bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of static and dynamic balance in healthy young adults: interactions between stance width and visual conditions
Authors: Luo Wei , Huang Zhirui , Li Hao , Zhong Tao , Chen Peishun , Min Yu
Published: January 2025

Objectives

This study investigates the impact of five distinct stance widths on static balance and limits of stability in healthy adults under varying visual conditions, specifically with eyes open and closed.

Methods

The Prokin Balance Instrument was used to evaluate static balance with both eyes open and closed, as well as limits of stability with eyes open, in 20 healthy adults (male, age = 21.55 ± 1.39). Participants were assessed at five stance widths (0 cm, 10 cm, 20 cm, 30 cm, and self-selected width) for each condition. Statistical analysis of the test indices was conducted using repeated measures ANOVA.

Results

In static balance tests, index values were higher with eyes closed than with eyes open, with this difference being most pronounced at narrower stance widths. Notably, a significant main effect was observed for all indicators, in the static balance test under varying visual and stance width conditions (P < 0.001). Significant interactions between visual conditions and stance width were identified for all static balance indicators (P < 0.001), except for average speed of anteroposterior sway (P = 0.195). Across both visual conditions, static balance indicators displayed a U-shaped distribution (a decrease followed by an increase) with increasing stance width, reaching a minimum at the self-selected width (16.35 ± 4.20 cm) and 20 cm. Additionally, significant main effects were observed for limits of stability in both the anteroposterior and mediolateral directions (P < 0.001). The limits of stability in the anteroposterior and mediolateral directions increased monotonically with stance width, peaking at 30 cm. The influence of stance width on static balance and limits of stability was significantly greater in the mediolateral direction compared to the anteroposterior direction, regardless of visual condition.

Conclusion

As stance width increases, the reliance on visual input for maintaining static balance decreases in healthy adults. We recommend using a self-selected stance width to optimize static balance and a 30 cm stance width to achieve maximum limits of stability during postural assessments.
Multi-omics study on the effect of moderate-intensity exercise on protein lactylation in mouse muscle tissue
Authors: Chang Jiahui , Wu Wanyu , Qian Ping , Lu Zhaoxu , He Xuejia , Wang Fang , Zhang Ting
Published: January 2025

Introduction

This study explores the effects of moderate-intensity exercise on protein lactylation in mouse muscle tissue metabolism.

Methods

Healthy adult mice running for 6 weeks as an exercise model and sedentary mice as the control were used to perform transcriptomic, proteomic, lactylation-proteomic, and metabolomic analyses. Correlation analysis between transcriptome and proteome and between proteome and metabolome was also conducted.

Results

In this study, 159 lactylation sites of 78 proteins were identified as being differentially regulated by moderate-intensity exercise. Enrichment analysis showed that the lactylation of proteins Atp5mg, and Atp5po exhibited ATP hydrolysis activity. Mtatp8 and Atp5po were involved in biological processes such as mitochondrial transmembrane transport, and Mtatp8, Atp5mg, and Atp5po participate in oxidative phosphorylation and thermogenesis pathways. The lactylation levels of Mtatp8, Atp5mg, and Atp5po proteins in the exercise group were significantly decreased, while their protein levels were significantly increased. The combined analysis of proteomics and metabolomics showed that the oxocarboxylic acid metabolism and sphingolipid signaling pathways had significant changes under the influence of moderate-intensity exercise.

Discussion

Our results indicate that moderate-intensity exercise has an effect on the lactylation level of mice, possibly by reducing the lactylation levels of Mtatp8, Atp5mg, and Atp5po and increasing the expression of their protein levels, thereby regulating the oxidative phosphorylation pathway and participating in energy metabolism. Further exploration is needed into the 2-oxocarboxylic acid metabolism pathway and the sphingolipid signaling pathway.
Porphyromonas gingivalis affects neutrophil pro-inflammatory activities
Authors: Zimny Agnieszka , Płonczyńska Alicja , Jakubowski Wiktor , Zubrzycka Natalia , Potempa Jan , Sochalska Maja
Published: January 2025

Porphyromonas gingivalis is the primary pathogen responsible for the development of periodontal inflammatory disease. Although gingipains are the major virulence factor of the pathogen, their role in impairing apoptosis and immune cell function is not fully understood. To investigate the impact of gingipains on neutrophil viability and function, we conducted studies using murine HoxB8 neutrophils and primary human neutrophils infected with wild-type strains of Porphyromonas gingivalis (W83 and ATCC 33277), or a gingipains-null mutant with deleted gingipains encoding genes, or wild-type bacteria preincubated with specific gingipain inhibitors. Flow cytometry revealed that wild-type Porphyromonas gingivalis had a marked effect on neutrophil viability regulated by anti-apoptotic proteins belonging to the Bcl-2 family; however, these effects were independent of gingipain expression or activity. Importantly, experiments using primary human neutrophils and macrophages revealed that gingipains play a significant role in the disruption of immune cell functions via the induction of reactive oxygen species and inactivation of neutrophil elastase activity. Additionally, although gingipains played a role in modulating the IL-8-dependent inflammatory response of human neutrophils, they did not affect the expression levels of pro-inflammatory cytokines TNF-α and IL-6.
Transcriptional profiles analysis of effects of Toxoplasma gondii rhoptry protein 16 on THP-1 macrophages
Authors: Yang Ningai , Li Mingyang , Yang Hong , Li Jiaming , Dang Tiantian , Li Guangqi , Zhao Zhijun
Published: January 2025

Introduction

Toxoplasma gondii, an intracellular parasitic protozoan, is globally recognized for its ability to cause parasitic diseases and has developed diverse strategies to evade immune-mediated elimination. The protein ROP16 of T.gondii plays a crucial role in this evasion process by specifically targeting macrophages and mononuclear phagocytes in vivo. However, the precise mechanisms underlying the involvement of type II ROP16 proteins in infection, inflammation, and other processes remain unknown.

