bluuebunny/crossref_metadata_2025 huggingface dataset:
2-Aminopiridin Türevleri ile 4-Kloro-5-sülfamoilbenzoik Asit Tuzlarının Sentezi, Karakterizasyonu ve Antimikrobiyal Özelliklerinin İncelenmesi
Authors: İlkimen Halil , Yenikaya Cengiz , Gülbandılar Aysel
Published: December 2024

Bu çalışmada, 4-kloro-5-sülfamoilbenzoik asit (HClsba) ile 2-aminopiridin (2ap), 2-amino-3-pikolin (2a3p), 2-amino-5-pikolin (2a5p) ve 2-amino-6-pikolin’in (2a6p) proton transfer tuzları (1-4) sentezlenmiştir. Sentezlenen bileşiklerin yapıları, 1H NMR, IR, elementel analiz ve UV ile açıklanmıştır. Çalışmada kullanılan ve sentezlenen tüm maddelerin $Candida$ $albicans$ (ATCC 14053) mayasına ve $Enterococcus$ $faecalis$ (ATCC 29212), $Staphylococcus$ $aureus$ (NRRL-B 767), $Bacillus$ $subtilis$, $Listeria$ $monocytogenes$ (ATCC 7644) (Gram pozitif), $Pseudomonas$ $aeruginosa$ (ATCC 27853) ve $Escherichia$ $coli$ (ATCC 25922) (Gram negatif) bakterilerine karşı antimikrobiyal aktiviteleri incelenmiştir. Antimikrobiyal aktiviteleri Flukonazol, Levofloksasin, Vankomisin ve Sefepim ile kıyaslanmıştır. Bileşiklerde en iyi aktivite değerleri $S.$ $aureus$ bakterisinde tüm bileşikler (HClsba hariç), $E.$ $coli$ bakterisinde HClsba ve 2ap, $P.$ $aeruginosa$ bakterisinde tüm bileşikler (2a6mp ve 3 hariç), $L.$ $monocytogenes$ bakterisinde HClsba, 2a3mp, 1, 3 ve 4, $E.$ $faecalis$ bakterisinde tüm bileşikler (3 hariç), $B.$ $subtilis$ bakterisinde 2a5mp ve $C.$ $albicans$ mayasında tüm bileşikler (3 hariç) gözlenmiştir.
Pelatihan Pembuatan Interactive Learning Module dengan Aplikasi Flipbook bagi Guru di SMA Negeri 1 Jonggol
Authors: Lumbantobing Septina Severina , Nugroho Andreas Rian , Guswantoro Taat , Saumanuk Theressa Eklesia , Nopemnanu Angriani , Hartoyo Joshua Dwi
Published: December 2024

Pendidikan abad 21 menuntut guru menguasai teknologi informasi dan komunikasi (ITC) yang mendukung proses pembelajaran. Guru-guru membutuhkan pelatihan dalam mengembangkan bahan ajar yang interaktif berupa elektronik modul dengan aplikasi flipbook. Flipbook mampu menggabungan teks dengan animasi, video, suara dan lain sebagainya, sehingga siswa tidak hanya dapat membaca buku tapi juga dapat berinteraksi dengan buku elektronik yang dimilikinya hal tersebut memudahkan siswa untuk belajar. Pengabdian Program Studi Pendidikan Fisika serta Bimbingan dan Konseling FKIP UKI berfokus pada menghasilkan media pembelajaran dengan memanfaatkan teknologi mengadakan Pelatihan Pembuatan Interactive Learning Module dengan Aplikasi Flipbook bagi Guru di SMA Negeri 1 Jonggol kepada para guru. Kegiatan ini berlangsung selama 2 hari dan diikuti oleh 61 orang guru. Pelatihan mendapatkan respon yang sangat baik dari guru peserta pelatihan. Dari hasil angket diperoleh respon dari peserta bahwa materi pelatihan memiliki kemampuan dalam menjawab kebutuhan guru, serta dapat disampaikan dengan kategori sangat baik (92.74%). Narasumber dinilai memiliki pemahaman, kemampuan dalam menyampaikan materi serta kemampuan dalam mengelola diskusi dengan sangat baik (93.05%). Secara keseluruhan peserta pelatihan merespon sangat baik (92.96%) terhadap terlaksananya kegiatan. Peserta kegiatan menyarankan agar memperhatikan spesifikasi komputer yang digunakan agar suport dengan software yang digunakan, pemilihan materi yang sesuai perkembangan teknologi khususnya kecerdasan buatan.
Kata Kunci: Flipbook; Media Pembelajaran; Alat Peraga; Pembelajaran.
HYPERBOLIC HORADAM SPINORS
Authors: Özçevik Selime Beyza , Dertli Abdullah , Karaahmetoğlu Savaş
Published: December 2024

In this study, a new definition of hyperbolic spinors is being introduced through a transformation from the Horadam split quaternion, which holds significant importance in both mathematics and physics. Subsequently, fundamental concepts such as conjugate and norm are elucidated. Leveraging the defined hyperbolic spinor and the recurrence relation of the Horadam sequence, a novel sequence is delineated, and its foundational equations, akin to generator function and Binet formula, are expressed through theorems.
Strategic Niche Management: past, present, and future
Authors: Raven Rob
Published: December 2024

