bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Use of Multiple Intravascular Imaging Techniques in Acute Coronary Syndrome
Authors: Kubo Takashi , Terada Kosei , Ino Yasushi , Shiono Yasutsugu , Tu Shengxian , Tsao Tien-Ping , Chen Yundai , Park Duk-Woo
Published: January 2022

Recent advances in intravascular imaging techniques have made it possible to assess the culprit lesions of acute coronary syndrome (ACS) in the clinical setting. Intravascular ultrasound (IVUS) is the most commonly used intravascular imaging technique that provides cross-sectional images of coronary arteries. IVUS can assess plaque burden and vessel remodeling. Optical coherence tomography (OCT) is a high-resolution (10 μm) intravascular imaging technique that uses near-infrared light. OCT can identify key features of atheroma, such as lipid core and thin fibrous cap. Near-infrared spectroscopy (NIRS) can detect lipid composition by analyzing the near-infrared absorption properties of coronary plaques. NIRS provides a chemogram of the coronary artery wall, which allows for specific quantification of lipid accumulation. These intravascular imaging techniques can depict histological features of plaque rupture, plaque erosion, and calcified nodule in ACS culprit lesions. However, no single imaging technique is perfect and each has its respective strengths and limitations. In this review, we summarize the implications of combined use of multiple intravascular imaging techniques to assess the pathology of ACS and guide lesion-specific treatment.
Maternal High-Fat Diet During Pre-Conception and Gestation Predisposes Adult Female Offspring to Metabolic Dysfunction in Mice
Authors: Akhaphong Brian , Gregg Brigid , Kumusoglu Doga , Jo Seokwon , Singer Kanakadurga , Scheys Joshua , DelProposto Jennifer , Lumeng Carey , Bernal-Mizrachi Ernesto , Alejandro Emilyn U.
Published: January 2022

The risk of obesity in adulthood is subject to programming in the womb. Maternal obesity contributes to programming of obesity and metabolic disease risk in the adult offspring. With the increasing prevalence of obesity in women of reproductive age there is a need to understand the ramifications of maternal high-fat diet (HFD) during pregnancy on offspring’s metabolic heath trajectory. In the present study, we determined the long-term metabolic outcomes on adult male and female offspring of dams fed with HFD during pregnancy. C57BL/6J dams were fed either Ctrl or 60% Kcal HFD for 4 weeks before and throughout pregnancy, and we tested glucose homeostasis in the adult offspring. Both Ctrl and HFD-dams displayed increased weight during pregnancy, but HFD-dams gained more weight than Ctrl-dams. Litter size and offspring birthweight were not different between HFD-dams or Ctrl-dams. A significant reduction in random blood glucose was evident in newborns from HFD-dams compared to Ctrl-dams. Islet morphology and alpha-cell fraction were normal but a reduction in beta-cell fraction was observed in newborns from HFD-dams compared to Ctrl-dams. During adulthood, male offspring of HFD-dams displayed comparable glucose tolerance under normal chow. Male offspring re-challenged with HFD displayed glucose intolerance transiently. Adult female offspring of HFD-dams demonstrated normal glucose tolerance but displayed increased insulin resistance relative to controls under normal chow diet. Moreover, adult female offspring of HFD-dams displayed increased insulin secretion in response to high-glucose treatment, but beta-cell mass were comparable between groups. Together, these data show that maternal HFD at pre-conception and during gestation predisposes the female offspring to insulin resistance in adulthood.
RETRACTED: Current Developments in Catalytic Methanation of Carbon Dioxide—A Review
Authors: Tan Chung Hong , Nomanbhay Saifuddin , Shamsuddin Abd Halim , Park Young-Kwon , Hernández-Cocoletzi H. , Show Pau Loke
Published: January 2022

The utilization of fossil fuel has increased atmospheric carbon dioxide (CO2) concentrations drastically over the last few decades. This leads to global warming and climate change, increasing the occurrence of more severe weather around the world. One promising solution to reduce anthropogenic CO2 emissions is methanation. Many researchers and industries are interested in CO2 methanation as a power-to-gas technology and carbon capture and storage (CCS) system. Producing an energy carrier, methane (CH4), via CO2 methanation and water electrolysis is an exceptionally effective method of capturing energy generated by renewables. To enhance methanation efficiency, numerous researches have been conducted to develop catalysts with high activity, CH4 selectivity, and stability against the reaction heat. Therefore, in this mini-review, the characteristics and recent advances of metal-based catalysts in methanation of CO2 is discussed.
Numerical Weather Prediction Correction Strategy for Short-Term Wind Power Forecasting Based on Bidirectional Gated Recurrent Unit and XGBoost
Authors: Li Yu , Tang Fei , Gao Xin , Zhang Tongyan , Qi Junfeng , Xie Jiarui , Li Xinang , Guo Yuhan
Published: January 2022

