bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of PPARD gene variants on the therapeutic responses to exenatide in chinese patients with type 2 diabetes mellitus
Authors: Song Jinfang , Li Na , Hu Ruonan , Yu Yanan , Xu Ke , Ling Hongwei , Lu Qian , Yang Tingting , Wang Tao , Yin Xiaoxing
Published: August 2022

Background

Exenatide is a GLP-1R agonist that often exhibits considerable interindividual variability in therapeutic efficacy. However, there is no evidence about the impact of genetic variants in the PPARD on the therapeutic efficacy of exenatide. This research was aimed to explore the influence of PPARD gene polymorphism on the therapeutic effect of exenatide, and to identify the potential mechanism futher.

Methods

A total of 300 patients with T2DM and 200 control subjects were enrolled to identify PPARD rs2016520 and rs3777744 genotypes. A prospective clinical study was used to collect clinical indicators and peripheral blood of T2DM patients treated with exenatide monotherapy for 6 months. The SNaPshot method was used to identify PPARD rs2016520 and rs3777744 genotypes, and then we performed correlation analysis between PPARD gene variants and the efficacy of exenatide, and conducted multiple linear regression analysis of factors affecting the therapeutic effect of exenatide. HepG2 cells were incubated with exenatide in the absence or presence of a PPARδ agonist or the siPPARδ plasmid, after which the levels of GLP-1R and the ratio of glucose uptake were determined.

Results

After 6 months exenatide monotherapy, we observed that homeostasis model assessment for insulin resistance (HOMA-IR) levels of the subjects with at least one C allele of the PPARD rs2016520 were significantly lower than those with the TT genotype, which suggested that the PPARD rs2016520 TT genotype conferred the poor exenatide response through a reduction of insulin resistance, as measured by HOMA-IR. The carriers of G alleles at rs3777744 exhibited higher levels of in waist to hip ratio (WHR), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and HOMA-IR compared to individuals with the AA genotype following 6 months of exenatide treatment, potentially accounting for the lower failure rate of exenatide therapy among the AA homozygotes. In an insulin resistant HepG2 cell model, the PPARδ agonists enhanced exenatide efficacy on insulin resistance, with the expression of GLP-1R being up-regulated markedly.

Conclusion

These data suggest that the PPARD rs2016520 and rs3777744 polymorphisms are associated with exenatide monotherapy efficacy, due to the pivotal role of PPARδ in regulating insulin resistance through affecting the expression of GLP-1R. This study was registered in the Chinese Clinical Trial Register (No. ChiCTR-CCC13003536).
The role of pregnane X receptor (PXR) in substance metabolism
Authors: Lv Ye , Luo Yi-Yang , Ren Hui-Wen , Li Cheng-Jie , Xiang Zhi-Xin , Luan Zhi-Lin
Published: August 2022

As a member of the nuclear receptor (NR) superfamily, pregnane X receptor (PXR; NR1I2) is a ligand-activated transcription factor that plays a crucial role in the metabolism of xenobiotics and endobiotics in mammals. The tissue distribution of PXR is parallel to its function with high expression in the liver and small intestine and moderate expression in the kidney, stomach, skin, and blood-brain barrier, which are organs and tissues in frequent contact with xenobiotics. PXR was first recognized as an exogenous substance receptor regulating metabolizing enzymes and transporters and functioning in detoxification and drug metabolism in the liver. However, further research revealed that PXR acts as an equally important endogenous substance receptor in the metabolism and homeostasis of endogenous substances. In this review, we summarized the functions of PXR in metabolism of different substances such as glucose, lipid, bile acid, vitamin, minerals, and endocrines, and also included insights of the application of PXR ligands (drugs) in specific diseases.
Research on core power maximization method of natural circulation lead-bismuth cooled fast reactor
Authors: Xiao Yingjie , Yang Junkang , Zhao Pengcheng , Yu Tao , Liu Zijing
Published: August 2022

To improve the inherent safety and cost-effectiveness of lead-bismuth cooled fast reactors, the SPALLER-100 reactor designed by the University of South China has been selected as the research object to determine the maximum power it can produce. This is a multi-objective, complex, multi-dimensional, nonlinear, and constrained optimization problem. To maintain the transportability, material durability, and long-term operation stability of the reactor core and ensure safety under accident conditions, three steady-state limitations and three accident limitations are proposed. The platform used to calculate the maximum neutronic power produced by the reactor at different core heights has been built using Latin hypercube sampling and the Kriging proxy model. Meanwhile, the cooling power of the reactor at different core heights is calculated by considering its natural circulation capacity. Finally, a design scheme is obtained that meets the requirements of neutronic and thermal-hydraulic assessments, while producing maximum power. Consequently, during the entire life-cycle of SPALLER-100, a safety analysis of three typical accident scenarios (unprotected loss of heat sink, unprotected transient over power, and unprotected coolant inlet temperature undercooling) is performed using a Quasi-Static Reactivity Balance (QSRB) approach. The results show that the platform used to calculate the maximum neutronic power exhibits high accuracy, and that the design scheme with maximum power is safe and economical. Overall, this study can provide reference ideas for designing natural circulation reactors that can maximize power output.
Using Google Street View photographs to assess long-term outdoor thermal perception and thermal comfort in the urban environment during heatwaves
Authors: Urban Jan , Pikl Miroslav , Zemek František , Novotný Jan
Published: August 2022

