bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of heavy metals on osteoporosis in postmenopausal women
Authors: Peng Shiyu , Zhang Gaoxiang , Wang Decheng , He Zhiliang
Published: February 2025

Objective

Heavy metals are present in many environmental pollutants, and have cumulative effects on the human body, which can lead to several diseases, including osteoporosis (OP). However, limited information was known about the correlation between OP and heavy metals, especially in postmenopausal women. The current research was aimed to explore the association heavy metals and bone mineral density (BMD) with OP risk among postmenopausal women in the US.

Methods

This cross-sectional study enrolled participants in NHANES 2013–2014 and 2017–2020. ICP–MS was applied to detect five metals, namely, Pb, Cd, Hg, Se and Mn, in blood. BMD was measured through DXA and then converted to T-scores. At the same time, the impacts of exposure to single and mixed metals on OP were assessed using multivariable logistic regression, WQS, and BKMR models. The relationship was examined based on age and BMI.

Results

Totally 905 postmenopausal women were enrolled for final analysis. Among them, 161 (17.80%) participants had OP. Logistic regression indicated that, Cd [OR (95% CI): 1.815 (1.076, 3.061) and 2.180 (1.309, 3.631), separately, P for trend = 0.006] and Se [OR (95% CI): 0.570 (0.356, 0.914), 0.454 (0.276, 0.747) and 0.689 (0.433, 1.097), separately, P for trend = 0.071] were related to OP in the adjusted model 1. Similar results to model 1 were obtained by the rest models. Multivariate linear regression model analysis suggested that subjects who had the greatest quartile of Cd level (Q4) exhibited lower BMD within the entire femur (β = −0.112, P = 0.007; P for trend = 0.003) compared to those in Q1. The WQS analysis suggested that Cd was correlated positively with increased OP risk, whereas Se inversely associated. In BKMR analysis, exposure to mixed metals was significantly positively related to OP. In subgroup analysis, Cd's impact on OP risk was most pronounced in the 50–60 year age and 25–30 kg/m2 BMI subgroups, and Se offered protection in older age and higher BMI groups.

Conclusion

This is the ﬁrst study to determine the correlation between OP and heavy metals among postmenopausal women in the US based on large data. The results showed that the increased mixed metal concentration may lead to an increased OP risk among postmenopausal women. Blood Cd level was associated with an increased OP risk, and blood Se level served as the predicting factor for OP. More investigations are warranted to demonstrate our findings and elucidate the underlying biological mechanism.
Assessment of human activities on soil contamination in Egypt: implications for the MENA region
Authors: Hendawy Ehab , Belal Abdel-Aziz , Sheta Abd El Aziz S. , Mohamed Elsayed Said , Kucher Dmitry E. , Jalhoum Mohamed E. M. , Shokr Mohamed S. , Ali Abdelraouf M. , Othman Yahia A. , Abou-Hadid Ayman F.
Published: February 2025

Introduction

Decision-makers around the world are very concerned about contaminated soil since it has a direct effect on soil and food security. This study seeks to evaluate soil contamination by a chosen heavy metal, Ni, Mn, Co, Cu, Cd, Pb, Fe, and Zn in the studied area located around the Kitchener drain in Egypt, its main source for irrigation water in the studied area and it extends 69 km and pass through Gharbia, Kafr El-Sheikh and Dakahlia Governorates, Egypt near).

Methodology

Principal component analysis (PCA), cluster analysis, contamination factor (CF) and degree of contamination (DC) indices, which Quantified the level of contamination hazard supported by GIS, were used to determine the level of soil contamination in the area under study.

Results

The spatial pattern of studied variables by kriging shows that The K-Bessel model is fitted for electrical conductivity (EC), Ni, and Cu, the exponential model is well-suited for pH, CaCO3%, and Fe in the soil, and the circular model fit for Mn. Stable model for silt, furthermore, a Gaussian model was fitted for Sand, Clay, and Cd and the hole Effect model for Co. As these models had low Mean Standardized Error (MSE) values (around zero) and Root-Mean-Square Standardized Error (RMSSE) values that were close to one. It indicates that the modals’ forecasts are roughly as precise as the baseline. The study area was divided into three zones based on the unconventional results of the integration of PCA and cluster analysis; each zone has a different heavy metal concentration and pattern. The results showed, that 0.82% of the studied area, the pollution was at a moderate level. Very high levels of heavy metal contamination were found throughout most of the area (79.24%); average concentrations of these metals were found to be 132.2+/-31.8,672.6 ± 125.4, 8.9 ± 5.1,103.8 ± 44.4, 25.5 ± 3.5,30.6 ± 10.3,223,021.4 ± 40484, and 246.5 ± 248.7 mg kg−1 for Ni, Mn, Co, Cu, Cd, Pb, Fe, and Zn, respectively. On the other hand, 19.92% of the studied area is contaminated considerably. There are various sources of contamination; such as household goods and industrial trash, including those from the textile, paint, sewage, and leather tanning industries; agricultural wastes, particularly those that contain pesticides and superphosphate fertilisers; and sewage sludge.