Accurate short-term wind power forecasting (WPF) plays a crucial role in grid scheduling and wind power accommodation. Numerical weather prediction (NWP) wind speed is the fundamental data for short-term WPF. At present, reducing NWP wind speed forecast errors contributes to improving the accuracy of WPF from the perspective of data quality. In this article, a variational mode decomposition combined with bidirectional gated recurrent unit (VMD-BGRU) method for NWP wind speed correction and XGBoost forecasting model are proposed. First, several NWP wind speed sub-series are divided by VMD to obtain more abundant multidimensional timing features. BGRU is applied to establish the potential relation between decomposed NWP wind speed sub-series and measured wind speed and get the proposed wind speed correction model. Then, a more clear regression forecasting model is trained based on XGBoost using historical measured wind speed and power. The corrected NWP wind speed is used to forecast wind power by XGBoost. Finally, the superiority of the proposed method is validated on a wind farm located in China. The results show that the proposed correction model and forecasting model outperform other compared models.
Impacts of Changbai Mountain Topography on the Extreme Precipitation From Super Typhoon Maysak
Authors: Zhu Dan , Zhi Xiefei , Wang Ning , Chen Changsheng , Tian Xiao , Yu Yueming
Published: January 2022

Based on hourly gridded precipitation data (0.1°) calculated by the China Meteorological Administration (CMA), the European Centre Medium-Range Weather Forecasts (ECMWF) reanalysis data, and microwave measurements, this paper investigated the extreme precipitation induced by the Typhoon Maysak in Northeast China (September 2020), using the Advanced Research dynamic core of the Weather Research and Forecasting Model (WRF-ARW). The study focused on Changbai Mountain topography and the extreme precipitation in Jilin Province. The results show that two extreme precipitation centers corresponded well to the local terrain height in Jilin Province. The Changbai Mountain range, which mainly lies in southeastern Jilin Province, affected the typhoon in three aspects: blocking drag, forcing uplift, and promoting moisture convergence. Because of the blocking drag of the mountain topography, the duration of severe precipitation was prolonged. The overlap of the area affected by the peripheral cloud band of the typhoon and the direction of the typhoon was largely responsible for the extreme rainfall. The dynamic lifting by the mountainous terrain and the reinforced moisture convergence also considerably increased precipitation. Microwave measurements show that water vapor density profile increased rapidly at the peak (14 g/m3), and the high moisture density was retained for at least 15 h in the lower layer. The prolonged, continuous, and abundant moisture transport offered a sufficient water vapor supply for this severe precipitation event. According to the estimation of precipitation rate, the increment of torrential rainfall on Changbai Mountain during the severe precipitation period reached 6.8 mm/h, about 41% of the total rainfall in this period. Finally, the topographic sensitivity test indicated that when the terrain of Changbai Mountain was lower, the convergent ascending motion, precipitable water, and storm-relative helicity were weaker, and the rainfall distribution markedly changed. This finding further verifies the importance of the Changbai orography in the extreme precipitation event induced by Typhoon Maysak.
What Are the Primary Cues Used by Mammalian Predators to Locate Freshwater Turtle Nests? A Critical Review of the Evidence
Authors: Geller Gregory A. , Parker Scott L.
Published: January 2022

Turtle biologists have long been interested in the biotic and abiotic factors that influence the detection of freshwater turtle nests by mammalian predators. Increased knowledge of nest predation dynamics may help develop conservation strategies to increase turtle nesting success by altering or reducing the signal strength of predominant nest location cues. However, despite this long-standing interest, the related research has produced inconsistent and sometimes conflicting results across studies. Here we review much of the existing literature on freshwater turtle nest predation by mammalian predators and attempt to synthesize some general, underlying themes. Available data suggest that raccoons (Procyon lotor) primarily use olfactory cues associated with nest cavity construction to locate turtle nests. However, some other predators, including red foxes (Vulpes vulpes) and other canids, may commonly use a wider array of cues, including scents from nesting turtles and their eggs as well as visual cues, while foraging. The literature also suggests that the length of the period turtle nests remain vulnerable to nest predation is dependent on the predator community, with raccoons exhibiting relatively short timelines relative to some other predators, including canids. This review has revealed a strong North American bias in published work, highlighting the need for additional studies of turtle nest predation dynamics in other areas of the world where chelonians are often imperiled elements of the biota.
The Role of Directed Dispersal in Driving Genetic and Morphological Structure in Invasive Smallmouth Bass
Authors: Diedericks Genevieve , Broeckhoven Chris , von der Heyden Sophie , Weyl Olaf L. F. , Hui Cang
Published: January 2022

Dispersal is an essential life-history trait crucial to species persistence and diversification. This is particularly important in spatiotemporal fluctuating environments such as freshwater habitats, where species movement is confined to the dendritic network and wetted boundaries. To persist in such fluctuating environments, a species can modify, adaptively and plastically, its phenotypic variation to better match the environment or escape via directed dispersal to a more suitable habitat (i.e., matching habitat choice). We use the invasive smallmouth bass, Micropterus dolomieu, sampled at 10 km intervals, to assess the effect of directed dispersal on the fine scale genetic and phenotypic variation in populations of M. dolomieu along a river course. Gene flow was used as a proxy for dispersal. By comparing population genetic structure, morphological variation (of linear traits and geometric landmarks), and environmental heterogeneity, we discovered a clear correlation between environmental variation and morphological traits. Although isolation by distance seemed to have shaped the overall genetic pattern detected among the populations, the strong genetic structuring observed within the Ratel tributary appeared to be non-random. These results provide novel insights into the potential mechanisms promoting the spread and establishment of invasive species and the possible influence multiple introductions may have on fine scale genetic structuring.
Hormone-Related Cancer and Autoimmune Diseases: A Complex Interplay to be Discovered
Authors: Losada-García A , Cortés-Ramírez SA , Cruz-Burgos M , Morales-Pacheco M , Cruz-Hernández Carlos D , Gonzalez-Covarrubias Vanessa , Perez-Plascencia Carlos , Cerbón MA , Rodríguez-Dorantes M
Published: January 2022

