bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between life’s crucial 9 and severe abdominal aortic calcification in U.S. Adults: the mediating role of the systemic inflammatory response index
Authors: Tang Kaifeng , Wang Linping , Ye Jinming , Yuan Feng
Published: February 2025

Background

Life’s Crucial 9 (LC9) is an emerging cardiovascular health scoring system that incorporates Life’s Essential 8 (LE8) alongside mental health factors. However, its relationship with severe abdominal aortic calcification (SAAC) remains poorly understood.

Objectives

The objective of this study is to investigate the relationship between LC9 scores and the incidence of SAAC in the US population.

Methods

Data from 2,323 participants were analyzed, originating from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) cycle. In exploring the dynamics of LC9, its constituents, and their relationship with SAAC, we employed advanced statistical methodologies, specifically multivariable logistic regression and weighted quantile sum regression. Subgroup interaction analyses were conducted to reinforce the conclusions, and mediation analysis was employed to investigate how the systemic inflammatory response index (SIRI) influences the connection between LC9 and SAAC.

Results

In fully adjusted models, an increase of 10 points in LC9 scores was associated with a 26% reduction in the prevalence of SAAC, achieving statistical significance (P < 0.001). As LC9 scores increased, a significant decline in SAAC prevalence was noted (P < 0.05). The WQS analysis pinpointed strong links between the occurrence of SAAC and variables including exposure to tobacco, blood pressure levels, blood glucose concentrations, and mental health status, the odds ratio stood at 0.244, with the 95% CI extending from 0.119 to 0.495. SIRI was positively correlated with SAAC (P < 0.05) and decreased with rising LC9 scores (β = -0.09, P < 0.001). Mediation analysis revealed that the SIRI significantly influenced the linkage between LC9 and SAAC, accounting for 5.8% of the mediation effect, with a statistically significant p-value (P < 0.001).

Conclusion

This research highlights a robust inverse relationship between elevated LC9 scores and reduced SAAC incidence, suggesting the significant role of LC9 as a key factor in diminishing the frequency of SAAC. Furthermore, SIRI mediates this relationship.
Ultrasound radiomics and genomics improve the diagnosis of cytologically indeterminate thyroid nodules
Authors: Chen Lu , Zhang Mingbo , Luo Yukun
Published: February 2025

Background

Increasing numbers of cytologically indeterminate thyroid nodules (ITNs) present challenges for preoperative diagnosis, often leading to unnecessary diagnostic surgical procedures for nodules that prove benign. Research in ultrasound radiomics and genomic testing leverages high-throughput data and image or sequence algorithms to establish assisted models or testing panels for ITN diagnosis. Many radiomics models now demonstrate diagnostic accuracy above 80% and sensitivity over 90%, surpassing the performance of less experienced radiologists and, in some cases, matching the accuracy of experienced radiologists. Molecular testing panels have helped clinicians achieve accurate diagnoses of ITNs, preventing unnecessary diagnostic surgical procedures in 42%–61% of patients with benign nodules.

Objective

In this review, we examined studies on ultrasound radiomics and genomic molecular testing for cytological ITNs conducted over the past 5 years, aiming to provide insights for researchers focused on improving ITN diagnosis.

Conclusion

Radiomics models and molecular testing have enhanced diagnostic accuracy before surgery and reduced unnecessary diagnostic surgical procedures for ITN patients.
Research on topology and control strategy of distribution network flexible interconnected device based on single-phase control unit and contact switch in series
Authors: Lu Yi , Ding Chao , Ni Xiaojun , Qiu Peng , Shang Yufei , Wang Zihan
Published: February 2025

There is an urgent need for flexible interconnection in the distribution network. However, due to the complex topology, control strategy and development cost of the existing flexible interconnected device (FID), the existing FID is difficult to be popularized and applied in the above scenarios. In view of the above problems, this paper constructs the FID topology based on the series connection of single-phase control unit and contact switch, and constructs the equivalent circuit of the interconnection line between FID and contact switch in series. The working principle of FID flexible closing loop and power flow control is studied from the dimension of FID output voltage and equivalent impedance. The FID flexible closing loop energy extraction strategy is proposed, and the FID system-level and device-level control strategies with flexible closing loop and power flow control functions are proposed. The simulation results show that the flexible interconnection device based on the proposed topology and control strategy can effectively compensate the pressure difference of the connecting points in the distribution network, regulate the power flow of the active distribution network, and realize the interconnection and mutual assistance of the distribution network.
China’s readiness for transitioning to a low-carbon economy: mitigant and catalyst factors for a geopolitical conflict
Authors: Chen Yan , Lyu Jiayi , Ortiz Jaime , Song Wenbin
Published: February 2025

The transition from a carbon-intensive economy to a carbon-neutral one has become a critical global objective to address climate change. This study examines the relationship between Low-Carbon Economic Development (LCED) and Geopolitical Risk (GPR) in China by focusing on the challenges and opportunities they present. We use a qualitative analysis to identify that rising GPR, exacerbated by market instability, resource allocation conflicts, and trade disputes, significantly hinders LCED progress. However, these geopolitical tensions also act as a catalyst for accelerating the development of renewable energy, reducing reliance on traditional energy sources, and fostering low-carbon technologies. Furthermore, LCED can ameliorate GPR by decreasing dependence on energy imports, promoting international cooperation, and encouraging scientific innovation. These findings suggest actionable policy recommendations to support the global transition to a low-carbon economy. This research underscores the potential LCED has as a fundamental tool for resolving geopolitical tensions and uniting global efforts to combat climate change.
Verbal consent in biomedical research: moving toward a future standard practice?
Authors: Noë Alycia , Vaillancourt Emilie , Zawati Ma’n H.
Published: February 2025

