sistem floating dapat melalui 2 mekanisme pembuatan, yakni secara effervescent dan non-effervescent. Telah banyak bentuk sediaan dengan sistem GRDDS yang diproduksi dalam skala industri sehingga dapat ditemukan di pasaran.
Uji Aktivitas Antihiperurisemia Ekstrak Daun Gatal (Laportea decumana (Roxb.) Wedd) Asal Papua
Authors: Simaremare Eva Susanty , Souisa Widya Veronicha
Published: May 2021

Daun gatal (Laportea decumana (Roxb.) Wedd) tersebar luas dari daerah pantai hingga pegunungan Papua yang dipercayai masyarakat dengan menempelkan daun pada bagian tubuh yang sakit akan dapat menyembuhkan. Daun gatal adalah tanaman asli Papua yang telah dipergunakan secara turun temurun oleh masyarakat Papua untuk berbagai pengobatan untuk mengatasi pegal, nyeri, reumatik, dan lain-lain. Hiperurisemia merupakan keadaan yang ditandai dengan adanya peningkatan kadar asam urat dalam darah melebihi normal. Tujuan dari penelitian ini adalah untuk mengetahui penurunan kadar antihiperurisemia ekstrak daun gatal pada mencit (Mus musculus). Penelitian ini menggunakan mencit sebagai hewan coba, sebanyak 24 ekor mencit dibagi menjadi 6 kelompok. Kelompok I tanpa diberi perlakuan, kelompok II diberi kontrol positif dari allopurinol 10 mg, kelompok III diberi kontrol negatif dari CMC-Na 0,5 mL/g BB, kelompok IV, V, dan VI diberi dosis ekstrak daun gatal 12,5mg / kg BB, 25mg / kg BB, dan 50mg / kg BB secara berurutan. Sebelum pemberian ekstrak daun gatal setiap mencit diberikan hati ayam hingga mendapatkan nilai total pemberian hati ayam, diukur dan digunakan alat uric acid sebagai kadar antihiperurisemia. Hasil pengujian dengan persentase penurunan kadar asam urat terbaik yaitu dengan dosis 50 mg/kg berat badan 20,5%, diikuti etil asetat 25 mg/Kg berat badan 15,25%, Kontrol negative dan 0,5 mL 15%.
Quanto valem esses corpos? Moradia, pobreza e pandemia na cidade de São Paulo
Authors: Mota André , Borysow Igor da Costa
Published: May 2021

Objetivamos identificar permanências históricas nas atuações dos governos municipais de São Paulo frente às epidemias e pandemias, considerando populações de moradias precárias e periféricas, em dois momentos: período de 1930 à 1970, e o primeiro ano da pandemia de Covid-19. Analisamos fontes jornalísticas e legislações em diálogo com a literatura existente sobre os períodos citados. O intenso processo de metropolização urbana, precarização das condições de moradia e de saneamento aprofundou as desigualdades sociais na cidade, a partir da alocação da população em determinados locais, das doenças que as abatiam, e da falta de acesso aos serviços médicos e de saúde, princi-palmente frente a epidemias. Em momentos de epidemias e pandemias, como a da COVID-19, os grupos mais vulneráveis têm reduzido seus corpos ao menor valor no jogo social, se tornando dispensáveis por parte da po-pulação e das autoridades de saúde pública, não incluídos adequadamente nas políticas assistenciais.
Conjunctival Provocation Test With Blomia tropicalis
Authors: Mourao Elizabeth Maria Mercer , Rosario Nelson Augusto
Published: May 2021

Background: Conjunctival provocation test (CPT) is used to demonstrate clinical relevance to a specific allergen. Blomia tropicalis (Bt) is a prevalent allergen in tropical regions. Its major allergen Blo t 5 is commonly detected in house dust in Brazil. Patients with allergic rhinoconjunctivitis (ARC) have IgE antibodies to Bt although it may not indicate clinical allergy.

Objective: The purpose of this study is to demonstrate the role of CPT in clinical allergy to Bt in allergic conjunctivitis (AC).

Methods: CPT was performed in asymptomatic subjects with ARC (n = 26) outside the grass pollen season. They had positive skin prick tests (SPT) to Bt and other common inhalant allergens and they were off topical or systemic antihistamines. Standardized allergens were used for CPT (Blo t 5 462.5 ng/mL in 1:1 solution, Alk Abelló). CPT was conducted on a control group of subjects (n = 29) without symptoms of ARC and with negative SPT. CPT was performed with progressive doses of allergen solutions in normal saline (1:32, 1:16, 1:8, 1:4, 1:2). CPT with the same allergen dose that elicited a positive reaction was repeated one week later. The protocol was approved by the local Ethics Board and signed informed consent was obtained from all participants.

Results: There were 92% (24/26) of positive CPT in subjects sensitized to Bt. Significant association was found between SPT and CPT results with Bt (p < 0.0001). CPT had 92% sensitivity and 100% specificity when compared to SPT results. Positive reactions with the same dose or one immediately higher occurred in 21 out of 22 subjects who repeated TPC 1 week later. Mild transient nasal symptoms (21/24) were the major side effects of positive CPT followed by moderate periorbital edema which occurred in 41% (10/24). One controlled asthmatic BT-sensitized subject developed wheezing and dyspnea during a positive CPT with Bt that cleared with inhaled albuterol (400 mcg). There were no reactions whatsoever of CPT in non-allergic subjects.