Neoplasic transformation is a continuous process that occurs in the body. Even before clinical signs, the immune system is capable of recognizing these aberrant cells and reacting to suppress them. However, transformed cells acquire the ability to evade innate and adaptive immune defenses through the secretion of molecules that inhibit immune effector functions, resulting in tumor progression. Hormones have the ability to modulate the immune system and are involved in the pathogenesis of autoimmune diseases, and cancer. Hormones can control both the innate and adaptive immune systems in men and women. For example androgens reduce immunity through modulating the production of pro-inflammatory and anti-inflammatory mediators. Women are more prone than men to suffer from autoimmune diseases such as systemic lupus erythematosus, psoriasis and others. This is linked to female hormones modulating the immune system. Patients with autoimmune diseases consistently have an increased risk of cancer, either as a result of underlying immune system dysregulation or as a side effect of pharmaceutical treatments. Epidemiological data on cancer incidence emphasize the link between the immune system and cancer. We outline and illustrate the occurrence of hormone-related cancer and its relationship to the immune system or autoimmune diseases in this review. It is obvious that some observations are contentious and require explanation of molecular mechanisms and validation. As a result, future research should clarify the molecular pathways involved, including any causal relationships, in order to eventually allocate information that will aid in the treatment of hormone-sensitive cancer and autoimmune illness.
Immune Checkpoint LAG3 and Its Ligand FGL1 in Cancer
Authors: Shi An-Ping , Tang Xi-Yang , Xiong Yan-Lu , Zheng Kai-Fu , Liu Yu-Jian , Shi Xian-Gui , Lv Yao , Jiang Tao , Ma Nan , Zhao Jin-Bo
Published: January 2022

LAG3 is the most promising immune checkpoint next to PD-1 and CTLA-4. High LAG3 and FGL1 expression boosts tumor growth by inhibiting the immune microenvironment. This review comprises four sections presenting the structure/expression, interaction, biological effects, and clinical application of LAG3/FGL1. D1 and D2 of LAG3 and FD of FGL1 are the LAG3-FGL1 interaction domains. LAG3 accumulates on the surface of lymphocytes in various tumors, but is also found in the cytoplasm in non-small cell lung cancer (NSCLC) cells. FGL1 is found in the cytoplasm in NSCLC cells and on the surface of breast cancer cells. The LAG3-FGL1 interaction mechanism remains unclear, and the intracellular signals require elucidation. LAG3/FGL1 activity is associated with immune cell infiltration, proliferation, and secretion. Cytokine production is enhanced when LAG3/FGL1 are co-expressed with PD-1. IMP321 and relatlimab are promising monoclonal antibodies targeting LAG3 in melanoma. The clinical use of anti-FGL1 antibodies has not been reported. Finally, high FGL1 and LAG3 expression induces EGFR-TKI and gefitinib resistance, and anti-PD-1 therapy resistance, respectively. We present a comprehensive overview of the role of LAG3/FGL1 in cancer, suggesting novel anti-tumor therapy strategies.
Integrated Population Genomic Analysis and Numerical Simulation to Estimate Larval Dispersal of Acanthaster cf. solaris Between Ogasawara and Other Japanese Regions
Authors: Horoiwa Mizuki , Nakamura Takashi , Yuasa Hideaki , Kajitani Rei , Ameda Yosuke , Sasaki Tetsuro , Taninaka Hiroki , Kikuchi Taisei , Yamakita Takehisa , Toyoda Atsushi , Itoh Takehiko , Yasuda Nina
Published: January 2022

The estimation of larval dispersal on an ecological timescale is significant for conservation of marine species. In 2018, a semi-population outbreak of crown-of-thorns sea star, Acanthaster cf. solaris, was observed on a relatively isolated oceanic island, Ogasawara. The aim of this study was to assess whether this population outbreak was caused by large-scale larval recruitment (termed secondary outbreak) from the Kuroshio region. We estimated larval dispersal of the coral predator A. cf. solaris between the Kuroshio and Ogasawara regions using both population genomic analysis and simulation of oceanographic dispersal. Population genomic analysis revealed overall genetically homogenized patterns among Ogasawara and other Japanese populations, suggesting that the origin of the populations in the two regions is the same. In contrast, a simulation of 26-year oceanographic dispersal indicated that larvae are mostly self-seeded in Ogasawara populations and have difficulty reaching Ogasawara from the Kuroshio region within one generation. However, a connectivity matrix produced by the larval dispersal simulation assuming a Markov chain indicated gradual larval dispersal migration from the Kuroshio region to Ogasawara in a stepping-stone manner over multiple years. These results suggest that the 2018 outbreak was likely the result of self-seeding, including possible inbreeding (as evidenced by clonemate analysis), as large-scale larval dispersal from the Kurishio population to the Ogasawara population within one generation is unlikely. Instead, the population in Ogasawara is basically sustained by self-seedings, and the outbreak in 2018 was also most likely caused by successful self-seedings including possible inbreeding, as evidenced by clonemate analysis. This study also highlighted the importance of using both genomic and oceanographic methods to estimate larval dispersal, which provides significant insight into larval dispersal that occurs on ecological and evolutionary timescales.
Polar Region Bathymetry: Critical Knowledge for the Prediction of Global Sea Level Rise
Authors: Jakobsson Martin , Mayer Larry A.
Published: January 2022