Methods

To investigate the mechanism of action of gonococcal ROP16 proteins in human macrophages, we constructed a lentivirus overexpressing ROP16 and established stably transfected cell lines. We then analyzed the gene transcriptional profiles of ROP16 II in THP-1 macrophages using transcriptome sequencing. Interaction networks were constructed by screening differentially expressed genes and performing gene function enrichment analysis.

Results

As a result, five differentially expressed genes were identified: AAMDC, GPR158, RAD9A, STOML1, and STRA13. Immuno-featured differential analysis showed that type 17 T helper cells were more strongly correlated with GPR158 and STRA13, while CD8 T-cell was most strongly correlated with STOML1.

Discussion

Therefore, we conclude that the ROP16 protein plays a pivotal role in THP-1 macrophage infection and these five differentially expressed genes may serve as promising molecular targets for the prevention or control of toxoplasmosis. These findings have significant implications for the diagnosis and treatment of toxoplasmosis.
Impact of climate warming on vegetation cover: positive effects of native artiodactyla vs. grazing pressure in Alborz Protected Area
Authors: Salmanpour Farid , Shakoori Zahra , Keshtkar Mostafa , Kia Mehdi , Sayahnia Romina
Published: January 2025

Introduction

Climate warming, combined with grazing pressures, poses significant challenges to vegetation cover and ecosystem stability. In particular, livestock grazing is a primary factor in vegetation degradation, adversely affecting plant diversity, soil health, and key ecological interactions.

Methods

This study investigates the impact of grazing on vegetation in the Alborz region of Iran, focusing on the comparison between native herbivores (Artiodactyla) and livestock in the Central Alborz Protected Area (CAPA). We utilized 30 years of NDVI (Normalized Difference Vegetation Index) data from May to June (1994–2024) to assess vegetation dynamics and evaluate the influence of climate and grazing. ANOVA, Pearson correlation, and regression analyses were performed to identify relationships between vegetation cover, climate variables (temperature and rainfall), and grazing intensity.

Results

Results show a significant increase in vegetation cover, with Golestanak (without livestock) exhibiting a stronger positive response to climate variables (R² = 65%), while Zānoos (higher livestock density) showed greater variability (R² = 58%). Vegetation in Golestanak demonstrated a more significant positive correlation with temperature and rainfall, reflecting resilience to climatic stressors and the beneficial effect of moderate grazing by native Artiodactyla. In contrast, Zānoos showed more fluctuation in vegetation trends due to high livestock grazing pressure.

Discussion

This study highlights that while climate warming can positively affect vegetation cover, intensive livestock grazing can impede these gains, underlining the importance of adaptive management strategies for maintaining ecosystem health.
Severe reversible cardiomyopathy associated with adrenal crisis caused by isolated adrenocorticotropin deficiency: a case report
Authors: Wang Li , Bu Fangfang , He Lanjie , Yao Guihua
Published: January 2025

Adrenal crisis, also known as acute adrenal insufficiency, is an endocrine emergency that is associated with high mortality rates. Reversible cardiomyopathy with severe heart failure is a rare complication of adrenal crisis. Isolated adrenocorticotropin deficiency (IAD) is a rare condition of pituitary adrenal insufficiency. In this case report, we describe a 74-year-old male patient who was in good physical health and was admitted to our hospital with a sudden onset of fever and confusion that was complicated by hyponatremia and hypotension. Cardiac ultrasound showed significantly reduced left ventricular ejection fraction (LVEF; 10%). The patients was initially diagnosed with “septic shock” because of elevated inflammatory indicators and treated with mechanical circulatory support, antibiotics, fluid resuscitation, and intravenous administration of 50 mg hydrocortisone every 6 h for 2 days (400 mg in total). The symptoms of the patient improved significantly by this treatment in 6 days. The LVEF improved from 10% to 40%. However, the initial treatment did not alleviate hypotension and confusion. Therefore, the status of adrenal function was analyzed using blood and urine cortisol tests. Blood and urinary cortisol levels were significantly reduced, but concurrent increase in the ACTH levels were not observed. This indicated adrenal crisis. Subsequently, the patient was initially administered intravenous injection of hydrocortisone (50–150 mg/day) for 5 days, and then transitioned to a physiological supplement dose orally. The LVEF value improved further to 52%. Finally, the patient was diagnosed with adult isolated ACTH deficiency. The patient was prescribed regular oral hydrocortisone. The patient has not shown any signs of heart failure during follow up for more than half a year. In summary, we described a rare and severe case of adrenal crisis complicated with reversible cardiomyopathy that was caused by isolated ACTH deficiency. In such a case, conventional guideline directed medical therapy (GDMT) for heart failure was not considered suitable because of the underlying hypotension, hypoglycemia, and hyponatremia. Our study showed that timely supplementation of glucocorticoids achieved better therapeutic effects in patients with adrenal crises complicated by severe cardiomyopathy.
Research on the movement process of erosion-denudation type debris flow in middle-low mountains based on particle algorithm model
Authors: He Xiaofeng , Gong Yongfeng , Yan Jinkai , Gao Shichang , He Zheng , Zhang Gang , Wang Guorui , Hu Zhiyong , Wang Hui
Published: January 2025