Conclusion: This study demonstrated that Bt may cause allergic conjunctivitis in our population. In addition, CPT is a safe and reproducible test if standardized allergens are used.
Perspective Applications and Associated Challenges of Using Nanocellulose in Treating Bone-Related Diseases
Authors: Khan Suliman , Siddique Rabeea , Huanfei Ding , Shereen Muhammad Adnan , Nabi Ghulam , Bai Qian , Manan Sehrish , Xue Mengzhou , Ullah Muhammad Wajid , Bowen Hu
Published: May 2021

Bone serves to maintain the shape of the human body due to its hard and solid nature. A loss or weakening of bone tissues, such as in case of traumatic injury, diseases (e.g., osteosarcoma), or old age, adversely affects the individual’s quality of life. Although bone has the innate ability to remodel and regenerate in case of small damage or a crack, a loss of a large volume of bone in case of a traumatic injury requires the restoration of bone function by adopting different biophysical approaches and chemotherapies as well as a surgical reconstruction. Compared to the biophysical and chemotherapeutic approaches, which may cause complications and bear side effects, the surgical reconstruction involves the implantation of external materials such as ceramics, metals, and different other materials as bone substitutes. Compared to the synthetic substitutes, the use of biomaterials could be an ideal choice for bone regeneration owing to their renewability, non-toxicity, and non-immunogenicity. Among the different types of biomaterials, nanocellulose-based materials are receiving tremendous attention in the medical field during recent years, which are used for scaffolding as well as regeneration. Nanocellulose not only serves as the matrix for the deposition of bioceramics, metallic nanoparticles, polymers, and different other materials to develop bone substitutes but also serves as the drug carrier for treating osteosarcomas. This review describes the natural sources and production of nanocellulose and discusses its important properties to justify its suitability in developing scaffolds for bone and cartilage regeneration and serve as the matrix for reinforcement of different materials and as a drug carrier for treating osteosarcomas. It discusses the potential health risks, immunogenicity, and biodegradation of nanocellulose in the human body.
CORO6 Promotes Cell Growth and Invasion of Clear Cell Renal Cell Carcinoma via Activation of WNT Signaling
Authors: Wang Xinjun , Xiao Yiming , Li Si , Yan Zhijian , Luo Guangcheng
Published: May 2021

Renal cell carcinoma (RCC) constitutes the most lethal type of genitourinary cancer. Understanding of RCC tumor biology helps to identify novel targets and develop directed treatments for patients with this type of cancer. Analysis from both The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma dataset and our RCC samples demonstrated that the expression level of CORO6 was significantly higher in RCC patients than in normal kidney tissues, and its level was highly associated with tumor stage and grade. Importantly, CORO6 expression level was an independent predictor of tumor metastasis and overall survival in RCC patients. Our cell line data also confirmed that CORO6 knockdown could suppress RCC cell growth as well as cell migration and invasion. The depletion of CORO6 led to cell cycle arrest at the G0/G1 phase and caused cell apoptosis. Further, mechanistic dissection showed that CORO6 mediated RCC cell growth, and cell invasion relied on WNT signaling. Moreover, thein vivodata suggested that CORO6 knockdown indeed suppressed RCC tumor growth. Overall, our study defines the oncogenic role of CORO6 in RCC progression and provides a rationale for developing CORO6-targeted therapies for improved treatment of RCC patients.
NADPH Oxidase 5 and Melatonin: Involvement in Ram Sperm Capacitation
Authors: Miguel-Jiménez Sara , Pina-Beltrán Blanca , Gimeno-Martos Silvia , Carvajal-Serna Melissa , Casao Adriana , Pérez-Pe Rosaura
Published: May 2021

Reactive oxygen species (ROS) play an essential role in mammalian sperm capacitation. NADPH oxidase 5 (NOX5) has been described as the main source of ROS production in some mammalian spermatozoa, such as human and equine. On the other hand, melatonin can decrease cellular ROS levels and regulates NOX activity in somatic cells. Therefore, the objectives of this work were (1) to identify NOX5 in ram spermatozoa and analyze its possible changes duringin vitrocapacitation and (2) to investigate the effect of melatonin on NOX5 expression and localization and on superoxide levels in capacitated ram spermatozoa. Protein bands associated with NOX5 were detected by Western blot analysis. Likewise, indirect immunofluorescence (IIF) revealed six different immunotypes for NOX5, which varied throughoutin vitrocapacitation. Superoxide (O2⋅–), evaluated by DHE/Yo-Pro-1, rose afterin vitrocapacitation and in the presence of the calcium ionophore A23187 but decreased in the presence of the NOX inhibitor GKT136901. GKT also reduced the percentage of capacitated and acrosome-reacted spermatozoa that had increased during incubation in capacitating conditions. The presence of melatonin at micromolar concentrations avoided the increment in O2⋅–and the changes in NOX5 immunotypes provoked by capacitation. In conclusion, NOX5 is present in ram spermatozoa and the changes in its distribution, associated with sperm capacitation, can be prevented by melatonin. To this extent, it could imply that melatonin exerts its antioxidant role, at least in part, by modulating NOX5 activity during ram sperm capacitation.
Applications of Surface-Enhanced Raman Scattering in Biochemical and Medical Analysis
Authors: Szaniawska Aleksandra , Kudelski Andrzej
Published: May 2021

