bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 infection induces activation of ferroptosis in human placenta
Authors: Wang Bingbing , Shen Wei-Bin , Yang Peixin , Turan Sifa
Published: November 2022

Ferroptosis, a regulated non-apoptotic form of cell death, has been implicated in the response to varied types of infectious agents including virus. In this study, we sought to determine whether SARS-CoV-2 infection can induce activation of ferroptosis in the human placenta. We collected placentas from 23 pregnant females with laboratory-confirmed SARS-CoV-2 following delivery and then used RNA in situ hybridization assay for detection of viral positive-sense strand (PSS) to confirm that these placentas have been infected. We also used immunohistochemistry assay to assess expression levels of acyl-CoA synthetase long-chain family member 4 (ACSL4), an essential executioner of ferroptosis in the same specimens. Our results showed that ACSL4 expression was significantly increased in the group with positive positive-sense strand staining compared to their negative counterparts (p = 0.00022). Furthermore, we found that there was a positive trend for increased PSS staining along with increased ACSL4 expression. Our study supports that ferroptosis is activated in the response to SARS-CoV-2 infection in the human placenta, highlighting a molecular mechanism potentially linking this coronavirus infection and pathogenesis of adverse pregnancy outcomes.
Repair effect of the poly (D,L-lactic acid) nanoparticle containing tauroursodeoxycholic acid-eluting stents on endothelial injury after stent implantation
Authors: Zhou Jiedong , Weng Jingfan , Huang Xingxiao , Sun Shimin , Yang Qi , Lin Hui , Yang Jinjin , Guo Hangyuan , Chi Jufang
Published: November 2022

Background

Chronic endoplasmic reticulum stress (ERS) plays a crucial role in cardiovascular diseases. Thus, it can be considered a therapeutic target for these diseases. In this study, poly (D,L-lactic acid) (PDLLA) nanoparticle-eluting stents loaded with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, was fabricated to assess their ability to reduce endothelial cell apoptosis and promote re-endothelialization after stent implantation.

Materials and methods

PDLLA nanoparticles loaded with TUDCA were prepared via the emulsification-solvent evaporation method. The cumulative release rates of TUDCA were measured in vitro via high-performance liquid chromatography. The carotid arteries of rabbits were subsequently implanted with stents in vivo. The rabbits were then sacrificed after 4 weeks for scanning electron microscopy. Meanwhile, TUDCA concentration in the homogenate of the peripheral blood and distal vascular tissue after stent implantation was measured. The effect of TUDCA on ERS, apoptosis, and human umbilical vein endothelial cell (HUVEC) function was investigated in vitro by performing cell migration assay, wound healing assay, cell proliferation assays, endoplasmic reticulum (ER)-specific fluorescence staining, immunofluorescence, and western blotting.

Results

TUDCA nanoparticles were released slowly over 28 days. In addition, TUDCA-eluting stents enhanced re-endothelialization and accelerated the recovery of endotheliocytes in vivo. ERS and apoptosis significantly increased in H2O2-treated HUVECs in vitro. Meanwhile, TUDCA reduced apoptosis and improved function by inhibiting ERS in H2O2-treated HUVECs. Decreased rates of apoptosis and ERS were observed after silencing XBP-1s in H2O2-treated HUVECs.

Conclusion

TUDCA can inhibit apoptosis and promote re-endothelialization after stent implantation by inhibiting IRE/XBP1s-related ERS. These results indicate the potential therapeutic application of TUDCA as a drug-coated stent.
Global research trends in in-stent neoatherosclerosis: A CiteSpace-based visual analysis
Authors: Wang Heng , Wang Qian , Hu Jie , Zhang Ruijing , Gao Tingting , Rong Shuling , Dong Honglin
Published: November 2022

Background

Recent studies have shown that in-stent neoatherosclerosis (ISNA/NA) is an important cause of late stent failure. A comprehensive understanding of the current state of research in this field will facilitate the analysis of its development trends and hot frontiers. However, no bibliometric correlation has been reported yet. Here, we analyze the relevant literature since the emergence of the concept and provide valuable insights.

Methods

Publications were collected from the Web of Science Core Collection (WoSCC) and PubMed. Microsoft Excel, SPSS and CiteSpace were used to analyze and present the data.

Results

A total of 498 articles were collected, with Japan and Cardiovasc Res Fdn being the main publishing forces in all country/region and institutions. J AM COLL CARDIOL is the journal with the most published and co-cited articles. According to co-citation analysis, optical coherence tomography, thrombosis, implantation, restenosis, drug-eluting stent, and bare metal stent have become more and more popular recently.

Conclusion

ISNA is a niche and emerging field. How to reduce the incidence of ISNA and improve the late patency rate of coronary stents may remain a hot spot for future research. The pathogenesis of ISNA also needs to be explored in more depth.
Cardiovascular adverse events in chronic myeloid leukemia patients treated with nilotinib or imatinib: A systematic review, meta-analysis and integrative bioinformatics analysis
Authors: Li Sicong , He Jinshan , Zhang Xinyi , Cai Yuchun , Liu Jian , Nie Xiaoyan , Shi Luwen
Published: November 2022

Objective

The aim of this article is to assess the risk and potential mechanisms of cardiovascular adverse events in patients treated with nilotinib or imatinib by conducting a systematic review, meta-analysis and integrative bioinformatics analysis.

