bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic and metabolomic analysis of GH deficiency-induced NAFLD in hypopituitarism: insights into oxidative stress
Authors: Zhang Yuwen , Chen Peizhan , Fang Xuqian
Published: May 2024

Objective

Individuals with hypopituitarism (HPs) have an increased risk of developing non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) due to growth hormone deficiency (GHD). We aimed to investigate the possible mechanisms underlying the relationship between GHD and NAFLD using proteomic and metabolomic insights.

Methods

Serum metabolic alternations were assessed in male HPs using untargeted metabolomics. A rat model of HP was established through hypophysectomy, followed by recombinant human growth hormone (rhGH) intervention. The mechanisms underlying GHD-mediated NAFLD were elucidated through the application of label-free proteomics and phosphorylation proteomics.

Results

Metabolomic analysis revealed that biomarkers of mitochondrial dysfunction and oxidative stress, such as alanine, lactate, and creatine, were significantly elevated in HPs compared to age-matched controls. In rats, hypophysectomy led to marked hepatic steatosis, lipid peroxidation, and reduced glutathione (GSH), which were subsequently modulated by rhGH replacement. Proteomic analysis identified cytochrome P450s, mitochondrial translation elongation, and PPARA activating genes as the major distinguishing pathways in hypophysectomized rats. The processes of fatty acid transport, synthesis, oxidation, and NADP metabolism were tightly described. An enhanced regulation of peroxisome β-oxidation and ω-oxidation, together with a decreased NADPH regeneration, may exacerbate oxidative stress. Phosphoproteome data showed downregulation of JAK2-STAT5B and upregulation of mTOR signaling pathway.

Conclusions

This study identified proteo-metabolomic signatures associated with the development of NAFLD in pituitary GHD. Evidence was found of oxidative stress imbalance resulting from abnormal fatty acid oxidation and NADPH regeneration, highlighting the role of GH deficiency in the development of NAFLD.
Improved typical scenario-based distributionally robust co-dispatch of energy and reserve for renewable power systems considering the demand response of fused magnesium load
Authors: Qian Junchen , Cai Jilin , Hao Lili , Meng Zhixiang
Published: May 2024

In recent years, the penetration of solar and wind power has rapidly increased to construct renewable energy-dominated power systems (RPSs). On this basis, the forecasting errors of renewable generation power have negative effects on the operation of the power system. However, traditional scheduling methods are overly dependent on the generation-side dispatchable resources and lack uncertainty modeling strategies, so they are inadequate to tackle this problem. In this case, it is necessary to enhance the flexibility of the RPS by both mining the load-side dispatchable resources and improving the decision-making model under uncertainty during the energy and reserve co-dispatch. In this paper, due to the great potential in facilitating the RPS regulation, the demand response (DR) model of fused magnesium load (FML) is first established to enable the deeper interaction between the load side and the whole RPS. Then, based on the principal component analysis and clustering algorithm, an improved typical scenario set generation method is proposed to obtain a much less conservative model of the spatiotemporally correlated uncertainty. On this basis, a two-stage distributionally robust optimization model of the energy and reserve co-dispatch is developed for the RPS considering the DR of FML. Finally, the proposed method is validated by numerical tests. The results show that the costs of day-ahead dispatch and re-dispatch are significantly decreased by using the improved typical scenario set and considering the DR of FML in regulation, which enhances the operation economy while maintaining the high reliability and safety of the RPS.
Effectiveness assessment of protected areas based on the states, trends, and relative changes in forest ecosystem: a case study in the Three Parallel Rivers Region, China
Authors: Shen Hua , Feng Chunting , Tian Jing , Fan Luqiong , Cao Ming , Wang Wei
Published: May 2024

Establishing protected areas (PAs) is a major measure of biodiversity conservation, and various methods have been explored to assess PAs’ effectiveness. However, those methods mainly compared the relative changes in land cover between treated samples inside the PAs and their matched samples outside the PAs, which would produce misjudgments, especially in some climax communities with a relatively steady state. Thus, in this study, we constructed an integrated framework through a series of assessments according to the state, trend, and relative change of each PA to explore the conservation effectiveness of PAs in the Three Parallel Rivers Region in China from 2000 to 2020. Here, “state” refers to the difference among samples from within and outside the PA, assessed through yearly sample mean comparison. “Trend” means linear regression of mean forest area of each PA throughout the assessment period. “Relative change” means the difference in the mean value of the slope of forest changes between the treated samples inside each PA and their matched control samples outside of PAs. The entire forest area within all PAs in the Three Parallel Rivers Region showed a significant increasing trend from 2000 to 2020 (R2 = 0.919, P<0.05). Among all the PAs, twelve (86%) had a positive effect on protecting the forest ecosystem, and two had a nonsignificant effect. Among the factors affecting the state and relative change in PAs’ forests, the annual total precipitation was the most important, followed by distance to the nearest road. Moreover, the management-level variable was an essential factor in the state of PAs’ forest ecosystems, which indicated that national PAs (nature reserves and natural parks) were in a better state than local (provincial- and county-level) nature reserves. Overall, the conservation effectiveness of forests in PAs was assessed at a regional scale in the Three Parallel Rivers Region, implying that our framework would be additional useful in regions with high biodiversity and steady ecosystems. This framework better avoids underestimating conservation effectiveness assessment tasks than traditional methods do. Thus, we posit that this framework is suitable for future global or country-level assessments.
Unveiling soil bacterial ecosystems in andean citrus orchards of Santander, Colombia
Authors: Castillo-Villamizar Genis Andrés , Tapia-Perdomo Valentina , Maldonado-Pava Julieth , Santamaría-Gálvis Pedro , Sayavedra Lizbeth , Hernandez-Torres Jorge , Puentes-Cala Edinson
Published: May 2024