The outdoor thermal comfort of urban residents is negatively affected by heatwaves that are becoming more frequent and severe with the ongoing climate crisis. As such, the assessment of outdoor perception and comfort during heatwaves has become an important ingredient of successful urban adaptation strategies. However, systematic assessment of long-term thermal perception across a large number of places and large populations of people is difficult. In this study, we consider an approach to the assessment of long-term thermal perception that combines features of currently used approaches (i.e., use of rating scales of thermal perception, use of surveys, and the use of photographs representing places) and we provide some preliminary validation of this approach. Specifically, across three studies conducted in two Czech cities, we show that long-term thermal perceptions for a large sample of 1,856 urban places can be elicited in a large sample of city residents (total N = 1,812) using rating scales in off-site surveys complemented with visual representations of the target locations. In Studies 1 and 2, we partially validate this approach by showing that such long-term thermal perceptions can be traced back to average surface temperature, sky-view factor, and the presence of blue and green infrastructure, all factors that the literature relates to thermal perception. Moreover, we show evidence that observers can reliably glean these properties from the visual representation of places. In Study 3, we provide additional evidence of the predictive validity of such long-term thermal perceptions by showing that they predict place-related activities (waiting and walking) and the place preference of other people more than one year later. Thus, this approach to the measurement of long-term thermal perception related to heatwaves can be a useful addition to currently used approaches.
Vegetated Steel Slag Substrate Constructed Wetlands can Achieve High Efficiency Simultaneous Nitrogen and Phosphorus Removal
Authors: Zhang Jingyao , Zou Yuanchun , Yu Xiaofei , Ding Shanshan , Yan Jiawen , Min Yongen
Published: August 2022

Steel slag substrate constructed wetlands (SSCWs) can effectively remove phosphorus (P) from sewage through Ca-P precipitation and adsorption. Nonetheless, the disadvantages of a high pH value of the effluent and low nitrogen (N) removal efficiency limit the practical application of SSCWs. To improve these shortcomings, plant cultivation and combining steel slag with other substrate materials have been applied in SSCWs. However, related studies have not obtained a unanimous consensus elucidating such improvements. To accurately evaluate improvements, we statistically analyzed the experimental data reported in 27 related papers and found that combining steel slag with other substrate materials in SSCWs significantly increased the removal amount of total nitrogen (TN) (51.58 mg TN/L) and ammonium nitrogen (NH4+-N) (74.15 mg NH4+-N/L) but reduced the removal amount of total phosphorus (TP) (7.76 mg TP/L). In these combined substrate SSCWs, plant cultivation could compensate for the decline in TP removal amount and improve upon the simultaneous removal of N and P (6.02 mg TP/L, 62.18 mg TN/L, and 69.16 mg NH4+-N/L). Moreover, compared with vertical flow SSCWs, horizontal flow enables plant-cultivated and combined substrate SSCWs to achieve a higher TP removal capacity (6.38 mg TP/L). In addition, operational parameters, including temperature, hydraulic retention time (HRT), pH value, and influent concentration, significantly affected the N and P removal capacity of SSCWs. Our research results provide a theoretical reference for the design and operation of SSCWs for efficient N and P removal.
Temporal coherence patterns of prairie pothole wetlands indicate the importance of landscape linkages and wetland heterogeneity in maintaining biodiversity
Authors: McLean Kyle I. , Mushet David M. , Sweetman Jon N.
Published: August 2022

Wetland ecosystems are diverse, productive habitats that are essential reservoirs of biodiversity. Not only are they home to numerous wetland-specialist species, but they also provide food, water, and shelter that support terrestrial wildlife populations. However, like observed patterns of biodiversity loss, wetland habitats have experienced widespread loss and degradation. In order to conserve and restore wetlands, and thereby the biodiversity they support, it is important to understand how biodiversity in wetland habitats is maintained. Habitat heterogeneity and connectivity are thought to be predominate drivers of wetland biodiversity. We quantified temporal coherence (i.e., spatial synchrony) of wetland invertebrate communities using intra-class correlations among 16 wetlands sampled continuously over 24 years to better understand the relative influences wetland heterogeneity (i.e., internal processes specific to individual wetlands and spatial connectivity and external processes occurring on the landscape) on wetland biodiversity. We found that while wetlands with different ponded-water regimes (temporarily ponded or permanently ponded) often hosted different invertebrate communities, temporal shifts in invertebrate composition were synchronous. We also found the relative importance of internal versus external forces in determining community assembly vary depending on a wetland’s hydrologic function and climate influences. Our results confirm that heterogeneity and spatial connectivity of wetland landscapes are important drivers of wetland biodiversity.
Spatiotemporal characteristics of the pharyngeal teeth in interspecific distant hybrids of cyprinid fish: Phylogeny and expression of the initiation marker genes
Authors: Gu Qianhong , Yuan Hui , Zhong Hui , Wei Zehong , Shu Yuqin , Wang Jing , Ren Li , Gong Dingbin , Liu Shaojun
Published: August 2022

