bluuebunny/crossref_metadata_2025 huggingface dataset:
CYP2C19 metabolizer phenotypes may affect the efficacy of statins on lowering small dense low-density lipoprotein cholesterol of patients with coronary artery disease
Authors: Dai Ruozhu , Zhao Xiaoyu , Zhuo Huilin , Wang Wei , Xu Yue , Hu Zixin , Zhang Tiexu , Zhao Jiangman
Published: December 2022

Background

Dyslipidemia is a major cause of arteriosclerotic cardiovascular disease (ASCVD), and low-density lipoprotein cholesterol (LDL-C) is the profile to be reduced to prevent disease progression. Small dense low-density lipoprotein cholesterol (sdLDL-C) has been proven to be a more effective biomarker than LDL-C for ASCVD primary and secondary prevention. CYP2C19 is an important drug metabolism gene. This study aimed to investigate the relationship between sdLDL-C and coronary artery disease (CAD) risk factors and explore the influence of CYP2C19 metabolizer phenotypes on the sdLDL-C lowering efficacy of statins.

Methods

This study recruited 182 patients with CAD and 200 non-CAD controls. Baseline laboratory indices of fasting blood were detected, including blood lipids, glucose, and creatinine. In addition, LDL-C subfractions were separated and quantified. Gene polymorphisms of SLCO1B1 and CYP2C19 were detected in patients with CAD. The LDL-C subfractions levels of patients with CAD were followed up after statin drug treatment.

Results

Total cholesterol, LDL-C, LDLC-2, LDLC-3, LDLC-4, LDLC-5, LDLC-6, LDLC-7, and sdLDL-C levels of patients with CAD were significantly higher than those in non-CAD controls. Meanwhile, sdLDL-C (AUC = 0.838) and LDLC-4 (AUC = 0.835) performed outstandingly in distinguishing patients with CAD from controls. Based on CYP2C19 metabolizer phenotypes, 113 patients with CAD were divided into the extensive metabolizer (EM, n = 49), intermediate metabolizer (IM, n = 52), and poor metabolizer (PM, n = 12) groups. The patients with IM and PM metabolizer phenotypes had better sdLDL-C lowering efficacy after taking statin drugs than patients with EM phenotype (P = 0.0268, FDR = 0.0536). The SLCO1B1 genotype had no significant impact on the efficacy of statins (P = 0.1611, FDR = 0.1611).

Conclusion

sdLDL-C and LDLC-4 outperformed other blood lipids such as LDL-C for CAD risk screening. CYP2C19 metabolizer phenotypes had the potential to predict the efficacy of statins in lowering sdLDL-C.
Assessment of aortic valve area on cardiac computed tomography in symptomatic bicuspid aortic stenosis: Utility and differences from Doppler echocardiography
Authors: Kim Kyu , Lee Soo Ji , Seo Jiwon , Suh Young Joo , Cho Iksung , Hong Geu-Ru , Ha Jong-Won , Kim Young Jin , Shim Chi Young
Published: December 2022

Background

In this study, we investigate the utility of geometric orifice area (GOA) on cardiac computed tomography (CT) and differences from effective orifice area (EOA) on Doppler echocardiography in patients with bicuspid aortic stenosis (AS).

Methods

A total of 163 patients (age 64 ± 10 years, 56.4% men) with symptomatic bicuspid AS who were referred for surgery and underwent both cardiac CT and echocardiography within 3 months were studied. To calculate the aortic valve area, GOACT was measured by multiplanar CT planimetry, and EOAEcho was calculated by the continuity equation with Doppler echocardiography. The relationships between GOACT and EOAEcho and patient symptom scale, biomarkers, and left ventricular (LV) functional variables were analyzed.

Results

There was a significant but modest correlation between EOAEcho and GOACT (r = 0.604, p < 0.001). Both EOAEcho and GOACT revealed significant correlations with mean pressure gradient and peak transaortic velocity, and the coefficients were higher in EOAEcho than in GOACT. EOAEcho of 1.05 cm2 and GOACT of 1.25 cm2 corresponds to hemodynamic cutoff values for diagnosing severe AS. EOAEcho was well correlated with the patient symptom scale and log NT-pro BNP, but GOACT was not. In addition, EOAEcho had a higher correlation coefficient with estimated LV filling pressure and LV global longitudinal strain than GOACT.

Conclusion

GOACT can be used to evaluate the severity of bicuspid AS. The threshold for GOACT for diagnosing severe AS should be higher than that for EOAEcho. However, EOAEcho is still the method of choice because EOAEcho showed better correlations with clinical and functional variables than GOACT.
Reservoir quality and facies modeling of the early Eocene carbonate stratigraphic unit of the Middle Indus Basin, Pakistan
Authors: Khalid Perveiz , Ehsan Muhammd Irfan , Khurram Shahzada , Ullah Irfan , Ahmad Qazi Adnan
Published: December 2022