Citrus cultivation is vital to global agriculture, necessitating a comprehensive understanding of the soil microbiome’s diversity for sustainable practices. This study provides initial insights into the bacteriome in citrus crops in Santander, Colombia, employing a holistic approach combining culture-based techniques, sequencing methods, and bioinformatics analyses. The study explores organic and non-organic cultivation systems, revealing statistically significant differences in bacterial community composition between both practices. In general, the communities are dominated by members of the Actinobacteria and Proteobacteria, along with bacterial orders Gaiellales and Burkholderiales, all contributing to intricate ecological processes. Culture-based methods aided in the isolation of potential biotechnologically relevant strains. Among them, strain CP102 showed a pronounced carboxymethylcellulose (CMC) degradation capacity. Genetic analysis of the isolate resulted in the generation of the first closed genome of a member of the species Enterobacter soli and identified an unreported 109 kb plasmid. Further genomic examination revealed genes potentially associated with cellulose degradation in this species, which provides the isolate with biotechnological potential. This research significantly advances the global understanding of citrus-associated bacteriomes, shaping future agricultural practices and promoting the development of sustainable bioproducts.
Distance models reveal biases associated with passive trapping methods for measuring wild bee abundance
Authors: Mathis Codey L. , McNeil Darin J. , Kammerer Melanie , Larkin Jeffery L. , Skvarla Michael J.
Published: May 2024

Introduction

There is overwhelming evidence of declines in native bee populations and therefore a need for increased monitoring to track these declines and assist in conservation and restoration efforts. Bees can be sampled non-lethally through visual surveys (e.g., distance transects) or lethally through active (e.g., hand netting) or passive (e.g., traps that lure insects from afar) methods. These lethal methods suffer from imperfect detection that is difficult to account for and can confound inferences about habitat characteristics. Additionally, evidence suggests that lethal sampling methods can even invert habitat quality patterns such that high-quality sites yield fewer individuals and low-quality sites yield more individuals.

Methods

To study potential biases associated with imperfect detection, we used hierarchical density estimation with visual surveys to estimate density of bees within 40 young forest patches across Pennsylvania, USA. We surveyed bee communities non-lethally using visual surveys and lethally using blue-vane traps and bee bowls every two weeks between May and September 2019. We collected data on blooming flowers, vegetation structure, and weather during times of survey.

Results

We found that bee densities estimated from distance transects had a positive relationship with floral resource availability. In contrast, abundance measured via bee bowls and blue-vane traps had no relationship, or sometimes even negative trends with habitat quality, including floral resource availability. Raw bee counts within 2-m of the transect always correlated with modeled densities, showing that some methods do not share the biases of attractive traps.

Discussion

Our study demonstrates that failing to account for imperfect detection can impact the interpretation of pollinator surveys and adds to a growing body of literature that acknowledges the value of distance sampling for insects like bees to better understand species’ habitat needs and to monitor populations for conservation.
Synergistic antitumor immune response mediated by paclitaxel-conjugated nanohybrid oncolytic adenovirus with dendritic cell therapy
Authors: Kim In-Wook , Yoon A-Rum , Hong JinWoo , Kasala Dayananda , Yun Chae-Ok
Published: May 2024

Dendritic cell (DC)-based vaccines have emerged as a promising strategy in cancer immunotherapy due to low toxicity. However, the therapeutic efficacy of DC as a monotherapy is insufficient due to highly immunosuppressive tumor environment. To address these limitations of DC as immunotherapeutic agent, we have developed a polymeric nanocomplex incorporating (1) oncolytic adenovirus (oAd) co-expressing interleukin (IL)-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) and (2) arginine-grafted bioreducible polymer with PEGylated paclitaxel (APP) to restore antitumor immune surveillance function in tumor milieu and potentiate immunostimulatory attributes of DC vaccine. Nanohybrid complex (oAd/APP) in combination with DC (oAd/APP+DC) induced superior expression level of antitumor cytokines (IL-12, GM-CSF, and interferon gamma) than either oAd/APP or DC monotherapy in tumor tissues, thus resulting in superior intratumoral infiltration of both endogenous and exogenous DCs. Furthermore, oAd/APP+DC treatment led superior migration of DC to secondary lymphoid organs, such as draining lymph nodes and spleen, in comparison with either monotherapy. Superior migration profile of DCs in oAd/APP+DC treatment group resulted in more prolific activation of tumor-specific T cells in these lymphoid organs and greater intratumoral infiltration of T cells. Additionally, oAd/APP+DC treatment led to lower subset of tumor infiltrating lymphocytes and splenocytes being immunosuppressive regulatory T cells than any other treatment groups. Collectively, oAd/APP+DC led to superior induction of antitumor immune response and amelioration of immunosuppressive tumor microenvironment to elicit potent tumor growth inhibition than either monotherapy.
MONET: a database for prediction of neoantigens derived from microsatellite loci
Authors: Deng Nan , Sinha Krishna M. , Vilar Eduardo
Published: May 2024

Background

Microsatellite instability (MSI) secondary to mismatch repair (MMR) deficiency is characterized by insertions and deletions (indels) in short DNA sequences across the genome. These indels can generate neoantigens, which are ideal targets for precision immune interception. However, current neoantigen databases lack information on neoantigens arising from coding microsatellites. To address this gap, we introduce The MicrOsatellite Neoantigen Discovery Tool (MONET).