Materials and methods

Three databases were systematically searched for studies published from inception to May 29, 2022. Differential expression analysis and weighted gene coexpression network analysis (WGCNA) were performed to search for modules of genes most associated with cardiotoxicity. Protein-protein interaction (PPI) network analysis was then performed to identify hub genes for the cardiotoxicity of nilotinib. Molecular docking was used to analyze the effects of rosuvastatin and aspirin on these targets.

Results

Patients treated with nilotinib as first-line treatment were associated with a higher risk of CAE (OR = 3.43 [95% CI 2.77–4.25]), CAD (OR = 5.30 [95% CI 3.85–7.29]), ACS (OR 2.7 [95% CI 1.60–4.54]), CVA (OR 5.76 [95% CI 2.84–11.28]), PAOD (OR 5.57 [95% CI 3.26–9.50]) and arrhythmia (OR 2.34 [1.17,4.67]) than those treated with imatinib, while no significant difference was found in the risk of HF (OR 1.40 [95% CI 0.42–4.69]) between the two groups. Patients who were treated with more than 600 mg daily dosage of nilotinib or followed up for more than 5 years had a higher risk of ACS and CVA. IL6, CXCL8, CCL2, SOD2, NFKBIA, and BIRC3 were identified as the top 6 hub genes in the magenta module (human cardiomyocyte samples) and were mainly enriched in the NOD-like receptor signaling pathway, IL-17 signaling pathway, TNF signaling pathway, lipid and atherosclerosis signaling pathway. TYROBP and CSF1R were identified as hub genes in the turquoise module (liver samples from Mus musculus). GSEA results showed that type II diabetes mellitus, B-cell receptor, apoptosis, insulin, natural killer cell mediated cytotoxicity,

mTOR, chemokine, and T-cell receptor signaling pathways were related to the higher risk of atherosclerosis caused by nilotinib. Rosuvastatin can effectively bind to most of the hub targets and proteins enriched in the inflammatory pathways above.

Conclusion

CML patients who start with nilotinib have a higher risk of CAE than those with imatinib. Atherosclerosis caused by the inflammatory response and glycolipid metabolism disorder is the key mechanism of nilotinib cardiotoxicity. Rosuvastatin may be an effective treatment for the cardiotoxicity of nilotinib.
Radiation therapy induces immunosenescence mediated by p90RSK
Authors: Imanishi Masaki , Cheng Haizi , Kotla Sivareddy , Deswal Anita , Le Nhat-Tu , Chini Eduardo , Ko Kyung Ae , Samanthapudi Venkata S. K. , Lee Ling-Ling , Herrmann Joerg , Xu Xiaolei , Reyes-Gibby Cielito , Yeung Sai-Ching J. , Schadler Keri L. , Yusuf Syed Wamique , Liao Zhongxing , Nurieva Roza , Amir El-ad David , Burks Jared K. , Palaskas Nicolas L. , Cooke John P. , Lin Steven H. , Kobayashi Michihiro , Yoshimoto Momoko , Abe Jun-ichi
Published: November 2022

Radiation therapy (RT) to the chest increases the patients’ risk of cardiovascular disease (CVD). A complete understanding of the mechanisms by which RT induces CVD could lead to specific preventive, therapeutic approaches. It is becoming evident that both genotoxic chemotherapy agents and radiation induce mitochondrial dysfunction and cellular senescence. Notably, one of the common phenotypes observed in cancer survivors is accelerated senescence, and immunosenescence is closely related to both cancer risk and CVD development. Therefore, suppression of immunosenescence can be an ideal target to prevent cancer treatment-induced CVD. However, the mechanism(s) by which cancer treatments induce immunosenescence are incompletely characterized. We isolated peripheral blood mononuclear cells (PBMCs) before and 3 months after RT from 16 thoracic cancer patients. We characterized human immune cell lineages and markers of senescence, DNA damage response (DDR), efferocytosis, and determinants of clonal hematopoiesis of indeterminant potential (CHIP), using mass cytometry (CyTOF). We found that the frequency of the B cell subtype was decreased after RT. Unsupervised clustering of the CyTOF data identified 138 functional subsets of PBMCs. Compared with baseline, RT increased TBX21 (T-bet) expression in the largest B cell subset of Ki67–/DNMT3a+naïve B cells, and T-bet expression was correlated with phosphorylation of p90RSK expression. CD38 expression was also increased in naïve B cells (CD27–) and CD8+ effector memory CD45RA T cells (TEMRA). In vitro, we found the critical role of p90RSK activation in upregulating (1) CD38+/T-bet+ memory and naïve B, and myeloid cells, (2) senescence-associated β-gal staining, and (3) mitochondrial reactive oxygen species (ROS) after ionizing radiation (IR). These data suggest the crucial role of p90RSK activation in immunosenescence. The critical role of p90RSK activation in immune cells and T-bet induction in upregulating atherosclerosis formation has been reported. Furthermore, T-bet directly binds to the CD38 promoter region and upregulates CD38 expression. Since both T-bet and CD38 play a significant role in the process of immunosenescence, our data provide a cellular and molecular mechanism that links RT-induced p90RSK activation and the immunosenescence with T-bet and CD38 induction observed in thoracic cancer patients treated by RT and suggests that targeting the p90RSK/T-bet/CD38 pathway could play a role in preventing the radiation-associated CVD and improving cancer prognosis by inhibiting immunosenescence.
Tropical cyclone rapid intensification and the excitation of inertia-gravity waves on the edges of an evolving potential vorticity structure
Authors: Schubert Wayne H. , Taft Richard K.
Published: November 2022