The ocean and the marine parts of the cryosphere interact directly with, and are affected by, the seafloor and its primary properties of depth (bathymetry) and shape (morphology) in many ways. Bottom currents are largely constrained by undersea terrain with consequences for both regional and global heat transport. Deep ocean mixing is controlled by seafloor roughness, and the bathymetry directly influences where marine outlet glaciers are susceptible to the inflow relatively warm subsurface waters - an issue of great importance for ice-sheet discharge, i.e., the loss of mass from calving and undersea melting. Mass loss from glaciers and the Greenland and Antarctic ice sheets, is among the primary drivers of global sea-level rise, together now contributing more to sea-level rise than the thermal expansion of the ocean. Recent research suggests that the upper bounds of predicted sea-level rise by the year 2100 under the scenarios presented in IPCC’s Special Report on the Ocean and Cryosphere in a Changing Climate (SROCCC) likely are conservative because of the many unknowns regarding ice dynamics. In this paper we highlight the poorly mapped seafloor in the Polar regions as a critical knowledge gap that needs to be filled to move marine cryosphere science forward and produce improved understanding of the factors impacting ice-discharge and, with that, improved predictions of, among other things, global sea-level. We analyze the bathymetric data coverage in the Arctic Ocean specifically and use the results to discuss challenges that must be overcome to map the most remotely located areas in the Polar regions in general.
The Relationship Between Plasma Tetrahydrocannabinol Levels and Intraocular Pressure in Healthy Adult Subjects
Authors: Mosaed Sameh , Smith Andrew K. , Liu John H. K. , Minckler Donald S. , Fitzgerald Robert L. , Grelotti David , Sones Emily , Weinreb Robert N. , Marcotte Thomas D.
Published: January 2022

Background

Δ9-tetrahydrocannabinol (THC) has been shown to decreased intraocular pressure (IOP). This project aims to define the relationship between plasma THC levels and IOP in healthy adult subjects.

Methods

Eleven healthy subjects received a single dose of inhaled cannabis that was self-administered in negative pressure rooms. Measurements of IOP and plasma THC levels were taken at baseline and every 30 min for 1 h and afterwards every hour for 4 h. IOP reduction and percent change in IOP over time were calculated. Linear regression models were used to measure the relationship between IOP and plasma THC levels. Two line linear regression models with F-tests were used to detect change points in the regression. Then, Pearson correlations were computed based on the change point.

Results

Twenty-two eyes met inclusion criteria. The average peak percentage decrease in IOP was 16% at 60 min. Percent IOP reduction as well as total IOP reduction demonstrated a negative correlation with THC plasma levels showing r-values of −0.81 and −0.70, respectively. F-tests revealed a change point in the regression for plasma levels >20 ng/ml. For levels >20 ng/ml, the correlation coefficients changed significantly with r-values of 0.21 and 0.29 (p < 0.01).

Conclusion

Plasma THC levels are significantly correlated with IOP reduction up to plasma levels of 20 ng/ml. Plasma levels >20 ng/ml were not correlated with further decrease in IOP. More research is needed to determine the efficacy of THC in reducing IOP for eyes with ocular hypertension and glaucoma.
Spatiotemporal Analysis of the Prevalence and Pattern of Multimorbidity in Older Chinese Adults
Authors: Chen Shimin , Wang Shengshu , Jia Wangping , Han Ke , Song Yang , Liu Shaohua , Li Xuehang , Liu Miao , He Yao
Published: January 2022

Background

Multimorbidity presents an enormous problem to societal and healthcare utilization under the context of aging population in low- and middle-income countries (LMICs). Currently, systematic studies on the profile of multimorbidity and its characteristics among Chinese elderly are lacking. We described the temporal and spatial trends in the prevalence of multimorbidity and explored chronological changes of comorbidity patterns in a large elderly population survey.

Methods

Data were extracted from the Chinese Longitudinal Healthy Longevity Study (CLHLS) conducted between 1998 and 2018 in a random selection of half of the counties and city districts. All the elderly aged 65 and older were included in the survey of eight waves. We used 13 investigated chronic diseases to measure the prevalence of multimorbidity by means of geography, subpopulation, and chronological changes. The patterns of multimorbidity were assessed by computing the value of relative risk (RR indicates the likelihood of certain diseases to be associated with multimorbidity) and the observed-to-expected ratio (O/E indicates the likelihood of the coexistence of a multimorbidity combination).

Results

From 1998 to 2018, the prevalence of multimorbidity went from 15.60 to 30.76%, increasing in the fluctuation across the survey of eight waves (pfor trend = 0.020). Increasing trends were observed similarly in a different gender group (pmale = 0.009; pfemale = 0.004) and age groups among female participants (p~80 = 0.009; p81−90 = 0.004; p91−100 = 0.035; p101~ = 0.018). The gap in the prevalence of multimorbidity between the north and the south was getting narrow across the survey of eight waves. Hypertension was the highest prevalent chronic condition while diabetes was most likely to coexist with other chronic conditions in the CLHLS survey. The most frequently occurring clusters were hypertension and heart disease, hypertension and cataract, and hypertension and chronic lung disease. And, the cancer, TB, and Parkinson's disease cluster took the domination of O/E rankings over time, which had a higher probability of coexistence in all the multimorbidity combinations.

