bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal stem cells: guardians of homeostasis in health and aging amid environmental challenges
Authors: Choi Jiahn , Augenlicht Leonard H. 
Published: March 2024

AbstractThe intestinal epithelium is the first line of defense and acts as an interface between the vast microbial world within the gastrointestinal tract and the body’s internal milieu. The intestinal epithelium not only facilitates nutrient absorption but also plays a key role in defending against pathogens and regulating the immune system. Central to maintaining a healthy epithelium are intestinal stem cells (ISCs), which are essential for replenishing the intestinal epithelium throughout an individual’s lifespan. Recent research has unveiled the intricate interplay between ISCs and their niche, which includes various cell types, extracellular components, and signaling molecules. In this review, we delve into the most recent advances in ISC research, with a focus on the roles of ISCs in maintaining mucosal homeostasis and how ISC functionality is influenced by the niche environment. In this review, we explored the regulatory mechanisms that govern ISC behavior, emphasizing the dynamic adaptability of the intestinal epithelium in the face of various challenges. Understanding the intricate regulation of ISCs and the impact of aging and environmental factors is crucial for advancing our knowledge and developing translational approaches. Future studies should investigate the interactive effects of different risk factors on intestinal function and develop strategies for improving the regenerative capacity of the gut.
Portable dielectrophoresis for biology: ADEPT facilitates cell trapping, separation, and interactions
Authors: Julius Lourdes Albina Nirupa , Akgül Dora , Krishnan Gowri , Falk Fabian , Korvink Jan , Badilita Vlad 
Published: March 2024

AbstractDielectrophoresis is a powerful and well-established technique that allows label-free, non-invasive manipulation of cells and particles by leveraging their electrical properties. The practical implementation of the associated electronics and user interface in a biology laboratory, however, requires an engineering background, thus hindering the broader adoption of the technique. In order to address these challenges and to bridge the gap between biologists and the engineering skills required for the implementation of DEP platforms, we report here a custom-built, compact, universal electronic platform termed ADEPT (adaptable dielectrophoresis embedded platform tool) for use with a simple microfluidic chip containing six microelectrodes. The versatility of the open-source platform is ensured by a custom-developed graphical user interface that permits simple reconfiguration of the control signals to address a wide-range of specific applications: (i) precision positioning of the single bacterium/cell/particle in the micrometer range; (ii) viability-based separation by achieving a 94% efficiency in separating live and dead yeast; (iii) phenotype-based separation by achieving a 96% efficiency in separating yeast and Bacillus subtilis; (iv) cell–cell interactions by steering a phagocytosis process where a granulocyte engulfs E. coli RGB-S bacterium. Together, the set of experiments and the platform form a complete basis for a wide range of possible applications addressing various biological questions exploiting the plug-and-play design and the intuitive GUI of ADEPT.
Designing patient-oriented combination therapies for acute myeloid leukemia based on efficacy/toxicity integration and bipartite network modeling
Authors: Mirzaie Mehdi , Gholizadeh Elham , Miettinen Juho J. , Ianevski Filipp , Ruokoranta Tanja , Saarela Jani , Manninen Mikko , Miettinen Susanna , Heckman Caroline A. , Jafari Mohieddin 
Published: March 2024

AbstractAcute myeloid leukemia (AML), a heterogeneous and aggressive blood cancer, does not respond well to single-drug therapy. A combination of drugs is required to effectively treat this disease. Computational models are critical for combination therapy discovery due to the tens of thousands of two-drug combinations, even with approved drugs. While predicting synergistic drugs is the focus of current methods, few consider drug efficacy and potential toxicity, which are crucial for treatment success. To find effective new drug candidates, we constructed a bipartite network using patient-derived tumor samples and drugs. The network is based on drug-response screening and summarizes all treatment response heterogeneity as drug response weights. This bipartite network is then projected onto the drug part, resulting in the drug similarity network. Distinct drug clusters were identified using community detection methods, each targeting different biological processes and pathways as revealed by enrichment and pathway analysis of the drugs’ protein targets. Four drugs with the highest efficacy and lowest toxicity from each cluster were selected and tested for drug sensitivity using cell viability assays on various samples. Results show that ruxolitinib-ulixertinib and sapanisertib-LY3009120 are the most effective combinations with the least toxicity and the best synergistic effect on blast cells. These findings lay the foundation for personalized and successful AML therapies, ultimately leading to the development of drug combinations that can be used alongside standard first-line AML treatment.
Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases
Authors: Qian Lu , Zhu Yanli , Deng Chao , Liang Zhenxing , Chen Junmin , Chen Ying , Wang Xue , Liu Yanqing , Tian Ye , Yang Yang 
Published: March 2024

AbstractPeroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1β, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators of many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, and inflammation. Accumulating evidence has shown that PGC-1s are implicated in many diseases, such as cancers, cardiac diseases and cardiovascular diseases, neurological disorders, kidney diseases, motor system diseases, and metabolic disorders. Examining the upstream modulators and co-activated partners of PGC-1s and identifying critical biological events modulated by downstream effectors of PGC-1s contribute to the presentation of the elaborate network of PGC-1s. Furthermore, discussing the correlation between PGC-1s and diseases as well as summarizing the therapy targeting PGC-1s helps make individualized and precise intervention methods. In this review, we summarize basic knowledge regarding the PGC-1s family as well as the molecular regulatory network, discuss the physio-pathological roles of PGC-1s in human diseases, review the application of PGC-1s, including the diagnostic and prognostic value of PGC-1s and several therapies in pre-clinical studies, and suggest several directions for future investigations. This review presents the immense potential of targeting PGC-1s in the treatment of diseases and hopefully facilitates the promotion of PGC-1s as new therapeutic targets.
A rapid identification method for soft tissue markers of dentofacial deformities based on heatmap regression
Authors: Zhou Guilong , Zhang Yu , Zhao Jinlong , Tian Lei , Jia Guang , Ma Qin 
Published: March 2024

Abstract
Objective
The purpose of this study was to construct a facial deformity dataset and a network model based on heatmap regression for the recognition of facial soft tissue landmarks to provide a basis for clinicians to perform cephalometric analysis of soft tissue.

Materials and methods
A 34-point face marker detection model, the Back High-Resolution Network (BHR-Net), was constructed based on the heatmap regression algorithm, and a custom dataset of 1780 facial detection images for orthognathic surgery was collected. The mean normalized error (MNE) and 10% failure rate (FR10%) were used to evaluate the performance of BHR-Net, and a test set of 50 patients was used to verify the accuracy of the landmarks and their measurement indicators. The test results were subsequently validated in 30 patients.

Results
Both the MNE and FR10% of BHR-Net were optimal compared with other models. In the test set (50 patients), the accuracy of the markers excluding the nose root was 86%, and the accuracy of the remaining markers reached 94%. In the model validation (30 patients), using the markers detected by BHR-Net, the diagnostic accuracy of doctors was 100% for Class II and III deformities, 100% for the oral angle plane, and 70% for maxillofacial asymmetric deformities.

Conclusions
BHR-Net, a network model based on heatmap regression, can be used to effectively identify landmarks in maxillofacial multipose images, providing a reliable way for clinicians to perform cephalometric measurements of soft tissue objectively and quickly.
AIM2 regulates autophagy to mitigate oxidative stress in aged mice with acute liver injury
Authors: Hu Chao , Li Mengjing , Chen Yongzhen , Cheng Wei , Wang Haining , Zhou Yiming , Teng Fengmeng , Ling Tao , Pan Jinshun , Xu Haozhe , Zheng Yanan , Ji Guozhong , Zhao Ting , You Qiang 
Published: March 2024

