bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracellular K+-Responsive Block Copolymer Micelles for Targeted Drug Delivery of Curcumin
Authors: Jiang Mingyue , Chen Le , Chen Bo , Yu Qinghua , Zhang Xianming , Jing Weihong , Ma Limei , Deng Tao , Yang Zhangyou , Yu Chao
Published: June 2022

Curcumin (CUR) is a natural bioactive compound that has attracted attention as a “golden molecule” due to its therapeutic properties against several types of tumors. Nonetheless, the antitumor application of CUR is hampered due to its extremely low aqueous solubility and chemical instability. Herein, a novel type of CUR-loaded polymeric micelles with intracellular K+-responsive controlled-release properties is designed and developed. The polymeric micelles are self-assembled by poly (N-isopropylacrylamide-co-acryloylamidobenzo-15-crown-5-co-N, N-dimethylacrylamide)-b-DSPE (PNDB-b-DSPE) block copolymers, and CUR. CUR is successfully loaded into the micelles with a CUR loading content of 6.26 wt%. The proposed CUR-PNDB-DSPE polymeric micelles exhibit a significant CUR release in simulated intracellular fluid due to the formation of 2 : 1 ‘‘sandwich’’ host–guest complexes of 15-crown-5 and K+, which lead to the hydrophilic outer shell of micelles to collapse and the drug to rapidly migrate out of the micelles. In vitro, the B16F10 cell experiment indicates that CUR-PNDB-DSPE micelles exhibit a high cellular uptake and excellent intracellular drug release in response to the intracellular K+ concentration. Moreover, CUR-PNDB-DSPE micelles show high cytotoxicity to B16F10 cells compared to free CUR and CUR-PEG-DSPE micelles. The polymeric micelles with intracellular K+-responsive controlled release properties proposed in this study provide a new strategy for designing novel targeted drug delivery systems for CUR delivery for cancer treatment.
Ketoreductase Catalyzed (Dynamic) Kinetic Resolution for Biomanufacturing of Chiral Chemicals
Authors: Huang Chenming , Liu Junling , Fang Jiali , Jia Xian , Zheng Zhendong , You Song , Qin Bin
Published: June 2022

Biocatalyzed asymmetric reduction of ketones is an environmentally friendly approach and one of the most cost-effective routes for producing chiral alcohols. In comparison with the well-studied reduction of prochiral ketones to generate chiral alcohols with one chiral center, resolution of racemates by ketoreductases (KREDs) to produce chiral compounds with at least two chiral centers is also an important strategy in asymmetric synthesis. The development of protein engineering and the combination with chemo-catalysts further enhanced the application of KREDs in the efficient production of chiral alcohols with high stereoselectivity. This review discusses the advances in the research area of KRED catalyzed asymmetric synthesis for biomanufacturing of chiral chemicals with at least two chiral centers through the kinetic resolution (KR) approach and the dynamic kinetic resolution (DKR) approach.
The Social and Emotional Well-being of Indigenous Peoples Living With Diabetes: A Systematic Review Protocol
Authors: Speight Jane , Baptista Shaira , Lee Christopher , Sher Louisa , Skinner Timothy C. , Brown Alex
Published: June 2022

Introduction

Globally, Indigenous people have a greater incidence and earlier onset of diabetes than the general population and have higher documented rates of emotional distress and mental illness. This systematic review will provide a synthesis and critical appraisal of the evidence focused on the social and emotional well-being of Indigenous peoples living with diabetes, including prevalence, impact, moderators, and the efficacy of interventions.

Methods

We will search MEDLINE Complete, EMBASE, APA PsycINFO, and CINAHL Complete from inception until late April 2021. Search strategies will include keywords related to Indigenous peoples, diabetes, and social and emotional well-being. All abstracts will be rated independently by two researchers against specified inclusion criteria. Eligible studies will report social and emotional well-being data for Indigenous people with diabetes, and/or report on the efficacy of interventions designed to address social and emotional well-being in this population. For each eligible study, quality will be rated using standard checklists to appraise each study’s internal validity, to be determined based on study type. Any discrepancies will be resolved through discussions and consultation with other investigators as needed. We expect to present a narrative synthesis of the evidence.

Discussion

The findings of the systematic review will enable greater understanding of the impact of relationships between diabetes and emotional well-being among Indigenous peoples to inform research, policy and practice. The findings will be accessible to Indigenous people affected by diabetes through a summary published in plain language on our research centre’s website.

Systematic Review Registration

PROSPERO registration number: CRD42021246560.
Homocysteine Metabolism in Pregnancy and Developmental Impacts
Authors: D’Souza Stephen W. , Glazier Jocelyn D.
Published: June 2022