In this mini-review, we briefly describe certain recently developed applications of the surface-enhanced Raman spectroscopy (SERS) for determining various biochemically (especially medically) important species from ones as simple as hydrogen cations to those as complex as specific DNA fragments. We present a SERS analysis of species whose characterization is important to our understanding of various mechanisms in the human body and to show its potential as an alternative for methods routinely used in diagnostics and clinics. Furthermore, we explain how such SERS-based sensors operate and point out future prospects in this field.
Targeting Epigenetics to Cure HIV-1: Lessons From (and for) Cancer Treatment
Authors: Svensson J. Peter
Published: May 2021

The Human Immunodeficiency Virus type 1 (HIV-1) integrates in the host genome as a provirus resulting in a long-lived reservoir of infected CD4 cells. As a provirus, HIV-1 has several aspects in common with an oncogene. Both the HIV-1 provirus and oncogenes only cause disease when expressed. A successful cure of both cancer and HIV-1 includes elimination of all cells with potential to regenerate the disease. For over two decades, epigenetic drugs developed against cancer have been used in the HIV-1 field to modulate the state of the proviral chromatin. Cells with an intact HIV-1 provirus exist in three states of infection: productive, inducible latent, and non-inducible latent. Here focus is on HIV-1, transcription control and chromatin structure; how the inducible proviruses are maintained in a chromatin structure that allows reactivation of transcription; and how transcription switches between different stages to allow for an abundance of different transcripts from a single promoter. Recently it was shown that a functional cure of HIV can be achieved by encapsulating all intact HIV-1 proviruses in heterochromatin, giving hope that epigenetic interventions may be used to end the HIV-1 epidemic.
When a Shark Is More Than a Shark: A Sociopolitical Problem-Solving Approach to Fisher-Shark Interactions
Authors: Iwane Mia A. , Leong Kirsten M. , Vaughan Mehana , Oleson Kirsten L. L.
Published: May 2021

Fisheries are often conceptualized through a biophysical lens resulting in management approaches that fail to account for stakeholder conflicts and sociopolitical inequities. Using a fisher engagement approach, this case study examines the sociopolitical dimensions of fisher-shark interactions in pursuit of more complete problem definitions and effective solutions. Through interviews with Hawai‘i small boat fishers and observations of a community-based shark-tagging project, we examined fisher perspective, socioeconomic landscapes, stakeholder relationships, and power dynamics. We interpreted these data using an adapted framework that mobilizes concepts from conflict theory and problem definition. We discovered that economic cost, sharks as fishing competitors, and factors of fishers' on-the-water decisions define the fisher-shark interaction problem at the dispute level. Deeper conflicts include fishers' poor perceptions of management legitimacy, degraded relationships with researchers and managers, threatened fisher identities, and poor enforcement capacity. Together, dispute and deeper conflicts limit the effectiveness of singular approaches (e.g., regulation) to mitigate fisher-shark interactions and necessitate multi-pronged solutions with substance-, process-, and relationships-based components. This case study documented one such multi-pronged strategy employing fisher-researcher knowledge exchange, collaborative research, and means of more transparent communication. This strategy has the potential to affect both dispute- and deeper-level outcomes by advancing collective understanding of sharks and shark-handling tools, fisher behavior, and reducing shark mortality. Thus, a sociopolitical approach to problem-solving may yield greater collective benefits to fisheries stakeholders and sharks, with broader implications for the systemic management of complex human and biophysical ecosystem components.
Role of N6-Methyladenosine RNA Modification in Cardiovascular Disease
Authors: Song Dandan , Hou Jianhua , Wu Junduo , Wang Junnan
Published: May 2021

Despite treatments being improved and many risk factors being identified, cardiovascular disease (CVD) is still a leading cause of mortality and disability worldwide. N6-methyladenosine (m6A) is the most common, abundant, and conserved internal modification in RNAs and plays an important role in the development of CVD. Many studies have shown that aabnormal m6A modifications of coding RNAs are involved in the development of CVD. In addition, non-coding RNAs (ncRNAs) exert post-transcriptional regulation in many diseases including CVD. Although ncRNAs have also been found to be modified by m6A, the studies on m6A modifications of ncRNAs in CVD are currently lacking. In this review, we summarized the recent progress in understanding m6A modifications in the context of coding RNAs and ncRNAs, as well as their regulatory roles in CVD.
Astrocyte-Neuron Metabolic Crosstalk in Neurodegeneration: A Mitochondrial Perspective
Authors: Mulica Patrycja , Grünewald Anne , Pereira Sandro L.
Published: May 2021

Converging evidence made clear that declining brain energetics contribute to aging and are implicated in the initiation and progression of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Indeed, both pathologies involve instances of hypometabolism of glucose and oxygen in the brain causing mitochondrial dysfunction, energetic failure and oxidative stress. Importantly, recent evidence suggests that astrocytes, which play a key role in supporting neuronal function and metabolism, might contribute to the development of neurodegenerative diseases. Therefore, exploring how the neuro-supportive role of astrocytes may be impaired in the context of these disorders has great therapeutic potential. In the following, we will discuss some of the so far identified features underlining the astrocyte-neuron metabolic crosstalk. Thereby, special focus will be given to the role of mitochondria. Furthermore, we will report on recent advancements concerning iPSC-derived models used to unravel the metabolic contribution of astrocytes to neuronal demise. Finally, we discuss how mitochondrial dysfunction in astrocytes could contribute to inflammatory signaling in neurodegenerative diseases.
A ‘Real Life’ Service Evaluation Model for Multidisciplinary Thyroid Eye Services
Authors: Farag Soma , Feeney Claire , Lee Vickie , Nagendran Sonali , Jain Rajni , Aziz Ahmad , Akishar Rashmi , Bravis Vassiliki , Meeran Karim
Published: May 2021