The early Eocene carbonate reservoir, Sui Main Limestone (SML), is the largest gas reservoir in Pakistan. In the Qadirpur area, more than 30 wells have been drilled, some of which have been declared dry or abandoned due to poor reservoir characteristics or facies variation. The aim of this work is to re-evaluate the reservoir characteristics and facies identification of Sui Main Limestone by using petrophysical analysis and rock physics modeling in the Qadirpur field in the Middle Indus Basin of Pakistan. The reservoir characterization of carbonate rocks is difficult because of their complex pore networking. The well data on five exploratory wells drilled in this gas field are used. The log-derived porosity varies in a very large range of 2%–36%, with an average of 14%–34%. The average porosity of the clean carbonate intervals is 10%–14% and thus has the capacity to accumulate hydrocarbon. The high porosity value indicates the presence of micro-fractures in Sui Main Limestone. These micro-fractures and secondary pores are well interconnected and allow the pore fluids to communicate. The secondary porosity is mainly due to the presence of vuggs and fractures in Sui Main Limestone. The volume of shale varies from 11%–38% in the wells. The net pay zones have hydrocarbon saturation in the range of 40%–70%, which is mainly gas. Using wireline log response, the formation is divided into three facies: limestone, shale, and shaly limestone. This comprehensive work may help improve the prediction of the reservoir quality in heterogeneous carbonate reservoirs and optimize field development.
Teachers’ alignment between a local initiated external assessment: The diagnostic literacy test—And teaching regarding special educational needs students’ needs
Authors: Sjunnesson Helena
Published: December 2022

The present study aims to study how external assessments are used by teachers, transforming summative test results into a formative approach for teaching, with a special focus on students with SEN. The data material consists of documents and interviews with teachers. The documents were the schools’ compilations of assessment results, including proposals for measures and action programs for individual students. The students’ action programs constitute data material for analysis of their needs regarding the outcomes of the DLS tests. Eight ordinary and six SEN teachers participated in follow-up interviews to express their understanding of the test results and their decisions regarding what adaptations and support the students needed. The results show the teachers’ expressions and understanding of aligning the results to better support the identified SEN students in education. The emerging results indicate that the primary purpose of the assessment was to identify students with SEN and to plan teaching for these students. SEN was identified by test results on or below stanine 3. The planned support was mainly directed toward special education conducted by SEN teachers. Within the same community, different interpretations of the assignment are possible. This may affect how the results are analyzed and implemented into teaching.
Effects of follicular output rate on cumulative clinical pregnancy rate and cumulative live birth rate in PCOS patients with different characteristics
Authors: Jiang Rulan , Cao Mingya , Hao Haomeng , Jia Rui , Chen Peipei , Liu Yuanyuan , Zhao Zhiming
Published: December 2022

Objective

We aim to explore the effects of follicular output rate (FORT) on cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLBR) in polycystic ovary syndrome (PCOS) patients with different characteristics undergoing in vitro fertilization (IVF) treatment.

Methods

This retrospective study analyzed 454 patients with PCOS undergoing their first IVF cycle at our center from January 2016 to December 2020. FORT was calculated as pre-ovulatory follicle count (PFC) × 100/antral follicle count (AFC). Multivariate regression analyses were conducted to explore the relationships between FORT and CCPR and CLBR. Curve fitting and threshold effect analyses were established to find nonlinear relationships. Effect modification in different subgroups were examined by stratification analyses.

Results

Based on the FORT values, individuals were classified into the following three groups: low-FORT group, middle-FORT group and high-FORT group. Multivariate regression analyses revealed that FORT was an independent factor affecting the CCPR and CLBR significantly (OR = 1.015, 95% CI: 1.001, 1.030 and OR = 1.010, 95% CI:1.001, 1.020). Curve fitting and threshold effect analyses showed that the CCPR and CLBR had a positive correlation with FORT when the FORT was less than 70% (OR = 1.039, 95% CI: 1.013, 1.065 and OR = 1.024, 95% CI: 1.004, 1.044). Stratification analyses showed that the CLBR increased by 1.3% with each additional unit of FORT for patients with hyperandrogenic manifestations (OR = 1.013, 95% CI: 1.001, 1.025). Compared with the low-FORT group, in the high-FORT group, CCPR increased 1.251 times for patients with polycystic ovarian morphology, while CCPR and CLBR increased 1.891 times and 0.99 times for those with ovulation disorder, respectively (OR = 2.251, 95% CI: 1.008, 5.028 and OR = 2.891, 95% CI: 1.332, 6.323 and OR = 1.990, 95% CI: 1.133, 3.494).

Conclusion

In patients with PCOS, cumulative IVF outcomes have a positive correlation with FORT when the FORT is less than 70%. For PCOS patients with polycystic ovarian morphology, ovulation disorder or hyperandrogenic manifestations, a high FORT could be conductive to achieving better pregnancy outcomes.
CCNB1 and AURKA are critical genes for prostate cancer progression and castration-resistant prostate cancer resistant to vinblastine
Authors: Chen Xi , Ma Junjie , Wang Xin’an , Zi Tong , Qian Duocheng , Li Chao , Xu Chengdang
Published: December 2022

Background

Prostate cancer (PCa) is a common malignancy occurring in men. As both an endocrine and gonadal organ, prostate is closely correlated with androgen. So, androgen deprivation therapy (ADT) is effective for treating PCa. However, patients will develop castration-resistant prostate cancer (CRPC) stage after ADT. Many other treatments for CRPC exist, including chemotherapy. Vinblastine, a chemotherapeutic drug, is used to treat CRPC. However, patients will develop resistance to vinblastine. Genetic alterations have been speculated to play a critical role in CRPC resistance to vinblastine; however, its mechanism remains unclear.

Methods

Various databases, such as Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Chinese Prostate Cancer Genome and Epigenome Atlas (CPGEA), were used to collect the RNA-sequence data of PCa and CRPC patients and vinblastine-resistant PCa cells. Using online tools, Metascape and TIMER, the pathways and immune infiltration associated with vinblastine resistance-related genes in PCa were analyzed. The function of these genes was verified in clinical samples and CRPC cells.