Method

MONET identifies potential mutated tumor-specific neoantigens (neoAgs) by predicting frameshift mutations in coding microsatellite sequences of the human genome. Then MONET annotates these neoAgs with key features such as binding affinity, stability, expression, frequency, and potential pathogenicity using established algorithms, tools, and public databases. A user-friendly web interface (https://monet.mdanderson.org/) facilitates access to these predictions.

Results

MONET predicts over 4 million and 15 million Class I and Class II potential frameshift neoAgs, respectively. Compared to existing databases, MONET demonstrates superior coverage (>85% vs. <25%) using a set of experimentally validated neoAgs.

Conclusion

MONET is a freely available, user-friendly web tool that leverages publicly available resources to identify neoAgs derived from microsatellite loci. This systems biology approach empowers researchers in the field of precision immune interception.
Transcriptomic signatures of classical monocytes reveal pro-inflammatory modules and heterogeneity in polyarticular juvenile idiopathic arthritis
Authors: Hounkpe Bidossessi W. , Sales Lucas P. , Ribeiro Surian C. R. , Perez Mariana O. , Caparbo Valéria F. , Domiciano Diogo Souza , Figueiredo Camille P. , Pereira Rosa M. R. , Borba Eduardo F.
Published: May 2024

Introduction

Polyarticular juvenile idiopathic arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite the crucial role of monocytes in arthritis, the precise involvement of classical monocytes in the pathogenesis of pJIA remains uncertain. Here, we aimed to uncover the transcriptomic patterns of classical monocytes in pJIA, focusing on their involvement in disease mechanism and heterogeneity.

Methods

A total of 17 healthy subjects and 18 premenopausal women with pJIA according to ILAR criteria were included. Classical monocytes were isolated, and RNA sequencing was performed. Differential expression analysis was used to compare pJIA patients and healthy control group. Differentially expressed genes (DEGs) were identified, and gene set enrichment analysis (GSEA) was performed. Using unsupervised learning approach, patients were clustered in two groups based on their similarities at transcriptomic level. Subsequently, these clusters underwent a comparative analysis to reveal differences at the transcriptomic level.

Results

We identified 440 DEGs in pJIA patients of which 360 were upregulated and 80 downregulated. GSEA highlighted TNF-α and IFN-γ response. Importantly, this analysis not only detected genes targeted by pJIA therapy but also identified new modulators of immuno-inflammation. PLAUR, IL1B, IL6, CDKN1A, PIM1, and ICAM1 were pointed as drivers of chronic hyperinflammation. Unsupervised learning approach revealed two clusters within pJIA, each exhibiting varying inflammation levels.

Conclusion

These findings indicate the pivotal role of immuno-inflammation driven by classical monocytes in pJIA and reveals the existence of two subclusters within pJIA, regardless the positivity of rheumatoid factor and anti-CCP, paving the way to precision medicine.
Single cell genomics based insights into the impact of cell-type specific microbial internalization on disease severity
Authors: Soni Jyoti , Pandey Rajesh
Published: May 2024

Host-microbe interactions are complex and ever-changing, especially during infections, which can significantly impact human physiology in both health and disease by influencing metabolic and immune functions. Infections caused by pathogens such as bacteria, viruses, fungi, and parasites are the leading cause of global mortality. Microbes have evolved various immune evasion strategies to survive within their hosts, which presents a multifaceted challenge for detection. Intracellular microbes, in particular, target specific cell types for survival and replication and are influenced by factors such as functional roles, nutrient availability, immune evasion, and replication opportunities. Identifying intracellular microbes can be difficult because of the limitations of traditional culture-based methods. However, advancements in integrated host microbiome single-cell genomics and transcriptomics provide a promising basis for personalized treatment strategies. Understanding host-microbiota interactions at the cellular level may elucidate disease mechanisms and microbial pathogenesis, leading to targeted therapies. This article focuses on how intracellular microbes reside in specific cell types, modulating functions through persistence strategies to evade host immunity and prolong colonization. An improved understanding of the persistent intracellular microbe-induced differential disease outcomes can enhance diagnostics, therapeutics, and preventive measures.
Genetic types and provenance indication of clastic amphibole in the South Yellow Sea
Authors: Wang Mengyao , Jin Bingfu , Liu Jian , Gao Maosheng , Gao Jianhua , Jia Jianjun
Published: May 2024

