bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of trans-4-hydroxyproline synthesis pathway by rearrangement center carbon metabolism in Escherichia coli
Authors: Gong Yu , Wang Ruiqi , Ma Ling , Wang Shuo , Li Changgeng , Xu Qingyang 
Published: November 2023

Abstract
Background
trans-4-Hydroxyproline (T-4-HYP) is a promising intermediate in the synthesis of antibiotic drugs. However, its industrial production remains challenging due to the low production efficiency of T-4-HYP. This study focused on designing the key nodes of anabolic pathway to enhance carbon flux and minimize carbon loss, thereby maximizing the production potential of microbial cell factories.

Results
First, a basic strain, HYP-1, was developed by releasing feedback inhibitors and expressing heterologous genes for the production of trans-4-hydroxyproline. Subsequently, the biosynthetic pathway was strengthened while branching pathways were disrupted, resulting in increased metabolic flow of α-ketoglutarate in the Tricarboxylic acid cycle. The introduction of the NOG (non-oxidative glycolysis) pathway rearranged the central carbon metabolism, redirecting glucose towards acetyl-CoA. Furthermore, the supply of NADPH was enhanced to improve the acid production capacity of the strain. Finally, the fermentation process of T-4-HYP was optimized using a continuous feeding method. The rate of sugar supplementation controlled the dissolved oxygen concentrations during fermentation, and Fe2+ was continuously fed to supplement the reduced iron for hydroxylation. These modifications ensured an effective supply of proline hydroxylase cofactors (O2 and Fe2+), enabling efficient production of T-4-HYP in the microbial cell factory system. The strain HYP-10 produced 89.4 g/L of T-4-HYP in a 5 L fermenter, with a total yield of 0.34 g/g, the highest values reported by microbial fermentation, the yield increased by 63.1% compared with the highest existing reported yield.

Conclusion
This study presents a strategy for establishing a microbial cell factory capable of producing T-4-HYP at high levels, making it suitable for large-scale industrial production. Additionally, this study provides valuable insights into regulating synthesis of other compounds with α-ketoglutaric acid as precursor.
Caregiver acceptance of malaria vaccination for children under 5 years of age and associated factors: cross-sectional household survey, Guinea and Sierra Leone, 2022
Authors: Röbl Klara , Fischer Hanna-Tina , Delamou Alexandre , Mbawah Abdul Karim , Geurts Brogan , Feddern Lukas , Baldé Habibata , Kaba Ibrahima , Pozo-Martin Francisco , Weishaar Heide , Menelik-Obbarius Sara , Burger Gerrit , Diaconu Viorela , Dörre Achim , El Bcheraoui Charbel 
Published: November 2023

Abstract
Background
Malaria is a leading cause of death and reduced life span in Guinea and Sierra Leone, where plans for rolling out the malaria vaccine for children are being made. There is little evidence about caregiver acceptance rates to guide roll-out policies. To inform future vaccine implementation planning, this analysis aimed to assess potential malaria vaccine acceptance by caregivers and identify factors associated with acceptance in Guinea and Sierra Leone.

Methods
A cross-sectional household survey using lot quality assurance sampling was conducted in three regions per country between May 2022 and August 2022. The first survey respondent in each household provided sociodemographic information. A household member responsible for childcare shared their likelihood of accepting a malaria vaccine for their children under 5 years and details about children’s health. The prevalence of caregiver vaccine acceptance was calculated and associated factors were explored using multivariable logistic regression modelling calculating adjusted odds ratios (aOR) with 95% confidence intervals (CI).

Results
Caregivers in 76% of 702 sampled households in Guinea and 81% of 575 households in Sierra Leone were accepting of a potential vaccine for their children. In both countries, acceptance was lower in remote areas than in urban areas (Guinea: aOR 0.22 [95%CI 0.09–0.50], Sierra Leone: 0.17 [0.06–0.47]). In Guinea, acceptance was lower among caregivers living in the richest households compared to the poorest households (0.10 [0.04–0.24]), among those whose children were tested for malaria when febrile (0.54 [0.34–0.85]) and in households adopting more preventative measures against malaria (0.39 [0.25–0.62]). Better knowledge of the cause of malaria infection was associated with increased acceptance (3.46 [1.01–11.87]). In Sierra Leone, vaccine acceptance was higher among caregivers living in households where the first respondent had higher levels of education as compared to lower levels (2.32 [1.05–5.11]).