Debris flow is a significant geological hazard in the mountainous regions of China, characterized by its sudden onset, high mobility, and considerable destructive potential. In the Helan Mountains, debris flows primarily consist of coarse-grained materials transported by water flows, exhibiting both high destructive potential and a broad impact range. Therefore, understanding the dynamics of debris flows in this region is of crucial importance. This study focuses on the Zhengguangou debris flow, utilizing the DAN-3D software based on Smoothed Particle Hydrodynamics (SPH) to construct a dynamic debris flow model. The movement characteristics of the debris flow were investigated by simulating various operating conditions, including differences in formation area conditions and rainfall intensity. The simulation results indicate that under extreme conditions (with a pore pressure coefficient of 0.8), the debris flow with the same initial volume traveled an average distance of 1503 m, significantly farther than the 1323 m travelled under normal conditions (with a pore pressure coefficient of 0.3). Under normal conditions, the final average deposition thickness of the debris flow was 8.9 m, which was thicker than the 8.3 m observed under extreme conditions. Regarding movement speed, the debris flow initially accelerated and then decelerated, with the extreme condition resulting in a greater travel distance compared to the normal condition. Additionally, the debris flow exhibited greater erosion depth and volume under normal conditions. In contrast, under extreme conditions, the debris flow had a larger scraping width, with the maximum width occurring at the point where the flow direction changed. This study enhances our understanding of the dynamic characteristics of debris flows in northern Ningxia and provides valuable insights for hazard prediction and mitigation efforts in the region.
Exploration of migration directions in different populations of Eothenomys miletus in the Hengduan Mountains of Yunnan Province: a genome-based analysis
Authors: Cai Yanfei , Jia Ting , Zhu Wanlong
Published: January 2025

Eothenomys miletus is an endemic species that inhabits the Hengduan Mountain regions (HDR) and serves as one of the primary hosts for plague and hantaviruses. While the physiological characteristics of E. miletus have been extensively studied, the molecular aspects, particularly the migration direction of E. miletus, remain unclear. In the present study, we utilized genomic data to investigate the migration direction of four populations: Ailaoshan (ALS), Jiangchuan (JC), Lijiang (LJ), and Deqin (DQ), which are distributed from south to north within the HDR. Our results indicated that the ALS population is positioned at the base of the phylogenetic tree, and admixture analysis revealed that the ALS population is more closely related to the JC and DQ populations. Integrate the molecular genetic structure, fossil records of E. miletus as well as the results of our research, we inferred that the migration direction of E. miletus may have been from south to north, suggesting that the DQ and JC populations may have originated from the migration of ALS. However, the migration patterns and origins of the LJ population require further investigation and discussion. Additionally, we focused on identifying genomic signatures of selection and local adaptation among the different populations. We identified three selected genes associated with the olfactory placode in DQ: Six1, Six4, and Sox2. We hypothesized that these genes may be linked to the DQ population’s adaptation to the region’s microclimate. In summary, the present study is the first to employ genomics to explore the migration direction of E. miletus, which is crucial for future research on the origins of Eothenomys.
Mendelian randomization analysis reveals genetic evidence for a causal link between inflammatory bowel disease and uterine cervical neoplasms
Authors: Cao Chunge , Sun Xiaorui , Chen Xiaohu , Zhang Ying , Yue Chaoyan
Published: January 2025

Background

Inflammatory bowel disease (IBD) has been reported to be associated with risk of uterine cervical neoplasm. We aimed to evaluate the causal relationship between IBD and uterine cervical neoplasm using a bidirectional Mendelian randomization analysis.

Methods

We derived instrumental variables for IBD, including Crohn’s disease and ulcerative colitis, from the IEU Open genome-wide association study (GWAS) database, and for the histological subtypes of uterine cervical neoplasm from the FinnGen repository’s GWAS data. The collected GWAS data predominantly represent individuals of European ancestry. The inverse-variance weighted (IVW) method was employed as primary analysis approach.

Results

IBD (IVW odds ratio = 1.127, 95% confidence interval = 1.016–1.251; p = 0.024) and CD (IVW odds ratio = 1.119, 95% confidence interval = 1.023–1.224; p = 0.014) exhibited a significant causal effect on malignant cervical carcinoma. Sensitivity analyses confirmed these findings.