The problem of tropical cyclone rapid intensification is reduced to a potential vorticity (PV) equation and a second order, inhomogeneous, partial differential equation for the azimuthal wind. The latter equation has the form of a Klein-Gordon equation, the right-hand side of which involves the radial derivative of the evolving PV field. When the PV field evolves rapidly, inertia-gravity waves are excited at the edges of the evolving PV structure. In contrast, when the PV field evolves slowly, the second order time derivative term in the Klein-Gordon equation is negligible, inertia-gravity waves are not excited, and the equation reduces to an invertibility principle for the PV. The above concepts are presented in the context of an axisymmetric shallow water model, in both its linear and nonlinear forms. The nonlinear results show a remarkable sensitivity of vortex intensification to the percentage of mass that is diabatically removed from the region inside a given absolute angular momentum surface.
Expansion/shrinkage history of the Paratethys Sea during the Eocene: New insights from eolian Red Clay records in the Altyn Mountains, northern China
Authors: Guo Benhong , Nie Junsheng , Li Jianxing , Xiao Wenjiao , Pan Feng
Published: November 2022

Uplift of the Tibetan Plateau, expansion/shrinkage of the Paratethys Sea, and global climate are three major forcings for central-east Asian climatic and environmental variations during the Cenozoic. However, knowledge of expansion/shrinkage history of the Paratethys Sea is much less well known in comparison with the other two forcings. Here, we present a first multiple-parameter environmental magnetic and diffuse reflectance spectroscopy study of the Eocene eolian Red Clay deposits (∼51–40 Ma) in the Xorkol Basin of the northeastern Tibetan Plateau, which is near the easternmost maximum boundary of the Eocene Paratethys Sea. The first detailed Eocene expansion/shrinkage history of the Paratethys Sea was reconstructed based on the hematite content of the Eocene Red Clay, which shows remarkable consistency with the previous low-resolution Paratethys Sea paleowater depth record in the southwestern Tarim Basin. These results demonstrate that the Paratethys Sea experienced a three-stage (shrinkage-expansion-shrinkage) evolution between ∼51 and 40 Ma, with boundaries at ∼46.2 and 42 Ma. Superimposed on this framework, the Paratethys Sea experienced four times of rapid shrinkages at the expansion phase (shows 400-kyr cycles) during ∼44–42 Ma modulated by eccentricity forcings. These new results are of great significance to evaluate respective role of Tibetan uplift, global climate, and Paratethys Sea area variations in Asian climate and environmental change over the Eocene.
SETTLE DOWN: Preliminary investigations and development of an online toolkit to support student self-regulation in higher education
Authors: Keane Carol A. , Miller Leonie M. , Eady Michelle J. , Green Corinne A.
Published: November 2022

The impact of stressors on student wellbeing and academic performance is widely documented within the Higher Education (HE) sector, with student drop-out rates linked to poor wellbeing. Identified connections between attrition rates and the levels of support offered to students has led to concerted efforts to better support student wellbeing–particularly for those in the first year of study. The COVID-19 pandemic and the rapid and abrupt shift toward online learning has complicated how students manage stress by reducing students’ access to the very resources that might otherwise buffer them (e.g., social connection) exposing them to risk factors (e.g., isolation and greater uncertainty). Accordingly, empowering students to better self-regulate during stressful times is, more than ever, essential to supporting the transition to the adult learning environment. The development of students’ self-awareness and self-knowledge of the influences of being stressed on their engagement in study is an important adjunct to self-regulated learning. This nexus between psychology and education is a point for an interventive program that meets a gap in current support efforts, and that recognises the need for such endeavours that situate within the digital landscape of HE. In this paper we describe the groundwork of a single cohort case study that outlines a novel approach to student wellbeing. We discuss the design and development process of the SETTLE DOWN program; an evidence-based and clinically informed series of self-regulation workshops for undergraduate students, which aimed to foster student self-awareness about personal stress responses, facilitate a guided self-discovery of self-regulation techniques, and embed self-knowledge through reflection and practice. Preliminary pilot data is presented with respect to the intended purpose of assessing the suitability of the program material to achieve desired outcomes. The translation of these workshops into an online format to maximise accessibility for students and teachers is extrapolated in discussion of future-directions and next steps for the SETTLE DOWN program. The case study offers an example of the development of an evidence-based approach to ultimately support students with online availability of the necessary knowledge and skills to foster self-awareness and self-knowledge in the context of engaging in study under stress.
Numerical Study on the performance of a heat pump-driven-DCMD for sustainable desalination
Authors: Oh Seung Jin , Kim Yeongmin , Hong Youngsun , Kim Jong Woo , Kang Byungchan
Published: November 2022