Conclusion
In both countries, malaria vaccine acceptance seems promising for future vaccine roll-out programmes. Policy makers might consider regional differences, sociodemographic factors, and levels of knowledge about malaria for optimization of implementation strategies. Raising awareness about the benefits of comprehensive malaria control efforts, including vaccination and other preventive measures, requires attention in upcoming campaigns.
Does the ketogenic diet improve neurological disorders by influencing gut microbiota? A systematic review
Authors: Mazandarani Mahdi , Lashkarbolouk Narges , Ejtahed Hanieh-Sadat , Qorbani Mostafa 
Published: November 2023

Abstract
Background
The aim of this systematic review is to evaluate the changes in gut microbiota (GM) induced by the Ketogenic Diets (KD) as a potential underlying mechanism in the improvement of neurological diseases.

Methods
A comprehensive search was conducted on three electronic databases, including PubMed/Medline, Web of Science, and Scopus until December 2022. The inclusion criteria were studies that described any changes in GM after consuming KD in neurological patients. Full text of studies such as clinical trials and cohorts were added. The quality assessment of cohort studies was conducted using the Newcastle–Ottawa Quality Assessment Scale and for the clinical trials using the Cochrane Collaboration tool. The search, screening, and data extraction were performed by two researchers independently.

Results
Thirteen studies examining the effects of the KD on the GM in neurological patients were included. Studies have shown that KD improves clinical outcomes by reducing disease severity and recurrence rates. An increase in Proteobacteria phylum, Escherichia, Bacteroides, Prevotella, Faecalibacterium, Lachnospira, Agaricus, and Mrakia genera and a reduction in Firmicutes, and Actinobacteria phyla, Eubacterium, Cronobacter, Saccharomyces, Claviceps, Akkermansia and Dialister genera were reported after KD. Studies showed a reduction in concentrations of fecal short-chain fatty acids and branched-chain fatty acids and an increase in beta Hydroxybutyrate, trimethylamine N-oxide, and N-acetylserotonin levels after KD.

Conclusion
The KD prescribed in neurological patients has effectively altered the GM composition and GM-derived metabolites.
IL-1β mediates the induction of immune checkpoint regulators IDO1 and PD-L1 in lung adenocarcinoma cells
Authors: Nawas Afshan Fathima , Solmonson Ashley , Gao Boning , DeBerardinis Ralph J. , Minna John D. , Conacci-Sorrell Maralice , Mendelson Carole R. 
Published: November 2023

Abstract
Introduction
Inflammation plays a significant role in various cancers, including lung cancer, where the inflammatory cytokine IL-1β is often elevated in the tumor microenvironment. Patients with lung adenocarcinoma show higher levels of serum IL-1β compared to healthy individual. Moreover, IL-1β blockade reduces the incidence and mortality of lung cancer. Our prior studies revealed that alveolar type-II cells, the precursors for lung adenocarcinoma, display an induction in the expression of the enzyme tryptophan 2,3-dioxygenase (TDO2) during normal lung development. This induction of TDO2 coincides with an increase in IL-1β levels and is likely caused by IL-1β. Given that cancer cells can co-opt developmentally regulated pathways, we hypothesized that IL-1β may exert its pro-tumoral function by stimulating TDO2 and indoleamine 2, 3-dioxygenase-1 (IDO1), parallel enzymes involved in the conversion of tryptophan (Trp) into the immune-suppressive oncometabolite kynurenine (Kyn). Our goal was to determine whether IL-1β is a common upstream regulator of immune checkpoint regulators.

Methods
To determine whether IL-1β regulates IDO1, TDO2, PD-L1, and PD-L2, we measured mRNA and protein levels in lung adenocarcinoma cells lines (A549, H1792, H1838, H2347, H2228, HCC364 and HCC827) grown in 2D or 3D and in immortalized normal lung epithelial cells (HBEC3-KT and HSAEC1-KT). To determine the importance of the NFκB pathway in mediating IL-1β -regulated cellular effects, we used siRNA to knockdown RelA/p65 in IL-1β treated cells. The levels of Trp and Kyn in the IL-1β-treated cells and media were measured by mass spectrometry.