Conclusion

Genetically predicted IBD and CD are risk factors for the development of malignant cervical carcinoma. Patients with IBD and CD require specific attention to prevent cervical squamous cell carcinoma. Further studies to elucidate the underlying mechanisms may reveal new therapeutic targets.
Recombinant SpTransformer proteins bind to specific sites on sea urchin phagocytes and modulate SpTransformer gene expression and immune responsiveness
Authors: Crow Ryley S. , Grayfer Leon , Smith L. Courtney
Published: January 2025

Introduction

The California purple sea urchin, Strongylocentrotus purpuratus, relies exclusively on an innate immune system to survive in its pathogen rich marine environment. Central to this defense is the SpTransformer (SpTrf) gene family that is unique to the euechinoid group of echinoderms. These genes were initially identified based on their striking upregulation in response to immune challenge. The SpTrf gene family encodes structurally similar proteins with a wide range of sequence diversity within and among individual sea urchins. A recombinant (r)SpTrf protein interacts specifically with a variety of non-self targets. Other rSpTrf proteins cross-linked to inert beads show distinct functions for cell binding and augmenting phagocytosis . However, whether the rSpTrf proteins bind to sea urchin phagocytes, and the cellular consequences of binding are largely unexplored.

Methods

rSpTrf protein binding to, and responses by phagocytes was investigated by cytology, flow cytometry, binding competitions using In-cell ELISA, and gene expression analyses.

Results

Soluble rSpTrf proteins bind specifically and exclusively to both live and fixed polygonal and small phagocytes. The different rSpTrf proteins appear to bind shared receptor(s) or other form of cell surface binding site. The phagocyte response to bound rSpTrf proteins culminates in modulated expression of the SpTrf gene family as well as other immune-related genes.

Conclusions

These findings underscore the multifaceted and dynamic functions of SpTrf proteins within the innate immune system of the purple sea urchin. Their varied functions enable a robust immune response while also providing a unique modulatory mechanism by which response levels are controlled and adjusted to the level of the foreign threat.
Single-cell RNA sequencing revealed PPARG promoted osteosarcoma progression: based on osteoclast proliferation
Authors: Sun Lei , Zhang Jinhao , Xiahou Zhikai , Zhao Zhenzhen , Liang Yanchen
Published: January 2025

Background

Osteosarcoma (OS) is one of the most common primary malignant bone tumors, primarily originating from mesenchymal tissue. It is notorious for its high invasiveness, high disability rate, high mortality rate, and poor prognosis. In most primary and metastatic malignant tumors, bone destruction can promote cancer progression, which is closely related to osteoclast activation and the imbalance between osteoblasts and osteoclasts. A large number of studies confirmed that osteoclasts are an important part of OS, which play an active role in destroying bone homeostasis and promoting the progress of OS. Therefore, we conducted a detailed study of osteoclasts at the single cell level, aiming to find new OS therapeutic targets to prevent tumor progression and local spread.

Methods

We analyzed the single-cell sequencing data of OS patients and usedMonocle2, Cytotrace, and Slingshot software to analyze the pseudo-sequential trajectory during OS progression. CellChat was used to reveal the communication between cells. PySCENIC was used to identify active transcription factors in osteoclasts. Finally, we further demonstrated the results by RT-qPCR analysis, CCK-8 assay, wound healing assay, Transwell assay, etc.

Results

Through the analysis of single-cell sequencing data in OS, we identified a highly specific subgroup, C2MKI67+ Osteoclast. The key signaling pathway APP and the top 1 transcription factor PPARG in this subgroup played essential roles in osteoclast proliferation and differentiation. Given the pivotal role of osteoclasts in OS progression, we speculated that these signaling pathways and transcription factors could emerge as novel therapeutic targets, offering innovative strategies for OS treatment.

Conclusion

This study enhanced our understanding of OS and osteoclasts through scRNA-seq. Furthermore, we discovered that PPARG amplifies osteoclast activation and proliferation, resulting in excessive bone resorption and degradation of the bone matrix, thereby creating a favorable environment for tumor cell proliferation and growth. By innovatively targeting PPARG, it affected osteoclast proliferation and thus affected tumor progression; this work offered new insights and directions for the clinical treatment of OS patients.
Case report: Advanced age at transplantation and pre-emptive treatment with dupilumab in DOCK8 deficiency
Authors: Trombello Sophia , Jarisch Andrea , Willasch Andre , Rettinger Eva , Fekadu-Siebald Julia , Holzinger Dirk , Adelmann Roland , Bader Peter , Bakhtiar Shahrzad
Published: January 2025

Dedicator of cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency (CID) due to biallelic mutations in the gene encoding DOCK8. Major clinical phenomena are recurrent severe infections of the lungs and skin, atopic eczema, and predisposition to malignancy leading to a poor prognosis. Typical findings include highly elevated IgE and eosinophilia. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is indicated as the only curative treatment option. We present a patient with advanced disease undergoing alloHSCT at the age of 11 years after individualized pre-treatment using dupilumab and rituximab resulting in a decrease in IgE levels and clinical improvement of the skin condition. Additionally, in a review of the literature, we summarize morbidity and outcome in DOCK8-deficient patients older than 8 years of age receiving alloHSCT. Life-threatening infections, malignancy, and disease-related complications with organ damage pre-transplant are challenging in older DOCK8-deficient patients. The therapeutic role of dupilumab in DOCK8 deficiency should be evaluated in larger studies.
Why is it so difficult to understand why we don’t understand human systemic lupus erythematosus? Contemplating facts, conflicts, and impact of “the causality cascade paradigm”
Authors: Rekvig Ole Petter
Published: January 2025