Properly obtaining informed consent is a core obligation for research conducted using human subjects. The traditional informed consent process involves written forms and obtaining signatures. This process remains the standard, but in various research settings, such as COVID-19 and rare disease research, verbal consent has increasingly become the norm. Although verbal consent is used in these settings, its use is still a subject of debate. This article reviews in what medical settings verbal consent is commonly seen today, various advantages and disadvantages of verbal consent, and its legislative and policy ecosystem. In doing so, this review article asserts that it is time for the debate over verbal consent to come to an end and for legislator and policymakers to acknowledge its use and to formalize the process. This will allow verbal consent to be regulated in a similar manner to written consent and will give clinician-researchers guidance on how to better implement verbal consent in their studies to addressing ongoing concerns with the consenting process as a whole.
Integration of scRNA-seq and bulk RNA-seq to reveal the association and potential molecular mechanisms of metabolic reprogramming regulated by lactylation and chemotherapy resistance in ovarian cancer
Authors: Ren Fang , Pang Xiaoao , Jin Feng , Luan Nannan , Guo Houhua , Zhu Liancheng
Published: February 2025

Objective

Ovarian cancer (OC) ranks among the foremost causes of mortality in gynecological malignancies, with chemoresistance being the primary factor contributing to unfavorable prognosis. This work seeks to clarify the mechanisms of resistance-related lactylation in OC, intending to offer novel theoretical foundations and therapy strategies for addressing chemoresistance.

Methods

Through the combined analysis of bulk RNA-seq and single-cell RNA-seq data, we initially found lactylation genes linked to chemoresistance. Subsequently, we employed differential expression analysis, survival analysis, enrichment analysis, and other methodologies to further investigate the roles and molecular mechanisms of these genes in tumor resistance. Ultimately, we investigated the differential expression of these genes in resistant and non-resistant tissues and cells via experimentation.

Results

We found two candidate genes associated with lactylation chemoresistance, ALDH1A1 and S100A4. Analysis of single-cell data indicated that tumor cells represent the primary cell subpopulation relevant to resistance studies. Subpopulation analysis indicated that several tumor cell subtypes were markedly linked to resistance, with elevated expression levels of ALDH1A1 and S100A4 in the resistant subpopulation, notably correlating with various immunological and metabolic pathways. Analysis of metabolic pathways indicated that oxidative phosphorylation and glycolysis activity was elevated in the resistant subpopulation, and lactic acid buildup was associated with chemoresistance. The investigation of the marker gene protein-protein interaction network in the resistant subgroup elucidated the intricate interactions among these genes. The expression levels of ALDH1A1 and S100A4 in the OC tissues of the platinum-resistant cohort were markedly elevated compared to the sensitive cohort, with a considerable rise in S100A4 expression observed in resistant OC cells, demonstrating co-localization with lactylation.

Conclusion

This work elucidates the significant function of lactylation in OC chemoresistance and identifies ALDH1A1 and S100A4 as possible genes associated with drug resistance. These findings enhance our comprehension of the mechanisms behind chemoresistance in OC and offer critical insights for the formulation of novel therapeutic options.
Metabolic pathway activation and immune microenvironment features in non-small cell lung cancer: insights from single-cell transcriptomics
Authors: Liu Yanru , Liu Hanmin , Xiong Ying
Published: February 2025

Introduction

In this study, we aim to provide a deep understanding of the tumor microenvironment (TME) and its metabolic characteristics in non-small cell lung cancer (NSCLC) through single-cell RNA sequencing (scRNAseq) data obtained from public databases. Given that lung cancer is a leading cause of cancer-related deaths globally and NSCLC accounts for the majority of lung cancer cases, understanding the relationship between TME and metabolic pathways in NSCLC is crucial for developing new treatment strategies.

Methods

Finally, machine learning algorithms were employed to construct a risk signature with strong predictive power across multiple independent cohorts. After quality control, 29,053 cells were retained, and PCA along with UMAP techniques were used to distinguish 13 primary cell subpopulations. Four highly activated metabolic pathways were identified within malignant cell subpopulations, which were further divided into seven distinct subgroups showing significant differences in differentiation potential and metabolic activity. WGCNA was utilized to identify gene modules and hub genes closely associated with these four metabolic pathways.

Results

Our analysis showed that DEGs between tumor and normal tissues were predominantly enriched in immune response and cell adhesion pathways. The comprehensive examination of our model revealed substantial variations in clinical and pathological characteristics, enriched pathways, cancer hallmarks, and immune infiltration scores between high-risk and low-risk groups. Wet lab experiments validated the role of KRT6B in NSCLC, demonstrating that KRT6B expression is elevated and it stimulates the proliferation of cancer cells.