Strategic Niche Management is one of four foundational frameworks of the field of sustainability transitions. Since its inception in the mid 1990s, the framework has evolved and expanded. Originally inspired by quasi-evolutionary theorising of technological change, SNM has incorporated and contributed to a range of contemporary debates in sustainability transitions, including the politics of transitions, institutional dynamics, and the geography of transitions. This chapter traces and summarises the key debates in the SNM literature and provides an overview of key challenges and ambiguities in applying SNM in practice. The chapter ends with four recommendations for future research related to behaviour, discontinuation, just transitions, and methodological considerations.
The rise of technological innovation systems in sustainability transitions
Authors: Van der Loos Adriaan , Elzinga Remi , Negro Simona , Hekkert Marko
Published: December 2024

Innovation systems take a holistic perspective to frame the dynamics that influence the emergence of innovation. Such systems consider a wide range of actors, institutions and networks to be the key structural building blocks. These structural elements interact, generating positive or negative feedback loops. Innovation systems initially emphasized the competitiveness of nations and were technology neutral. The introduction of technological innovation systems (TIS), the central focus of this book chapter, narrowed the lens to the emergence of specific technologies. In doing so, TIS became largely oriented towards sustainable technologies, which are often hard to bring to market. It hence became a foundational framework in the sustainability transitions research field. The introduction of the TIS ‘functions’, i.e., key dynamics, demonstrated a milestone in the development of the field. TIS has further grown, evolved and matured over the years and remains a popular theoretical lens to grasp the dynamics of innovation, engaging with subjects such as context and geography. Scholars continue to push the bounds of the many different innovation system frameworks, generating new empirical observations and furthering theory. Topics include system interaction, missions, life-cycles and destabilization, giving space to both technological and social innovation for a more sustainable future.
Soil degradation status in China
Authors: Muhammad Wajid Muhammad , Xiao Yannong
Published: December 2024

Soil degradation can be described as either erosion or salinization, depending on the type of soil and the degree of depletion of organic matter in the soil. A fundamental understanding of soil degradation is that its expressions are as diverse as its causes.   China has an area of arable land that is more than 40% degraded, which represents a major problem. There are a number of direct and indirect consequences of soil degradation in China that are reviewed in this paper. As a consequence of soil degradation, nutrient content in soil is lost, salinity increases, acidification increases, and desertification occurs. The importance of soil resources will only increase in the future as the world's population increases to around eight billion. By 2020, the global population will be one-third higher than in 1995, yet food and fiber demand will increase by even greater proportions than in 1995, despite growing incomes, a more diverse diet, and rapid urbanization. As a result of the loss of soil layers that contain organic matter and nutrients, there will be a reduction in the amount of land that can be used for agriculture and a decrease in the amount of land that will produce crops, since the soil will be less fertile and less capable of retaining moisture. In China, the amount of arable land that has been degraded exceeds 40%. As a result of soil degradation, several negative impacts are observed and measured, such as soil nutrient loss, salinization, acidification, and desertification, among others
Physiological response of diverse maize genotypes to heat stress and simple sequence repeats markers-based genotyping in Rawalpindi, Punjab Pakistan
Authors: Gohar Suleman , Malik Saad Imran , Wattoo Fahad Masoud , Adil Kamal , Ahmed Zubair , Farooq Umar , Hussain Aamir , Sabahat Sanjeela , Javed Kamran
Published: December 2024

The current study was designed to observe the response of maize genotypes under high-temperature stress conditions and to check their diversity using simple sequence repeats (SSR) markers in in-vitro conditions. Maize genotypes (n=10) were subjected to heat stress at ~45 °C for 72 h after growing into young seedlings. Their physiological responses were determined by measuring the changes in proline content (PC), chlorophyll content (CC), cell membrane stability (CMS), relative water content (RWC) and osmotic potential (Ψπ). The analysed data disclosed significant differences (P ≤ 0.01) among all the characters. Comparison between control and heat-treated genotypes depicted a notable increase in PC, Ψπ while a decrease in CC, RWC and CMS index in heat-treated plants. Maize genotypes viz. NCEV-1230, NARC-4, HN Gold and OPV-20 performed better under heat stress and also showed a strong genetic relationship for similarity index in dendrogram based on selected SSR markers related to abiotic stress tolerance. This study is beneficial for understanding the physiological behaviour of maize plants under heat stress and for further genetic studies on maize to select heat-tolerant lines for breeding programs
Collagen scaffold-seeded iTenocytes accelerate the healing and functional recovery of Achilles tendon defects in a rat model
Authors: Später Thomas , Del Rio Patricia , Shelest Oksana , Wechsler Jacob T. , Kaneda Giselle , Chavez Melissa , Sheyn Julia , Yu Victoria , Metzger Wolfgang , Huang Dave , Metzger Melodie , Tawackoli Wafa , Sheyn Dmitriy
Published: December 2024

Introduction

Tendon injuries represent an ongoing challenge in clinical practice due to poor regenerative capacity, structure, and biomechanical function recovery of ruptured tendons. This study is focused on the assessment of a novel strategy to repair ruptured Achilles tendons in a Nude rat model using stem cell-seeded biomaterial.

Methods

Specifically, we have used induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) overexpressing the early tendon marker Scleraxis (SCX, iMSCSCX+, iTenocytes) in combination with an elastic collagen scaffold. Achilles tendon defects in Nude rat models were created by isolating the tendon and excising 3 mm of the midsection. The Achilles tendon defects were then repaired with iTenocyte-seeded scaffolds, unseeded scaffolds, or suture only and compared to native Nude rat tendon tissue using gait analyses, biomechanical testing, histology, and immunohistochemistry.