Conclusion

Overall mapping soil contamination could help decision-makers create suitable heavy metal mitigation strategies. To lessen human harmful behaviors that create environmental contamination, the study suggests enacting farm management legislation. Future research will also concentrate on strategies for controlling and lessening the consequences of soil pollution.
Uncovering the surge: dengue fever on the rise
Authors: Wheaton Noah , Wong Christian , Gasmelseed Huda , Zinabu Samrawit , Sood Aseem , Rajendran Rithika , Shead Madison , Sanders Amaya , Norton Tabitha , Michael Miriam
Published: February 2025

Introduction

Dengue fever, traditionally a tropical disease, has shown a notable increase in incidence within the United States over recent decades. This paper focuses on the increase in dengue fever cases in Maryland during increasing temperature and humidity and the expanding geographical range of Aedes mosquitoes, the primary vectors for dengue virus transmission.

Methods

Electronic health data was used to identify patterns in dengue incidence from 2014 to 2024. Correlation analysis between temperature and dengue incidence and a review of humidity factors was conducted.

Results

Results indicate an increased incidence of dengue fever cases over the past decade. However, a reduction in dengue incidence was observed in 2019–2020, likely due to COVID-19-related travel restrictions.

Discussion

As global temperatures increase, the habitats suitable for Aedes mosquitoes have expanded, allowing for their proliferation in previously inhospitable regions. Additionally, higher temperatures can accelerate the life cycle and viral replication rates in these mosquitoes, further enhancing transmission potential. Humidity, another key environmental factor, influences the life expectancy of dengue mosquitoes. This research underscores the urgency of addressing climate change as a public health issue, emphasizing the need for integrated vector management strategies and public health preparedness to mitigate the growing threat of dengue in temperate regions. By understanding the interplay between global warming, humidity, and dengue transmission, we can better inform policy decisions and healthcare practices to curb the spread of this disease in Maryland and the United States.
Research progress of T cells in cholangiocarcinoma
Authors: Wang Zhiming , Dai Yunyan , Zhou Yunpeng , Wang Yi , Chen Pinggui , Li Yaoxuan , Zhang Yunfei , Wang Xiaocui , Hu Ying , Li Haonan , Li Gaopeng , Jing Yukai
Published: February 2025

Cholangiocarcinoma (CCA), a malignant tumor, is typically challenging to detect early and often results in a poor prognosis. In recent years, research interest has grown in the potential application of immunotherapy for CCA treatment. T cells, as a crucial component of the immune system, play a significant role in immune surveillance and therapy for cholangiocarcinoma. This article provides a review of the research advancements concerning T cells in cholangiocarcinoma patients, including their distribution, functional status, and correlation with patient prognosis within the tumor microenvironment. It further discusses the potential applications and challenges of immunotherapy strategies targeting T cells in CCA treatment and anticipates future research directions. A more profound understanding of T cells’ role in cholangiocarcinoma can guide the development of clinical treatment strategies, thereby enhancing patient survival rates and quality of life. Finally, we explored the potential risks and side effects of immunotherapy for T-cell cholangiocarcinoma.
Efficacy and safety of PD-1/PD-L1 inhibitors alone or in combination in the treatment of metastatic or advanced renal cell carcinoma: a network meta-analysis
Authors: Zhang Dongli , Shen Chong , Zhang Weichuan , Chen Haibin , Zhao Jianjun
Published: February 2025

Background

This study systematically reviews the efficacy and safety of the single or combined use of programmed factor 1 (PD-1)/programmed factor 1 ligand (PD-L1) inhibitors for treating metastatic or advanced renal cell carcinoma (RCC).

Methods

Relevant articles were collected for meta-analysis through searches on PubMed, Web of Science, Embase, Cochrane Library, and Clinical Trials, as well as for relevant randomized controlled experiments.

Results

Based on eleven studies, the effectiveness of the experimental group was found to be significantly better than the control in terms of overall survival (OS) [R=0.74, 95%CI: 0.69~0.80, P<0.00001], progression-free survival (PFS) [HR=0.68, 95%CI: 0.57~0.81, P<0.0001], objective response rate (ORR) [RR=1.71, 95%CI: 1.39~2.12, P<0.00001], complete response rate (CR) [RR=2.99 95%CI: 2.34~3.83, P<0.0001], partial response rate (PR) [RR=1.56, 95%CI: 1.20~2.01, P=0.001], and disease control rate (DCR) [RR=1.13, 95%CI: 1.06~1.20, P<0.0001]. No statistical significance was observed between the experimental and control groups in overall adverse reactions (AEs) [RR=1.01, 95%CI: 0.98~1.04, P=0.598], the incidence of stage I~II adverse reactions [RR=1.02, 95%CI: 0.88~1.17, P=0.818], or stage III~V adverse reactions [RR=0.98, 95%CI: 0.81~1.18, P=0.817]. Regarding subgroup analysis, the incidence of dysphonia, rash, hypothyroidism, arthralgia, and pruritus in the experimental group was significantly higher than in the control. Compared with the control group, the incidence of diarrhea, nausea, indigestion, and fatigue in the experimental group was not statistically significant.