Discussion

These observations not only enhance our understanding of metabolic reprogramming and its biological functions in NSCLC but also provide new perspectives for early detection, prognostic evaluation, and targeted therapy. However, future research should further explore the specific mechanisms of these metabolic pathways and their application potentials in clinical practice.
Mechanisms of tumor-associated macrophages in breast cancer and treatment strategy
Authors: Jin Hong , Meng Xinyue , Feng Jianwei
Published: February 2025

Breast cancer (BC) is the most common cancer in women and a leading cause of cancer-related mortality. Despite advances in screening and treatment, outcomes for advanced or recurrent BC remain poor, highlighting the need for new strategies. Recent research emphasizes the tumor microenvironment (TME), particularly tumor-associated macrophages (TAMs), as key drivers of tumor growth, metastasis, and resistance to therapy. The presence of M2-like TAMs in the TME promotes immune evasion and tumor progression across BC subtypes. This review summarizes TAMs classification, their role in BC, and emerging therapies targeting TAMs, including depletion, inhibition of recruitment, and reprogramming from pro-tumoral M2 to anti-tumoral M1 phenotypes. Targeting TAMs offers a promising strategy to improve BC treatment outcomes.
Exploring antigenic variation in autoimmune endocrinopathy
Authors: Mavridou Maria , Pearce Simon H.
Published: February 2025

Autoimmune disorders develop owing to a misdirected immune response against self-antigen. Genetic studies have revealed that numerous variants in genes encoding immune system proteins are associated with the development of autoimmunity. Indeed, many of these genetic variants in key immune receptors or transcription factors are common in the pathogenesis of several different autoimmune conditions. In contrast, the proclivity to develop autoimmunity to any specific target organ or tissue is under-researched. This has particular relevance to autoimmune endocrine conditions, where organ-specific involvement is the rule. Genetic polymorphisms in the genes encoding the targets of autoimmune responses have been shown to be associated with predisposition to several autoimmune diseases, including type 1 diabetes, autoimmune thyroid disease and Addison’s disease. Mechanistically, variations leading to decreased intrathymic expression, overexpression, different localisation, alternative splicing or post-translational modifications can interfere in the tolerance induction process. This review will summarise the different ways genetic variations in certain genes encoding endocrine-specific antigens (INS, TSHR, TPO, CYP21A2, PIT-1) may predispose to different autoimmune endocrine conditions.
Unravelling the complete mitochondrial genomes of Thrips tabaci Lindeman and Thrips parvispinus Karny (Thysanoptera: Thripidae) and their phylogenetic implications
Authors: Soumia P.S. , Shirsat Dhananjay V. , Karuppaiah Vadivelu , Divekar Pratap A. , Mahajan Vijay
Published: February 2025

Onion (Allium cepa Linnaeus) is an important vegetable crop valued for its nutritional properties and economics worldwide. Onion cultivation faces serious threats from pests and diseases, particularly onion thrips (Thrips tabaci), which cause substantial yield losses. Recently, Black thrips (Thrips parvispinus), an invasive key pest of chili, have been reported to cause severe damage in onion crop and is likely to devastate the onion cultivation in near future. Therefore, this study was conducted to address the knowledge gap concerning the genetic basis and evolutionary history of T. tabaci and T. parvispinus through sequencing of their mitochondrial genomes. T. tabaci and T. parvispinus were collected from different locations in Maharashtra, India, and reared in the laboratory. The mitochondrial genomes of T. tabaci and T. parvispinus were sequenced to a length of 15,277 and 15,285 bp, respectively. Both genomes exhibited similar gene organization with regard to thirteen protein-coding genes and two rRNA genes. T. tabaci contained 19 tRNA genes whereas T. parvispinus contained 18 tRNA genes. The evolutionary positions of T. tabaci and T. parvispinus within the Thysanoptera order were elucidated through phylogenetic analysis of the mitogenomes of 15 thrips species. These findings provide crucial insights into the genetic makeup and evolutionary dynamics of both the thrips species, thereby aiding the development of novel and sustainable pest management strategies to mitigate their impacts on crops in the changing climate scenario.
Use of tusks by narwhals, Monodon monoceros, in foraging, exploratory, and play behavior
Authors: O’Corry-Crowe Greg , Ghazal Maha , Gillespie Mark , Galvin Paul , Harasimo Jason , Storrie Luke , Watt Cortney A.
Published: February 2025

Despite the universal fascination with the tusk of the narwhal, the function of this long, spiraled tooth is still debated, primarily because few people have observed how narwhals (Monodon monoceros) use their tusks in the wild. Using an unmanned aerial vehicle (UAV), we recorded previously unreported interactions between multiple narwhals, Arctic char (Salvelinus alpinus) and glaucous gulls (Larus hyperboreus) in Canada’s High Arctic. Narwhals were recorded chasing char and using their tusks to hit, manipulate and influence the behavior of fish. Differences in tusk use likely reflected differences in behavioral intent with some actions associated with prey capture and others with exploration and likely play. Kleptoparasitic behavior by gulls when narwhals pursued char near the surface substantially reduced prey capture for narwhals. Associative and interactive behaviors among narwhals were linked to the ecological context including fish density and gull behavior. Some interactions appeared competitive in nature while others may have been communicative and affiliative. This study revealed that narwhals can use their tusks to investigate and manipulate objects, including prey, and deliver sufficient force with their tusks to stun and possibly kill fish. The speed and agility of char combined with kleptoparasitic behavior of gulls indicate that char may be a challenging species to predate while aspects of the narwhals’ actions may include social learning and exploration of a novel prey species, and are the first reported evidence of likely play, specifically exploratory-object play, in narwhals.
Case report: Gouty renal abscess and gouty sacroiliitis associated with genetic variants of a young woman
Authors: Tang Dabin , Jiang Yubao , Ling Guichen , Zhang Jianyong , Xie Jingjing
Published: February 2025