Conclusions

The prevalence of multimorbidity has been increasing nationwide, and more attention should be paid to a rapid growth in the southern part of China. It demands the effective diagnosis and treatment adopted to the highly prevalent comorbidities, and strategies and measures were adjusted to strongly relevant clusters.
Low Circulating Monocytes Is in Parallel With Lymphopenia Which Predicts Poor Outcome in Anti-melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis-Associated Interstitial Lung Disease
Authors: Lv Xia , Jin Yuyang , Zhang Danting , Li Yixuan , Fu Yakai , Wang Suli , Ye Yan , Wu Wanlong , Ye Shuang , Yan Bing , Chen Xiaoxiang
Published: January 2022

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM)-associated interstitial lung disease (ILD) may progress rapidly and lead to high mortality within 6 or 12 months. Except for reported prognostic factors, simple but powerful prognostic biomarkers are still in need in practice. In this study, we focused on circulating monocyte and lymphocyte counts and their variation tendency in the early stage of ILD. A total of 351 patients from two inception anti-MDA5 antibody-positive cohorts were included in this study, with various treatment choices. Lymphocyte count remained lower in the first month after admission in the non-survivor patients. Although baseline monocyte count showed no significant differences, average monocyte count in the following 4 weeks was also lower in the non-survivor group. Based on the C-index and analysis by the “survminer” R package in the discovery cohort, we chose 0.24 × 109/L as the cutoff value for Mono W0-2, 0.61 × 109/L as the cutoff value for lymph W0-2, and 0.78 × 109/L as the cutoff value for peripheral blood mononuclear cell (PBMC) W0-2, to predict the 6-month all-cause mortality. The Kaplan–Meier survival curves and adjusted hazard ratio with age, gender, and the number of immunosuppressants used all validated that patients with lower average monocyte count, lower average lymphocyte count, or lower average PBMC count in the first 2 weeks after admission had higher 6-month death risk, no matter in the validation cohort or in the pooled data. Furthermore, flow cytometry figured out that non-classical monocytes in patients with anti-MDA5 antibody-positive DM were significantly lower than healthy controls and patients with DM without anti-MDA5 antibodies. In conclusion, this study elucidated the predictive value of monocyte and lymphocyte counts in the early stage and may help rheumatologists to understand the possible pathogenesis of this challenging disease.
Use of Transposon Directed Insertion-Site Sequencing to Probe the Antibacterial Mechanism of a Model Honey on E. coli K-12
Authors: Masoura Maria , Milner Mathew T. , Overton Tim W. , Gkatzionis Konstantinos , Lund Peter A.
Published: January 2022

Antimicrobial resistance is an ever-growing health concern worldwide that has created renewed interest in the use of traditional anti-microbial treatments, including honey. However, understanding the underlying mechanism of the anti-microbial action of honey has been hampered due to the complexity of its composition. High throughput genetic tools could assist in understanding this mechanism. In this study, the anti-bacterial mechanism of a model honey, made of sugars, hydrogen peroxide, and gluconic acid, was investigated using genome-wide transposon mutagenesis combined with high-throughput sequencing (TraDIS), with the strain Escherichia coli K-12 MG1655 as the target organism. We identified a number of genes which when mutated caused a severe loss of fitness when cells were exposed to the model honey. These genes encode membrane proteins including those involved in uptake of essential molecules, and components of the electron transport chain. They are enriched for pathways involved in intracellular homeostasis and redox activity. Genes involved in assembly and activity of formate dehydrogenase O (FDH-O) were of particular note. The phenotypes of mutants in a subset of the genes identified were confirmed by phenotypic screening of deletion strains. We also found some genes which when mutated led to enhanced resistance to treatment with the model honey. This study identifies potential synergies between the main honey stressors and provides insights into the global antibacterial mechanism of this natural product.
Prognostic Value and Immunological Role of KIFC1 in Hepatocellular Carcinoma
Authors: Li Dan , Yu Tao , Han Jingjing , Xu Xu , Wu Jie , Song Wei , Liu Gang , Zhu Hua , Zeng Zhi
Published: January 2022

As one of the members of the kinesin family, the role and potential mechanism of kinesin family member C1 (KIFC1) in the development of liver hepatocellular carcinoma (LIHC), especially in the immune infiltration, have not been fully elucidated. In this study, multiple databases and immunohistochemistry were employed to analyze the role and molecular mechanism including the immune infiltration of KIFC1 in LIHC. Generally, KIFC1 mRNA expression was overexpressed in LIHC tissues than normal tissues, and its protein was also highly expressed in the LIHC. KIFC1 mRNA expression was correlated with tumor grade and TNM staging, which was negatively correlated with overall survival and disease-free survival. Moreover, univariable and multivariate Cox analysis revealed that upregulated KIFC1 mRNA is an independent prognostic factor for LIHC. The KIFC1 promoter methylation level was negatively associated with KIFC1 mRNA expression and advanced stages and grade in LIHC. The different methylation sites of KIFC1 had a different effect on the prognosis of LIHC. Specifically, the KIFC1 mRNA expression level showed intense correlation with tumor immunity, such as tumor-infiltrating immune cells and immune scores as well as multiple immune-related genes. Moreover, KIFC1 co-expressed with some immune checkpoints and related to the responses to immune checkpoint blockade (ICB) and chemotherapies. Significant GO analysis showed that genes correlated with KIFC1 served as catalytic activity, acting on DNA, tubulin binding, histone binding, ATPase activity, and protein serine/threonine kinase activity. KEGG pathway analysis showed that these genes related to KIFC1 are mainly enriched in signal pathways such as cell cycle, spliceosome, pyrimidine metabolism, and RNA transport. Conclusively, KIFC1 was upregulated and displayed a prognostic value in LIHC. Moreover, KIFC1 may be involved in the LIHC progression partially through immune evasion and serve as a predictor of ICB therapies and chemotherapies.
Intrinsic Brain Activity Alterations in Patients With Mild Cognitive Impairment-to-Normal Reversion: A Resting-State Functional Magnetic Resonance Imaging Study From Voxel to Whole-Brain Level
Authors: Hu Qili , Wang Qianqian , Li Yunfei , Xie Zhou , Lin Xiaomei , Huang Guofeng , Zhan LinLin , Jia Xize , Zhao Xiaohu
Published: January 2022