As an important feeding organ and taxonomical characteristic, the pharyngeal teeth of cyprinid fish have very high morphological diversity and exhibit species-specific numbers and arrangements. Many genes have been verified to regulate the pharyngeal teeth development and act as the initiation marker for teeth. Six initiation marker genes for pharyngeal teeth were used as RNA probes to investigate the expression pattern, and these genes were further used to construct a phylogenetic tree for cyprinid fish including some distant hybrids. The results fromin situhybridization showed that similarities and differences existed in the expression ofdlx2b,dlx4b,dlx5a,pitx2, fth1b, andscpp5in the pharyngeal region of the hybrids (BT) by the crosses of blunt snout bream (BSB, ♀) × topmouth culter (TC, ♂). Particularly, we found a high specificity marker genescpp5for the early development of pharyngeal teeth. TheScpp5expression pattern established a clear graphic representation on the spatiotemporal characteristics of the early morphogenesis of pharyngeal teeth in BT and BSB. Our results suggested that the scpp5expression in 4V1, 3V1, and 5V1in BT occurred earlier than that in BSB, while the replacement rate of pharyngeal teeth (4V2, 3V2, and 5V2) was faster in BSB. Phylogenetic analysis revealed that the six marker genes were highly conserved and could be used as the molecular marker for identifying the parents of the distant hybrids in cyprinid fish. The expression patterns of thescpp5gene was examined in various tissues, including the brain, gill, heart, liver, muscle, skin, fins, gonad, eye, and kidney, showing that thescpp5gene was ubiquitously expressed, indicating its important role in cyprinid fish.
Eugenol alleviates transmissible gastroenteritis virus-induced intestinal epithelial injury by regulating NF-κB signaling pathway
Authors: Wang Kang , Chen Daiwen , Yu Bing , He Jun , Mao Xiangbing , Huang Zhiqing , Yan Hui , Wu Aimin , Luo Yuheng , Zheng Ping , Yu Jie , Luo Junqiu
Published: August 2022

Increasing evidence supports the ability of eugenol to maintain intestinal barrier integrity and anti-inflammatory in vitro and in vivo; however, whether eugenol alleviates virus-mediated intestinal barrier damage and inflammation remains a mystery. Transmissible gastroenteritis virus (TGEV), a coronavirus, is one of the main causative agents of diarrhea in piglets and significantly impacts the global swine industry. Here, we found that eugenol could alleviate TGEV-induced intestinal functional impairment and inflammatory responses in piglets. Our results indicated that eugenol improved feed efficiency in TGEV-infected piglets. Eugenol not only increased serum immunoglobulin concentration (IgG) but also significantly decreased serum inflammatory cytokine concentration (TNF-α) in TGEV-infected piglets. In addition, eugenol also significantly decreased the expression of NF-κB mRNA and the phosphorylation level of NF-κB P65 protein in the jejunum mucosa of TGEV-infected piglets. Eugenol increased villus height and the ratio of villus height to crypt depth in the jejunum and ileum, and decreased serum D-lactic acid levels. Importantly, eugenol increased tight junction protein (ZO-1) and mRNA expression levels of nutrient transporter-related genes (GluT-2 and CaT-1) in the jejunum mucosa of TGEV-infected piglets. Meanwhile, compared with TGEV-infected IPEC-J2 cells, treatment with eugenol reduced the cell cytopathic effect, attenuated the inflammatory response. Interestingly, eugenol did not increase the expression of ZO-1 and Occludin in IPEC-J2 cells. However, western blot and immunofluorescence results showed that eugenol restored TGEV-induced down-regulation of ZO-1 and Occludin, while BAY11-7082 (The NF-κB specific inhibitor) enhanced the regulatory ability of eugenol. Our findings demonstrated that eugenol attenuated TGEV-induced intestinal injury by increasing the expression of ZO-1 and Occludin, which may be related to the inhibition of NF-κB signaling pathway. Eugenol may offer some therapeutic opportunities for coronavirus-related diseases.
High baseline expression of IL-6 and IL-10 decreased CCR7 B cells in individuals with previous SARS-CoV-2 infection during BNT162b2 vaccination
Authors: Ponciano-Gómez Alberto , Valle-Solis Martha Iris , Campos-Aguilar Myriam , Jijón-Lorenzo Rafael , Herrera-Cogco Elena de la C. , Ramos-Alor Roberto , Bazán-Mendez César Isaac , Cervantes Gustavo Antonio Pérez-Gil , Ávila-García Ricardo , Aguilar Abdiel González , Texale Moises Geovani Salmerón , Tapia-Sánchez Wilfrido David , Duarte-Martínez Carlos Leonardo , Olivas-Quintero Sandra , Sigrist-Flores Santiago Cristobal , Gallardo-Ortíz Itzell Alejandrina , Villalobos-Molina Rafael , Méndez-Cruz Adolfo Rene , Jimenez-Flores Rafael , Santos-Argumedo Leopoldo , Luna-Arias Juan Pedro , Romero-Ramírez Hector , Rosales-García Victor Hugo , Avendaño-Borromeo Bartolo
Published: August 2022

The current pandemic generated by SARS-CoV-2 has led to mass vaccination with different biologics that have shown wide variations among human populations according to the origin and formulation of the vaccine. Studies evaluating the response in individuals with a natural infection before vaccination have been limited to antibody titer analysis and evaluating a few humoral and cellular response markers, showing a more rapid and intense humoral response than individuals without prior infection. However, the basis of these differences has not been explored in depth. In the present work, we analyzed a group of pro and anti-inflammatory cytokines, antibody titers, and cell populations in peripheral blood of individuals with previous SARS-CoV-2 infection using BNT162b2 biologic. Our results suggest that higher antibody concentration in individuals with an earlier disease could be generated by higher production of plasma cells to the detriment of the presence of memory B cells in the bloodstream, which could be related to the high baseline expression of cytokines (IL-6 and IL-10) before vaccination.
COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds
Authors: Tappe Beeke , Lauruschkat Chris D. , Strobel Lea , Pantaleón García Jezreel , Kurzai Oliver , Rebhan Silke , Kraus Sabrina , Pfeuffer-Jovic Elena , Bussemer Lydia , Possler Lotte , Held Matthias , Hünniger Kerstin , Kniemeyer Olaf , Schäuble Sascha , Brakhage Axel A. , Panagiotou Gianni , White P. Lewis , Einsele Hermann , Löffler Jürgen , Wurster Sebastian
Published: August 2022

