bluuebunny/crossref_metadata_2025 huggingface dataset:
Nurturing a New Industry Rooted in Geoscience: Stakeholder Insights on Minewater Thermal in Scotland
Authors: Deeming K. B. , Dickie J. , Roberts J. J. , Shipton Z. K.
Published: November 2024

Heat decarbonisation is crucial for climate action and the transition to a sustainable society. Abandoned, flooded mines can be used to provide low-carbon heating and cooling for buildings or as thermal energy storage for district heating networks (“minewater thermal resources”). Due to the capital-intensive nature of the infrastructure required for minewater thermal, its use should be considered early in project development. Developers therefore need to be aware of the full range of low-carbon heating solutions to implement the most sustainable solutions. Through interviews with twelve key stakeholders in Scotland, this study aims to determine the level of awareness of this technology among stakeholders who require heat for their developments, and stakeholders who would be involved in the development or construction of such schemes. Our findings have implications for how the geoscience community could aid the development of a minewater thermal industry. Stakeholders perceived a range of advantages of minewater, including use as thermal storage and the co-location of minewater resources with heat demand. Perceived disadvantages included the high capital cost and pre-construction risks associated with determining the feasibility minewater resources. Building trust and confidence in minewater thermal technology was identified as a key factor for success. Issues relevant for low-carbon heat in general were also raised including, high retail cost of electricity, skills gaps and labour shortages. Geoscientists can identify prospective minewater resources and assess the risks associated with exploration, development and operation of that resource, contributing to building confidence and reducing up-front capital costs. Given the multidisciplinary nature of the heat decarbonisation challenge, geoscientists must be able to communicate clearly and transparently about the science underpinning resource estimates and risk mitigation measures. For minewater thermal projects to succeed, geoscientists must be equipped with skills, knowledge and understanding to embrace these wider roles in nurturing this nascent industry.
Detaching cells in culture medium using forced vibration for removing a centrifugation from culture process
Authors: Shimoguchi Hayato , Imashiro Chikahiro , Takemura Kenjiro
Published: November 2024

Recent advancements in cell culture have significantly impacted various fields, including drug discovery and regenerative medicine. Consequently, there is an increasing need to minimize the contamination risks and labor involved in cell culture processes. Traditional cell detachment methods typically employ proteolytic enzymes followed by centrifugation to remove these enzymes after cell detachment. This process often requires numerous manual interventions which can lead to potential contamination and deterioration of cell quality. In this study, we propose a novel cell detachment method that eliminates the need for centrifugation even with less trypsinization time. Our approach involves reducing the duration of trypsinization, collecting the trypsin before complete cell detachment, and subsequently detaching the cells using forced vibration within the culture medium. We conducted experiments to optimize the enzyme treatment time and vibration conditions. Our results demonstrated that this method achieved an 82.8% detachment rate of cells from the culture surface. These findings indicate that the proposed cell detachment technique is effective in removing cells from the culture substrate and the following subculture process without the need for centrifugation.
Assessment of the bioactivity of bioinspired magnesium oxide nanoparticles from the Azadirachta indica extract
Authors: Al-Harbi Laila M. , Ezzeldien Mohammed , Elhenawy Ahmed A. , Said Alaa Hassan
Published: November 2024

Azadirachta indica (neem) extract was used to biologically synthesize magnesium oxide nanoparticles (MgO NPs). The synthesized NPs were characterized using X-ray diffraction (XRD), thermogravimetric analysis (TGA), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), and UV-vis spectroscopy. Antioxidant, anticancer, antibacterial, antidiabetic, and anti-inflammatory activities were analyzed for the synthesized MgO NPs and neem extract. The obtained results confirmed the synthesis of spherical magnesium oxide nanoparticles with an average particle size of 23 nm using XRD. The samples exhibited good thermal stability and high stability in biological media. Compared to the neem extract and chemically synthesized magnesium oxide nanoparticles, the bioinspired magnesium oxide nanoparticles showed considerable free radical scavenging activity, with an IC50 value of 69.03 μg/mL. In addition, they reflected high selectivity to liver hepatic cancer cells with an IC50 value of 94.85 μg/mL without inducing any damage to human umbilical vein endothelial cells. The antibacterial activity of the bioinspired magnesium oxide nanoparticles demonstrated comparable effectiveness in treating both Gram-positive and Gram-negative bacterial strains. Furthermore, the produced bioinspired magnesium oxide nanoparticles showed a high percentage of inhibition for both α-amylase and α-glucosidase enzymes with an IC50 value of 61. 53 and 50.6 μg/mL, respectively. In addition, the bioinspired magnesium oxide nanoparticles also showed a higher denaturation inhibition percentage with an IC50 value of 6.66 μg/mL, indicating strong anti-inflammatory action. These enhanced abilities usher in a new bioinspired magnesium oxide nanoparticle bio-application era. Consequently, further in vivo studies are needed to assess the kinetic properties of these nanoparticles.
Generation of an inducible dCas9-SAM human PSC line for endogenous gene activation
Authors: Petazzi Paolo , Gutierrez-Agüera Francisco , Roca-Ho Heleia , Castaño Julio , Bueno Clara , Alvarez Niuska , Forrester Lesley M. , Sevilla Ana , Fidanza Antonella , Menendez Pablo
Published: November 2024

