bluuebunny/crossref_metadata_2025 huggingface dataset:
AIP56, an AB toxin secreted by Photobacterium damselae subsp. piscicida, has tropism for myeloid cells
Authors: Freitas Inês Lua , Macedo Maria Fátima , Oliveira Liliana , Oliveira Pedro , do Vale Ana , dos Santos Nuno M.S.
Published: January 2025

Introduction

The AB-type toxin AIP56 is a key virulence factor of Photobacterium damselae subsp. piscicida (Phdp), inducing apoptosis in fish immune cells. The discovery of AIP56-like and AIP56-related toxins in diverse organisms, including human-associated Vibrio strains, highlights the evolutionary conservation of this toxin family, suggesting that AIP56 and its homologs may share conserved receptors across species. These toxins have potential for biotechnological applications, such as therapeutic protein delivery and immune modulation.

Methods

Herein, the cell specificity of AIP56 for immune cells was characterized. The tropism of AIP56 for cells of the sea bass, mouse and human immune system was analyzed by following toxin internalization by flow cytometry and arrival of the toxin in the cytosol by evaluating the cleavage of NF-kB p65 by western blotting.

Results

Only a small population of sea bass neutrophils internalized AIP56, indicating that most of the neutrophilic destruction during Phdp infection and/or AIP56 intoxication does not result from the direct action of the toxin. Moreover, the cellular tropism of AIP56 for myeloid cells was observed in the three species, including its preference for macrophages. Further, mouse and human M0 and M2-like macrophages internalized more toxin than M1-like macrophages. Despite the limited interaction of lymphoid cells with AIP56, mouse B1-cells were able to internalize the toxin, possibly due to its myeloid features.

Conclusion

AIP56 has tropism for sea bass, mouse and human myeloid cells, with greater affinity for macrophages. This points to an evolutionary conservation of its receptor(s) and mechanism of action across species, raising the possibility that AIP56-like and -related toxins may also play a role in pathogenesis. These findings are relevant for both pathogenicity and biomedical contexts.
Proteomics and transcriptomics combined reveal specific immunological markers in autoimmune thyroid disease
Authors: Chen Xia , Chen Hui
Published: January 2025

Objective

The pathogenesis of AITD remains unclear to date. This study employs a combination of proteomics and transcriptomics analysis to identify and validate specific immune response markers in patients with hyperthyroidism and hypothyroidism, thereby providing a scientific basis for the clinical diagnosis and treatment of AITD.

Methods

By collecting serum and whole blood tissue samples from patients with hyperthyroidism, hypothyroidism, and healthy controls, this study utilizes a combination of transcriptomics and proteomics to analyze changes in immune-related signaling molecules in patients. Specific biomarkers were identified, and the ELISA method was employed to determine the expression levels of these clinical markers and their correlation with clinical features of the patients, ultimately establishing a predictive model.

Results

Transcriptomic and proteomic analyses were conducted to identify differentially expressed genes and proteins in patients with hyperthyroidism and hypothyroidism compared to healthy controls. Enrichment analysis revealed that these differentially expressed genes and proteins are primarily associated with immune function, antigen-antibody binding, and alterations in immune cells. Through the combined analysis of transcriptomics and proteomics, key genes IGHG3, ISG15, and ZNF683 were identified. ELISA results from clinical patient serum samples indicated that the levels of IGHG3 were significantly higher in both the hyperthyroid and hypothyroid groups compared to the control group (P<0.05). Additionally, the serum levels of ISG15 in the hyperthyroid group were greater than those in both the control and hypothyroid groups (P<0.05), while the serum levels of ZNF683 in the hypothyroid group exceeded those in the control and hyperthyroid groups (P<0.05). Furthermore, all three biomarkers correlated with the thyroid function of the patients. Prediction models for hyperthyroid and hypothyroid patients were constructed using IGHG3, ISG15, and ZNF683, demonstrating good performance metrics and decision effect.

Conclusion

In patients with hyperthyroidism and hypothyroidism, significant changes primarily occur in immune function and immune cells when compared to healthy individuals. Key signaling molecules were identified: ISG15 for hyperthyroidism, ZNF683 for hypothyroidism, and IGHG3 common to both conditions. These findings provide new biomarkers for the diagnosis and monitoring of clinical patients, thereby offering a scientific basis for research on AITD and personalized treatment approaches.
Detecting and quantifying deep sea benthic life using advanced object detection
Authors: Iyer Karthik H. , Marnor Camilla M. , Schmid Daniel W. , Hartz Ebbe H.
Published: January 2025

We present a new dataset combined with the DeepSee model, which utilizes the YOLOv8 architecture, designed to rapidly and accurately detect benthic lifeforms in deep-sea environments of the North Atlantic. The dataset consists of 2,825 carefully curated images, encompassing 20,076 instances across 15 object-detection classes based on morphospecies from the phyla Arthropoda, Chordata, Cnidaria, Echinodermata, and Porifera. When benchmarked against a published dataset from the same region, DeepSee achieves high performance metrics, including an impressive mean Average Precision (mAP) score of 0.84, and produces very few false positives, ensuring reliable detection. The model processes images at 28–50 frames per second (fps) for images sized at 1280 pixels, significantly increasing processing speed and reducing annotation workloads by over 1000 times when compared to manual annotation. While the model is not intended to replace the expertise of experienced biologists, it provides a valuable tool for accelerating data analysis and increasing efficiency. As additional data becomes available, augmenting the dataset and retraining the model will enable further improvements in detection capabilities. The dataset and model are designed for extensibility, allowing for the inclusion of other benthic lifeforms from the North Atlantic and beyond. This capability supports the creation of high-resolution maps of benthic life on the largely unexplored ocean floor of the Norwegian Continental Shelf (NCS) and other regions. This will facilitate informed decision-making in marine resource exploration, including mining operations, bottom trawling, and deep-sea pipeline laying, while also contributing to marine conservation and the sustainable management of deep-sea ecosystems.
How the fish community structure change with seasons in Zhoushan Fishing Ground, China?
Authors: Li Yuru , Yan Chenchen , Ju Peilong , Liu Baogui , Wang Jing , Zhang Chang , Zhang Wenchao , Wang Yingbin
Published: January 2025

