bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and expression characterization of a WRKY transcription factor affecting squalene synthesis in Camellia oleifera
Authors: Du Qinhui , Ge Luyao , Zeng YanLing , Li Aori , Zhu Ziyan , Tan Xiaofeng 
Published: April 2024

Abstract
WRKY-like transcriptional regulators are widely involved in physiological processes such as growth and development, metabolic regulation and environmental response. In this study, we obtained six CoWRKY transcription factors by yeast one-hybrid screening library with reference to the Camellia oleifera genome sequence, using squalene synthase gene (CoSQS) as bait. AOS (Antibody Optimization System) analysis showed that CoWRKY15 had the highest interactions with a confidence level of 0.9026. Bioinformatics analysis showed that CoWRKY15 encodes 346 amino acid residues, was a basic hydrophilic protein, did not contain a transmembrane region, contained one WRKY conserved structural domain and one C2H2 zinc finger structural domain. and belonged to class 2 of the WRKY gene family, and had the closest genetic distance of 0.5564 to the homologous protein of Panax quinquefolius PqWRKY1. The results of prokaryotic expression showed that the CoWRK15 protein with a size of 38.3 kD was successfully induced by adding a final concentration of 0.5 mM ITPG for 4 h at 37℃. The results of subcellular localization showed that CoWRKY15 functioned in the nucleus. The results of CoWRKY15 promoter analysis showed that 8 out of 14 cis-elements with annotatable functions were related to the light response, indicating that the expression of CoWRKY15 was strongly affected by light. The correlation analysis of CoWRKY15 expression and squalene content in Camellia oleifera seed kernels treated under different light quality conditions showed a significant positive correlation.
An investigation of the agriculture vulnerability and risk from climate change in Liberia: an institutional-socio-economic-technological-system framework approach.
Authors: Masike Sennye , Urich Peter , Li Yinpeng , Mmereki Daniel 
Published: April 2024

Abstract

Climate change presents unprecedented challenges to the agricultural sector particularly in Africa where adaptive capacity and sensitivity are extremely low and high. Adequately addressing climate change risks and impacts in the agricultural sector through mainstreaming in the national development planning process is critical. Therefore, to plan and mainstream climate change into development planning processes, gaining an in-depth characterization of the agricultural sector’s vulnerability to climate change is needed. To this end, we proposed an institutional, social, earth, economic and technical (ISEETS) framework based on the systems approach. Due to limited data, we constructed climate scenarios to present the earth subsector of the ISEETS and provided both theoretical and analytical analyses of the climate change impact on the agricultural sector. Based on the RCP4.5, the results showed that temperature would increase by a range of 1 to 1.25 oC. In terms of precipitation, it would increase by a range of 0.36–1.13%. Analysis of extreme events for precipitation indicated that the country would experience an increase in extreme precipitation of 3–14%, suggesting increased flooding in the country. From the ISEETS perceptive, the sector vulnerability could be amplified by the weak institutional, social, economic, earth, and technology subsectors. The study provided information that could help strengthen all aspects of the ISEETS to reduce vulnerability to climate change.
Tracing N utilization and distribution during development of grape seedlings by applying different forms of 15N labeled fertilizer with fruit tree hole storage brick
Authors: Yao Dongdong , jia Haifeng , Zhang Huanhuan , Li Xujiao , Salah Hossam , Zhao fengyun , Yu SongLin , Yu Kun 
Published: April 2024

Abstract
Background and aims
Application of soil conditioner can promote the NUE in plants by increasing N retention in soil as an effective method to reduce chemical fertilizer consumption and environmental pollution.
Methods
We have prepared fruit tree hole storage brick (FTHSB) suitable for perennial fruit trees using natural nanomaterials, vermiculite and montmorillonite, and organic fertilizers, then recommended a new fertilization strategy combining N fertilizer and FTHSB based on subsurface drip irrigation.
Results
Application of FTHSB significantly increased the amount of dry matter in each organ of grape (Vitis vinifera L.) seedlings, significantly promoted fine root growth of soil layer in the range of 15–30 cm, reduced the leaching loss of 15N to deep soil and significantly improved the use efficiency of 15N. In the treatment without FTHSB, NO3−-N is better than NH4+-N and CO(NH2)2-N in terms of plant growth index of soil layer in the range of 15–30 cm and 15N use efficiency in plants. After the application of FTHSB, CO(NH2)2-N is better than NO3−-N and NH4+-N according to the above indicators.
Conclusions
In general, compared with ammonium and nitrate N FTHSB had the strongest adsorption capacity for amide N, so the N content of the soil in the vicinity of the FTHSB with amide N was also the highest, which improved the dry matter of all organs, the growth of the fine roots and the efficiency of N utilization in the grape seedlings.
Enhanced Anti-Tumor Effects by Combination of Tucatinib and Radiation in HER2-Overexpressing Human Cancer Cell Lines
Authors: Amrell Lukas , Bär Eric , Glasow Annegret , Kortmann Rolf-Dieter , Seidel Clemens , Patties Ina 
Published: April 2024