Results

Using GSE81277 dataset, we collected the RNA-sequence data of vinblastine sensitive and resistant LNCaP cells and found nine genes (CDC20, LRRFIP1, CCNB1, GPSM2, AURKA, EBLN2, CCDC150, CENPA and TROAP) that correlated with vinblastine resistance. Furthermore, CCNB1, GPSM2 and AURKA were differently expressed between normal prostate and PCa tissues, even influencing PCa progression. The GSE35988 dataset revealed that CCNB1 and AURKA were upregulated in PCa and CRPC samples. Various genes were also found to affect the survival status of PCa patients based on TCGA. These genes were also related to immune cell infiltration. Finally, we verified the function of CCNB1 and AURKA and observed that they were upregulated in PCa and CRPC clinical samples and increased the sensitivity of CRPC cells to vinblastine.

Conclusion

CCNB1 and AURKA are central to CRPC resistance to vinblastine and affect PCa progression.
The harmful intestinal microbial community accumulates during DKD exacerbation and microbiome–metabolome combined validation in a mouse model
Authors: Shang Jin , Cui Wen , Guo Ruixue , Zhang Yiding , Wang Peipei , Yu Wei , Zheng Xuejun , Wang Ting , Dong Yijun , Zhao Jing , Ding Suying , Xiao Jing , Ren Zhigang , Zhao Zhanzheng
Published: December 2022

Objective

Diabetic kidney disease (DKD) is one of the most prevalent complications of diabetes mellitus (DM) and is associated with gut microbial dysbiosis. We aim to build a diagnostic model to aid clinical practice and uncover a crucial harmful microbial community that contributes to DKD pathogenesis and exacerbation.

Design

A total of 528 fecal samples from 180 DKD patients and 348 non-DKD populations (138 DM and 210 healthy volunteers) from the First Affiliated Hospital of Zhengzhou University were recruited and randomly divided into a discovery phase and a validation phase. The gut microbial composition was compared using 16S rRNA sequencing. Then, the 180 DKD patients were stratified into four groups based on clinical stages and underwent gut microbiota analysis. We established DKD mouse models and a healthy fecal microbiota transplantation (FMT) model to validate the effects of gut microbiota on DKD and select the potential harmful microbial community. Untargeted metabolome–microbiome combined analysis of mouse models helps decipher the pathogenetic mechanism from a metabolic perspective.

Results

The diversity of the gut microbiome was significantly decreased in DKD patients when compared with that of the non-DKD population and was increased in the patients with more advanced DKD stages. The DKD severity in mice was relieved after healthy gut microbiota reconstruction. The common harmful microbial community was accumulated in the subjects with more severe DKD phenotypes (i.e., DKD and DKD5 patients and DKD mice). The harmful microbial community was positively associated with the serum injurious metabolites (e.g., cholic acid and hippuric acid).

Conclusion

The fecal microbial community was altered markedly in DKD. Combining the fecal analysis of both human and animal models selected the accumulated harmful pathogens. Partially recovering healthy gut microbiota can relieve DKD phenotypes via influencing pathogens’ effect on DKD mice’s metabolism.
Determination of the spent fuel decay heat with the VERA core simulator
Authors: Kromar Marjan , Godfrey Andrew T.
Published: December 2022

VERA core simulator capabilities to predict spent fuel decay heat have been explored. The comparison with the Serpent2 and NEWT/TRITON sequence from the SCALE package, performed on the NPP Krško fuel test cases, has enabled independent verification of the successful implementation of the VERA depletion/decay calculation sequence applied on the extended nuclide set. Since the VERA is a 3-D core simulator, the focus in the rest of the paper was on the investigation of the 3-D effects and non-linearity of the soluble boron concentration averaging process, which are difficult to assess with most of available computational tools. A difference in the decay heat prediction between the 3-D and 2-D model approaches was analyzed. In addition, the impact of the Inconel grids on the decay heat was determined. Averaging the concentration of soluble boron over the fuel irradiation period has been found to be a viable approach, since it results in slight decay heat overprediction, which is considered conservative for most applications. Finally, demonstration on the Watts Bar Unit 1 cycle 1 depletion has shown formidable VERA capabilities to accurately predict spent fuel decay heat.
Macrophages and γδ T cells interplay during SARS-CoV-2 variants infection
Authors: Atmeh Perla Abou , Gay Laetitia , Levasseur Anthony , La Scola Bernard , Olive Daniel , Mezouar Soraya , Gorvel Jean-Pierre , Mege Jean-Louis
Published: December 2022

Introduction

The emergence of several SARS-CoV-2 variants during the COVID pandemic has revealed the impact of variant diversity on viral infectivity and host immune responses. While antibodies and CD8 T cells are essential to clear viral infection, the protective role of innate immunity including macrophages has been recognized. The aims of our study were to compare the infectivity of different SARS-CoV-2 variants in monocyte-derived macrophages (MDM) and to assess their activation profiles and the role of ACE2 (Angiotensin-converting enzyme 2), the main SARS-CoV-2 receptor. We also studied the ability of macrophages infected to affect other immune cells such as γδ2 T cells, another partner of innate immune response to viral infections.

Results

We showed that the SARS-CoV-2 variants α-B.1.1.7 (United Kingdom), β-B.1.351 (South Africa), γ-P.1 (Brazil), δ-B.1.617 (India) and B.1.1.529 (Omicron), infected MDM without replication, the γ-Brazil variant exhibiting increased infectivity for MDM. No clear polarization profile of SARS-CoV-2 variants-infected MDM was observed. The β-B.1.351 (South Africa) variant induced macrophage activation while B.1.1.529 (Omicron) was rather inhibitory. We observed that SARS-CoV-2 variants modulated ACE2 expression in MDM. In particular, the β-B.1.351 (South Africa) variant induced a higher expression of ACE2, related to MDM activation. Finally, all variants were able to activate γδ2 cells among which γ-P.1 (Brazil) and β-B.1.351 (South Africa) variants were the most efficient.