Gout is a form of inflammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals in the joints, resulting from a disorder in purine metabolism. It occurs more frequently in men than in women prior to menopause and is rare in young women. Gout can lead to various health complications, with many patients experiencing a significant burden of chronic kidney disease (CKD) and joint deformities. The development of gout is influenced by a complex interplay of genetic, environmental, and lifestyle factors, with elevated serum MSU levels serving as a key risk factor for its onset. However, only 10% of individuals with hyperuricemia go on to develop clinical gout, and several susceptibility loci are associated with the condition. Here, we present a case of a young woman with gouty sacroiliitis and gouty nephropathy linked to susceptibility loci.
Typing of Echinococcus multilocularis by Region-Specific Extraction and Next-Generation Sequencing of the mitogenome
Authors: Rachel Franziska , Luttermann Christine , Höper Dirk , Conraths Franz Josef , Dapprich Johannes , Maksimov Pavlo
Published: February 2025

Background

Infection by the fox tapeworm Echinococcus multilocularis may lead to a severe zoonosis in humans, alveolar echinococcosis, which may be fatal if left untreated. Typing is important to understand the epidemiology of this parasite, yet there is limited knowledge on the microdiversity of E. multilocularis on the local scale, since the typing resolution of established methods is restricted.

Methods

The mitogenome of E. multilocularis was used as the target regions to modify, apply and validate the Region-Specific Extraction (RSE) method in combination with Next-Generation Sequencing (NGS). Single Nucleotide Polymorphisms (SNPs) were detected in the mitochondrial DNA (mtDNA) and analysed bioinformatically. To validate the success and the accuracy of the RSE protocol, the mitogenomes of some E. multilocularis isolates were also analysed by the Whole-Genome Sequencing (WGS).

Results

With the chosen combination of methods, the entire mitogenome (~13 kb) of E. multilocularis could be captured and amplified. The read depth (median ≥ 156X) was sufficient to detect existing SNPs. The comparison of mitogenome sequences extracted by RSE with mitogenome sequences obtained by WGS showed that the accuracy of the RSE method was consistently comparable to direct Whole-Genome Sequencing.

Conclusion

The results demonstrate that the RSE method in combination with NGS is suitable to analyse the microdiversity of E. multilocularis at the whole mitogenome level. For the capture and sequencing of large (several kb) genomic regions of E. multilocularis and other applications, this method can be very helpful.
Differentiation of soil metabolic function and microbial communities between plantations and natural reforestation
Authors: Zhang Nannan , Chen Xiaoxia , Ren Tingju , Luo Jiangcheng , Liang Jin , Wang En Tao , Shi Fusun
Published: February 2025

Reforestation plays a vital role in restoring the soil degradation areas. However, the mechanisms by which different restoration approaches affect the soil properties and microbial communities remain unclear. Aiming to understand the interactions between plant species, soil properties, and microbial communities in different restoration approaches, we investigated the soil microbial community using nontargeted metabolomics to explore how the reforestation approach affects soil physicochemical properties, soil metabolites, and soil microbial communities. The results showed that the reforestation approach, soil layer, and their interactive effects significantly affected soil organic carbon, total nitrogen, dissolved organic carbon, available phosphorus concentrations, and root traits. The diversity and composition of bacterial and fungal communities in natural reforestation (NR) were different from those in artificial mono-plantations, and their network interactions were more significant in NR than in artificial plantations. A clear separation of metabolites between the artificial plantations and NR was observed in the soil metabolite analysis. Two pathways, linoleic acid metabolism, and valine, leucine, and isoleucine biosynthesis, were significantly regulated between the artificial mono-plantations and NR. Different soil traits were significantly correlated with dominant microbial taxa in the four reforestation approaches. 13-L-hydroperoxylinoleic acid, 13-S-hydroxyoctadecadienoic acid, homovanillin, and 9,10-epoxyoctadecenoic acid showed the highest correlation with the microbial taxa in the network. Partial least squares path modeling (PLS-PM) shows that root-mediated soil physicochemical properties were the primary factors affecting the bacterial community among the reforestation approaches. The soil fungal community is directly regulated by plant roots in the subsoil and indirectly regulated by the root-mediated physicochemical properties in the topsoil. We conclude that different reforestation approaches affect the soil microbial community through root and soil physicochemical properties rather than soil metabolites.
Neurophysiological approaches for managing pain in multiple sclerosis: a mini review
Authors: Ayache Samar S. , Chalah Moussa A.
Published: February 2025