The CRISPR/Cas9 system has transformed genome editing by enabling precise modifications for diverse applications. Recent advancements, including base editing and prime editing, have expanded its utility beyond conventional gene knock-out and knock-in strategies. Additionally, several catalytically dead Cas9 (dCas9) proteins fused to distinct activation domains have been developed to modulate endogenous gene expression when directed to their regulatory regions by specific single-guide RNAs. Here, we report the development of the H9 human pluripotent stem cell (hPSC) line expressing an inducible dCas9-SAM activator (H9-iCas9.SAM), designed to activate transcription of endogenous genes. The H9-iCas9.SAM cells were generated through targeted integration of an inducible CRISPR/Cas9-based gene activator cassette into the AAVS1 “safe-harbour” locus. Molecular analyses confirmed precise and specific integration, ensuring minimal off-target effects. Functional characterization revealed that H9-iCas9.SAM cells retain pluripotency and display inducible endogenous gene activation upon doxycycline treatment. The versatility of H9-iCas9.SAM cells was demonstrated in directed in vitro differentiation assays, yielding neural stem cells (ectoderm), hematopoietic progenitor cells (mesoderm), and hepatocytes (endoderm). This underscores their potential in developmental biology studies and cell therapy applications. The engineered H9-iCas9.SAM line provides a robust platform for investigating gene function and advancing next-generation cell-based therapies.
Preclinical evaluation of vascular closure devices
Authors: Perkins Laura E. Leigh , Tu Merry
Published: November 2024

Vascular closure devices (VCDs) are a diverse class of cardiovascular devices intended to achieve hemostasis following arteriotomy in the common femoral artery for diagnostic and therapeutic interventional procedures. While the preclinical evaluation of VCDs parallel that of many other cardiovascular devices, there are device-specific nuances and model-specific technical considerations in assessing in vivo performance and handling, determining safety, and satisfying regulatory requirements. Despite the multi-decade use and continued development of novel VCD technologies, there is a paucity of published literature on their preclinical evaluation. This review intends to help mitigate this gap through a discussion of conventional animal models, their attributes and limitations, and standards in the in vivo assessment of performance and safety of VCDs.
Engaging an international professional learning community to support underrepresented educators in sports leadership
Authors: Sterrett William L. , Mahmood Aisha , Magnusen Mar , Bashir Ahsan , Sukhera Sohail , Saeed M. A. , Khan Ayaz Muhammad , Ramsey Brooke , Ramsey Charles , Boersma Jess , Abel Hina , Frey Meredith
Published: November 2024

This article provides insights from a collaborative grant effort centered on supporting women in sports leadership through the context of a global professional learning community. This grant initiative, called IDEA-SPORT, focused on enhancing the leadership and sports knowledge of girls and other vulnerable and under-served populations in sports-related fields by encouraging leadership and sports collaboration through curricular design and leadership exercises. This article will focus on leveraging an international, bi-directional professional learning community and deliver a collaborative data-informed workshop focused on leadership education for social responsibility.
Impact of confirmatory test results on subtype classification and biochemical outcome following unilateral adrenalectomy in patients with primary aldosteronism
Authors: Daneshpour Hediyeh , Brüdgam Denise , Stüfchen Isabel , Heinrich Daniel Alexander , Bidlingmaier Martin , Beuschlein Felix , Kürzinger Lydia , Williams Tracy Ann , Reincke Martin , Schneider Holger , Adolf Christian
Published: November 2024

Context

Primary aldosteronism (PA) is the most common form of endocrine hypertension. According to the Endocrine Society Practice Guidelines, the diagnosis of PA requires a pathological screening test result and non-suppressible aldosterone levels during confirmatory testing. Sequential testing with more than one confirmatory test may result in discordant test results.

Objective and patients

We investigated the association of discordant results of captopril challenge test (CCT) and saline infusion test (SIT) on patient subtype classification by adrenal vein sampling (AVS) and outcome in 111 consecutive patients from the German Conn’s Registry. Concordance was defined as non-suppressible aldosterone levels upon both tests, while discordance was defined as conflicting test results. Patients with unilateral disease were offered adrenalectomy (ADX). Biochemical and clinical outcomes were assessed using the PASO criteria.

Results

85 of 111 (77%) patients had concordant results of CCT and SIT. Although baseline characteristics were comparable between patients with concordant and discordant tests, the latter had significantly lower aldosterone levels after testing (CCT: 170 vs. 114pg/ml; SIT: 139 vs. 101pg/ml; p=0.004). In 35% of patients with discordant (n=9) and 46% of concordant test results (n=39), AVS suggested lateralized PA. In 36 of 48 cases ADX was performed. 86% of patients with discordant and 72% with concordant results had complete biochemical success.

Conclusion

The use of two confirmatory tests in patients with PA results in discordant results in approximately 23% of cases. Patients having discordant confirmatory test results had a comparable rate of lateralized PA and underwent adrenalectomy with similar long-term outcome.
Whole mitochondrial genome analyses of Han population from Shandong of China using massively parallel sequencing
Authors: Zhang Jiashuo , Li XueBo , Chen Anqi , Ding Mingxia , Li Liangliang , Qi Yinghua , Ding Chunli , Cai Dawei , Zhang Suhua
Published: November 2024

Introduction

Mitochondrial DNA (mtDNA) has been extensively utilized in archeology, human evolutionary genetics, and forensic genetic for over three decades, primarily due to its maternal inheritance and relatively high mutation rate. The Chinese Han, the largest and most widely distributed ethnic group in China, have been the focus of numerous genetic studies. However, the forensic parameters and genetic structure of the Shandong Han, specifically in relation to the whole mitochondrial genome, remain undocumented.