Understanding seasonal variations in fish communities is important for fishery resources conservation and management in fishery economic zones. However, there are still knowledge gaps regarding to the differential responses of fish functional traits to various disturbances. Here, we sampled fish communities of 20 sites during autumn (November 2023) and spring (April 2024) in Zhoushan Fishing Ground. Taxonomic diversity (TD), functional diversity (FD), and functional redundancy (FR) were calculated to investigate the state of the fish communities and their seasonal changes. Beta diversity was calculated based on the pairwise communities of spring and autumn and decomposed into turnover and nestedness proportions, to investigate the dissimilarities of the fish communities between the two seasons and their drive mechanisms. We also applied R-mode linked to Q-mode (RLQ) and fourth-corner methods to test the relationships between fish functional traits and environmental variables (trait-environment relationships). These results showed that the mean values of taxonomic and functional beta diversities were 0.852 and 0.769, respectively, which indicate that taxonomic and functional structures of the fish communities have high dissimilarities between spring and autumn. However, the taxonomic and functional structures showed different ecological processes of seasonal changes with the former were mainly driven by species turnover (occupied 89.9% of the total dissimilarity) and the latter were driven by both functional turnover and nestedness (occupied 57.9% and 42.1% of the total dissimilarity, respectively). Species occurrence, environmental variables, and functional traits matrices were closely correlated, which mainly result from the significant trait-environmental relationships. Combining with TD, FD, and FR, we concluded that the fish communities in autumn had higher resistance to environmental changes than in spring. Our findings are accepted to serve as a basis for fishery management.
MiR-4298 and lncKRTAP5-6-3 regulated Cathepsin D expression through ERK-MAPK signaling pathway in chronic UVB-damaged HaCaT cells
Authors: Chen Xinling , Zhou Feng , Lin Yao , Xia Yue , Zhang Jie , Hou Wenyi , Sun Yu , Lai Wei , Zheng Yue
Published: January 2025

Objective

MiRNAs and lncRNAs are important regulators in the process of skin photoaging. In this study, we investigated the expression changes and interactions between miR4298 and lncKRTAP5-6-3 in chronically UVB-damaged human keratinocyte cell line (HaCaT) cells and explored miR4298-MAPK/ERK signaling pathway-Cathepsin D-lncKRTAP5-6-3 mechanisms in photoaging cells.

Methods

HaCaT cells were irradiated with 12 mJ/cm2 UVB once a day for 7 days. miR-4298 mimics and miR-4298 inhibitors were transfected into HaCaT cells by lipo3000 transfection reagent, and the HaCaT cells were divided into three groups: blank control group; UVB-damaged group; and UVB damage+miR-4298 regulation (overexpression or inhibition) group. The expression levels of miR4298 and lncKRTAP5-6-3 were quantitatively analyzed using RT-PCR, while the expression of Cathepsin D and MAPK/ERK signaling pathway proteins was detected using Western blot.

Results

After 7 consecutive days of UVB irradiation, the expression of miR-4298 decreased by 0.64 ± 0.06 (P < 0.001) compared to the un-irradiated HaCaT cells, and the expression of the KRTAP5-6-3 decreased by 0.80 ± 0.13 (P < 0.001) compared to the control group. The expression of p-ERK signaling was increased by 0.9437 ± 0.1186 (P < 0.0001), and Cathepsin D was decreased by 0.6163 ± 0.075 (P < 0.0001). In HaCaT cells transfected with miR-4298 mimics and then irradiated by UVB for 7 days, the expression of lncKRTAP5-6-3 was increased to 0.5114 ± 0.1438 (P < 0.05)-fold, and the phosphorylation level of ERK signaling was decreased by 0.3880 ± 0.1185 (P < 0.01), while Cathepsin D expression was increased by 0.2617 ± 0.0749 (P < 0.0001) compared to the UVB-damaged group. In HaCaT cells transfected with miR-4298 inhibitors and then irradiated by UVB for 7 days, lncKRTAP5-6-3 was decreased by 0.1697 ± 0.1383, the phosphorylation level of ERK signaling was increased by 1.096 ± 0.7836 (P < 0.05), while Cathepsin D expression was decreased by 0.05197 ± 0.24827 compared to the UVB-damaged group.

Conclusion

The synergistic effects of miR4298 and lncKRTAP5-6-3 play important roles in chronic UVB-damaged HaCaT cells by regulating the MAPK/ERK signaling pathway and Cathepsin D expression. This study presents novel targets for intervening in chronic ultraviolet damage (photoaging) skin and UV-related dermatoses.
VV-ECMO adjuvant therapy for Leptospira complicated with H1N1 infection: a case report
Authors: Zhang YuChou , Yin MingJing , Wen HanChun
Published: January 2025

Background

Leptospirosis is an acute infectious disease that occurs by infection, progresses rapidly, and has a high mortality rate, with an estimated 1.2 million new cases and nearly 59,000 deaths each year. Due to its diverse clinical manifestations, diagnosis is often delayed. Therefore, it is necessary to pay attention to its clinical manifestations, diagnostic techniques, and treatment methods.