Patients suffering from coronavirus disease-2019 (COVID-19) are susceptible to deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis and COVID-19-associated mucormycosis. Despite this clinical observation, direct experimental evidence for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-driven alterations of antifungal immunity is scarce. Using an ex-vivo whole blood stimulation assay, we challenged blood from twelve COVID-19 patients with Aspergillus fumigatus and Rhizopus arrhizus antigens and studied the expression of activation, maturation, and exhaustion markers, as well as cytokine secretion. Compared to healthy controls, T-helper cells from COVID-19 patients displayed increased expression levels of the exhaustion marker PD-1 and weakened A. fumigatus- and R. arrhizus-induced activation. While baseline secretion of proinflammatory cytokines was massively elevated, whole blood from COVID-19 patients elicited diminished release of T-cellular (e.g., IFN-γ, IL-2) and innate immune cell-derived (e.g., CXCL9, CXCL10) cytokines in response to A. fumigatus and R. arrhizus antigens. Additionally, samples from COVID-19 patients showed deficient granulocyte activation by mold antigens and reduced fungal killing capacity of neutrophils. These features of weakened anti-mold immune responses were largely decoupled from COVID-19 severity, the time elapsed since diagnosis of COVID-19, and recent corticosteroid uptake, suggesting that impaired anti-mold defense is a common denominator of the underlying SARS-CoV-2 infection. Taken together, these results expand our understanding of the immune predisposition to post-viral mold infections and could inform future studies of immunotherapeutic strategies to prevent and treat fungal superinfections in COVID-19 patients.
Protection against influenza-induced Acute Lung Injury (ALI) by enhanced induction of M2a macrophages: possible role of PPARγ/RXR ligands in IL-4-induced M2a macrophage differentiation
Authors: Gopalakrishnan Archana , Joseph John , Shirey Kari Ann , Keegan Achsah D. , Boukhvalova Marina S. , Vogel Stefanie N. , Blanco Jorge C. G.
Published: August 2022

Many respiratory viruses cause lung damage that may evolve into acute lung injury (ALI), a cytokine storm, acute respiratory distress syndrome, and ultimately, death. Peroxisome proliferator activated receptor gamma (PPARγ), a member of the nuclear hormone receptor (NHR) family of transcription factors, regulates transcription by forming heterodimers with another NHR family member, Retinoid X Receptor (RXR). Each component of the heterodimer binds specific ligands that modify transcriptional capacity of the entire heterodimer by recruiting different co-activators/co-repressors. However, the role of PPARγ/RXR ligands in the context of influenza infection is not well understood. PPARγ is associated with macrophage differentiation to an anti-inflammatory M2 state. We show that mice lacking the IL-4Rα receptor, required for M2a macrophage differentiation, are more susceptible to mouse-adapted influenza (A/PR/8/34; “PR8”)-induced lethality. Mice lacking Ptgs2, that encodes COX-2, a key proinflammatory M1 macrophage mediator, are more resistant. Blocking the receptor for COX-2-induced Prostaglandin E2 (PGE2) was also protective. Treatment with pioglitazone (PGZ), a PPARγ ligand, increased survival from PR8 infection, decreased M1 macrophage gene expression, and increased PPARγ mRNA in lungs. Conversely, conditional knockout mice expressing PPARγ-deficient macrophages were significantly more sensitive to PR8-induced lethality. These findings were extended in cotton rats: PGZ blunted lung inflammation and M1 cytokine gene expression after challenge with non-adapted human influenza. To study mechanisms by which PPARγ/RXR transcription factors induce canonical M2a genes, WT mouse macrophages were treated with IL-4 in the absence or presence of rosiglitazone (RGZ; PPARγ ligand), LG100754 (LG; RXR ligand), or both. IL-4 dose-dependently induced M2a genes Arg1, Mrc1, Chil3, and Retnla. Treatment of macrophages with IL-4 and RGZ and/or LG differentially affected induction of Arg1 and Mrc1 vs. Chil3 and Retnla gene expression. In PPARγ-deficient macrophages, IL-4 alone failed to induce Arg1 and Mrc1 gene expression; however, concurrent treatment with LG or RGZ + LG enhanced IL-4-induced Arg1 and Mrc1 expression, but to a lower level than in WT macrophages, findings confirmed in the murine alveolar macrophage cell line, MH-S. These findings support a model in which PPARγ/RXR heterodimers control IL-4-induced M2a differentiation, and suggest that PPARγ/RXR agonists should be considered as important tools for clinical intervention against influenza-induced ALI.
Nitrogen utilization analysis reveals the synergetic effect of arginine and urea in promoting fucoxanthin biosynthesis in the mixotrophic marine diatom Phaeodactylum tricornutum
Authors: Yang Runqing , Wei Dong , Pohnert Georg
Published: August 2022