Homocysteine is a metabolite generated by methionine cycle metabolism, comprising the demethylated derivative of methionine. Homocysteine can be metabolised by the transsulphuration pathway to cystathionine, which requires vitamin B6, or can undergo remethylation to methionine. Homocysteine remethylation to methionine is catalysed by methionine synthase activity which requires vitamin B12, regenerating methionine to allow synthesis of the universal methyl donor S-adenosylmethionine required for methylation and gene transcription regulation. The methyl-group donated for homocysteine remethylation comes from 5-methyltetrahydrofolate generated by the folate cycle, which allows tetrahydrofolate to be returned to the active folate pool for nucleotide biosynthesis. Therefore the integrated actions of the methionine and folate cycles, required to metabolise homocysteine, also perpetuate methylation and nucleotide synthesis, vitally important to support embryonic growth, proliferation and development. Dysregulated activities of these two interdependent metabolic cycles, arising from maternal suboptimal intake of nutrient co-factors such as folate and vitamin B12 or gene polymorphisms resulting in reduced enzymatic activity, leads to inefficient homocysteine metabolic conversion causing elevated concentrations, known as hyperhomocysteinemia. This condition is associated with multiple adverse pregnancy outcomes including neural tube defects (NTDs). Raised homocysteine is damaging to cellular function, binding to proteins thereby impairing their function, with perturbed homocysteine metabolism impacting negatively on embryonic development. This review discusses the “cross-talk” of maternal-fetal homocysteine interrelationships, describes the placental transport of homocysteine, homocysteine impacts on pregnancy outcomes, homocysteine and methylation effects linking to NTD risk and proposes a putative pathway for embryonic provision of folate and vitamin B12, homocysteine-modulating nutrients that ameliorate NTD risk.
The Kinetoplastid-Specific Protein TcCAL1 Plays Different Roles During In Vitro Differentiation and Host-Cell Invasion in Trypanosoma cruzi
Authors: Rodríguez-Durán Jessica , Gallardo Juan Pablo , Alba Soto Catalina Dirney , Gómez Karina Andrea , Potenza Mariana
Published: June 2022

In the pathogen Typanosoma cruzi, the calcium ion (Ca2+) regulates key processes for parasite survival. However, the mechanisms decoding Ca2+ signals are not fully identified or understood. Here, we investigate the role of a hypothetical Ca2+-binding protein named TcCAL1 in the in vitro life cycle of T. cruzi. Results showed that the overexpression of TcCAL1 fused to a 6X histidine tag (TcCAL1-6xHis) impaired the differentiation of epimastigotes into metacyclic trypomastigotes, significantly decreasing metacyclogenesis rates. When the virulence of transgenic metacyclic trypomastigotes was explored in mammalian cell invasion assays, we found that the percentage of infection was significantly higher in Vero cells incubated with TcCAL1-6xHis-overexpressing parasites than in controls, as well as the number of intracellular amastigotes. Additionally, the percentage of Vero cells with adhered metacyclic trypomastigotes significantly increased in samples incubated with TcCAL1-6xHis-overexpressing parasites compared with controls. In contrast, the differentiation rates from metacyclic trypomastigotes to axenic amastigotes or the epimastigote proliferation in the exponential phase of growth have not been affected by TcCAL1-6xHis overexpression. Based on our findings, we speculate that TcCAL1 exerts its function by sequestering intracellular Ca2+ by its EF-hand motifs (impairing metacyclogenesis) and/or due to an unknown activity which could be amplified by the ion binding (promoting cell invasion). This work underpins the importance of studying the kinetoplastid-specific proteins with unknown functions in pathogen parasites.
Streamlined and Robust Stage-Specific Profiling of Gametocytocidal Compounds Against Plasmodium falciparum
Authors: Reader Janette , van der Watt Mariette E. , Birkholtz Lyn-Marié
Published: June 2022

Malaria elimination is dependent on the ability to target both the pathogenic and transmissible stages of the human malaria parasite, Plasmodium falciparum. These forms of the parasite are differentiated by unique developmental stages, each with their own biological mechanisms and processes. These individual stages therefore also respond differently to inhibitory compounds, and this complicates the discovery of multistage active antimalarial agents. The search for compounds with transmission-blocking activity has focused on screening for activity on mature gametocytes, with only limited descriptions available for the activity of such compounds on immature stage gametocytes. This therefore poses a gap in the profiling of antimalarial agents for pan-reactive, multistage activity to antimalarial leads. Here, we optimized an effective and robust strategy for the simple and cost-effective description of the stage-specific action of gametocytocidal antimalarial compounds.
Metavirome Analysis of Culex tritaeniorhynchus Reveals Novel Japanese Encephalitis Virus and Chikungunya Virus
Authors: Zhang Duo , Peng Chengcheng , Li Chenghui , Li Yiquan , Zhang He , Li Nan , Xiao Pengpeng
Published: June 2022

To explore the Culex tritaeniorhynchuses–specific virome, 6400 C. tritaeniorhynchuses were collected in Honghe autonomous prefecture, China. Abundant virus sequences were obtained from 28 viral families using metavirome sequencing. Herein, several viruses in C. tritaeniorhynchuses virome were verified using the PCR technique, which covers Japanese encephalitis virus (JEV), Getah virus, and even Chikungunya virus (CHIKV). Seven JEV gene sequences were amplified successfully, of which JEV-China/CT2016E-1 shared the highest homology with the known JEV sequence isolated in Korea, 1946, with at least 96.1% nucleotide (nt) identity, which belonged to genotype III. Nine CHIKV gene sequences were amplified, which shared the highest with at least 93.0% nt identity with CHIKV from Thailand isolated in 2007, which was assigned to genotype Asian. Remarkably, CHIKV was isolated from C. tritaeniorhynchus in China for the first time. It was initially confirmed that the isolated virus CHIKV-China/CT2016-1 may increase infectivity after passaging in Vero cells from BHK-21 cells. Collectively, our study reveals the diversity, properties, and potential virus susceptibility dynamics of the C. tritaeniorhynchus virome and sheds new perspectives on the viral ecology in other important biological vectors.
Macrophages-Related Genes Biomarkers in the Deterioration of Atherosclerosis
Authors: Zheng Yue , Qi Bingcai , Gao Wenqing , Qi Zhenchang , Liu Yanwu , Wang Yuchao , Feng Jianyu , Cheng Xian , Luo Zhiqiang , Li Tong
Published: June 2022

Background

The macrophages are involved in all stages of cardiovascular diseases, demonstrating the correlation between inflammation, atherosclerosis, and myocardial infarction (MI). Here, we aim to investigate macrophages-related genes in the deterioration of atherosclerosis.