Mild cognitive impairment (MCI) reversion refers to patients with MCI who revert from MCI to a normal cognitive state. Exploring the underlying neuromechanism of MCI reverters may contribute to providing new insights into the pathogenesis of Alzheimer’s disease and developing therapeutic interventions. Information on patients with MCI and healthy controls (HCs) was collected from the Alzheimer’s Disease Neuroimaging Initiative database. We redefined MCI reverters as patients with MCI whose logical memory scores changed from MCI to normal levels using the logical memory criteria. We explored intrinsic brain activity alterations in MCI reverters from voxel, regional, and whole-brain levels by comparing resting-state functional magnetic resonance imaging metrics of the amplitude of low-frequency of fluctuation (ALFF), the fractional amplitude of low-frequency fluctuation (fALFF), percent amplitude of fluctuation (PerAF), regional homogeneity (ReHo), and degree centrality (DC) between MCI reverters and HCs. Finally, partial correlation analyses were conducted between cognitive scale scores and resting-state functional magnetic resonance imaging metrics of brain regions, revealing significant group differences. Thirty-two patients with MCI from the Alzheimer’s Disease Neuroimaging Initiative database were identified as reverters. Thirty-seven age-, sex-, and education-matched healthy individuals were also enrolled. At the voxel level, compared with the HCs, MCI reverters had increased ALFF, fALFF, and PerAF in the frontal gyrus (including the bilateral orbital inferior frontal gyrus and left middle frontal gyrus), increased PerAF in the left fusiform gyrus, and decreased ALFF and fALFF in the right inferior cerebellum. Regarding regional and whole-brain levels, MCI reverters showed increased ReHo in the left fusiform gyrus and right median cingulate and paracingulate gyri; increased DC in the left inferior temporal gyrus and left medial superior frontal; decreased DC in the right inferior cerebellum and bilateral insular gyrus relative to HCs. Furthermore, significant correlations were found between cognitive performance and neuroimaging changes. These findings suggest that MCI reverters show significant intrinsic brain activity changes compared with HCs, potentially related to the cognitive reversion of patients with MCI. These results enhance our understanding of the underlying neuromechanism of MCI reverters and may contribute to further exploration of Alzheimer’s disease.
The Effect of Body Adiposity and Alcohol Consumption on Serum Uric Acid: A Quantile Regression Analysis Based on the China National Health Survey
Authors: He Huijing , Pan Li , Ren Xiaolan , Wang Dingming , Du Jianwei , Cui Ze , Zhao Jingbo , Wang Hailing , Wang Xianghua , Liu Feng , Pa Lize , Peng Xia , Wang Ye , Yu Chengdong , Shan Guangliang
Published: January 2022

Adiposity and alcohol consumption are reported to be associated with a higher level of serum uric acid (SUA), but whether their effect differs on SUA percentile distribution is still unclear. In this study, we aimed to investigate how alcohol intake and body fat percentage (%BF) integrated with body mass index (BMI) influence the distribution of SUA in Chinese adults. Data from the China National Health Survey (CNHS) which included adults from 10 provinces of China were used (n = 31,746, aged 20–80 years, 40% male). %BF and BMI were integrated into eight expanded body composition groups to understand how excess body adiposity affects the distribution of SUA in the populational level. Self-report alcohol intake information was collected by face-to-face questionnaire interview. Quantile regression (QR) was used to analyze the data. We found that adiposity and alcohol consumption were associated with SUA, especially at the upper percentile in both sexes. In obese men, the QR coefficients at the 75th and 95th percentiles were 74.0 (63.1–84.9) and 80.9 (52.5–109.3) μmol/L, respectively. The highest quartile of %BF in men had a 92.6 (79.3–105.9) μmol/L higher SUA levels at its 95th percentile than the 5th quartile (p < 0.001). Compared with normal or underweight with the lowest %BF group (NWBF1), the obesity-highest %BF group (OBBF4) had the strongest positive effect on SUA, especially at the higher percentile of SUA. In BMI-defined normal or underweight participants, a higher quartile of %BF had greater effect size in all SUA percentiles. In men, current alcohol drinking had the strongest effect at the 95th percentile of SUA (QR coefficient: 31.8, with 95% CI: 22.6–41.0) comparing with 14.5, 95% CI of 8.4 to 20.6 in the 5th SUA percentile. High risk of alcohol consumption had a greater effect on SUA, especially in the higher SUA percentile. The observation of stronger association at the higher percentile of SUA suggests that decreasing body adiposity and alcohol intake at the populational level may shift the upper tails of the SUA distributions to lower values, thereby reducing the incidence of hyperuricemia.
The Amino Acids Sensing and Utilization in Response to Dietary Aromatic Amino Acid Supplementation in LPS-Induced Inflammation Piglet Model
Authors: Duanmu Qing , Tan Bie , Wang Jing , Huang Bo , Li Jianjun , Kang Meng , Huang Ke , Deng Qiuchun , Yin Yulong
Published: January 2022

