bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Cardiac AMP-Activated Protein Kinase in a Non-pathological Setting: Evidence From Cardiomyocyte-Specific, Inducible AMP-Activated Protein Kinase α1α2-Knockout Mice
Authors: Tokarska-Schlattner Malgorzata , Kay Laurence , Perret Pascale , Isola Raffaella , Attia Stéphane , Lamarche Frédéric , Tellier Cindy , Cottet-Rousselle Cécile , Uneisi Amjad , Hininger-Favier Isabelle , Foretz Marc , Dubouchaud Hervé , Ghezzi Catherine , Zuppinger Christian , Viollet Benoit , Schlattner Uwe
Published: October 2021

AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis under conditions of energy stress. Though heart is one of the most energy requiring organs and depends on a perfect match of energy supply with high and fluctuating energy demand to maintain its contractile performance, the role of AMPK in this organ is still not entirely clear, in particular in a non-pathological setting. In this work, we characterized cardiomyocyte-specific, inducible AMPKα1 and α2 knockout mice (KO), where KO was induced at the age of 8 weeks, and assessed their phenotype under physiological conditions. In the heart of KO mice, both AMPKα isoforms were strongly reduced and thus deleted in a large part of cardiomyocytes already 2 weeks after tamoxifen administration, persisting during the entire study period. AMPK KO had no effect on heart function at baseline, but alterations were observed under increased workload induced by dobutamine stress, consistent with lower endurance exercise capacity observed in AMPK KO mice. AMPKα deletion also induced a decrease in basal metabolic rate (oxygen uptake, energy expenditure) together with a trend to lower locomotor activity of AMPK KO mice 12 months after tamoxifen administration. Loss of AMPK resulted in multiple alterations of cardiac mitochondria: reduced respiration with complex I substrates as measured in isolated mitochondria, reduced activity of complexes I and IV, and a shift in mitochondrial cristae morphology from lamellar to mixed lamellar-tubular. A strong tendency to diminished ATP and glycogen level was observed in older animals, 1 year after tamoxifen administration. Our study suggests important roles of cardiac AMPK at increased cardiac workload, potentially limiting exercise performance. This is at least partially due to impaired mitochondrial function and bioenergetics which degrades with age.
G Protein-Coupled Receptors in Osteoarthritis: A Novel Perspective on Pathogenesis and Treatment
Authors: Wen Ze-qin , Liu Di , Zhang Yi , Cai Zi-jun , Xiao Wen-feng , Li Yu-sheng
Published: October 2021

G protein-coupled receptors (GPCRs) are transmembrane receptor proteins that trigger numerous intracellular signaling pathways in response to the extracellular stimuli. The GPCRs superfamily contains enormous structural and functional diversity and mediates extensive biological processes. Until now, critical roles have been established in many diseases, including osteoarthritis (OA). Existing studies have shown that GPCRs play an important role in some OA-related pathogenesis, such as cartilage matrix degradation, synovitis, subchondral bone remodeling, and osteophyte formation. However, current pharmacological treatments are mostly symptomatic and there is a paucity of disease-modifying OA drugs so far. Targeting GPCRs is capable of inhibiting cartilage matrix degradation and synovitis and up-regulating cartilage matrix synthesis, providing a new therapeutic strategy for OA. In this review, we have comprehensively summarized the structures, biofunctions, and the novel roles of GPCRs in the pathogenesis and treatment of OA, which is expected to lay the foundation for the development of novel therapeutics against OA. Even though targeting GPCRs may ameliorate OA progression, many GPCRs-related therapeutic strategies are still in the pre-clinical stage and require further investigation.
Metataxonomic and Metabolic Impact of Fecal Microbiota Transplantation From Patients With Pancreatic Cancer Into Germ-Free Mice: A Pilot Study
Authors: Genton Laurence , Lazarevic Vladimir , Stojanovic Ozren , Spiljar Martina , Djaafar Souad , Koessler Thibaud , Dutoit Valérie , Gaïa Nadia , Mareschal Julie , Macpherson Andrew James , Herrmann Francois , Trajkovski Mirko , Schrenzel Jacques
Published: October 2021

Background

Body weight (BW) loss is prevalent in patients with pancreatic cancer (PC). Gut microbiota affects BW and is known to directly shape the host immune responses and antitumor immunity. This pilot study evaluated the link between gut microbiota, metabolic parameters and inflammatory/immune parameters, through the fecal material transplantation (FMT) of PC patients and healthy volunteers into germ-free (GF) mice.

Methods

We transplanted the feces from five PC patients and five age- and gender-matched healthy volunteers into two GF mice each. Mouse BW and energy intake were measured every 1-5 days, oral glucose on day 21, insulin tolerance on day 26, fecal bacterial taxonomic profile by 16S rRNA gene sequencing on day 5, 10, 15 and 30, and gut-associated lymphoid tissue T cells, plasma cytokines and weights of fat and muscle mass at sacrifice (day 34). Results are presented as mean ± SD. The continuous parameters of mice groups were compared by linear univariate regressions, and their bacterial communities by Principal Coordinates Analysis (PCoA), Bray-Curtis similarity and ANCOM test.

Results

Recipients of feces from PC patients and healthy volunteers had similar BW gain and food intake. Visceral fat was lower in recipients of feces from PC patients than from healthy individuals (0.72 ± 0.17 vs. 0.92 ± 0.14 g; coeff -0.19, 95% CI -0.38, -0.02, p=0.035). The other non-metataxonomic parameters did not differ between groups. In PCoA, microbiota from PC patients clustered apart from those of healthy volunteers and the same pattern was observed in transplanted mice. The proportions of Clostridium bolteae, Clostridium scindens, Clostridium_g24_unclassified and Phascolarctobacterium faecium were higher, while those of Alistipes obesi, Lachnospiraceae PAC000196_s and Coriobacteriaceae_unclassified species were lower in PC patients and in mice transplanted with the feces from these patients.

