bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatty acids abrogate the growth-suppressive effects induced by inhibition of cholesterol flux in pancreatic cancer cells
Authors: Li Yuchuan , Amrutkar Manoj , Finstadsveen Anette Vefferstad , Dalen Knut Tomas , Verbeke Caroline S. , Gladhaug Ivar P. 
Published: November 2023

Abstract
Background
Despite therapeutic advances, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains extremely poor. Metabolic reprogramming is increasingly recognized as a key contributor to tumor progression and therapy resistance in PDAC. One of the main metabolic changes essential for tumor growth is altered cholesterol flux. Targeting cholesterol flux appears an attractive therapeutic approach, however, the complex regulation of cholesterol balance in PDAC cells remains poorly understood.

Methods
The lipid content in human pancreatic duct epithelial (HPDE) cells and human PDAC cell lines (BxPC-3, MIA PaCa-2, and PANC-1) was determined. Cells exposed to eight different inhibitors targeting different regulators of lipid flux, in the presence or absence of oleic acid (OA) stimulation were assessed for changes in viability, proliferation, migration, and invasion. Intracellular content and distribution of cholesterol was assessed. Lastly, proteome profiling of PANC-1 exposed to the sterol O-acyltransferase 1 (SOAT1) inhibitor avasimibe, in presence or absence of OA, was performed.

Results
PDAC cells contain more free cholesterol but less cholesteryl esters and lipid droplets than HPDE cells. Exposure to different lipid flux inhibitors increased cell death and suppressed proliferation, with different efficiency in the tested PDAC cell lines. Avasimibe had the strongest ability to suppress proliferation across the three PDAC cell lines. All inhibitors showing cell suppressive effect disturbed intracellular cholesterol flux and increased cholesterol aggregation. OA improved overall cholesterol balance, reduced free cholesterol aggregation, and reversed cell death induced by the inhibitors. Treatment with avasimibe changed the cellular proteome substantially, mainly for proteins related to biosynthesis and metabolism of lipids and fatty acids, apoptosis, and cell adhesion. Most of these changes were restored by OA.

Conclusions
The study reveals that disturbing the cholesterol flux by inhibiting the actions of its key regulators can yield growth suppressive effects on PDAC cells. The presence of fatty acids restores intracellular cholesterol balance and abrogates the alternations induced by cholesterol flux inhibitors. Taken together, targeting cholesterol flux might be an attractive strategy to develop new therapeutics against PDAC. However, the impact of fatty acids in the tumor microenvironment must be taken into consideration.
Sex difference of pre- and post-natal exposure to six developmental neurotoxicants on intellectual abilities: a systematic review and meta-analysis of human studies
Authors: Goodman Carly V. , Green Rivka , DaCosta Allya , Flora David , Lanphear Bruce , Till Christine 
Published: November 2023

Abstract
Background
Early life exposure to lead, mercury, polychlorinated biphenyls (PCBs), polybromide diphenyl ethers (PBDEs), organophosphate pesticides (OPPs), and phthalates have been associated with lowered IQ in children. In some studies, these neurotoxicants impact males and females differently. We aimed to examine the sex-specific effects of exposure to developmental neurotoxicants on intelligence (IQ) in a systematic review and meta-analysis.

Method
We screened abstracts published in PsychINFO and PubMed before December 31st, 2021, for empirical studies of six neurotoxicants (lead, mercury, PCBs, PBDEs, OPPs, and phthalates) that (1) used an individualized biomarker; (2) measured exposure during the prenatal period or before age six; and (3) provided effect estimates on general, nonverbal, and/or verbal IQ by sex. We assessed each study for risk of bias and evaluated the certainty of the evidence using Navigation Guide. We performed separate random effect meta-analyses by sex and timing of exposure with subgroup analyses by neurotoxicant.

Results
Fifty-one studies were included in the systematic review and 20 in the meta-analysis. Prenatal exposure to developmental neurotoxicants was associated with decreased general and nonverbal IQ in males, especially for lead. No significant effects were found for verbal IQ, or postnatal lead exposure and general IQ. Due to the limited number of studies, we were unable to analyze postnatal effects of any of the other neurotoxicants.