Dietary supplementation with aromatic amino acids (AAAs) has been demonstrated to alleviate intestinal inflammation induced by lipopolysaccharide (LPS) in the piglets. But the mechanism of AAA sensing and utilization under inflammatory conditions is not well-understood. The study was conducted with 32 weanling piglets using a 2 × 2 factorial arrangement (diet and LPS challenge) in a randomized complete block design. Piglets were fed as basal diet or the basal diet supplemented with 0.16% tryptophan (Trp), 0.41% phenylalanine (Phe), and 0.22% tyrosine (Tyr) for 21 days. The results showed that LPS treatment significantly reduced the concentrations of cholecystokinin (CCK) and total protein but increased leptin concentration, the activities of alanine transaminase, and aspartate aminotransferase in serum. Dietary supplementation with AAAs significantly increased the serum concentrations of CCK, peptide YY (PYY), and total protein but decreased the blood urea nitrogen. LPS challenge reduced the ileal threonine (Thr) digestibility, as well as serum isoleucine (Ile) and Trp concentrations, but increased the serum concentrations of Phe, Thr, histidine (His), alanine (Ala), cysteine (Cys), and serine (Ser) (P < 0.05). The serum-free amino acid concentrations of His, lysine (Lys), arginine (Arg), Trp, Tyr, Cys, and the digestibilities of His, Lys, Arg, and Cys were significantly increased by feeding AAA diets (P < 0.05). Dietary AAA supplementation significantly increased the serum concentrations of Trp in LPS-challenged piglets (P < 0.05). In the jejunal mucosa, LPS increased the contents of Ala and Cys, and the mRNA expressions of solute carrier (SLC) transporters (i.e., SLC7A11, SLC16A10, SLC38A2, and SLC3A2), but decreased Lys and glutamine (Gln) contents, and SLC1A1 mRNA expression (P < 0.05). In the ileal mucosa, LPS challenge induced increasing in SLC7A11 and SLC38A2 and decreasing in SLC38A9 and SLC36A1 mRNA expressions, AAAs supplementation significantly decreased mucosal amino acid (AA) concentrations of methionine (Met), Arg, Ala, and Tyr, etc. (P < 0.05). And the interaction between AAAs supplementation and LPS challenge significantly altered the expressions of SLC36A1 and SLC38A9 mRNA (P < 0.05). Together, these findings indicated that AAAs supplementation promoted the AAs absorption and utilization in the small intestine of piglets and increased the mRNA expressions of SLC transports to meet the high demands for specific AAs in response to inflammation and immune response.
Non-Coding RNAs Regulate the Resistance to Anti-EGFR Therapy in Colorectal Cancer
Authors: Chu Jinjin , Fang Xianzhu , Sun Zhonghou , Gai Linlin , Dai Wenqing , Li Haibo , Yan Xinyi , Du Jinke , Zhang Lili , Zhao Lu , Xu Donghua , Yan Shushan
Published: January 2022

Colorectal cancer (CRC) is the third prevalent cancer worldwide, the morbidity and mortality of which have been increasing in recent years. As molecular targeting agents, anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (McAbs) have significantly increased the progression-free survival (PFS) and overall survival (OS) of metastatic CRC (mCRC) patients. Nevertheless, most patients are eventually resistant to anti-EGFR McAbs. With the intensive study of the mechanism of anti-EGFR drug resistance, a variety of biomarkers and pathways have been found to participate in CRC resistance to anti-EGFR therapy. More and more studies have implicated non-coding RNAs (ncRNAs) primarily including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are widely involved in tumorigenesis and tumor progression. They function as essential regulators controlling the expression and function of oncogenes. Increasing data have shown ncRNAs affect the resistance of molecular targeted drugs in CRC including anti-EGFR McAbs. In this paper, we have reviewed the advance in mechanisms of ncRNAs in regulating anti-EGFR McAbs therapy resistance in CRC. It provides insight into exploring ncRNAs as new molecular targets and prognostic markers for CRC.
GPX7 Is Targeted by miR-29b and GPX7 Knockdown Enhances Ferroptosis Induced by Erastin in Glioma
Authors: Zhou Yan , Wu Haiyang , Wang Fanchen , Xu Lixia , Yan Yan , Tong Xiaoguang , Yan Hua
Published: January 2022

Background

Glioma is a lethal primary tumor of central nervous system. Ferroptosis is a newly identified form of necrotic cell death. Triggering ferroptosis has shown potential to eliminate aggressive tumors. GPX7, a member of glutathione peroxidase family (GPXs), has been described to participate in oxidative stress and tumorigenesis. However, the biological functions of GPX7 in glioma are still unknown.

Methods

Bioinformatics method was used to assess the prognostic role of GPX7 in glioma. CCK8, wound healing, transwell and cell apoptosis assays were performed to explore the functions of GPX7 in glioma cells. In vivo experiment was also conducted to confirm in vitro findings. Ferroptosis-related assays were carried out to investigate the association between GPX7 and ferroptosis in glioma.