In attempts to understand systemic lupus erythematosus (SLE), we find ourselves in the intellectual cross-point between nosology, pathogenicity-oriented science, philosophy, empiricism, and qualified conjectures. A vital consequence in science theory is that scientific hypotheses that are not critically investigated are in danger of being transformed into scientific dogmas1. This statement has consequences for this study. Two central problematic aspects are discussed. For the first, we have to consider new selection principles for classification criteria—implying integration of the causality principle. Second, central historical data must be implemented if we aim to understand SLE. These data comprise famous descriptions of distinct, dynamically changing DNA structures linked to the genetic machinery. These unique structures have since their discoveries decades ago mostly been ignored in SLE research. Likewise, inconclusive dogmatic data indicate that different glomerular ligands are recognized by nephritogenic anti-dsDNA antibodies—exposed chromatin fragments or inherent membrane ligands. These incongruent models have not been comparatively and systematically investigated. Three research areas will be critically discussed: (i) selection and role of SLE classification criteria, a process that must imply the causality principle; (ii) definition and impact of anti-dsDNA structure-specific antibodies; (iii) incongruent pathogenic models that account for lupus nephritis. A precise and critically important question is if SLE itself is a response to a dominant unified cause that initiates a cascade of downstream effects (criteria) or if SLE represents combined responses to a random interplay of multiple cause-effect events. These principally different explanations are formally not excluded or accepted today. Currently, SLE may be regarded as a disease with phenotypic diversity, independently segregated manifestations with unresolved etiologies that are not unique to a single SLE phenotype. The focus for the present discussion is basically how we, by critical hypotheses, can re-consider science-based selection of SLE classification criteria in order to delimitate and rationalize SLE. Classification criteria, autoimmunity, DNA structures, and anti-dsDNA antibodies are integrated aspects in this discussion.
Regulatory role of S1P and its receptors in sepsis-induced liver injury
Authors: Wang Bin , Wu Xiaoyu , Cheng Jiangfeng , Ye Junming , Zhu Hongquan , Liu Xiaofeng
Published: January 2025

As an immune and metabolic organ, the liver affects the progression and prognosis of sepsis. Despite the severe adverse effects of sepsis liver injury on the body, treatment options remain limited. Sphingosine-1-phosphate (S1P) is a widely distributed lipid signaling molecule that binds to five sphingosine-1-phosphate receptors (S1PR) to regulate downstream signaling pathways involved in the pathophysiological processes of sepsis, including endothelial permeability, cytokine release, and vascular tone. This review summarizes current research on the role of S1P in normal liver biology and describes the mechanisms by which changes in S1P/S1PR affect the development of liver-related diseases. At the same time, the pathological processes underlying liver injury, as evidenced by clinical manifestations during sepsis, were comprehensively reviewed. This paper focused on the mechanistic pathways through which S1P and its receptors modulate immunity, bile acid metabolism, and liver-intestinal circulation in septic liver injury. Finally, the relationships between S1P and its receptors with liver inflammation and metabolism and the use of related drugs for the treatment of liver injury were examined. By elucidating the role of S1P and its receptor in the pathogenesis of sepsis liver injury, this review established a molecular targeting framework, providing novel insights into clinical and drug development.
A novel approach to digital characterisation of Tertiary Lymphoid Structures in colorectal cancer
Authors: Munoz-Erazo Luis , Park Saem Mul , Lin Shelly , Chen Chun-Jen J. , Zhou Lisa Y. Y. , Rhodes Janet L. , Jeon Taesung , Fenton Sonya , McCall John L. , Kemp Roslyn A. , Dunbar P. Rod
Published: January 2025

Introduction

Tertiary Lymphoid Structures (TLS) in cancer tissue are potential sites for the organisation of immune responses to cancer, and correlate positively with improved clinical outcomes for patients including in colorectal cancer (CRC). However it has proven challenging to standardise assessment of TLS due to the highly variable appearances of circumscribed domains of TLS within tissue sections. A recent three-dimensional reconstruction of TLS in CRC tissue showed that TLS are often large, multi-lobular structures, suggesting that assessing TLS across whole sections may be necessary to provide an accurate view of TLS activity in a patient’s tumour.

Methods

We used whole-section scans of multiplexed immunofluorescence images to characterise TLS from 22 subjects with CRC. Multiplexed staining for CD20, CD3, CD8, Foxp3 and Ki-67 enabled us to identify B-cells, CD8+ T-cells, Foxp3– CD4 T-cells, and Foxp3+ CD4 Tcells in all sections, and quantify both the presence of these cell subsets in lymphocytic clusters and their degree of proliferation within those clusters.

Results

In total we identified 524 lymphocytic clusters with morphology consistent with TLS. TLS domains varied substantially between samples in size, morphology, cellular constituents, count (from 4 to 100), and proportion of total section area they occupied (0.2%-7.8%). We quantified proliferation of B-cells and T-cell subsets within TLS domains across entire sections and compared data to the canonical approach of counting and phenotyping individual TLS domains. The whole-slide approach proved simpler, generating digital summaries that readily identified patients with strikingly different levels of immune activity within their TLS. Strong correlations were observed between the proliferation of B-cells and T-cell subsets. The presence of non-proliferating Foxp3+ CD4 T-cells within TLS showed no correlation with the level of proliferation of other lymphocyte subsets.