Conclusion

Our data show that SARS-CoV-2 variants can infect MDM and modulate their activation, which was correlated with the ACE2 expression. They also affect γδ2 T cell activation. The macrophage response to SARS-CoV-2 variants was stereotypical.
Case report: Variable response to immunotherapy in ovarian cancer: Our experience within the current state of the art
Authors: Provinciali Nicoletta , Greppi Marco , Pesce Silvia , Rutigliani Mariangela , Briata Irene Maria , Buttiron Webber Tania , Fava Marianna , DeCensi Andrea , Marcenaro Emanuela
Published: December 2022

Despite recent advances in ovarian cancer (OC) treatment, including the introduction of bevacizumab and PARP-inhibitors, OC remains a lethal disease. Other therapeutic options are being explored, such as immunotherapy (IT), which has been proved effective in many solid tumors. Findings about tumor-infiltrating cytotoxic and regulatory T cells, together with the expression of PD-1 on immune cells and of PD-L1 on tumor cells, gave the rationale for an attempt to the use of IT also in OC. We treated two patients with avelumab, an anti-PD-L1 monoclonal antibody, after the first line of chemotherapy: Patient A underwent 19 cycles of maintenance therapy with avelumab with a disease-free interval of 12 months, whereas patient B showed a slight progression of disease after only eight cycles. A higher PD-L1 expression in tumor cells of patient A was detected. She also underwent a genomic assessment that described the presence of a high Tumor Mutational Burden (TMB) and a status of Loss of Heterozygosity (LoH). This different response to the same treatment puts in evidence that some genomic and immune features might be investigated.
Neurotrophic and immunomodulatory effects of olfactory ensheathing cells as a strategy for neuroprotection and regeneration
Authors: Denaro Simona , D’Aprile Simona , Alberghina Cristiana , Pavone Anna Maria , Torrisi Filippo , Giallongo Sebastiano , Longhitano Lucia , Mannino Giuliana , Lo Furno Debora , Zappalà Agata , Giuffrida Rosario , Tibullo Daniele , Li Volti Giovanni , Vicario Nunzio , Parenti Rosalba
Published: December 2022

Accumulating evidence sustains glial cells as critical players during central nervous system (CNS) development, homeostasis and disease. Olfactory ensheathing cells (OECs), a type of specialized glia cells sharing properties with both Schwann cells and astrocytes, are of critical importance in physiological condition during olfactory system development, supporting its regenerative potential throughout the adult life. These characteristics prompted research in the field of cell-based therapy to test OEC grafts in damaged CNS. Neuroprotective mechanisms exerted by OEC grafts are not limited to axonal regeneration and cell differentiation. Indeed, OEC immunomodulatory properties and their phagocytic potential encourage OEC-based approaches for tissue regeneration in case of CNS injury. Herein we reviewed recent advances on the immune role of OECs, their ability to modulate CNS microenvironment via bystander effects and the potential of OECs as a cell-based strategy for tissue regeneration.
An offshore subsurface thermal structure inversion method by coupling ensemble learning and tide model for the South Yellow Sea
Authors: Yu Fangjie , Sun Fengzhi , Li Jianchao , Chen Ge
Published: December 2022

The South Yellow Sea Cold Water Mass (SYSCWM), which occurs in the South Yellow Sea (SYS) during summer, significantly impacts the hydrological characteristics and marine ecosystems but lacks fine interior data. With satellite observations, significant achievements have been made in reconstructing high-resolution ocean subsurface thermohaline structure based on machine learning. However, the accuracy of offshore subsurface parameter estimation will be affected due to the macro-tidal environment and fewer in situ observations. In this paper, we coupled the TPXO tide model and Light Gradient Boosting Machine algorithm to develop an inversion model of offshore subsurface thermal structure for the SYS using sea surface data and in situ observations. After light modelling, the subsurface temperature structure in the SYS is retrieved from sea surface parameters with a spatial resolution of 0.25° at depths of 0-55 m. Observation-based dataset (ARMOR3D) and in situ observations are used for model evaluation. According to the validation of the mooring buoy observations, the overall coefficient of determination (R2), which determines the percentage of variance in the dependent variable that can be explained by the independent variable, is more than 0.95. Furthermore, the R2 is improved by 12% due to coupling tide model below the thermocline during the maturity stage of SYSCWM, which is helpful for a better reconstruction of SYSCWM. Comparing with the cruise data, the average R2 of the proposed model is 0.927 which is slightly better than the accuracy of the observation-based ARMOR3D dataset. Since the R2 exceeds 0.8 in the most area of 121°E~123.5°E, 33°N~36°N, the reconstruction is reliable in this area. The method provides a new explorable direction for reconstructing the ocean thermal structure in offshore areas.
A control method for hydraulic fracturing of the hard roof with long and short boreholes
Authors: Ma Jinkui , Li Hong , Guo Xiaomin , Tian Fuchao , Guo Huaiguang
Published: December 2022