Abstract

Background
Tucatinib (TUC), a HER2-directed tyrosine kinase inhibitor, is the first targeted drug demonstrating intracranial efficacy and significantly prolonged survival in metastatic HER2-positive breast cancer (BC) patients with brain metastases. Current treatments for brain metastases often include radiotherapy, but little is known about the effects of combination treatment with TUC. Therefore, we examined the combined effects of irradiation and TUC in human HER2-overexpressing BC, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC) cell lines. For the latter two, a standard therapy successfully targeting HER2 is yet to be established.
Methods
Nine HER2-overexpressing (BC: BT474, ZR7530, HCC1954; CRC: LS411N, DLD1, COLO201; NSCLC: DV90, NCI-H1781) and three control cell lines (BC: MCF7, HCC38; NSCLC: NCI-H2030) were examined. Changes in metabolic activity, proliferation, DNA double-strand break (DSB) induction/repair, apoptosis, and clonogenicity after treatment with TUC and/or irradiation (IR) were measured. The relevance of the treatment sequence was analyzed exemplarily.
Results
In BC, combinatorial treatment with TUC and IR significantly decreased metabolic activity, cell proliferation, clonogenicity and enhanced apoptotis compared to IR alone, whereby cell line-specific differences occurred. In the more resistant PI3KCA-mutated HCC1954 cell line, addition of alpelisib (ALP) further decreased clonogenic survival. TUC delayed the repair of IR-induced DNA damage but did not induce DSB itself. Investigation of treatment sequence indicated a benefit of IR before TUC versus IR after TUC. Also in CRC and NSCLC, the combination led to a stronger inhibition of metabolic activity, proliferation, and clonogenic survival (only in NSCLC) than IR alone, whereby about 10-fold higher concentrations of TUC had to be applied than in BC to induce significant changes.
Conclusion
Our data indicate that combination of TUC and IR could be more effective than single treatment strategies for BC. Thereby, treatment sequence seems to be an important factor. The lower sensitivity to TUC in NSCLC and particularly in CRC (compared to BC) implicates, that tumor promotion there might be less HER2-related. Combination with inhibitors of other driver mutations may aid in overcoming partial TUC resistance. These findings are of high relevance to improve long-time prognosis especially in brain-metastasized situations given the intracranial activity of TUC.
Using Machine learning to identify metabolomic signatures of ulcerative colitis with the classification according to disease extent
Authors: Ge Changchang , Lu Yi , Shen Zhaofeng , Lu Yizhou , Liu Xiaojuan , Zhang Mengyuan , Liu Yijing , Shen Hong , Zhu Lei 
Published: April 2024