AbstractThe cytoplasmic pattern recognition receptor, absent in melanoma 2 (AIM2), detects cytosolic DNA, activating the inflammasome and resulting in pro-inflammatory cytokine production and pyroptotic cell death. Recent research has illuminated AIM2’s contributions to PANoptosis and host defense. However, the role of AIM2 in acetaminophen (APAP)-induced hepatoxicity remains enigmatic. In this study, we unveil AIM2’s novel function as a negative regulator in the pathogenesis of APAP-induced liver damage in aged mice, independently of inflammasome activation. AIM2-deficient aged mice exhibited heightened lipid accumulation and hepatic triglycerides in comparison to their wild-type counterparts. Strikingly, AIM2 knockout mice subjected to APAP overdose demonstrated intensified liver injury, compromised mitochondrial stability, exacerbated glutathione depletion, diminished autophagy, and elevated levels of phosphorylated c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). Furthermore, our investigation revealed AIM2’s mitochondrial localization; its overexpression in mouse hepatocytes amplified autophagy while dampening JNK phosphorylation. Notably, induction of autophagy through rapamycin administration mitigated serum alanine aminotransferase levels and reduced the necrotic liver area in AIM2-deficient aged mice following APAP overdose. Mechanistically, AIM2 deficiency exacerbated APAP-induced acute liver damage and inflammation in aged mice by intensifying oxidative stress and augmenting the phosphorylation of JNK and ERK. Given its regulatory role in autophagy and lipid peroxidation, AIM2 emerges as a promising therapeutic target for age-related acute liver damage treatment.
SOX2 and OCT4 mediate radiation and drug resistance in pancreatic tumor organoids
Authors: Roy Sanjit , Dukic Tijana , Keepers Zachery , Bhandary Binny , Lamichhane Narottam , Molitoris Jason , Ko Young H. , Banerjee Aditi , Shukla Hem D. 
Published: March 2024

AbstractPancreatic cancer has a five-year survival rate of only 10%, mostly due to late diagnosis and limited treatment options. In patients with unresectable disease, either FOLFIRINOX, a combination of 5-fluorouracil (5-FU), oxaliplatin and irinotecan, or gemcitabine plus nab-paclitaxel combined with radiation are frontline standard regimens. However, chemo-radiation therapy has shown limited success because patients develop resistance to chemotherapy and/or radiation. In this study, we evaluated the role of pancreatic cancer stem cells (CSC) using OCT4 and SOX2, CSC markers in mouse pancreatic tumor organoids. We treated pancreatic tumor organoids with 4 or 8 Gy of radiation, 10 μM of 5-FU (5-Fluorouracil), and 100 μM 3-Bromopyruvate (3BP), a promising anti-cancer drug, as a single treatment modalities, and in combination with RT. Our results showed significant upregulation of, OCT4, and SOX2 expression in pancreatic tumor organoids treated with 4 and 8 Gy of radiation, and downregulation following 5-FU treatment. The expression of CSC markers with increasing treatment dose exhibited elevated upregulation levels to radiation and downregulation to 5-FU chemotherapy drug. Conversely, when tumor organoids were treated with a combination of 5-FU and radiation, there was a significant inhibition in SOX2 and OCT4 expression, indicating CSC self-renewal inhibition. Noticeably, we also observed that human pancreatic tumor tissues exhibited heterogeneous and aberrant OCT4 and SOX2 expression as compared to normal pancreas, indicating their potential role in pancreatic cancer growth and therapy resistance. In addition, the combination of 5-FU and radiation treatment exhibited significant inhibition of the β-catenin pathway in pancreatic tumor organoids, resulting in sensitization to treatment and organoid death. In conclusion, our study emphasizes the crucial role of CSCs in therapeutic resistance in PC treatment. We recommend using tumor organoids as a model system to explore the impact of CSCs in PC and identify new therapeutic targets.
Coculture with macrophages alters ferroptosis susceptibility of triple-negative cancer cells
Authors: Konishi Hiroto , Haga Yuya , Okumura Moe , Tsujino Hirofumi , Higashisaka Kazuma , Tsutsumi Yasuo 
Published: March 2024