Conclusion
During fetal development, males may be more vulnerable than females to general and nonverbal intellectual deficits from neurotoxic exposures, especially from lead. More research is needed to examine the nuanced sex-specific effects found for postnatal exposure to toxic chemicals.
Comprehensive insights into the mechanism of keratin degradation and exploitation of keratinase to enhance the bioaccessibility of soybean protein
Authors: Zhou Beiya , Guo Yandong , Xue Yaju , Ji Xiuling , Huang Yuhong 
Published: November 2023

AbstractKeratin is a recalcitrant protein and can be decomposed in nature. However, the mechanism of keratin degradation is still not well understood. In this study, Bacillus sp. 8A6 can completely degrade the feather in 20 h, which is an efficient keratin degrader reported so far. Comprehensive transcriptome analysis continuously tracks the metabolism of Bacillus sp. 8A6 throughout its growth in feather medium. It reveals for the first time how the strain can acquire nutrients and energy in an oligotrophic feather medium for proliferation in the early stage. Then, the degradation of the outer lipid layer of feather can expose the internal keratin structure for disulfide bonds reduction by sulfite from the newly identified sulfite metabolic pathway, disulfide reductases and iron uptake. The resulting weakened keratin has been further proposedly de-assembled by the S9 protease and hydrolyzed by synergistic effects of the endo, exo and oligo-proteases from S1, S8, M3, M14, M20, M24, M42, M84 and T3 families. Finally, bioaccessible peptides and amino acids are generated and transported for strain growth. The keratinase has been applied for soybean hydrolysis, which generates 2234 peptides and 559.93 mg/L17 amino acids. Therefore, the keratinases, inducing from the poultry waste, have great potential to be further applied for producing bioaccessible peptides and amino acids for feed industry.
Deciphering cell wall sensors enabling the construction of robust P. pastoris for single-cell protein production
Authors: Gao Le , Meng Jiao , Dai Wuling , Zhang Zhaokun , Dong Haofan , Yuan Qianqian , Zhang Wuyuan , Liu Shuguang , Wu Xin 
Published: November 2023

AbstractSingle-cell protein (SCP) production in the methylotrophic yeast Pichia pastoris has the potential to achieve a sustainable protein supply. However, improving the methanol fermentation efficiency and reducing carbon loss has been a long-standing challenge with far-reaching scientific and practical implications. Here, comparative transcriptomics revealed that PAS_0305, a gene directly associated with cell wall thickness under methanol stress, can be used as a target for unlocking cell wall sensors. Intracellular trehalose accumulation confirmed that cell wall sensors were activated after knocking out PAS_0305, which resulted in increased cell wall permeability. Genome-wide signal perturbations were transduced through the HOG module and the CWI pathway, which was confirmed to connected by Pbs2-Mkk. As a consequence of CWI pathway activation, ΔPAS_0305 elicited a rescue response of cell wall remodeling by increasing the β-1,3-glucan content and decreasing the chitin/mannose content. Remarkably, perturbations in global stress signals led to a fine-tuning of the metabolic network of ΔPAS_0305, resulting in a superior phenotype with highest crude protein and methanol conversion rate of 67.21% and 0.46 gDCW/g. Further genome-scale metabolic models were constructed to validate the experimental results, confirming that unlocking cell wall sensors resulted in maximized flux from methanol towards SCP and effectively addressing the issue of carbon loss in methanol fermentation. This work sheds new light on the potential of manipulating cellular signaling pathways to optimize metabolic networks and achieve exceptional phenotypic characteristics, providing new strategies for constructing versatile cell factories in P. pastoris.
1H-NMR based-metabolomics reveals alterations in the metabolite profiles of chickens infected with ascarids and concurrent histomonosis infection
Authors: Oladosu Oyekunle John , Correia Banny Silva Barbosa , Grafl Beatrice , Liebhart Dieter , Metges Cornelia C. , Bertram Hanne Christine , Daş Gürbüz 
Published: November 2023

Abstract
Background
Gut infections of chickens caused by Ascaridia galli and Heterakis gallinarum are associated with impaired host performance, particularly in high-performing genotypes. Heterakis gallinarum is also a vector of Histomonas meleagridis that is often co-involved with ascarid infections. Here, we provide a first insight into the alteration of the chicken plasma and liver metabolome as a result of gastrointestinal nematode infections with concomitant histomonosis. 1H nuclear magnetic resonance (1H-NMR) based-metabolomics coupled with a bioinformatics analysis was applied to explore the variation in the metabolite profiles of the liver (N = 105) and plasma samples from chickens (N = 108) experimentally infected with A. galli and H. gallinarum (+H. meleagridis). This was compared with uninfected chickens at different weeks post-infection (wpi 2, 4, 6, 10, 14, 18) representing different developmental stages of the worms.