Results

The results show faster functional recovery of gait in iTenocyte-seeded scaffold group comparing to scaffold only and suture only groups. Both iTenocyte-seeded scaffold and scaffold only treatment groups had improved biomechanical properties when compared to suture only treatment group, however no statistically significant difference was found in comparing the cell seeding scaffold an scaffold only group in terms of biomechanical properties. Immunohistochemistry staining further demonstrated that iTenocytes successfully populated the collagen scaffolds and survived 9 weeks after implantation in vivo. Additionally, the repaired tissue of iTenocyte-treated injuries exhibited a more organized structure when compared to tendon defects that were repaired only with suturing or unseeded scaffolds.

Conclusion

We suggest that iTenocyte-seeded DuRepair™ collagen scaffold can be used as potential treatment to regenerate the tendon tissue biomechanically and functionally.
Impact of galectin-3 on neurotrophic factor expression by PCR array: potential implications for the human cornea
Authors: Woodward Ashley M. , Argüeso Pablo
Published: December 2024

The cornea is densely innervated to maintain the integrity of the ocular surface, facilitating functions such as sensation and tear production. Following damage, alterations in the corneal microenvironment can profoundly affect its innervation, potentially impairing healing and sensory perception. One protein frequently upregulated at the ocular surface following tissue damage is galectin-3, but its contribution to corneal nerve regeneration remains unclear. Here, we sought to delineate the role of galectin-3 in regulating the expression of neurotrophic factors by different human cell types. Using a pathway-focused PCR array, we first evaluated the expression of neurotrophic factors in primary cultures of human corneal epithelial cells and fibroblasts. We found that these cell types contributed differently to the expression of these factors, with fibroblasts exhibiting higher levels of nerve growth factor, brain-derived neurotrophic factor, and GDNF compared to epithelial cells. Treatment with exogenous galectin-3 did not significantly affect epithelial cells; however, it did lead to increased synthesis and secretion of IL6, a cytokine known to influence neuronal survival and modulate inflammatory responses, by corneal fibroblasts. Using the human-derived SH-SY5Y cell line as a neuron-like cell model, we also found that galectin-3 stimulated the expression of FOS and LIF, two genes involved in neural differentiation and survival. In summary, these in vitro findings suggest that the presence of galectin-3 in the corneal environment may influence the neuronal response to injury.
Applications of artificial intelligence in regenerative dentistry: promoting stem cell therapy and the scaffold development
Authors: Saberian Elham , Jenča Andrej , Jenča Andrej , Zare-Zardini Hadi , Araghi Mohammad , Petrášová Adriána , Jenčová Janka
Published: December 2024

Tissue repair represents a critical concern within the domain of dentistry. On a daily basis, countless individuals seek dental clinic services due to inadequate dental care. Many of the treatments that patients receive have unfavorable side effects. The employment of innovative methodologies, including gene therapy, tissue engineering, and stem cell (SCs) applications for regenerative purposes, has garnered significant interest over the past years. In recent times, artificial intelligence, particularly neural networks, has emerged as a topic of considerable attention among many medical professionals. Artificial intelligence possesses the capability to analyze data patterns through learning algorithms. Research opportunities in the rapidly expanding field of health sciences have been made possible by the use of artificial intelligence (AI) technologies. Though its uses are not restricted to these situations, artificial intelligence (AI) has the potential to improve and accelerate many aspects of regenerative medicine research and development, especially when working with complicated patterns. This review article is to investigate how artificial intelligence might be used to enhance regenerative processes in dentistry by using scaffolds and stem cells, in light of the continuous advances in artificial intelligence in the fields of medicine and tissue regeneration. It highlights the difficulties that still exist in this developing sector and explores the possible uses of AI with a particular emphasis on dentistry practices.
Synergistic efficacy of phage Henu10 with antibiotics against Shigella dysenteriae with insight into phage resistance and fitness trade-offs
Authors: Zhao Jing , Chen Baohong , Wang Weizhen , Kang Yu , Hu Erli , Zhang Yuan , Chen Huiling , Xu Xiao , Ji Xinying , Wang Yuhan , Teng Tieshan , Gomaa Salwa E.
Published: December 2024

Introduction

The irrational use of antibiotics has facilitated the emergence of multidrug- resistant Shigella spp., undermining the effectiveness of the currently available antibiotics. Consequently, there is an urgent need to explore new approaches, with phage therapy emerging as a promising alternative.

Methods

In this study, we isolated a phage targeting Shigella dysenteriae from sewage samples using DLA methold, designated Henu10. The morphology, biological characteristics, genomic composition, and phylogenetic relationships of Henu10 were thoroughly characterized. To investigate the trade-off relationship between phage resistance and bacterial fitness, phage Henu10-resistant strains R6 and R11 were identified using continuous passage and bidirectional validation methods.

Results

Phage-resistant strains R6 and R11 exhibited impaired adsorption, increased sensitivity to temperature and pH stress, heightened susceptibility to certain antibiotics (such as ciprofloxacin and kanamycin), reduced biofilm-forming capacity, and diminished colonization ability in vivo compared to the wild-type strain.