Abstract

Background: Ulcerative colitis (UC) is a metabolic-related chronic intestinal inflammatory disease. Disease extent is an intrinsic aspect of UC and influences the treatment modality. Identifying serum metabolic profiling of different disease extent may help to elucidate the underlying molecular mechanisms of UC.
Methods: UC patients with different disease extent and healthy controls were included in this study. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method detected the metabolites, and the orthogonal partial least squares-discriminant analysis (OPLS-DA) were performed to identify metabolites. Lasso regression and support vector machine-recursive feature elimination (SVM-RFE) were used to screen metabolites. Receiver operating characteristic curves (ROC) were plotted to represent the diagnostic value of metabolites.
Results: 93 differential metabolites between the UC and HCs, and57, 66, 44 in E1 and E2, E1 and E3, E2 and E3 groups were confirmed by OPLS-DA in the positive and negative ion mode. KEGG pathway analysis show that Arachidonic acid metabolism, Glycerophospholipid metabolism and Pentose phosphate pathway were the main disturbed metabolic pathway related to UC. Glycerophospholipid metabolism, Sphingolipid metabolism, Pyrimidine metabolism and Linoleic acid metabolism are involved UC site phenotype. Lasso and SVM-RFE screened differential metabolites relating to disease extent, and 8 metabolites were confirmed. The area under the ROC curve of all metabolites predicting the disease extent is greater than 0.7.
Conclusions: There are significant differences in metabolomics among UC patients with different disease extent. Tridecanoic acid may be a potential biomarker for identifying patients with extensive colitis.
Pharmacokinetic analysis of crushed venetoclax tablets combined with azacitizine for recurrent pediatric acute myeloid leukemia (AML)
Authors: Matsui Motohiro , Yasu Takeo , Makimoto Atsushi , Yuza Yuki 
Published: April 2024

Abstract

Background: The efficacy of a combination therapy consisting of venetoclax (VEN) and azacytidine (AZA) for newly diagnosed acute myeloid leukemia (AML) has been confirmed in elderly patients. However, the clinical data on VEN for pediatric AML are limited. A combination therapy consisting of crushed VEN tablets and AZA (VEN/AZA) was administered to two children with recurrent AML. The pharmacokinetics of VEN were then analysed.
Case Presentation: [Patient 1] A 1-year-old, male patient who experienced an AML relapse following an allogeneic hematopoietic stem cell transplantation received three courses of VEN/AZA. At the initial dosage of VEN (8 mg/kg), the minimum plasma concentration (Cmin) was only 0.44 μg/ml, which was far less than the optimal Cmin of 1.2 μg/ml. Subsequent dose-escalation to 10 mg/kg only achieved Cmin 0.42 μg/ml. [Patient 2] A 3-year-old, female patient in whom infantile acute lymphoblastic leukemia was originally diagnosed experienced a recurrence in the form of AML after lineage-switching. Three courses of VEN/AZA were administered with the same therapeutic drug monitoring as in Case 1. The Cmin of VEN was 0.15 μg/ml at 8 mg/kg. Afterwards, voliconazole 16 mg/kg/day was begun for a concomitant fungal infection together with VEN 2 mg/kg. This combination finally achieved Cmin 1.14 μg/ml probably through CYP3A4 inhibition by voriconazole. In terms of safety, only grade 4 hematological adverse events were observed in both patients. In terms of efficacy, patient 1 and patient 2 achieved stable disease status for two months and six months, respectively.
Conclusion: Pediatric patients barely attain an effective plasma concentration of VEN when crushed tablets are used at the same dosage as in adults.
Is seven days enough? Comparing a 7-day exposure to the classical 21-day OECD TG 229 fish short-term reproduction assay in fathead minnow
Authors: Robitaille Julie , Desrosiers Mélanie , Veilleux Éloïse , Métivier Marianne , Guay Isabelle , Lefebvre Molly , Langlois Valerie 
Published: April 2024

Abstract

The OECD (Organisation for Economic Co-operation and Development) test guidelines (TG) 229 - fish short-term reproduction assay (FSTRA) is one of the gold standard methods used to identify endocrine disrupting chemicals (EDCs). While informative, the FSTRA’s 5 to 6-week duration makes it difficult to use routinely. Prior studies have shown that EDCs’ impact on fecundity, vitellogenin (VTG) and steroid levels can be detected after less than one week of exposure suggesting the FSTRA could be shortened. This study compares both 7- and 21-day FSTRAs using fathead minnows (Pimephales promelas) for three known EDCs: 17α-ethinylestradiol (EE2; 40 ng/L), 17β-trenbolone (TRB; 50 µg/L), and propiconazole (PRP; 500 µg/L). All three compounds led to arrested fertility after 24 h of exposure, except for the 7-day EE2 treatment which still decreased reproduction. Moreover, independently of time of exposure, EE2 induced VTG production in males, and decreased estrogen levels in females and testosterone levels in males. In contrast, TRB induced VTG production in males, while the levels were not different from controls in females even though testosterone levels increased, and masculinization was observed. Finally, PRP led to a decrease in VTG levels which was only significant during the 21-day exposure, and surprisingly, no effect on steroid levels were observed despite its known effects on steroidogenesis. Apart from minor differences, both times of exposure led to similar outcomes supporting the shortening of the FSTRA to seven days. This proposed 7-day FSTRA could be used to screen EDCs in routine monitoring of environmental samples.
Implementation of the STEPPS program for the treatment of self-harm behaviors in Catalonia’s prisons: Barriers and facilitators
Authors: Lorente-Català Rosa , Jaén Irene , Busca-Huertas Xavier , Berta Framis , García-Palacios Azucena 
Published: April 2024