Methods

We performed whole mitochondrial genome sequencing on 141 unrelated Han individuals from Shandong province using massively parallel sequencing.

Results

A total of 135 unique mtDNA haplotypes were identified, classified into 105 haplogroups, resulting in a haplotype diversity value of 0.9993. The discriminatory capacity of whole mitochondrial genome was calculated at 0.9574, compared to 0.8936 when only the control region was analyzed. The majority of the haplogroups observed were specific to East Asian lineages, including D4, D5 and F1. Population comparisons revealed that the modern Shandong Han share genetic connections with ancient populations from the Yellow River and West Liao River basins. Additionally, the Shandong Han may have integrated a significant number of maternal lineages from other regions during their development. The demographic expansion of the Shandong Han is estimated to have occurred approximately 9,000 years ago, corresponding to the Neolithic period, a time of significant cultural and technological development.

Discussion

The dataset generated in this study is available in the EMPOP database under the accession number EMP00886 and will serve as an important mtDNA reference for forensic casework in China. The study of whole mitochondrial genome based on the analysis of matrilineal genetic structure of the Shandong Han population can help to enrich the forensic mtDNA reference database in East Asia and provide reference for future archeology and forensic genetics research.
Unraveling smallholder food loss and value for sustainable cold chain investments: a case of horticultural value chains in Kiambu County, Kenya
Authors: Kilelu Catherine W. , Musyoka Daniel M. , Kalele Dorcas N.
Published: November 2024

Initiatives to address food loss and waste (FLW) are gaining attention especially in smallholder-dominated food systems in developing regions. This is in effort to meet some of the Sustainable Development Goals (SDGs) targets. Countries are seeking innovative solutions to address the FLW challenge to contribute food and nutrition security and to reduce environmental impacts of greenhouse gas emissions through food waste. The lack of effective sustainable cold chain targeting smallholders is a key gap and driver of this challenge. There are gaps in system diagnostic of key factors and practices related to value preservation of food loss but is equally important in capturing value in market opportunities for smallholders and other value chain actors that can guide structuring of such cold chain investments. This article provides findings from a diagnostic study conducted to understand these factors and practices in smallholder focused horticultural value chains in Kenya. The mixed-method study collected quantitative and qualitative data through a household survey of 460 farmers and 25 key informant interviews. Results showed that postharvest loss (PHL) is a major challenge affecting all horticultural crops but with different magnitude. Despite the high PHL experienced, most farmers (96%) don’t undertake any postharvest management measures during and/or after harvest. Market related challenges were rated as the most (85%) causes to PHL followed by pest and disease (56%), weather impacts (24%), lack of storage facilities (17%), and damage during harvest (8%). Most smallholders sell to brokers at farm gate, capturing a small share of the value that is linked to lack of aggregation, gaps in cold chain infrastructure along value chain and the transactions costs of marketing. Results showed that other market outlets other than brokers offered higher prices linked to quality and safer product handling. Thus, integrating end-to-end cold chain solutions in smallholder systems through inclusive business models will shape interactions with markets and enable farmers to tap into new opportunities. Enhancing access to cold chain is key to supporting farmers and other value chain actors reduce PHL and facilitate better market integration, contribute to profitability of smallholder farming enterprises and improve socio-economic development.
IL-17A in gastric carcinogenesis: good or bad?
Authors: Li Weidong , Huang Xiaodong , Han Xiaowen , Zhang Jiayi , Gao Lei , Chen Hao
Published: November 2024

Cytokines, which are important to the tumor microenvironment (TME), play critical roles in tumor development, metastasis, and immune responses. Interleukin-17(IL-17) has emerged as a key biomarker in many malignancies; however, its precise involvement in gastric cancer is less fully understood. Elevated levels of IL-17 have been observed in stomach diseases such as Helicobacter pylori infection and autoimmune gastritis, indicating that a sustained Th17 response may precede the development of gastric cancer. While IL-17 is related to inflammatory processes that may lead to cancer, its specific influence on gastric cancer development and therapy needs to be completely understood. Specifically, the release of IL-17A by diverse immune cells has been associated with both tumor development and inhibition in gastric cancer. It may impact tumor development through mechanisms such as boosting cell proliferation, inducing angiogenesis, and enabling immune cell recruitment or, conversely, suppressing tumor growth via the activation of anti-tumor immune responses. The dual role of IL-17 in cancer, along with its various effects depending on the TME and immune cell composition, highlights the complexity of its activity. Current research reveals that although IL-17 might serve as a target for immunotherapy, its therapeutic potential is hindered by its various activities. Some studies have shown that anti-IL-17 drugs may be helpful, especially when paired with immune checkpoint inhibitors, whereas others point to concerns about the validity of IL-17 in gastric cancer therapy. The lack of clinical trials and the heterogeneity of human tumors underscore the necessity for individualized treatment approaches. Further studies are needed to identify the specific mechanisms of IL-17 in gastric cancer and to design targeted therapeutics appropriately.
Dynamics of the immune microenvironment and immune cell PANoptosis in colorectal cancer: recent advances and insights
Authors: Wan Jinlong , Zhao Jianzhong , Fang Xiaolu
Published: November 2024