AbstractVarious treatment options, such as molecular targeted drugs and immune checkpoint blockades, are available for patients with cancer. However, some cancer types are refractory to molecular targeted therapies or acquire drug resistance after long-term treatment. Thus, ferroptosis, a newly defined type of programmed cell death caused by the iron-dependent accumulation of lipid peroxidation, has gained attention as a novel cancer treatment strategy. Understanding cell–cell interactions in the tumor microenvironment is important for the clinical application of ferroptosis inducers. However, the effects of cell–cell interactions on ferroptosis sensitivity remain unclear. Thus, we aimed to evaluate the effects of macrophage–cancer cell interactions on ferroptosis induction. Coculture experiments showed that conditioned medium prepared from macrophages did not alter the ferroptosis sensitivity of cancer cells. By contrast, coculture via transwell, which enables cell–cell interactions through secretion, increased the sensitivity of cancer cells to ferroptosis inducers. Additionally, direct coculture increased the susceptibility of cancer cells to RSL3-induced ferroptosis. Mechanistically, coculture with macrophages upregulated the levels of intracellular ferrous ions and lipid peroxidation in cancer cells. These findings provide novel insights into the mechanisms by which cell–cell interactions influence ferroptosis induction and application of ferroptosis inducers as a cancer treatment option.
Optimization of an in vitro Pseudomonas aeruginosa Biofilm Model to Examine Antibiotic Pharmacodynamics at the Air-Liquid Interface
Authors: Tan Xing , Huang Yanqin , Rana Amisha , Singh Nidhi , Abbey Taylor C. , Chen Hui , Toth Peter T. , Bulman Zackery P. 
Published: March 2024

AbstractPseudomonas aeruginosa is an important cause of lower respiratory tract infections, such as ventilator-associated bacterial pneumonia (VABP). Using inhaled antibiotics to treat VABP can achieve high drug concentrations at the infection site while minimizing systemic toxicities. Despite the theoretical advantages, clinical trials have failed to show a benefit for inhaled antibiotic therapy in treating VABP. A potential reason for this discordance is the presence of biofilm-embedded bacteria in lower respiratory tract infections. Drug selection and dosing are often based on data from bacteria grown planktonically. In the present study, an in vitro air-liquid interface pharmacokinetic/pharmacodynamic biofilm model was optimized to evaluate the activity of simulated epithelial lining fluid exposures of inhaled and intravenous doses of polymyxin B and tobramycin against two P. aeruginosa strains. Antibiotic activity was also determined against the P. aeruginosa strains grown planktonically. Our study revealed that inhaled antibiotic exposures were more active than their intravenous counterparts across biofilm and planktonic populations. Inhaled exposures of polymyxin B and tobramycin exhibited comparable activity against planktonic P. aeruginosa. Although inhaled polymyxin B exposures were initially more active against P. aeruginosa biofilms (through 6 h), tobramycin was more active by the end of the experiment (48 h). Together, these data slightly favor the use of inhaled tobramycin for VABP caused by biofilm-forming P. aeruginosa that are not resistant to either antibiotic. The optimized in vitro air-liquid interface pharmacokinetic/pharmacodynamic biofilm model may be beneficial for the development of novel anti-biofilm agents or to optimize antibiotic dosing for infections such as VABP.
Effects of plasma treatment on biodegradation of natural and synthetic fibers
Authors: Nyssanbek Marzhan , Kuzina Natalya , Kondrashchenko Valery , Azimov Abdugani 
Published: March 2024

AbstractThis study investigates the application of plasma treatment as a means to enhance biodegradation and modify the structural characteristics of fibrous composites. The methodological component of the study includes the selection of the research object; production of composites; low-temperature plasma treatment, and treatment of biodegradability and mechanical strength of samples. The strengthening of fibers with cellulose leads to a significant improvement in mechanical strength. Such an indicator as mechanical strength increases from 18 to 21 MPa. Treatment of natural fibers with low-temperature plasma led to an increase in mechanical strength from 18 to 25 MPa. Treating reinforced fibers with low-temperature plasma currently results in an even greater enhancement in mechanical strength, increasing from 18 to 29 MPa.The electron microscopy of samples reveals some differences in cell wall microfibrils between plasma-treated and non-treated samples. The non-treated fibres are found to have chips and voids. Meantime, the plasma-treated fibres show structural changes in certain regions which resemble wood charring. Through a comprehensive analysis, this research underscores the substantial impact of plasma treatment on the degradation kinetics and morphological features of cellulose-based composites. The results reveal distinct alterations in the composition and behavior of plasma-treated fibres, signifying a shift towards enhanced biodegradability. The natural fibres examined in this study contained 28–30% lignin, whereas the composites exhibited a lower lignin content of 21–23%. These findings corroborate the inference that plasma treatment induces significant changes in fibre structure, accelerating the biodegradation process by 7 days.
Denervation alters the secretome of myofibers and thereby affects muscle stem cell lineage progression and functionality
Authors: Henze Henriette , Hüttner Sören S. , Koch Philipp , Schüler Svenja C. , Groth Marco , von Eyss Björn , von Maltzahn Julia 
Published: March 2024