During the mining of the working face, the hard roof can lead to a series of problems, such as air leakage in goafs, gas emission and concentration, casualties, and damages to buildings and ecological environment. The treatment of the hard roof has always been a difficult problem in major coal-producing countries. Although many scholars have conducted some theoretical research and field practice in this field in recent years, the aforementioned safety problems still occur frequently. In order to understand the mechanism of crack propagation caused by hydraulic fracturing of the roof, based on the theoretical analysis of linear elastic fracture mechanics and coal rock mechanics, the shear fracture criterion was determined for the formation of horizontal fractures in the natural cracks. The anisotropy of the crack tip, the adhesion forces in the coal and rock fracture surface and the conditions for hydraulic-induced crack propagation were also considered. The formation of cracks involves a vertical main crack and multiple extended-airfoil branch cracks which interconnect transversely and longitudinally. Under the effect of hydrodynamic water wetting and hydraulic fracturing, the stress of coal and mass changed. Meanwhile, the mechanical parameeters, such as compression, tensile strength and elasticity modulus and etc., were weakened, thus achieving the goal of structural transformation and slight weakening of coal and rock mass. According to the bidirectional stress of coal and rock mass, the maximum principal compressive stress of crack opening was calculated, and the propagation mechanism of hydraulic fracturing cracks in the hard roof was obtained. The hydraulic fracturing technology for controlling the hard roof was illustrated and has been applied in No. 2 Well of Sihe Coal Mine for many years. The research results could provide reference for the control of the hard roof in other similar mines.
Polyurethane biodegradation by Serratia sp. HY-72 isolated from the intestine of the Asian mantis Hierodula patellifera
Authors: Kim Jong-Hoon , Choi Seung Hoon , Park Min Gu , Park Dong Hwan , Son Kwang-Hee , Park Ho-Yong
Published: December 2022

Polyurethane (PU), currently replacing existing synthetic materials worldwide, is a synthetic polymer derived from polyols, isocyanates, and a chain extender added by condensation reactions. PU wastes which are difficult to recycle, are commonly discarded in landfills and flow into ecosystems, thereby causing serious environmental problems. In recent years, insect-associated microbes have become a promising, eco-friendly strategy as an alternative to plastic recycling. This study aimed to evaluate the potential of Serratia sp. HY-72 strain isolated from the intestine of the Asian mantis (Hierodula patellifera) for PU degradation. The 65 kDa family I.3 lipase which degrades PU was identified and characterized, with a specific activity of 2,883 U mg−1. The bacterial filtrates and the recombinant lipase degraded Impranil (a colloidal polyester-PU dispersion, 100 g l−1) by 85.24 and 78.35% after 72 h incubation, respectively. Fourier transform infrared spectroscopy analysis revealed changes in Impranil functional groups, with decreased C=O functional group and aliphatic chain signals, and increased N-H bending with C-N stretching and C-O stretching. The current study also revealed that the HY-72 strain biodegraded the commercial PU foams (polyester- and polyether- PU) with 23.95 and 10.95% weight loss after 2 weeks, respectively with changes in surface morphology and structure such as cracks, roughness, and surface roughening. Altogether, this is one of the few studies reporting biodegradation of PU by the insect-associated microbe. These findings suggest that the insect-associated microbe could be a promising resource for biodegradation and recycling of plastic waste.
A shift from inorganic to organic nitrogen-dominance shapes soil microbiome composition and co-occurrence networks
Authors: Xin Yue , Shi Yu , He Wei-Ming
Published: December 2022

Soil microbiomes are characterized by their composition and networks, which are linked to soil nitrogen (N) availability. In nature, inorganic N dominates at one end and organic N dominates at the other end along soil N gradients; however, little is known about how this shift influences soil microbiome composition and co-occurrence networks, as well as their controls. To this end, we conducted an experiment with the host plant Solidago canadensis, which was subject to three N regimes: inorganic N-dominated, co-dominated by inorganic and organic N (CIO), and organic N-dominated. Organic N dominance exhibited stronger effects on the composition and co-occurrence networks of soil microbiomes than inorganic N dominance. The predominant control was plant traits for bacterial and fungal richness, and soil pH for keystone species. Relative to the CIO regime, inorganic N dominance did not affect fungal richness and increased keystone species; organic N dominance decreased fungal richness and keystone species. Pathogenic fungi and arbuscular mycorrhizal fungi were suppressed by organic N dominance but not by inorganic N dominance. These findings suggest that the shift from soil inorganic N-dominance to soil organic N-dominance could strongly shape soil microbiome composition and co-occurrence networks by altering species diversity and topological properties.
Systematic analysis of virus nucleic acid sensor DDX58 in malignant tumor
Authors: Huang Zhijian , Yi Limu , Jin Liangzi , Chen Jian , Han Yuanyuan , Zhang Yan , Shi Libin
Published: December 2022

Introduction

In December 2019, a novel epidemic of coronavirus pneumonia (COVID-19) was reported，and population-based studies had shown that cancer was a risk factor for death from COVID-19 infection. However, the molecular mechanism between COVID-19 and cancer remains indistinct. In this paper, we analyzed the nucleic acid sensor (DDX58) of SARS-CoV-2 virus, which is a significant gene related to virus infection. For purpose of clarifying the characteristics of DDX58 expression in malignant tumors, this study began to systematically analyze the DDX58 expression profile in the entire cancer type spectrum.

Methods

Using TCGA pan-cancer database and related data resources, we analyzed the expression, survival analysis, methylation expression, mutation status, microsatellite instability (MSI), immune related microenvironment, gene related network, function and drug sensitivity of DDX58.

Results

The expression level of DDX58 mRNA in most cancers was higher than the expression level in normal tissues. Through TIMER algorithm mining, we found that DDX58 expression was closely related to various levels of immune infiltration in pan-cancer. The promoter methylation level of DDX58 was significantly increased in multiple cancers. In addition, abnormal expression of DDX58 was related to MSI and TMB in multiple cancers, and the most common type of genomic mutation was “mutation.” In the protein–protein interaction (PPI) network, we found that type I interferon, phagocytosis, ubiquitinase, and tumor pathways were significantly enriched. Finally, according to the expression of DDX58 indicated potential sensitive drugs such as Cediranib, VE−821, Itraconazole, JNJ−42756493, IWR−1, and Linsitinib.