Colorectal cancer (CRC) is one of the most significant oncological threats to human health globally. Patients often exhibit a high propensity for tumor recurrence and metastasis post-surgery, resulting in suboptimal prognoses. One of the underlying reasons for the metastatic potential of CRC is the sustained abnormal state of the tumor immune microenvironment, particularly characterized by the atypical death of critical immune cells. In recent years, a novel concept of cell death known as PANoptosis has emerged. This form of cell death is regulated by the PANoptosome complex and encompasses key features of apoptosis, pyroptosis, and necroptosis, yet cannot be entirely substituted by any of these processes alone. Due to its widespread occurrence and complex mechanisms, PANoptosis has been increasingly reported in various malignancies, enhancing our understanding of its pathological mechanisms, particularly in the context of CRC. However, the characteristics of immune cell PANoptosis within the CRC immune microenvironment have not been thoroughly elucidated. In this review, we focus on the impact of CRC progression on various immune cell types and summarize the distinctive features of immune cell PANoptosis. Furthermore, we highlight the future research trends and challenges associated with the mechanisms of immune cell PANoptosis in CRC.
The close association of Muribaculum and PA (10:0/a-17:0) with the occurrence of pancreatic ductal adenocarcinoma and immunotherapy
Authors: Wang Enzhao , Ren Kuiwu , Wang Xiangyu , Du Sen , Gao Xiang , Niu Wang , Guan Chenyue , Liu Xue , Wu Panpan , Liu Chunlong , Yu Jiangtao , Song Kun
Published: November 2024

Background

Progress in immunotherapy for pancreatic ductal adenocarcinoma (PDAC) has been slow, yet the relationship between microorganisms and metabolites is crucial to PDAC development. This study compares the biliary microbiota and metabolomic profiles of PDAC patients with those of benign pancreatic disease patients to investigate PDAC pathogenesis and its relationship with immunotherapy.

Methods

A total of 27 patients were recruited, including 15 diagnosed with PDAC and 12 with benign pancreaticobiliary conditions, all of whom underwent surgical treatment. Intraoperative bile samples were collected and analyzed using 16S rRNA sequencing in conjunction with liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical methods and correlation analyzes were employed to assess differences in microbial composition, structure, and function between malignant and benign pancreatic diseases. Additionally, a retrospective analysis was conducted on PDAC patients post-surgery regarding immunotherapy and its correlation with metabolic components.

Results

PDAC patients exhibited a significantly higher abundance of bile microbiota compared to controls, with notable differences in microbiota structure between the two groups (P < 0.05). At the genus level, Muribaculum was markedly enriched in the bile of PDAC patients and was strongly correlated with phosphatidic acid (PA) (10:0/a-17:0). Both of these components, along with the tumor marker CA199, formulated a predictor of PDAC. Furthermore, PA (10:0/a-17:0) demonstrated a strong correlation with PDAC immunotherapy outcomes (Rho: 0.758; P=0.011).

Conclusion

These findings suggest that the biliary microbiota and associated metabolites play a crucial role in the development of PDAC and may serve as potential predictive biomarkers and therapeutic targets for disease management.
Comparative skin transcriptome analysis as a potential tool to investigate intra- and inter-population differences in belugas
Authors: Unal Ebru , Singh Vijender , Suydam Robert , Goertz Caroline E. C. , Romano Tracy A.
Published: November 2024

Introduction

As long-lived top predators inhabiting the Arctic and subarctic, belugas are under threat of anthropogenic stressors including climate change, pollution, noise, and habitat degradation, which in turn can negatively affect their health and viability. There is currently a need for health indicators that can be easily collected and used to assess and monitor the response to stressors in whales. Comparative transcriptomics using skin tissue can be used to provide understanding of organismal responses to stressors at the cellular level.

Methods

For this study, intra- and inter-population comparisons were performed using the skin transcriptomes obtained from Bristol Bay (BB) belugas sampled in spring and late summer, and Eastern Chukchi Sea (ECS) belugas sampled in early summer in Alaska to investigate significantly differentially expressed genes over 2-fold change (padj<0.05).

Results

Both principal component and hierarchical clustering analysis showed separate clustering of ECS whales, with further clustering of BB whales based on season. Intra-population comparisons carried out between different sexes and age groups did not result in any significant changes. However, the samples collected in spring versus summer within BB stock resulted in 541 significantly regulated genes, with significant activation (z-score≥|2|) predictions in pathways related with extracellular matrix organization, collagen biosynthesis and degradation, wound healing and cytokine signaling, potentially suggesting epidermal changes occurring in preparation for the seasonal molt in BB whales. The inter-population comparisons performed separately for BB-Spring versus ECS and BB-Summer versus ECS resulted in 574 and 938 significantly regulated genes, respectively. The significantly enriched canonical pathways common to both comparisons suggest increased cell survival and host defense responses along with increased cellular maintenance and growth in BB whales, and increased inflammation in ECS whales.