Conclusion

In this pilot study, FMT from PC patients was associated with a decrease in visceral fat as compared to FMT from healthy individuals. Some of the differences in fecal microbiota between PC and control samples are common to humans and mice. Further research is required to confirm that feces contain elements involved in metabolic and immune alterations.
Data-Driven Modeling of Breast Cancer Tumors Using Boolean Networks
Authors: Sgariglia Domenico , Conforte Alessandra Jordano , Pedreira Carlos Eduardo , Vidal de Carvalho Luis Alfredo , Carneiro Flavia Raquel Gonçalves , Carels Nicolas , Silva Fabricio Alves Barbosa da
Published: October 2021

Cancer is a genomic disease involving various intertwined pathways with complex cross-communication links. Conceptually, this complex interconnected system forms a network, which allows one to model the dynamic behavior of the elements that characterize it to describe the entire system’s development in its various evolutionary stages of carcinogenesis. Knowing the activation or inhibition status of the genes that make up the network during its temporal evolution is necessary for the rational intervention on the critical factors for controlling the system’s dynamic evolution. In this report, we proposed a methodology for building data-driven boolean networks that model breast cancer tumors. We defined the network components and topology based on gene expression data from RNA-seq of breast cancer cell lines. We used a Boolean logic formalism to describe the network dynamics. The combination of single-cell RNA-seq and interactome data enabled us to study the dynamics of malignant subnetworks of up-regulated genes. First, we used the same Boolean function construction scheme for each network node, based on canalyzing functions. Using single-cell breast cancer datasets from The Cancer Genome Atlas, we applied a binarization algorithm. The binarized version of scRNA-seq data allowed identifying attractors specific to patients and critical genes related to each breast cancer subtype. The model proposed in this report may serve as a basis for a methodology to detect critical genes involved in malignant attractor stability, whose inhibition could have potential applications in cancer theranostics.
Impact of Upward Oxygen Diffusion From the Oceanic Crust on the Magnetostratigraphy and Iron Biomineralization of East Pacific Ridge-Flank Sediments
Authors: Höfken Adrian Felix , von Dobeneck Tilo , Kuhn Thomas , Kasten Sabine
Published: October 2021

Recent measurements of pore-water oxygen profiles in ridge flank sediments of the East Pacific Rise revealed an upward-directed diffusive oxygen flux from the hydrothermally active crust into the overlying sediment. This double-sided oxygenation from above and below results in a dual redox transition from an oxic sedimentary environment near the seabed through suboxic conditions at sediment mid-depth back to oxic conditions in the deeper basal sediment. The potential impact of this redox reversal on the paleo- and rock magnetic record was analyzed for three sediment cores from the Clarion-Clipperton-Zone (low-latitude eastern North Pacific). We found that the upward-directed crustal oxygen flux does not impede high quality reversal-based and relative paleointensity-refined magnetostratigraphic dating. Despite low and variable sedimentation rates of 0.1–0.8 cm/kyr, robust magnetostratigraphic core chronologies comprising the past 3.4 resp. 5.2 million years could be established. These age-models support previous findings of significant local sedimentation rate variations that are probably related to the bottom current interactions with the topographic roughness of the young ridge flanks. However, we observed some obvious paleomagnetic irregularities localized at the lower oxic/suboxic redox boundaries of the investigated sediments. When analyzing these apparently remagnetized sections in detail, we found no evidence of physical disturbance or chemical alteration. A sharp increase in single-domain magnetite concentration just below the present lower oxic/suboxic redox boundary suggests secondary magnetite biomineralization by microaerophilic magnetotactic bacteria living as a separate community in the lower, upward oxygenated part of the sediment column. We therefore postulate a two-phased post-depositional remanent magnetization of ridge flank sediments, first by a shallow and later by a deep-living community of magnetotactic bacteria. These findings are the first evidence of a second, deep population of probably inversely oriented magnetotactic bacteria residing in the inverse oxygen gradient zone of ridge flank sediments.
Quantitatively Estimating Carbon Sequestration Potential in Soil and Large Wood in the Context of River Restoration
Authors: Hinshaw Sarah , Wohl Ellen
Published: October 2021

Restoration aimed at rewetting the valley floor has the potential to increase organic carbon stock in the form of floodplain soil carbon, downed wood, and riparian vegetation. The primary goal of stream restoration is typically to restore habitat or maintain balance between natural ecosystem function and human land use. Although many benefits result from stream restoration, the carbon sequestration potential of different restoration approaches in diverse geographic settings has not yet been quantified. We investigate the carbon storage potential of restored stream segments (known as treatment segments) relative to otherwise analogous degraded and reference segments. We develop a conceptual framework to identify the conditions that maximize carbon storage in relation to characteristics of the river corridor and specific restoration practices and propose response surfaces for carbon storage. We illustrate application and quantification of the conceptual framework using data from a pilot study of treatment, degraded, and reference stream segments along two streams in Oregon, United States. The conceptual model is designed to help managers identify levels of hydrologic connectivity, channel and floodplain dynamics, floodplain vegetation, and other variables that may optimize carbon storage at a treatment site.
Multistage Genesis of the Haerdaban Pb-Zn Deposit, West Tianshan: Constraints From Fluid Inclusions and H-O-S-Pb Isotopes
Authors: Xia Fang , Li Shun-Da , Chen Chuan , Gao Ling-Ling , Zhang Xue-Bing , Wang Ke-Yong
Published: October 2021