The study presents an energy-efficient desalination system that combines direct contact membrane distillation (DCMD) and a heat pump to improve thermal efficiency and integrate with photovoltaics. DCMD is a sort of thermal desalination process, and it requires a lot of thermal energy. A heat pump is a device that produces both hot and cold energy simultaneously with less electrical energy input compared to other heating devices, such as a boiler and an electrical heater. A hollow-fiber DCMD and a 10-kW water-to-water heat pump were considered for a numerical simulation in this study. Numerical models were established for each device and validated against the results obtained from the literature. The simulation was first carried out to identify the performance of the system based on the baseline. After that, a series of simulations were carried out in order to investigate the performance of the proposed system in terms of specific energy consumption (SEC), gained output ratio (GOR), and the coefficient of performance (COP) under various operating conditions. Results showed that the minimum SEC and the maximum GOR were achieved at the inlet feed water temperature of 66.5°C with a mass flow rate of 20 kg/min and the inlet permeate temperature of 19.8°C with a mass flow rate of 10 lpm. On the other hand, it was found that the maximum COP can be observed at the inlet feed water temperature of 23.6°C with a mass flow rate of 10 lpm and at the inlet permeate temperature of 8.9°C with a mass flow rate of 20 lpm.
Evaluating the barrier of typical production factor flow in the Chengdu-Chongqing Urban Agglomeration based on multi-source big data
Authors: Zhang Yang , Wang Xingping , Ji Mengrong , Chen Yulu , Yan Feng
Published: November 2022

Promoting the free flow of production factors and improving the efficiency of resource allocation is a necessary requirement for China to achieve high-quality development. Therefore, it is significant to evaluate the barrier of production factors flow and analyze its influencing factors. This study, based on the flow space theory, takes the Chengdu-Chongqing urban agglomeration as an example, constructs the factor flow barrier index (FFBI) with multi-source big data (Baidu Migration data, investment data of listed companies and patent transfer data) and statistical data to evaluate the barriers of three typical product factors flow (labor flow, technology flow and capital flow). Moreover, quadratic assignment procedure regression model is used to analyze how system, economic, society, culture, policy and facility factors affect the barrier of the three typical production factors flow. The results demonstrate that: 1) The intensity of the three typical production factors flow of Chengdu-Chongqing are the highest, and the intensity of three typical production factors flow between the two cities and other cities are higher than that between other 14 cities. 2) In 120 city pairs, 87, 100 and 106 city pairs have positive FFBI of labor flow, capital flow and technology flow, respectively. The FFBI of Chongqing between other cities are mostly positive, indicating the three typical production factors flow are hindered to some extent. Labor flow is less hindered than capital flow and technology flow. 3) Administrative division relationships and administrative level differences have important impact on the barriers of the three typical production factors flow. City pairs belonging to different provincial administrative regions or within the same administrative level have larger FFBI. The barrier of labor and capital are positively affected by the transportation cost and the similarity of the industrial structure, respectively. The framework and findings are of great significance for revealing the formation mechanism of the barrier of production factors flow and provide some guidance for promoting the free flow of production factors and forming a new pattern of high-quality development in the Chengdu-Chongqing Urban Agglomeration.
Body size and age estimation of Chinese sea bass (Lateolabrax maculatus) and evidence of Late Neolithic fishing strategies, a case study from the Guye site
Authors: Yu Chong , Cui Yong
Published: November 2022

Fishing was an important form of subsistence economy among ancient societies. However, details of past fishing activities have been rarely studied in China. This paper uses data extracted from a modern fish collection to estimate the body size and age of Chinese sea bass from the Guye site, a common species that is frequently discovered in archaeological sites of coastal South China. The distribution of body size and age were reconstructed and combined with fish biology and ecology; the current dataset revealed that the main fishing grounds of the Late Neolithic Guye people were close to the shoreline, and the main fishing season was from spring to early autumn.
Assessing the effectiveness of landscape-scale forest adaptation actions to improve resilience under projected climate change
Authors: Maxwell Charles J. , Scheller Robert M. , Wilson Kristen N. , Manley Patricia N.
Published: November 2022

Climate change will increase disturbance pressures on forested ecosystems worldwide. In many areas, longer, hotter summers will lead to more wildfire and more insect activity which will substantially increase overall forest mortality. Forest treatments reduce tree density and fuel loads, which in turn reduces fire and insect severity, but implementation has been limited compared to the area needing treatment. Ensuring that forests remain near their reference conditions will require a significant increase in the pace and scale of forest management. In order to assess what pace and scale may be required for a landscape at risk, we simulated forest and disturbance dynamics for the central Sierra Nevada, USA. Our modeling framework included forest growth and succession, wildfire, insect mortality and locally relevant management actions. Our simulations accounted for climate change (five unique global change models on a business-as-usual emissions pathway) and a wide range of plausible forest management scenarios (six total, ranging from less than 1% of area receiving management treatments per year to 6% per year). The climate projections we considered all led to an increasing climatic water deficit, which in turn led to widespread insect caused mortality across the landscape. The level of insect mortality limited the amount of carbon stored and sequestered while leading to significant composition changes, however, only one climate change projection resulted in increased fire over contemporary conditions. While increased pace and scale of treatments led to offsets in fire related tree mortality, managing toward historic reference conditions was not sufficient to reduce insect-caused forest mortality. As such, new management intensities and other adaptation actions may be necessary to maintain forest resilience under an uncertain future climate.
The advanced lung cancer inflammation index predicts chemotherapy response and infection risk in multiple myeloma patients receiving induction chemotherapy
Authors: Cheng Jie , Li Qianyuan , Xiao Sheng , Nie Lu , Liao Jianping , Jiang Qingjie , Xiang Biyu , Zhang Hongfei , Jiang Yanhong , Yao Chenjiao
Published: November 2022

Objective: This study aims to determine the clinical significance of the advanced lung cancer inflammation index (ALI) in predicting prognosis, chemotherapy response, and infection risk in newly diagnosed multiple myeloma (MM) patients receiving induction therapy.