The main focus of studying sediment sources in marine areas is to determine the properties of clastic minerals originating from different rivers. Variations in the characteristics of clastic minerals occur due to differences in the types of source rocks within the watershed. Determining the source rock of clastic minerals in the marine area can improve the accuracy of provenance analysis. Electron probe microanalysis of 258 amphibole grains from six surface stations in the South Yellow Sea (SYS) was conducted to calculate the numerical and characteristic values of cations in the crystal structure. The results showed that amphibole in the SYS is mainly magnesiohornblende (52.2% ~ 81.4%) in the calcic amphibole subgroup, followed by tschermakite. The source rock types of amphibole are mainly different types of magmatic (ultrabasic, basic, and intermediate acidic) and metamorphic rocks. Amphibole derived from intermediate-acid intrusive rocks accounts for a large proportion (>40%). The genetic analysis of clastic amphibole in the SYS showed that most of the medium-acid invading amphibole belong to crust-mantle type, followed by mantle type. Most of the amphibole from metamorphic origins are of medium-low pressure type (± 80%). Combined with electron probe analysis of amphibole from the Huanghe River (the Yellow River, HH) and Changjiang River (the Yangtze River, CJ), the amphibole in the SYS exhibits characteristics inherited from these two rivers. The northern sea area has a strong resemblance to the sediments from the HH, while the southern area is more influenced by sediments supply from the CJ. The central area represents a mixed zone with a higher sediment supply from the HH. The clastic amphibole deduces the type of source rock in different watersheds, serving as a crucial link between the source rock, watershed, and marine area, providing a basis for provenance analysis.
Ocean deoxygenation dampens resistance of diatoms to ocean acidification in darkness
Authors: Sun Jia-Zhen , Zhang Di , Yi Xiangqi , Beardall John , Gao Kunshan
Published: May 2024

Respiratory activity in the oceans is declining due to the expansion of hypoxic zones and progressive deoxygenation, posing threats to marine organisms along with impacts of concurrent ocean acidification. Therefore, understanding the combined impacts of reduced pO2 and elevated pCO2 on marine primary producers is of considerable significance. Here, to simulate diatoms’ sinking into the aphotic zone of turbid coastal water, we exposed the diatoms Thalassiosira pseudonana and Thalassiosira weissflogii in darkness at 20°C to different levels of pO2 and pCO2 conditions for ~3 weeks, and monitored their biomass density, photosynthetic activity and dark respiration, and examined their recovery upon subsequent exposure to light at 20°C, simulating surface water conditions. Along with decreased cell abundance and size, measured photosynthetic capacity and dark respiration rates in these two diatoms both gradually decreased during the prolonged darkness. Reduced pO2 alone did not negatively affect the photosynthetic machinery in both the dark-survived diatom, and enhanced their subsequent recovery upon light exposure. Nevertheless, the combination of the elevated pCO2 and reduced pO2 (equivalent to hypoxia) led to the biomass loss by about 90% in T. pseudonana, and delayed the recovery of both species upon subsequent exposure to light, though it did not reduce the cell concentration of T. weissflogii during the elongated darkness. Our results suggest that reduced O2 availability diminishes the abilities of the diatoms to cope with the acidic stress associated with ocean acidification, and the expansion of hypoxic waters could delay the photosynthetic recovery of coastal diatoms when they are transported upwards through mixing from dark layers to sunlit waters.
Long-lasting renewable antibacterial N-halamine coating enable dental unit waterlines to prevention and control of contamination of dental treatment water
Authors: Xing Min , Zhang Haifeng , Li Zhiyao , Zhang Ling , Qian Wenhao
Published: May 2024

Developing bacterial biofilm on the dental unit waterlines increases the risk of cross-infection among oral patients. Although chemical disinfectants can achieve disinfection effects in a short period of time, corrosion damage of dental unit waterlines and water contamination can also occur after continuous use of it. Herein, this study explored a one-step deposition method to prepare a durable and renewable antibacterial N-halamine polymeric coating on polyurethane waterlines. The method utilized polyelectrolyte complexes formed with polyethylenimine (PEI) and phytic acid (PA), followed by chlorination to activate the antibacterial properties. The N-halamine polymeric coating reduces the polyurethane waterline’s water contact angle, thus reducing biofouling deposits and the obstruction of the active halide site on the waterlines, thereby facilitating the maintenance of the cleanliness of the coating. In addition, benefiting both from the active chlorine release and the high density of positive charges on the coating, the polyurethane waterline antimicrobial activity is significantly enhanced. Besides, the N-halamine polymeric coating is biocompatible. This study showed that long-lasting and renewable antimicrobial requirements can be achieved by simple surface modification of N-halamine polymer coatings, which provides a practicable strategy for the production of long-term and reproducible antibacterial dental unit waterlines to reduce the incidence of hospital infection in oral department.
Biodegradable flexible triboelectric nanogenerator for winter sports monitoring
Authors: Liu Bocong , Xie Zhenning , Feng Qingyang , Wang Yunlu , Zhang Mengqi , Lu Zhuo , Mao Yupeng , Zhang Shouwei
Published: May 2024

With the energy crisis and environmental pollution becoming a growing concern worldwide, the development of clean and renewable energy from the environment has become an imperative for human survival and development. However, the equipment used to harvest clean renewable energy is large, subject to environmental impacts and regional differences (such as wind, solar and tidal energy). In this study, a biodegradable eggshell membrane triboelectric nanogenerator (EM-TENG) is introduced for the purpose of harvesting low-frequency mechanical energy. A Wireless Intelligent Motion Monitoring System (WIMMS) has been created using EM-TENG. It includes a Bluetooth sensor terminal and an intelligent processing terminal for digital signal reception on a host computer. The EM-TENG can be attached to knee and ankle joints to monitor posture. Therefore, for real-time monitoring of joint and kinetic chain changes during land training of ice dance athletes, the intelligent ice dance land training aid system is important. As a wearable motion monitoring sensor, EM-TENGs application in intelligent motion monitoring, intelligent wearable devices and big data analytics is being promoted.
Mining bone metastasis related key genes of prostate cancer from the STING pathway based on machine learning
Authors: Li Guiqiang , Zhao Runhan , Xie Zhou , Qu Xiao , Duan Yingtao , Zhu Yafei , Liang Hao , Tang Dagang , Li Zefang , He Weiyang
Published: May 2024

Background

Prostate cancer (PCa) is the second most prevalent malignant tumor in male, and bone metastasis occurs in about 70% of patients with advanced disease. The STING pathway, an innate immune signaling mechanism, has been shown to play a key role in tumorigenesis, metastasis, and cancerous bone pain. Hence, exploring regulatory mechanism of STING in PCa bone metastasis will bring novel opportunities for treating PCa bone metastasis.