Fucoxanthin is a new dietary ingredient applied in healthy foods with specific benefits of body weight loss and liver fat reduction. The marine diatom Phaeodactylum tricornutum is a highly suitable species for fucoxanthin production. In the present study, aiming to promote fucoxanthin biosynthesis in mixotrophic P. tricornutum, NaNO3, tryptone, and urea were evaluated as nitrogen sources with 0.10 mol L−1 of glycerol as the organic carbon source for mixotrophic growth in shake flasks. Compared to NaNO3, the mixture of tryptone and urea (referred to as T+U, 1:1, mol N:mol N) as organic nitrogen sources could induce a higher biomass and fucoxanthin production. Through nitrogen utilization analysis, leucine, arginine, lysine, and phenylalanine in the T+U medium were identified as the amino acids that primarily support cell growth. Among those amino acids, arginine causes the highest rate of nitrogen utilization and cell growth promotion. After 12 days of cultivation, the highest biomass concentration (3.18 g L−1), fucoxanthin content (12.17 mg g−1), and productivity (2.68 mg L−1 day−1) were achieved using 25 mmol N L−1 of arginine and 5 mmol N L−1 of urea as nitrogen sources, indicating that arginine and urea performed synergistically on enhancing biomass and pigment production. This study provides new insights into the promotion of fucoxanthin biosynthesis by nitrogen utilization analysis and verifies the synergetic effect of arginine and urea on facilitating the development of a promising strategy for efficient enhancement of fucoxanthin production through mixotrophic cultivation of P. tricornutum.
Evaluating the physiological and biochemical responses of different mangrove species to upwelling
Authors: Li Xiaomei , Wang Yutu , Zhang Yuhang , Xiang Jingchang , Yang Zhihao , Gu Fangfang , Wu Meilin
Published: August 2022

Mangroves are unique forest communities with an abundance of species, high productivity and high ecological, social and economic value. Evaluation of the stress resistance of mangrove plants has mainly focused on the effects of high salinity, heavy metals and flooding, with fewer studies evaluating resistance to upwelling stress. Mangrove species of Avicennia marina, Aegiceras corniculatum and Kandelia obovata were submitted to three temperature upwelling (5, 10 and 15°C) and several physiological and biochemical parameters were measured at six time points (0, 6, 12, 24, 72 and 168 h). The data demonstrated: a certain amount of damage occurred to mangrove plants in the face of prolonged upwelling; different mangrove plants have different response strategies to upwelling; mangrove plants are not sensitive to different upwelling temperatures; the resistance of mangrove plants to upwelling stress was in the following order: A. marina< K. obovata< A. corniculatum. Markers of damage such as relative electrical conductivity (REC), malondialdehyde (MDA) and reactive oxygen species (ROS) among all mangrove species were significantly higher with prolonged upwelling stress. The contents of photosynthetic pigments in all three mangrove species also increased. Superoxide dismutase activity (SOD) was maintained at a high level in both control and treatment groupss. By contrary, the change of peroxidase activity (POD) of A. marina and K. obovata was larger than that of A. corniculatum. Catalase activity (CAT) in A. marina and K. obovata significantly increased under upwelling at both 5 and 10°C while there was no obvious variation of CAT in A. corniculatum. Soluble protein and Soluble sugar contents showed no clear variation but stayed at fairly high levels. However, proline content in A. corniculatum significantly increased under long-term upwelling stress while this was not the case in the other two species. High correlation could be observed between A. marina and MDA, O2- and POD in PCA while A. corniculatum showed association with proline and soluble sugar. In conclusion, the ability of A. corniculatum to tolerate upwelling stress might be due mainly to increases in the activities of SOD and the inducing of proline biosynthesis, while, A marina and K. obovata tolerated upwelling stress by adjusting activity levels of SOD, POD and CAT. Segregation in both principal component analysis (PCA) and hierarchical cluster analysis (HCA) further indicated different tolerances and resistances to upwelling between the three species. Our study provides new insights into the stress response of mangroves to upwelling.
MNet-10: A robust shallow convolutional neural network model performing ablation study on medical images assessing the effectiveness of applying optimal data augmentation technique
Authors: Montaha Sidratul , Azam Sami , Rafid A. K. M. Rakibul Haque , Hasan Md. Zahid , Karim Asif , Hasib Khan Md. , Patel Shobhit K. , Jonkman Mirjam , Mannan Zubaer Ibna
Published: August 2022

Interpretation of medical images with a computer-aided diagnosis (CAD) system is arduous because of the complex structure of cancerous lesions in different imaging modalities, high degree of resemblance between inter-classes, presence of dissimilar characteristics in intra-classes, scarcity of medical data, and presence of artifacts and noises. In this study, these challenges are addressed by developing a shallow convolutional neural network (CNN) model with optimal configuration performing ablation study by altering layer structure and hyper-parameters and utilizing a suitable augmentation technique. Eight medical datasets with different modalities are investigated where the proposed model, named MNet-10, with low computational complexity is able to yield optimal performance across all datasets. The impact of photometric and geometric augmentation techniques on different datasets is also evaluated. We selected the mammogram dataset to proceed with the ablation study for being one of the most challenging imaging modalities. Before generating the model, the dataset is augmented using the two approaches. A base CNN model is constructed first and applied to both the augmented and non-augmented mammogram datasets where the highest accuracy is obtained with the photometric dataset. Therefore, the architecture and hyper-parameters of the model are determined by performing an ablation study on the base model using the mammogram photometric dataset. Afterward, the robustness of the network and the impact of different augmentation techniques are assessed by training the model with the rest of the seven datasets. We obtain a test accuracy of 97.34% on the mammogram, 98.43% on the skin cancer, 99.54% on the brain tumor magnetic resonance imaging (MRI), 97.29% on the COVID chest X-ray, 96.31% on the tympanic membrane, 99.82% on the chest computed tomography (CT) scan, and 98.75% on the breast cancer ultrasound datasets by photometric augmentation and 96.76% on the breast cancer microscopic biopsy dataset by geometric augmentation. Moreover, some elastic deformation augmentation methods are explored with the proposed model using all the datasets to evaluate their effectiveness. Finally, VGG16, InceptionV3, and ResNet50 were trained on the best-performing augmented datasets, and their performance consistency was compared with that of the MNet-10 model. The findings may aid future researchers in medical data analysis involving ablation studies and augmentation techniques.
Investigation of a combination therapy approach for the treatment of melioidosis
Authors: Barnes Kay B. , Richards Mark I. , Burgess Gary , Armstrong Stuart J. , Bentley Christine , Maishman Thomas C. , Laws Thomas R. , Nelson Michelle , Harding Sarah V.
Published: August 2022