Results
Upon IL-1β stimulation, lung adenocarcinoma cells exhibited significant increases in IDO1 mRNA and protein levels, a response that depended on the NFκB pathway. Interestingly, this induction was more pronounced in 3D spheroid cultures compared to monolayer cultures and was not observed in normal immortalized lung epithelial cells. Furthermore, the conversion of Trp to Kyn increased in cells exposed to IL-1β, aligning with the heightened IDO1 expression. Remarkably, IL-1β also upregulated the expression of programmed death ligand-1 (PD-L1) and PD-L2 in multiple cell lines, indicating that IL-1β triggers parallel immune-suppressive mechanisms in lung adenocarcinoma cells.

Conclusions
Our studies demonstrate that lung adenocarcinoma cells, but not normal immortalized lung epithelial cells, respond to IL-1β signaling by inducing the expression of parallel immune checkpoint proteins that have the potential to promote immune evasion.
Sex differences in the association between plasma polyunsaturated fatty acids levels and moderate-to-severe plaque psoriasis severity: a cross-sectional and longitudinal study
Authors: Wang Xin , Ma Rui , Shi Rongcan , Qin Hui , Chen Wenjuan , Yu Zengyang , Ding Yangfeng , Peng Chen , Shi Yuling 
Published: November 2023

Abstract
Background
Psoriasis is a chronic inflammatory skin disease with metabolic abnormalities serving as important contributors for pathogenesis and progression. Polyunsaturated fatty acids (PUFAs) have been found to be associated with human diseases, including psoriasis. However, differences and controversies exist regarding their content and roles.

Methods
Plasma PUFAs concentrations were measured in 296 patients with moderate-to-severe plaque psoriasis from the Shanghai Psoriasis Effectiveness Evaluation CoHort. Disease severity was assessed using Clinician-Reported Outcomes (ClinROs), including Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and Physician Global Assessment (PGA), as well as Patient-Reported Outcomes (PROs), including Patient Global Assessment (PtGA) and Dermatology Life Quality Index (DLQI). Multivariate generalized linear regression models (GLMs), subgroup and interaction analysis, and restricted cubic spline were used to estimate the cross-sectional associations between PUFAs concentrations and disease severity. Longitudinal assessments of PASI scores and PASI response were conducted at a 12-week follow-up. Associations between baseline plasma PUFAs levels and prospective PASI scores or PASI response were assessed using multivariate GLMs or logistic regression models.

Results
Males suffered severer psoriasis and presented lower plasma docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels compared to females. Among males, plasma eicosadienoic acid (EDA) level was positively associated with PASI, BSA and PGA scores, while total Omega-3 PUFAs and/or eicosapentaenoic acid (EPA) levels exhibited non-linear associations with PASI and/or BSA scores. α-Linolenic acid (ALA) was negatively, whereas ARA was positively, associated with DLQI scores. In females, Omega-3 PUFAs, including EPA, DHA, and total Omega-3 PUFAs, showed inverse associations with PASI and BSA scores. Longitudinally, plasma total Omega-6 PUFAs were positively associated with the likelihood of achieving PASI 100 at 12 weeks in males. In females, concentrations of dohomo-γ-linolenic acid were prospectively associated with an increase in PASI scores, and DHA was associated with the likelihood of achieving PASI 75 and PASI 90 decline.

Conclusions
Sex differences cross-sectionally exist in disease severity and plasma PUFAs levels. The association between PUFAs and psoriasis severity also varies cross-sectionally and longitudinally between males and females. Sex differences should be considered when studying the function and clinical application of PUFAs in psoriasis.
Assistive diagnostic indicators for infections related to lumbar posterior interbody fusion internal fixation: platelet count and mean platelet volume
Authors: Zhang Yadong , Li Houkun , Wang Wentao , Shan Lequn , Hao Dingjun 
Published: November 2023