Methods

GSE41571 was downloaded and the abundance of immune cells was estimated by utilizing the xCell. By utilizing the limma test and correlation analysis, differentially expressed macrophages-related genes (DEMRGs) were documented. The functional pathways and the protein–protein interaction (PPI) network were analyzed and the hub DEMRGs were obtained. The hub DEMRGs and their interactions were analyzed using NetworkAnalyst 3.0 and for validation, the expressions of hub DEMRGs were analyzed using the GSE135055 and GSE116250 datasets as well as atherosclerosis and MI mice model.

Results

A total of 509 differentially expressed genes (DEGs) were correlated with the abundance of macrophages and were identified as DEMRGs (Pearson correlation coefficients (PCC) > 0.6), which were mainly enriched in extracellular structure organization, lysosomal membrane, MHC protein complex binding, and so on. After screening out, 28 hub DEMRGs were obtained with degrees ≥20, including GNAI1 (degree = 113), MRPS2 (degree = 56), HCK (degree = 45), SOCS3 (degree = 40), NET1 (degree = 28), and so on. After validating using Gene Expression Omnibus (GEO) datasets and the atherosclerosis and MI mice model, eight proteins were validated using ApoE-/- and C57 mice. The expression levels of proteins, including SYNJ2, NET1, FZD7, LCP2, HCK, GNB2, and PPP4C were positively correlated to left ventricular ejection fraction (LVEF), while that of EIF4EBP1 was negatively correlated to LVEF.

Conclusion

The screened hub DEMRGs, SYNJ2, NET1, FZD7, LCP2, HCK, GNB2, EIF4EBP1, and PPP4C, may be therapeutic targets for treatment and prediction in the patients with plaque progression and MI recurrent events. The kit of the eight hub DEMRGs may test plaque progression and MI recurrent events and help in the diagnosis and treatment of MI-induced heart failure (HF), thus decreasing mortality and morbidity.
First-in-Human Implantation of Gutter-Free Design Stent-Graft in in situ Fenestration TEVAR for Aortic Arch Pathology
Authors: Li Xin , Shu Chang , Wang Lunchang , Li Quanming , Fang Kun , Luo Mingyao , Zhang Weichang , Zhou Yang , Zhou Haiyang
Published: June 2022

Purpose

To report the technology and preliminary result of gutter-free design stent-grafted in in situ fenestration thoracic endovascular aortic repair (TEVAR).

Description

The gutter-free stent-graft has a nickel-titanium self-expanding skeleton, double polytetrafluoroethylene coating, and an outer-skirt fabric structure (named C-skirt endograft). The outer skirt fabric prevents endoleak from the gutter around the stent graft fenestration. Further, the skirt structure right under the fenestration in the aortic stent graft can function as a fixation of the side-branch artery endograft. These designs have the following advantages, such as: 1) prevention of endoleak; and 2) fixation tightly between the branch and aorta endograft pieces.

Evaluation

A patient who was diagnosed with an aortic arch aneurysm, combined with localized dissection, has successfully implanted the aortic stent graft and C-skirt endograft for the left subclavian artery. The 6-month follow-up result of the C-skirt in situ fenestration TEVAR is satisfactory without obvious endoleak.

Conclusions

The new gutter-free C-skirt stent graft is being safely and effectively used for aortic arch TEVAR. Long-term evaluation of safety, effectivity, and durability needs to be proven by future multi-center studies.
A System-Wide Investigation and Stratification of the Hemostatic Proteome in Premature Myocardial Infarction
Authors: Dunster Joanne L. , Wright Joy R. , Samani Nilesh J. , Goodall Alison H.
Published: June 2022

Introduction

Advancing understanding of key factors that determine the magnitude of the hemostatic response may facilitate the identification of individuals at risk of generating an occlusive thrombus as a result of an atherothrombotic event such as an acute Myocardial Infarction (MI). While fibrinogen levels are a recognized risk factor for MI, the association of thrombotic risk with other coagulation proteins is inconsistent. This is likely due to the complex balance of pro- and anticoagulant factors in any individual.

Methods

We compared measured levels of pro- and anticoagulant proteins in plasma from 162 patients who suffered an MI at an early age (MI <50 y) and 186 age- and gender-matched healthy controls with no history of CAD. We then used the measurements from these individuals as inputs for an established mathematical model to investigate how small variations in hemostatic factors affect the overall amplitude of the hemostatic response and to identify differential key drivers of the hemostatic response in male and female patients and controls.

Results

Plasma from the MI patients contained significantly higher levels of Tissue Factor (P = 0.007), the components of the tenase (FIX and FVIII; P < 0.0001 for both) and the prothrombinase complexes (FX; P = 0.003), and lower levels of Tissue Factor Pathway Inhibitor (TFPI; P = 0.033) than controls. The mathematical model, which generates time-dependent predictions describing the depletion, activation, and interaction of the main procoagulant factors and inhibitors, identified different patterns of hemostatic response between MI patients and controls, and additionally, between males and females. Whereas, in males, TF, FVIII, FIX, and the inhibitor TFPI contribute to the differences seen between case and controls, and in females, FII, FVIII, and FIX had the greatest influence on the generation of thrombin. We additionally show that further donor stratification may be possible according to the predicted donor response to anticoagulant therapy.