The efficacy of finafloxacin as a component of a layered defense treatment regimen was determined in vitro and in vivo against an infection with Burkholderia pseudomallei. Doxycycline was down-selected from a panel of antibiotics evaluated in vitro and used in combination with finafloxacin in a Balb/c mouse model of inhalational melioidosis. When treatment was initiated at 24 h post-infection with B. pseudomallei, there were no differences in the level of protection offered by finafloxacin or doxycycline (as monotherapies) when compared to the combination therapy. There was evidence for improved bacterial control in the groups treated with finafloxacin (as monotherapies or in combination with doxycycline) when compared to mice treated with doxycycline. Survival comparisons of finafloxacin and doxycycline (as monotherapies) or in combination initiated at 36 h post-infection indicated that finafloxacin was superior to doxycycline. Doxycycline was also unable to control the levels of bacteria within tissues to the extent that doxycycline and finafloxacin used in combination or finafloxacin (as a sole therapy) could. In summary, finafloxacin is a promising therapy for use in the event of exposure to B. pseudomallei.
Developing methods to study conformational changes in RNA crystals using a photocaged ligand
Authors: Lee Hyun Kyung , Conrad Chelsie E. , Magidson Valentin , Heinz William F. , Pauly Gary , Yu Ping , Ramakrishnan Saminathan , Stagno Jason R. , Wang Yun-Xing
Published: August 2022

Crystallographic observation of structural changes in real time requires that those changes be uniform both spatially and temporally. A primary challenge with time-resolved ligand-mixing diffraction experiments is asynchrony caused by variable factors, such as efficiency of mixing, rate of diffusion, crystal size, and subsequently, conformational heterogeneity. One method of minimizing such variability is use of a photolabile caged ligand, which can fully saturate the crystal environment (spatially), and whose photoactivation can rapidly (temporally) trigger the reaction in a controlled manner. Our recently published results on a ligand-mixing experiment using time-resolved X-ray crystallography (TRX) with an X-ray free electron laser (XFEL) demonstrated that large conformational changes upon ligand binding resulted in a solid-to-solid phase transition (SSPT), while maintaining Bragg diffraction. Here we investigate this SSPT by polarized video microscopy (PVM) after light-triggered release of a photo-caged adenine (pcADE). In general, the mean transition times and transition widths of the SSPT were less dependent on crystal size than what was observed in previous PVM studies with direct ADE mixing. Instead, the photo-induced transition appears to be heavily influenced by the equilibrium between caged and uncaged ADE due to relatively low sample exposure and uncaging efficiency. Nevertheless, we successfully demonstrate a method for the characterization of phase transitions in RNA crystals that are inducible with a photocaged ligand. The transition data for three crystals of different sizes were then applied to kinetic analysis by fitting to the known four-state model associated with ligand-induced conformational changes, revealing an apparent concentration of uncaged ADE in crystal of 0.43–0.46 mM. These results provide further insight into approaches to study time-resolved ligand-induced conformational changes in crystals, and in particular, highlight the feasibility of triggering phase transitions using a light-inducible system. Developing such approaches may be paramount for the rapidly emerging field of time-resolved crystallography.
Continuous theta burst stimulation over left supplementary motor area facilitates auditory-vocal integration in individuals with Parkinson’s disease
Authors: Dai Guangyan , Wang Meng , Li Yongxue , Guo Zhiqiang , Jones Jeffery A. , Li Tingni , Chang Yichen , Wang Emily Q. , Chen Ling , Liu Peng , Chen Xi , Liu Hanjun
Published: August 2022

Accumulating evidence suggests that impairment in auditory-vocal integration characterized by abnormally enhanced vocal compensations for auditory feedback perturbations contributes to hypokinetic dysarthria in Parkinson’s disease (PD). However, treatment of this abnormality remains a challenge. The present study examined whether abnormalities in auditory-motor integration for vocal pitch regulation in PD can be modulated by neuronavigated continuous theta burst stimulation (c-TBS) over the left supplementary motor area (SMA). After receiving active or sham c-TBS over left SMA, 16 individuals with PD vocalized vowel sounds while hearing their own voice unexpectedly pitch-shifted two semitones upward or downward. A group of pairwise-matched healthy participants was recruited as controls. Their vocal responses and event-related potentials (ERPs) were measured and compared across the conditions. The results showed that applying c-TBS over left SMA led to smaller vocal responses paralleled by smaller P1 and P2 responses and larger N1 responses in individuals with PD. Major neural generators of reduced P2 responses were located in the right inferior and medial frontal gyrus, pre- and post-central gyrus, and insula. Moreover, suppressed vocal compensations were predicted by reduced P2 amplitudes and enhanced N1 amplitudes. Notably, abnormally enhanced vocal and P2 responses in individuals with PD were normalized by c-TBS over left SMA when compared to healthy controls. Our results provide the first causal evidence that abnormalities in auditory-motor control of vocal pitch production in PD can be modulated by c-TBS over left SMA, suggesting that it may be a promising non-invasive treatment for speech motor disorders in PD.
Prognostic significance of combined score of fibrinogen and neutrophil-lymphocyte ratio for functional outcome in patients with aneurysmal subarachnoid hemorrhage
Authors: Hou Yuyang , Li Hua , Yang Hongkuan , Chen Rudong , Yu Jiasheng
Published: August 2022

Objective

To explore the relationship between fibrinogen and neutrophil to lymphocyte ratio (F-NLR) score and functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH).