Background/Aims

There is no universal consensus on the practical implementation and evaluation of the Amsterdam Declaration on Graves Orbitopathy in a Multidisciplinary Thyroid Eye Disease (MDTED) pathway. Recent recommendations from the UK TEAMeD-5 and BOPSS initiative highlight the importance of prevention, screening, and prompt referral of patients with moderate to severe and sight-threatening thyroid eye disease to multidisciplinary (MDTED) clinics and recommends annual auditing. We propose a practical service evaluation model with Key Performance Indicators (KPI) that are achievable and could be implemented across most TED pathways.

Material and Methods

We conducted a service evaluation from an integrated TED pathway in London with three MDTED clinics. Data was collected retrospectively from consecutive TED patients included: 1) Patient demographics, 2) Referral to first appointment time, 3) Documented smoking cessation and selenium supplementation advice, 4) Presenting disease activity and severity, 5) Investigations and treatments, including radio-iodine, 6) Time from decision to treatment initiation, 7) Initial and subsequent thyroid status.

Results

The median age was 49.0 yrs, 77.5% (183/236) were female and 49.5% (101/204) Afro-Caribbean or Asian. At their first clinic attendance, 47.6% (110/231) were biochemically euthyroid and 76.7% (79/103) at discharge. All 23.1% (52/225) current smokers received smoking cessation advice and 64.8% (153/236) received selenium supplementation advice. Intravenous methylprednisolone was given to 33.9% (80/236) patients and 12.7% (30/236) received second-line immunosuppression. All 7.2% (17/236) patients with sight-threatening disease received treatment within two weeks of diagnosis.

Conclusions

This study forms a waymark for other units using TEAMeD-5 and BOPSS audit criteria. Dedicated electronic patient records with ongoing data capture, including quality of life assessments, and diagnostic coding would significantly aid future auditing, improve patient care, and facilitate a national audit of TED management. A future survey when the TED standards have become embedded would be instructive to see whether this has improved TED care.
Mouse Spexin: (III) Differential Regulation by Glucose and Insulin in Glandular Stomach and Functional Implication in Feeding Control
Authors: Chen Yuan , He Mulan , Lei Martina M. L. , Ko Wendy K. W. , Lin Chengyuan , Bian Zhaoxiang , Wong Anderson O. L.
Published: May 2021

Spexin (SPX), a neuropeptide with diverse functions, is a novel satiety factor in fish models and its role in feeding control has been recently confirmed in mammals. In mouse, food intake was shown to trigger SPX expression in glandular stomach with parallel rise in serum SPX and these SPX signals could inhibit feeding via central actions within the hypothalamus. However, the mechanisms for SPX regulation by food intake are still unclear. To examine the role of insulin signal caused by glucose uptake in SPX regulation, the mice were IP injected with glucose and insulin, respectively. In this case, serum SPX was elevated by glucose but not altered by insulin. Meanwhile, SPX transcript expression in the glandular stomach was up-regulated by glucose but the opposite was true for insulin treatment. Using in situ hybridization, the differential effects on SPX gene expression were located in the gastric mucosa of glandular stomach. Co-injection experiments also revealed that glucose stimulation on serum SPX and SPX mRNA expressed in glandular stomach could be blocked by insulin. In gastric mucosal cells prepared from glandular stomach, the opposite effects on SPX transcript expression by glucose and insulin could still be noted with similar blockade of the stimulatory effects of glucose by insulin. In this cell model, SPX gene expression induced by glucose was mediated by glucose uptake via GLUT, ATP synthesis by glycolysis/respiratory chain, and subsequent modulation of KATP channel activity, but the voltage-sensitive Ca2+ channels were not involved. The corresponding inhibition by insulin, however, was mediated by PI3K/Akt, MEK1/2/ERK1/2, and P38MAPK cascades coupled to insulin receptor but not IGF-1 receptor. Apparently, glucose uptake in mice can induce SPX expression in the glandular stomach through ATP synthesis via glucose metabolism and subsequent modification of KATP channel activity, which may contribute to SPX release into circulation to act as the satiety signal after food intake. The insulin rise caused by glucose uptake, presumably originated from the pancreas, may serve as a negative feedback to inhibit the SPX response by activating MAPK and PI3K/Akt pathways in the stomach.
Optimal Electricity Allocation Model Under China's Planning-Market Double-Track Mechanism Considering Bidding Game of Generation Companies
Authors: Cui Jinrui , Li Yating , He Chuan , Zhang Zhi , Wang Haichao , Tang Jiajun , Li Yongbo , Cai Hualin , Lin Zhenzhi , Yang Li
Published: May 2021