Results
A total of 31 and 54 metabolites were quantified in plasma and aqueous liver extracts, respectively. Statistical analysis showed no significant differences (P > 0.05) in any of the 54 identified liver metabolites between infected and uninfected hens. In contrast, 20 plasma metabolites including, amino acids, sugars, and organic acids showed significantly elevated concentrations in the infected hens (P < 0.05). Alterations of plasma metabolites occurred particularly in wpi 2, 6 and 10, covering the pre-patent period of worm infections. Plasma metabolites with the highest variation at these time points included glutamate, succinate, trimethylamine-N-oxide, myo-inositol, and acetate. Differential pathway analysis suggested that infection induced changes in (1) phenylalanine, tyrosine, and tryptophan metabolism, (2) alanine, aspartate and glutamate metabolism; and 3) arginine and proline metabolism (Pathway impact > 0.1 with FDR adjusted P-value < 0.05).

Conclusion
In conclusion, 1H-NMR based-metabolomics revealed significant alterations in the plasma metabolome of high performing chickens infected with gut pathogens—A. galli and H. gallinarum. The alterations suggested upregulation of key metabolic pathways mainly during the patency of infections. This approach extends our understanding of host interactions with gastrointestinal nematodes at the metabolic level.
Helicobacter pylori infection attenuates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in C57/BL6 mice
Authors: Wang Shuxian , Wang Xiaokang , Liu Jiaqi , Li Yaqian , Sun Minghui , Zhu Guoqiang , Zhu Xiaofang 
Published: November 2023

Abstract
Background
Although numerous studies have suggested a negative correlation between Helicobacter pylori (H. pylori) infection and allergies, there has been limited research on the relationship between H. pylori infections and atopic dermatitis (AD). The present study aimed to investigate the effects of H. pylori infection in an AD mouse model and identify potential mechanisms related to type 2 immunity, skin barrier defects, and pruritus.

Methods
A model of AD-like symptoms was established with 2,4-dinitrochlorobenzene (DNCB) after infection of the gastric cavity with H. pylori. Analysis of the expression of key inflammatory cytokines and serum levels of immunoglobulin E (IgE) was based on enzyme-linked immunosorbent assay (ELISA). The expression of filaggrin (FLG) and loricrin (LOR) were analyzed by immunohistochemistry staining. The evaluation of STAT1, STAT3, phosphorylated STAT1 (phospho-STAT1), and phosphorylated STAT3 (phospho-STAT1) expression levels in skin lesions was performed using western blot.

Results
The present study showed that the H. pylori-positive AD group (HP+AD+) exhibited milder skin lesions, including erythema, erosion, swelling, and scaling, than the H. pylori-negative AD group (HP−AD+). Additionally, HP+AD+ displayed lower levels of IgE in serum, and downregulated expression of interleukins 4 and 31 (IL-4 and IL-31) in serum. Furthermore, HP+AD+ demonstrated higher expression of filaggrin and loricrin than HP−AD+. Notably, H. pylori significantly reduced the amount of phosphorylated STAT1 and STAT3.