The Haerdaban Pb-Zn deposit is located on the western edge of the Chinese Western Tianshan Orogen. This deposit consists of stratiform and veined mineralization hosted in Proterozoic carbonaceous and dolomitic limestone. Three metallogenic stages were recognized: an early sedimentary exhalative stage (stage 1), an intermediate metamorphic remobilization stage (stage 2), and a late magmatic-hydrothermal stage (stage 3). Fluid inclusions (FIs) present in stage 1 are liquid-rich aqueous, with homogenization temperatures of 206–246 C and salinities of 5.9–11.6 wt% NaCl eq. FIs present in stage 2 are also liquid-rich aqueous, with homogenization temperatures of 326–349 C and salinities of 3.4–6.6 wt% NaCl eq. FIs present in stage 3 include halite-bearing, vapor-rich aqueous, and liquid-rich aqueous FIs. Homogenization temperatures for these FIs span a range of 249–316 C. Halite-bearing, vapor-rich aqueous, and liquid-rich aqueous FIs yield salinities of 33.8–38.9, 2.6–3.5, and 4.2–8.1 wt% NaCl eq., respectively. Oxygen and hydrogen isotopic data (δ18OH2O = 2.6–13.6‰, δDH2O = −94.7 to −40.7‰) indicate that the ore-forming fluids of stages 1–3 were derived from modified seawater, metamorphic water, and magmatic-meteoric mixed water, respectively. Sulfur isotopic data (δ34S = 2.1–16.3‰) reveal that ore constituents were derived from mixing of marine sulfate and magmatic materials. Lead isotopic data (206Pb/204Pb = 17.002–17.552, 207Pb/204Pb = 15.502–15.523, 208Pb/204Pb = 37.025–37.503) reveal that ore constituents were derived from a mixed crust-mantle source. We propose that the Haerdaban deposit was a Proterozoic sedimentary exhalative deposit overprinted by later metamorphic remobilization and magmatic-hydrothermal mineralization.
Optimization and Comparative Economic Analysis of Standalone and Grid-Connected Hybrid Renewable Energy System for Remote Location
Authors: Jain Siddharth , Sawle Yashwant
Published: October 2021

Due to rising population growth and economic development, there is indeed a growing demand for electricity. Both in aspects of generation and transmission, conventional power firms are striving to manage these demands. Moreover, the ubiquitous utilization of electricity and other power generators, which are mainly driven from fossil fuels, seems to have some limitations, like declining performance and restricted energy production. As a result, use of renewable energy sources is incredibly important. Decentralized power generation in remote regions has become the primary requirement of society, based on renewable energy. Particularly in comparison with the electrification of urban areas, rural electrification is quite expensive. Microgrid’s development utilizing hybrid power is a potential solution for the electrification of rural regions where the transmission chain of network’s extension is unfeasible or inefficient. This research aims to structure a power generation model associated with different HRES combinations using a HOMER software application at a location in India. In the findings of this research, it has been observed that NPC, O&M, COEs, and RF of on-grid energy systems are better than off-grid energy systems. In the study, between eight hybrid system combinations, the lowest COE of 0.034 $/kWh is obtained with the PV-WT-MH-GRID-CT system in the on-grid scenario. This analysis shows NPC, COE, O&M, and renewable fraction are sensitive to the variation in all the considered sensitivity parameters1,2,3,4.
Decentralized and Multi-Objective Coordinated Optimization of Hybrid AC/DC Flexible Distribution Networks
Authors: Wang Xiaoxue , Gu Liting , Liang Dong
Published: October 2021

The increasing penetration of distributed energy resources and flexible electrical loads makes hybrid AC/DC distribution networks become a crucial trend for future modern distribution networks. To increase the flexibility and energy efficiency of hybrid AC/DC distribution networks, a decentralized and multi-objective coordinated optimization method by considering different control means is proposed. The salient feature of this method is that it comprehensively and properly models the full variety of possible control means (i.e., active/reactive power of distributed generation, on load tap changers, flexible distribution switch, voltage source converter). The abundant means are utilized to optimize operational cost, voltage deviation and network losses simultaneously. Then, a fully decentralized optimization method based on alternating direction multiplier method (ADMM) is proposed. The hybrid AC/DC distribution networks are divided into several sub-networks. Flexible interconnected electronic devices are utilized to transfer energy between different sub-networks to achieve the efficient and flexible utilization of controllable resources in hybrid AC/DC distribution networks. Finally, the proposed coordinated optimization method is tested on a modified dual IEEE 33-node network to demonstrate its effectiveness and advantages, and the performance of the centralized method and our proposed method is compared.
Adaptive Control for Parallel-Connected Energy Storage Converters with Line Parameter Mismatch
Authors: Wang Cheng , Hua Hongting , Peng He , Wang Ze
Published: October 2021

