bluuebunny/crossref_metadata_2025 huggingface dataset:
Untargeted Metabolomics Reveals Key Differences Between Yak, Buffalo, and Cow Colostrum Based on UHPLC-ESI-MS/MS
Authors: Wang Yuzhuo , Li Changhui , Huang Jiaxiang , Zeng Qingkun , Li Ling , Yang Pan , Wang Pengjie , Chu Min , Luo Jie , Ren Fazheng , Zhang Hao
Published: January 2025

Background: Colostrum, abundant in immunoglobulins and growth factors, plays a vital role in supporting immunity. Both yak and buffalo milk are characterized by their high protein and fat content. However, the metabolomic profiles of yak colostrum (YC), buffalo colostrum (BC), and bovine colostrum (CC) remain largely unexplored. The objective of this study is to identify unique metabolites that may impact the nutritional value of colostrum. Methods: This study employed ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) for untargeted metabolomics analysis of YC, BC, and CC. Results: The analysis revealed 97, 70, and 75 differentially expressed metabolites in the YC-CC, BC-CC, and YC-BC comparisons, respectively. In comparison to CC, both YC and BC shared common features, including reduced choline levels and elevated O-acetylcarnitine. Moreover, metabolites such as 2-hydroxy-6-pentadecylbenzoic acid, DL-glycerol-1-phosphate, thiamine, L-carnitine, methyl β-D-galactoside, and uridine diphosphate (UDP) were identified as potential biomarkers for YC, while 21-deoxycortisol, D-synephrine, uridine, mannitol-1-phosphate, nonadecanoic acid, and perillic acid were specific to BC. Conclusions: YC has greater advantages in energy supply, antioxidant activity, immune regulation, and cell homeostasis, and BC holds unique significance in physical development and energy balance regulation. These findings provide valuable insights, enabling the selection of unique bioactive metabolites to develop targeted functional foods from colostrum, catering to diverse nutritional needs.
Interaction Effects of Tannic Acid and Gluten on Bread-Making and Its Starch Digestion
Authors: Nam Seonghyeon , Ozturk Oguz K. , Lim Jongbin
Published: January 2025

In this study, we explored the binding mechanism between tannic acid (TA) and gluten to apply TA as an ingredient in bread-making to evaluate its baking performance and starch digestion. The interaction was systematically investigated by analyzing binding affinity, binding mode, and matrix structure of the TA–gluten complex using fluorescence quenching, molecular docking, and confocal laser scanning microscopy. TA strongly interacted with gluten via non-covalent interactions, mainly hydrogen bonds, and formed the major hydrogen bonds with six different glutamines (Q32, Q108, Q313, Q317, Q317, and Q349), which play a critical role in gluten network construction among amino acid residues of gluten. Additionally, TA showed lower binding affinity toward glutenin (−10.4 kcal/mol) compared to gliadin (−8.9 kcal/mol), implying stronger binding with glutenin. Consequently, the interaction between TA and gluten created a dense and compact gluten network structure. It influenced baking performance, causing a decrease in bread loaf volume while an increase in firmness and lowering the starch digestion rate, increasing slowly digestible starch and resistant starch fractions. This study identified the binding mechanism of TA toward gluten and provides better insights into how to apply TA or perhaps other polyphenols to design functional bakery products to control starch digestion rate.
Biocomposite Polyvinyl Alcohol/Ferritin Hydrogels with Enhanced Stretchability and Conductivity for Flexible Strain Sensors
Authors: Fu Qiang , Tang Junxiao , Wang Weimin , Wang Rongjie
Published: January 2025

Protein-based hydrogels with stretchability and conductivity have potential applications in wearable electronic devices. However, the development of protein-based biocomposite hydrogels is still limited. In this work, we used natural ferritin to develop a PVA/ferritin biocomposite hydrogel by a repetitive freeze–thaw method. In this biocomposite hydrogel, ferritin, as a nano spring, forms a hydrogen bond with the PVA networks, which reduces the crystallinity of PVA and significantly improves the stretchability of the hydrogel. The fracture strain of the PVA/ferritin hydrogel is 203%, and the fracture stress is 112.2 kPa. The fracture toughness of the PVA/ferritin hydrogel is significantly enhanced to 147.03 kJ/m3, more than 3 times that of the PVA hydrogel (39.17 kJ/m3). In addition, the free residues and iron ions of ferritin endow the biocomposite hydrogel with enhanced ionic conductivity (0.15 S/m). The strain sensor constructed from this hydrogel shows good sensitivity (gauge factor = 1.7 at 150% strain), accurate real-time resistance response, and good long cyclic working stability when used for joint motion monitoring. The results indicate that a PVA/ferritin biocomposite hydrogel prepared by a facile method has enhanced stretchability and conductivity for flexible strain sensors. This work develops a new method for the preparation of protein-based hydrogels for wearable electronic devices.
Hyperbaric Oxygen Therapy as a Renewed Hope for Ischemic Craniomaxillofacial Diseases
Authors: He Chan , Huang Dou , Liu Lei
Published: January 2025