In China, under the planning-market double-track mechanism implemented on the generation side of electricity, unreasonable market-oriented power generation proportion may lead to unnecessary vicious competition and market price changes, and it is against the will of power exchange (PX). Given this background, in this study, a bi-level model for planning-market electricity allocation that considers the bidding game of generation companies is proposed for a smooth transition of power system reform. In the upper level of the model, the proportion of planned electricity is optimized by PX to minimize the average social electricity purchase price. In the lower level of the model, considering the impact of market power on the bidding strategy of generation companies, the bidding strategy of generation companies set as price makers is proposed using the residual demand curve analysis method, while the price takers adopt the lowest bidding strategy. Simulations based on data from a provincial electricity market in China illustrate that the proposed model can effectively reflect the impact of market-oriented electricity proportion on market power and market-clearing price, thus providing a quantitative basis for PX to determine the proportion of market-oriented electricity in total electricity consumption.
Full Life Cycle Management of Power System Integrated With Renewable Energy: Concepts, Developments and Perspectives
Authors: Wang Kang , Li Yikai , Wang Xiaojun , Zhao Zengtao , Yang Ning , Yu Shengcan , Wang Yi , Huang Zhanhong , Yu Tao
Published: May 2021

Under high-penetration of renewable energy, power grid is facing with the development problems such as production delay, wind and solar power abandoning. With the continuous growth of renewable energy installation such as wind power, photovoltaic (PV), as well as the increase of power generation capacity, it is urgent to increase peak-load and frequency regulation capacity on a large scale to alleviate the consumption problems caused by large renewable energy integration, and then requires power generation enterprises of peak-load and frequency regulation to increase relevant equipment assets. As a result, peak-load and frequency regulation enterprises must carry out scientific cost management of equipment assets. This paper introduces the concepts, developments and perspectives of life cycle cost (LCC) management of equipment assets in high-penetrated renewable energy power grid, and probes into cost collection and estimation scheme in the process of equipment asset management.
Physicochemical Characterization and Seasonal Variations of PM10 Aerosols in a Harsh Environment
Authors: Hamdan Nasser M. , Alawadhi Hussain , Shameer Mohamed
Published: May 2021

We have conducted a comprehensive sampling campaign of PM10 pollutants at a site next to a major highway, using standard protocols. Particulate matter (PM) total mass, elemental and chemical/mineral compositions of the fine and coarse fractions of traffic-related PM pollutants were determined using several complementary techniques, including gravimetric analysis, x-ray fluorescence, scanning electron microscopy, energy dispersive spectroscopy, and x-ray diffraction. The PM mass concentrations show that PM10 is within acceptable international standards except during dust storms within the sampled periods. Desert dust, crustal minerals, and sea salts are the major natural sources of PM10 pollution. Examples of these minerals are quartz [SiO2], calcite [CaCO3], gypsum [CaSO4·2H2O], palygorskite [(Mg,Al)2Si4O10(OH)•4(H2O], chlorite-serpentine [(Mg,Fe)6AlSi3O10(OH)8], halite [NaCl] and nitratine [NaNO3]. Anthropogenic mineral-based pollutants, such as mascagnite [(NH4)2SO4] and koktaite [(NH4)2Ca(SO4)2·H2O], were also observed to contribute to PM10. Trace elements such as Zn, Cu, Fe, Cr and Mn that are markers for traffic sources, Ni and V that are markers for heavy oil combustion, and Pb, which is attributed to industrial emissions, were also identified in PM10. Seasonal variation of the average total mass concentrations and the average mass concentration of elements emitted from natural sources show that the hot season is associated with higher pollution levels compared to the cold season due to increased dust events in the spring and summer. Correlation coefficients between elements have identified elements originating from common sources such as dust storms (e.g., Si, Ca, Al, Fe, Ti, Mn) and sea breeze (Cl and Na), in addition to anthropogenic elements. Enrichment factors calculations have identified elements that mainly have crustal origins, and elements that are partially or highly enriched by humans. Anthropogenic elements were more enriched during the cold season due to reduced human activities in the summer.
Evolutionary Change in Locomotion Close to the Origin of Amniotes Inferred From Trackway Data in an Ancestral State Reconstruction Approach
Authors: Buchwitz Michael , Jansen Maren , Renaudie Johan , Marchetti Lorenzo , Voigt Sebastian
Published: May 2021