Power electronics interfaced microgrid has become a major trend for modern power systems. In this paper, a three-phase microgrid system formed by multiple distributed energy storages (DES) converters is presented. To improve the reliability and flexibility, DESs are connected in parallel to feed the critical loads, and meanwhile, inject real power to the medium voltage (MV) distributed grid and the local dc bus through an interfacing smart transformer (ST). The ST is working at current control mode while the ac bus voltage is regulated in a sharing way through the DESs. However, due to the physical differences and different environment conditions, filter parameters are not likely to be matched for all the DES modules. Accurate load sharing is therefore the first challenging target. Furthermore, both DES module and ST can fail in event of single-point fault. Fast bus voltage restoring thus becomes the second challenging target. In this paper, the parameter mismatch is considered within the system modeling process. A control framework is then presented in form of a virtual current controller and a backstepping adaptive voltage controller. Adaptive laws are designed to fully compensate for the unknown dynamics within the system transient response. Convergence and boundedness of the signals in the closed-loop control system are demonstrated through rigorous Lyapunov-based stability analysis. Simulation results and experimental results are presented and have demonstrated the effectiveness of the proposed algorithm in terms of both fast bus voltage restoring and accurate power sharing.
Numerical Investigation of Pool Boiling Under Ocean Condition with Lattice Boltzmann Simulation. Part Ⅱ: Rolling Condition
Authors: Zou Qifan , Liu Xiuliang , Hu Yongyan , Chang Yuxuan , Li Pengkun
Published: October 2021

Rolling motion caused by ocean condition will induce more complicated inertial forces with their force directions changing all the time, which results more complex bubble behaviors and unique heat transfer characteristics. In this work, pool boiling under rolling condition is numerically simulated using multiple relaxation time phase change lattice Boltzmann method (LBM). Pool boiling patterns, boiling curve of time-averaged heat flux, transient heat flux and rolling effects on different pool boiling regions are investigated. The results show that pool boiling curve of time-averaged heat flux between rolling condition and static condition are not obvious until close to critical heat flux, and 9.3% higher CHF is achieved under rolling condition while worse heat transfer is discovered at film boiling. Moreover, distinct fluctuation of transient heat flux of pool boiling under rolling condition is found for all boiling regimes, and its variation pattern along with the rolling motion and bubble behavior is investigated. Furthermore, tangential inertial force caused by rolling motion has positive influence on heat transfer of pool boiling, while the centrifugal force has negative influence on heat transfer, since it is opposite to the gravity and hence decreases the buoyancy force. Besides, larger rolling amplitude and smaller rolling period will induce larger additional inertial forces, and thus make greater influences on the bubbles’ behavior and pool boiling heat transfer.
Impact of Green Financing on Carbon Drifts to Mitigate Climate Change: Mediating Role of Energy Efficiency
Authors: Chang Lei , Wang Jianhe , Xiang Ziman , Liu Hongda
Published: October 2021

Climate change mitigation (CCM) has not been mainly understood and assessed in the terms of carbon drifts persisting at provincial level of China, and to respond the question that how green financing is better financing option for CCM. Thus, our study intends to test the role of green finance on carbon drifts to manage for the mitigation of climate change. For this, unit root test and panel co-integration technique is applied. Study findings reported that the intricate connection between place-and-time-specific GHG emission reduction responsibilities is significant with 18% and the ‘production’, trading and consumption of carbon allowances with 21% and offsets across vast time-space stretches related carbon drift is significant with 19.5% for climate change mitigation. For such significance, green financing is found imperative indicators which is significant at 27.1% with carbon drifts, and mitigates the climate change with 31.3%, which is, relatively high than usual climate change control practices. Our study also provides detailed policy implication on this topicality for associated stakeholder.
Comparative Signatures of Selection Analyses Identify Loci Under Positive Selection in the Murrah Buffalo of India
Authors: Tyagi Shiv K. , Mehrotra Arnav , Singh Akansha , Kumar Amit , Dutt Triveni , Mishra Bishnu P. , Pandey Ashwni K.
Published: October 2021

India is home to a large and diverse buffalo population. The Murrah breed of North India is known for its milk production, and it has been used in breeding programs in several countries. Selection signature analysis yield valuable information about how the natural and artificial selective pressures have shaped the genomic landscape of modern-day livestock species. Genotype information was generated on six buffalo breeds of India, namely, Murrah, Bhadawari, Mehsana, Pandharpuri, Surti, and Toda using ddRAD sequencing protocol. Initially, the genotypes were used to carry out population diversity and structure analysis among the six breeds, followed by pair-wise comparisons of Murrah with the other five breeds through XP-EHH and FST methodologies to identify regions under selection in Murrah. Admixture results showed significant levels of Murrah inheritance in all the breeds except Pandharpuri. The selection signature analysis revealed six regions in Murrah, which were identified in more than one pair-wise comparison through both XP-EHH and FST analyses. The significant regions overlapped with QTLs for milk production, immunity, and body development traits. Genes present in these regions included SLC37A1, PDE9A, PPBP, CXCL6, RASSF6, AFM, AFP, ALB, ANKRD17, CNTNAP2, GPC5, MYLK3, and GPT2. These genes emerged as candidates for future polymorphism studies of adaptability and performance traits in buffaloes. The results also suggested ddRAD sequencing as a useful cost-effective alternative for whole-genome sequencing to carry out diversity analysis and discover selection signatures in Indian buffalo breeds.
Integrated Single-Cell Bioinformatics Analysis Reveals Intrinsic and Extrinsic Biological Characteristics of Hematopoietic Stem Cell Aging
Authors: Zeng Xiangjun , Li Xia , Shao Mi , Xu Yulin , Shan Wei , Wei Cong , Li Xiaoqing , Wang Limengmeng , Hu Yongxian , Zhao Yanmin , Qian Pengxu , Huang He
Published: October 2021