Although the advancements in craniomaxillofacial surgery have been significant, ischemic craniomaxillofacial diseases remain challenging to treat due to insufficient blood supply. Hyperbaric oxygen therapy (HBOT) has emerged as a promising adjunctive treatment, exhibiting the potential to promote angiogenesis, exert anti-inflammatory effects, enhance bone regeneration, and possess antibacterial properties. Numerous studies have demonstrated its efficacy in stimulating healing processes, particularly in cases such as medication-related osteonecrosis of the jaw, osteoradionecrosis, chronic jaw osteomyelitis, and refractory wounds. Hyperbaric oxygen therapy not only accelerates healing and shortens recovery times but also reduces postoperative complications, infection risks, and enhances patients’ overall quality of life. This review aims to synthesize the research progress on the application of hyperbaric oxygen therapy in ischemic craniomaxillofacial diseases, providing a valuable reference for clinicians.
The Safety Profile of Inclisiran in Patients with Dyslipidemia: A Systematic Review and Meta-Analysis
Authors: Maliha Maisha , Satish Vikyath , Kumar Sriram Sunil , Chi Kuan Yu , Shama Nishat , Kharawala Amrin , Duarte Gustavo , Li Weijia , Purkayastha Sutopu , Mangeshkar Shaunak , Borkowski Pawel , Gashi Eleonora , Behuria Supreeti
Published: January 2025

Introduction: Inclisiran is a novel drug that employs ribonucleic acid (RNA) interference to lower the levels of the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. It has demonstrated a significant reduction in LDL cholesterol levels compared to a placebo. We aim to comprehensively evaluate the safety of using Inclisiran in patients with dyslipidemia and ASCVD or an ASCVD risk equivalent. Methods: Four electronic databases, namely, Pubmed/MEDLINE, Web of Science, Embase, and ClinicalTrials.gov, were searched from inception to June 2024 to identify relevant randomized controlled trials (RCTs) comparing safety profiles of Inclisiran and the control group. The outcomes investigated were all-cause mortality, major adverse cardiovascular events (MACEs), injection-site adverse events, new-onset or worsening type 2 diabetes mellitus (T2DM), and nasopharyngitis. The effect estimates of outcomes were assessed using the risk ratio (RR) with a 95% confidence interval (CI). Random-effects meta-analysis was conducted using the restricted maximum likelihood method. Subgroup analysis was performed based on different dosing regimens. Results: The study included 7 RCTs, enrolling 4790 patients (age 63.8 ± 9.7 years, 33.2% females) who received Inclisiran. Compared to the control group, Inclisiran use did not yield a significant effect on all-cause mortality (RR, 0.92; 95% CI, 0.54 to 1.54; I2 = 0%), MACEs (RR, 0.98; 95% CI, 0.82 to 1.17; I2 = 0%), nasopharyngitis (RR, 1.10; 95% CI, 0.83 to 1.45; I2 = 0%), and T2DM (RR, 1.02; 95% CI, 0.85 to 1.21; I2 = 0%). However, Inclisiran use demonstrated a significant increase in injection-site adverse events (RR, 6.50; 95% CI, 3.20 to 13.20; I2 = 29%). Conclusions: Inclisiran use significantly increased injection-site reactions, with no increase in mortality, T2DM, or nasopharyngitis. It demonstrates a generally favorable safety profile, making it a promising option for lipid management in individuals at high cardiovascular risk, such as those with ASCVD or equivalent conditions. While it effectively improves dyslipidemia, decision-makers should be aware of an increased incidence of injection-site reactions, which, though typically mild, warrant consideration in clinical practice. Further trials are required to assess the safety of Inclisiran, particularly the association of the severity of injection-site adverse events over longer treatment durations.
A Spray Foliar Containing Methylobacterium symbioticum Did Not Increase Nitrogen Concentration in Leaves or Olive Yield Across Three Rainfed Olive Orchards
Authors: Rodrigues Manuel Ângelo , Lopes João Ilídio , Martins Sandra , Brito Cátia , Correia Carlos Manuel , Arrobas Margarida
Published: January 2025

Biological nitrogen (N) fixation has been advocated in agricultural fields due to being considered a more sustainable way to introduce N into agrosystems than industrial N fertilizers. In this study, a foliar spray inoculant containing the microorganism Methylobacterium symbioticum was applied. This microorganism is known for fixing N in the phyllosphere, regardless of the cultivated species. This study was conducted in three rainfed olive orchards over three years. In two orchards managed according to European Union (EU) integrated production rules, the experiment was organized as a factorial design with inoculant (applied at two levels, yes and no) and N fertilization (applied to the soil at three levels, 0, 40, and 80 kg ha−1 of N). The third trial, managed according to EU organic farming rules, was organized in a completely randomized design with three treatments: with (yes) and without (no) inoculant and with a treatment involving a seaweed extract, also for foliar application. The microbiological inoculant did not consistently influence olive yield or N concentration in leaves across the three trials. Conversely, N application to the soil significantly influenced N concentration in leaves and olive yield. In one of the trials, in the third year of the study, soil N application (80 kg ha−1) resulted in an olive yield of ~eight times higher than the unfertilized control treatment. The seaweed extract also did not lead to significant differences in leaf mineral composition or olive yield compared with the other treatments. These findings from the on-farm research highlight the importance of accurately determining the conditions under which commercial products can deliver effective results. It is crucial to acknowledge that these products involve expenses not only in their acquisition but also in their application.
Assessing the Impacts of Climatic and Water Management Scenarios in a Small Mountainous Greek River
Authors: Mentzafou Angeliki , Papadopoulos Anastasios , Dimitriou Elias
Published: January 2025