Case report

A 51-year-old male patient from the Han ethnic group experienced fever, chills, headache, and overall fatigue after being exposed to rain, followed by yellowing of the skin and worsening of breathing difficulties. Metagenomic next-generation sequencing (mNGS) indicates infection with leptospirosis and influenza A. After 5 days of treatment with venovenous extracorporeal membrane oxygenation (VV-ECMO), Penicillium, and Oseltamivir, the condition improved.

Conclusion

Leptospirosis improves with VV-ECMO support and anti-infective treatment with penicillin and oseltamivir. VV-ECMO provides a therapeutic time window for rescue, and mNGS lays a foundation for early detection of etiology of leptospirosis.
Effect of invasive acupuncture on awakening quality after general anesthesia: systematic review and meta-analysis
Authors: Bu Fan-dong , Si Shang-kun , Zhang Dong-bin , Chi Yong-liang
Published: January 2025

Background

The process of waking up from general anesthesia is still not well understood, and recovery issues such as delayed awakening, agitation, postoperative cognitive dysfunction, continue to be a challenge for anesthesiologists. Currently, the treatment of these complications is mainly achieved through the antagonistic action of specific drugs, but sometimes the antagonistic drugs are not as effective as they should be and can add to the financial burden of the patient. Acupuncture, a common treatment in Traditional Chinese Medicine, is widely used around surgery. However, there is no enough evidence to show it improves recovery after anesthesia. To explore this, we reviewed relevant randomized trials and conducted a meta-analysis.

Objective

This systematic review was conducted to explore the effect of perioperative application of invasive acupuncture on the quality of postoperative awakening after general anesthesia.

Methods

By searching PubMed, Embase, Cochrane Clinical Trials Center, China Knowledge Network (CNKI), China Biomedical Database (CBM), Wanfang Medical Database, Weipu Database, to include randomized controlled trials of invasive acupuncture applied perioperatively. Search is limited from the build-up of the database to March 2022. The statistical analysis was conducted using RevMan 5.3. Quality assessment of the included research literature using Cochrane-recommended risk of bias assessment tool.

Results

18 randomized controlled trials were included with 1,127 patients. 565 patients in invasive acupuncture intervention group, 562 patients in control group. Results showed that invasive acupuncture group had a shorter eye opening time than control group (MD = −6.42, 95% CI [−8.17, −4.66], p < 0.001), shorter extubation times (MD = -5.84, 95% CI [−8.12, −3.56], p < 0.001), lower MAP at extubation (MD = −18.54, 95% CI [−22.69, −14.39], p < 0.001), lower HR at extubation (MD = −14.85, 95% CI [−23.90, −5.81], p < 0.001). No statistical difference in the occurrence of POCD (OR = 0.56, 95% CI [0.28, 1.11], p = 0.10) and postoperative agitation (OR = 0.42, 95% CI [0.11, 1.65], p = 0.21).

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, CRD42023410260.
Evaluation of a modified sutureless technique for scleral fixation of one-piece posterior chamber intraocular lens: a retrospective study
Authors: Johari Mohammadkarim , Attar Alireza , Eghtedari Dorna , Razavizadegan Seyed Ahmad
Published: January 2025

Background

This study presents the one-year outcomes of a modified technique for transscleral suture fixation of a posterior chamber intraocular lens (PCIOL) in aphakic eyes.

Methods

A retrospective chart review was conducted on 45 patients who underwent transscleral suture fixation of a foldable one-piece PCIOL through scleral pockets. Preoperative data and follow-up data for a minimum of 12 months were collected for all patients.

Results

The mean preoperative and postoperative uncorrected distance visual acuity (UDVA) in LogMAR was 2.49 ± 0.54 and 0.54 ± 0.25, respectively (p < 0.01). The mean preoperative and postoperative best-corrected visual acuity (BCVA) in LogMAR was 0.52 ± 0.22 and 0.45 ± 0.24, respectively (p < 0.01). The mean endothelial cell loss was 110.46 ± 11.5 cells/mm2. Postoperative complications included transient corneal edema (17.7%), transient elevated intraocular pressure (22.2%), and non-significant vitreous hemorrhage (11.1%). No severe complications were observed.

Conclusion

The modified technique provides stable PCIOL placement in aphakic eyes with long-term follow-up.
The change of inflammatory markers may predict long-term major adverse cardiovascular events in elderly patients with coronary heart disease: a retrospective cohort study
Authors: He Li , Chen Sisi , Zhu Xuan , He Fang
Published: January 2025

Background

At present, the relationship among inflammatory markers [monocytes/HDL-c (MHR), neutrophils/HDL-c (NHR) and lymphocytes/HDL-c (LHR)] and long-term prognosis of coronary heart disease (CHD) is still unclear. Therefore, this study explores the relationship between inflammatory indicators and the risk of long-term major adverse cardiovascular events (MACE) in elderly patients with CHD.

Methods

A retrospective analysis was conducted on 208 elderly patients who underwent coronary angiography at Wuhan Fourth Hospital from August 2022 to August 2023. They were divided into the CHD group (N = 116) and control group (N = 92). Patients in the CHD group were followed up for 1 year and divided into the MACE group (N = 36) and the non-MACE group (N = 80) according to whether MACE occurred.