Methods

First, key genes were screened from STING-related genes (SRGs) based on random forest algorithm and their predictive performance was evaluated. Subsequently, a comprehensive analysis of key genes was performed to explore their roles in prostate carcinogenesis, metastasis and tumor immunity. Next, cellular experiments were performed to verify the role of RELA in proliferation and migration in PCa cells, meanwhile, based on immunohistochemistry, we verified the difference of RELA expression between PCa primary foci and bone metastasis. Finally, based on the key genes to construct an accurate and reliable nomogram, and mined targeting drugs of key genes.

Results

In this study, three key genes for bone metastasis were mined from SRGs based on the random forest algorithm. Evaluation analysis showed that the key genes had excellent prediction performance, and it also showed that the key genes played a key role in carcinogenesis, metastasis and tumor immunity in PCa by comprehensive analysis. In addition, cellular experiments and immunohistochemistry confirmed that overexpression of RELA significantly inhibited the proliferation and migration of PCa cells, and RELA was significantly low-expression in bone metastasis. Finally, the constructed nomogram showed excellent predictive performance in Receiver Operating Characteristic (ROC, AUC = 0.99) curve, calibration curve, and Decision Curve Analysis (DCA) curve; and the targeted drugs showed good molecular docking effects.

Conclusion

In sum, this study not only provides a new theoretical basis for the mechanism of PCa bone metastasis, but also provides novel therapeutic targets and novel diagnostic tools for advanced PCa treatment.
Pharmacy students’ interprofessional experience and performance in advanced pharmacy practice experience rotations amid COVID-19 pandemic
Authors: Alrasheed Marwan , Alsuhibani Abdulrahman , Alotaibi Wadha , Gari Musaab , Alashgar Amin , Doherty Michael , Boone Jill , Almangour Thamer A. , Hincapie Ana
Published: May 2024

Introduction

Interprofessional education (IPE) is essential in pharmacy training, providing students with vital collaborative skills for real-world healthcare. Advanced Pharmacy Practice Experience (APPE) is integral to IPE, allowing students to apply their knowledge in diverse healthcare settings. The COVID-19 pandemic has disrupted healthcare education and raised concerns about its impact on IPE during APPE rotations. Our study investigates the pandemic’s influence on pharmacy students’ interprofessional interactions and APPE performance.

Objective

To assess the interprofessional experiences of fourth-year pharmacy students before and during the COVID-19 pandemic in the context of APPE.

Methods

This retrospective observational study examined the experiences of P4 pharmacy students in the United States during APPEs before and during the pandemic. We employed electronic surveys with 21 questions to gauge interactions and interprofessional team effectiveness, employing Likert scale response options. We compared responses between the 2019–2020 and 2020–2021 APPE rotations using statistical tests.

Results

Our study encompassed 83 and 86 students for the 2019–2020 and 2020–2021 APPE rotations, respectively, achieving a 100% response rate. Amid the pandemic, written communications between pharmacy students and healthcare providers in general medicine rotations increased, while in-person engagement decreased. Pre-COVID, students reported higher colleague referrals and greater interprofessional utilization during ambulatory care rotations.

Conclusion

COVID-19 shifted interactions from in-person to written communication between pharmacy students and healthcare providers. Students reported decreased satisfaction with their interprofessional experiences. This research offers insights into the changing landscape of pharmacy education, helping students prepare for evolving challenges in healthcare delivery and education.
TP-GCL: graph contrastive learning from the tensor perspective
Authors: Li Mingyuan , Meng Lei , Ye Zhonglin , Yang Yanglin , Cao Shujuan , Xiao Yuzhi , Zhao Haixing
Published: May 2024

Graph Neural Networks (GNNs) have demonstrated significant potential as powerful tools for handling graph data in various fields. However, traditional GNNs often encounter limitations in information capture and generalization when dealing with complex and high-order graph structures. Concurrently, the sparse labeling phenomenon in graph data poses challenges in practical applications. To address these issues, we propose a novel graph contrastive learning method, TP-GCL, based on a tensor perspective. The objective is to overcome the limitations of traditional GNNs in modeling complex structures and addressing the issue of sparse labels. Firstly, we transform ordinary graphs into hypergraphs through clique expansion and employ high-order adjacency tensors to represent hypergraphs, aiming to comprehensively capture their complex structural information. Secondly, we introduce a contrastive learning framework, using the original graph as the anchor, to further explore the differences and similarities between the anchor graph and the tensorized hypergraph. This process effectively extracts crucial structural features from graph data. Experimental results demonstrate that TP-GCL achieves significant performance improvements compared to baseline methods across multiple public datasets, particularly showcasing enhanced generalization capabilities and effectiveness in handling complex graph structures and sparse labeled data.
Research hotspots and trends of microRNAs in spinal cord injury: a comprehensive bibliometric analysis
Authors: Hu Baoyang , Zhao Yue , Chen Chao , Wu Bin , Zhang Hongbin , Liu Bin , Zheng Runquan , Fang Fang
Published: May 2024

Background

Spinal cord injury (SCI) is a nervous system disease leading to motor and sensory dysfunction below the injury level, and can result in paralysis. MicroRNAs (miRNAs) play a key role in SCI treatment, and related research provides insights for SCI diagnosis and treatment. Bibliometrics is an important tool for literature statistics and evaluation, objectively summarizing multidimensional information. This study comprehensively overviews the field through bibliometric analysis of miRNA and SCI research, providing contemporary resources for future collaboration and clinical treatment.