Discussion

These results indicate that phage Henu10 may effectively control the pathogenic bacteria associated with S. dysenteriae, representing a promising new therapeutic option for treating S. dysenteriae infections.
STEM and the creative and cultural industries: the factors keeping engineers from careers in the CCIs
Authors: Turegeldinova Aliya , Amralinova Bakytzhan , Fodor Máté Miklós , Rakhmetullina Saule , Konurbayeva Zhadyra , Kiizbayeva Zhadyra
Published: December 2024

Engineers in the Creative and Cultural Industries (CCIs) are underrepresented, despite high demand for their expertise resulting from digitalization. Increasing the quantity of engineers in CCIs has emerged as a policy goal, since experiments have shown that combining engineering and creative abilities enhances productivity and innovation output. It is therefore unsurprising that the high and unmet demand for engineers in CCIs is well documented. However, the factors contributing to them not taking up jobs in these sectors are not well understood. The existing knowledge mostly comes from the analysis of deficiencies within the CCIs, including cultural disparities, skill profiles and economic factors. But why engineers themselves consider CCIs to provide inappropriate career tracks is little understood. The present study aims to bridge this knowledge gap through two main pillars. First, it develops a novel theoretical framework that aims to provide a taxonomy operationalizing the reasons for which engineers do not engage with the CCIs. This framework categorizes the social and economic barriers that keep engineers from pursuing careers in the CCIs. It includes economic factors, educational path dependencies, integration and interest. Second, our study offers preliminary quantitative insights into how the framework operates in practice, identifying key barriers without drawing definitive classifications. This analysis serves to highlight patterns and considerations for the future. The data source used is a survey among 104 university engineering and STEM students. Our results indicate that economic factors, such as poor salaries and job instability that are both prevalent in the CCIs are not the major barriers keeping engineers from the CCIs. They do not feel that educational investment would bear insufficient return. Instead, they feel ill-equipped to integrate into CCIs because of perceived deficiencies in artistic abilities. Furthermore, educational path dependencies for engineers do not necessarily support multidisciplinary education or counseling toward careers in the CCIs. These further exacerbate their worries regarding integration in the CCIs. These issues identified by our exploratory study can be resolved, predominantly because engineering students demonstrate inherent interest in arts and culture. Our research identifies the need for implementing specific changes to promote education and career guidance that span several disciplines.
Atherogenic circulating lipoproteins in ischemic stroke
Authors: Benitez Sonia , Puig Núria , Camps-Renom Pol , Sánchez-Quesada José Luis
Published: December 2024

The fundamental role of qualitative alterations of lipoproteins in the early development of atherosclerosis has been widely demonstrated. Modified low-density lipoproteins (LDL), such as oxidized LDL (oxLDL), small dense LDL (sdLDL), and electronegative LDL [LDL(-)], are capable of triggering the atherogenic process, favoring the subendothelial accumulation of cholesterol and promoting inflammatory, proliferative, and apoptotic processes characteristic of atherosclerotic lesions. In contrast, high-density lipoprotein (HDL) prevents and/or reverses these atherogenic effects. However, LDL's atherogenic and HDL's anti-atherogenic actions may result altered in certain pathological conditions. The molecular mechanisms underlying the impaired effects of altered lipoproteins have been studied in numerous in vitro and in vivo studies, and have been extensively analyzed in coronary atherosclerosis, especially in the context of pathologies such as dyslipidemia, diabetes, obesity, and metabolic syndrome. However, the corresponding studies are scarcer in the field of ischemic stroke, despite carotid arteriosclerosis progression underlies at least 20% of ischemic strokes. The present review relates qualitative alterations of LDL and HDL with the development of carotid arteriosclerosis and the occurrence of ischemic stroke.
Quantitative characterization of damage and the cross-scale evolution mechanism of soft rock under dry-wet cycles
Authors: Liang Ning , Jin Tao , Su Dingli
Published: December 2024

Soft rock undergoes internal structural redistribution and random damage under the action of dry–wet cycles, with these processes ultimately affecting its mechanical properties. In order to analyze the evolution mechanism of mineral composition inside soft rocks, an effective method for the characterization of the nonlinear damage of soft rock using a multifractal spectrum is presented. Moreover, a cross-scale correlation model of internal structural changes and strength degradation is established. Based on scanning electron microscopy (SEM) images of soft rock subjected to a varying number of dry–wet cycles, the damage propagation path was tracked via a rock-like compression failure test. The study results indicate that soft rock exhibits a random fractal damage effect under the action of dry–wet cycles. As the number of cycles increases, the multifractal spectrum becomes more asymmetric and the discretization degree becomes more uneven. The soft rock exhibits cross-scale evolution characteristics from mesostructural to macroscopic damage after encountering water. After a series of reactions between water and soft rock, the bonding between particles weakens and recombines, ultimately affecting the mechanical properties of the soft rock. The research results have enriched the research framework of soft rock failure mechanisms, and provided an effective method for quantitatively characterizing the correlation analysis between soft rock damage and damage at different scales.
Comparative analysis of clinical characteristics of symptomatic pituitary adenomas in elderly patients: a consecutive series of 114 patients
Authors: Wang Run , Han Xiaodi , Xie Cheng , Zhang Qinghua , Kan Liang , Han Sheng
Published: December 2024

Background

Pituitary adenomas (PAs) present with clinical features such as neuroendocrine abnormalities and mass effects, common in the general morbidity population. However, in elderly patients, the disease progression renders some clinical features difficult to detect and identify in time. Consequently, elderly patients with PAs are often not identified and receive sufficient intervention on time to achieve a satisfactory outcome.