Conclusions

We suggest that modeling could be of value in enhancing our prediction of risk of premature MI, recurrent risk, and therapeutic efficacy.
Multi-Factor Evaluation of Deep Karst Dolomite Reservoir Based on Paleogeomorphological Reconstruction, a Case Study From the 4th Member of the Dengying Formation in the Central Sichuan Basin, China
Authors: Zhou Zikun , Wang Xingzhi , Yang Xiyan , Wen Long , Wang Wenzhi , Zeng Deming , Wei Mingyang , Xie Shengyang , Huo Fei
Published: June 2022

The evaluation of reservoirs is of great importance in exploration practices, and reservoir distribution is dependent on multiple geological factors. The carbonate platform of the fourth member (Z2dn4) of the Dengying Formation (Z2dn) in the Gaoshiti-Moxi area (GMA) was uplifted above sea level during episode II of the Tongwan movement and underwent prolonged karstification by meteoric freshwater in the terminal Sinian, leading to a strong heterogeneity in reservoirs. Paleogeomorphology reflects hydraulic gradients that can affect the intensities of surface karstification and may be approximated by terrain slope gradients. Karst products (especially solution vugs and caverns) exist prevailingly in the Z2dn4; their development mirrors the extents of internal dissolution. Based on paleogeomorphological reconstruction using the elevation method, the slope angles of single boreholes were calculated through the digital elevation model (DEM). In accordance with single-borewell Fullbore Formation MicroImager (FMI) logging data, four electrofacies (host rock, vug, fracture, and cave) were identified in boreholes possessing FMI data. The identified electrofacies were matched with corresponding conventional logging curves to obtain the training data. A model generalized for other boreholes without FMI data was established with the random forest algorithm and the thicknesses of the four electrofacies in each borehole were determined to characterize the extent of karstification. Slope gradients and electrofacies thicknesses, together with multiple physical parameters of reservoirs in boreholes, were utilized for factor analysis. Four factors were obtained and fused into one comprehensive score based on their ratios of variance proportions. The favorability of reservoirs was described by the comprehensive scores of each borehole. These analyses showed that the most advantageous reservoirs are distributed in the vicinity of the platform margin in the west of the GMA, where they enjoy several benefits. Deposition of porous mound-shoal complexes occurs predominantly in the platform margin where large-scale caves are more developed in the mixing karst zone of seawater and freshwater. Meanwhile, the transmeridional lateral migration of hydrocarbons from the regional hydrocarbon-generating center abutting the west of the GMA contributes to earlier entrapment and accumulation in the mound-shoal complexes in the platform margin.
Sparse Gaussian Process Regression for Landslide Displacement Time-Series Forecasting
Authors: Yang Weiqi , Feng Yuran , Wan Jian , Wang Lingling
Published: June 2022

Landslide hazards are complex nonlinear systems with a highly dynamic nature. Accurate forecasting of landslide displacement and evolution is crucial for the prevention and mitigation of landslide hazards. In this study, a probabilistic landslide displacement forecasting model based on the quantification of epistemic uncertainty is proposed. In particular, the displacement forecasting problem is cast as a time-series regression problem with limited training samples and must be solved by statistical inference. The epistemic uncertainty of the landslide displacement series is depicted by the statistical properties of the function space constituted by the nonlinear mappings generated by the sparse Gaussian process regression. Data for our study was collected from the study area located in northwestern China. Other state-of-the-art probabilistic forecasting models have also been utilized for comparative analysis. The experimental results confirmed the superiority of the sparse Gaussian process in the modeling of landslide displacement series in terms of forecasting accuracy, uncertainty quantification, and robustness to overfitting.
Thyroid Function at Age Fifty After Prenatal Famine Exposure in the Dutch Famine Birth Cohort
Authors: Keestra Sarai M. , Motoc Irina , Ravelli Anita C.J. , Roseboom Tessa J. , Finken Martijn J.J.
Published: June 2022

Background

Early-life exposures during gestation may permanently alter thyroid physiology and health in adulthood. We investigated whether exposure to the Dutch Famine (1944-1945) in late, mid, or early gestation influences thyroid function (i.e., incidence of thyroid disease, thyroid autoantibodies, thyroid stimulating hormone (TSH), and free thyroxine (FT4) levels) in adulthood. We specifically assessed whether potential effects of famine differed for men and women.

Methods

This study includes 910 men and women born as term singletons in the Wilhelmina Gasthuis in Amsterdam, the Netherlands, shortly before, during, or after the Dutch Famine. We evaluated medical histories for previous diagnosis or current treatment for thyroid dysfunction. At age 50 blood samples were drawn from 728 individuals for tests of thyroid function. We studied the prevalence of overt hypo- and hyperthyroidism and thyroid autoimmunity using medical histories, and measurements of TSH, FT4, anti-TPO and anti-TG, comparing participants exposed to famine at different pregnancy trimesters or born before or conceived after the famine. Additionally, we studied associations of TSH and FT4 levels with in utero famine exposure in a subsample of men and women free of thyroid disease that were exposed in late, mid, or early gestation.