AbstractSkeletal muscle function crucially depends on innervation while repair of skeletal muscle relies on resident muscle stem cells (MuSCs). However, it is poorly understood how innervation affects MuSC properties and thereby regeneration of skeletal muscle. Here, we report that loss of innervation causes precocious activation of MuSCs concomitant with the expression of markers of myogenic differentiation. This aberrant activation of MuSCs after loss of innervation is accompanied by profound alterations on the mRNA and protein level. Combination of muscle injury with loss of innervation results in impaired regeneration of skeletal muscle including shifts in myogenic populations concomitant with delayed maturation of regenerating myofibers. We further demonstrate that loss of innervation leads to alterations in myofibers and their secretome, which then affect MuSC behavior. In particular, we identify an increased secretion of Osteopontin and transforming growth factor beta 1 (Tgfb1) by myofibers isolated from mice which had undergone sciatic nerve transection. The altered secretome results in the upregulation of early activating transcription factors, such as Junb, and their target genes in MuSCs. However, the combination of different secreted factors from myofibers after loss of innervation is required to cause the alterations observed in MuSCs after loss of innervation. These data demonstrate that loss of innervation first affects myofibers causing alterations in their secretome which then affect MuSCs underscoring the importance of proper innervation for MuSC functionality and regeneration of skeletal muscle.
Inflammation-suppressing cornea-in-a-syringe with anti-viral GF19 peptide promotes regeneration in HSV-1 infected rabbit corneas
Authors: Simoliunas Egidijus , Ruedas-Torres Inés , Jiménez-Gómez Yolanda , Edin Elle , Aghajanzadeh-Kiyaseh Mozhgan , Zamani-Roudbaraki Mostafa , Asoklis Rimvydas , Alksne Milda , Thathapudi Neethi C. , Poudel Bijay K. , Rinkunaite Ieva , Asoklis Kasparas , Iesmantaite Monika , Ortega-Llamas Laura , Makselis Almantas , Munoz Marcelo , Baltriukiene Daiva , Bukelskiene Virginija , Gómez-Laguna Jaime , González-Andrades Miguel , Griffith May 
Published: March 2024

AbstractPathophysiologic inflammation, e.g., from HSV-1 viral infection, can cause tissue destruction resulting in ulceration, perforation, and ultimately blindness. We developed an injectable Cornea-in-a-Syringe (CIS) sealant-filler to treat damaged corneas. CIS comprises linear carboxylated polymers of inflammation-suppressing 2-methacryloyloxyethyl phosphorylcholine, regeneration-promoting collagen-like peptide, and adhesive collagen-citrate glue. We also incorporated GF19, a modified anti-viral host defense peptide that blocked HSV-1 activity in vitro when released from silica nanoparticles (SiNP-GF19). CIS alone suppressed inflammation when tested in a surgically perforated and HSV-1-infected rabbit corneal model, allowing tissue and nerve regeneration. However, at six months post-operation, only regenerated neocorneas previously treated with CIS with SiNP-GF19 had structural and functional features approaching those of normal healthy corneas and were HSV-1 virus-free. We showed that composite injectable biomaterials can be designed to allow regeneration by modulating inflammation and blocking viral activity in an infected tissue. Future iterations could be optimized for clinical application.