Among amniote and non-amniote tetrapod trackways from late Carboniferous to early Permian deposits, certain trackway measures vary notably. Some of this variability can be attributed to evolutionary changes in trackmaker anatomy and locomotion style close to the origin of amniotes. Here we demonstrate that steps in early amniote locomotion evolution can be addressed by applying methods of ancestral state reconstruction on trackway data – a novel approach in tetrapod ichnology. Based on (a) measurements of 186 trackways referred to the Carboniferous and early Permian ichnogenera Batrachichnus, Limnopus, Hylopus, Amphisauropus, Matthewichnus, Ichniotherium, Dimetropus, Tambachichnium, Erpetopus, Varanopus, Hyloidichnus, Notalacerta and Dromopus, (b) correlation of these ichnotaxa with specific groups of amphibian, reptiliomorph, synapsid, and reptilian trackmakers based on imprint morphology and (c) known skeletal-morphology-based phylogenies of the supposed trackmakers, we infer ancestral states for functionally controlled trackway measures in a maximum likelihood approach. The most notable finding of our analysis is a concordant change in trackway parameters within a series of ancestral amniote trackmakers, which reflects an evolutionary change in locomotion: In the ancestors of amniotes and diadectomorphs, an increase in body size was accompanied by a decrease in (normalized) gauge width and glenoacetabular length and by a change in imprint orientation toward a more trackway-parallel and forward-pointing condition. In the subsequent evolution of diadectomorph, synapsid and reptilian trackmakers after the diversification of the clades Cotylosauria (Amniota + Diadectomorpha) and Amniota, stride length increased whereas gauges decreased further or remained relatively narrow within most lineages. In accordance with this conspicuous pattern of evolutionary change in trackway measures, we interpret the body size increase as an underlying factor that triggered the reorganization of the locomotion apparatus. The secondary increase in stride length, which occurred convergently within distinct groups, is interpreted as an increase in locomotion capability when the benefits of reorganization came into effect. The track-trackmaker pair of Ichniotherium sphaerodactylum and Orobates pabsti from the early Permian Bromacker locality of the Thuringian Forest, proposed in earlier studies as a suitable ancestral amniote track-trackmaker model, fits relatively well with our modeled last common ancestor of amniotes – with the caveat that the Bromacker material is younger and some of the similarities appear to be due to convergence.
Public Forests Under Threat in the Brazilian Amazon: Strategies for Coping Shifts in Environmental Policies and Regulations
Authors: Moraes Iranilda , Azevedo-Ramos Claudia , Pacheco Jessica
Published: May 2021

Brazil has 310.5 million hectares of public forests, almost 92% of which in the Amazon. Since the 1980s, Brazilian environmental legislation has been improving and, along with other measures, has contributed to a significant reduction in deforestation in the Amazon since 2005. However, changes in the legal framework and dismantling of successful socio-environmental policies threaten public forests in the Amazon. Here, we highlighted some relevant changes in the legal and political framework and prioritized some actions to safeguard the largest tropical forest in the world considering an adverse political context. We emphasized strategies associated with (1) the institutionalization of practices and processes; and (2) market-driven influence on sustainable production. The purpose is to inhibit current threats until more favorable and participatory circumstances are present and a comprehensive range of past success measures may be revisited.
Total Flavonoids of Glycyrrhiza uralensis Alleviates Irinotecan-Induced Colitis via Modification of Gut Microbiota and Fecal Metabolism
Authors: Yue Shi-Jun , Qin Yi-Feng , Kang An , Tao Hui-Juan , Zhou Gui-Sheng , Chen Yan-Yan , Jiang Jian-Qin , Tang Yu-Ping , Duan Jin-Ao
Published: May 2021

Irinotecan (CPT-11)-induced gastrointestinal toxicity strongly limits its anticancer efficacy. Glycyrrhiza uralensis Fisch., especially flavonoids, has strong anti-inflammatory and immunomodulatory activities. Herein, we investigate the protective effect of the total flavonoids of G. uralensis (TFGU) on CPT-11–induced colitis mice from the perspective of gut microbiota and fecal metabolism. The body weight and colon length of mice were measured. Our results showed that oral administration of TFGU significantly attenuated the loss of body weight and the shortening of colon length induced by CPT-11. The elevated disease activity index and histological score of colon as well as the up-regulated mRNA and protein levels of TNF-α, IL-1β, and IL-6 in the colonic tissue of CPT-11–treated mice were significantly decreased by TFGU. Meanwhile, TFGU restored the perturbed gut microbial structure and function in CPT-11–treated mice to near normal level. TFGU also effectively reversed the CPT-11–induced fecal metabolic disorders in mice, mainly call backing the hypoxanthine and uric acid in purine metabolism. Spearman’s correlation analysis further revealed that Lactobacillus abundance negatively correlated with fecal uric acid concentration, suggesting the pivotal role of gut microbiota in CPT-11–induced colitis. Since uric acid is a ligand of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, TFGU was further validated to inhibit the activation of NLRP3 inflammasome by CPT-11. Our findings suggest TFGU can correct the overall gut microbial dysbiosis and fecal metabolic disorders in the CPT-11–induced colitis mice, underscoring the potential of using dietary G. uralensis as a chemotherapeutic adjuvant.
In Situ Vaccination as a Strategy to Modulate the Immune Microenvironment of Hepatocellular Carcinoma
Authors: Lurje Isabella , Werner Wiebke , Mohr Raphael , Roderburg Christoph , Tacke Frank , Hammerich Linda
Published: May 2021

Hepatocellular Carcinoma (HCC) is a highly prevalent malignancy that develops in patients with chronic liver diseases and dysregulated systemic and hepatic immunity. The tumor microenvironment (TME) contains tumor-associated macrophages (TAM), cancer-associated fibroblasts (CAF), regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) and is central to mediating immune evasion and resistance to therapy. The interplay between these cells types often leads to insufficient antigen presentation, preventing effective anti-tumor immune responses. In situ vaccines harness the tumor as the source of antigens and implement sequential immunomodulation to generate systemic and lasting antitumor immunity. Thus, in situ vaccines hold the promise to induce a switch from an immunosuppressive environment where HCC cells evade antigen presentation and suppress T cell responses towards an immunostimulatory environment enriched for activated cytotoxic cells. Pivotal steps of in situ vaccination include the induction of immunogenic cell death of tumor cells, a recruitment of antigen-presenting cells with a focus on dendritic cells, their loading and maturation and a subsequent cross-priming of CD8+ T cells to ensure cytotoxic activity against tumor cells. Several in situ vaccine approaches have been suggested, with vaccine regimens including oncolytic viruses, Flt3L, GM-CSF and TLR agonists. Moreover, combinations with checkpoint inhibitors have been suggested in HCC and other tumor entities. This review will give an overview of various in situ vaccine strategies for HCC, highlighting the potentials and pitfalls of in situ vaccines to treat liver cancer.
Molecular and Biological Mechanisms Underlying Gender Differences in COVID-19 Severity and Mortality
Authors: Wehbe Zena , Hammoud Safaa Hisham , Yassine Hadi M. , Fardoun Manal , El-Yazbi Ahmed F. , Eid Ali H.
Published: May 2021