Conclusion

A good efficacy was found in treating metastatic or advanced RCC using PD-1/PD-L1 inhibitors alone or in combination, which significantly improved and enhanced OS, PFS, ORR, CR, PR, and DCR in patients with RCC. The incidence of adverse reactions in patients was not increased, and adverse reactions were controllable. These findings indicate that the single or combined use of PD-1/PD-L1 inhibitors shows good efficacy and safety in the treatment of metastatic or advanced RCC.
Reinforcement learning-based multi-model ensemble for ocean waves forecasting
Authors: Huang Weinan , Wu Xiangrong , Xia Haofeng , Zhu Xiaowen , Gong Yijie , Sun Xuehai
Published: February 2025

This study addresses the challenges of uncertainty in wave simulations within complex and dynamic ocean environments by proposing a reinforcement learning-based model ensemble algorithm. The algorithm combines the predictions of multiple base models to achieve more accurate simulations of ocean variables. Utilizing the soft actor-critic reinforcement learning framework, the method dynamically adjusts the weights of each base model, enabling the model ensemble algorithm to effectively adapt to varying ocean conditions. The algorithm was validated using two SWAN models results for China’s coastal regions, with ERA5 reanalysis data serving as a reference. Results show that the ensemble model significantly outperforms the base models in terms of root mean square error, mean absolute error, and bias. Notable improvements were observed across different significant wave height ranges and in scenarios with large discrepancies between base model errors. The model ensemble algorithm effectively reduces systematic biases, improving both the stability and accuracy of wave predictions. These findings confirm the robustness and applicability of the proposed method for integrating multi-source data and handling complex ocean conditions, highlighting its potential for broader applications in ocean forecasting.
Effectiveness of glucocorticoids in preventing esophageal stricture and predictors of stricture after esophageal ESD: 5 years of experience in a single medical center
Authors: Wang Qingxia , Ding Yuan , Qian Qiliu , Zhu Yinnan , Shi Ruihua
Published: February 2025

Background

Esophageal stricture is one of the major complications after endoscopic submucosal dissection (ESD) of the esophagus. However, even with steroid prophylaxis, stenosis still occurs in up to 45% of patients. Accordingly, the aim of this study was to evaluate the efficacy and safety of steroid therapy in preventing esophageal strictures after ESD, as well as to assess the predictors of esophageal strictures after the application of steroids.

Methods

Between February 2018 and March 2023, 207 patients who underwent esophageal ESD at Southeast University Affiliated Zhongda Hospital were retrospectively enrolled. We evaluated stenosis rate, number of endoscopic dilations after ESD, the interval between the first endoscopic dilatation after ESD and explored risk factors for strictures after steroid prophylaxis.

Results

In the control group, the oral steroids group, and the combined group, the stenosis rates were 83/87 (95.4%), 44/53 (83.0%), and 56/67 (83.6%), respectively; the number of endoscopic dilations were 3.43 (±2.22), 2.34 (±2.17), and 1.52 (±1.25), respectively; the time intervals between first endoscopic dilation and ESD procedure were 38.36 (±6.87), 68.18 (±9.49), and 96.82 (±8.41) days, respectively; all these indicators were significantly better in the oral and combined groups than in the control group (p < 0.05). Multivariate analysis identified lesion circumference ≥ 5/6th and submucosal injection of solution were two independent factors on esophageal stricture formation (p < 0.05).

Conclusion

Steroid prophylaxis is effective and safe in preventing esophageal stenosis. Moreover, lesion circumference and submucosal injection of sodium hyaluronate were two independent factors on esophageal stricture formation even with steroids administration.
Doctor for a day: the impact of a health professions enrichment program on self-efficacy
Authors: Coler Celeste , Patel Kareena , Balatico A. J. , Ro Kumhee , Villarreal Joshua , Coronado Nora , Williams Estell
Published: February 2025

Introduction

Health profession enrichment programs for underrepresented minority students are crucial to supporting students’ interest in healthcare careers and improving preparedness for important academic and professional milestones. Doctor for a Day, an enrichment program at the University of Washington School of Medicine, hosts monthly events where underrepresented kindergarten-12th grade students are exposed to careers in medicine by healthcare professionals from diverse backgrounds.

Methods

This study investigates to what extent participation in Doctor for a Day programming improves self-efficacy using a survey study of 958 students who attended at least one Doctor for a Day event between 2017 and 2023.

Results

Using an evaluation tool composed of six questions, our results demonstrate that participation in Doctor for a Day programming increases self-efficacy and interest in medicine as a career. Analysis of these results found significant differences in responses based on grade level, with students in high school demonstrating the largest improvement in self-efficacy.

Discussion

These findings underscore the value of such enrichment programs and offer insights for the development of similar initiatives.
Dose determination of VV116 in COVID-19 patients with severe liver dysfunction: a case report
Authors: Yang Jing , Jiang Wenwen , Deng Jianqing , Liu Min , Xue Ya , Bao Jizhang , Jia Tingting , Hu Qi , Zhang Lichao
Published: February 2025

VV116 is an oral antiviral drug against SARS-CoV-2, known for its favorable efficacy and safety profile. But its application in patients with severe liver dysfunction has not been evaluated. Here, we report a case in which a patient with aplastic anemia and liver impairment (recovery phase of acute liver failure) was infected with SARS-CoV-2. Based on clinical trials and pharmacokinetic analysis about VV116, we initiated a reduced dose of 300 mg every 12 h on day 1, 200 mg every 12 h on days 2–5 for antiviral therapy. Finally, the patient’s viral load rapidly dropped to an undetected level, and no drug-related adverse effects were observed.
Diversity of arbuscular mycorrhizal fungi and its response to seasonal variation in alpine grassland of the eastern Tibetan Plateau
Authors: Dong Wanqing , Ding Tingting , Duan Tingyu
Published: February 2025

Introduction

Arbuscular mycorrhizal (AM) fungi play a crucial role in maintaining diversity and ensuring the proper functioning of grassland ecosystems. A comprehensive understanding of the diversity, distribution patterns, and drivers of AM fungi in different habitats is essential for exploring the ecological roles in grassland ecosystems.