Chronic pain is a prevalent yet often under-recognized symptom among individuals with multiple sclerosis (MS), affecting 29–86% of the population. This condition can significantly impact the individuals' functionality, including their capacity to engage in professional activities. The pathophysiology underlying this condition remains intricate and not fully elucidated, and inadequate responses to pharmacological interventions or adverse effects can hinder its management. In light of these observations, there is an urgent need to identify new therapeutic interventions. Non-invasive brain stimulation (NIBS) techniques hold promise for addressing MS-related pain. This mini-review aims to analyze the findings from studies using NIBS techniques, such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), to assess their analgesic potential in people with MS. Seven relevant reports are available. Five of these studies used tDCS, one utilized a transcranial random noise stimulation (tDCS variant), and one compared rTMS with transcranial theta burst stimulation (rTMS variant). The results indicate the potential benefits of NIBS for pain management in MS. However, the study's limitations, including the scarcity of data, small sample size, the limited number of sessions, sham design, and brief follow-up, are also noted and discussed. Finally, directions for future research are suggested.
Behavioral alterations in antibiotic-treated mice associated with gut microbiota dysbiosis: insights from 16S rRNA and metabolomics
Authors: Bibi Asma , Zhang Famin , Shen Jilong , Din Ahmad Ud , Xu Yuanhong
Published: February 2025

The gut and brain interact through various metabolic and signaling pathways, each of which influences mental health. Gut dysbiosis caused by antibiotics is a well-known phenomenon that has serious implications for gut microbiota-brain interactions. Although antibiotics disrupt the gut microbiota’s fundamental structure, the mechanisms that modulate the response and their impact on brain function are still unclear. It is imperative to comprehend and investigate crucial regulators and factors that play important roles. We aimed to study the effect of long-term antibiotic-induced disruption of gut microbiota, host metabolomes, and brain function and, particularly, to determine the basic interactions between them by treating the C57BL/6 mice with two different, most commonly used antibiotics, ciprofloxacin and amoxicillin. Anxiety-like behavior was confirmed by the elevated plus-maze test and open field test. Gut microbes and their metabolite profiles in fecal, serum, and brain samples were determined by 16S rRNA sequencing and untargeted metabolomics. In our study, long-term antibiotic treatment exerted anxiety-like effects. The fecal microbiota and metabolite status revealed that the top five genera found were Lactobacillus, Bacteroides, Akkermansia, Ruminococcus_gnavus_group, and unclassified norank_f_Muribaculaceae. The concentration of serotonin, L-Tyrosine, 5-Hydroxy-L-tryptophan, L-Glutamic acid, L-Glutamate, 5-Hydroxyindole acetic acid, and dopaminergic synapsis was comparatively low, while adenosine was high in antibiotic-treated mice. The KEGG enrichment analysis of serum and brain samples showed that amino acid metabolism pathways, such as tryptophan metabolism, threonine metabolism, serotonergic synapsis, methionine metabolism, and neuroactive ligand-receptor interaction, were significantly decreased in antibiotic-treated mice. Our study demonstrates that long-term antibiotic use induces gut dysbiosis and alters metabolic responses, leading to the dysregulation of brain signaling molecules and anxiety-like behavior. These findings highlight the complex interactions between gut microbiota and metabolic functions, providing new insights into the influence of microbial communities on gut-brain communication.
Trajectories of working memory and decision making abilities along juvenile development in mice
Authors: Thies Ann Marlene , Pochinok Irina , Marquardt Annette , Dorofeikova Maria , Hanganu-Opatz Ileana L. , Pöpplau Jastyn A.
Published: February 2025

Rodents commonly serve as model organisms for the investigation of human mental disorders by capitalizing on behavioral commonalities. However, our understanding of the developmental dynamics of complex cognitive abilities in rodents remains incomplete. In this study, we examined spatial working memory as well as odor-and texture-based decision making in mice using a delayed non-match to sample task and a two-choice set-shifting task, respectively. Mice were investigated during different stages of development: pre-juvenile, juvenile, and young adult age. We show that, while working memory abilities in mice improve with age, decision making performance peaks during juvenile age by showing a sex-independent trajectory. Moreover, cFos expression, as a first proxy for neuronal activity, shows distinct age-and brain area-specific changes that relate to task-specific behavioral performance. The distinct developmental trajectories of working memory and decision making in rodents resemble those previously reported for humans.
Dietary protein requirements of older adults with sarcopenia determined by the indicator amino acid oxidation technology
Authors: Wu Wenxuan , Chen Fengge , Ma Hui , Lu Jiaxi , Zhang Yanhong , Zhou Haisong , Yang Yunqi , Nie Shuhui , Wang Rui , Yue Weixiao , Li Min , Yang Xiaoguang
Published: February 2025

Background

Although protein supplementation may be desirable in the management of sarcopenia, the appropriate protein requirements for older adults with sarcopenia are presently unclear.

Objective

The aim of this study was to determine the protein requirements of older adults (65–81 year) with sarcopenia by using the indicator amino acid oxidation (IAAO) technology.