Discussion

In conclusion, we had gained new insights into how DDX58 might contribute to tumor development, and DDX58 could be used as an immune-related biomarker and as a potential immunotherapeutic target for COVID-19 infected cancer patients.
Acanthamoeba spp. aggregate and encyst on contact lens material increasing resistance to disinfection
Authors: Campolo Allison , Pifer Reed , Walters Rhonda , Thomas Megan , Miller Elise , Harris Valerie , King Jamie , Rice Christopher A. , Shannon Paul , Patterson Brian , Crary Monica
Published: December 2022

Introduction

Acanthamoeba keratitis is often caused when Acanthamoeba contaminate contact lenses and infect the cornea. Acanthamoeba is pervasive in the environment as a motile, foraging trophozoite or biocide-resistant and persistent cyst. As contact lens contamination is a potential first step in infection, we studied Acanthamoeba’s behavior and interactions on different contact lens materials. We hypothesized that contact lenses may induce aggregation, which is a precursor to encystment, and that aggregated encystment would be more difficult to disinfect than motile trophozoites.

Methods

Six clinically and/or scientifically relevant strains of Acanthamoeba (ATCC 30010, ATCC 30461, ATCC 50370, ATCC 50702, ATCC 50703, and ATCC PRA-115) were investigated on seven different common silicone hydrogel contact lenses, and a no-lens control, for aggregation and encystment for 72 h. Cell count and size were used to determine aggregation, and fluorescent staining was used to understand encystment. RNA seq was performed to describe the genome of Acanthamoeba which was individually motile or aggregated on different lens materials. Disinfection efficacy using three common multi-purpose solutions was calculated to describe the potential disinfection resistance of trophozoites, individual cysts, or spheroids.

Results

Acanthamoeba trophozoites of all strains examined demonstrated significantly more aggregation on specific contact lens materials than others, or the no-lens control. Fluorescent staining demonstrated encystment in as little as 4 hours on contact lens materials, which is substantially faster than previously reported in natural or laboratory settings. Gene expression profiles corroborated encystment, with significantly differentially expressed pathways involving actin arrangement and membrane complexes. High disinfection resistance of cysts and spheroids with multi-purpose solutions was observed.

Discussion

Aggregation/encystment is a protective mechanism which may enable Acanthamoeba to be more disinfection resistant than individual trophozoites. This study demonstrates that some contact lens materials promote Acanthamoeba aggregation and encystment, and Acanthamoeba spheroids obstruct multi-purpose solutions from disinfecting Acanthamoeba.
Canonical and non-canonical roles for ATG8 proteins in autophagy and beyond
Authors: Reid Steven Edward , Kolapalli Srinivasa Prasad , Nielsen Thorbjørn M. , Frankel Lisa B.
Published: December 2022

During autophagy, the ATG8 family proteins have several well-characterized roles in facilitating early, mid, and late steps of autophagy, including autophagosome expansion, cargo recruitment and autophagosome-lysosome fusion. Their discovery has importantly allowed for precise experimental monitoring of the pathway, bringing about a huge expansion of research in the field over the last decades. In this review, we discuss both canonical and non-canonical roles of the autophagic lipidation machinery, with particular focus on the ATG8 proteins, their post-translational modifications and their increasingly uncovered alternative roles mediated through their anchoring at different membranes. These include endosomes, macropinosomes, phagosomes and the plasma membrane, to which ATG8 proteins can bind through canonical or alternative lipidation. Beyond new ATG8 binding partners and cargo types, we also explore several open questions related to alternative outcomes of autophagic machinery engagement beyond degradation. These include their roles in plasma membrane repair and secretion of selected substrates as well as the physiological implications hereof in health and disease.
Behavioral restriction, lorazepam, and escitalopram uniquely influence the expression of naturalistic stereotypy in deer mice: perspectives on anxiety- and compulsive-like behavior
Authors: Burke Johann T. , Mograbi Daniel C. , Wolmarans De Wet
Published: December 2022

Introduction: Stereotypical expression in laboratory-housed rodents can be explained by different motivational, coping, and motor dysfunction theories. Here, we aimed to explore the neurocognitive underpinnings of high stereotypical (HS) expression in deer mice (Peromyscus maniculatus bairdii), previously proposed as a model system of compulsive-like behavioral persistence. Specifically, we aimed to establish whether HS behavior is related to an underlying escape-related trigger.

Methods: One-hundred and sixteen deer mice were classified as either non-stereotypical (NS) or HS. Mice of each cohort were further subdivided and exposed to either sub-acute (3-day) or chronic (25-day) behavioral restriction (R), and high-dose escitalopram (ESC), lorazepam (LOR), alone and in combination with R (ESC+R and LOR+R, respectively). Mice were reassessed for stereotypical behavior at both time points.

Results: Our results indicate that HS behavior is likely not temporally and functionally related to an anxiogenic trigger, i.e., R, but rather that HS is associated with parallel changes in anxiogenic feedback processing. We also show that chronic R alone significantly decreased the time spent in expressing HS behavior in animals of the HS, but not NS phenotype.