Methods: A retrospective analysis of the clinical characteristics and laboratory data of 111 newly diagnosed MM patients from the Haematology Department of the Third Xiangya Hospital of Central South University from January 2014 to March 2020 was performed. We first determined the relationship between ALI and overall survival (OS), as well as clinical and laboratory parameters. Second, predictive factors for chemotherapy response were analysed by univariate and multivariate regression analyses. Third, univariate regression analysis of risk factors was performed using infection as the evaluable outcome.

Results: Of the 111 evaluable patients, the low ALI group (<32.7) exhibited significantly poorer survival than the high ALI group (51 months versus 77 months). Multivariable analysis showed that advanced age, chemotherapy response and serum calcium level were independent prognostic factors for OS. Better chemotherapy efficacy in the high ALI group (89.3%) than in the low ALI group (42.2%) (p < 0.001) was noted. Multivariate analysis suggested that only ALI [HR: 0.110, 95% CI (0.035–0.350), p = 0.000] is an independent predictive factor in evaluating the efficiency of induction chemotherapy. Forty patients (36.04%) presented with infection after induction chemotherapy. Univariate analysis suggested that low ALI and abnormal renal function increase risk of infection in newly diagnosed MM patients.

Conclusion: Our study confirmed that ALI is not only a prognostic biomarker for newly diagnosed patients, but also predicts chemotherapy efficacy in newly diagnosed MM patients receiving induction therapy.
Genome-wide identification and characterization profile of phosphatidy ethanolamine-binding protein family genes in carrot
Authors: Liu Xing , Zhao Donghang , Ou Chenggang , Hao Weidong , Zhao Zhiwei , Zhuang Feiyun
Published: November 2022

Members of the family of Phosphatidy Ethanolamine-Binding Protein (PEBP) have been shown to be key regulators of the transition of plants from vegetative to reproductive phases. Here, a total of 12 PEBP proteins were identified in the carrot (Daucus carota L.) genome and classified into FT-like (4), TFL1-like (6), and MFT-like 2) subfamilies, that had different lengths (110–267 aa) and were distributed unevenly across seven chromosomes. Moreover, 13 and 31 PEBP proteins were identified in other two Apiaceae species, celery (Apium graveolens L.) and coriander (Coriandrum sativum L.). The phylogenetic and evolutionary results of these PEBP family proteins were obtained based on the protein sequences. In the three Apiaceae species, purifying selection was the main evolutionary force, and WGD, segmental duplication, and dispersed duplication have played key roles in the PEBP family expansion. The expression analysis showed that carrot PEBP genes exhibited relatively broad expression patterns across various tissues. In the period of bolting to flowering, the carrot FT-like subfamily genes were upregulated as positive regulators, and TFL1-like subfamily genes remained at lower expression levels as inhibitors. More interestingly, the members of carrot FT-like genes had different temporal-spatial expression characteristics, suggesting that they have different regulatory functions in the carrot reproductive phase. In summary, this study contributes to our understanding of the PEBP family proteins and provides a foundation for exploring the mechanism of carrot bolting and flowering for the breeding of cultivars with bolting resistance.
Identification of polyunsaturated fatty acids related key modules and genes in metabolic dysfunction-associated fatty liver disease using WGCNA analysis
Authors: Xiao Cheng , Chen Siliang , Yang Chunru , Liu Jieying , Yu Miao
Published: November 2022

Polyunsaturated fatty acids (PUFAs) play important roles in the aetiology and pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD). However, the underlying molecular mechanisms are not understood. We analysed a public GEO dataset, GSE89632, to identify differentially expressed genes (DEGs) in MAFLD. Weighted gene coexpression network analysis (WGCNA) was used to reveal the core gene regulation network and to explore the PUFA-related hub genes in MAFLD. We experimentally verified these genes by quantitative reverse transcription PCR in high-fat diet (HFD)-fed mice. A total of 286 common DEGs (89 upregulated; 197 downregulated), mostly related to inflammatory and immune responses, were identified. Six modules were constructed using WGCNA, and 2 modules showed significant correlations with PUFAs. After combining these 2 modules with DEGs, the top 10 hub genes were identified. We further established a MAFLD mouse model with liver steatosis, as proved by HE and Oil Red O staining. Of the hub genes, ADAM metallopeptidase with thrombospondin type 1 motif 1 (adamts1) (p = 0.005) and transforming growth factor β3 (tgfβ3) (p < 0.001) showed significantly lower mRNA expression in MAFLD in vivo. adamts1 and tgfβ3 bridged PUFAs and MAFLD, which might be potential causative genes and therapeutic targets of MAFLD.
Fibroblast growth factor receptor family mutations as a predictive biomarker for immune checkpoint inhibitors and its correlation with tumor immune microenvironment in melanoma
Authors: Zhang Wengang , Xia Handai , Yang Rui , Zhang Yuqing , Zheng Qi , Shang Xiaoling , Liu Ni , Ma Xinchun , Wei Chenxi , Chen Hang , Mu Xin , Wang Xiuwen , Liu Yanguo
Published: November 2022

Background

The emergence of immune checkpoint inhibitors (ICIs) has significantly improved the clinical outcomes of patients with metastatic melanoma. However, survival benefits are only observed in a subset of patients. The fibroblast growth factor receptor (FGFR) family genes are frequently mutated in melanoma, yet their impacts on the efficacy of ICIs remain unclear. Our study aimed to explore the association of FGFR mutations with ICIs efficacy in metastatic melanoma.