Conclusion
Helicobacter pylori infection negatively regulates the inflammatory response by affecting inflammatory factors in the immune response, and repairs the defective epidermal barrier function. In addition, H. pylori infection may reduce IL-31, thereby alleviating pruritus. These effects may be associated with the inhibition of JAK–STAT signaling activation.
LppA is a novel plasminogen receptor of Mycoplasma bovis that contributes to adhesion by binding the host extracellular matrix and Annexin A2
Authors: Liu Shuang , Li Zhangcheng , Lan Shimei , Hao Huafang , Jin Xiangrui , Liang Jinjia , Baz Ahmed Adel , Yan Xinmin , Gao Pengcheng , Chen Shengli , Chu Yuefeng 
Published: November 2023

AbstractMycoplasma bovis is responsible for various inflammatory diseases in cattle. The prevention and control of M. bovis are complicated by the absence of effective vaccines and the emergence of multidrug-resistant strains, resulting in substantial economic losses worldwide in the cattle industry. Lipoproteins, vital components of the Mycoplasmas cell membrane, are deemed potent antigens for eliciting immune responses in the host upon infection. However, the functions of lipoproteins in M. bovis remain underexplored due to their low sequence similarity with those of other bacteria and the scarcity of genetic manipulation tools for M. bovis. In this study, the lipoprotein LppA was identified in all examined M. bovis strains. Utilizing immunoelectron microscopy and Western blotting, it was observed that LppA localizes to the surface membrane. Recombinant LppA demonstrated dose-dependent adherence to the membrane of embryonic bovine lung (EBL) cells, and this adhesion was inhibited by anti-LppA serum. In vitro binding assays confirmed LppA’s ability to associate with fibronectin, collagen IV, laminin, vitronectin, plasminogen, and tPA, thereby facilitating the conversion of plasminogen to plasmin. Moreover, LppA was found to bind and enhance the accumulation of Annexin A2 (ANXA2) on the cell membrane. Disrupting LppA in M. bovis significantly diminished the bacterium’s capacity to adhere to EBL cells, underscoring LppA’s function as a bacterial adhesin. In conclusion, LppA emerges as a novel adhesion protein that interacts with multiple host extracellular matrix proteins and ANXA2, playing a crucial role in M. bovis’s adherence to host cells and dissemination. These insights substantially deepen our comprehension of the molecular pathogenesis of M. bovis.
Prehabilitation programs for individuals with cancer: a systematic review of randomized-controlled trials
Authors: Meneses-Echavez Jose F. , Loaiza-Betancur Andrés F. , Díaz-López Víctor , Echavarría-Rodríguez Andrés M. , Triana-Reina Héctor Reynaldo 
Published: November 2023

Abstract
Background
Prehabilitation programs focusing on exercise training as the main component are known as a promising alternative for improving patients’ outcomes before cancer surgery. This systematic review determined the benefits and harms of prehabilitation programs compared with usual care for individuals with cancer.

Methods
We searched CENTRAL, MEDLINE, and EMBASE from inception to June 2022, and hand searched clinical trial registries. We included randomized-controlled trials (RCTs) in adults, survivors of any type of cancer, that compared prehabilitation programs that had exercise training as the major component with usual care or other active interventions. Outcome measures were health-related quality of life (HRQL), muscular strength, postoperative complications, average length of stay (ALOS), handgrip strength, and physical activity levels. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias and the certainty of the evidence.

Results
Twenty-five RCTs (2682 participants) published between 2010 and 2022 met our inclusion criteria. Colorectal and lung cancers were the most common diagnoses. The studies had methodological concerns regarding outcome measurement, selective reporting, and attrition. Five prehabilitation programs were compared to usual care (rehabilitation): combined training, aerobic training, respiratory muscle training plus aerobic training, respiratory muscle training plus resistance training, and pelvic floor training. The studies provided no clear evidence of an effect between groups. We assessed the overall certainty of the evidence as very low, downgraded due to serious study limitations and imprecision.

Conclusion
Prehabilitation programs focusing on exercise training may have an effect on adults with cancer, but the evidence is very uncertain. We have very little confidence in the results and the true effect is likely to be substantially different from these. Further research is needed before we can draw a more certain conclusion.