Results

In elderly patients, logistic regression analysis shows that MHR is an independent risk factor for CHD (OR = 3.050, 95% CI 1.318–1.772). ROC curve analysis found that MHR (AUC = 0.865, 95% CI 0.811–0.919, p < 0.001) is higher than NHR and LHR. In patients with CHD, the spearman analysis show that MHR is positively correlated with Gensini score (R = 0.266, p = 0.004). The logistic regression analysis found that MHR is independent risk factors for MACE (OR = 6.048, 95% CI 1.224–1.941, p = 0.002). ROC analysis showed that the critical value of MHR to predict MACE was 0.651, the sensitivity of 58.3% and specificity of 90.0% could predict MACE, and the AUC was 0.793 (95% CI 0.702–0.884, p < 0.001) is higher than LHR.

Conclusion

In elderly patients, MHR is an independent predictor of CHD and long-term MACE and is positively correlated with the severity of coronary artery lesions.
Biological function of d-tryptophan: a bibliometric analysis and review
Authors: Wang Fei , Du Runyu , Shang Yunxiao
Published: January 2025

Background

d-Tryptophan is recognised for its unique physiological properties. In this study, we aimed to explore the dynamic trends and emerging topics in d-tryptophan research to offer fresh perspectives for future studies.

Methods

Employing bibliometric analysis, we examined the literature on d-tryptophan indexed in the Web of Science Core Collection from January 1987 to December 2023. The “Bibliometrix” R package and CiteSpace were utilised for data processing.

Results

Analyses of 865 publications revealed 2209 keywords, 4068 authors, 2094 institutions, and contributors from 302 regions. The USA was at the forefront of publications concerning d-tryptophan, but the European Journal of Pharmacology, Journal of Biological Chemistry, and Journal of Medicinal Chemistry were notable for their contributions, co-citations, and impact, respectively. This literature review reveals that since 1987, studies have developed from a focus on d-tryptophan metabolism to the exploration of its functions in organic and medicinal chemistry and food science. Recent findings highlight the potential of d-tryptophan as a non-nutritional sweetener and food preservative as well as its role in inhibiting the growth of bacterial biofilms. Additionally, its immunomodulatory properties are being investigated in relation to allergic diseases. Furthermore, d-tryptophan plays a role in the therapy of atherosclerosis, osteoporosis, tuberculosis, and cancer.

Conclusion

The results of bibliometric analysis highlight that future research should focus on the biological functions of d-tryptophan as a food preservative and its use in immunomodulation and drug development, providing strong guidance for future research.
Characterization of the oxygen-tolerant formate dehydrogenase from Clostridium carboxidivorans
Authors: Brouwer Eva-Maria , Medipally Hitesh K. R. , Schwab Saskia , Song Shanshan , Nowaczyk Marc M. , Hagemann Martin
Published: January 2025

Fixation of CO2 into the organic compound formate by formate dehydrogenases (FDHs) is regarded as the oldest autotrophic process on Earth. It has been proposed that an FDH-dependent CO2 fixation module could support CO2 assimilation even in photoautotrophic organisms. In the present study, we characterized FDH from Clostridium carboxidivorans (ccFDH) due to its ability to reduce CO2 under aerobic conditions. During the production of recombinant ccFDH, in which the selenocysteine codon was replaced by Cys, we were able to replace the W with Mo as the transition metal in the ccFDH metal cofactor, resulting in a two-fold increase of 6 μmol formate min−1 in enzyme activity. Then, we generated ccFDH variants in which the strict NADH preference of the enzyme was changed to NADPH, as this reducing agent is produced in high amounts during the photosynthetic light process. Finally, we showed that the native ccFDH can also directly use ferredoxin as a reducing agent, which is produced by the photosynthetic light reactions at photosystem I. These data collectively suggest that ccFDH and, particularly, its optimized variants can be regarded as suitable enzymes to couple formate production to photosynthesis in photoautotroph organisms, which could potentially support CO2 assimilation via the Calvin–Benson–Bassham (CBB) cycle and minimize CO2 losses due to photorespiration.
Association between social networks and cognitive impairment among older Chinese adults: the mediating effect of depression
Authors: Zhang Zhuo , Bian Ying
Published: January 2025

Objectives

This study aimed to explore the rationality of the social networks-depression-cognitive impairment pathway and to provide recommendations for the development of mild cognitive impairment intervention strategies.

Methods

A cross-sectional survey was conducted in 2021. Sixteen urban communities in Xi 'an, Shaanxi China were selected as sample sites. The cognitive function, social networks and depression were measured by the Montreal Cognitive Assessment (MoCA), the Lubben Social Network Scale-6 (LSNS-6) and the Geriatric Depression Scale-15 (GDS-15), respectively. The generalized linear model was used to analysis the impact of social networks on cognitive impairment, and further analysis the mediating effect of depression.

Results

A total of 745 elderly people aged 60 and above was included in this survey, with an average age of 68.90 ± 6.00 years. The prevalence of cognitive impairment was 18.52%, and the prevalence of cognitive impairment increased with age. According to the generalized linear model, poor social networks (relative network, friend network) was associated with higher risk of cognitive impairment (OR = 2.08, 95% CI: 1.27–3.41), and this association was more significant in women and older adults <70 years of age. Mediation analysis results showed that depression was the mediating path between social networks and cognitive impairment, with the indirect effects accounting for 34.44%.