Methods

The Cancer Genome Atlas (TCGA) data (PanCancer Atlas, skin cutaneous melanoma (SKCM), n = 448) in cBioPortal were collected as a TCGA cohort to investigate the association between FGFR mutations and prognosis of melanoma patients. To explore the impact of FGFR mutations on the efficacy of ICIs in melanoma, clinical and tumor whole-exome sequencing (WES) data of four ICI-treated studies from cBioPortal were consolidated as an ICIs-treated cohort. Moreover, the relationship between FGFR mutations and immunogenicity (tumor mutation burden (TMB), neo-antigen load (NAL), mismatch repair (MMR)-related genes and DNA damage repair (DDR)-related genes) of melanoma was evaluated utilizing data from the ICIs-treated cohort. The influence of FGFR mutations on the tumor immune microenvironment (TIME) of melanoma was also analyzed using the TCGA cohort.

Results

In the TCGA cohort, survival in melanoma patients with or without FGFR mutations was nearly equivalent. In the ICIs-treated cohort, patients with FGFR mutations had better survival than those without (median overall survival: 60.00 vs. 31.00 months; hazard ratio: 0.58, 95% CI: 0.42-0.80; P = 0.0051). Besides, the objective response rate was higher for patients harboring FGFR mutations (55.56%) compared to wild-type patients (22.40%) (P = 0.0076). Mechanistically, it was revealed that FGFR mutations correlated with increased immunogenicity (e.g., TMB, NAL, MMR-related gene mutations and DDR-related gene mutations). Meanwhile, FGFR mutant melanoma tended to exhibit an enhanced antitumor TIME compared with its wild-type counterparts.

Conclusions

Our study demonstrated that FGFR mutations is a promising biomarker in stratifying patients with advanced melanoma who might benefit from ICIs therapy.
The CARD8 T60 variant associates with NLRP1 and negatively regulates its activation
Authors: Xu Zhihao , Deng Shasha , Huang Yuluo , Yang Yunru , Sun Liangqi , Liu Hanyuan , Zhao Dan , Zeng Weihong , Yin Xueying , Zheng Peiyi , Wang Yingying , Liu Muziying , Zhao Weidong , Xiao Tsan Sam , Zhou Ying , Jin Tengchuan
Published: November 2022

The NLRP1 inflammasome functions as canonical cytosolic sensor in response to intracellular infections and is implicated in auto-inflammatory diseases. But the regulation and signal transduction mechanisms of NLRP1 are incompletely understood. Here, we show that the T60 variant of CARD8, but not the canonical T48 isoform, negatively regulates the NLRP1 inflammasome activation by directly interacting with the receptor molecule NLRP1 and inhibiting inflammasome assembly. Furthermore, our results suggest that different ASC preference in three types of inflammasomes, namely the ASC-indispensable NLRP1 inflammasome, ASC-dispensable mNLRP1b inflammasome and ASC-independent CARD8 inflammasome, is mainly caused by the CARD domain, not the UPA subdomain. Based on the systematic site-directed mutagenesis and structural analysis, we find that signal transduction of the NLRP1 inflammasome relies on multiple interaction surfaces at its CARD domain. Finally, our results partly explain how mutations in NLRP1 lead to its constitutive activation in auto-inflammatory diseases. In conclusion, our study not only reveals how CARD8 downregulates the NLRP1 inflammasome activation, but also provides insights into the assembly mechanisms of CARD-containing inflammasomes.
Translating the observed differences in interleukin-6 levels between some antiretroviral regimens into potential long-term risk of serious non-AIDS events: A modeling study
Authors: Serrano-Villar Sergio , Cohen Calvin , Baker Jason V. , Janeiro Maria João , Aragão Filipa , Melbourne Kathleen , Gonzalez Jose Luis , Lara Laura , Kim Connie , Moreno Santiago
Published: November 2022

Introduction

Variable levels of systemic inflammation are observed in people with HIV (PWH), but the clinical significance of differences among antiretroviral therapy (ART) regimens on associated levels of inflammatory markers is unclear. Based on data from previous epidemiologic studies that defined the predicted change in risk of serious non-AIDS events (SNAEs)/death by changes in interleukin-6 (IL-6) and D-dimer, we modeled the effects of differences in these markers between specific ART regimens on the long-term risk of clinical outcomes.

Methods

We used a Markov model to compare the risk of SNAEs/death with differences in IL-6 and D-dimer levels associated with remaining on specific three-drug regimens versus switching to specific two-drug ART regimens over 5 years of treatment. We used IL-6 and D-dimer data based on trajectories over time from the randomized TANGO and observational AIR studies. Age at model entry was set at 39 years. The primary endpoint was the number needed to treat for one additional SNAE/death.

Results

Over 3 years, PWH on one of the three-drug regimens studied were predicted to spend 13% more time in the low IL-6 quartile and 11% less time in the high IL-6 quartile compared with those on one of the two-drug regimens. Over 3 years, the predicted mean number of SNAEs/deaths per 100 PWH was 6.58 for a three-drug regimen associated with lower IL-6 levels versus 6.90 for a two-drug regimen associated with higher IL-6 levels. The number needed to treat for one additional SNAE/death among PWH receiving a two-drug versus three-drug regimen for 3 years was 81. Approximately 7,500 participants would be required for a 5-year clinical study to evaluate the accuracy of the model.