Discussion

These changes observed could potentially be due to differences in molting, bias in hunting preferences and/or differences in environmental conditions during the time of sampling. Findings from this study suggest comparative skin transcriptomics as a useful tool towards understanding biologically relevant gene expression differences at different temporal and spatial scales among beluga stocks with potential to inform and contribute to conservation and recovery of endangered beluga stocks.
Biomass and stable carbon isotope distributions in the Amazon plume region
Authors: Alriyami Zainab , Montoya Joseph P.
Published: November 2024

We investigated the distribution, C:N elemental ratio, and δ¹³C of suspended particulate carbon in the surface and upper 100 m of the water column during three seasons in areas of the Western Tropical North Atlantic influenced by the Amazon River Plume: the Spring high flow period (KN197 Cruise, May-June), the late Summer period of reduced flow (AT2104 cruise, July), and the low flow period in the Fall (MV1110 cruise, Sept-Oct). We used a habitat delineation method to examine spatial and temporal variability in our biogeochemical parameters. We found the highest biomass concentration ([PC]=259.7 µM), high C:N ratio (13.6), and the most negative δ¹³C (-26.8 ‰) in the area proximate to the river mouth during the late summer cruise. We measured elevated [PC] (64.5 µM), C:N ratios (14.1), and δ¹³C (max -15.7 ‰) in the plume core habitats during the peak flow season, reflecting the impact of both the outflow and in situ phytoplankton production. We found that the western margin of the plume had relatively higher biomass, C:N ratios, and organic matter more enriched in 13C than the east margins. In our work area, oceanic waters had the lowest [PC] (1.3 µM), a C:N ratio higher than the Redfield ratio (6.6), and an average δ¹³C of -22 ‰. We explored the relationships between PC and Chla, and δ¹³C and C:N ratio to estimate the contribution of phytoplankton production and terrigenous sources to the suspended particulate carbon pool. We found terrestrial and detrital sources contributing more to the organic matter of the river mouth area. However, the contribution of phytoplankton and living sources dominate most of our study area in all seasons. Our findings emphasize the role of the Amazon River Plume in enhancing biomass and productivity of the WTNA and the biogeochemical dynamic of the carbon cycle.
Predicting cancer-related mycobiome aspects in gastrointestinal cancers: a systematic review
Authors: Szklenarik György , Kiraly Peter , Szegvari Gabor , Dora David , Lohinai Zoltan
Published: November 2024

Background

Colonization of the human gut and tumor tissue by non-pathogenic fungi has emerged as a potential risk factor associated with cancer epidemics. Therefore, we aimed to conduct a systematic review to assess the role of fungal colonization in gastrointestinal (GI) tumors in increasing diagnostic efficiency.

Methods

A PubMed citation search was conducted for publications up to and including March 2023, followed by full-text screening. Results were reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. According to the Patient, Intervention, Comparison, Outcome (PICO) framework, patients diagnosed with early-and advanced-stage GI cancers, GI adenoma patients, and healthy subjects were included with metagenomic (MG) or internal transcribed spacer (ITS) sequencing on tumor tissue, adjacent normal tissue, stool, and blood samples.

Results

Fourteen studies were eligible based on the inclusion criteria and methodological quality. Studies were conducted in stool (n = 8) or tissue (n = 7) as the most common specimens to be used for molecular analysis. In the collected data, ITS was used in n = 10 cases and metagenomic analyses in n = 3 cases. Observing the interindividual variability, we found that the Ascomycota/Basidiomycota (A/B) ratio from healthy to cancer state decreased in n = 2, increased in n = 1 cases, and did not change significantly in n = 2 studies. An increase in the relative abundance of Malassezia was identified in n = 4, of Candida in n = 5, of Saccharomyces in n = 2, and of Aspergillus in n = 2 cases. Intraindividual differences in the A/B ratio were identified in cancer and adjacent tissue (n = 4) and cancer vs. stool (n = 1) studies. Intraindividual variability of the A/B ratio showed an increase in n = 2 and no change in n = 3 studies for cancer tissue.

Conclusion

In conclusion, the advent of highly sensitive sequencing methods may aid in the identification and the differentiation of cancerous from healthy human fungal colonizations with potential future diagnostic applications. Further studies are needed to establish reliable biomarkers for GI cancer screening.
Bacillus coagulans MF-06 alleviates intestinal mucosal barrier from damage in chicks infected with Salmonella pullorum via activating the Wnt/β-catenin pathway
Authors: Ma Li , Tian Guangming , Pu Yuejin , Qin Xuguang , Zhang Yinghu , Wang Haojie , You Lei , Zhang Gaofeng , Fang Chun , Liang Xiongyan , Wei Hongbo , Tan Lei , Jiang Liren
Published: November 2024

Introduction

This study aimed to assess the protective efficacy of Bacillus coagulans MF-06 as a potential alternative to antibiotics in mitigating intestinal mucosal damage in chicks infected with Salmonella pullorum.

Methods

A total of 150 one-day-old SPF chicks were selected and randomly divided into five groups: control group (CK), probiotics group (EM), probiotics treatment group (PT), antibiotic treatment group (AT), Salmonella pullorum group (SI), CK, AT and SI groups were fed a basal diet, EM and PT groups were fed a basal diet supplemented with 1.0 × 108 CFU/g Bacillus coagulans; PT, AT and SI groups were gavaged with 1.0 × 109 CFU/0.5 mL Salmonella pullorum at 7 days of age; AT group were fed with 0.375 g/kg neomycin sulfate in the basal diet from days 7–14.