Methods

Clinical data were collected from 114 consecutive patients older than 70 years with PAs who had undergone surgery. Based on the average age, the patients were categorized into a younger group and an elder group, and were statistically analyzed and compared.

Results

Sixty-five males (57.0%) and 49 females (43.0%) were included in the study, with an average age of 73.2 years. Their common preoperative symptoms included vision impairment, followed by headache and vomiting, and visual field defect. The milder the preoperative visual impairment, the greater the possibility of post-operative visual improvement (P=0.001). The tumors were primarily non-functional pituitary adenomas (NFPAs, 73.7%), with a high degree of suprasellar invasion but a low degree of parasellar invasion (P<0.0001). For further analysis, based on the average age, we categorized the patients into younger (age< 73 years, 59 cases) and elder (age≥ 73 years, 55 cases) groups. The elder group was more likely to have preoperative vision impairment problems (P=0.044), whilst post-operative visual improvement was worse (P=0.001). The elder group also had a more severe suprasellar invasion (P=0.009), with a higher proportion of NFPA than the younger group (P=0.006). Compared to the younger group, the tumors in the elder group were larger (P=0.039), and had a higher rate of apoplexy (P=0.039), and were more likely to have comorbid postoperative complications (P=0.031), such as fever and cerebrospinal fluid (CSF) leakage, compared to the younger group.

Conclusions

Elderly patients with PA had specific clinical characteristics. Their relatively worse pre- and post-operative conditions and intraoperative findings illustrated the need for early surgery.
Dissolved nitrous oxide emissions associated with agricultural drainage water as influenced by manure application
Authors: Burton D. L. , Wilts H. D. M. , MacLeod J. A.
Published: December 2024

Nitrous oxide (N2O) is highly water soluble and can be readily transported in waters draining from agricultural fields. Relatively few studies have quantified N2O losses through agricultural tile drainage systems and none have compared the effect of different sources of applied nitrogen or their timing of application. While IPCC guidelines provide estimates of emissions from agricultural drainage water, the uncertainty in these estimates is relatively high. This research quantifies N2O loss in tile drainage water, as influenced by nitrogen source and timing. The study site was located at Agriculture Canada research station, Harrington, PE, Canada and consisted of 12 plots with subsurface drainage systems installed at approximately 80 cm, separated by buffer drains. Three swine manure treatments were considered with inorganic fertilizer (ammonium nitrate) as a control, each replicated three times. Manure treatments included fall and spring application of solid swine manure and spring application of liquid swine manure, all applied to supply 120 kg N ha−1. The magnitude of N2O loss, as measured from samples collected at the tile outlets, demonstrated significant episodic emissions. Annual cumulative dissolved N2O emissions ranged from 0.1 to 5.69 kg N ha−1 (mean 0.83 kg N ha−1), while emissions from the soil surface were 0.09–1.16 kg N ha−1 (mean 0.33 kg N ha−1). N2O emissions in tile water were not significantly affected by the form of N applied, however tile drain length significantly impacted tile water N2O concentration. IPCC coefficients for N2O emissions from agricultural drainage water would underestimate actual N2O emissions at this site.
Remodeling of the chromatin landscape in peripheral blood cells in patients with severe Delta COVID-19
Authors: Akimov Vasiliy E. , Tychinin Dmitriy I. , Antonova Olga A. , Shaymardanov Abusaid M. , Voronina Maria D. , Deinichenko Kseniia A. , Fateev Oleg D. , Yudin Vladimir S. , Yudin Sergey M. , Mukhin Vladimir E. , Romanova Svetlana V. , Nekrasova Aleksandra I. , Zhdanova Anastasia S. , Tsypkina Anastasia V. , Vladimirov Ivan S. , Makhotenko Antonida V. , Keskinov Anton A. , Kraevoy Sergey A. , Snigir Ekaterina A. , Svetlichnyy Dmitry V. , Skvortsova Veronika I.
Published: December 2024

COVID-19 is characterized by systemic pro-inflammatory shifts with the development of serious alterations in the functioning of the immune system. Investigations of the gene expression changes accompanying the infection state provide insight into the molecular and cellular processes depending on the sickness severity and virus variants. Severe Delta COVID-19 has been characterized by the appearance of a monocyte subset enriched for proinflammatory gene expression signatures and a shift in ligand–receptor interactions. We profiled the chromatin accessibility landscape of 140,000 nuclei in PBMC samples from healthy individuals or individuals with COVID-19. We investigated cis-regulatory elements and identified the core transcription factors governing gene expression in immune cells during COVID-19 infection. In severe cases, we discovered that regulome and chromatin co-accessibility modules were significantly altered across many cell types. Moreover, cases with the Delta variant were accompanied by a specific monocyte subtype discovered using scATAC-seq data. Our analysis showed that immune cells of individuals with severe Delta COVID-19 underwent significant remodeling of the chromatin accessibility landscape and development of the proinflammatory expression pattern. Using a gene regulatory network modeling approach, we investigated the core transcription factors governing the cell state and identified the most pronounced chromatin changes in CD14+ monocytes from individuals with severe Delta COVID-19. Together, our results provide novel insights into cis-regulatory module organization and its impact on gene activity in immune cells during SARS-CoV-2 infection.
From nature to clinic: Quercetin’s role in breast cancer immunomodulation
Authors: Fang Liguang , Gao Dandan , Wang Tong , Zhao Haijun , Zhang Yanan , Wang Shijun
Published: December 2024