Conclusions

Our Markov model suggests that higher IL-6 levels associated with switching from specific three- to two- drug ART regimens may be associated with an increase in the risk of SNAEs/death. Clinical studies are warranted to confirm or refute these results.
Applications of nanobodies in brain diseases
Authors: Zheng Fang , Pang Yucheng , Li Luyao , Pang Yuxing , Zhang Jiaxin , Wang Xinyi , Raes Geert
Published: November 2022

Nanobodies are antibody fragments derived from camelids, naturally endowed with properties like low molecular weight, high affinity and low immunogenicity, which contribute to their effective use as research tools, but also as diagnostic and therapeutic agents in a wide range of diseases, including brain diseases. Also, with the success of Caplacizumab, the first approved nanobody drug which was established as a first-in-class medication to treat acquired thrombotic thrombocytopenic purpura, nanobody-based therapy has received increasing attention. In the current review, we first briefly introduce the characterization and manufacturing of nanobodies. Then, we discuss the issue of crossing of the brain-blood-barrier (BBB) by nanobodies, making use of natural methods of BBB penetration, including passive diffusion, active efflux carriers (ATP-binding cassette transporters), carrier-mediated influx via solute carriers and transcytosis (including receptor-mediated transport, and adsorptive mediated transport) as well as various physical and chemical methods or even more complicated methods such as genetic methods via viral vectors to deliver nanobodies to the brain. Next, we give an extensive overview of research, diagnostic and therapeutic applications of nanobodies in brain-related diseases, with emphasis on Alzheimer’s disease, Parkinson’s disease, and brain tumors. Thanks to the advance of nanobody engineering and modification technologies, nanobodies can be linked to toxins or conjugated with radionuclides, photosensitizers and nanoparticles, according to different requirements. Finally, we provide several perspectives that may facilitate future studies and whereby the versatile nanobodies offer promising perspectives for advancing our knowledge about brain disorders, as well as hopefully yielding diagnostic and therapeutic solutions.
A genomic approach to analyze the cold adaptation of yeasts isolated from Italian Alps
Authors: Turchetti Benedetta , Buzzini Pietro , Baeza Marcelo
Published: November 2022

Microorganisms including yeasts are responsible for mineralization of organic matter in cold regions, and their characterization is critical to elucidate the ecology of such environments on Earth. Strategies developed by yeasts to survive in cold environments have been increasingly studied in the last years and applied to different biotechnological applications, but their knowledge is still limited. Microbial adaptations to cold include the synthesis of cryoprotective compounds, as well as the presence of a high number of genes encoding the synthesis of proteins/enzymes characterized by a reduced proline content and highly flexible and large catalytic active sites. This study is a comparative genomic study on the adaptations of yeasts isolated from the Italian Alps, considering their growth kinetics. The optimal temperature for growth (OTG), growth rate (Gr), and draft genome sizes considerably varied (OTG, 10°C–20°C; Gr, 0.071–0.0726; genomes, 20.7–21.5 Mpb; %GC, 50.9–61.5). A direct relationship was observed between calculated protein flexibilities and OTG, but not for Gr. Putative genes encoding for cold stress response were found, as well as high numbers of genes encoding for general, oxidative, and osmotic stresses. The cold response genes found in the studied yeasts play roles in cell membrane adaptation, compatible solute accumulation, RNA structure changes, and protein folding, i.e., dihydrolipoamide dehydrogenase, glycogen synthase, omega-6 fatty acid, stearoyl-CoA desaturase, ATP-dependent RNA helicase, and elongation of very-long-chain fatty acids. A redundancy for several putative genes was found, higher for P-loop containing nucleoside triphosphate hydrolase, alpha/beta hydrolase, armadillo repeat-containing proteins, and the major facilitator superfamily protein. Hundreds of thousands of small open reading frames (SmORFs) were found in all studied yeasts, especially in Phenoliferia glacialis. Gene clusters encoding for the synthesis of secondary metabolites such as terpene, non-ribosomal peptide, and type III polyketide were predicted in four, three, and two studied yeasts, respectively.
Seminal and vagino-uterine microbiome and their individual and interactive effects on cattle fertility
Authors: Luecke Sarah M. , Webb Emily M. , Dahlen Carl R. , Reynolds Lawrence P. , Amat Samat
Published: November 2022

Reproductive failure is a major economical drain on cow-calf operations across the globe. It can occur in both males and females and stem from prenatal and postnatal influences. Therefore, the cattle industry has been making efforts to improve fertility and the pregnancy rate in cattle herds as an attempt to maintain sustainability and profitability of cattle production. Despite the advancements made in genetic selection, nutrition, and the implementation of various reproductive technologies, fertility rates have not significantly improved in the past 50 years. This signifies a missing factor or factors in current reproductive management practices that influence successful fertilization and pregnancy. Emerging lines of evidence derived from human and other animals including cattle suggest that the microbial continuum along the male and female reproductive tracts are associated with male and female fertility—that is, fertilization, implantation, and pregnancy success—highlighting the potential for harnessing the male and female reproductive microbiome to improve fertility in cattle. The objective of this narrative review is to provide an overview of the recent studies on the bovine seminal and vagino-uterine microbiome and discuss individual and interactive roles of these microbial communities in defining cattle fertility.
Diversity of endophytic fungi isolated from different plant parts of Acacia mangium, and antagonistic activity against Ceratocystis fimbriata, a causal agent of Ceratocystis wilt disease of A. mangium in Malaysia
Authors: Ahmad Mohd Farid , Zahari Rozihawati , Mohtar Mastura , Wan-Muhammad-Azrul Wan Azhar , Hishamuddin Muhammad Syahmi , Samsudin Nik Iskandar Putra , Hassan Affendy , Terhem Razak
Published: November 2022