The water resource management of transboundary mountainous river basins under climate change is expected to be challenging. In order to contribute to the better understanding of climate change effects on the water resources of the mountainous and transboundary Prespa Lakes basin, a hydrological model of the Agios Germanos River, one of the main rivers discharging to Great Prespa Lake, was developed, and two water management plans under two different climate scenarios were examined. Based on the results, the impact of climate change on surface water resources was evident in all climate change scenarios examined, even under the most favorable water abstraction practices. Nevertheless, sensible water management can moderate the impact of climate change by up to 10% in an optimistic scenario in both the near- and long-term, and by up to 6% and 1% for the near- and long-term, respectively, in a pessimistic scenario. Integrated water management practices that moderate the impact of climate change on the water ecosystem services should be prioritized. Nature-based approaches could provide solutions regarding climate change adaptation and mitigation. Transboundary cooperation, data exchange mechanisms, common policy frameworks, and monitoring, reporting, and evaluation systems, could reduce human and ecosystems’ vulnerabilities and improve the water security of the area.
Outdoor Exercise for People with Rheumatic Disease–Study Protocol and Baseline Characteristics of the OUTdoor Physical ACtivity Cohort (OUTPAC)
Authors: Ahler Jonas R. , Tang Lars H. , Poulsen Dorthe V. , Skou Søren T. , Holm Pætur M.
Published: January 2025

The OUTPAC cohort study evaluates the setup and implementation of a nationwide Danish initiative focused on the impact of structured outdoor physical activity (PA) on individuals with rheumatic diseases. This prospective cohort study includes more than 1600 participants, predominantly women (92%), with an average age of 65 years (range: 28–93). The cohort primarily consists of individuals with osteoarthritis (72%), rheumatoid arthritis (18%) and nonspecific lower back pain (13%). Volunteer instructors conducted interventions in outdoor settings, targeting strength, balance, physical capacity, mental health, and interaction with nature. Data collection involved questionnaires and physical tests in four primary outcome domains: quality of life, pain, physical function and activity, and mental health. Despite moderate pain (VAS mean: 48.3), high medication use (71%), and serious fatigue (54%), participants indicated having a good quality of life (EQ-5D-5L mean: 0.81) and average mental health (WHO-5 mean: 62.9). Baseline scores from physical tests showed results comparable to the general population aged 60–69 years. The OUTPAC project offers clinical insight into the implications of outdoor PA interventions on individuals with rheumatic disease while shedding light on the development and implementation of a large-scale nationwide outdoor PA intervention. Future analyses will examine short- and long-term changes and potential determinants.
Artificial Intelligence-Driven Translation Tools in Intensive Care Units for Enhancing Communication and Research
Authors: Bahrami Sahar , Rubulotta Francesca
Published: January 2025

There is a need to improve communication for patients and relatives who belong to cultural minority communities in intensive care units (ICUs). As a matter of fact, language barriers negatively impact patient safety and family participation in the care of critically ill patients, as well as recruitment to clinical trials. Recent studies indicate that Google Translate and ChatGPT are not accurate enough for advanced medical terminology. Therefore, developing and implementing an ad hoc machine translation tool is essential for bridging language barriers. This tool would enable language minority communities to access advanced healthcare facilities and innovative research in a timely and effective manner, ensuring they receive the comprehensive care and information they need. Method: Key factors that facilitate access to advanced health services, in particular ICUs, for language minority communities are reviewed. Results: The existing digital communication tools in emergency departments and ICUs are reviewed. To the best of our knowledge, no AI English/French translation app has been developed for deployment in ICUs. Patient privacy and data confidentiality are other important issues that should be addressed. Conclusions: Developing an artificial intelligence-driven translation tool for intensive care units (AITIC) which uses language models trained with medical/ICU terminology datasets could offer fast and accurate real-time translation. An AITIC could support communication, and consolidate and expand original research involving language minority communities.
Probing Spatiotemporal Effects of Intertrack Recombination with a New Implementation of Simultaneous Multiple Tracks in TRAX-CHEM
Authors: Castelli Lorenzo , Camazzola Gianmarco , Fuss Martina C. , Boscolo Daria , Krämer Michael , Tozzini Valentina , Durante Marco , Scifoni Emanuele
Published: January 2025

Among the most investigated hypotheses for a radiobiological explanation of the mechanism behind the FLASH effect in ultra-high dose rate radiotherapy, intertrack recombination between particle tracks arriving at a close spatiotemporal distance has been suggested. In the present work, we examine these conditions for different beam qualities and energies, defining the limits of both space and time where a non-negligible chemical effect is expected. To this purpose the TRAX-CHEM chemical track structure Monte Carlo code has been extended to handle several particle tracks at the same time, separated by pre-defined spatial and temporal distances. We analyzed the yields of different radicals as compared to the non-interacting track conditions and we evaluated the difference. We find a negligible role of intertrack for spatial distances larger than 1 μm, while for temporal distances up to μs, a non-negligible interaction is observed especially at higher LET. In addition, we emphasize the non-monotonic behavior of some relative yield as a function of the time separation, in particular of H2O2, due to the onset of a different reaction involving solvated electrons besides well-known OH· recombination.
Advancing Inflammatory Bowel Disease Treatment by Targeting the Innate Immune System and Precision Drug Delivery
Authors: Kiilerich Kat F. , Andresen Trine , Darbani Behrooz , Gregersen Laura H. K. , Liljensøe Anette , Bennike Tue B. , Holm René , Moeller Jesper B. , Andersen Vibeke
Published: January 2025

Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Current immune-modulating therapies are insufficient for 30–50% of patients or cause significant side effects, emphasizing the need for new treatments. Targeting the innate immune system and enhancing drug delivery to inflamed gut regions are promising strategies. Neutrophils play a central role in IBD by releasing reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) —DNA-based structures with cytotoxic proteins—that contribute to mucosal damage and inflammation. Recent studies linking ROS production, DNA repair, and NET formation have identified NETs as potential therapeutic targets, with preclinical models showing positive outcomes from NET inhibition. Innovative oral drug delivery systems designed to target gut inflammation directly—without systemic absorption—could improve treatment precision and reduce side effects. Advanced formulations utilize properties such as particle size, surface modifications, and ROS-triggered release to selectively target the distal ileum and colon. A dual strategy that combines a deeper understanding of IBD pathophysiology to identify inflammation-related therapeutic targets with advanced drug delivery systems may offer significant promise. For instance, pairing NET inhibition with ROS-responsive nanocarriers could enhance treatment efficacy, though further research is needed. This synergistic approach has the potential to greatly improve outcomes for IBD patients.
Harnessing Molecular Insights for Translational Impact: Highlights from the Special Issue Titled “New Insights in Translational Bioinformatics”
Authors: Quek Camelia
Published: January 2025

The field of translational bioinformatics is rapidly evolving, driving the convergence of molecular sciences and computational methods with their applications in industrial and clinical practice [...]
Exogenous 24-Epibrassinolide Improves Low-Temperature Tolerance of Maize Seedlings by Influencing Sugar Signaling and Metabolism
Authors: Sun Siqi , Zhao Xiaoqiang , Shi Zhenzhen , He Fuqiang , Qi Guoxiang , Li Xin , Niu Yining , Zhou Wenqi
Published: January 2025

Low-temperature (LT) stress seriously affects the distribution, seedling survival, and grain yield of maize. At the seedling emergence stage, maize’s coleoptile is one of the most sensitive organs in sensing LT signaling and, in general, it can envelop young leaves to protect them from LT damage. In addition, brassinolides (BRs) have been shown to enhance LT tolerance from various species, but the effects of BRs on coleoptiles in maize seedlings under LT stress are unclear. Therefore, in this study, the pre-cultured coleoptiles of Zheng58 seedlings were treated with or without 2.0 μM 24-epibrassinolide (EBR) at 25 °C and 10 °C environments for five days to analyze their physiological and transcriptomic changes. Physiological analysis showed that a 10°C LT stress increased the content of glucose (0.43 mg g−1 FW), sucrose (0.45 mg g−1 FW), and starch (0.76 mg g−1 FW) of Zheng58 coleoptiles compared to a 25°C environment. After the coleoptiles were exposed to a 2.0 μM EBR application under 10°C temperature for five days, the contents of these three sugars continued to increase, and reached 2.68 mg g−1 FW, 4.64 mg g−1 FW, and 9.27 mg g−1 FW, respectively, indicating that sugar signaling and metabolism played key roles in regulating LT tolerance in the coleoptiles of maize seedlings. Meanwhile, a transcriptome analysis showed that 84 and 15 differentially expressed genes (DEGs) were enriched in the sucrose and starch metabolism and photosynthesis pathways, respectively, and multiple DEGs involved in these pathways were significantly up-regulated under LT stress and EBR stimulation. Further analysis speculated that the four DEGs responsible for sucrose-phosphate synthetase (SPS, i.e., Zm00001d048979, probable sucrose-phosphate synthase 5 and Zm00001d012036, sucrose-phosphate synthase 1), sucrose synthase (SUS, Zm00001d029091, sucrose synthase 2 and Zm00001d029087, sucrose synthase 4) were crucial nodes that could potentially link photosynthesis and other unknown pathways to form the complex interaction networks of maize LT tolerance. In conclusion, our findings provide new insights into the molecular mechanisms of exogenous EBR in enhancing LT tolerance of maize seedlings and identified potential candidate genes to be used for LT tolerance breeding in maize.
T Cell-Specific Inactivation of the PI3K p110α Catalytic Subunit: Effect in T Cell Differentiation and Antigen-Specific Responses
Authors: Briones Alejandro C. , del Estal Laura , Villa-Gómez Cristina , Bermejo Verónica , Cervera Isabel , Gutiérrez-Huerta Pedro , Montes-Casado María , Ortega Sagrario , Barbacid Mariano , Rojo José María , Portolés Pilar
Published: January 2025

Class IA PI3K p110δ and p110α subunits participate in TCR and costimulatory receptor signals involved in T cell-mediated immunity, but the role of p110α is not completely understood. Here, we analyzed a mouse model of the Cre-dependent functional inactivation of p110α (kinase dead) in T lymphocytes (p110αKD-T, KD). KD mice showed increased cellularity in thymus and spleen and altered T cell differentiation with increased number of CD4+CD8+ DP thymocytes, enhanced proportion of CD4+ SP lymphocytes linked to altered apoptosis, lower Treg cells, and increased AKT and ERK phosphorylation in activated thymocytes. In the spleen, the percentages of CD4+ Treg cells and CD8+ naive lymphocytes were reduced. In vitro, the differentiation of CD4+ cells from p110αKD-T mice showed lower induced Treg (iTreg) cell yield or IL-10 secretion. Moreover, Tfh cell yield, IL-21 secretion, and PI3-K-dependent elongation were hampered, as was Erk and Akt activation. Th1 or Th17 differentiation in vitro was not altered. The immunization of p110α-KD-T mice with KLH protein antigen induced an enhanced proportion of CXCR5+ CD4+ cells and germinal center B cells, increased ICOS expression in CD4+ cells, or IFN-γ secretion upon antigen re-activation in vitro. However, anti-KLH antibody responses in serum was similar in WT or p110α KD mice. These data show that T cell-specific p110α inactivation alters T cell differentiation and function.
Transcriptome Analysis Suggests PKD3 Regulates Proliferative Glucose Metabolism, Calcium Homeostasis and Microtubule Dynamics After MEF Spontaneous Immortalization
Authors: Loaiza-Moss Jocshan , Braun Ursula , Leitges Michael
Published: January 2025