Discussion

Whole-section digital quantification of immune cell activity within TLS has advantages over canonical approaches, and could accelerate research into correlations between TLS status and clinical outcomes, with potential to enable a standardised assay for clinical use.
In silico design of a multi-epitope vaccine against Mycobacterium avium subspecies paratuberculosis
Authors: Guo Weiqi , Wang Xinyu , Hu Jiangang , Zhang Beibei , Zhao Luru , Zhang Guangdong , Qi Jingjing , Wei Zuzhang , Bao Yanqing , Tian Mingxing , Wang Shaohui
Published: January 2025

The widespread chronic enteritis known as Paratuberculosis (PTB) or Johne's disease (JD) is caused by Mycobacterium avium subspecies paratuberculosis (MAP), posing a significant threat to global public health. Given the challenges associated with PTB or JD, the development and application of vaccines are potentially important for disease control. The aim of this study was to design a multi-epitope vaccine against MAP. A total of 198 MAP genomes were analyzed using pan-genome and reverse vaccinology approaches. B-cell and T-cell epitope analysis was performed on the selected promising cross-protective antigens followed by selection of epitopes with high antigenicity, no allergenicity, and no toxicity for the design of the vaccine. The designed vaccine was evaluated through molecular dynamics simulations, molecular docking, and immunological simulations. The results revealed the identification of five promising cross-protective antigens. In total, 10 B-cell epitopes, 10 HTL epitopes, and 9 CTL epitopes were selected for the design of the vaccine. Both the vaccine candidate and the vaccine-TLR4 complex demonstrated considerable stability in molecular dynamics simulations. Molecular docking studies confirmed that the vaccine candidate successfully interacted with TLR4. Immunological simulations showed an increase in both B-cell and T-cell populations after vaccination. Additionally, the vaccine candidate exhibited a codon adaptability index of 1.0 and a GC content of 53.64%, indicating strong potential for successful expression in Escherichia coli. This research developed a multi-epitope vaccine targeting MAP through pan-genomes and reverse vaccinology methods, offering innovative strategies for creating effective vaccines against MAP.
Case report: Therapeutic use of bortezomib in a patient with Schnitzler syndrome
Authors: Bai Hua , Zhou Dongming , Liu Jinwen , He Jie , Min Zhou , Fan Wenyong , Chen Bing , Xu Yong
Published: January 2025

Schnitzler syndrome (SchS) is a rare acquired systemic autoinflammatory disorder, characterized by chronic urticarial rash and immunoglobulin M (IgM) monoclonal gammopathy. Anti-interleukin-1 (IL-1) therapies have been shown to be more effective in managing the clinical symptoms of SchS compared to anti-IL-6 therapies. In this case report, we present a male patient with urticarial rash, fever, and arthralgia. Laboratory tests identified the presence of IgMκ monoclonal protein, and the absence of IL-1β in serum. Whole exome sequencing (WES) did not reveal any pathological variants associated with monogenic autoinflammatory diseases or the MYD88 L265P mutation. He met the diagnostic criteria for SchS and was treated with bortezomib, leading to a significant improvement in clinical symptoms and a decline in IgMκ monoclonal protein levels. The patient tolerated the treatment well. This case suggests that bortezomib may be considered as a potential treatment option for SchS, in addition to anti-IL-1 therapies and bruton tyrosine kinase (BTK) inhibitors.
Case report: Successful perioperative intervention with efgartigimod in a patient in myasthenic crisis
Authors: Shelly Shahar
Published: January 2025

Introduction

This case describes successful response to efgartigimod in the treatment of myasthenic crisis secondary to paraneoplastic disease, and in the perioperative setting.

Methods

An elderly female presented with speech difficulties, cessation of eating and 10kg weight loss over 4 months.

Results

Examination revealed ptosis, dysarthria, nasal speech, and weakness in limbs and neck flexors. Single fiber electromyography demonstrated abnormal jitter response in the orbicularis oculi muscle. Nicotinic acetylcholine receptor antibodies were detected in serum. The patient was diagnosed with very-late-onset myasthenia gravis (MG) in a myasthenic crisis and later required intubation and admission to intensive care but was unresponsive to plasma exchange. Paraneoplastic disease was suspected and computed tomography revealed a bladder mass. Efgartigimod 10 mg/kg was administered intravenously to stabilize her condition before surgery. The patient’s Myasthenia Gravis Activities of Daily Living (MG-ADL) score decreased from 19 to 14 after the first dose and she subsequently underwent surgical removal of the bladder tumor without complication. Her condition continued to improve post-operatively with completion of the first treatment cycle. Four cycles of efgartigimod over 10 months resulted in an MG-ADL score of 3.