Abstract

Background
The Systems Training for Emotional Predictability and Problem Solving (STEPPS) is an evidence-based program that has been shown to be effective in reducing self-harm behaviors in Correctional Settings (CS). However, there is limited understanding of the contextual factors that impact the implementation of this intervention within such complex environments. A comprehensive understanding of the implementation process is crucial for the successful adoption of this program. This study aims to examine the factors that influence the implementation of the STEPPS program in CS, specifically regarding the management of self-harm behaviors.
Method
A hybrid implementation effectiveness type III study was conducted in penitentiary centers in Catalonia (Spain). Eight Focus Group Discussions based on the Consolidated Framework for Implementation Research (CFIR) were conducted with 17 professionals who implemented the STEPPS program. Additionally, quantitative data were gathered using an open-closed questionnaire based on a CFIR questionnaire.
Results
The results indicated that the scientific evidence and knowledge acquired during the implementation process were seen as facilitators. Also, meetings and support from the external research team were considered positive factors. Conversely, implementation barriers of the STEPPS program in CS included the complexity of the intervention format and the mobility of inmates between modules and centers during the duration of the program.
Trial registration
NCT06297460 (ClinicalTrials.gov, retrospectively registered).
SARS-CoV-2 disrupts host gene networks: unveiling key hub genes as potential therapeutic targets for COVID-19 management
Authors: Marta Majewska , Maździarz Mateusz , Krawczyk Katarzyna , Paukszto Łukasz , Makowczenko Karol G. , Lepiarczyk Ewa , Lipka Aleksandra , Wiszpolska Marta , Górska Anna , Moczulska Beata , Kocbach Piotr , Sawicki Jakub , Gromadziński Leszek 
Published: April 2024

Abstract
Background
Although the end of COVID-19 as a public health emergency was declared on May 2023, still new cases of the infection are reported and the risk remains of new variants emerging that may cause new surges in cases and deaths. While clinical symptoms have been rapidly defined worldwide, the basic body responses and pathogenetic mechanisms acting in patients with SARS-CoV-2 infection over time until recovery or death require further investigation. The understanding of the molecular mechanisms underlying the development and course of the disease is essential in designing effective preventive and therapeutic approaches, and ultimately reducing mortality and disease spreading.
Methods
The current investigation aimed to identify the key genes engaged in SARS-CoV-2 infection and uncover their molecular implication in disease severity. To achieve this goal high-throughput RNA sequencing of peripheral blood samples collected from healthy donors and COVID-19 patients was performed. The resulting sequence data were processed using a wide range of bioinformatics tools to obtain detailed modifications within five transcriptomic phenomena: expression of genes and long non-coding RNAs, alternative splicing, allel-specific expression and circRNA production. The in silico procedure was completed with a functional analysis of the identified alterations.
Results
The transcriptomic analysis revealed that SARS-CoV-2 has a significant impact on multiple genes encoding ribosomal proteins (RPs). Results show that these genes differ not only in terms of expression but also manifest biases in alternative splicing and ASE ratios. The integrated functional analysis exposed that RPs mostly affected pathways and processes related to infection—COVID-19 and NOD-like receptor signaling pathway, SARS-CoV-2-host interactions and response to the virus. Furthermore, our results linked the multiple intronic ASE variants and exonic circular RNA differentiations with SARS-CoV-2 infection, suggesting that these molecular events play a crucial role in mRNA maturation and transcription during COVID-19 disease.
Conclusions
By elucidating the genetic mechanisms induced by the virus, the current research provides significant information that can be employed to create new targeted therapeutic strategies for future research and treatment related to COVID-19. Moreover, the findings highlight potentially promising therapeutic biomarkers for early risk assessment of critically ill patients.
Role of Plasma Fatty Acid in Age-Related Macular Degeneration: Insights from a Mendelian Randomization Analysis
Authors: Han Guoge , Wei Pinghui , He Meiqin 
Published: April 2024