Cell immortalization corresponds to a biologically relevant clinical feature that allows cells to acquire a high proliferative potential during carcinogenesis. In multiple cancer types, Protein Kinase D3 (PKD3) has often been reported as a dysregulated oncogenic kinase that promotes cell proliferation. Using mouse embryonic fibroblasts (MEFs), in a spontaneous immortalization model, PKD3 has been demonstrated as a critical regulator of cell proliferation after immortalization. However, the mechanisms by which PKD3 regulates proliferation in immortalized MEFs require further elucidation. Using a previously validated Prkd3-deficient MEF model, we performed a poly-A transcriptomic analysis to identify putative Prkd3-regulated biological processes and downstream targets in MEFs after spontaneous immortalization. To this end, differentially expressed genes (DEGs) were identified and further analyzed by gene ontology (GO) enrichment and protein–protein interaction (PPI) network analyses to identify potential hub genes. Our results suggest that Prkd3 modulates proliferation through the regulation of gene expression associated with glucose metabolism (Tnf, Ucp2, Pgam2, Angptl4), calcium homeostasis and transport (Calcr and P2rx7) and microtubule dynamics (Stmn2 and Map10). These candidate processes and associated genes represent potential mechanisms involved in Prkd3-induced proliferation in spontaneously immortalized cells as well as clinical targets in several cancer types.
Correction: Hu et al. Dynamics of Nanomotors Propelled by Enzyme Cascade Reactions. Int. J. Mol. Sci. 2024, 25, 12586
Authors: Hu Jia-Qi , Zhao Rui , Cui Ru-Fei , Kou Jian-Long , Chen Jiang-Xing
Published: January 2025

There was an error in the original publication [...]
The Pentose Phosphate Pathway: From Mechanisms to Implications for Gastrointestinal Cancers
Authors: Qiao Jincheng , Yu Zhengchen , Zhou Han , Wang Wankun , Wu Hao , Ye Jun
Published: January 2025

The pentose phosphate pathway (PPP), traditionally recognized for its role in generating nicotinamide adenine dinucleotide phosphate (NADPH) and ribose-5-phosphate (R5P), has emerged as a critical metabolic hub with involvements in various gastrointestinal (GI) cancers. The PPP plays crucial roles in the initiation, development, and tumor microenvironment (TME) of GI cancers by modulating redox homeostasis and providing precursors for nucleotide biosynthesis. Targeting PPP enzymes and their regulatory axis has been a potential strategy in anti-GI cancer therapies. In this review, we summarize the regulatory mechanisms of PPP enzymes, elucidate the relationships between the PPP and TME’s elements, and discuss the therapeutic potential of targeting the PPP in GI cancers.
The AP2/ERF Transcription Factor ERF56 Negatively Regulating Nitrate-Dependent Plant Growth in Arabidopsis
Authors: Yao Guoqi , Mu Chunhua , Yan Zhenwei , Ma Shijun , Liu Xia , Sun Yue , Hou Jing , Liu Qiantong , Cao Bing , Shan Juan , Leng Bingying
Published: January 2025

ERF56, a member of the APETALA2/ETHYLENE-RESPONSIVE FACTOR (AP2/ERF) transcription factor (TF) family, was reported to be an early nitrate-responsive TF in Arabidopsis. But the function of ERF56 in nitrate signaling remains not entirely clear. This study aimed to investigate the role of ERF56 in nitrate-dependent plant growth and nitrate signaling. We confirmed with reverse transcription quantitative PCR (RT-qPCR) that the transcription of ERF56 is quickly induced by nitrate. ERF56 overexpressors displayed decreased nitrate-dependent plant growth, while erf56 mutants exhibited increased plant growth. Confocal imaging demonstrated that ERF56 is localized into nuclei. Assays with the glucuronidase (GUS) reporter showed that ERF56 is mainly expressed at the region of maturation of roots and in anthers. The dual-luciferase assay manifested that the transcription of ERF56 is not directly regulated by NIN-LIKE PROTEIN 7 (NLP7). The transcriptome analysis identified 1038 candidate genes regulated by ERF56 directly. A gene ontology (GO) over-representation analysis showed that ERF56 is involved in the processes of water transport, inorganic molecule transmembrane transport, secondary metabolite biosynthesis, and cell wall organization. We revealed that ERF56 represses nitrate-dependent growth through regulating the processes of inorganic molecule transmembrane transport, the secondary metabolite biosynthesis, and cell wall organization.
COVID-19: Lessons Learned from Molecular and Clinical Research
Authors: Rizzi Manuela , Sainaghi Pier Paolo
Published: January 2025