Discussion: This points to the possibility that HS-expressing mice represent a subgroup of P. maniculatus bairdii in which unique interactions between neurobiology and processes of gradual behavioral organization, may contribute to the expression of the typical behaviors observed in this cohort. Collectively, our findings highlight the value of the deer mouse model system to investigate the potential neurocognitive mechanisms that may underlie the development of persistent phenotypes that can likely not be explained entirely by current theories.
Identification of immunogenic cell death-related gene classification patterns and immune infiltration characterization in ischemic stroke based on machine learning
Authors: Cai Jiayang , Ye Zhang , Hu Yuanyuan , Yang Ji’an , Wu Liquan , Yuan Fanen , Zhang Li , Chen Qianxue , Zhang Shenqi
Published: December 2022

Ischemic stroke (IS) accounts for more than 80% of strokes and is one of the leading causes of death and disability in the world. Due to the narrow time window for treatment and the frequent occurrence of severe bleeding, patients benefit less from early intravenous thrombolytic drug therapy. Therefore, there is an urgent need to explore the molecular mechanisms poststroke to drive the development of new therapeutic approaches. Immunogenic cell death (ICD) is a type of regulatory cell death (RCD) that is sufficient to activate the adaptive immune response of immunocompetent hosts. Although there is growing evidence that ICD regulation of immune responses and immune responses plays an important role in the development of IS, the role of ICD in the pathogenesis of IS has rarely been explored. In this study, we systematically evaluated ICD-related genes in IS. The expression profiles of ICD-related genes in IS and normal control samples were systematically explored. We conducted consensus clustering, immune infiltration analysis, and functional enrichment analysis of IS samples using ICD differentially expressed genes. The results showed that IS patients could be classified into two clusters and that the immune infiltration profile was altered in different clusters. In addition, we performed machine learning to screen nine signature genes that can be used to predict the occurrence of disease. We also constructed nomogram models based on the nine risk genes (CASP1, CASP8, ENTPD1, FOXP3, HSP90AA1, IFNA1, IL1R1, MYD88, and NT5E) and explored the immune infiltration correlation, gene-miRNA, and gene-TF regulatory network of the nine risk genes. Our study may provide a valuable reference for further elucidation of the pathogenesis of IS and provide directions for drug screening, personalized therapy, and immunotherapy for IS.
Untargeted lipidomics and metagenomics reveal the mechanism of aspirin eugenol ester relieving hyperlipidemia in ApoE−/− mice
Authors: Lu Xiao-Rong , Liu Xi-Wang , Li Shi-Hong , Qin Zhe , Bai Li-Xia , Ge Wen-Bo , Li Jian-Yong , Yang Ya-Jun
Published: December 2022

Hyperlipidemia is induced by abnormal lipid metabolism, which can cause the occurrence of cardiovascular diseases and lead to grievous injury to health. Studies showed that AEE had a significant therapeutic effect on hyperlipidemia and is likely to be associated with the up-regulation of cholesterol 7-alpha hydroxylase (CYP7A1), the key enzyme for cholesterol conversion to bile acids, but no research confirmed whether the effect of AEE on hyperlipidemia was related to the gut microbiota and liver lipids. At the same time, more and more studies have shown that gut microbiota and lipids are closely related to hyperlipidemia. Hence, in this study, we investigated the effects of AEE on liver lipids through LC-MS-based untargeted lipidomics and the effects of AEE on gut microbiota based on cecal contents metagenomics by Illumina sequencing in HFD-induced hyperlipidemia ApoE−/− mice at the overall level. The results of lipidomics showed that AEE relieved hyperlipidemia by decreasing the concentration of 10 PEs and 12 SMs in the liver and regulating the pathways of glycerophospholipid metabolic pathway, sphingolipid signaling pathway, and NF-kB signaling pathway. The results of metagenomics concluded that AEE treatment changed the composition of gut microbiota and regulated the functions of lipid transport and metabolism, as well as the metabolism of bile acids and secondary bile acids. The results of the joint analysis between lipidomics and metagenomics showed that the abundance of Verrucomicrobia, Verrucomicrobiales, Candidatus_Gastranaerophilales, and Candidatus_Melainabacteria was significantly positively correlated with the concentration of SM (d18:1/18:0) and PE (16:0/18:1) in the process of AEE alleviating hyperlipidemia in mice. In conclusion, these results suggested that the effect of AEE on hyperlipidemia was closely related to the gut microbiota by the change of bile acids and liver lipids.
Dietary intake of fructose increases purine de novo synthesis: A crucial mechanism for hyperuricemia
Authors: Zhang Pengfei , Sun Huimin , Cheng Xinyu , Li Yajing , Zhao Yanli , Mei Wuxuan , Wei Xing , Zhou Hairong , Du Yunbo , Zeng Changchun
Published: December 2022

Background

Fructose consumption is a potential risk factor for hyperuricemia because uric acid (UA) is a byproduct of fructose metabolism caused by the rapid consumption of adenosine triphosphate and accumulation of adenosine monophosphate (AMP) and other purine nucleotides. Additionally, a clinical experiment with four gout patients demonstrated that intravenous infusion of fructose increased the purine de novo synthesis rate, which implied fructose-induced hyperuricemia might be related to purine nucleotide synthesis. Moreover, the mechanistic (mammalian) target of rapamycin (mTOR) is a key protein both involved in fructose metabolism and purine de novo synthesis. The present study was conducted to elucidate how fructose influences mTOR and purine de novo synthesis in a hepatic cell line and livers of mice.

Materials and methods

RNA-sequencing in NCTC 1469 cells treated with 0- and 25-mM fructose for 24 h and metabolomics analysis on the livers of mice fed with 0- and 30-g/kg fructose for 2 weeks were assessed. Gene and protein expression of phosphoribosyl pyrophosphate synthase (PRPSAP1), Glutamine PRPP aminotransferase (PPAT), adenyl succinate lyase (ADSL), adenyl succinate synthetase isozyme-1 (Adss1), inosine-5’-monophosphate dehydrogenase (IMPDH), and guanine monophosphate synthetase (GMPS) was measured. The location of PRPSAP1 and PPAT in the liver was assessed by an immunofluorescence assay.