Results

There were no differences in thyroid dysfunction diagnosis or current treatment between participants at age 50 years who been exposed to famine during different periods of gestation and those born before or conceived after. There was no association between famine exposure and overt hypo- or hyperthyroidism or thyroid autoantibody positivity. Women who had been exposed to famine in mid gestation had slightly lower TSH levels than women who had not been exposed to famine prenatally (b=-0.06; 95%; CI=[-0.11,-0.02]; p<0.01). No differences in TSH levels were observed in men, and no differences in FT4 levels were observed in men or women.

Conclusions

There are no differences in adult thyroid disease at age 50 years according to prenatal famine exposure. However, the lower TSH levels in women exposed to famine in the second trimester suggest that there may be sex-specific effects of famine exposure during a critical period of thyroid development on hypothalamic-pituitary-thyroid axis regulation in adulthood.
A Prospective Cohort Study of Metformin as an Adjuvant Therapy for Infertile Women With Endometrial Complex Hyperplasia/Complex Atypical Hyperplasia and Their Subsequent Assisted Reproductive Technology Outcomes
Authors: Kong Wei-ya , Liu Zheng-ai , Zhang Na , Wu Xue , Zhao Xing-bo , Yan Lei
Published: June 2022

Objective

To investigate the adjuvant efficacy of metformin treatment to achieve pathological complete response (CR) in patients with endometrial complex hyperplasia (CH) and complex atypical hyperplasia (CAH), and secondarily, to evaluate their pregnancy outcomes after following assisted reproductive technology (ART).

Study Design

This prospective cohort study analyzed 219 patients diagnosed with infertility and CH/CAH from January 2016 to December 2020. Among these patients, 138 were assigned to the control group (progesterone alone) and 81 were assigned to the study group (progesterone+metformin). After 8/12 weeks of therapy, the treatment responses were assessed by histological examination of curettage specimens obtained by hysteroscopy. Once the pathological results indicated CR, the patients were able to receive ART. The ART treatment and follow-up data of these patients were collected and analyzed.

Results

116 patients in the control group achieved CR, compared with 76 patients in the study group. The CR rate in the control group was significantly lower than that in the study group (P=0.034). We then divided the patients into subgroups to compare the treatment responses. In the subgroup analyses, patients with body mass index (BMI) ≥25 kg/m2 and patients with polycystic ovarian syndrome (PCOS) had higher CR rates in the metformin group compared with the control group (P=0.015, P=0.028 respectively). Subsequently, 68 patients in the control group and 47 patients in the study group received an ART cycle. We examined the pregnancy indications and found no significant differences in the clinical pregnancy rate and live birth rate between the two groups (P>0.05).

Conclusion

Regression of CH/CAH may be improved by progesterone+metformin compared with progesterone alone. The effect was particularly pronounced in patients with BMI ≥25 kg/m2 and patients with PCOS. Metformin had no obvious effect on subsequent ART outcomes. The trial is registered on the publicly accessible website:

Clinical Trial Registration

http://www.chictr.org.cn/showproj.aspx?proj=15372, identifier ChiCTR-ONR-16009078.
Diabetic Muscular Atrophy: Molecular Mechanisms and Promising Therapies
Authors: Shen Yuntian , Li Ming , Wang Kexin , Qi Guangdong , Liu Hua , Wang Wei , Ji Yanan , Chang Mengyuan , Deng Chunyan , Xu Feng , Shen Mi , Sun Hualin
Published: June 2022

Diabetes mellitus (DM) is a typical chronic disease that can be divided into 2 types, dependent on insulin deficiency or insulin resistance. Incidences of diabetic complications gradually increase as the disease progresses. Studies in diabetes complications have mostly focused on kidney and cardiovascular diseases, as well as neuropathy. However, DM can also cause skeletal muscle atrophy. Diabetic muscular atrophy is an unrecognized diabetic complication that can lead to quadriplegia in severe cases, seriously impacting patients’ quality of life. In this review, we first identify the main molecular mechanisms of muscle atrophy from the aspects of protein degradation and synthesis signaling pathways. Then, we discuss the molecular regulatory mechanisms of diabetic muscular atrophy, and outline potential drugs and treatments in terms of insulin resistance, insulin deficiency, inflammation, oxidative stress, glucocorticoids, and other factors. It is worth noting that inflammation and oxidative stress are closely related to insulin resistance and insulin deficiency in diabetic muscular atrophy. Regulating inflammation and oxidative stress may represent another very important way to treat diabetic muscular atrophy, in addition to controlling insulin signaling. Understanding the molecular regulatory mechanism of diabetic muscular atrophy could help to reveal new treatment strategies.
Sources of Energy Poverty: A Factor Analysis Approach for Spain
Authors: Taltavull de La Paz Paloma , Juárez Tárrega Francisco , Su Zhenyu , Monllor Paloma
Published: June 2022