AbstractBackgroundThe most severe complication after posterior single-segment lumbar interbody fusion and internal fixation (PIFIF) surgery for degenerative lumbar diseases is deep surgical site infection (DSSI). Preoperatively diagnosing such complications proves to be challenging. Platelets, as acute-phase reactants, undergo changes in response to infections and inflammation. This study aims to assess whether platelet indices can further aid in the diagnosis of DSSI.MethodsA single-center retrospective study was conducted from January 2016 to February 2021 at Xi'an Jiaotong University-Affiliated Honghui Hospital, involving 83 patients who underwent revision surgery after PIFIF due to lumbar degenerative diseases. Among them, 24 patients were diagnosed with DSSI based on combined bacterial culture and imaging data. Preoperative complete serological indicators including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and platelet count and mean platelet volume ratio (P/M ratio) were analyzed using receiver operating characteristic (ROC) curve analysis to determine cutoff values, sensitivity, and specificity. This was done to further assess the ability of these serological indicators to identify the occurrence of DSSI after PIFIF.ResultsThere were no significant differences in baseline demographic characteristics between the two patient groups (P > 0.05). The P/M ratio was 13.54 ± 5.05 in the aseptic revision group, while it was 19.21 ± 6.30 in the DSSI revision patients, showing a significant difference (P < 0.001). ROC curve analysis revealed that the optimal cutoff value for the P/M ratio was 17.50, with a sensitivity of 58.3% and a specificity of 78.6%. The areas under the curve (AUC) for ESR, CRP, and P/M ratio were 0.797, 0.845, and 0.756, respectively. The negative predictive value (NPV) was 87.04%, 89.47%, and 82.45%, respectively; the positive predictive value (PPV) was 58.62%, 69.23%, and 53.84%, respectively, for ESR, CRP, and P/M ratio, respectively. When P/M ratio is used in combination with ESR and CRP, the AUC is 0.887, with a sensitivity of 95.4%, specificity of 67.8%, NPV of 97.56%, PPV of 54.76%. The diagnostic performance of the model for evaluating DSSI is significantly improved compared to using ESR and CRP alone (P < 0.05).ConclusionPlatelets and their related serum biomarkers are closely associated with DSSI. The P/M ratio can serve as a reliable test for screening DSSI and is worth considering for inclusion in the assessment of patients at risk of developing DSSI after potential PIFIF surgery.
Attenuation of estrogen and its receptors in the post-menopausal stage exacerbates dyslipidemia and leads to cognitive impairment
Authors: Meng Qinghai , Chao Ying , Zhang Shurui , Ding Xue , Feng Han , Zhang Chenyan , Liu Bowen , Zhu Weijie , Li Yu , Zhang Qichun , Tong Huangjin , Wu Lixing , Bian Huimin 
Published: November 2023

AbstractCognitive dysfunction increases as menopause progresses. We previously found that estrogen receptors (ERs) contribute to dyslipidemia, but the specific relationship between ERs, dyslipidemia and cognitive dysfunction remains poorly understood. In the present study, we analyzed sequencing data from female hippocampus and normal breast aspirate samples from normal and Alzheimer’s disease (AD) women, and the results suggest that abnormal ERs signaling is associated with dyslipidemia and cognitive dysfunction. We replicated a mouse model of dyslipidemia and postmenopausal status in LDLR−/− mice and treated them with β-estradiol or simvastatin, and found that ovariectomy in LDLR−/− mice led to an exacerbation of dyslipidemia and increased hippocampal apoptosis and cognitive impairment, which were associated with reduced estradiol levels and ERα, ERβ and GPER expression. In vitro, a lipid overload model of SH-SY-5Y cells was established and treated with inhibitors of ERs. β-estradiol or simvastatin effectively attenuated dyslipidemia-induced neuronal apoptosis via upregulation of ERs, whereas ERα, ERβ and GPER inhibitors together abolished the protective effect of simvastatin on lipid-induced neuronal apoptosis. We conclude that decreased estrogen and its receptor function in the postmenopausal stage promote neuronal damage and cognitive impairment by exacerbating dyslipidemia, and that estrogen supplementation or lipid lowering is an effective way to ameliorate hippocampal damage and cognitive dysfunction via upregulation of ERs.
Graphical Abstract
The long non-coding RNA NEAT1 promotes the progression of human ovarian cancer through targeting miR-214-3p and regulating angiogenesis
Authors: Liu Yang , Li Yan , Wu Yanzhi , Zhao Yiyue , Hu Xi , Sun Chunyi 
Published: November 2023