Hematopoietic stem cell (HSC) aging, which is accompanied by loss of self-renewal capacity, myeloid-biased differentiation and increased risks of hematopoietic malignancies, is an important focus in stem cell research. However, the mechanisms underlying HSC aging have not been fully elucidated. In the present study, we integrated 3 independent single-cell transcriptome datasets of HSCs together and identified Stat3 and Ifngr1 as two markers of apoptosis-biased and inflammatory aged HSCs. Besides, common differentially expressed genes (DEGs) between young and aged HSCs were identified and further validated by quantitative RT-PCR. Functional enrichment analysis revealed that these DEGs were predominantly involved in the cell cycle and the tumor necrosis factor (TNF) signaling pathway. We further found that the Skp2-induced signaling pathway (Skp2→Cip1→CycA/CDK2→DP-1) contributed to a rapid transition through G1 phase in aged HSCs. In addition, analysis of the extrinsic alterations on HSC aging revealed the increased expression levels of inflammatory genes in bone marrow microenvironment. Colony formation unit assays showed that inflammatory cytokines promoted cellular senescence and that blockade of inflammatory pathway markedly rejuvenated aged HSC functions and increased B cell output. Collectively, our study elucidated the biological characteristics of HSC aging, and the genes and pathways we identified could be potential biomarkers and targets for the identification and rejuvenation of aged HSCs.
Non-Coding RNAs in the Etiology and Control of Major and Neglected Human Tropical Diseases
Authors: Tamgue Ousman , Mezajou Cybelle Fodieu , Ngongang Natacha Njike , Kameni Charleine , Ngum Jubilate Afuoti , Simo Ulrich Stephane Fotso , Tatang Fabrice Junior , Akami Mazarin , Ngono Annie Ngane
Published: October 2021

Non-coding RNAs (ncRNAs) including microRNAs (miRs) and long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression in immune cells development and function. Their expression is altered in different physiological and disease conditions, hence making them attractive targets for the understanding of disease etiology and the development of adjunctive control strategies, especially within the current context of mitigated success of control measures deployed to eradicate these diseases. In this review, we summarize our current understanding of the role of ncRNAs in the etiology and control of major human tropical diseases including tuberculosis, HIV/AIDS and malaria, as well as neglected tropical diseases including leishmaniasis, African trypanosomiasis and leprosy. We highlight that several ncRNAs are involved at different stages of development of these diseases, for example miR-26-5p, miR-132-3p, miR-155-5p, miR-29-3p, miR-21-5p, miR-27b-3p, miR-99b-5p, miR-125-5p, miR-146a-5p, miR-223-3p, miR-20b-5p, miR-142-3p, miR-27a-5p, miR-144-5p, miR-889-5p and miR-582-5p in tuberculosis; miR-873, MALAT1, HEAL, LINC01426, LINC00173, NEAT1, NRON, GAS5 and lincRNA-p21 in HIV/AIDS; miR-451a, miR-let-7b and miR-106b in malaria; miR-210, miR-30A-5P, miR-294, miR-721 and lncRNA 7SL RNA in leishmaniasis; and miR-21, miR-181a, miR-146a in leprosy. We further report that several ncRNAs were investigated as diseases biomarkers and a number of them showed good potential for disease diagnosis, including miR-769-5p, miR-320a, miR-22-3p, miR-423-5p, miR-17-5p, miR-20b-5p and lncRNA LOC152742 in tuberculosis; miR-146b-5p, miR-223, miR-150, miR-16, miR-191 and lncRNA NEAT1 in HIV/AIDS; miR-451 and miR-16 in malaria; miR-361-3p, miR-193b, miR-671, lncRNA 7SL in leishmaniasis; miR-101, miR-196b, miR-27b and miR-29c in leprosy. Furthermore, some ncRNAs have emerged as potential therapeutic targets, some of which include lncRNAs NEAT1, NEAT2 and lnr6RNA, 152742 in tuberculosis; MALAT1, HEAL, SAF, lincRNA-p21, NEAT1, GAS5, NRON, LINC00173 in HIV/AIDS; miRNA-146a in malaria. Finally, miR-135 and miR-126 were proposed as potential targets for the development of therapeutic vaccine against leishmaniasis. We also identify and discuss knowledge gaps that warrant for increased research work. These include investigation of the role of ncRNAs in the etiology of African trypanosomiasis and the assessment of the diagnostic potential of ncRNAs for malaria, and African trypanosomiasis. The potential targeting of ncRNAs for adjunctive therapy against tuberculosis, leishmaniasis, African trypanosomiasis and leprosy, as well as their targeting in vaccine development against tuberculosis, HIV/AIDS, malaria, African trypanosomiasis and leprosy are also new avenues to explore.
Antibody- Based Immunotherapy Combined With Antimycotic Drug TMP- SMX to Treat Infection With Paracoccidioides brasiliensis
Authors: Boniche-Alfaro Camila , Kischkel Brenda , Thomaz Luciana , Carvalho-Gomes Monique Maria , Lopes-Bezerra Leila M. , Nosanchuk Joshua Daniel , Taborda Carlos Pelleschi
Published: October 2021