Discussion

Efgartigimod may be a novel treatment for perioperative management of MG, myasthenic crisis, and paraneoplastic MG. Further study is warranted.
Case report: Single infusion of combined anti-CD20 and anti-CD38 monoclonal antibodies in pediatric refractory lupus nephritis
Authors: Chiarenza Decimo Silvio , Mancini Raul , Bigatti Carolina , Caridi Gianluca , Consolaro Alessandro , Natoli Valentina , Mortari Gabriele , Kajana Xhuliana , Lugani Francesca , Gattorno Marco , Ghiggeri Gian Marco , La Porta Edoardo , Gaggero Gabriele , Verrina Enrico E. , Angeletti Andrea
Published: January 2025

Lupus nephritis (LN), present in 30%–50% of systemic lupus erythematosus (SLE) patients, often necessitates standard immunosuppressive therapy (glucocorticoids, MMF, CYC) as suggested by the European League Against Rheumatism/European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) and Kidney Disease Improving Global Outcomes (KDIGO) guidelines. However, a subset of subjects remains refractory. Recent findings suggested the efficacy of targeting CD38-long-lived plasma cells in LN and SLE refractory to standard treatment. However, previous experiences were limited to adult patients and described different therapeutical schemes based on daratumumab, with the addition or absence of belimumab. Moreover, the minimal effective dose of daratumumab has yet to be fully defined. In this report, we describe two cases of juvenile-onset refractory LN/SLE successfully managed with a combination of a single infusion of rituximab (targeting CD20 on B cells) and daratumumab (targeting CD38 on long-lived plasma cells), unlike prior regimens requiring prolonged daratumumab infusions. Our approach was safe and effective and may potentially reduce adverse effects and costs, providing a novel therapeutic option for juvenile refractory LN.
Dietary supplementation of mulberry leaf oligosaccharides improves the growth, glucose and lipid metabolism, immunity, and virus resistance in largemouth bass (Micropterus salmoides)
Authors: Zhou Donglai , Zhong Wenhao , Fu Bing , Li Erna , Hao Le , Li Qingrong , Yang Qiong , Zou Yuxiao , Liu Zhenxing , Wang Fubao , Liao Sentai , Xing Dongxu
Published: January 2025

This study investigated the effects of dietary supplementation of mulberry leaf oligosaccharides (MLO) on the growth performance, serum biochemistry, glucose and lipid metabolism, antioxidant activity, liver health, and virus resistance in largemouth bass (Micropterus salmoides). The fish were fed with CK (basal diet), MLOL (basal diet supplemented with 0.5%MLO), and MLOH (basal diet supplemented with 1.0% MLO) for 80 days, and then subjected to a 21-day viral challenge experiment. The results showed that MLO supplementation had no adverse effect on the weight gain rate, specific growth rate, feed intake, and condition factor (P > 0.05), but significantly decreased the feed conversion rate and viscerosomatic index (P< 0.05). Moreover, the MLOL and MLOH group had significantly lower contents of triglyceride, blood glucose, and malondialdehyde and activities of serum alanine aminotransferase and aspartate aminotransferase, while significantly higher levels of serum and liver total superoxide dismutase and lower levels of glutathione than the CK group (P< 0.05). MLO supplementation significantly up-regulated the relative expression of glycolytic genes gk and pfk and lipid catabolism genes ppar-α and cpt-1, while obviously down-regulated that of acc, fas, and dgat related to fatty acid synthesis in the liver tissue (P< 0.05). In terms of liver health, MLO supplementation significantly up-regulated the relative expression of anti-inflammatory cytokines il-10 and tgf-β, while decreased that of pro-inflammatory cytokines nf-κb, il-8, and tnf-α in the liver tissue (P< 0.05). The viral challenge test showed that MLO supplementation significantly improved the survival rate of M. salmoides after largemouth bass ranavirus (LMBV) infection. Dietary MLO supplementation promoted liver glucose and lipid metabolism, and improved the immunity and resistance of M. salmoides to LMBV by regulating the PPAR signaling way and inhibiting the NF-kB signaling pathway. The appropriate addition amount of MLO to the diet was determined to be 1.0%.
IL-33 signaling is dispensable for the IL-10-induced enhancement of mast cell responses during food allergy
Authors: Krajewski Dylan , Ranjitkar Saurav , Jordan Nathan , Schneider Sallie S. , Mathias Clinton B.
Published: January 2025

Background

The IL-33/ST2 axis plays a pivotal role in the development of IgE-mediated mast cell (MC) responses during food allergy. We recently demonstrated that the pleiotropic cytokine, IL-10, not only exerts proinflammatory effects on IgE-mediated MC activation, but also promotes IL-33-induced MC responses. However, whether IL-33 is necessary for IL-10’s proinflammatory effects has not been examined.

Methods

To therefore determine the role of the IL-33/ST2 axis in this pathway, we assessed the effects of IL-10 on IgE-mediated MC activation and food allergy development in wild-type (WT) and ST2-/- mice.

Results

IL-10 stimulation significantly enhanced IL-33 gene expression, ST2 receptor expression, cytokine production, mMCP-1 secretion, and proliferation in IgE and antigen-activated bone marrow-derived MCs (BMMCs) from WT mice. ST2-/- BMMCs exhibited reduced cytokine secretion in response to IgE-dependent activation. However, IL-10 enhanced cytokine production, mMCP-1 secretion, and proliferation in these cells as well. To further assess the role of IL-10, food allergy was induced in WT and ST2-/- mice subjected to antibody-mediated IL-10 depletion. IL-10-depleted WT mice exhibited a significant attenuation in MC-mediated responses to OVA challenge. While ST2-/- mice also exhibited a profound suppression of MC responses, IL-10 depletion had no additional effects. However, ST2-/-/IL-10-/- mice exhibited further decreases in OVA-IgE and antigen-specific MC activation compared to ST2-/- mice.