SARS-CoV-2 virus, the etiological agent of the novel coronavirus disease 19 (COVID-19), was first identified in late 2019, following the sudden appearance of a cluster of pneumonia cases of unknown origin in China [...]
Viability and Radiosensitivity of Human Tumor Cells from Breast and Colon Are Influenced by Hypericum perforatum Extract HP01
Authors: Haake Linda Rebecca , El Menuawy Ahmed , Rennau Hannes , Marthe Frank , Hähnel Urs , Bock Felix , Hildebrandt Guido , Manda Katrin
Published: January 2025

To enhance the treatment of tumors that are resistant to radio- and chemotherapy while minimizing the side effects of radiochemotherapy, researchers are continuously seeking new active compounds for use in combination with radiotherapy. Therefore, the aim of our study was to examine the cytotoxic and radiosensitizing effects of an extract from St. John’s Wort (Hypericum perforatum), referred to as HP01, on human epithelial tumor cells in vitro. The growth of MCF-7 (breast carcinoma) and HT-29 (colon carcinoma) cells was examined under the influence of HP01. In combination with radiation, the effects of HP01 on cytotoxicity and long-term survival were assessed using a colony formation assay. The number of DNA double-strand breaks was analyzed using the γH2AX assay, while cell cycle distribution was examined via flow cytometry. A growth-inhibiting and cytotoxic effect was observed for both tumor cell lines starting at a concentration of 10 µg/mL HP01. Treatment with HP01 resulted in an inhibition of clonogenic survival of tumor cells after ionizing radiation (6 Gy). The number of DNA double-strand breaks (DSBs) in tumor cells increased with HP01 treatment, but the repair of radiation-induced DNA DSBs was not affected. Cell cycle analysis revealed that HP01, in addition to radiation, enhanced G2/M arrest in MCF-7 and HT-29 cells. Overall, HP01 not only showed a growth-inhibiting effect but also demonstrated a radiosensitizing effect on human tumor cells for the first time. We conclude that the HP01-induced G2/M accumulation of cells may be the main rationale for the drug-induced radiosensitivity. It is therefore a promising candidate for combined therapy in tumor diseases and warrants further investigation.
Identification of Immune Infiltration-Associated CC Motif Chemokine Ligands as Biomarkers and Targets for Colorectal Cancer Prevention and Immunotherapy
Authors: Liu Minghao , Wang Teng , Li Mingyang
Published: January 2025

Colorectal cancer (CRC) is the third most common cancer globally, with limited effective biomarkers and sensitive therapeutic targets. An increasing number of studies have highlighted the critical role of tumor microenvironment (TME) imbalances, particularly immune escape due to impaired chemokine-mediated trafficking, in tumorigenesis and progression. Notably, CC chemokines (CCLs) have been shown to either promote or inhibit angiogenesis, metastasis, and immune responses in tumors, thereby influencing cancer development and patient outcomes. However, the diagnostic and prognostic significance of CCLs in CRC remains unclear. In this study, multiple online tools for bioinformatics analyses were utilized. The findings revealed that the mRNA expression levels of CCL3, CCL4, and CCL26 were significantly elevated in CRC tissues compared to normal tissues, whereas CCL2, CCL5, CCL11, CCL21, and CCL28 mRNA levels were markedly downregulated. Additionally, dysregulation of CCL4, CCL5, and CCL21 was strongly associated with clinical staging, and elevated levels of CCL4, CCL11, and CCL28 were linked to significantly prolonged survival in CRC patients. Functional enrichment analysis indicated that the cellular roles of CCLs were predominantly associated with the chemokine, Wnt, and Toll-like receptor signaling pathways, as well as protein kinase activity. Furthermore, transcriptional regulation of most CCLs involved RELA and NFKB1. Key downstream targets included members of the SRC family of tyrosine kinases (HCK, LYN, and LCK), serine/threonine kinases (ATR and ATM), and others such as CSNK1G2, NEK2, and CDK2. Moreover, CCLs (CCL2, CCL3, CCL4, CCL5, CCL11, CCL21, and CCL28) exhibited strong correlations with major infiltration-related immune cells, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. In conclusion, our study provides novel insights into the potential utility of CCLs as biomarkers and therapeutic targets for CRC prevention and immunotherapy.
Impact of Water Stress on Metabolic Intermediates and Regulators in Broccoli Sprouts, and Cellular Defense Potential of Their Extracts
Authors: Šola Ivana , Gmižić Daria , Miškec Karlo , Ludwig-Müller Jutta
Published: January 2025