Immunotherapy has brought hope to many breast cancer patients, but not all patients benefit from it. Quercetin (Qu), a natural product found in various sources, has anti-inflammatory and anti-tumor properties. We conducted a review of the pharmacological research of Qu in regulating anti-tumor immunity in vivo and in vitro. Qu can directly regulate the local tumor microenvironment (TME) by enhancing the activity of immune cells which includes promoting the infiltration of T cells and natural killer (NK) cells, inhibiting the recruitment of myeloid-derived suppressor cells and tumor-associated macrophages. Additionally, Qu inhibits anaerobic glycolysis in tumor cells, thereby reducing the production and transport of lactic acid. It also suppresses tumor angiogenesis by targeting the vascular endothelial growth factor (VEGF) pathway and the vitamin D pathway. Furthermore, Qu can enhance the efficacy of immunotherapy for breast cancer by modulating the systemic microenvironment. This includes inhibiting obesity-related chronic inflammation to decrease the production of inflammatory factors, regulating the composition of intestinal microbiota, and intervening in the metabolism of intestinal flora. At the same time, we also address challenges in the clinical application of Qu, such as low absorption rates and unknown effective doses. In conclusion, we highlight Qu as a natural immunomodulator that enhances immune cell activity and has the potential to be developed as an adjunct for breast cancer.
Rituximab-IgG2 is a phagocytic enhancer in antibody-based immunotherapy of B-cell lymphoma by altering CD47 expression
Authors: Nguyen Oanh T. P. , Lara Sandra , Ferro Giovanni , Peipp Matthias , Kleinau Sandra
Published: December 2024

Antibody-dependent cellular phagocytosis (ADCP) by monocytes and macrophages contributes significantly to the efficacy of many therapeutic monoclonal antibodies (mAbs), including anti-CD20 rituximab (RTX) targeting CD20+ B-cell non-Hodgkin lymphomas (NHL). However, ADCP is constrained by various immune checkpoints, notably the anti-phagocytic CD47 molecule, necessitating strategies to overcome this resistance. We have previously shown that the IgG2 isotype of RTX induces CD20-mediated apoptosis in B-cell lymphoma cells and, when combined with RTX-IgG1 or RTX-IgG3 mAbs, can significantly enhance Fc receptor-mediated phagocytosis. Here, we report that the apoptotic effect of RTX-IgG2 on lymphoma cells contributes to changes in the tumor cell’s CD47 profile by reducing its overall expression and altering its surface distribution. Furthermore, when RTX-IgG2 is combined with other lymphoma-targeting mAbs, such as anti-CD59 or anti-PD-L1, it significantly enhances the ADCP of lymphoma cells compared to single mAb treatment. In summary, RTX-IgG2 acts as a potent phagocytic enhancer by promoting Fc-receptor mediated phagocytosis through apoptosis and reduction of CD47 in CD20+ malignant B-cells. RTX-IgG2 represents a valuable therapeutic component in enhancing the effectiveness of different mAbs targeting B-cell NHL.
Time-dependent variation in immunoparalysis biomarkers among patients with sepsis and critical illness
Authors: Samuelsen Abigail , Lehman Erik , Burrows Parker , Bonavia Anthony S.
Published: December 2024

Introduction

Immunoparalysis is a state of immune dysfunction characterized by a marked reduction in the immune system’s responsiveness, often observed following severe infections, trauma, or critical illness. This study aimed to perform a longitudinal assessment of immune function over the initial two weeks following the onset of sepsis and critical illness.

Methods

We compared ex vivo-stimulated cytokine release from whole blood of critically ill patients to traditional markers of immunoparalysis, including monocyte Human Leukocyte Antigen (mHLA)-DR expression and absolute lymphocyte count (ALC). A total of 64 critically ill patients were recruited in a tertiary care academic medical setting, including 31 septic and 33 non-septic patients.

Results

While mHLA-DR expression significantly increased over time, this was primarily driven by the non-septic subset of critically ill patients. ALC recovery was more pronounced in septic patients. Ex vivo stimulation of blood from septic patients revealed significant increases in TNF and IL-6 production over time. However, interferon-gamma production varied depending on the ex vivo stimulant used, and after normalization of cytokine concentrations to lymphocyte counts, it did not show significant recovery over time from illness onset. No significant correlation was found between mHLA-DR expression and other immunoparalysis biomarkers.

Discussion

These findings suggest the need for more nuanced immune monitoring approaches beyond the traditional ‘sepsis’ versus ‘non-sepsis’ classifications in critically ill patients. Additionally, they provide further evidence of a potential window for targeted immunotherapy in the first weeks of critical illness.
From understanding to action: a juncture-factor framework for advancing social responsiveness in health professions education
Authors: Botha G. C. , Crafford L.
Published: December 2024

Background

Low- to middle-income countries face critical healthcare challenges. Equipping graduates with social responsiveness, the ability to address community health needs effectively, is essential. Despite its importance, research on integrating social responsiveness principles into medical and pharmacy curricula remains limited. This study explores how understanding of social responsiveness translates to practice in a resource-constrained context and identifies critical factors for future direction.