Materials and methods

In this study, we searched the Web of Science Core Collection (WOSCC) database. After careful screening and data import, we extracted annual publications, citation counts, countries, institutions, authors, journals, highly cited articles, co-cited articles, keywords, and H-index. Bibliometrics and visualization analyses employed VOSviewer, CiteSpace, the R package “bibliometrix,” and online analytic platforms. Using Arrowsmith,1 we determined miRNA-SCI relationships and discussed potential miRNA mechanisms in SCI.

Results

From 2008 to 2024, the number of related papers increased annually, reaching 754. The number of yearly publications remained high and entered a period of rapid development. Researchers from 50 countries/regions, 802 institutions, 278 journals, and 3,867 authors participated in the field. Currently, China has advantages in the number of national papers, citations, institutions, and authors. However, it is necessary to strengthen cooperation among different authors, institutions, and countries to promote the production of important academic achievements. The research in the field currently focuses on nerve injury, apoptosis, and gene expression. Future research directions mainly involve molecular mechanisms, clinical trials, exosomes, and inflammatory reactions.

Conclusion

Overall, this study comprehensively analyzes the research status and frontier of miRNAs in SCI. A systematic summary provides a complete and intuitive understanding of the relationship between SCI and miRNAs. The presented findings establish a basis for future research and clinical application in this field.
Intervention effects of low-molecular-weight chondroitin sulfate from the nasal cartilage of yellow cattle on lipopolysaccharide-induced behavioral disorders: regulation of the microbiome-gut-brain axis
Authors: Deng Yuxuan , Li Qingyuan , Song Junxian , Guo Rui , Ma Tianchen , Liu Zhigang , Liu Qian
Published: May 2024

Chondroitin sulfate (CS) is a sulfated linear polysaccharide with different functional activities, including antioxidant, anti-inflammatory, lipid-lowering, and immune regulation. As natural sulfated polysaccharides have high molecular weight, high apparent viscosity, low water solubility, complex structure, and high negative charge, they have difficulty binding to receptors within cells across tissue barriers, resulting in low bioavailability and unclear structure–activity relationships. In this study, an H2O2-Vc oxidative degradation system was employed to perform environmentally friendly and controllable degradation of CS extracted from the nasal cartilage of Shaanxi Yellow cattle. Two low-molecular-weight chondroitin sulfates (LMWCSs), CS-1 (14.8 kDa) and CS-2 (50.9 kDa), that exhibit strong in vitro free radical scavenging ability were obtained, and their structures were characterized. Mice intraperitoneally administered lipopolysaccharide (LPS) were used to explore the cognitive intervention effects of LMWCS. Supplementing CS-1 and CS-2 significantly downregulated the levels of the serum inflammatory factors, TNF-α and IL-1β, promoted the expression of GSH in the brain, and inhibited the production of the lipid peroxidation product, malondialdehyde (MDA), ultimately inhibiting LPS-induced cognitive impairment in mice. Surprisingly, compared to the LPS model group, the abundances of Streptococcus, Eisenbergiella, Vampirovibrio, Coprococcus, Enterococcus and Lachnoanaerobaculum were significantly increased in the intestines of mice in the CS-1 and CS-2 group, whereas those of Parabacteroides and Mycoplasma were significantly decreased. Altogether, this study provides a theoretical basis for the comprehensive utilization of agricultural and animal resources and the application of brain nutrition, anti-inflammatory, and LMWCS health products.
A case of left atrial intimal sarcoma with rhabdomyosarcoma differentiation: a case report and literature review
Authors: Shu Hongyun , Xiao Duan , Han Sisi , Du Yongkang , Lin Jinduan , Li Qiaowen
Published: May 2024

Primary cardiac malignancies are rare, with cardiac sarcomas being the main type. Among these, intimal sarcomas are the most common. However, they tend to occur in the great vessels and are rare in the heart, with only a few isolated cases reported. We report a challenging case of a patient with left atrial intimal sarcoma with rhabdomyosarcoma differentiation. The patient was admitted after a physical examination detected left heart occupancy, and initial imaging suspected a left atrial thrombus. The patient then underwent extracorporeal circulation-assisted open cardiac surgery with resection of an atrial mass. The postoperative pathological findings were suggestive of an arterial intimal sarcoma, which included areas of rhabdomyosarcoma differentiation within the tumor tissue. Unfortunately, the patient’s tumor recurred 4 months later, and she died due to treatment failure. This case highlights the rarity and risk of misdiagnosis of cardiac intimal sarcoma. Additionally, we aim to improve the understanding of intimal sarcoma through a review of immunohistochemistry and gene amplification techniques.
Perioperative systemic treatments in renal cell carcinoma
Authors: Goswamy Rohit , Kalemoglu Ecem , Master Viraj , Bilen Mehmet Asim
Published: May 2024