Drought and flood (water stress) alter plant metabolism, impacting the phytochemical content and biological effects. Using spectrophotometric, HPLC, and electrophoretic methods, we analyze the effects of water stress on broccoli (Brassica oleracea L. convar. botrytis (L.) Alef. var. cymosa Duch.) sprouts. Drought and flood differently influenced chlorophylls, carotenoids, and porphyrins, with drought having a stronger inhibitory effect on chlorophyll a, total chlorophyll, and porphyrins. Carotenoids and glucosinolates increased under drought but decreased with flooding, suggesting that these compounds play a crucial role in drought tolerance. Nitrate increased with drought from 13.11 ± 1.05 mg/g dw to 22.41 ± 1.20 mg/g dw but decreased under flooding to 5.17 ± 1.03 mg/g dw, and oxalic acid was reduced by drought only (from 48.94 ± 1.30 mg/g dw to 46.43 ± 0.64 mg/g dw). Flood reduced proteins by 29%, phenolics by 15%, flavonoids by 10%, flavonols by 11%, tannins by 36%, and proanthocyanidins by 19%, while drought decreased flavonoids by 23%. Total phenolics and proanthocyanidins were increased by drought by 29% and 7%, respectively, while flooding decreased hydroxycinnamic acids by 13%. Both stress types influenced individual polyphenols differently: drought diminished ferulic acid by 17% and increased sinapic acid by 30%, while flooding reversed these effects and enhanced kaempferol by 22%. These compounds, along with proline (which increased by 139% under drought), emerged as biomarkers of water stress. Flood impacted antioxidant capacity more significantly, while drought-stressed broccoli extracts better protected plasmid DNA against oxidative damage. These findings underline the metabolic plasticity of broccoli sprouts and their potential in targeted crop management for water stress resilience.
Chinese Mathematical Knowledge Entity Recognition Based on Linguistically Motivated Bidirectional Encoder Representation from Transformers
Authors: Song Wei , Zheng He , Ma Shuaiqi , Zhang Mingze , Guo Wei , Ning Keqing
Published: January 2025

We assessed whether constructing a mathematical knowledge graph for a knowledge question-answering system or a course recommendation system, Named Entity Recognition (NER), is indispensable. The accuracy of its recognition directly affects the actual performance of these subsequent tasks. In order to improve the accuracy of mathematical knowledge entity recognition and provide effective support for subsequent functionalities, this paper adopts the latest pre-trained language model, LERT, combined with a Bidirectional Gated Recurrent Unit (BiGRU), Iterated Dilated Convolutional Neural Networks (IDCNNs), and Conditional Random Fields (CRFs), to construct the LERT-BiGRU-IDCNN-CRF model. First, LERT provides context-related word vectors, and then the BiGRU captures both long-distance and short-distance information, the IDCNN retrieves local information, and finally the CRF is decoded to output the corresponding labels. Experimental results show that the accuracy of this model when recognizing mathematical concepts and theorem entities is 97.22%, the recall score is 97.47%, and the F1 score is 97.34%. This model can accurately recognize the required entities, and, through comparison, this method outperforms the current state-of-the-art entity recognition models.
Temperature and Host Fruit During Immature Development Shape Adult Life History Traits of Different Ceratitis capitata Populations
Authors: Papadogiorgou Georgia D. , Papadopoulos Nikos T.
Published: January 2025

Temperature and host fruit availability are key factors influencing the life history traits of the Mediterranean fruit fly (medfly) (Ceratitis capitata). This study examines how developmental temperature and host fruit type affect adult longevity and fecundity in medflies from six populations spanning Southern to Central Europe. Larvae were reared on apples and bitter oranges at three constant temperatures (15, 20, and 25 °C), with pupae maintained under the same thermal conditions until adult emergence. Adults were then kept at 25 °C, with longevity and fecundity recorded daily. The results showed that higher developmental temperatures increased adult lifespan across all populations, regardless of host fruit. Similarly, fecundity rates in ovipositing females were higher at higher temperatures. Reproductive periods (pre-oviposition, oviposition, and post-oviposition) varied among populations, indicating population-specific responses. These findings underscore how temperature and host fruit availability shape medfly invasion dynamics, highlighting the species’ biological plasticity and adaptation to different environments. This research provides valuable insights for pest management, particularly in the context of climate change, offering strategies to mitigate the spread of medflies into new regions.
Advancing Food Security with Farmed Edible Insects: Economic, Social, and Environmental Aspects
Authors: Aguilar-Toalá José E. , Vidal-Limón Abraham M. , Liceaga Andrea M.
Published: January 2025

Farmed edible insects are considered a potential resource to help address food security concerns toward the year 2050. The sustainability (e.g., lower environmental impact), nutritional (e.g., high-quality proteins, essential amino acids, fiber, unsaturated fats, vitamins, and minerals) and health (e.g., antioxidant, antihypertensive, anti-inflammatory, antimicrobial, and immunomodulatory) benefits are the main reasons for the rise in interest for insects as alternative protein sources for food and feed production. Thus, edible insects can address the future global protein demand of an ever-increasing world population. In this context, several aspects related to their sustainability have been explored and addressed from an environmental perspective. This review describes the rationale for using insects as alternative protein sources and provides a comprehensive viewpoint, integrating economic, environmental, and social aspects into their sustainability framework toward addressing food insecurity concerns. For example, edible insects offer a more sustainable protein source comparable to, or even better than, that of conventional livestock. Considering their sustainability advantages, insects are noted for their lower impact on natural resources (e.g., water and agrarian land) and lower greenhouse gas emissions (e.g., carbon dioxide and methane). From a socioeconomic point of view, edible insects have lower production costs compared to conventional animal protein sources because of their high feed efficiency conversion, rapid growth rate, and short life cycles. Currently, the market for edible, farmed insects is becoming a significant economic activity that not only meets the needs of industry and consumers but also supports the ability of future generations to maintain a secure and sustainable community.
Effective Mixed-Type Tissue Crusher and Simultaneous Isolation of RNA, DNA, and Protein from Solid Tissues Using a TRIzol-Based Method
Authors: Santos Kelly Karoline dos , Daniel Isabelle Watanabe , Delabio Letícia Carani , Costa Manoella Abrão da , Dutra Júlia de Paula , Ruginsk Bruna Estelita , Nardin Jeanine Marie , Campos Louryana Padilha , Rego Fabiane Gomes de Moraes , Picheth Geraldo , Valdameri Glaucio , Moure Vivian Rotuno
Published: January 2025