Conclusion

Social isolation increases the risk of cognitive impairment and depression has a significant mediating effect on the relationship between social isolation and cognitive impairment.
Cryopreservation of primary neonatal rat oligodendrocytes and recapitulation of in vitro oligodendrocyte characteristics
Authors: Kim Hanki , Kim Bum Jun , Koh Seungyon , Cho Hyo Jin , Kim Byung Gon , Choi Jun Young
Published: January 2025

Introduction

In vitro, primary rat oligodendrocytes (OLs) are widely used for research on OL development, physiology, and pathophysiology in demyelinating diseases such as multiple sclerosis. Primary culture methods for OLs from rats have been developed and improved over time, but there are still multiple aspects in which efficiency can be boosted.

Methods

To make use of excess oligodendrocyte progenitor cells (OPCs) from primary cultures, a cryopreservation process utilizing a commercially available serum-free cryopreservation medium was established to passage and freeze OPCs at −80°C for later use.

Results

Cryopreserved OPCs stored for up to 6 months were viable, and retained their OL lineage purity of ~98%. While OPCs cryopreserved for 3–6 months showed a decrease in cell density after two days of proliferation, ~17% of cryopreserved OPCs maintained the potential for proliferation comparable to control OPCs that had not frozen. After induction of differentiation for four days, ~43% of both control and cryopreserved OPCs differentiated into mature OLs, and when differentiation was induced on aligned nanofibers mimicking axonal structure, myelin sheath-like structures indicative of in vitro myelination was observed in all experimental groups.

Conclusion

The validation of cryopreserved primary OLs as a functionally robust in vitro model can help improve the efficiency of primary OL culture, expand its applications, and reduce the inevitable sacrifice of animals.
Strengths of pelvic floor muscles in women with multiple sclerosis and its relationship with urinary incontinence and quality of life
Authors: Afshari Poorandokht , Abedi Parvin , Majdinasab Nastaran , Tafakh Samaneh , Haghighizadeh Mohammadhossein
Published: January 2025

Background

Multiple sclerosis (MS) is a debilitating autoimmune disease that mostly affects women.

Objectives

In this study we evaluated the relationship of pelvic muscle strengths with urinary incontinence and quality of life in women with MS.

Materials and methods

In this cross-sectional study 87 women with MS were recruited. Data collected using a demographic questionnaire, the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF), and Quality of Life Questionnaire (QOL-SF-36). A perineometer was used to measure the strengths of pelvic muscle. Data analyzed using Pearson correlation test, and multiple linear regression tests.

Results

There was a positive correlation between pelvic muscle strengths with all domains of quality of life except for body pain and role limitations due to emotional problems. A significant inverse correlation was found between urinary incontinence and all domains of quality of life except for body pain. Also, an inverse correlation was found between muscle strength and urinary incontinence (r = −0.838, p < 0.001). A one-unit increase in the quality of physical life was associated with a 0.15-unit increase in the strengths of pelvic floor muscles (p = 0.035). On the other hand, each additional year of marriage or disease duration significantly weakened pelvic floor muscles by 0.24 and 0.509 units, respectively (p < 0.05).

Conclusion

Our findings showed that pelvic muscle strength, urinary incontinence, and quality of life were significantly interrelated among female patients with MS. An inverse correlation was also found between muscle strength and urinary incontinence. Duration of marriage and length of MS disease were inversely associated with the strength of the pelvic floor muscles. Health providers are recommended to educate MS patients on the importance of pelvic muscle strengths.
Altered amplitude of low-frequency fluctuation and functional connectivity in patients with acute unilateral vestibulopathy: a resting-state fMRI study
Authors: Chen Zhengwei , Rong Liangqun , Xiao Lijie , Rao Jie , Liu Haiyan , Liu Tengfei , Chen Fei , Zhang Jun , Wang Lu , Li Xi , Wei Xiue
Published: January 2025

Objective

To investigate changes of brain functional activity in patients with acute unilateral vestibulopathy (AUVP) using functional magnetic resonance imaging (fMRI).

Methods

We studied 32 AUVP patients and 30 healthy controls (HC) who received resting-state fMRI scanning. Methods of voxel-based amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were adopted to compare the difference in brain function between the two groups. In addition, we evaluated the associations between abnormal neuroimaging results and clinical data in AUVP patients.

Results

Compared with HC, patients with AUVP showed lower ALFF in brain regions of bilateral insular, right precentral gyrus, left inferior frontal gyrus and right middle frontal gyrus, as well as higher ALFF in left cerebellar anterior lobe. Using these abnormal brain areas as seeds, we observed decreased FC between left insular and left precuneus in AUVP patients. Furthermore, AUVP patients showed increased FC between left insular and left supplementary motor area. Results of correlation analysis indicated that ALFF value (z-value) in left insular was negatively correlated with the canal paresis value (p = 0.005, r = −0.483), and the FC (z-value) between left insular and left precuneus was negatively correlated with dizziness handicap inventory score (p = 0.012, r = −0.438) in patients with AUVP.