Methods

In this study, we utilized high-throughput sequencing technology to explore the diversity of AM fungi and their distribution at an altitude of approximately 3,500 m in the alpine grassland of the eastern Tibetan Plateau. Additionally, we investigated the impacts of seasonal variation on AM fungal communities.

Results

A total of 97 species of AM fungi, comprising 937 operational taxonomic units (OTUs) belong to 9 families and 10 genera, were identified from the soil samples. Notably, the genera Glomus and Paraglomus were the most abundant and dominant within the identified communities. The composition, distribution, and diversity of the AM fungal communities in the alpine grassland of the eastern Tibetan Plateau were significantly affected by seasonal variation (p < 0.05), with geographic distance being a determining factor. Total nitrogen (TN), soil organic matter (SOM), and pH were identified as the key soil factors driving changes in AM fungal communities.

Discussion

The results demonstrated that the characteristics of AM fungal communities in the alpine grasslands of the eastern Tibetan Plateau were affected by seasonal variations and geographic location, and these findings are significant for the application of AM fungi in the restoration of grassland in similar ecosystems.
Influence of calcium sources on the bio-mineralization behavior of Shewanella putrefaciens and induced microbiologically influenced corrosion inhibition
Authors: Lou Yuntian , Zhang Hao , Chang Weiwei , Yang Jingzhi , Chen Xudong , Hao Xiangping , Qian Hongchang , Zhang Dawei
Published: February 2025

The influence of different calcium sources on the mineralization behavior of Shewanella putrefaciens and their roles in microbiologically influenced corrosion inhibition (MICI) of Q235 carbon steel were investigated. Calcium lactate, calcium nitrate, and calcium L-aspartate were selected as alternative calcium sources to assess their effects on bacterial growth, carbonate deposition, and corrosion resistance. S. putrefaciens exhibited stable growth in all tested media, with the pH exceeding 8 after 14 days, promoting carbonate precipitation. Under sterile conditions, all calcium sources provided some corrosion inhibition, with calcium L-aspartate demonstrating the most effective protection. In bacterial inoculated systems, calcium lactate and calcium L-aspartate facilitated the formation of a continuous CaCO3 mineralized layer, significantly reducing corrosion, whereas calcium nitrate resulted in discontinuous carbonate deposits, promoting localized corrosion. Electrochemical impedance spectroscopy and potentiodynamic polarization analyses confirmed that the mineralized layers formed with calcium lactate and calcium L-aspartate significantly enhanced corrosion resistance, while calcium nitrate exacerbated corrosion due to nitrate-reducing bacterial activity. These findings emphasize the crucial role of calcium source selection in MICI and provide insights for optimizing microbial mineralization strategies for corrosion mitigation.
Detection of antimicrobial resistance via state-of-the-art technologies versus conventional methods
Authors: Elbehiry Ayman , Marzouk Eman , Abalkhail Adil , Abdelsalam Moustafa H. , Mostafa Mohamed E. A. , Alasiri Mazen , Ibrahem Mai , Ellethy Abousree T. , Almuzaini Abdulaziz , Aljarallah Sahar N. , Abu-Okail Akram , Marzook Naif , Alhadyan Satam , Edrees Husam M.
Published: February 2025

Antimicrobial resistance (AMR) is recognized as one of the foremost global health challenges, complicating the treatment of infectious diseases and contributing to increased morbidity and mortality rates. Traditionally, microbiological culture and susceptibility testing methods, such as disk diffusion and minimum inhibitory concentration (MIC) assays, have been employed to identify AMR bacteria. However, these conventional techniques are often labor intensive and time consuming and lack the requisite sensitivity for the early detection of resistance. Recent advancements in molecular and genomic technologies—such as next-generation sequencing (NGS), matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), lateral flow immunoassays (LFIAs), PCR-based diagnostic methods, and CRISPR-based diagnostics—have revolutionized the diagnosis of AMR. These innovative approaches provide increased sensitivity, reduced turnaround times, and the ability to identify genetic resistance mechanisms. This review seeks to examine the advantages and disadvantages of both emerging technologies and traditional methods for detecting AMR, emphasizing the potential benefits and limitations inherent to each. By understanding the strengths and limitations of these technologies, stakeholders, including researchers, healthcare professionals, regulatory agencies, health authorities, financial managers, and patients, can make informed decisions aimed at preventing the emergence and dissemination of antibiotic-resistant strains, thereby ultimately increasing patient safety.
TaiChi-MSS protocol: enhancing cognitive and brain function in MCI patients through Tai Chi exercise combined with multisensory stimulation
Authors: Zhou Chunhui , Yang Ganfeng , Wang Yinying , Zhu Ruiting , Zhu Dong
Published: February 2025

Background

The aging population in China is confronted with considerable challenges, with 14.71% of elderly individuals affected by mild cognitive impairment (MCI). The practice of Tai Chi has been demonstrated to enhance cognitive function, while sensory stimulation has been shown to facilitate neural activity. Nevertheless, the combined impact of Tai Chi and sensory stimulation on cognitive, sensory functions, and brain activation in older adults with MCI remains uncertain. This study aims to ascertain whether the integration of Tai Chi with sensory stimulation can facilitate more efficacious interventions for these outcomes.