In this review, we aim to provide a comprehensive assessment of the evolving landscape of the perioperative management in renal cell carcinoma (RCC), emphasizing its dynamic and intricate nature. We explore academic and clinical insights into the perioperative treatment paradigm of RCC. Up-to-date treatment options are discussed and the evolving role of neoadjuvant and adjuvant therapy in RCC is highlighted.
Detection and comparison of tumor cell-associated microbiota from different compartments of colorectal cancer
Authors: Zuo Yanzhen , Lu Yanjie , Pang Jiayu , Jin Shunkang , Zhang Xinyu , Zhao Enhong , Li Yuhong
Published: May 2024

Introduction

Intratumoral microbes play an important role in the development of colorectal cancer (CRC). However, studying intratumoral microbes in CRC faces technical challenges, as tumor microbe communities are often contaminated by fecal microbes due to the structure of the gut folds and villi. The present study aimed to develop a new method for isolating tumor cell-associated microbiota and comparing microbial populations from different compartments.

Materials and methods

The distribution of intestinal bacteria was detected using immunohistochemistry combined with 5R-16s rRNA gene sequencing to explore the effects of the sampling site and number of washes on the detection of microbiota. The 5R-16s rRNA gene sequencing was performed using 44 samples from 11 patients with CRC, including CRC tumor tissues (TT), normal tissues adjacent to CRC (NT), tumor cells (TC), and normal cells (NC). TC and NC were obtained from the TT and NT using an enzymatic digestion method. The microbiota and their potential functions in the four groups were analyzed and compared to determine the differential microbiota related to CRC.

Results

Bacteria were mainly distributed in the feces covering intestinal tissues and in the epithelial cells and macrophages within the tissues. Different sampling sites and number of washes led to detection of different microbiota distributions. Although the cleaning method could be controlled, sampling sites varied and led to different microbiota distributions. The phyla of Firmicutes and Bacteroidetes were highly abundant in the conventionally used tissue samples, whereas Proteobacteria was the most abundant phyla in the cell samples isolated with the new method (i.e., after cell enzymatic hydrolysis). Detection of CRC cell-associated microbiota using a cell enzymatic digestion method showed that some bacteria, such as Fusobacterium, Eikenella, Shewanella, and Listeria, were more abundant in TT than NT, whereas the abundance of Akkermansia was lower in TT than NT. The tumor/normal ratios of some bacteria, such as Gemella, Escherichia, Shigella, and Blautia, were different between the cell and tissue samples.

Conclusion

The cell enzymatic digestion method reduced fecal bacterial contamination, enabling low biomass intratumoral microbiota to be detected and allowing prediction of bacterial distributions.
Case report: Axillary lymph node metastases from primary ovarian cancer: a report of two cases and literature review
Authors: Abdullah Norlia , Rosly Nadiah , Pauzi Suria Hayati Md , Mustapha Aida Widure , Arifuddin Yulianty
Published: May 2024

Ovarian cancer is usually confined intraperitoneally. Distant metastases at presentation is unusual. Its spread via lymphatics is uncommon, and metastasis to axillary lymph nodes is very rare. We report two cases with presentation of axillary lymphadenopathy without breast involvement. Computed tomography scan identified the ovarian masses. Both had elevated Serum Ca 125. The first case had a Grade 2 ovarian endometrioid carcinoma. The second case had a high-grade serous ovarian carcinoma. These cases illustrate the rarity of axillary lymphadenopathy from ovarian cancer. It is important to identify the primary ovarian carcinoma in order to offer appropriate management. Despite surgery and chemotherapy, both succumbed within 3 years from diagnosis.
The impact of Bruton’s tyrosine kinase inhibitor treatment on COVID-19 outcomes in Chinese patients with chronic lymphocytic leukemia
Authors: Yang Shenmiao , Wei Rong , Shi Hongxia , Wang Yazhe , Lai Yueyun , Zhao Xiaosu , Lu Jin , Schmitz Norbert
Published: May 2024

Background

Impact of B-cell depletion following treatment with Bruton tyrosine kinase-inhibitors (BTKi) on the outcome of SARS-CoV-2 infection in chronic lymphocytic leukemia (CLL) patients remain controversial. We investigated the impact of BTKi on susceptibility and the severity of COVID-19 in Chinese patients with CLL during the first wave of COVID-19 (Omicron variant).

Methods

CLL patients (n=171) visiting the Institute of Hematology, Peoples’ Hospital, China (November 15, 2022- January 20, 2023) were included in the study. Seventeen patients receiving BTKi and venetoclax with or without obinutuzumab were excluded. Data from 117 patients receiving treatment with BTKi were collected using a standardized questionnaire through telephone interviews. Thirty-four patients without CLL-specific treatment served as controls. The data was analysed using IBM SPSS Software version 21 and a P value of <0.05 was considered statistically significant.

Results

The median age of patients was 67 years and majority were males (n=100). Treatment with BTKi was not associated with higher incidence of COVID-19 (74% [95% Confidence Interval (CI) 60%, 92%]) versus 74% (CI 48%, 100%) without any treatment (P=0.92). Hypoxemia was reported by 45% (32%, 61%) and 16% (4%, 41%) (P=0.01). BTKi was the only independent risk factor of hypoxemia (Hazard Ratio [HR], 4.22 [1.32, 13.50]; P = 0.02). Five (5.7%) patients with COVID-19 under BTKi required ICU admission; 4 of them died. No ICU admissions/deaths were observed in the control group.