Conclusion

Patients with AUVP during acute period showed altered functional activity and connectivity in brain regions mainly involved in motor control and vestibular information processing. These changes in brain functional activity and connectivity were potentially attributed to decreased vestibular input resulting from unilateral peripheral vestibular impairment.
Neurons with larval synaptic targets pioneer the later nervous system in the annelid Malacoceros fuliginosus
Authors: Seybold Anna , Kumar Suman , Tumu Sharat Chandra , Hausen Harald
Published: January 2025

Comparative studies on the development of nervous systems have a significant impact on understanding animal nervous system evolution. Nevertheless, an important question is to what degree neuronal structures, which play an important role in early stages, become part of the adult nervous system or are relevant for its formation. This is likely in many direct developers, but it is not the case in forms with catastrophic metamorphosis. It is not clear in many forms with gradual metamorphosis. This introduces uncertainty in tracing the evolution of nervous systems and of larval forms. One of the prominent larval characteristics of numerous planktonic marine organisms is the epidermal ciliation used for swimming and steering, which disappears during metamorphosis. Therefore, the neuronal elements controlling the ciliary beating are often assumed to vanish with the cilia and regarded as purely larval specializations. With volume EM, we followed the neuronal targets of the very first pioneer neurons at the apical and posterior ends of the larva of the annelid Malacoceros fuliginosus. We observed that all of these pioneers appear to have a dual function. Although they are laying the paths for the later adult nervous system, they also make synaptic contact with the main ciliated ring of the larva. We propose that the formation of the later adult nervous system and the innervation of the larval locomotory organ are indeed closely linked to each other. This has implications for understanding the early nervous system development of marine larvae and for existing hypotheses on nervous system evolution.
Camrelizumab-induced immune-related toxic epidermal necrolysis in lung adenocarcinoma: a case report and literature review
Authors: Sun Man , Zhou Huan , Zang Dan , Liu Chen-Guang , Chen Jun
Published: January 2025

Toxic epidermal necrolysis (TEN) is a rare and serious skin reaction. This study reports a case of a patient with lung adenocarcinoma (LUAD) who developed severe TEN after 8 days of treatment with Camrelizumab monotherapy. The patient’s condition was effectively relieved with high-dose corticosteroids and intravenous immunoglobulin therapy. The diagnosis and treatment of immune-related TEN are challenging. This is a rare and severe case of TEN associated with the use of Camrelizumab. Additionally, we provide an in-depth understanding of immune-related TEN, summarizing its characteristics and treatment progress through a literature review, aiming to provide reference for the clinical safe application of immune checkpoint inhibitors (ICIs).
Brucea javanica oil inhibited the proliferation, migration, and invasion of oral squamous carcinoma by regulated the MTFR2 pathway
Authors: Lai Yihan , Li Mingkang , Zhan Juan , Jiang Lin , Wu Yuan , Fang Zhiyi , Zhou Jianhan , Ma Yujie , Shao Yisen , Wang Wei
Published: January 2025

Introduction

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in oral and maxillofacial region. The development of new chemotherapy agents and new drug combinations may improve patient survival and quality of life, but both surgery and radiotherapy have significant functional side effects and drug resistance, ultimately resulting in a 5-year survival rate of no more than 60% for OSCC patients. Studies have shown that Brucea javanica oil (BJO) extracts have anti-cancer effects against a variety of cancers, but little research has been reported on OSCC.

Methods

CCK8, Colony formation, Scratch test and Transwell invasion assays were applied to determine the effects of BJO on the proliferation, migration, and invasion ability of OSCC cells in vitro. MTFR2 knockdown (shRNA) and overexpression (cDNA) OSCC cells were constructed to evaluate the effect of MTFR2 on the proliferation and invasion of OSCC cells. The nude mouse model of subcutaneous xenograft tumor was used to evaluate the effect of BJO on OSCC cells in vivo. PCR, western blot and immunohistochemistry were used to verify the expression of MTFR2, glycolysis markers and related pathway molecules after BJO treatment.

Results

In vivo experiments using nude mice with xenografted OSCC cells and in vitro experiments with OSCC cell lines demonstrated that BJO treatment significantly inhibited the proliferation, migration, and invasiveness of OSCC cells. WB and PCR proved that BJO could effectively reduce the expression levels of MTFR2 and SOD2/H2O2 related signal transduction pathways. At the same time, the expression of oxidative phosphorylation markers increased, the expression of glycolytic markers decreased, and glycolysis-mediated decomposition of reactive oxygen species decreased, and H2O2 and oxygen levels decreased.In addition, when MTFR2 expression increased or decreased, SOD2/H2O2 expression also increased or decreased.

Discussion

In this study, we concluded through in vitro and in vivo experiments that BJO may affect the SOD2/H2O2 signaling pathway by down-regulating MTFR2-mediated aerobic glycolysis, thereby inhibiting cell proliferation, Migration, and Invasion. The elucidation of this mechanism helps us to understand the molecular mechanism ofinhibiting OSCC invasion and metastasis by BJO, which has important clinical value or improving the survival rate of OSCC patients.
Gastric schwannoma with post-surgical gastroparesis: a case report and literature review
Authors: Miao Ganggang , Zhang De , Li Jiajing , Deng Yanxiang , Gu Xingwei , Feng Tingting
Published: January 2025