Methods and analysis

The TaiChi-MSS (Tai Chi and Multisensory Stimulation for Cognitive Function) study is a multi-center, randomized controlled trial (RCT) conducted in Suzhou and Shanghai, enrolling 88 participants aged 60 years or older with MCI. Participants will be randomly assigned to one of four groups: Tai Chi, multisensory stimulation, Tai Chi combined with multisensory stimulation or control. The intervention will last 6 months, with follow-up assessments at 3, 6, and 9 months. Primary outcomes include cognitive and sensory assessments, assessed using the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), domain-specific cognitive tests, Pure Tone Audiometry (PTA), and Sniffin’ Sticks Odor Identification Test. Secondary outcomes involve brain activation, measured through functional Magnetic Resonance Imaging (fMRI) scans. fMRI will be used to assess brain structure and connectivity changes, focusing on neuroplasticity. Data will be analyzed using mixed-effects models. The False Discovery Rate (FDR) will be the correction method for multiple comparisons to control for the expected proportion of false positives.

Ethics and dissemination

This study was approved by the ethics committee of Shanghai University of Sport (No. 102772023RT200). The results of this study will be disseminated in peer-reviewed journals and presented at academic conferences.
Typing of HLA susceptibility alleles as complementary tool in diagnosis of controversial cases of pediatric celiac disease
Authors: Ruera Carolina Naymé , Guzman Luciana , Menendez Lorena , Orellano Laura , Girard Bosch María Cecilia , Catassi Carlo , Chirdo Fernando Gabriel
Published: February 2025

Objectives

Diagnosis of celiac disease (CeD), an immune-mediated disorder, is based on clinical presentation, a panel of serological markers, and the histopathological findings in duodenal biopsies. Commonly, pediatric CeD patients fulfill these criteria for diagnosis. However, lack of correlation between serology tests and histology, or no accessible biopsies because of clinical conditions or during the COVID pandemic, are conditions that led to inconclusive diagnoses. Since the majority of CeD patients carry HLA-DQ2 and/or DQ8 alleles, HLA testing is used as a complementary tool in diagnosis though is costly and not broadly available for gastroenterology centers.

Methods

We performed a retrospective study to assess the performance of HLA testing when applied to selected groups of patients who could not be definitely diagnosed following the common algorithm. Eighty patients underwent testing for CeD-related HLA-DQ2 and DQ8 alleles.

Results

HLA typing contributed to diagnosis in 34 patients with positive serology but normal mucosa or those who presented negative serology or slightly positive serology (less than 3 times ULN) and duodenal histopathological changes. In patients with normal histology and negative or slightly positive serology, or those who did not undergo intestinal biopsy (39 in total), HLA typing contributed to CeD diagnosis in 23 cases, only 16 patients were admitted for a clinical follow-up program.

Conclusion

HLA-DQ typing supported the diagnosis in 57 of 80 children (71.2%) with previously inconclusive results, providing a beneficial approach for diagnosing celiac disease (CeD) in selected cases.
Emerging roles of intratumoral microbiota: a key to novel cancer therapies
Authors: Fang Pengzhong , Yang Jing , Zhang Huiyun , Shuai Diankui , Li Min , Chen Lin , Liu Liping
Published: February 2025

Microorganisms, including bacteria, viruses, and fungi, have been found to play critical roles in tumor microenvironments. Due to their low biomass and other obstacles, the presence of intratumor microbes has been challenging to definitively establish. However, advances in biotechnology have enabled researchers to reveal the association between intratumor microbiota and cancer. Recent studies have shown that tumor tissues, once thought to be sterile, actually contain various microorganisms. Disrupted mucosal barriers and adjacent normal tissues are important sources of intratumor microbiota. Additionally, microbes can invade tumors by traveling through the bloodstream to the tumor site and infiltrating through damaged blood vessels. These intratumor microbiota may promote the initiation and progression of cancers by inducing genomic instability and mutations, affecting epigenetic modifications, activating oncogenic pathways, and promoting inflammatory responses. This review summarizes the latest advancements in this field, including techniques and methods for identifying and culturing intratumor microbiota, their potential sources, functions, and roles in the efficacy of immunotherapy. It explores the relationship between gut microbiota and intratumor microbiota in cancer patients, and whether altering gut microbiota might influence the characteristics of intratumor microbiota and the host immune microenvironment. Additionally, the review discusses the prospects and limitations of utilizing intratumor microbiota in antitumor immunotherapy.
Network pharmacology combined with molecular docking and experimental validation of the mechanism of action of columbianetin acetate in the treatment of ovarian cancer
Authors: Hu Mengling , Wang Luyao , Zhang Feiyue , Xie Yiluo , Zhang Tingting , Liu Hongli , Li Zhenghong , Zhang Jing
Published: February 2025

Background

Ovarian cancer is the most prevalent malignant tumor of the female reproductive system and has the highest mortality rate among gynecological cancers. Columbianetin acetate (CE) is one of the active ingredients of Angelica sinensis, which has good antifungal and anti-inflammatory activities. However, its potential mechanism of action in ovarian cancer remains unclear. This study used network pharmacology and molecular docking technology to investigate the molecular mechanism and material basis of CE in the treatment of ovarian cancer, and further verified by in vitro experiments.

Methods

Relevant targets for CE were obtained from TCMSP and SwissTargetPrediction databases. OMIM, GeneCards and DisGeNET databases were applied to screen ovarian cancer-related targets. The STRING database to obtain protein-protein interaction (PPI) network. Then key targets were obtained using Cytoscape software, followed by expression, survival and ROC diagnostic analyses of core genes using R software. GO and KEGG enrichment analyses were performed using the DAVID database. Binding ability of CE to core targets was assessed by molecular docking. KEGG sites were used to predict core gene-related pathways. Subsequently, in vitro cellular experiments were performed to further investigate the molecular mechanism of CE treatment for ovarian cancer.