Results

Subsequently, the study evaluated alterations in growth performance, the integrity of the intestinal mucosal barrier, cytokines associated with the Wnt/β-catenin signaling pathway, and gut microbiota composition. The results revealed that the administration of Bacillus coagulans MF-06 significantly reduced the feed conversion ratio of chicks (p < 0.05), and significantly increased the average daily weight gain and average daily feed intake in chicks challenged with Salmonella Pullorum (p < 0.05). Furthermore, Bacillus coagulans MF-06 treatment diminished the presence of Salmonella pullorum colonies in the intestinal tract. Additionally, the administration of Bacillus coagulans MF-06 restored levels of (Diamine oxidase) DAO and (D-lactic acid) D-LA levels, as well as the levels of tight junction protein, including TJP1, CLDN1, CLDN2, Occludin, and MUC2 (p < 0.05). The study noted a significant decrease in cell apoptosis (p < 0.05) and a significant increase in the expression of Proliferating Cell Nuclear Antigen (PCNA) and v-myc avian myelocytomatosis viral oncogene homolog (C-MYC) (p < 0.05), which activated the Wnt/β-catenin signaling pathway. Analysis through 16S rRNA sequencing revealed that the intake of Bacillus coagulans MF-06 led to a significant decrease in the relative abundance of Lachnoclostridium, Shuttleworthia, and unidentified-Eggerthellaceae (p < 0.05).

Discussion

Collectively, the Bacillus coagulans MF-06 may provide a protective effect against Salmonella pullorum infection in chicks by enhancing growth performance, strengthening the integrity of the intestinal mucosal barrier, and stabilizing the gut microbiota.
The Bro-Xre toxin-antitoxin modules in Weissella cibaria: inducing persister cells to escape tetracycline stress by disrupting metabolism
Authors: Xiang Wen-Liang , Xiong Jie , Wang Han-Yang , Cai Ting , Shi Pei , Zhao Qiu-Huan , Tang Jie , Cai Yi-Min
Published: November 2024

Toxin-antitoxin (TA) modules are important mediators of persister cell formation in response to environmental stresses. However, the mechanisms through which persistence is controlled remain poorly understood. Weissella cibaria, a novel probiotic, can enter a persistent state upon exposure to tetracycline stress. This study found that the Bro-Xre TA modules of W. cibaria function as typical tetracycline regulators. The Bro-Xre TA modules were activated when exposed to tetracycline stress, and the released toxin Bro acted on various cellular metabolic processes, including energy, amino acid, and nucleotide metabolism. Among them, the genes related to intracellular energy pathways, such as PTS, EMP, HMP, TCA, and oxidative phosphorylation, were downregulated, leading to reduced ATP synthesis and proton motive force. This metabolic disruption resulted in cells adopting a persistent phenotype, characterized by an increase in cell length in W. cibaria. Additionally, the frequency of persister cells increased under tetracycline stress. These results provide a novel perspective for understanding the mechanism by which TA modules induce persistence in probiotics, allowing them to evade antibiotic stress through metabolic disruption.
Modeling healthcare demands and long-term costs following pediatric traumatic brain injury
Authors: Wiegand Jared G. , Moazzam Zorays , Braga Bruno P. , Messiah Sarah E. , Qureshi Faisal G.
Published: November 2024

Introduction

Traumatic brain injury (TBI) is a leading cause of death and disability in children, but data on the longitudinal healthcare and financial needs of pediatric patients is limited in scope and duration. We sought to describe and predict these metrics following acute inpatient treatment for TBI.

Methods

Children surviving their initial inpatient treatment for TBI were identified from Optum’s deidentified Clinformatics® Data Mart Database (2007-2018). Treatment cost, healthcare utilization, and future inpatient readmission were stratified by follow-up intervals, type of claim, and injury severity. Both TBI-related and non-TBI related future cost and healthcare utilization were explored using linear mixed models. Acute inpatient healthcare utilization metrics were analyzed and used to predict future treatment cost and healthcare demands using linear regression models.

Results

Among 7,400 patients, the majority suffered a mild TBI (50.2%). For patients with at least one-year follow-up (67.7%), patients accrued an average of 28.7 claims and $27,199 in costs, with 693 (13.8%) readmitted for TBI or non-TBI related causes. Severe TBI patients had a greater likelihood of readmission. Initial hospitalization length of stay and discharge disposition other than home were significant positive predictors of healthcare and financial utilization at one-and five-years follow-up. Linear mixed models demonstrated that pediatric TBI patients would accrue 21.1 claims and $25,203 in cost in the first year, and 9.4 claims and $4,147 in costs every additional year, with no significant differences based on initial injury severity.

Discussion

Pediatric TBI patients require long-term healthcare and financial resources regardless of injury severity. Our cumulative findings provide essential information to clinicians, caretakers, researchers, advocates, and policymakers to better shape standards, expectations, and management of care following TBI.
The origins of light-independent magnetoreception in humans
Authors: Shibata Takashi , Hattori Noriaki , Nishijo Hisao , Kuroda Satoshi , Takakusaki Kaoru
Published: November 2024