Methods

Nine older adults with sarcopenia (four male participants and five female participants) participated in the study, with protein intakes ranging from 0.1 to 1.8 g/(kg·d). Each participant consumed an adapted diet with a protein level of 1.0 g/(kg·d) and 1.7 resting energy expenditure (REE) for 2 day. Day 3 was the oxidation day of the study. Diets that delivered energy at a 1.5 × REE were isocaloric. The amounts of phenylalanine and tyrosine maintained at a constant across intakes. Therefore, phenylalanine and tyrosine were added to the protein doses of 0.1–1.5 g/kg, which was based on the highest dose of lactalbumin content [1.8 g/(kg·d)]. Applying a non-linear mixed-effects model analysis of F13CO2, the protein requirement was determined by identifying the breakpoint in the F13CO2 data with graded amounts of dietary protein.

Results

The mean estimated average requirement (EAR) and recommended nutrient intake (RNI) of protein for older adults with sarcopenia were 1.21 (95% CI: 0.95, 1.46) and 1.54 (95% CI: 1.13, 1.95) g/(kg·d), respectively.

Conclusions

To our knowledge, this is the first study of protein intake in older adults with sarcopenia and indicates that older adults with sarcopenia may require a higher intake of dietary protein.

Clinical trial registration

http://www.chictr.org.cn, ChiCTR2200061383.
Case Report: Multiple mesenchymal hamartomas showing spontaneous motility in the nasopharynx
Authors: Kinoshita Tetsuya , Kono Masamitsu , Iwamoto Ryuta , Hijiya Masayoshi , Takeda Saori , Ohtani Makiko , Doyama Mikako , Murakami Daichi , Tamagawa Shunji , Murata Shin-Ichi , Hotomi Muneki
Published: February 2025

Hamartomas are classified as either epithelial, mesenchymal, or epithelium-mesenchymal mixed types. They occur extremely rarely in the nasopharynx. A 58-year-old man had multiple tumors with repeating contraction and relaxation in the nasopharynx shown on endoscopy. One of the tumors was endoscopically resected under general anesthesia for histological examination and was finally diagnosed as mesenchymal hamartoma. Smooth muscle tissue is sometimes confirmed in mesenchymal hamartomas, but spontaneous contraction in nasopharyngeal hamartomas is rare. In this case, coexistence of muscle tissue, Cajal interstitial cell-like cells, and ganglion cells was thought to be a mechanism of spontaneous motility of the tumors. Aberrant or residual foregut tissue in the nasopharynx due to embryological factors may be a contributing factor to the multiple occurrences.
Development and validation of a prognostic nomogram for early hepatocellular carcinoma treated with microwave ablation
Authors: Zhang Jing , Guo Guanya , Li Tao , Guo Changcun , Han Ying , Zhou Xinmin
Published: February 2025

Objective

An effective model for risk stratification and prognostic assessment of early hepatocellular carcinoma (HCC) patients following microwave ablation (MWA) is lacking in clinical practice. The aim of this study is to develop and validate a prognostic model specifically for these patients.

Methods

Between January 2008 and December 2018, 345 treatment-naïve patients with HCC conforming to the Milan criteria who underwent MWA were enrolled and randomly assigned to the training (n=209) and validation (n=136) cohorts. The nomogram model was constructed based on the predictors assessed by the multivariate Cox proportional hazards model and validated. Predictive accuracy and discriminative ability were further evaluated and compared with other prognostic models.

Results

After a median follow-up of 59.0 months, 52.5% (187/356) of the patients had died. Prognostic factors for overall survival (OS) were α-fetoprotein (AFP), albumin-bilirubin (ALBI) score, platelets, and ablation margins, which generated the nomograms. The nomogram model consistently achieved good calibration and discriminatory ability with a concordance index of 0.64 (95% confidence interval (CI): 0.59-0.69) and 0.69 (95% CI: 0.63-0.75) in both the training and validation cohorts. The performance of the nomogram model also outperformed other prognostic models. By using the nomogram model, the patient population could be correctly divided into low- and high-risk strata presenting significantly different median OS of 105.0 (95% CI: 84.1-125.9) months, and 45.0 (95% CI: 28.0-62.0) months, respectively.

Conclusion

The nomogram model based on AFP, PLT, ablation margins, and ALBI score was a simple visualization model that could stratify patients with early‐stage HCC after MWA and predict individualized long-term survival with favorable performance.
Photodynamic therapy and tumor-treating fields therapy for newly diagnosed glioblastoma
Authors: Fukami Shinjiro , Nagai Kenta , Onodera Sho , Saito Yuki , Akimoto Jiro , Kohno Michihiro
Published: February 2025

Introduction and purpose

Various treatment methods, including photodynamic therapy (PDT), are used for glioblastoma (GBM), which is an intractable tumor. Our therapeutic strategy for glioblastoma has been based on resection (if possible), and PDT. On the other hand, after tumor-treating fields therapy (TTF) became available, we have actively recommended it to our patients who are eligible for it. In this report, we describe the clinical characteristics and disease course of glioblastoma patients treated by PDT + TTF at our hospital.

Methods

A total of 14 patients with newly diagnosed glioblastoma, who underwent PDT + TTF from the time of insurance coverage of TTF were analyzed. The median age of the patients was 48 years. There were 10 men and 4 women, with a high prevalence of younger men.