Method

A retrospective study was conducted that involved all consecutive patients with aSAH admitted to our institution from March 2018 to October 2021. Factors, such as demographics, comorbidities, clinical characteristics, neuroradiological data, and laboratory parameters, were collected from institutional databases. All patients achieved neurological assessment using the modified Rankin Scale (mRS) score 3 months after discharge to clarify the functional outcomes. The results were classified as favorable (mRS score 0–2) and unfavorable (mRS score 3–6). Univariate and multivariable analyses were performed to identify the relevant factors between inflammatory markers and functional outcomes after aSAH. Subsequently, a receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predicting performance of variables. A propensity score match (PSM) was performed to correct imbalances in patients' baseline characteristics.

Results

Finally, 256 patients with aSAH were included in the study cohort. A total of 94 (36.7%) patients had an unfavorable outcome. F-NLR scores were 0 [interquartile range (IQR) 0–1] and 1 (IQR 1–2) in patients with favorable and unfavorable outcomes, respectively (p < 0.001). After adjustment, the F-NLR score on admission remained significantly associated with unfavorable outcomes in patients with aSAH. In the multivariable analysis, the F-NLR score was regarded as an independent risk factor of unfavorable outcomes [odds ratio (OR) 3.113, 95% CI 1.755–5.523, p < 0.001]. In ROC analysis, the optimal cutoff value of the F-NLR score was 0.5 points. Two cohorts (n = 86 in each group) obtained from PSM with low F-NLR scores (0 points) and high F-NLR scores (1–2 points) were used for analysis. A significantly higher unfavorable functional outcome rate was observed in patients with high F-NLR scores (33.7 vs. 9.3%, p < 0.001). The area under the curve (AUC) values of F-NLR scores before and after PSM were 0.767 and 0.712, respectively.

Conclusion

Fibrinogen and neutrophil to lymphocyte ratio score was an independent risk parameter associated with unfavorable functional outcomes at 3 months after aSAH. A higher F-NLR score predicts the occurrence of poor functional outcomes.
Enhancing organic selenium content and antioxidant activities of soy sauce using nano-selenium during soybean soaking
Authors: Chen Jingru , Feng Tuo , Wang Bo , He Ronghai , Xu Yanling , Gao Peipei , Zhang Zhi-Hong , Zhang Lei , Fu Jiangyan , Liu Zhan , Gao Xianli
Published: August 2022

Nano-selenium has a greater potential than inorganic selenium in preventing selenium-deficiency diseases due to its higher safety. In this study, spherical nano-selenium particles (53.8 nm) were prepared using sodium selenite, ascorbic acid and chitosan. Selenium-enriched soy sauces were prepared by soaking soybean in nano-selenium and sodium selenite solutions (2–10 mg/L), respectively. Total selenium and organic selenium contents of soy sauces prepared by nano-selenium and sodium selenite were increased by 32–191-fold and 29–173-fold compared to the control (without selenium), and organic selenium accounted for over 90% of total selenium. Soy sauce prepared using 6 mg/L nano-selenium had the strongest antioxidant activities, which were 9.25–28.02% higher than the control. Nano-selenium (6 mg/L) markedly enhanced the koji's enzyme activities (9.76–33.59%), then the latter promoted the release of total phenolics (27.54%), total flavonoids (27.27%) and the formation of free amino acids (16.19%), Maillard reaction products (24.50%), finally the antioxidant activities of selenium-enriched soy sauce were enhanced.
Case Report: A case of uterine leiomyosarcoma metastasized to the vena cava, excised with the aid of preoperative CT three-dimensional imaging
Authors: Long Ling , Zhou Ling , Ying Demei , Huang Yan , Yang Juan , Zhou Lu , Li Sufen , He Xuan , Xie Rongkai
Published: August 2022

Leiomyosarcoma of the uterus (ULMS) is a rare malignant tumor originating from embryonic mesenchymal cells. ULMS tends to metastasize to the lungs, lymph nodes, liver, and bone. Computed tomography three-dimensional (CT 3D) imaging is an advanced diagnostic technique that can track the vessels and their relationships with tumors and reveal the invasion of vessels, including small vessels, around tumors in any slice. Here, we describe a case in which ULMS extended to the retrohepatic inferior vena cava. To date, no report has described resection of metastatic ULMS of the vena cava through supplemental CT 3D imaging. Our patient presented with right lumbar abdominal pain as the main symptom. After using CT 3D reconstruction to accurately assess the relationship between the tumor and the surrounding organs and blood vessels before the operation, the operation was successfully completed through multidisciplinary surgical collaboration.
Intersections of endocrine pathways and the epithelial mesenchymal transition in endometrial cancer
Authors: Gelissen Julia H. , Huang Gloria S.
Published: August 2022