This study estimates housing quality and features explaining energy poverty in Spain and its regions. By using the EU-SILC dataset for 2008–2019, it calculates the hidden links between energy poverty indicators and housing features, controlled by other variables such as type of household, poverty, and housing tenancy. Confirmatory factor analysis is used to identify the role of different dimensions in explaining energy poverty at the household level. The empirical evidence finds three hidden factors associating energy poverty with poverty, poor housing quality, and housing size and outskirts location. These three factors enable classifying households accordingly, revealing their distribution across Spain and three of its 17 Spanish regions: Madrid, Cataluña, and Valencian Community. Findings indicate how the impact of energy poverty differs by region, rejecting the general hypothesis that all households in poverty live in poor housing because they cannot afford the maintenance costs, thus causing energy poverty. Results suggest that energy poverty due to poor housing quality and location affects many households that are not necessarily poor, with different impacts depending on location. The association between energy poverty and larger houses located on the outskirts represents new evidence in the literature and is one of the contributions of this study, together with the methodology for classification. Results suggest that retrofitting investment would be crucial in reducing energy poverty problems in Spain.
The Role of Spatial Patterns of Low Impact Development in Urban Runoff Pollution Control Within Parcel Based Catchments
Authors: Ma Yukun , Zhao Hongtao
Published: June 2022

Landscape patterns significantly affect urban runoff pollution, and a reasonable arrangement of pervious patches in urban catchments is critical to control urban non-point-source pollution. Low impact development (LID) can be recognized as a pervious surface type, and many previous studies have analyzed the LID performance at a system scale. However, the influence of the LID spatial distribution on runoff pollutant transport at a catchment scale remains unclear. This study analyzed the influence of pervious/impervious patterns on runoff pollution within two urban catchments constructed with LID. It was found that the runoff pollution was influenced by the area ratio, circumference, shape, and pervious patch connectivity of pervious surfaces (i.e., LID). Catchments with high perviousness ratios are more efficient in reducing the runoff volume and suspended solids, and LID should focus on removing runoff pollutants at catchments with high imperviousness ratios. Six typical landscape metrics that represented the fragmentation, complexity and vergence of pervious surfaces were selected to investigate the influence of pervious/impervious patterns on runoff pollution. The results show that larger fragmentation, smaller complexity and smaller vergence of pervious patches result in larger runoff volumes and more pollutants. Therefore, it is recommended that large pervious areas should be retained and close to one another to enhance the retention capacity of LID, and the outline of pervious patches should be long and irregular to reduce pollution confluence. The results of this study are helpful in arranging LID structures for efficient runoff regulation and pollution control at an urban catchment scale.
A Metabolism-Related Gene Prognostic Index Bridging Metabolic Signatures and Antitumor Immune Cycling in Head and Neck Squamous Cell Carcinoma
Authors: Du Kunpeng , Zou Jingwen , Wang Baiyao , Liu Chunshan , Khan Muhammad , Xie Tao , Huang Xiaoting , Shen Piao , Tian Yunhong , Yuan Yawei
Published: June 2022

Background

In the era of immunotherapy, predictive or prognostic biomarkers for head and neck squamous cell carcinoma (HNSCC) are urgently needed. Metabolic reprogramming in the tumor microenvironment (TME) is a non-negligible reason for the low therapeutic response to immune checkpoint inhibitor (ICI) therapy. We aimed to construct a metabolism-related gene prognostic index (MRGPI) for HNSCC bridging metabolic characteristics and antitumor immune cycling and identified the immunophenotype, genetic alternations, potential targeted inhibitors, and the benefit of immunotherapy in MRGPI-defined subgroups of HNSCC.

Methods

Based on The Cancer Genome Atlas (TCGA) HNSCC dataset (n = 502), metabolism-related hub genes were identified by the weighted gene co-expression network analysis (WGCNA). Seven genes were identified to construct the MRGPI by using the Cox regression method and validated with an HNSCC dataset (n = 270) from the Gene Expression Omnibus (GEO) database. Afterward, the prognostic value, metabolic activities, genetic alternations, gene set enrichment analysis (GSEA), immunophenotype, Connectivity map (cMAP), and benefit of immunotherapy in MRGPI-defined subgroups were analyzed.

Results

The MRGPI was constructed based on HPRT1, AGPAT4, AMY2B, ACADL, CKM, PLA2G2D, and ADA. Patients in the low-MRGPI group had better overall survival than those in the high-MRGPI group, consistent with the results in the GEO cohort (cutoff value = 1.01). Patients with a low MRGPI score display lower metabolic activities and an active antitumor immunity status and more benefit from immunotherapy. In contrast, a higher MRGPI score was correlated with higher metabolic activities, more TP53 mutation rate, lower antitumor immunity ability, an immunosuppressive TME, and less benefit from immunotherapy.

Conclusion

The MRGPI is a promising indicator to distinguish the prognosis, the metabolic, molecular, and immune phenotype, and the benefit from immunotherapy in HNSCC.
The Immune Change of the Lung and Bowel in an Ulcerative Colitis Rat Model and the Protective Effect of Sodium Houttuyfonate Combined With Matrine
Authors: Ni Lulu , Jing Shan , Zhu Li , Yang Xue , Wang Xinyue , Tu Su
Published: June 2022

Objective

To explore the immune change of lung injury of Ulcerative colitis (UC) by observing the changes of inherent immunity and adaptive immunity of the lung and bowel in UC rat models after the treatment of Sodium Houttuyfonate combined with Matrine.