Conclusion

In Chinese patients with CLL and treated with BTKi experienced more severe lung disease and ICU admissions due to COVID-19 than patients without CLL therapy. Frequency of infections with SARS-CoV-2, however, was not different in patients with or without BTKi treatment.
Cang-ai volatile oil alleviates nasal inflammation via Th1/Th2 cell imbalance regulation in a rat model of ovalbumin-induced allergic rhinitis
Authors: Zhou Yang , Chen Bojun , Fu Yi , Wan Chunping , Li Huayan , Wang Lin , Huang Xiaoyi , Wu Zhao , Li Gang , Xiong Lei , Qin Dongdong
Published: May 2024

We previously revealed that Cang-ai volatile oil (CAVO) regulates T-cell activity, enhancing the immune response in people with chronic respiratory diseases. However, the effects of CAVO on allergic rhinitis (AR) have not been investigated. Herein, we established an ovalbumin (OVA)-induced AR rat model to determine these effects. Sprague–Dawley (SD) rats were exposed to OVA for 3 weeks. CAVO or loratadine (positive control) was given orally once daily for 2 weeks to OVA-exposed rats. Behavior modeling nasal allergies was observed. Nasal mucosa, serum, and spleen samples of AR rats were analyzed. CAVO treatment significantly reduced the number of nose rubs and sneezes, and ameliorated several hallmarks of nasal mucosa tissue remodeling: inflammation, eosinophilic infiltration, goblet cell metaplasia, and mast cell hyperplasia. CAVO administration markedly upregulated expressions of interferon-γ, interleukin (IL)-2, and IL-12, and downregulated expressions of serum tumor necrosis factor-α, IL-4, IL-5, IL-6, IL-13, immunoglobulin-E, and histamine. CAVO therapy also increased production of IFN-γ and T-helper type 1 (Th1)-specific T-box transcription factor (T-bet) of the cluster of differentiation-4+ T-cells in splenic lymphocytes, and protein and mRNA expressions of T-bet in nasal mucosa. In contrast, levels of the Th2 cytokine IL-4 and Th2-specific transcription factor GATA binding protein-3 were suppressed by CAVO. These cumulative findings demonstrate that CAVO therapy can alleviate AR by regulating the balance between Th1 and Th2 cells.
Ji-Ni-De-Xie ameliorates type 2 diabetes mellitus by modulating the bile acids metabolism and FXR/FGF15 signaling pathway
Authors: Tao Yiwen , Peng Fang , Wang Lijie , Sun Jiayi , Ding Yin , Xiong Shuangfeng , Tenzin Ugen , MiMa  , Nhamdriel Tsedien , Fan Gang
Published: May 2024

Introduction: Ji-Ni-De-Xie (JNDX) is a traditional herbal preparation in China. It is widely used to treat type 2 diabetes mellitus (T2DM) in traditional Tibetan medicine system. However, its antidiabetic mechanisms have not been elucidated. The aim of this study is to elucidate the underlying mechanism of JNDX on bile acids (BAs) metabolism and FXR/FGF15 signaling pathway in T2DM rats.

Methods: High-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QQQ-MS) and UPLC-Q-Exactive Orbitrap MS technology were used to identify the constituents in JNDX. High-fat diet (HFD) combined with streptozotocin (45 mg∙kg−1) (STZ) was used to establish a T2DM rat model, and the levels of fasting blood-glucose (FBG), glycosylated serum protein (GSP), homeostasis model assessment of insulin resistance (HOMA-IR), LPS, TNF-α, IL-1β, IL-6, TG, TC, LDL-C, HDL-C, and insulin sensitivity index (ISI) were measured to evaluate the anti-diabetic activity of JNDX. In addition, metagenomic analysis was performed to detect changes in gut microbiota. The metabolic profile of BAs was analyzed by HPLC-QQQ-MS. Moreover, the protein and mRNA expressions of FXR and FGF15 in the colon and the protein expressions of FGF15 and CYP7A1 in the liver of T2DM rats were measured by western blot and RT-qPCR.

Results: A total of 12 constituents were identified by HPLC-QQQ-MS in JNDX. Furthermore, 45 chemical components in serum were identified from JNDX via UPLC-Q-Exactive Orbitrap MS technology, including 22 prototype components and 23 metabolites. Using a T2DM rat model, we found that JNDX (0.083, 0.165 and 0.33 g/kg) reduced the levels of FBG, GSP, HOMA-IR, LPS, TNF-α, IL-1β, IL-6, TG, TC, and LDL-C, and increased ISI and HDL-C levels in T2DM rats. Metagenomic results demonstrated that JNDX treatment effectively improved gut microbiota dysbiosis, including altering some bacteria (e.g., Streptococcus and Bacteroides) associated with BAs metabolism. Additionally, JNDX improved BAs disorder in T2DM rats, especially significantly increasing cholic acid (CA) levels and decreasing ursodeoxycholic acid (UDCA) levels. Moreover, the protein and mRNA expressions of FXR and FGF15 of T2DM rats were significantly increased, while the expression of CYP7A1 protein in the liver was markedly inhibited by JNDX.

Discussion: JNDX can effectively improve insulin resistance, hyperglycemia, hyperlipidemia, and inflammation in T2DM rats. The mechanism is related to its regulation of BAs metabolism and activation of FXR/FGF15 signaling pathway.