The Earth’s abundance of iron has played a crucial role in both generating its geomagnetic field and contributing to the development of early life. In ancient oceans, iron ions, particularly around deep-sea hydrothermal vents, might have catalyzed the formation of macromolecules, leading to the emergence of life and the Last Universal Common Ancestor. Iron continued to influence catalysis, metabolism, and molecular evolution, resulting in the creation of magnetosome gene clusters in magnetotactic bacteria, which enabled these unicellular organisms to detect geomagnetic field. Although humans lack a clearly identified organ for geomagnetic sensing, many life forms have adapted to geomagnetic field—even in deep-sea environments—through mechanisms beyond the conventional five senses. Research indicates that zebrafish hindbrains are sensitive to magnetic fields, the semicircular canals of pigeons respond to weak potential changes through electromagnetic induction, and human brainwaves respond to magnetic fields in darkness. This suggests that the trigeminal brainstem nucleus and vestibular nuclei, which integrate multimodal magnetic information, might play a role in geomagnetic processing. From iron-based metabolic systems to magnetic sensing in neurons, the evolution of life reflects ongoing adaptation to geomagnetic field. However, since magnetite-activated, torque-based ion channels within cell membranes have not yet been identified, specialized sensory structures like the semicircular canals might still be necessary for detecting geomagnetic orientation. This mini-review explores the evolution of life from Earth’s formation to light-independent human magnetoreception, examining both the magnetite hypothesis and the electromagnetic induction hypothesis as potential mechanisms for human geomagnetic detection.
Brain structure and function differences across varying levels of endurance training: a cross-sectional study
Authors: Zhang Keying , Cao Chunmei , Wang Yaxue , Zhang Dong
Published: November 2024

Background

Although previous studies have shown that athletes engaged in endurance sports exhibit unique characteristics of brain plasticity, there has been no systematic investigation into the structural and functional brain characteristics of endurance athletes with varying training levels.

Methods

Utilizing the “expert-novice paradigm” design, we employed functional magnetic resonance imaging (fMRI) to obtain images of brain structure and functional activity. We compared differences in gray matter volume (GMV), fractional amplitude of low-frequency fluctuations (fALFF), and degree centrality (DC) among high-level endurance athletes, moderate-level endurance athletes, and non-athlete controls.

Results

(1) High-level endurance athletes exhibited significantly greater GMV in the left parahippocampal gyrus, bilateral thalamus, right temporal lobe, and bilateral cerebellum compared to both moderate-level endurance athletes and controls. The GMV in these regions showed an increasing trend with more years of endurance training and higher endurance capacity. Additionally, these athletes had significantly higher fALFF in the left superior medial frontal gyrus and right precuneus, as well as higher DC in the right lateral occipital lobe compared to moderate-level endurance athletes. They also had significantly higher DC in the right precuneus and cerebellum compared to the control group. (2) Moderate-level endurance athletes demonstrated significantly greater GMV in the right prefrontal cortex, bilateral medial frontal lobe, right temporal pole, right striatum, and bilateral insula compared to high-level endurance athletes. They also had significantly higher fALFF in the left posterior cingulate gyrus compared to high-level endurance athletes. (3) Control group showed significantly greater GMV in the right amygdala, higher fALFF in the left medial frontal lobe, and greater DC in the left lateral occipital lobe compared to moderate-level endurance athletes.

Conclusion

Adaptive benefits exhibit different characteristics across different endurance levels. High-level endurance athletes exhibit pronounced enhancements in gray matter volume and functional activity in regions associated with memory, motor control, and sensory processing. While moderate-level athletes demonstrate distinct functional reorganization in the default mode network and cerebellum.
Case report: Favorable efficacy of combined afatinib and anlotinib treatment in a lung adenocarcinoma patient harboring uncommon EGFR L858M/L861R mutations
Authors: He Yueming , Wu Yitao , He Rongqi , Xu Meng , Chen Heshan , Meng Yiran , Zheng Liuqing , Wang Li
Published: November 2024

Targeted therapy has significantly prolonged survival of non-small cell lung cancer (NSCLC) patients carrying common EGFR mutations, but the standard care for patients with rare mutations has not been well established. Here, we report a 65-year-old female diagnosed with stage IIIC lung adenocarcinoma located in the right inferior lobe, harboring uncommon EGFR L858M/L861R mutations. Remarkably, 24 days post-treatment of afatinib and anlotinib, chest CT scans demonstrated significant shrinkage of primary lesion, indicating a partial response. Except for mild hand-foot syndrome and diarrhea, no other severe adverse symptoms were observed throughout treatment. The patient, now on combination therapy for exceeding 12 months, exhibits further decreased tumor size and a high quality of life. This case underscores the importance of precise molecular diagnosis in guiding therapeutic strategies and provides a valuable reference for clinical decision-making in EGFR-positive NSCLC cases with atypical mutations.
Discovery of novel PARP1/NRP1 dual-targeting inhibitors with strong antitumor potency
Authors: Liu Juanjuan , Geng Yifei , Jiang Su , Guan Lixia , Gao Junyi , Niu Miao-Miao , Li Jindong
Published: November 2024