Method

UC rat models were established with the mucous membrane of colon allergize combined with TNBS-alcohol enteroclysis for 1 week and 5 weeks. 1-week experimental rats were divided into normal group and model group, 5/each group. 5-weeks experimental rats were divided into normal group, model group, Sodium Houttuyfonate (2.9mg/ml) combined with Matrine (1.47mg/ml), and positive control sulfasalazine (10mg/ml), 5/each group. All rats were administered by gavage for 5 weeks. The histopathological and fibrotic changes in the lung and bowel were observed, and the expressions of Tumor Necrosis Factor (TNF)- α, interleukin (IL)-8 in the lung, bowel, and serum were detected by radio-immunity and immunohistochemistry, and the mRNA expressions of Toll-like receptor (TLR)-4, nuclear factor kappa (NF-κB), Macrophage migration inhibitory factor (MIF), Mucosal addressing cell adhesion molecule-1 (MadCAM1) and Pulmonary surfactant protein-A (SP-A) in the lung and bowel were detected by Real time-PCR.

Result

Compared with the normal group, the model rats had significant histopathological and fibrotic changes both in the lung and bowel, and all treatment groups were improved. After treatment, TLR4, IL-8, MIF, and TNF-α in the lung decreased (P<0.05); NF-KB, IL-8, and MIF in the bowel increased (P<0.05); MadCAM1 both in lung and bowel decreased (P<0.05); SP-A decreased in bowel and increased in the lung (P<0.05).

Conclusion

The cause of lung injury in this model was found to be related to inherent immunity and adaptive immunity, while the cause of bowel injury in this model was found to be mainly related to adaptive immunity. Sodium Houttuyfonate combined with Matrine could improve bowel and lung injury.
Zika Virus Induces Sex-Dependent Metabolic Changes in Drosophila melanogaster to Promote Viral Replication
Authors: Tafesh-Edwards Ghada , Kalukin Ananda , Eleftherianos Ioannis
Published: June 2022

Zika is a member of the Flaviviridae virus family that poses some of the most significant global health risks, causing neurologic complications that range from sensory neuropathy and seizures to congenital Zika syndrome (microcephaly) in infants born to mothers infected during pregnancy. The recent outbreak of Zika virus (ZIKV) and its serious health threats calls for the characterization and understanding of Zika pathogenesis, as well as host antiviral immune functions. Although ZIKV has been associated with activating the RNA interference (RNAi) immune pathway and altering host metabolism, in-depth studies are still required to uncover the specifics of the complex host-virus interactions and provide additional insights into the molecular components that determine the outcome of this disease. Previous research establishes the fruit fly Drosophila melanogaster as a reliable model for studying viral pathogens, as it shares significant similarities with that of vertebrate animal systems. Here, we have developed an in vivo Drosophila model to investigate ZIKV-mediated perturbed metabolism in correlation to the RNAi central mediator Dicer-2. We report that ZIKV infection reprograms glucose and glycogen metabolism in Dicer-2 mutants to maintain efficient replication and successful propagation. Flies that exhibit these metabolic effects also show reduced food intake, which highlights the complicated neurological defects associated with ZIKV. We show that ZIKV infection significantly reduces insulin gene expression in Dicer-2 mutants, suggesting an insulin antiviral role against ZIKV and a direct connection to RNAi immunity. Moreover, we find that the insulin receptor substrate chico is crucial to the survival of ZIKV-infected flies. These observations are remarkably more severe in adult female flies compared to males, indicating possible sex differences in the rates of infection and susceptibility to the development of disease. Such findings not only demonstrate that metabolic alterations can be potentially exploited for developing immune therapeutic strategies but also that preventive measures for disease development may require sex-specific approaches. Therefore, further studies are urgently needed to explore the molecular factors that could be considered as targets to inhibit ZIKV manipulation of host cell metabolism in females and males.
Role of Fc Core Fucosylation in the Effector Function of IgG1 Antibodies
Authors: Golay Josée , Andrea Alain E. , Cattaneo Irene
Published: June 2022

The presence of fucose on IgG1 Asn-297 N-linked glycan is the modification of the human IgG1 Fc structure with the most significant impact on FcɣRIII affinity. It also significantly enhances the efficacy of antibody dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells in vitro, induced by IgG1 therapeutic monoclonal antibodies (mAbs). The effect of afucosylation on ADCC or antibody dependent phagocytosis (ADCP) mediated by macrophages or polymorphonuclear neutrophils (PMN) is less clear. Evidence for enhanced efficacy of afucosylated therapeutic mAbs in vivo has also been reported. This has led to the development of several therapeutic antibodies with low Fc core fucose to treat cancer and inflammatory diseases, seven of which have already been approved for clinical use. More recently, the regulation of IgG Fc core fucosylation has been shown to take place naturally during the B-cell immune response: A decrease in α-1,6 fucose has been observed in polyclonal, antigen-specific IgG1 antibodies which are generated during alloimmunization of pregnant women by fetal erythrocyte or platelet antigens and following infection by some enveloped viruses and parasites. Low IgG1 Fc core fucose on antigen-specific polyclonal IgG1 has been linked to disease severity in several cases, such as SARS-CoV 2 and Dengue virus infection and during alloimmunization, highlighting the in vivo significance of this phenomenon. This review aims to summarize the current knowledge about human IgG1 Fc core fucosylation and its regulation and function in vivo, in the context of both therapeutic antibodies and the natural immune response. The parallels in these two areas are informative about the mechanisms and in vivo effects of Fc core fucosylation, and may allow to further exploit the desired properties of this modification in different clinical contexts.
Movement, Behavior, and Habitat Use of Whale Sharks (Rhincodon typus) in the Tropical Eastern Pacific Ocean
Authors: Guzman Hector M. , Collatos Caroline M. , Gomez Catalina G.
Published: June 2022