Monoclonal antibodies (mAbs) are promising alternatives to treat infectious diseases, especially given their potential for applications in combination therapies with antimicrobial drugs to enhance the antifungal efficacy. Protection mediated by mAbs used to treat experimental paracoccidioidomycosis (PCM) has been demonstrated previously. Our aim in the present work was to characterize a monoclonal antibody (mAbF1.4) raised against a cell wall glycoconjugate fraction of Paracoccidioides spp. and to analyze its efficacy combined with trimethoprim-sulfamethoxazole (TMP/SMX) as treatment for experimental PCM. We demonstrated that the epitope recognized by mAbF1.4 is consistent with branched glucose residues present on a cell wall β-glucan polymer. In vitro, mAbF1.4 increased the phagocytic capacity and nitric oxide concentration induced by the macrophage cell line J774.1A, and this resulted in a significant reduction in the viability of the opsonophagocytized yeasts. In vivo, we detected a significant reduction in pulmonary fungal burdens of mice treated with mAbF1.4 in association with TMP/SMX, which correlated with increased pulmonary concentrations (determined by ELISA) of IFN- γ, TNF-α, IL-10 and IL-17. In parallel, we observed a decrease in IL-4, suggesting that the treatment was associated with a mixed Th1-Th17 type immune response. Histopathology of lung segments from mice receiving the combination therapy showed a significant reduction in granulomas, which were well-defined, and improved maintenance of lung architecture. These findings demonstrate that mAbF1.4 + TMP/SMX therapy is a promising approach to combat PCM as well as decrease disease sequelae and highlights the potential benefits of immune mediators in PCM combined immunotherapy.
Role of Eosinophils in Intestinal Inflammation and Fibrosis in Inflammatory Bowel Disease: An Overlooked Villain?
Authors: Jacobs Inge , Ceulemans Matthias , Wauters Lucas , Breynaert Christine , Vermeire Séverine , Verstockt Bram , Vanuytsel Tim
Published: October 2021

Eosinophils are leukocytes which reside in the gastrointestinal tract under homeostatic conditions, except for the esophagus which is normally devoid of eosinophils. Research on eosinophils has primarily focused on anti-helminth responses and type 2 immune disorders. In contrast, the search for a role of eosinophils in chronic intestinal inflammation and fibrosis has been limited. With a shift in research focus from adaptive to innate immunity and the fact that the eosinophilic granules are filled with inflammatory mediators, eosinophils are becoming a point of interest in inflammatory bowel diseases. In the current review we summarize eosinophil characteristics and recruitment as well as the current knowledge on presence, inflammatory and pro-fibrotic functions of eosinophils in inflammatory bowel disease and other chronic inflammatory conditions, and we identify research gaps which should be covered in the future.
FUCA2 Is a Prognostic Biomarker and Correlated With an Immunosuppressive Microenvironment in Pan-Cancer
Authors: Zhong Anyuan , Chen Ting , Xing Yufei , Pan Xue , Shi Minhua
Published: October 2021

Background

The expression of Fucosidase, alpha-L-2 (FUCA2) varies across tumors. However, its role in various tumor types and relationship with the tumor immune microenvironment (TIME) is poorly defined.

Methods

We analyzed profiles of FUCA2 expression using datasets from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Next, gene alteration, clinical characteristics and prognostic values of FUCA2 were elucidated based on TCGA pan-cancer data. This was followed by gene set enrichment analysis by R software. Relationships between FUCA2 expression and immune infiltration and immune-related genes were also evaluated. Moreover, the association of immune cell infiltration with FUCA2 expression was evaluated across three different sources of immune cell infiltration data, namely the TIMER online, ImmuCellAI databases, as well as a published study. In addition, MTT assays was also conducted to validate the oncogene role of FUCA2 in lung cancer cells.

Results

FUCA2 was upregulated in most tumors, and this was significantly associated with poor survival rates. Gene set enrichment analysis uncovered that FUCA2 correlated with immune pathways in different tumor types. FUCA2 expression was positively related to tumor associated macrophages (TAMs), especially M2-like TAMs. Moreover, FUCA2 level showed a positive relationship with most immunosuppression genes, including programmed death-ligand 1 (PD-L1), transforming growth factor beta 1 (TGFB1), and interleukin-10 (IL10) in most cancer types. FUCA2 knockdown inhibited the cell viability in lung cancer cells.

Conclusions

Our study reveals that FUCA2 is a potential oncogene and is indicative biomarker of a worse prognosis in pan-cancer. High FUCA2 expression may contribute to increased infiltration of TAMs and associates with an immunosuppressive microenvironment, providing a potential target for tumor therapy.
First Record of Bioluminescence in a Sipunculan Worm
Authors: Oliveira Anderson G. , Amaral Danilo T. , Hannon Mary Colleen , Schulze Anja
Published: October 2021

During a search for bioluminescent marine annelids around the island of Carrie Bow Cay, Belize, we discovered bioluminescence in the sipunculan worm Nephasoma pellucidum. The identification of N. pellucidum was verified by DNA barcoding of ∼650 bp of the mitochondrial cytochrome c oxidase I gene, using sequences of the same species from previous studies as references. Our study constitutes the first record of a bioluminescent sipunculan species. Green luminescence was detected in four of the five individuals of N. pellucidum collected from coral rubble from a shallow reef flat and one deeper (14 m) site. To test for bioluminescent activity, all collected annelids (including sipunculans) were sorted into morphotypes and identified to the lowest taxonomic level possible. After several hours of dark adaptation, they were mechanically stimulated, and luminescent reactions were noted and recorded by photography and/or video whenever possible. Of a total of nine examined sipunculan species, N. pellucidum was the only one that showed bioluminescent activity. The underlying biochemical processes for the bioluminescence are so far unknown, but transcriptome data indicate the presence of proteins with similarities to Renilla-type luciferases. We did not find similarities to any known photoproteins. Our findings broaden the known diversity of bioluminescent annelid taxa and support the notion that bioluminescence arose multiple times in annelids. The bioluminescent properties of N. pellucidum add a new reason to pursue this species as a model species, as has been previously proposed.
Luminescent Zn (II)-Based Nanoprobes: A Highly Symmetric Supramolecular Platform for Sensing of Biological Targets and Living Cell Imaging
Authors: Diana Rosita , Sessa Lucia , Concilio Simona , Piotto Stefano , Panunzi Barbara
Published: October 2021