Given that overexpression of Poly (ADP-ribose) polymerase-1 (PARP1) and Neuropilin-1 (NRP1) is implicated in the pathogenesis of human breast cancer, the design of dual PARP1/NRP1 inhibitors has wide therapeutic prospect. However, there have been no reports of such inhibitors so far. Herein, we discovered novel small molecule inhibitors that simultaneously target PARP1 and NRP1 using structure-based virtual screening for the treatment of breast cancer. Notably, PPNR-4 was the most potent inhibitor targeting PARP1 (IC50 = 7.71 ± 0.39 nM) and NRP1 (IC50 = 24.48 ± 2.16 nM). PPNR-4 showed high affinity and binding stability to PARP1 and NRP1. The cytotoxicity assays showed that PPNR-4 demonstrated significant antiproliferative activity on MDA-MB-231 cells (IC50 = 0.21 μM) without effect on normal human cells. In vivo experiments exhibited that PPNR-4 showed more effective than the positive controls in inhibiting the growth of tumors. Overall, these data suggest that PPNR-4 is an effective antitumor candidate and deserves further research.
Hypoxia induces robust ATP release from erythrocytes in ApoE-LDLR double-deficient mice
Authors: Alcicek Fatih Celal , Dybas Jakub , Bulat Katarzyna , Mohaissen Tasnim , Szczesny-Malysiak Ewa , Franczyk-Zarow Magdalena , Marzec Katarzyna M.
Published: November 2024

Red blood cells (RBCs) play a role in the regulation of vascular tone via release of adenosine triphosphate (ATP) into the vasculature in response to various stimuli. Interestingly, ApoE/LDLR double-deficient (ApoE/LDLR−/−) mice, a murine model of atherosclerosis, display a higher exercise capacity compared to the age-matched controls. However, it is not known whether increased exercise capacity in ApoE/LDLR−/− mice is linked to the altered ATP release from RBCs. In this work, we characterized the ATP release feature of RBCs from ApoE/LDLR−/− mice by exposing them to various stimuli in vitro. The results are linked to the previously reported mechanical and biochemical alterations in RBCs. 3V-induced ATP release from RBCs was at comparable levels for all groups, which indicated that the activity of adenylyl cyclase and the components of upstream signal-transduction pathway were intact. Moreover, hypoxia- and low pH-induced ATP release from RBCs was higher in ApoE/LDLR−/− mice compared to their age-matched controls, a potential contributing factor and a finding in line with the higher exercise capacity. Taken together, augmented hypoxia-induced ATP release from RBCs in ApoE/LDLR−/− mice indicates a possible deterioration in the ATP release pathway. This supports our previous reports on the role of the protein structure alterations of RBC cytosol in hypoxia-induced ATP release from RBCs in ApoE/LDLR−/− mice. Thus, we emphasize that the presented herein results are the first step to future pharmacological modification of pathologically impaired microcirculation.
A segmentation-combination data augmentation strategy and dual attention mechanism for accurate Chinese herbal medicine microscopic identification
Authors: Zhu Xiaoying , Pang Guangyao , He Xi , Chen Yue , Yu Zhenming
Published: November 2024

Introduction

Chinese Herbal Medicine (CHM), with its deep-rooted history and increasing global recognition, encounters significant challenges in automation for microscopic identification. These challenges stem from limitations in traditional microscopic methods, scarcity of publicly accessible datasets, imbalanced class distributions, and issues with small, unevenly distributed, incomplete, or blurred features in microscopic images.

Methods

To address these challenges, this study proposes a novel deep learning-based approach for Chinese Herbal Medicine Microscopic Identification (CHMMI). A segmentation-combination data augmentation strategy is employed to expand and balance datasets, capturing comprehensive feature sets. Additionally, a shallow-deep dual attention module enhances the model's ability to focus on relevant features across different layers. Multi-scale inference is integrated to process features at various scales effectively, improving the accuracy of object detection and identification.

Results

The CHMMI approach achieved an Average Precision (AP) of 0.841, a mean Average Precision at IoU=.50 (mAP@.5) of 0.887, a mean Average Precision at IoU from .50 to .95 (mAP@.5:.95) of 0.551, and a Matthews Correlation Coefficient of 0.898. These results demonstrate superior performance compared to state-of-the-art methods, including YOLOv5, SSD, Faster R-CNN, and ResNet.

Discussion

The proposed CHMMI approach addresses key limitations of traditional methods, offering a robust solution for automating CHM microscopic identification. Its high accuracy and effective feature processing capabilities underscore its potential to modernize and support the growth of the CHM industry.
Insights into the aroma volatiles and the changes of expression of ester biosynthesis candidate genes during postharvest storage of European pear
Authors: Zhu Xinxin , Xu Xiaofei , Jiang Fudong , Li Qingyu , Zhang Aidi , Li Jianzhao , Zhang Hongxia
Published: November 2024

During the storage period after harvest, the presence of volatile esters is essential for European pear aroma. Nevertheless, the specific molecular process underlying the production of volatile esters in European pear remains elusive. In this research, head space solid phase microextraction and gas chromatography-mass spectrometry were employed to examine the volatile compounds of two varieties of European pear. The results revealed the identification of a collective of 149 volatile compounds, which were categorized into 8 groups: esters (37), alcohols (25), alkanes (24), aldehydes (22), terpenes (15), acids (8), ketones (6) and other categories (12). Notably, there were 79 volatile compounds that coexisted in both varieties, which esters are the primary group of volatile compounds found in both varieties. Through transcriptome analysis, we identified 12 candidate genes associated with ester biosynthesis and established their correlation with firmness, ethylene production, and predominant volatile esters. The results from gene expression analysis revealed significant up-regulation of PcFAD2 and PcLIP2 in both varieties and PcFAD6 exhibits low expression levels. The results indicate that the involvement of these three genes in the synthesis of esters in European pear may have a significant level of importance. This study enhances our understanding of the mechanisms involved in the formation of European pear flavor.