Results

The average duration of TTF was 8.9 (1–19) months, and the main reasons for its discontinuation were recurrence of the tumor and scalp problems. The median progression-free survival of the 14 patients who underwent PDT + TTF was 13.4 months, which tended to be longer than that of the 30 patients who underwent PDT without TTF (11 months). Of the 10 patients who relapsed, 2 had local recurrence and 8 had distant or disseminated recurrence. Two patients with local recurrence underwent repeat resection together with PDT. To date, the prognosis for patient survival of PDT + TTF appears favorable, with 6 patients surviving for more than 2 years.

Conclusion

PDT + TTF treatment for newly diagnosed glioblastoma can be performed without any major adverse events, although there are some problems with the continuation of TTF, such as scalp problems and its high cost. More patients who underwent PDT + TTF relapsed with distant and/or disseminated recurrence than local recurrence, suggesting that this treatment strategy targets local recurrence. Our results demonstrate that combination therapy for newly diagnosed glioblastoma with PDT + TTF may prolong the time to recurrence and improve survival outcomes of patients, although the data in this study are preliminary.
Neuropeptides as regulators of bone metabolism: from molecular mechanisms to traditional Chinese medicine intervention strategies
Authors: Lin Qing , Zhao Biyi , Huang Jiajia , Chen Rumeng , Sun Weipeng , Ye Qianyun , Yang Li , Zhu Xiaofeng , Li Xiaoyun , Zhang Ronghua
Published: February 2025

Osteoporosis (OP) is a complex bone metabolism disorder disease that affects the skeleton, nervous system, muscles, and multiple tissues. Neuropeptides, which are endogenous substances derived from both bone and brain, play a critical role in maintaining the balance of bone metabolism. This review summarizes research conducted from 1986 to 2024 on the pathological mechanisms of neuropeptides and their receptors in the context of OP. Specifically, the roles of Neuropeptide Y, Vasoactive Intestinal Peptide, Calcitonin Gene-Related Peptide, and Substance P and their receptors in key processes of OP were examined, including their function of bone formation and resorption, osteoblast differentiation, and osteoclast differentiation. Our study showed that these neuropeptides could promote bone formation and inhibit bone resorption, while their receptors in osteocytes exhibit distinct functions, indicating complex regulatory mechanisms that require further investigation. Additionally, we summarize the progress of Traditional Chinese Medicine (TCM) formulae, single TCM herbs, and bioactive compounds derived from TCM in exerting anti-OP effects through neuropeptide modulation. These studies highlight the multi-targeted and multi-mechanistic pharmacological actions of TCM in treating OP. By integrating these findings, we aim to enhance the understanding of neuropeptides’ roles in bone metabolism and to explore the development of neuropeptide-targeted TCM therapies for OP management. This comprehensive perspective highlights the potential of neuropeptides as therapeutic targets, paving the way for innovative approaches to treating OP.
Effect of sodium-glucose Co-transporter 2 inhibitors on coronary microcirculation
Authors: Chen Shaoxin , Ou Weiqian , Gan Shuguang , Chen Lixian , Liu Baohua , Zhang Zhenhong
Published: February 2025

Coronary microvascular disease (CMVD) has emerged as a new target for the occurrence and development of heart failure treatment. Various indicators such as Index of Microvascular Resistance, Coronary Flow Reserve, Microvascular Resistance Reserve, Hyperemic Microvascular Resistance and Coronary Flow Velocity Reserve can be used to assess CMVD. Coronary microcirculation dysfunction is one of the important pathogenic mechanisms of heart failure. Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors have been widely used in the treatment of various types of heart failure, but their specific pharmacological mechanisms are not yet fully understood. Studies have shown that SGLT2 inhibitors may be involved in the pathophysiology of CMVD by regulating cellular pathophysiological processes such as oxidative stress, mitochondrial function, energy metabolism, vascular genesis, and signalling pathways. Therefore, coronary microvascular dysfunction may be one of the treatment targets of using SGLT2 inhibitors in heart failure. Several animal experiments have found that SGLT2 inhibitors can improve microcirculatory dysfunction. However, the results of several clinical trials on the effects of SGLT2 inhibitors on coronary microcirculation have been different. Therefore, it is still lack of conclusive evidence on the effects of SGLT2 inhibitors on microcirculatory dysfunction. This review aims to summarize the completed and ongoing experiments regarding the effects of SGLT2 inhibitors on coronary microcirculation, in order to better elucidate the impact of SGLT2 inhibitors on microcirculation. It seeks to provide valuable information for the pharmacological mechanisms of SGLT2 inhibitors, the study of diseases related to coronary microcirculation disorders, and the treatment of heart failure.
Antitumor components and mechanisms of Zanthoxylum bungeanum Maxim with medicine and food homology
Authors: Du Yuhua , Duan Shuai , Yang Yi , Tibenda Joanna Japhet , Huang Shicong , Nan Yi , Zhang Zhe , Yuan Ling
Published: February 2025