Results

A total of 55 CE-ovarian cancer interaction targets were identified using network pharmacology techniques. Among these, eight key targets —ESR1, GSK3B, JAK2, MAPK1, MDM2, PARP1, PIK3CA, and SRC—were screened using Cytoscape software. Core genes ESR1, GSK3B and JAK2 were obtained based on expression, prognostic and diagnostic values using R software. GO and KEGG enrichment analyses indicated that CE treatment of ovarian cancer might be related to PI3K/Akt signaling pathway, MAPK signaling pathway, ErbB signaling pathway and Ras signaling pathway. The molecular docking results showed that CE had good binding ability with core targets ESR1, GSK3B and JAK2. The results of in vitro cellular experiments indicated that CE may inhibit the proliferation and metastasis of ovarian cancer and promote apoptosis by inhibiting the PI3K/AKT/GSK3B pathway.

Conclusions

Based on the network pharmacology approach, we predicted the potential mechanism of CE for the treatment of ovarian cancer, which provided a new idea for further research on its pharmacological mechanism.
Exploring the potential anti-senescence effects of soybean-derived peptide Soymetide in mice hippocampal neurons via the Wnt/β-catenin pathway
Authors: Garg Asmita , Saroj Jyotshana , Tiwari Saurabh , Das Uttara , Shukla Neetu , Ghosh Jimut Kanti , Bandyopadhyay Sanghamitra
Published: February 2025

Soybean-based foods enhance cognitive functions by influencing hippocampal mechanisms. These salutary effects have so far been attributed to isoflavones present in soybeans. Considering cellular senescence contributes to cognitive decline and that no specific soy-derived peptides are known for their potential to mitigate senescence, we examined the efficacy of a thirteen amino acid soy-derived peptide, Soymetide, on a doxorubicin-induced senescence mice model. Soymetide pretreatment lowered the senescence markers p53, p21 and p16, pro-inflammatory cytokines, and Senescence β-Galactosidase staining while enhancing the mature neuronal marker NeuN in the hippocampus. This anti-senescent effect was comparable with that of a well-known senolytic combination (dasatinib and quercetin). Research indicates that Wnt signaling influences cellular senescence, and our findings here demonstrate that doxorubicin decreased hippocampal Wnt3a, p-LRP6, Frizzled, Dishevelled, Axin1, and β-catenin levels and increased GSK-3β, while Soymetide mitigated these effects. Additionally, upon inhibition of the Wnt/β-catenin pathway, Soymetide’s ability to reduce senescence markers and restore NeuN expression was reduced. We validated the anti-senescence impact on hippocampal neurons by co-immunostaining Wnt/β-catenin and senescence indicators alongside NeuN in mice and assessed it in primary hippocampal neurons. Further examining the neuronal survival and functions revealed that Soymetide blocked the doxorubicin-induced loss in Nissl-stained surviving neurons and learning-memory performances, measured by Y-Maze and Passive Avoidance tests, which Wnt/β-catenin inhibitors could counteract. In conclusion, our study identifies a novel Wnt/β-catenin-linked mechanism of doxorubicin-induced senescence in the hippocampal neurons and demonstrates Soymetide’s effectiveness in reversing this process. Hence, this suggests Soymetide’s potential therapeutic application in addressing cognitive decline associated with cellular aging.
Pharmacokinetics and pharmacodynamics of insulin lispro 25 versus the original preparation (Humalog®25) in Chinese healthy male volunteers
Authors: Zhu Mingxue , Chen Yuan , Wan Lei , Li Zhongping , Pu Junliang , Tang Chengyong
Published: February 2025

Background: There are approximately 537 million adults with diabetes worldwide, and insulin still plays an important role in its treatment. However, the long-term use of insulin imposes a significant financial burden on patients. This study aims to explore the pharmacokinetic (PK)/ pharmacodynamic (PD) parameters of generic premixed insulin lispro 25 (25% insulin lispro and 75% protamine zinc lispro) and evaluate the bio-equivalence between generic and brand-name preparations to reduce medical costs while ensuring the effectiveness and safety of treatment.

Research design and method: This is a single-center, randomized, open-label, two-period, crossover study. This study recruited 52 healthy volunteers and randomly divided them into two sequences to receive either the test (T) preparation or the reference (R) preparation in each period (Chinese Drug Trial Identifier: CTR20202288, URL: http://www.chinadrugtrials.org.cn). The C-peptide and plasma concentration of lispro 25 were analyzed using ELISA and high-performance liquid chromatography, respectively. A euglycemic clamp was used to measure the glucose infusion rate (GIR). The main PK parameters (AUC0-t and Cmax) and PD parameters (GIRmax and GIRAUC0-t) and the evaluation of bioequivalence were calculated using WinNonlin 8.3.1.

Results: The quality of the clamp was approved by stable blood glucose and inhibited C-peptide levels. For PK parameters, the Cmax values of the T and R preparations were 1.40 ± 0.452 and 1.36 ± 0.418 ng·mL-1, respectively, and the AUC0–24h values were 497 ± 107 and 510 ± 86.2 ng h·mL-1, respectively. For PD parameters, GIRmax values were 4.47 ± 2.12 and 4.12 ± 1.81 mg kg·min-1, and AUCGIR0–24h values were 2,994 ± 1,232 and 2,994 ± 941 mg h·kg·min-1 for T and R, respectively. The 90% confidence intervals (CIs) for the geometric mean ratio (test/reference) of the main PK parameters (AUC0-t and Cmax) and PD parameters (GIRmax and GIRAUC0-t) in both cohorts were within the range of 80%–125%. Furthermore, there was no significant hypoglycemia and serious adverse events (SAEs) observed in this study.