Gastric schwannoma is a relatively rare submucosal mesenchymal tumor with low probability of metastasis and arises from Schwann cells of the gastrointestinal nervous plexus. Surgical therapy is the main treatment of gastric schwannoma with symptoms or malignant tendency. Gastroparesis is a potential complication following gastrointestinal surgery, which is a clinical syndrome caused by gastric emptying disorder and characterized by nausea, vomiting, and bloating, resulting in insufficient nutrient intake. Generally, post-surgical etiology is the main potential etiology of gastroparesis, while the most common underlying etiology is diabetes mellitus. So far, reports of gastroparesis arising from resection of gastric schwannoma are rare. We present an 80-year-old woman who was diagnosed with gastrointestinal stromal tumor (GIST) primarily and has undergone laparoscopic wedge-shaped gastrectomy. The pathological and immunohistochemical examination ultimately established the diagnosis of gastric schwannoma. The patient experienced belching, nausea, vomiting, and bloating 1 week after the surgery and confirmed as gastroparesis through gastrointestinal series and gastroscopic examination. A series of treatments were performed, including correcting fluid-electrolyte disorders and vitamin deficiencies, and nutritional support and pharmacological treatments. The patient ultimately recovered well, and the relevant literatures were reviewed to identify and handle similar cases hereafter.
Integrative analysis of ferroptosis in the hypoxic microenvironment of gastric cancer unveils the immune landscape and personalized therapeutic strategies
Authors: Xu Xiao , Fa Liangling , Sun Xiaoxiao , Yang Fangfang , Liu Yongrui , Song Jifu , Zhao Yongli , Dong Jigang
Published: January 2025

Background

Ferroptosis is a cell death mode caused by excessive accumulation of lipid peroxides caused by disturbance of intracellular metabolic pathway, which is closely related to iron and cholesterol metabolism homeostasis. Its regulation within the hypoxic metabolic tumor microenvironment (TME) has the potential to improve the effectiveness of tumor immunotherapy. The predictive role of ferroptosis in gastric cancer (GC) hypoxia TME, particularly in relation to TME immune cell infiltration, has not been fully explained.

Methods

By analyzing the mRNA expression data of ferroptosis and hypoxia-related genes, a prediction model was constructed to evaluate further the predictive value of immune cell infiltration, clinical characteristics, and immunotherapy efficacy of gastric cancer, and the essential genes were validated.

Results

Two distinct molecular states of ferroptosis-hypoxia were identified in GC. Notably, patients with high ferroptosis-hypoxia risk scores (FHRS) displayed significant levels of hypoxia and epithelial-mesenchymal transition (EMT), which were associated with unfavorable prognosis, increased chemoresistance, and heightened immunosuppression.

Conclusions

This study demonstrates that ferroptosis under hypoxic conditions significantly affects the modulation of the tumor immune microenvironment. The FHRS can independently predict prognosis in gastric cancer. Assessing the molecular status of ferroptosis-hypoxia in individual patients will help in selecting more suitable immunotherapy regimens by providing a better understanding of TME characteristics and predicting immunotherapeutic outcomes.
Serum stromal cell-derived factor 1α as a prognostic indicator in elderly patients with acute myeloid leukemia receiving CAG-based chemotherapy
Authors: Wang Zhenzhen , Yuan Jing , Zhou Nan , Zhang Jianfeng
Published: January 2025

Background

Stromal-cell-derived factor 1 (SDF-1) plays a crucial role in hematopoiesis and has been implicated in acute myeloid leukemia (AML) pathogenesis. Understanding its relationship with chemotherapy outcomes could lead to improved therapeutic approaches for elderly AML patients.

Methods

This study retrospectively analyzed the medical records of elderly AML patients (n = 187) and compared serum SDF-1α levels with age-matched controls (n = 120). Patients received CAG (cytarabine, aclarubicin, and G‐CSF)-based chemotherapy, and serum SDF-1α levels were assessed using ELISA.

Results

Serum SDF-1α levels were significantly elevated in elderly AML patients compared to controls (p < 0.001). Receiver operating characteristic (ROC) analysis confirmed its diagnostic relevance, revealing the area under the ROC curve (AUC) of 0.76. Factors such as age, French-American-British (FAB) classification, Eastern Cooperative Oncology Group (ECOG) performance status, primary AML status, white blood cell count, and bone marrow blast cell ratio, were confirmed to be prognostically relevant. Serum SDF-1α levels were elevated in patients who did not achieve complete remission (NCR) compared to those in complete remission (CR). ROC analysis further highlighted the predictive capability of serum SDF-1α for chemotherapy responsiveness. Independent predictors of treatment failure included age, FAB classification, ECOG status, and serum SDF-1α levels. Following chemotherapy, serum SDF-1α levels decreased in patients in CR but remained unchanged in those in NCR. Higher baseline levels of SDF-1α were associated with shorter overall survival.

Conclusions

Elevated serum SDF-1α levels in elderly AML patients are associated with poor chemotherapy response and shorter survival. Baseline serum SDF-1α levels could serve as a prognostic marker for CAG-based treatment outcomes.
Icariin modulates osteogenic and adipogenic differentiation in ADSCs via the Hippo-YAP/TAZ pathway: a novel therapeutic strategy for osteoporosis
Authors: Lin Shaozi , Meng Zuyu , Wang Mei , Ye Zixuan , Long Mengsha , Zhang Yiyao , Liu Fang , Chen Hongling , Li Menghan , Qin Jiajia , Liu Haiquan
Published: January 2025

Background

Adipose-derived stem cell (ADSC) transplantation presents a promising approach for osteoporosis (OP) treatment. However, the therapeutic efficacy of ADSCs is hindered by low post-transplantation survival rates and limited capacities for adhesion, migration, and differentiation. Icariin (ICA), the primary active compound of Epimedium, has been shown to promote cell proliferation and induce osteogenic differentiation; however, its specific effects on ADSC osteogenesis and the mechanisms by which ICA enhances osteoporosis treatment through cell transplantation remain inadequately understood.