Methods

Semi-structured focus groups were conducted with curriculum developers, academic staff, and alumni (n = 27) using purposive sampling. Thematic analysis yielded an emergent “juncture-factor” framework for integrating SR into curricula.

Results

Our analysis revealed a four-stage framework for integrating social responsiveness. It categorizes existing and evolving efforts into four key junctures (points in time) and 12 factors for consideration at each juncture. The Illuminate juncture emphasizes raising awareness, fostering agreement, and aligning institutional values with community needs. The Construct stage focuses on inclusivity, contextualizing learning, developing relevant content, and employing appropriate pedagogy. The Influence juncture ensures validated social responsiveness action, effective implementation, and faculty and student capacity building. Finally, the Coalesce juncture promotes collaboration and internalization of social responsiveness principles among stakeholders.

Conclusion

This framework aligns with international social responsiveness literature while offering a unique low-to middle income country perspective. It acknowledges the complexities of integrating social responsiveness and provides practical ways to address them. This framework serves as a valuable tool for curriculum review in resource-constrained contexts. Future research could explore its applicability across diverse settings, and investigate its long-term impact on student learning and professional development, ultimately shaping future healthcare professionals equipped to address their communities’ needs.
Comparison of sexual function between laparoscopic lateral suspension and laparoscopic sacrocervicopexy with the use of the PISQ-IR questionnaire
Authors: Malanowska-Jarema Ewelina , Starczewski Andrzej , Melnyk Mariia , Fidalgo Daniel , Oliveira Dulce , Dubuisson Jean
Published: December 2024

Introduction and hypothesis

We aimed to analyze the quality of sexual life of patients with apical vaginal wall prolapse who had undergone laparoscopic lateral suspension (LLS) and laparoscopic sacrocolpopexy (LSC).

Methods

We performed a secondary analysis of sexual outcomes of a previous randomized control trial comparing LLS and LSC in 89 women with symptomatic POP stage ≥ II. We evaluated sexually active (SA) and non-sexually active women (NSA) using the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-IUGA-Revised (PISQ-IR). Women were reviewed over a period of 1 year post-surgery.

Results

Analysis of the entire PISQ-IR questionnaire indicates that surgical treatment of POP resulted in an improvement of the quality of sexual life in 21 (80.76%) in the group of sexually active women after LSC and in 20 (83.33%) in the group of SA patients after LLS. In both groups of patients, dyspareunia was not observed.

Conclusion

In conclusion, the quality of sexual life in SA group of patients improved significantly after both surgical procedures. The quality of sexual life of surveyed women significantly improved after curing POP symptoms.
Nomogram for predicting post-progression-free survival in patients with recurrent pancreatic ductal adenocarcinoma after radical surgery: a retrospective analysis
Authors: Qin Dailei , Xi Pu , Huang Kewei , Jiang Lingmin , Yao Zehui , Wei Ran , Li Shengping
Published: December 2024

Background

Radical resection is the only curative method for patients with pancreatic adenocarcinoma (PDAC). However, nearly 85% of PDAC patients suffer from local or distant recurrence within 5 years after curative resection. The progression of recurrent lesions accelerates the mortality rate in PDAC patients. However, the influence of clinicopathological factors on post-progression-free survival (PPFS), defined as the period from tumor recurrence to the timing of the progression of recurrent lesions, has rarely been discussed. The present study aimed to explore the independent prognostic factors for PPFS and construct a nomogram for PPFS prediction.

Materials and methods

The 200 recurrent PDAC patients were divided into training and validation groups by leave-one-out cross-validation. The patients’ clinicopathological characteristics were compared through a chi-square test. Meanwhile, these factors were enrolled in the univariate and multivariate COX regression to find the independent prognostic factors of PPFS. Moreover, the Kaplan–Meier survival analysis based on the independent prognostic factors was performed. Finally, we constructed a nomogram model for PPFS prediction, followed by an effectiveness examination.

Results

PDAC patients who received multi-agent chemotherapy after surgery showed a longer PPFS than the single-agent chemotherapy group. PDAC patients who received multi-agent chemotherapy after recurrence showed a similar PPFS compared to the single-agent chemotherapy group. Local recurrence with distant metastases, early recurrence, lympho-vascular invasion, higher T stage, and higher N stage predicted shorter PPFS in recurrent PDAC patients. Finally, a nomogram to indicate the progression of recurrent lesions was constructed.

Conclusion

Multi-agent chemotherapy is recommended for PDAC patients after surgery. Meanwhile, single-agent chemotherapy also deserves consideration after tumor recurrence. Moreover, the nomogram could be used in PPFS prediction.
Antioxidant capacities and non-volatile metabolites changes after solid-state fermentation of soybean using oyster mushroom (Pleurotus ostreatus) mycelium
Authors: He Mengxin , Peng Qing , Xu Xiaoqing , Shi Bo , Qiao Yu
Published: December 2024