Conclusion: Bio-equivalence between insulin lispro (R) (Humalog®25) and insulin lispro (T) was demonstrated, with both showing good tolerance in healthy Chinese volunteers. The results provide evidence supporting the interchangeability of different drug formulations and offer more options for clinical drug use.
Fenvalerate exposure induces AKT/AMPK-dependent alterations in glucose metabolism in hepatoma cells
Authors: Sun Lu , Cui Zheng-Guo , Feng Qianwen , Muhammad Jibran Sualeh , Jin Yu-Jie , Zhao Songji , Zhou Lingqi , Wu Cheng-AI
Published: February 2025

Background

Fenvalerate (Fen) is a synthetic pyrethroid insecticide significantly associated with an increased risk of type 2 diabetes. Tumor cells exhibit a shift in glucose metabolism, known as the Warburg effect. Accordingly, we aimed to elucidate whether Fen interferes with insulin signaling and affects hepatoma cell metabolism.

Methods

The cells were subjected to Fen to assess glucose uptake, acidification, oxygen consumption, and ATP production. ROS generation, mitochondrial membrane potentials, and protein expression were evaluated by flow cytometry, immunofluorescence microscopy, and western blot analyses.

Results

Our results demonstrated that Fen promotes glucose uptake, lactate production, and ATP generation in various cancer cells. Moreover, Fen enhanced insulin receptor phosphorylation and upregulated p-AKT/p-AMPK expression. Fen enhanced insulin receptor sensitivity and endocytosis via reactive oxygen species generation rather than the PP2B pathway. Additionally, the antioxidants N-acetyl-L-cysteine and ascorbic acid reversed the Fen-induced increase in glycolysis. Finally, chronic Fen exposure protected hepatoma cells against metformin-induced cell death via the AKT/AMPK pathway.

Conclusion

These findings raise concerns regarding the safety of Fen and its potential role in altering cancer cell metabolism, affecting insulin signaling and treating drug resistance, thereby necessitating further research.
A study on the effects of modified sprint interval trainingon physical fitness test scores and the quantitative and dose-response relationships among Chinese male university students
Authors: Huang Guoyuan , Chen Yang , Lee ByungChan , Qiu Yipeng , Mao Aqiang , Liang Maolong , Liu Maojie
Published: February 2025

Introduction

This study primarily investigates the impact of a 6-week Sprint Interval Training (SIT) intervention on the physical fitness test results of male university students, as well as the dose-response relationship in adjusting the experimental protocol.

Methods

A total of 26 male university students (aged 20 ± 2 years; height 174 ± 7 cm; weight 70 ± 14 kg; mean ± SD) with no systematic training in the past 3 months, no physiological diseases, and healthy physical condition voluntarily participated in the experiment. The SIT protocol was designed based on a classic Wingate sprint protocol (4-6 x 30 s sprints with 4 m of recovery), and adjustments were made based on the participants' actual adaptation. The final intervention consisted of 6 weeks of training, three times per week, with 2-3 repetitions of 30-s Wingate sprints (Cd = 0.075, resistance on the ergometer = weight/kg x Cd) and 4–5 m of recovery.

Results

The results showed significant improvements in key anaerobic capacity indicators after the 6-week intervention: Average Power (AP) increased from 77.4 ± 10.1 to 132.6 ± 21.1 (p < 0.01, Adjusted p < 0.03 ment, with a maximum effect size of 3.344), Peak Power (PP) increased from 102.9 ± 14.5 to 189.5 ± 28.8 (p < 0.01, Adjusted p < 0.02, maximum effect 3.790), and Time to Peak Power (TTP) decreased from 12.3 ± 3.3 to 9.5 ± 2.6 (p < 0.01), confirming that the intervention enhanced the participants' anaerobic capacity. Additionally, The results of the physical fitness test showed significant improvements: standing long jump (SLJ) increased from 2.31 ± 0.15 m to 2.45 ± 0.18 m (significance level p < 0.01), 50 m sprint time decreased from 7.32 ± 0.42 s to 6.98 ± 0.38 s (significance level p < 0.01), and 1,000 m from 235.6 ± 18.4 s to 220.3 ± 16.8 s (significance level p < 0.01). Other metrics such as Body mass, BMI, Vital capacity, and Pull-ups also showed minor increases. Interestingly, Sit forward in a sitting position scores showed a noticeable improvement (from 12.9 ± 6.8 to 15.8 ± 6.2, p = 0.091).

Discussion

Furthermore, The adjustment of the training programme has achieved good results, as evidenced by the fact that participants have achieved a training completion rate of over 95%, maintained a moderate subjective fatigue rating (RPE score of 13-15), and no one has withdrawn from the training due to discomfort.