Purpose

This study investigates the effects of different concentrations of ICA on the osteogenic and adipogenic differentiation of rat ADSCs, aiming to elucidate the underlying mechanisms. ADSCs were isolated from female SPF-grade SD rats, with surface markers identified through flow cytometry. Osteogenic and adipogenic differentiation were assessed using Alizarin Red and Oil Red O staining, respectively. Third-generation ADSCs were divided into five groups: control, resveratrol (100 μmol/L), and four ICA treatment groups (1, 10, 50, and 100 μmol/L). Western blotting was performed to analyze the expression of factors associated with the Hippo-YAP/TAZ signaling pathway and the adipogenic marker PPARγ. Additionally, ADSCs were labeled with lentiviruses carrying enhanced green fluorescent protein (EGFP) and 5-bromo-2-deoxyuridine (BrdU) to assess their in vivo distribution, survival, proliferation, and differentiation of ADSCs post-ICA intervention.

Results

In vitro, ICA significantly inhibited the Hippo pathway, reducing YAP and TAZ phosphorylation and enhancing their transcriptional activity, while simultaneously suppressing PPARγ. This promoted osteogenesis and inhibited adipogenesis in ADSCs. In vivo, ICA-treated ADSCs demonstrated effective distribution, survival, and osteogenic differentiation following subcutaneous injection into allogeneic rats.

Conclusion

Our study demonstrates that ICA significantly enhances the osteogenic differentiation of ADSCs while inhibiting adipogenesis, providing novel insights and therapeutic strategies for osteoporosis and related conditions.
Integration of histone modification-based risk signature with drug sensitivity analysis reveals novel therapeutic strategies for lower-grade glioma
Authors: Wang Jingyuan , Yan Shuai
Published: January 2025

Background

Lower-grade glioma (LGG) exhibits significant heterogeneity in clinical outcomes, and current prognostic markers have limited predictive value. Despite the growing recognition of histone modifications in tumor progression, their role in LGG remains poorly understood. This study aimed to develop a histone modification-based risk signature and investigate its relationship with drug sensitivity to guide personalized treatment strategies.

Methods

We performed single-cell RNA sequencing analysis on LGG samples (n = 4) to characterize histone modification patterns. Through integrative analysis of TCGA-LGG (n = 513) and CGGA datasets (n = 693 and n = 325), we constructed a histone modification-related risk signature (HMRS) using machine learning approaches. The model's performance was validated in multiple independent cohorts. We further conducted comprehensive analyses of molecular mechanisms, immune microenvironment, and drug sensitivity associated with the risk stratification.

Results

We identified distinct histone modification patterns across five major cell populations in LGG and developed a robust 20-gene HMRS from 129 candidate genes that effectively stratified patients into high- and low-risk groups with significantly different survival outcomes (training set: AUC = 0.77, 0.73, and 0.71 for 1-, 3-, and 5-year survival; P < 0.001). Integration of HMRS with clinical features further improved prognostic accuracy (C-index >0.70). High-risk tumors showed activation of TGF-β and IL6-JAK-STAT3 signaling pathways, and distinct mutation profiles including TP53 (63% vs 28%), IDH1 (68% vs 85%), and ATRX (46% vs 20%) mutations. The high-risk group demonstrated significantly elevated immune and stromal scores (P < 0.001), with distinct patterns of immune cell infiltration, particularly in memory CD4+ T cells (P < 0.001) and CD8+ T cells (P = 0.001). Drug sensitivity analysis revealed significant differential responses to six therapeutic agents including Temozolomide and targeted drugs (P < 0.05).

Conclusion

Our study establishes a novel histone modification-based prognostic model that not only accurately predicts LGG patient outcomes but also reveals potential therapeutic targets. The identified associations between risk stratification and drug sensitivity provide valuable insights for personalized treatment strategies. This integrated approach offers a promising framework for improving LGG patient care through molecular-based risk assessment and treatment selection.
Photon budgets and the relative effects of CDOM and pigment absorptions on primary production along a coastal salinity gradient
Authors: Berezovski Aleksandr , Hessen Dag O. , Andersen Tom
Published: January 2025

The study highlights the critical role of CDOM in coastal light attenuation and its impact on primary production (PP). We investigated the spectral attenuation of light due to water, phytoplankton pigments, detritus and coloured dissolved organic matter (CDOM) along a salinity gradient in the outer Oslofjord, Norway. By examining the effects of these components across different seasons, we aimed to elucidate their relative contributions to light absorption and PP. The findings suggest that increased terrestrial CDOM inputs, driven by climate, changed atmospheric deposition and land-use changes, could significantly affect coastal ecosystems by altering light attenuation and consequently PP and potentially leading to other ecological pressures. CDOM consistently dominated light absorption across all stations and seasons, contributing 50%–80% of the total absorption of photosynthetically active radiation. The absorption by CDOM and detritus decreased with increasing salinity, while phytoplankton absorption followed a seasonal succession. PP estimates show high seasonal variability from maximums in June to minimums in November, mainly attributed to, changes in seasonal light availability and phytoplankton biomass, followed by light attenuation by CDOM and differences in quantum yields of photosystem II (PSII). Nutrient analysis showed a seasonal pattern, with the highest nitrogen concentrations in November and depletion during more productive seasons, as well as conservative mixing throughout the salinity gradient. CDOM absorption played substantial, albeit not leading, role in influencing PP estimates, derived from a bio-optical model. CDOM was the main determinant of light attenuation across most wavelegnths.