One of the major challenges of studying biomarkers in tumor samples is the low quantity and quality of isolated RNA, DNA, and proteins. Additionally, the extraction methods ideally should obtain macromolecules from the same tumor biopsy, allowing better-integrated data interpretation. In this work, an in-house, low-cost, mixed-type tissue crusher combining blade and beating principles was made and the simultaneous isolation of macromolecules from human cells and tissues was achieved using TRIzol. RT-qPCR, genotyping, SDS-PAGE, and Western blot analysis were used to validate the approach. For tissue samples, RNA, DNA, and proteins resulted in an average yield of 677 ng/mg, 225 ng/mg, and 1.4 µg/mg, respectively. The same approach was validated using cell lines. The isolated macromolecule validation included the detection of mRNA levels of ATP-binding cassette (ABC) transporters through RT-qPCR, genotyping of TNFR1 (rs767455), and protein visualization through SDS-PAGE following Coomassie blue staining and Western blot. This work contributed to filling a gap in knowledge about TRIzol efficiency for the simultaneous extraction of RNA, DNA, and proteins from a single human tissue sample. A low-cost, high yield, and quality method was validated using target biomarkers of multidrug resistance mechanisms. This approach might be advantageous for future biomarker studies using different tissue specimens.
Guided Personalized Surgery (GPS) in Posterostabilized Total Knee Replacement: A Radiological Study
Authors: de Andrés-Torán Ana , Padilla-Eguiluz Norma G. , Hernández-Esteban Pablo , Gómez-Barrena Enrique
Published: January 2025

Background: Surgical accuracy in total knee replacement (TKR) may vary with the surgeon, the patient preoperative deformity, and the guiding system to perform the procedure. Navigation systems attempt to increase the intraoperative information the surgeon requires to make the appropriate decisions, sometimes associating cumbersome procedures and unclear effectiveness to place the implant more precisely than conventional instruments. Methods: We conducted a retrospective case-control study with prospective data collection of radiographic measurements (alignment, joint line and patellar height) in a sample of 100 consecutive patients receiving TKR Optetrak Logic PS, either with standard surgical technique with Trulion Instrumentation (n = 59) or with the Guided Personalized Surgery (GPS) system (n = 41). Results: The GPS group improved the alignment of the mechanical Lateral Distal Femoral Angle (mLDFA) in 1.6° compared to the control (p = 0.003), but not evident in the mechanical Medial Proximal Tibial Angle (mMPTA) (p = 0.132). The GPS system achieved a normal patellar height in 98% of cases, according to the Blackburne–Peel Index (BP), compared to 71% in the control group (p = 0.002). This was obtained in the femoral side, as measured in the Epicondylar Ratio (ER) (p = 0.004). A lower dispersion of postoperative measurements was observed in the GPS group in comparison with the control, being statistically significant in mMPTA (p = 0.000), CD-Index (p = 0.011), IS-Index (p = 0.002), mIS-Index (p = 0.008), BP-Index (p = 0.011), and ER (p = 0.004). Conclusions: Better post-surgical restoration of joint line and patellar height is observed in surgeries performed with the GPS system, as well as a tendency to more accurate mechanical alignment and lower inter-patient variability, suggesting higher reproducibility.
Positive Intraoperative Bile Culture and Antibiotic Resistance Increase the Risk of Pancreatic Fistula in Patients After Pancreatoduodenectomy
Authors: Hoffmann Michael , Anthuber Lena , Anthuber Matthias , Pinto David , Schrempf Matthias
Published: January 2025

Background/Objectives: A positive intraoperative bile culture (bacterobilia) is considered to be a risk factor for increased morbidity after pancreatoduodenectomy. The aim of our study was to describe the frequency of bacterobilia with a special emphasis on antibiotic resistance and to analyze the association of these findings with postoperative complications, in particular with postoperative pancreatic fistula. Methods: From a prospective database, patients with available intraoperative bile cultures (n = 95) were selected and analyzed. Microbiological test results reported the type of bacteria as well as sensitivity and resistance patterns. Associations between culture results, antibiotic resistance, and postoperative outcomes were assessed. Results: Among 95 patients that were included in this trial, 71 (74.7%) had a positive bile culture. A total of 29.6% (21/71) of patients with positive bile cultures developed POPF grade B/C compared to 8.3% (2/24) of patients with negative bile cultures (p = 0.052). The difference in CR-POPF became statistically significant when at least one of the isolated microorganisms was resistant to ampicillin/sulbactam, the perioperative antibiotic administered for prophylaxis. CR-POPF was diagnosed in 38.5% (15/39) of patients with antibiotic resistance vs. 14.3% (8/56) of patients without resistant microorganisms (p = 0.007). We also identified the isolation of Enterococcus spp. (p = 0.006), resistant Enterobacter (p = 0.031), or resistant Escherichia coli (p = 0.027) as risk factors for pancreatic fistula. Conclusions: The isolation of antibiotic-resistant strains in a positive bile culture is a major risk factor for the development of pancreatic fistula after pancreatoduodenectomy. The most relevant bacteria in our study were Enterococcus spp., Enterobacter cloacae, and Escherichia coli. Thus, broad-spectrum antimicrobial prophylaxis with efficacy against these microorganisms and with low resistance rates should be routinely administered perioperatively.