Globally, over two million people have perished due to the recent pandemic caused by SARS-CoV-2. The available epidemiological global data for SARS-CoV-2 portrays a higher rate of severity and mortality in males. Analyzing gender differences in the host mechanisms involved in SARS-CoV-2 infection and progression may offer insight into the more detrimental disease prognosis and clinical outcome in males. Therefore, we outline sexual dimorphisms which exist in particular host factors and elaborate on how they may contribute to the pronounced severity in male COVID-19 patients. This includes disparities detected in comorbidities, the ACE2 receptor, renin-angiotensin system (RAS), signaling molecules involved in SARS-CoV-2 replication, proteases which prime viral S protein, the immune response, and behavioral considerations. Moreover, we discuss sexual disparities associated with other viruses and a possible gender-dependent response to SARS-CoV-2 vaccines. By specifically highlighting these immune-endocrine processes as well as behavioral factors that differentially exist between the genders, we aim to offer a better understanding in the variations of SARS-CoV-2 pathogenicity.
CXCL8 Associated Dendritic Cell Activation Marker Expression and Recruitment as Indicators of Favorable Outcomes in Colorectal Cancer
Authors: Li Enhao , Yang Xiaobao , Du Yuzhang , Wang Guanzheng , Chan David W. , Wu Di , Xu Peiqing , Ni Peihua , Xu Dakang , Hu Yiqun
Published: May 2021

Accumulating evidence suggests that tumor-infiltrating immune cells (TICs) in the tumor microenvironment (TME) serve as promising therapeutic targets. CXCL8 (IL-8) may also be a potential therapeutic target in cancer. CXCL8 is a potent chemotactic factor for neutrophils, myeloid-derived suppressor cells (MDSCs) and monocytes, which are considered immunosuppressive components in cancer-bearing hosts. Here, we identified the TME-related gene CXCL8 in a high-ImmuneScore population that contributed to better survival in colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) database. An integrated gene profile and functional analysis of TIC proportions revealed that the dendritic cell (DC) activation markers CD80, CD83, and CD86 were positively correlated with CXCL8 expression, suggesting that CXCL8 may be functional as antitumor immune response status in the TME. The gene signature was further validated in independent GSE14333 and GSE38832 cohorts from the Gene Expression Omnibus (GEO). To test the differential contributions of immune and tumor components to progression, three CRC cell lines, CT26, MC38 and HCT116, were used. In vitro results suggested no significant growth or survival changes following treatment with an inhibitor of the CXCL8 receptor (CXCR1/2) such as reparixin or danirixin. In vivo treatment with danirixin (antagonists of CXCR2) promoted tumor progression in animal models established with CT26 cells. CXCR2 antagonism may function via an immune component, with CXCR2 antagonist treatment in mice resulting in reduced activated DCs and correlating with decreased Interferon gamma (IFN-γ) or Granzyme B expressed CD8+ T cells. Furthermore, CXCL8 induced DC migration in transwell migration assays. Taken together, our data suggested that targeting the CXCL8-CXCR2 axis might impede DC activation or recruitment, and this axis could be considered a favorable factor rather than a target for critical antitumor effects on CRC.
Inhibition of TLR4 Signaling Impedes Tumor Growth in Colitis-Associated Colon Cancer
Authors: Pastille Eva , Faßnacht Tabea , Adamczyk Alexandra , Ngo Thi Phuong Nhi , Buer Jan , Westendorf Astrid M.
Published: May 2021

Patients suffering from ulcerative colitis are at increased risk of developing colorectal cancer. Although the exact underlying mechanisms of inflammation-associated carcinogenesis remain unknown, the intestinal microbiota as well as pathogenic bacteria are discussed as contributors to inflammation and colitis-associated colon cancer (CAC). In the present study, we analyzed the impact of TLR4, the receptor for Gram-negative bacteria derived lipopolysaccharides, on intestinal inflammation and tumorigenesis in a murine model of CAC. During the inflammatory phases of CAC development, we observed a strong upregulation of Tlr4 expression in colonic tissues. Blocking of TLR4 signaling by a small-molecule-specific inhibitor during the inflammatory phases of CAC strongly diminished the development and progression of colonic tumors, which was accompanied by decreased numbers of infiltrating macrophages and reduced colonic pro-inflammatory cytokine levels compared to CAC control mice. Interestingly, inhibiting bacterial signaling by antibiotic treatment during the inflammatory phases of CAC also protected mice from severe intestinal inflammation and almost completely prevented tumor growth. Nevertheless, application of antibiotics involved rapid and severe body weight loss and might have unwanted side effects. Our results indicate that bacterial activation of TLR4 on innate immune cells in the colon triggers inflammation and promotes tumor growth. Thus, the inhibition of the TLR4 signaling during intestinal inflammation might be a novel approach to impede CAC development.
High-Resolution Characterization of KIR Genes in a Large North American Cohort Reveals Novel Details of Structural and Sequence Diversity
Authors: Amorim Leonardo M. , Augusto Danillo G. , Nemat-Gorgani Neda , Montero-Martin Gonzalo , Marin Wesley M. , Shams Hengameh , Dandekar Ravi , Caillier Stacy , Parham Peter , Fernández-Viña Marcelo A. , Oksenberg Jorge R. , Norman Paul J. , Hollenbach Jill A.
Published: May 2021