Systematic review registration
CRD42019125658.
Re-estimation of the savings retention coefficient in OECD countries: a new measure of home country bias
Authors: Takahashi Harutaka 
Published: November 2023

AbstractThe recent home bias is primarily related to the equity bias as measured by the international capital asset pricing model (CAPM); this measure has declined over the past two decades amid financial globalization, but remains high in most developed countries. The key to understanding this puzzling phenomenon lies in how accurately this indicator can be predicted. In this paper, we propose to use the savings retention coefficient estimated by the Feldstein–Horioka (F–H) regression as a cross-country measure of home bias. We re-estimate the savings retention coefficient based on an estimation model in which the FH regression is embedded in the model derived from Tobin's q-theory of saddle-road dynamics of investment under convex adjustment costs. We then use dynamic panel estimation to estimate the new measure in OECD countries. The main empirical results are as follows. The new measure of home country bias, such as the equity bias measure, declined steadily until 2008, but recovered to the level of the 60 s and 70 s after the 2008 financial crisis. Interestingly, people expected home country bias to be very high after the financial crisis, but in fact it simply returned to its previous level.
Medium-term interactive effects of herbivores and plant life form on the biochemistry of shallow sandy soils in a protected semi-arid savanna
Authors: Malongweni Siviwe Odwa , van Tol Johan 
Published: November 2023

AbstractSavannas are characterized by the co-occurrence of two different plant life forms: grasses and trees. Herbivory plays a major role in the balance between grasses and trees in savanna ecosystems. The present study aimed to investigate the impact and interactions between long-term (i.e. 20 years) herbivory and/or its exclusion and plant life form on the soil biochemistry of a protected semi-arid savanna ecosystem in the Kruger National Park (KNP), South Africa. To study the effects of herbivory on soil properties, herbivore exclosures (fully fenced areas, partially fenced areas, and an unfenced area) were used in conjunction with plant life form (trees and grasses) were considered. Interaction effects of herbivory and plant life form on soil pH, electrical conductivity (EC), total nitrogen (TN), total carbon (TC), available phosphorus (available P), exchangeable cations (K+, Na+, Mg2+and Ca2+) cation exchange capacity (CEC), organic matter (OM) and total microbial activity were determined on savanna soils in the Nkuhlu exclosures, KNP. Exclosures where herbivores were present had significantly higher soil pH, The presence of herbivores caused an increase in soil pH, EC, exchangeable Na, CEC, and OM. The influence of the tree canopy was significantly more pronounced in elevating total C and N, exchangeable K+, Mg2+and Ca2+, CEC and OM than observed in the open grassland zones across all exclosures. The two-way interaction between herbivory and plant life form resulted in significant decreases in TN, TC, exchangeable K, Na and Mg in open grassland areas outside of herbivore exclosures where large animals had direct access, as compared to areas within the exclosures which was protected from animal entry herbivory. This data can be used by national parks as an indicator to increase their knowledge of environmental issues relating to maintaining and preserving landscape features of savannas.
Optimal distribution of VLBI transmitters in the Galileo space segment for frame ties
Authors: Wolf Helene , Böhm Johannes 
Published: November 2023

AbstractEquipping Galileo satellites with a VLBI transmitter (VT) will allow to observe satellites next to quasars with Very Long Baseline Interferometry (VLBI) radio telescopes. This concept will facilitate the direct estimation of the satellite orbits in the celestial reference frame. Moreover, these observations along with usual Galileo observations can be used to transfer the space tie between the VT and the antenna on the Galileo satellite to the Earth surface realizing the frame tie at the geodetic site with VLBI radio telescope and Galileo antenna. In this study, we assess the accuracy of that frame tie by simulating the estimation of station coordinates from VLBI observations to Galileo satellites next to quasars. We find that at least two or three satellites need to be equipped with a VT with the best results if all satellites with a VT are placed in the same plane. Concerning the ratio between satellite and quasar observations within a schedule, the results suggest that the optimal ratio is around 30% to 40% satellite observations out of the total number of observations in order to have enough observations for the estimation of the station coordinates but still enough quasar observations to ensure a sufficient sky-coverage for the estimation of troposphere parameters. The best scenario with two satellites yields repeatabilities for the east and north components between 7.5 and 10 mm, and for the up component between 9.5 and 12 mm. In case there is a third satellite with a VLBI transmitter in the same plane, the repeatabilities are reduced by up to 2 mm for the horizontal components and up to 3 to 4 mm for the up component. Rotating the schedules over the constellation repeat cycle of Galileo of 10 days reveals that there are differences between the individual days, but there are no days with a significantly worse precision of the estimated station coordinates.
Graphical Abstract