Results

Metabolite profiling showed that the level of AMP, adenine, adenosine, hypoxanthine, and guanine was increased significantly. RNA-sequencing showed that gene expression of phosphoribosyl pyrophosphate synthase (PRPS2), phosphoribosyl glycinamide formyl transferase (GART), AICAR transformylase (ATIC), ADSL, Adss1, and IMPDH were raised, and gene expression of adenosine monophosphate deaminase 3 (AMPD3), adenosine deaminase (ADA), 5’,3’-nucleotidase, cytosolic (NT5C), and xanthine oxidoreductase (XOR) was also increased significantly. Fructose increased the gene expression, protein expression, and fluorescence intensity of PRPSAP1 and PPAT in mice livers by increasing mTOR expression. Fructose increased the expression and activity of XOR, decreased the expression of uricase, and increased the serum level of UA.

Conclusion

This study demonstrated that the increased purine de novo synthesis may be a crucial mechanism for fructose-induced hyperuricemia.
Study on the protective effect of berberine treatment on sepsis based on gut microbiota and metabolomic analysis
Authors: Pan Huibin , Huo Lixia , Shen Weiyun , Dai Zhuquan , Bao Ying , Ji Chaohui , Zhang Jie
Published: December 2022

Introduction

Sepsis, an infection with multiorgan dysfunction, is a serious burden on human health. Berberine (BBR), a bioactive component, has a protective effect on sepsis and the effect may be related to gut microbiota. However, studies on the role of BBR with gut microbiota in sepsis are lacking. Therefore, this study investigated the ameliorative effects and the underlying mechanisms of BBR on cecal ligature and puncture (CLP) rats.

Methods

This study has observed the effect of BBR on pathological injury, Inflammation, intestinal barrier function, gut microbiota, and metabolite change in CLP rats by Hematoxylin-eosin staining, enzyme-linked immunosorbent assays, flow cytometry, 16S rDNA, and metabolomics analyses.

Results

The inhibition effects of BBR treatment on the histological damage of the lung, kidney, and ileum, the interleukin (IL)-1b, IL-6, IL-17A, and monocyte chemokine-1 levels in serum in CLP rats were proved. Also, the BBR inhibited the diamine-oxidase and fluorescein isothiocyanate-dextran 40 levels, suggesting it can improve intestinal barrier function disorders. The cluster of differentiation (CD) 4+, CD8+, and CD25+ Forkhead box protein P3 (Foxp3) + T lymphocytes in splenocytes were up-regulated by BBR, while the IL-17A+CD4+ cell level was decreased. The abundance of gut microbiota in CLP rats was significantly different from that of the sham and BBR treatment rats. The significantly changed metabolites in the serum mainly included carbohydrates, phenols, benzoic acids, alcohols, vitamins et al. Additionally, this study predicted that the biological mechanism of BBR to ameliorate sepsis involves glycolysis-, nucleotide-, and amino acid-related metabolic pathways.

Discussion

This study proved the strong correlation between the improvement effect of BBR on sepsis and gut microbiota and analyzed by metabolomics that gut microbiota may improve CLP rats through metabolites, providing a scientific basis for BBR to improve sepsis and a new direction for the study of the biological mechanism.
Identification of potential target genes of honokiol in overcoming breast cancer resistance to tamoxifen
Authors: Hermawan Adam , Putri Herwandhani , Hanif Naufa , Fatimah Nurul , Prasetio Heri Himawan
Published: December 2022

Background

Honokiol (HON) inhibits epidermal growth factor receptor (EGFR) signaling and increases the activity of erlotinib, an EGFR inhibitor, in human head and neck cancers. In this study, using a bioinformatics approach and in vitro experiments, we assessed the target genes of HON against breast cancer resistance to tamoxifen (TAM).

Materials and methods

Microarray data were obtained from GSE67916 and GSE85871 datasets to identify differentially expressed genes (DEGs). DEGs common between HON-treated and TAM-resistant cells were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and protein-protein interaction (PPI) networks were constructed. Selected genes were analyzed for genetic alterations, expression, prognostic value, and receiver operating characteristics (ROC). TAM-resistant MCF-7 (MCF-7 TAM-R) cells were generated and characterized for their resistance toward TAM. A combination of HON and TAM was used for cytotoxicity and gene expression analyses. Molecular docking was performed using the Molecular Operating Environment software.

Results

PPI network analysis revealed that FN1, FGFR2, and RET were the top three genes with the highest scores. A genetic alteration study of potential target genes revealed MMP16 and ERBB4 as the genes with the highest alterations among the breast cancer samples. Pathway enrichment analysis of FGFR2, RET, ERBB4, SOX2, FN1, and MMP16 showed that the genetic alterations herein were likely to impact the RTK-Ras pathway. The expression levels of RET, MMP16, and SOX2 were strongly correlated with prognostic power, with areas under the ROC curves (AUC) ​​of 1, 0.8, and 0.8, respectively. The HON and TAM combination increased TAM cytotoxicity in MCF-7 TAM-R cells by regulating the expression of potential target genes ret, ERBB4, SOX2, and FN1, as well as the TAM resistance regulatory genes including HES1, VIM, PCNA, TP53, and CASP7. Molecular docking results indicated that HON tended to bind RET, ErbB4, and the receptor protein Notch1 ankyrin domain more robustly than its native ligand.

Conclusion

HON could overcome breast cancer resistance to TAM, potentially by targeting FGFR2, RET, ERBB4, MMP16, FN1, and SOX2. However, further studies are required to validate these results.