The epithelial mesenchymal transition (EMT) is the process by which cancer cells of epithelial origin, including endometrial cancer, acquire a mesenchymal phenotype with enhanced migratory and invasive capacity, to facilitate metastasis. The regulation of EMT is tissue-specific, and in endometrial cancer, endocrine signaling pathways serve as critical regulators of EMT. The intersections of endocrine signaling and EMT highlight potential avenues for therapeutic intervention to target cancer metastasis with the aim of reduced mortality.
A computational method for large-scale identification of esophageal cancer-related genes
Authors: He Xin , Li Wei-Song , Qiu Zhen-Gang , Zhang Lei , Long He-Ming , Zhang Gui-Sheng , Huang Yang-Wen , Zhan Yun-mei , Meng Fan
Published: August 2022

The incidence of esophageal cancer has obvious genetic susceptibility. Identifying esophageal cancer-related genes plays a huge role in the prevention and treatment of esophageal cancer. Through various sequencing methods, researchers have found only a small number of genes associated with esophageal cancer. In order to improve the efficiency of esophageal cancer genetic susceptibility research, this paper proposes a method for large-scale identification of esophageal cancer-related genes by computational methods. In order to improve the efficiency of esophageal cancer genetic susceptibility research, this paper proposes a method for large-scale identification of esophageal cancer-related genes by computational methods. This method fuses graph convolutional network and logical matrix factorization to effectively identify esophageal cancer-related genes through the association between genes. We call this method GCNLMF which achieved AUC as 0.927 and AUPR as 0.86. Compared with other five methods, GCNLMF performed best. We conducted a case study of the top three predicted genes. Although the association of these three genes with esophageal cancer has not been reported in the database, studies by other reseachers have shown that these three genes are significantly associated with esophageal cancer, which illustrates the accuracy of the prediction results of GCNLMF.
The potential of soluble programmed death-ligand 1 (sPD-L1) as a diagnosis marker for colorectal cancer
Authors: Shao Weifang , Xu Yanhua , Lin Suzhen , Gao Junli , Gao Junshun , Wang Hong
Published: August 2022

Colorectal cancer (CRC) is one of the most significant neoplasms with high morbidity and mortality. Activation of the programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) signaling pathway results in tumor immune evasion by suppressing the activity of T cells. The correlation of soluble PD-L1 (sPD-L1) in serum/plasma with clinicopathological features, lymph node metastasis, diagnosis and prognosis is less clear. The aim of this study was to investigate the relationship between sPD-L1 and clinicopathological features, and diagnosis potentialof CRC. Three hundred patients with CRC were included in this study. sPD-L1 was measured by ELISA. Pretreatment levels of sPD-L1 were significantly elevated in CRC patient sera compared to healthy control (HC) (P<0.001). The median value of sPD-L1 in HC, CRC with non-lymph node metastasis, and CRC with lymph node metastasis were 246.78±50.2pg/mL, 284.12±52.7pg/mL, and 321.31±55.3pg/mL, respectively. ROC analysis of sPD-L1 allowed significant differentiation between HC group and CRC group (lymph node metastasis and non lymph node metastasis (AUC=0.861, 95% CI 0.830-0.887, p<0.001). sPD-L1 is a potential biomarker for the diagnosis of CRC. Multivariate analysis showed that lymph node metastasis and tumor differentiation were independent prognostic factors (all P< 0.01), and sPD-L1 was not correlated with the CRC prognosis (p>0.05).
Case report: Late-onset hypertrophic pyloric stenosis in a 3-year-old boy: It is never too late
Authors: Iacoviello Onofrio , Verriello Giuseppe , Castellaneta Stefania , Palladino Stefano , Wong Michela , Mattioli Girolamo , Giordano Paola , Francavilla Ruggiero , Cristofori Fernanda
Published: August 2022

Hypertrophic Pyloric Stenosis (HPS) represents a relatively rare occurrence beyond infancy. Here, we present the case of a barely 3-year-old boy diagnosed with late-onset HPS and successfully treated with extra-mucosal pyloromyotomy. We review the literature, challenging the principle that more aggressive surgical approaches should be preferred over less invasive ones.
Morinda officinalis oligosaccharides mitigate chronic mild stress-induced inflammation and depression-like behaviour by deactivating the MyD88/PI3K pathway via E2F2
Authors: Zhu Zhen-Hua , Yin Xu-Yuan , Xu Tu-Sun , Tao Wei-Wei , Yao Guang-Da , Wang Pei-Jie , Qi Qi , Jia Qiu-Fang , Wang Jing , Zhu Yue , Hui Li
Published: August 2022

Morinda officinalis oligosaccharides (MOs) are natural herbal extracts that have been shown to exert antidepressant effects. However, the mechanism of this effect remains unclear. Here, we explored the mechanism by which MOs improved experimental depression. Using a chronic mild stress (CMS) murine model, we examined whether MOs could protect against depressive-like behaviour. Lipopolysaccharide (LPS)- and ATP-treated BV2 cells were used to examine the potential mechanism by which MOs mediate the inflammatory response. We found that MOs prevented the CMS-induced reduction in the sucrose preference ratio in the sucrose preference test (SPT) and shortened the immobility durations in both the tail suspension test (TST) and forced swim test (FST). We also noticed that MOs suppressed inflammatory effects by deactivating the MyD88/PI3K pathway via E2F2 in CMS mice or LPS- and ATP-stimulated BV2 cells. Furthermore, overexpression of E2F2 blunted the beneficial effects of MOs in vitro. Collectively, these data showed that MOs exerted antidepressant effects in CMS mice by targeting E2F2-mediated MyD88/PI3K signalling pathway.