Abstract
Background
An imbalance in lipid metabolism has been linked to the development of AMD, but the causal relationship between AMD and plasma fatty acids (FAs) remains controversial. Using a two-sample Mendelian randomization (MR) approach, we sought to evaluate the impact of specific FA plasma levels on various AMD subtypes’ risk.
Methods
We analysed genome-wide association data of circulating FAs from 115,006 European-descended individuals in the UK Biobank. This data was used in a two-sample MR framework to assess the potential role of circulating FAs in developing wet and dry AMD. Sensitivity analyses were conducted to ensure the robustness of our findings. Additional multivariable and locus-specific MR analyses were conducted to evaluate FA’s direct effects on AMD subtypes, minimizing biases from lipoprotein-related traits and triglycerides.
Results
Mendelian randomization revealed associations of omega-3 was associated with decreased wet (OR 0.78, 95%CI 0.66–0.92) and dry AMD (0.85, 0.74–0.97) risk. Notably, the omega-6 to omega-3 ratio showed potential causal effects on both wet (1.27, 1.03–1.56) and dry AMD (1.18, 1.02–1.37). Multivariable MR suggested that the causal relationship of omega-3, omega-6 to omega-3 ratio on wet AMD persists after conditioning on other lipids, albeit with slightly diminished evidence strength. These results, however, did not withstand multiple testing correction and the exclusion of SNPs within the FADS locus from dry AMD samples.
Conclusions
The connections between plasma FA concentrations and AMD, suggest potential causal role of omega-3, and the omega-6 to omega-3 ratio in wet AMD. These results underscore the impact of imbalanced circulating omega-3 and omega-6 FA ratio on AMD pathophysiology from MR perspective.
DDX39A: A Key Proliferation-Promoting Protein in Gastric Cancer Identified through Proteomic Analysis
Authors: Yan Jingjing , Liu Bingbing , Li Shuo , Cheng Kai , Yang Yan , Liu Mengru , Li Zhijia , Wang Han , Huo Zhongchao , Zhang Zhiwei 
Published: April 2024

Abstract

Purpose:Gastric cancer (GC) is a significant global health concern, with a particularly high prevalence in the southern Hebei province of China. This study aims to uncover key proteins associated with the occurrence of GC and thus provide new potential for the treatment of GC.Methods:In this study, we performed high-throughput proteomic analysis on GC and adjacent non-tumor tissues to identify abnormally expressed proteins, and then made GO enrichment, KEGG pathway and cluster analysis. Differentially expressed proteins were further screened and validated by parallel reaction monitoring (PRM) test, including DDX39A et al. Using immunohistochemistry (IHC), we examined DDX39A's expression and its clinical relevance in GC. We then knocked down DDX39A in AGS and MKN-74 cell lines using shRNA technology, and investigated the effects of DDX39A knockdown on cell proliferation and cell cycle progression using CCK-8 assay and flow cytometry assay.Result:In our proteomic analysis of GC tissues, 569 proteins were differentially expressed, with 248 up-regulated and 321 down-regulated. GO enrichment, KEGG pathway, and cluster analysis linked them to key pathways like cell proliferation and immune response.Nine promising proteins were screened by proteomics analysis and validated using PRM, DDX39A was recognized as the critical functional protein. IHC further demonstrated DDX39A was high expressed in GC, and its expression was correlated with N stage and TNM stage. The knockdown of DDX39A significantly reducing the proliferation and survival of GC cell lines, as confirmed by RT-qPCR and Western blot. Additionally, cell cycle analysis showed an increase in the G1 phase and a decrease in the S phase after knockdown. That highlighted DDX39A's critical role in GC cell cycle regulation and growth.Conclusion:In this study, a series of differentially expressed proteins were successfully identified using proteomic analysis, and DDX39A was identified as a key proliferation-promoting protein in GC. DDX39A is potential to be a therapeutic target for GC and further research into it would be worthwhile.