The KIR (killer-cell immunoglobulin-like receptor) region is characterized by structural variation and high sequence similarity among genes, imposing technical difficulties for analysis. We undertook the most comprehensive study to date of KIR genetic diversity in a large population sample, applying next-generation sequencing in 2,130 United States European-descendant individuals. Data were analyzed using our custom bioinformatics pipeline specifically designed to address technical obstacles in determining KIR genotypes. Precise gene copy number determination allowed us to identify a set of uncommon gene-content KIR haplotypes accounting for 5.2% of structural variation. In this cohort, KIR2DL4 is the framework gene that most varies in copy number (6.5% of all individuals). We identified phased high-resolution alleles in large multi-locus insertions and also likely founder haplotypes from which they were deleted. Additionally, we observed 250 alleles at 5-digit resolution, of which 90 have frequencies ≥1%. We found sequence patterns that were consistent with the presence of novel alleles in 398 (18.7%) individuals and contextualized multiple orphan dbSNPs within the KIR complex. We also identified a novel KIR2DL1 variant, Pro151Arg, and demonstrated by molecular dynamics that this substitution is predicted to affect interaction with HLA-C. No previous studies have fully explored the full range of structural and sequence variation of KIR as we present here. We demonstrate that pairing high-throughput sequencing with state-of-art computational tools in a large cohort permits exploration of all aspects of KIR variation including determination of population-level haplotype diversity, improving understanding of the KIR system, and providing an important reference for future studies.
The Path to an Ecosystem Approach for Forage Fish Management: A Case Study of Atlantic Menhaden
Authors: Anstead Kristen A. , Drew Katie , Chagaris David , Schueller Amy M. , McNamee Jason E. , Buchheister Andre , Nesslage Geneviève , Uphoff Jr. Jim H. , Wilberg Michael J. , Sharov Alexei , Dean Micah J. , Brust Jeffrey , Celestino Michael , Madsen Shanna , Murray Sarah , Appelman Max , Ballenger Joseph C. , Brito Joana , Cosby Ellen , Craig Caitlin , Flora Corrin , Gottschall Kurt , Latour Robert J. , Leonard Eddie , Mroch Ray , Newhard Josh , Orner Derek , Swanson Chris , Tinsman Jeff , Houde Edward D. , Miller Thomas J. , Townsend Howard
Published: May 2021

Atlantic menhaden (Brevoortia tyrannus) support the largest fishery by volume on the United States East Coast, while also playing an important role as a forage species. Managers’ and stakeholders’ increasing concerns about the impact of Atlantic menhaden harvest on ecosystem processes led to an evolution in the assessment and management of this species from a purely single-species approach to an ecosystem approach. The first coastwide stock assessment of Atlantic menhaden for management used a single-species virtual population analysis (VPA). Subsequent assessments used a forward projecting statistical catch-at-age framework that incorporated estimates of predation mortality from a multispecies VPA while analytical efforts continued toward the development of ecosystem models and explicit ecological reference points (ERPs) for Atlantic menhaden. As an interim step while ecosystem models were being developed, a series of ad hoc measures to preserve Atlantic menhaden biomass for predators were used by managers. In August 2020, the Atlantic States Marine Fisheries Commission formally adopted an ecological modeling framework as a tool to set reference points and harvest limits for the Atlantic menhaden that considers their role as a forage fish. This is the first example of a quantitative ecosystem approach to setting reference points on the United States Atlantic Coast and it represents a significant advance for forage fish management. This case study reviews the history of Atlantic menhaden stock assessments and management, outlines the progress on the current implementation of ERPs for this species, and highlights future research and management needs to improve and expand ecosystem-based fisheries management.
4D Printing Dual Stimuli-Responsive Bilayer Structure Toward Multiple Shape-Shifting
Authors: Ren Luquan , Li Bingqian , Liu Qingping , Ren Lei , Song Zhengyi , Zhou Xueli , Gao Peng
Published: May 2021

4D printing has been attracting widespread attention because its shape and performance can change under stimuli. The existing 4D printing technology is mostly limited to responsive to single stimulus, which means that the printing structure can only change under a pre-specified stimulus. Here we propose a 4D printing strategy with dual stimuli-responsive shape-shifting that responds to both temperature and water, by using a direct ink writing 3D printing method to deposit a polyurethane elastomer material with water-swelling characteristics on a heat-shrinkage shape memory polymer material to form a bilayer structure. Based on the systematic study of the adapted printing parameters of the polyurethane elastomer, the effect of programmable variables on the deformation shape was investigated. The diversified printing structure exhibits rich structural changes under one or both of the two stimuli of temperature and water. This research provides a universal multiple stimuli-responsive 4D printing method, which can effectively improve the intelligent responsiveness of 4D printing structures by combining multiple smart materials.