Acacia mangium is an important wood for commercial products especially pulp and medium-density fibreboard. However, it is susceptible to Ceratocystis fimbriata infection, leading to Ceratocystis wilt. Therefore, the present work aimed to (i) establish the diversity of endophytic fungi in different plant parts of A. mangium,and (ii) evaluate the antifungal potentials of the isolated and identified endophytic fungi against C. fimbriata. Endophytic fungal identification was conducted by PCR amplification and sequencing of the internal transcribed spacer 1 (ITS1) and ITS4 regions of nuclear ribosomal DNA. A total of 66 endophytic fungi were successfully isolated from different parts of A. mangium; leaf (21), stem (13), petiole (12), root (9), flower (6), and fruit (5). The endophytic fungal isolates belonged to Ascomycota (95.5%) and Zygomycota (4.5%). For Ascomycota 13 genera were identified: Trichoderma (28.6%), Nigrospora (28.6%), Pestalotiopsis (12.7%), Lasiodiplodia (9.5%), Aspergillus (6.3%), Sordariomycetes (3%), and Neopestalotiopsis, Pseudopestalotiopsis, Eutiarosporella, Curvularia, Fusarium, Penicillium, and Hypoxylon each with a single isolate. For Zygomycota, only Blakeslea sp. (5%) was isolated. Against C. fimbriata, Trichoderma koningiopsis (AC 1S) from stem, Nigrospora oryzae (AC 7L) from leaf, Nigrospora sphaerica (AC 3F) from the flower, Lasiodiplodia sp. (AC 2 U) from fruit, Nigrospora sphaerica (AC 4P) from petiole, and Trichoderma sp. (AC 9R) from root exhibited strong inhibition for C. fimbriata between 58.33 to 69.23%. Thus, it can be concluded that certain endophytic fungi of A. mangium have the potential to be harnessed as anti-Ceratocystis agent in future biotechnological applications.
Acrylamide adsorption by Enterococcus durans and Enterococcus faecalis: In vitro optimization, simulated digestive system and binding mechanism
Authors: Albedwawi Amal S. , Al Sakkaf Reem , Osaili Tareq M. , Yusuf Ahmed , Al Nabulsi Anas , Liu Shao-Quan , Palmisano Giovanni , Ayyash Mutamed M.
Published: November 2022

Acrylamide is an unsaturated amide that forms in heated, starchy food products. This study was conducted to (1) examine the ability of 38 LAB to remove acrylamide; (2) optimize acrylamide removal of selected LAB under various conditions (pH, temperature, time and salt) using the Box–Behnken design (BBD); (3) the behavior of the selected LAB under the simulated gastrointestinal conditions; and (4) investigate the mechanism of adsorption. Out of the 38 LAB, Enterococcus durans and Enterococcus faecalis had the highest results in removing acrylamide, with 33 and 30% removal, respectively. Those two LAB were further examined for their binding abilities under optimized conditions of pH (4.5–6.5), temperature (32°C - 42°C), time (14–22 h), and NaCl (0–3% w/v) using BBD. pH was the main factor influenced the acrylamide removal compared to other factors. E. durans and E. faecalis exhibited acrylamide removal of 44 and 53%, respectively, after the in vitro digestion. Zeta potential results indicated that the changes in the charges were not the main cause of acrylamide removal. Transmission electron microscopes (TEM) results indicated that the cell walls of the bacteria increased when cultured in media supplemented with acrylamide.
ToLCNDV-ES infection in tomato is enhanced by TYLCV: Evidence from field survey and agroinoculation
Authors: Vo Thuy Thi Bich , Troiano Elisa , Lal Aamir , Hoang Phuong Thi , Kil Eui-Joon , Lee Sukchan , Parrella Giuseppe
Published: November 2022

The tomato leaf curl New Delhi virus (ToLCNDV), a bipartite begomovirus (family Geminiviridae), poses a significant threat to various horticultural crops in many Asian and Mediterranean countries. Since its identification, the Asian strain of this virus has exhibited severe infectivity and caused high yield loss in tomato and cucurbit production in the Indian subcontinent and other parts of Asia. ToLCNDV-ES, a different strain of ToLCNDV, emerged recently in the Mediterranean Basin and caused significant outbreaks in Cucurbitaceae species but has shown low adaptation to tomatoes. In a field survey, tomato plants infected with this Mediterranean strain were not discovered. Nevertheless, the same field survey revealed that ToLCNDV-ES occurred in natural double infection with tomato yellow leaf curl virus (TYLCV) in tomato plants with an infection ratio of up to 50%. Moreover, results obtained from experiments where tomato plants agro-inoculated simultaneously with infectious clones of ToLCNDV-ES and TYLCV showed that ToLCNDV-ES was detected in tomatoes while synergized with TYLCV with infection ratios similar to those found under field conditions. Quantitative PCR data indicated the highest amount of ToLCNDV in co-infected plants and no significant change in TYLCV titers among the different mixed infections. Moreover, it was ascertained that not all begomoviruses can enhance the infectivity of Mediterranean ToLCNDV isolates in tomato plants. Our study reports a new finding regarding the ToLCNDV-ES response in tomato while synergized with TYLCV with evidence from both field and laboratory conditions.