Results

GPX7 was aberrantly expressed in glioma and higher expression of GPX7 was correlated with adverse outcomes. GPX7 silencing enhanced ferroptosis-related oxidative stress in glioma cells and the loss of GXP7 sensitized glioma to ferroptosis induced by erastin. Furthermore, we found that miR-29b directly suppressed GPX7 expression post-transcriptionally. Reconstitution of miR-29b enhanced erastin sensitivity, partly via GPX7 suppression.

Conclusions

Our study clarified the prognostic role of GPX7 in glioma and preliminarily revealed the role of GPX7 in ferroptosis, which may be conducive to the exploration of therapeutic targets of glioma.
Functional Outcomes and Morbidity in Pediatric Sepsis Survivors: A Tanzanian Experience
Authors: Lau-Braunhut Sarah A. , Smith Audrey M. , Steurer Martina A. , Murray Brittany L. , Sawe Hendry , Matthay Michael A. , Reynolds Teri , Kortz Teresa Bleakly
Published: January 2022

Pediatric sepsis remains a significant cause of childhood morbidity and mortality, disproportionately affecting resource-limited settings. As more patients survive, it is paramount that we improve our understanding of post-sepsis morbidity and its impact on functional outcomes. The functional status scale (FSS) is a pediatric validated outcome measure quantifying functional impairment, previously demonstrating decreased function following critical illnesses, including sepsis, in resource-rich settings. However, functional outcomes utilizing the FSS in pediatric sepsis survivors have never been studied in resource-limited settings or in non-critically ill septic children. In a Tanzanian cohort of pediatric sepsis patients, we aimed to evaluate morbidity associated with an acute septic episode using the FSS modified for resource-limited settings. This was a prospective cohort study at an urban referral hospital in Tanzania, including children with sepsis aged 28 days to 14 years old over a 12-month period. The FSS was adapted to the site's available resources. Functional status scale scores were obtained by interviewing guardians both at the time of presentation to determine the child's baseline and at 28-day follow-up. The primary outcome was “decline in functional status,” as defined by a change in FSS score of at least 3. In this cohort, 4.3% of the 1,359 surviving children completing 28-day follow-up had a “decline in functional status.” Conversely, 13.8% of guardians reported that their child was not yet back to their pre-illness state. Three-quarters of children reported as not fully recovered were not identified via the FSS as having a decline in functional status. In our cohort of pediatric sepsis patients, we identified a low rate of decline in functional status when using the FSS adapted for resource-limited settings. A higher proportion of children were subjectively identified as not being recovered to baseline. This suggests that the FSS has limitations in this population, despite being adapted for resource-limited settings. Next steps include developing and validating a further revised FSS to better capture patients identified as not recovered but missed by the current FSS.
Recent Advances in Chinese Herbal Medicine for Cerebral Ischemic Reperfusion Injury
Authors: Huang Ping , Wan Haitong , Shao Chongyu , Li Chang , Zhang Ling , He Yu
Published: January 2022

Cerebral ischemic reperfusion injury (CI/RI) is a critical factor that leads to a poor prognosis in patients with ischemic stroke. It is an extremely complicated pathological process that is clinically characterized by high rates of disability and mortality. Current available treatments for CI/RI, including mechanical and drug therapies, are often accompanied by significant side effects. Therefore, it is necessary to discovery new strategies for treating CI/RI. Many studies confirm that Chinese herbal medicine (CHM) was used as a potential drug for treatment of CI/RI with the advantages of abundant resources, good efficacy, and few side effects. In this paper, we investigate the latest drug discoveries and advancements on CI/RI, make an overview of relevant CHM, and systematically summarize the pathophysiology of CI/RI. In addition, the protective effect and mechanism of related CHM, which includes extraction of single CHM and CHM formulation and preparation, are discussed. Moreover, an outline of the limitations of CHM and the challenges we faced are also presented. This review will be helpful for researchers further propelling the advancement of drugs and supplying more knowledge to support the application of previous discoveries in clinical drug applications against CI/RI.
Inflammatory Cytokines and Risk of Ischemic Stroke: A Mendelian Randomization Study
Authors: Li Yalan , Lu Jun , Wang Jie , Deng Peizhi , Meng Changjiang , Tang Haibo
Published: January 2022

Background: Observational studies have revealed the association between some inflammatory cytokines and the occurrence of ischemic stroke, but the causal relationships remain unclear.

Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal effects of thirty inflammatory cytokines and the risk of ischemic stroke. For exposure data, we collected genetic variants associated with inflammatory cytokines as instrumental variables (IVs) from a genome-wide association study (GWAS) meta-analysis from Finland (sample size up to 8,293). For the outcome data, we collected summary data of ischemic stroke from a large-scale GWAS meta-analysis involved 17 studies (34,217 cases and 406,111 controls). We further performed a series of sensitivity analyses as validation of primary MR results.

Results: According to the primary MR estimations and further sensitivity analyses, we established one robust association after Bonferroni correction: the odds ratio (95% CI) per unit change in genetically increased IL-4 was 0.84 (0.89–0.95) for ischemic stroke. The chemokine MCP3 showed a nominally significant association with ischemic stroke risk (OR: 0.93, 95% CI: 0.88–0.99, unadjusted p < 0.05). There was no evidence of a causal effect of other inflammatory cytokines and the risk of ischemic stroke.

Conclusions: Our study suggested that genetically increased IL-4 levels showed a protective effect on the risk of ischemic stroke, which provides important new insights into the potential therapeutic target for preventing ischemic stroke.