Given the abundance of beneficial properties and enzymes secreted by edible oyster mushrooms, their mycelium could serve as a starter for fermented foods to enhance their nutritional and bioactive quality. This study aimed to investigate the effects on the nutritional ingredients, antioxidant activity, and non-volatile metabolites during solid-state fermentation (SSF) of soybeans by Pleurotus ostreatus mycelium. The results indicated that the contents of dietary fiber and starch in fermented soybeans decreased, while the amounts of protein and lipid increased after SSF (P < 0.05). Analysis of the total phenolic content (TPC) and antioxidant activities of the fermented soybeans revealed that the methanolic extracts significantly increased TPC and antioxidant activities against intracellular reactive oxygen species (ROS) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, as well as against DPPH and ABTS radicals in vitro. A total 154 differential metabolites were identified after SSF, and a Spearman correlation study revealed a direct relationship between antioxidant activities and certain metabolites including phenolic compounds, oligopeptides, and free fatty acids etc. Among these metabolites, phenolic compounds produced by the shikimic acid pathway were diverse in variety and had the greatest multiple differences. The study discovered that a potential mechanism involving SSF with P. ostreatus mycelium increased the antioxidant activity of soybeans.
Metabolomics study of APETx2 post-conditioning on myocardial ischemia-reperfusion injury
Authors: Li Jing , Wei Yiyong , Wang Yi , Zhang Yue , Xu Ying , Ma Huanhuan , Ma Lulin , Zeng Qingfan
Published: December 2024

Background

Acid-sensing ion channels are activated during myocardial ischemia and are implicated in the mechanism of myocardial ischemia-reperfusion injury (MIRI). Acid-sensing ion channel 3 (ASIC3), the most pH-sensitive member of the ASIC family, is highly expressed in myocardial tissues. However, the role of ASIC3 in MIRI and its precise effects on the myocardial metabolome remain unclear. These unknowns might be related to the cardioprotective effects observed with APETx2 post-conditioning.

Method

Rat hearts subjected to Langendorff perfusion were randomly assigned to the normal (Nor) group, ischemia/reperfusion (I/R) group, ASIC3 blockade (AP) group. Rat hearts in group AP were treated with the ASIC3-specific inhibitor APETx2 (630 nM). Molecular and morphological changes were observed to elucidate the role of ASIC3 in MIRI. Bioinformatics analyses identified differential metabolites and pathways associated with APETx2 post-conditioning.

Results

APETx2 post-conditioning stabilized hemodynamics in the isolated rat heart model of MIRI. It also reduced myocardial infarct size, mitigated mitochondrial damage at the ultrastructural level, and improved markers of myocardial injury and oxidative stress. Further more, we observed that phosphatidylcholine, phosphatidylethanolamine, citric acid, cyanidin 5-O-beta-D-glucoside, and L-aspartic acid decreased after MIRI. The levels of these metabolites were partially restored by APETx2 post-conditioning. These metabolites are primarily involved in autophagy and endogenous cannabinoid signaling pathways.

Conclusion

ASIC3 is potentially a key player in MIRI. APETx2 post-conditioning may improve MIRI through specific metabolic changes. This study provides valuable data for future research on the metabolic mechanisms underlying the effects of APETx2 post-conditioning in MIRI.
Discovery of quality markers of Meconopsis quintuplinervia based on an absorption-based metabolite approach and rapid quantification using polarity-switching UPLC-QQQ-MS/MS
Authors: Tian Yifan , Liu Yuan , Kong Yuanlin , Li Limin , Yang Zhengming , Li Wenbin , Li Qiang , Ren Chaoqin , Sun Wenxia , Huang Yanfei
Published: December 2024

Background

Meconopsis quintuplinervia Regel (MQ) is a traditional Chinese medicine (TCM) used for clearing liver and lung heat in Tibetan medicine for over a thousand years. However, the lack of quality markers that correlate with pharmacological actions and absorption in vivo limits the safety and efficacy in its clinical application and on the drug market. Furthermore, a universal and rapid method for simultaneously determining quality markers in the MQ crude drug is still lacking.

Purpose

An absorption-based metabolite approach was used to discover and identify the quality markers of MQ. An efficient method based on polarity-switching ultra-performance liquid chromatography triple quadrupole mass spectrometry (UPLC-QQQ-MS/MS) was then established to determine the quality markers.

Methods

The absorbed compounds and metabolites were first characterized using UPLC plus Q-Exactive Orbitrap tandem mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) after giving oral MQ extract to rats. Subsequently, the absorbed compounds and precursors of metabolites correlating with the hepatocyte protection activity were screened as quality markers. Finally, a polarity-switching UPLC-QQQ-MS/MS method was developed for the quantitative analysis of the MQ crude drug, enabling the detection of quality markers in both negative and positive ion modes in a single run. The MS2 characteristics of target compounds were investigated to select appropriate product ions.

Results

A total of 13 absorbed compounds and 30 metabolites were characterized. Among these, nine compounds, including five absorbed compounds and four precursors of metabolites intimately correlated with hepatocyte protection activity and absorption in vivo, were considered the quality markers of MQ in the current study. The quantification of quality markers was conducted using an Acquity UPLC HSS T3 (2.1 × 100 mm, 1.8 μm) column, the mobile phase consisting of acetonitrile and 0.1% formic acid solution (containing 10 mmol/L ammonium acetate). The validated UPLC-QQQ-MS/MS method was successfully applied to quantify the quality markers in the MQ crude drug.

Conclusion

We defined the quality markers and established a universal and rapid method for simultaneously determining the quality markers of MQ, which will be helpful for further investigation of the quality evaluation of MQ in clinical application and the drug market.