Whale sharks (Rhincodon typus) are found circumglobally in tropical, subtropical, and warm temperate waters, and their known seasonal aggregations and migratory movements are influenced by factors such as ocean currents, thermobiological systems, and patterns of productivity. Several locations in the eastern tropical Pacific Ocean are known habitats for R. typus; Although it has long been known that whale sharks aggregate along the Panama coast, little is known in relation to their movement patterns, behavior, and habitat use. In this study, we investigated the movements and behaviors of R. typus tagged in Panama in relation to oceanographic variables and examined the overlap of foraging habitat and migratory routes with marine protected areas (MPAs), industrial fishing areas, and marine traffic. Satellite tracks from 30 R. typus tagged in the coastal waters of Panama were examined, including nine tags suspicious of earlier detachment. A hidden Markov model was then used to identify different behavioral states (foraging and migrating) and their relationships with environmental variables (sea surface temperature, primary productivity, chlorophyll-a concentrations, and eddy location/speed) Tracks were also superimposed on maps of MPAs, industrial fishing areas, and regional marine vessel traffic to identify the degree of overlap. Rhincodon typus foraged mainly within the Panamanian exclusive economic zone but also moved north and south along the coast and out to the open ocean. Significant differences in environmental conditions were found between sites in which foraging and migrating behaviors were recorded. Higher productivity and chlorophyl concentration were associated with foraging behavior, while higher eddy speeds were observed when sharks migrated. Rhincodon typus used MPAs; however, there was a high degree of overlap between their habitat and areas of industrial fishing and marine vessel traffic. Our results highlight the use of the coastal waters of Panama, oceanic seamounts, and ridges, MPAs and industrial fishing areas by R. typus for foraging and migration. Additionally, our findings highlight the importance of satellite tracking studies for understanding the behavior and habitat use of highly mobile migratory species, such as R. typus.
Challenges and Advances in the Taxonomy of Deep-Sea Peracarida: From Traditional to Modern Methods
Authors: Frutos Inmaculada , Kaiser Stefanie , Pułaski Łukasz , Studzian Maciej , Błażewicz Magdalena
Published: June 2022

As one of the oldest branches of biology, taxonomy deals with the identification, classification and naming of living organisms, using a variety of tools to explore traits at the morphological and molecular level. In the deep sea, particular challenges are posed to the taxonomic differentiation of species. Relatively limited sampling effort coupled with apparent high diversity, compared to many other marine environments, means that many species sampled are undescribed, and few specimens are available for each putative species. The resulting scarce knowledge of intraspecific variation makes it difficult to recognize species boundaries and thus to assess the actual diversity and distribution of species. In this review article, we highlight some of these challenges in deep-sea taxonomy using the example of peracarid crustaceans. Specifically, we offer a detailed overview of traditional as well as modern methods that are used in the taxonomic analysis of deep-sea Peracarida. Furthermore, methods are presented that have not yet been used in peracarid taxonomy, but have potential for the analysis of internal and external structures in the future. The focus of this compilation is on morphological methods for the identification, delimitation and description of species, with references to molecular analysis included where relevant, as these methods are an indispensable part of an integrative taxonomic approach. The taxonomic impediment, i.e. the shortage of taxonomists in view of a high undescribed biodiversity, is discussed in the context of the existing large taxonomic knowledge gaps in connection with the increasing threat to deep-sea ecosystems. Whilst peracarid crustaceans are used here as an exemplary taxon, the methodology described has broad relevance to many other deep-sea taxa, and thus will support broader research into deep-sea biodiversity and ecology more widely.
Medial Collagen Type and Quantity Influence Mechanical Properties of Aneurysm Wall in Bicuspid Aortic Valve Patients
Authors: Neave Louise , Tahir Maria , Nightingale Miriam , Jadli Anshul S. , Patel Vaibhav B. , Barker Alexander J. , Malaisrie S. Chris , McCarthy Patrick M. , Markl Michael , Fedak Paul W. M. , Di Martino Elena S.
Published: June 2022

Collagen has an essential role in aortic biomechanics, and collagen remodeling has been associated with the development and progression of aortic aneurysm. However, the exact mechanisms behind collagen remodeling and the biomechanical implications are not well understood. This study presents an investigation of the relationship between collagen remodeling in the aortic wall and biomechanics, by means of collagen assays, smooth muscle cell gene expression, and mechanical testing on human aortic specimens collected from patients with bicuspid aortic valve. Collagen assay analysis was employed to determine collagen-I and total collagen content; quantitative real-time PCR was used to determine amountsCOL1A1andCOL3A1expression in the tissue. These parameters were compared with the local biomechanical properties determined from biaxial and uniaxial tensile testing. Collagen-I content was found to relate to improved mechanical properties, while total collagen content did not exhibit a relationship with biomechanics.COL1A1andCOL3A1expression were found to relate to the collagen-I content of the tissue, but not the total collagen content or biomechanical performance. Relationships between variables appeared to be dependent on the collagen content in specific layers of the aortic wall. The effect of age is also noted, as total collagen content and biomechanics were found to have significant associations with increasing age, while collagen-I content and collagen gene expression did not exhibit any correlation. Varying relationships were observed when looking at younger versus older patients. Findings highlight the importance of type and location in determining the influence of collagen on aortic biomechanics, as well as the role of gene expression in the onset and progression of collagen remodeling in aortic aneurysm.