Conclusion

The modified SIT protocol proves to be an efficient and practical training method for improving college students' physical fitness.
Genotyping by sequencing reveals the genetic diversity and population structure of Peruvian highland maize races
Authors: Arbizu Carlos I. , Bazo-Soto Isamar , Flores Joel , Ortiz Rodomiro , Blas Raul , García-Mendoza Pedro J. , Sevilla Ricardo , Crossa José , Grobman Alexander
Published: February 2025

Peruvian maize exhibits abundant morphological diversity, with landraces cultivated from sea level (sl) up to 3,500 m above sl. Previous research based on morphological descriptors, defined at least 52 Peruvian maize races, but its genetic diversity and population structure remains largely unknown. Here, we used genotyping-by-sequencing (GBS) to obtain single nucleotide polymorphisms (SNPs) that allow inferring the genetic structure and diversity of 423 maize accessions from the genebank of Universidad Nacional Agraria la Molina (UNALM) and Universidad Nacional Autónoma de Tayacaja (UNAT). These accessions represent nine races and one sub-race, along with 15 open-pollinated lines (purple corn) and two yellow maize hybrids. It was possible to obtain 14,235 high-quality SNPs distributed along the 10 maize chromosomes of maize. Gene diversity ranged from 0.33 (sub-race Pachia) to 0.362 (race Ancashino), with race Cusco showing the lowest inbreeding coefficient (0.205) and Ancashino the highest (0.274) for the landraces. Population divergence (FST) was very low (mean = 0.017), thus depicting extensive interbreeding among Peruvian maize. A cluster containing maize landraces from Ancash, Apurímac, and Ayacucho exhibited the highest genetic variability. Population structure analysis indicated that these 423 distinct genotypes can be included in 10 groups, with some maize races clustering together. Peruvian maize races failed to be recovered as monophyletic; instead, our phylogenetic tree identified two clades corresponding to the groups of the classification of the races of Peruvian maize based on their chronological origin, that is, anciently derived or primary races and lately derived or secondary races. Additionally, these two clades are also congruent with the geographic origin of these maize races, reflecting their mixed evolutionary backgrounds and constant evolution. Peruvian maize germplasm needs further investigation with modern technologies to better use them massively in breeding programs that favor agriculture mainly in the South American highlands. We also expect this work will pave a path for establishing more accurate conservation strategies for this precious crop genetic resource.
Formulation and evaluation of nanoemulsions from Jasminum officinale essential oil for controlling postharvest browning and maintaining quality in jasmine (Jasminum sambac) flowers
Authors: Yeamsuriyotai Kittiya , Pradabkun Natthamon , Manichart Nutcha , Yonsawad Nipaporn , Khamchatra Na-monrug , Laosinwattana Chamroon , Teerarak Montinee , Somala Naphat
Published: February 2025

The jasmine (Jasminum sambac (L.) Aiton) flower has delicate petals, resulting in rapid browning after harvest. The aim of this study was to search for an innovative postharvest treatment for delaying browning of jasmine petals using plant essential oils. J. officinale L. f. var. grandiflorum (L.) essential oil was found to reduce peroxidase activity in jasmine flower by 44.21% in the in vitro condition. The antioxidant activities and chemical composition of J. officinale essential oil were subsequently characterized. The essential oil exhibited the ability to scavenge 2,2-diphenyl-1-picrylhydrazil (DPPH) radicals with a 50% inhibition (EC50) value of 6.72 ± 0.89 mg/mL, a chelating effect with EC50 value of 7.42 ± 1.59 mg/mL, and reducing power with EC0.5 value of 14.89 ± 0.73 mg/mL. GC-MS analysis detected 29 compounds in the oil, with benzyl alcohol (20.68%) and benzyl acetate (19.87%) predominating. As plant essential oils have restricted water solubility, an oil-in-water emulsion was formulated using a spontaneous emulsification method. The resulting J. officinale essential oil naonoemulsion (JEN) had an oil droplet size of 70.2 ± 0.39 nm and a narrow polydispersity index. In vivo testing confirmed the inhibitory effects of JEN on jasmine flower browning and relevant enzyme activities. Jasmine flowers were soaked in various concentrations of JEN for 5 min, packed in polyethylene plastic bags, and stored in a refrigerator at 10 ± 3°C with relative humidity 66 ± 5%. Flowers treated with 1 and 2 mg/mL JEN showed effective delay of petal browning and maintained good quality with minimum flower opening index, high freshness score, and high color retention index. JEN treatment also reduced phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), and peroxidase (POD) activities, indicating postponement of the browning process. In addition, scanning electron microscopy micrographs of treated flower epidermis cells revealed delayed cell wall collapse, indicating retention of intact cells. Taken together, these results support JEN as a potential preventative of enzymatic browning and hence petal browning in jasmine flower.
Lobbying in the EU: prospects and challenges of the mandatory transparency register
Authors: Ridao Martín Joan , Araguàs Galcerà Irene
Published: February 2025

Lobbying practice is an essential part of the decision-making process in the European Union. The promotion of the practice of lobbying in institutions of the European Union quite naturally raised the question of regulating this activity according to the standards that arise from the EU-founding treaties and the Charter of Fundamental Rights of the European Union. The European Parliament and the European Commission set up in 2021 the EU Transparency Register through an interinstitutional agreement, later joined by the Council. The interinstitutional agreement of 2021 states a mandatory register system to eliminate the deficiencies of the voluntary system and provide additional registration incentives. A big role for improving of lobbying regulations has been played by the Court of Justice of the European Union. In recent years, the ultimate interpreter of European law has passed several judgments that set lobbying activities boundaries and the rules applicable to conflict-of-interest situations. The objective of this work is to analyse the regulation and operation of the EU Transparency Register and the most relevant jurisprudential pronouncements as well as the prospects and challenges of the mandatory system recently implemented.