Zinc (II) cation is an environmentally friendly metal, less expensive, easy to dispose of, and managed. Highly engineered symmetric systems can be built using zinc (II) atoms as the metal nodes of hybrid organic-inorganic supramolecular structures. In biological contexts, luminescent zinc-based nanoprobes are in growing demand. Specifically, they are currently employed to detect biologically and environmentally relevant analytes, in therapeutic drug delivery, and for bioimaging and diagnostic techniques monitoring aspects of cellular functions. This review will provide a systematic and consequential approach to zinc-based nanoprobes, including zinc-based MOFs and other zinc-based organized nanoparticles. A progression from detecting the biological target to the intracellular sensing/marking/carriage has been followed. A selection of significant cutting-edge articles collected in the last five years has been discussed, based on the structural pattern and sensing performance, with special notice to living cell bioimaging as the most targeted and desirable application.
Effect of Cr6+ on the Properties of Alkali-Activated Slag Cement
Authors: Bo Fu , Zhenyun Cheng
Published: October 2021

In order to investigate the effect of Cr6+ on the properties of alkali-activated slag cement (AAS), the effects of added dosage of Na2Cr2O4 on the setting time and compressive strength of AAS were measured. The leaching concentration of Cr6+ from AAS cement stone was measured using dual-beam UV-visible spectrophotometry. The effect of Na2Cr2O4 on the hydration kinetics of AAS cement was monitored by microcalorimetry and the corresponding kinetic parameters were analyzed. The pore solution from AAS was collected and analyzed using the high pressure press method. The effects of Na2Cr2O4 on the hydration products of AAS cement were observed and compared using X-ray diffraction (XRD) and scanning electron microscopy (SEM). The experimental results showed that the AAS hydration process was markedly affected by Na2Cr2O4 dosage. The setting time of AAS pastes was increased and the compressive strength of cement stones was reduced with increasing dosage of Na2Cr2O4. With the development of AAS hydration, the leaching concentration of Na2Cr2O4 gradually decreased. Na2Cr2O4 did not affect the dissolution of slag particles, but impeded the formation of C-S-H gel. The Cr6+ was immobilized chemically in the form of needle-like CaCrO4 particles formed by the chemical reaction between Na2Cr2O4 and Ca2+ leaching from the slag.
Impacts of CAD/CAM Metallic Materials on Trace Metals and Biocompatibilities: An in vivo Study in Beagle Dogs
Authors: Lin Yunzhi , Chen Jinbing , Jiang Fangke , Pan Yu , Xu Caiming , Lin Donghong , Lin Honglei , Jiang Lei , Zheng Dali , Qiu Jing , Cheng Hui
Published: October 2021

CAD/CAM (computer-aided design and computer-aided manufacturing) technology has been widely applied in clinical dentistry, but the material safety remains a concern. To investigate the impacts of CAD/CAM metallic materials on trace metals and biocompatibilities, selective laser melted (SLM) cobalt-chromium (Co-Cr) alloys and computer numeric controlled milled (CNC milled) commercially pure titanium (CP-Ti) were placed on the maxilla of beagle dogs for 6 months. The trace metals in the oral mucosa, blood, liver, kidney, and hair were then determined by inductively coupled plasma mass spectrometry (ICP-MS). The histopathologic changes and biocompatibilities of tissues were examined by hematoxylin and eosin (H&E) staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) method, immunohistochemistry (IHC) assay, Western blot analysis, and liver and kidney function tests. Our results showed that trace metals released from these two CAD/CAM metallic materials accumulated transiently in the oral mucosa and whole blood. The trace metals released from SLM Co-Cr alloys could also transiently accumulate in the plasm and hair. In addition, these two CAD/CAM metallic materials both induced apoptosis and histopathologic changes in the oral mucosa, with SLM Co-Cr alloys inducing a higher level of apoptosis. In contrast, both materials did not exert autophagic effects on the oral mucosa or affect the trace metals, functions, or biocompatibilities of the liver and kidney. Therefore, this study suggests that CAD/CAM metallic materials should be selected carefully, especially in patients with metal- and apoptosis-related diseases, and CNC-milled CP-Ti can be recommended to patients on account of its better biocompatibility and safety.
Severe Patients With ARDS With COVID-19 Treated With Extracorporeal Membrane Oxygenation in China: A Retrospective Study
Authors: Lai Wei , Li Shuanglei , Du Zhongtao , Ma Xinhua , Lu Junyu , Gao Wei Dong , Abbott Geoffrey W. , Hu Zhaoyang , Kang Yan
Published: October 2021

Background: The novel coronavirus disease 2019 (COVID-19) pandemic has become a global health crisis affecting over 200 countries worldwide. Extracorporeal membrane oxygenation (ECMO) has been increasingly used in the management of COVID-19-associated end-stage respiratory failure. However, the exact effect of ECMO in the management of these patients, especially with regards to complications and mortality, is unclear.

Methods: This is the largest retrospective study of ECMO treated COVID-19 patients in China. A total of 50 ECMO-treated COVID-19 patients were recruited. We describe the main characteristics, the clinical features, ventilator parameters, ECMO-related variables and management details, and complications and outcomes of COVID-19 patients with severe acute respiratory distress syndrome (ARDS) that required ECMO support.

Results: For those patients with ECMO support, 21 patients survived and 29 died (mortality rate: 58.0%). Among those who survived, PaO2 (66.3 mmHg [59.5–74.0 mmHg] and PaO2/FiO2 (68.0 mmHg [61.0–76.0 mmHg]) were higher in the survivors than those of non-survivors (PaO2: 56.8 mmHg (49.0–65.0 mmHg), PaO2/FiO2 (58.2 mmHg (49.0–68.0 mmHg), all P < 0.01) prior to ECMO. Patients who achieved negative fluid balance in the early resuscitation phase (within 3 days) had a higher survival rate than those who did not (P = 0.0003).