Zanthoxylum bungeanum Maxim (Z. bungeanum) is a medicinal and edible plant commonly used to improve the flavor of Chinese cuisine due to its unique numbing taste. It is recognized for its medicinal properties, including bodywarming, relieving cold, promoting blood circulation, and alleviating pain. Additionally, Z. bungeanum has been extensively studied for its antitumor properties. In this study, various scientific databases and network pharmacology were used to search for information about Z. bungeanum and its components for the treatment of tumors. Numerous active components of Z. bungeanum have been identified, demonstrating antitumor properties. We discovered that Z. bungeanum can modulate multiple signaling pathways across various targets using network pharmacological predictions, highlighting its strong antitumor potential. The components of Z. bungeanum and the traditional Chinese medicine compound containing Z. bungeanum can promote apoptosis, arrest the cell cycle, inhibit cell invasion and metastasis, promote autophagy, and increase the sensitivity of chemotherapeutic drugs through P53, PI3K/AKT, Wnt/β-catenin and other signaling pathways, which are effective against various cancers, including hepatocellular cancer, gastric cancer, and breast cancer. Z. bungeanum and its extracts have demonstrated promising effects against various tumors, indicating their potential use in future cancer therapies and offering new strategies for tumor treatment. However, clinical studies evaluating the antitumor efficacy and toxicity of Z. bungeanum in humans are scarce. Therefore, well-designed clinical trials should be prioritized in the future to establish a solid foundation for its use in cancer treatment.
Undergraduate pharmacy students’ preference for case-based learning: a discrete choice experiment in China
Authors: Guo Zhibo , He Yuxing , Yan Jianzhou
Published: February 2025

Background

Understanding students’ preferences is crucial for developing targeted teaching strategies and improving educational outcomes. This study aimed to investigate Chinese undergraduate pharmacy students’ preferences for case-based learning (CBL).

Methods

We conducted a discrete choice experiment (DCE) to quantify preferences for CBL. Six key attributes associated with CBL preferences were identified: case modality, provider type, group size, case authenticity, case complexity, and examination format. An online questionnaire was administered to undergraduate pharmacy students from two universities in China. The data were analyzed using a mixed logit model to estimate preference weights, assess the relative importance of the attributes, and predict uptake rates. Additionally, interaction effects and subgroup analysis were employed to identify heterogeneity in preferences among different student groups.

Results

A total of 613 participants completed the questionnaire and 482 participants were included in the analysis. The most influential attribute was case modality, with scenario simulation strongly preferred over paper modality. Case authenticity and provider type were also significant factors, followed by group size and case complexity. Examination format did not significantly affect preferences. We found heterogeneity in preferences between different groups of students. The highest uptake was achieved when cases were presented in scenario simulations by clinical instructors in small groups, using real cases of low complexity alongside the traditional written examination.

Conclusion

The study highlights the importance of case modality with scenario simulation, case authenticity, and provider by clinical instructors among Chinese undergraduate pharmacy students for CBL, and suggests the need for personalized CBL approaches to accommodate different preferences.
Administration of the KCa channel activator SKA-31 improves endothelial function in the aorta of atherosclerosis-prone mice
Authors: Vera O. Daniel , Mishra Ramesh C. , Khaddaj-Mallat Rayan , Hamm Liam , Almarzouq Barak , Chen Yong-Xiang , Belke Darrell D. , Singh Latika , Wulff Heike , Braun Andrew P.
Published: February 2025

Introduction

Atherosclerosis remains a major risk factor for vascular dysfunction and cardiovascular (CV) disease. Pharmacological enhancement of endothelial Ca2+-activated K+ channel activity (i.e., KCa2.3 and KCa3.1) opposes vascular dysfunction associated with ageing and type 2 diabetes (T2D) in ex vivo and in vivo preparations. In the current study, we have investigated the efficacy of this strategy to mitigate endothelial dysfunction in the setting of atherogenesis.

Methods

Male apolipoprotein E knockout (Apoe−/−) mice fed a high fat diet (HFD) were treated daily with the KCa channel activator SKA-31 (10 mg/kg), the KCa3.1 channel blocker senicapoc (40 mg/kg), or drug vehicle for 12-weeks. Endothelium-dependent and -independent relaxation and vasocontractility were measured in abdominal aorta by wire myography. The development of atherosclerosis in the thoracic aorta was characterized by Oil Red O staining and immunohistochemistry. Key vasorelaxant signaling proteins were quantified by q-PCR.

Results

Endothelium-dependent relaxation of phenylephrine-constricted aortic rings was impaired in Apoe−/− HFD mice (53%) vs. wild-type (WT) controls (80%, P < 0.0001), consistent with endothelial dysfunction. Treatment of Apoe−/− HFD mice with SKA-31, but not senicapoc, restored maximal relaxation to the WT level. Phenylephrine-evoked contraction was similar in WT and vehicle/drug treated Apoe−/− mice, as was the maximal relaxation induced by the endothelium-independent vasodilator sodium nitroprusside. mRNA expression for eNOS, KCa3.1, KCa2.3 and TRPV4 channels in the abdominal aorta was unaffected by either SKA-31 or senicapoc treatment. Fatty plaque formation, tissue collagen, α-smooth muscle actin and resident macrophages in the aortic sinus were also unaltered by either treatment vs. vehicle treated Apoe−/− HFD mice.

Conclusion

Our data show that prolonged administration of the KCa channel activator SKA-31 improved endothelial function without modifying fatty plaque formation in the aorta of Apoe−/− mice.