Conclusion

Our data demonstrates that IL-10 can enhance MC responses in both WT and ST2-/- mice, further corroborating its proinflammatory effects on MCs and suggesting that they are not regulated by IL-33 signaling.
Exploring the impact of xenobiotic drugs on forensic entomology for accurate post-mortem interval estimation
Authors: Jain Sapna , Parrott Jonathan J. , Javan Gulnaz T.
Published: January 2025

Forensic entomotoxicology is an emerging field within forensic entomology that investigates the effects of chemicals, drugs, and toxins on insect development and their implications for postmortem interval (PMI) estimation. This systematic overview delves into the influence of drugs such as Morphine, heroin, Opiates, and cocaine on the variables affecting the use of forensically significant insects as evidence tools. Notably, it has been observed that the presence of drugs does not appear to alter the progression of the lifecycle from the first instar to the emergence of flies, indicating that PMI estimations based on fly emergence remain unaffected by drugs. However, larvae treated with drugs frequently show delayed pupation, suggesting the need for further research into the impact of different compounds on various insect species over more extended observation periods. Additionally, conflicting results have been noted regarding how toxins can influence the developmental process in larvae, underscoring the necessity to assess the effect of different classes of compounds on other insect species. The study also recommends exploring factors such as the samples’ collection site and the drugs’ pathological implications to inspire future research. Furthermore, the paper underscores the potential for varying drug effects across insect species, emphasizing the complexity of interpreting drug impacts on PMI estimations. This systematic review was conducted by the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines.
Bug off or bug out: mapping flight secrets of Triatoma garciabesi (Hemiptera: Reduviidae) through climate, geography, and greenery
Authors: Verly Thaiane , Fiad Federico G. , Carbajal-de-la-Fuente Ana Laura , Pita Sebastián , Piccinali Romina V. , Lobbia Patricia A. , Sánchez-Casaccia Paz , Rojas de Arias Antonieta , Cavallo María José , Gigena Gisel V. , Rodríguez Claudia S. , Vega-Gómez María C. , Rolón Miriam , Nattero Julieta
Published: January 2025

Introduction

Triatoma garciabesi is a vector of Trypanosoma cruzi, the causative agent of Chagas disease, and is found across northwest and central Argentina, southern Bolivia, and western Paraguay. It frequently invades rural houses during the warm seasons and is common in peridomestic and wild environments. Recently, the existence of two lineages has been demonstrated based on variation in cytochrome c oxidase I gene (coI). These lineages occur across the species distribution range and coincide with different ecological regions. Here, we aim to examine how phenotypic variation in flight-related traits is structured, determine the association between these traits and geographic distance, and identify the climatic, geographic, and/or vegetation cover variables that best explain the morphometric variation in flight-related traits.

Methods

A total of 198 males of T. garciabesi from 24 populations in Argentina and Paraguay were included in this study, covering almost the entire T. garciabesi distribution range. Size and shape components of the forewing, membranous, and stiff portions of the forewing and head were measured using a landmark-based methodology.

Results

Our study documents that the size component of the membranous and stiff portions showed significant variation across the species range. Although forewing and head shape did not show significant differences in Procrustes distances across all pairs of populations, the membranous and stiff portions did. There is a strong and consistent association between shape and geographic distances at all levels of comparison (species and lineage ranges). The size and shape components and the geographic, climatic, and/or vegetation indexes explained covariation in all flight-related traits.

Discussion

T. garciabesi appears to be a species sensitive to vegetation cover and landscape features. This study provides evidence for this by showing clear variation in flight-related traits across the species and lineage distribution range, as well as indications of isolation by distance and variation in flight-related traits according to climate, geography, and vegetation cover.
Validation of wing geometric morphometrics in Chrysodeixis spp. (Lepidoptera: Noctuidae) to support pest identification in invasive species survey programs
Authors: Smith-Pardo Allan H. , Torres Karina M. , Paula-Moraes Silvana V.
Published: January 2025

Looper moths of the genus Chrysodeixis (Lepidoptera: Noctuidae: Plusiinae) are important pests of many crops and native plants worldwide. Chrysodeixis chalcites (Esper) is listed as an invasive species for the United States with records of interception. Native species of the Plusiinae subfamily are morphologically similar and commonly cross-attracted in survey trapping programs for C. chalcites, such as Chrysodeixis includens (Walker), a native economic pest. The species identification relies on male genitalia dissection and DNA analysis. These processes are time and cost-consuming and require expertise. In this work, we evaluated the use of wing geometric morphometrics (GM) as a tool to overcome the identification challenges associated with the complex morphologies of Chrysodeixis spp. The cleaned wings of specimens with validated identification were photographed under a digital microscope, and seven venation landmarks were annotated from the images. The digital coordinates of the wing landmarks were analyzed in MorphoJ. Our results validated the use of GM for distinguishing the invasive C. chalcites from the native C. includens. A limited number of landmarks on the center of the wing was used to address the challenges in GM for trap-collected lepidopteran pests. Future automation of the novel application of GM for identifying C. includens can be explored in trapping systems for IPM and surveys for the invasive C. chalcites.