Conclusions: In this study of 50 cases of ECMO-treated COVID-19 patients, a low PO2/FIO2 ratio before ECMO commencement may indicate a poor prognosis. Negative fluid balance in the early resuscitation phase during ECMO treatment was a predictor of increased survival post-ECMO treatment.
Is qSOFA Suitable for Early Diagnosis of Sepsis Among Bacteremia Patients in Emergency Departments? Time for a Reappraisal of Sepsis-3 Criteria
Authors: Lee Ching-Chi , Ho Ching-Yu , Chen Po-Lin , Hsieh Chih-Chia , Wang William Yu Chung , Lin Chih-Hao , Ko Wen-Chien
Published: October 2021

Background: For early recognition of patients with sepsis, quick Sequential Organ Failure Assessment (qSOFA) was proposed by Sepsis-3 criteria as initial sepsis identification outside of intensive care units. However, the new definition has subsequently led to controversy and prompted much discussion for delayed treatment efforts. We aimed to validate Sepsis-3 criteria on bacteremia patients by investigating prognostic impacts of inappropriate administration of empirical antimicrobial therapy (EAT) and delayed source control (SC) compared to Sepsis-2 criteria.

Methods: In the multicenter cohort of adults with community-onset bacteremia in emergency departments (EDs), adverse effects of delayed treatment efforts on 30-day mortality were examined in septic and non-septic patients by fulfilling the Sepsis-2 or Sepsis-3 criteria using the Cox regression model after adjusting independent determinants of mortality.

Results: Of the 3,898 total adults, septic patients accounted for 92.8% (3,619 patients) by Sepsis-2 criteria (i.e., SIRS criteria). Using Sepsis-3 criteria, 1,827 (46.9%) patients were diagnosed with early sepsis (i.e., initial qSOFA scores ≥ 2) in EDs and 2,622 (67.3%) with sepsis during hospitalization (i.e., increased SOFA scores of ≥ 2 from ED arrival). The prognostic impacts of inappropriate EAT or delayed SC (for complicated bacteremia) were both significant in septic patients with fulfilling the Sepsis-2 or Sepsis-3 (i.e., SOFA) criteria, respectively. Meanwhile, these delayed treatment efforts trivially impact prognoses of non-septic patients recognized by the Sepsis-2 or Sepsis-3 (i.e., SOFA) definitions. Notably, prognostic effects of inappropriate EAT or delayed SC were disclosed for septic patients in EDs, specifically those with qSOFA scores of ≥ 2, and prognostic impacts of delayed treatment efforts remained significant for patients initially recognized early as being non-septic (i.e., initial qSOFA scores of <2).

Conclusions: For patients with community-onset bacteremia, inappropriate EAT and delayed SC might result in unfavorable outcomes of patients early identified as being non-septic on ED arrival based on the qSOFA scores (by Sepsis-3 criteria). Accordingly, a more prudent diagnosis of sepsis adopted among bacteremia patients in the ED is necessary.
The Efficacy and Safety of Fecal Microbiota Transplantation Combined With Biofeedback for Mixed Constipation: A Retrospective Cohort Study
Authors: Yang Bo , Tian Hongliang , Ye Chen , Lin Zhiliang , Zhao Di , Ma Chunlian , Zhao Jiangman , Wu Shouxin , Jiang Rongfeng , Li Ning , Qin Huanlong , Chen Qiyi
Published: October 2021

This study aims to assess the effectiveness and safety of fecal microbiota transplantation (FMT) combined with biofeedback for patients with mixed constipation. Patients who received biofeedback (biofeedback group, n = 40) and those who received FMT combined with biofeedback (FMT combination group, n = 45) were enrolled. Spontaneous bowel movements (SBMs) frequency, Bristol Stool Form Scale (BSFS), and Patient Assessment of Constipation Symptoms (PAC-SYM) score were analyzed to evaluate the effect of treatment. Gastrointestinal Quality of Life Index (GIQLI) scores of patients were used to assess the quality of life, and the safety of FMT combination therapy was evaluated by the presence of adverse events. The 16S rRNA gene sequencing was performed on the fecal samples of 12 donors, feces of 31 patients before and after receiving FMT combination treatment. Comparing the biofeedback group and the FMT combination group 1 month after the treatment, significant differences were observed in the mean value of SBM frequency, BSFS, and PAC-SYM scores, which were 2.15 ± 1.05 vs. 3.61 ± 0.89 (p = 0.0031), 2.1 ± 0.9 vs. 2.5 ± 1.2 (p = 0.008), and 2.4 ± 0.5 vs. 2.2 ± 0.6 (p = 0.0021), respectively. Meanwhile, FMT combination therapy had long-term beneficial effects according to the data collected at six months and 12 months after the treatment. With respect to the quality of life, GIQLI scores were higher in the FMT combination group (103.6 ± 15.1) compared with that in the biofeedback group (88.7 ± 10.1) one month after administration (p = 0.0042). In addition, there were no significant differences between the two groups in adverse events, including abdominal pain, diarrhea, dizziness, nausea, vomiting, and other side effects. Results of 16S rRNA gene sequencing showing some well-known probiotics had significantly increased after FMT combination treatment compared with pre-FMT samples, such as Prevotella and Bifidobacterium. Findings of this study suggested that FMT combined with biofeedback could be effective and safe for patients with mixed constipation.