Abstract
Background
Angiogenesis and metastasis contributes substantially to the poor outcome of patients with ovarian cancer. We aimed to explore the role and mechanisms of the long non-coding RNA NEAT1 (nuclear enriched abundant transcript 1) in regulating angiogenesis and metastasis of human ovarian cancer. NEAT1 expression in human ovarian cancer tissues and cell lines including SKOV-3 and A2780 was investigated through in situ hybridization. Gene knockdown and overexpressing were achieved through lentivirus infection, transfection of plasmids or microRNA mimics. Cell viability was measured with the cell counting kit-8 assay, while apoptosis was determined by flow cytometry. Cell migration and invasion were evaluated by transwell experiments, and protein expression was determined by western blot assays or immunohistochemistry. Duo-luciferase reporter assay was employed to confirm the interaction between NEAT1 and target microRNA. In vivo tumor growth was evaluated in nude mice with xenografted SKOV-3/A2780 cells, and blood vessel formation in tumor was examined by histological staining.

Results
NEAT1 was highly expressed in ovarian cancer tissues of patients and cell lines. MiR-214-3p was identified as a sponging target of NEAT1, and they antagonizedeach other in a reciprocal manner. NEAT1-overexpressing SKOV-3 and A2780 cells had significantly increased proliferation, reduced apoptosis, and augmented abilities of migration and invasion, while cells with NEAT1-knockdown displayed markedly attenuated traits of malignancies. Additionally, the levels of NEAT1 appeared to be positively correlated with the expression levels of angiogenesis-related molecules, including Semaphorin 4D (Sema4D), Sema4D receptor Plexin B1, T-lymphoma invasion and metastasis-inducing protein-1 (Tiam1), and Rho-like GTPases Rac1/2/3. In the xenograft mouse model, more NEAT1 expression resulted in faster in vivo tumor growth, more blood vessel formation in tumor tissues, as well as higher expression levels of angiogenesis-related molecules and CD31.

Conclusions
NEAT1 promotes angiogenesis and metastasis in human ovarian cancer. NEAT1 and miR-214-3p are promising targets for developing therapeutics to treat human ovarian cancer.
Phenolic content, antioxidant and antimicrobial activities evaluation and relationship of commercial spices in the lebanese market
Authors: Rayess Youssef El , Nehme Lea , Ghanem Chantal , Beyrouthy Marc El , Sadaka Carmen , Azzi-Achkouty Samar , Nehme Nancy , Gürer Eda Sönmez , Sharifi-Rad Javad 
Published: November 2023

AbstractLebanese cuisine is renowned for its distinctive flavours and vibrant aromas. In Lebanese cuisine, spices are not just used for their flavour; they are also valued for their medicinal properties. This study consists of evaluating and comparing the total phenolic content and the antioxidant capacity of 21 samples of spices used in the Lebanese daily diet, such as cinnamon, allspice, coriander, cloves, etc. and the mixtures prepared in well-defined proportions. Several solvents were tested for the extraction of the phenolic compounds from spices, and the water and ethanol (v/v) mixture were retained for this study. Results showed that clove presented the highest polyphenol content (173.7 ± 2.98 mg Gallic Acid Equivalent (GAE)/g Dry Matter (DM)) and the highest antioxidant capacity by ABTS test (4875.68 ± 480.40 µmol trolox / g DM). and DPPH test (85.84 ± 0.5%). The examination of the results showed a positive significant correlation between the polyphenol contents and the antioxidant activity of the spices. The antimicrobial activity tested by the broth microdilution method was determined against Escherichia coli, Listeria monocytogenes, Staphylococcus aureus and Salmonella Enteritidis. The results showed high antimicrobial activity manifested by low value of minimum inhibitory concentration (MIC) (MIC < 2.4 µg/mL) for cinnamon, turmeric, white pepper, red pepper, allspice, clove and nutmeg. In conclusion, spices used in Lebanese cuisine, such as clove, cinnamon, allspice and spices, were rich in phenolic compounds and presented important potential health benefits.