Unusual coexistence: branchial cleft cyst harboring papillary thyroid carcinoma with lymph node metastasis - a rare case report and clinical insights.

Background: The simultaneous occurrence of Branchial Cleft Cyst (BCC) and Papillary Thyroid Carcinoma (PTC) represents an unusual malignant tumor, with cases featuring associated lymph node metastasis being particularly rare. This combination underscores an increased potential for metastasis, and the assessment of neck masses, particularly on the lateral aspect, may inadvertently overlook the scrutiny of the thyroid. Therefore, healthcare providers should exercise vigilance, especially in patients over the age of 40, regarding the potential for neck masses to signify metastasis from thyroid malignancies. Currently, surgical intervention stands as the primary effective curative method, while the postoperative administration of radioactive iodine therapy remains a topic of ongoing debate. Case report: In the presented case, a 48-year-old male patient with a right neck mass underwent surgical intervention. The procedure included the excision of the right neck mass, unilateral thyroidectomy with isthmus resection, and functional neck lymph node dissection under tracheal intubation and general anesthesia. Postoperative pathology findings revealed the coexistence of a BCC with metastatic PTC in the right neck mass, as well as papillary carcinoma in the right thyroid lobe. Lymph node metastasis was observed in the central and levels III of the right neck. Conclusion: The rare amalgamation of a BCC with PTC and concurrent lymph node metastasis underscores the invasive nature of this malignancy. Healthcare professionals should be well-acquainted with its clinical presentation, pathological characteristics, and diagnostic criteria. A multidisciplinary approach is strongly recommended to enhance patient outcomes.

Overexpressed FKBP5 mediates colorectal cancer progression and sensitivity to FK506 treatment via the NF-κB signaling pathway.

Colorectal cancer (CRC) is a common and deadly tumor. FK506-binding protein 5 (FKBP5) is associated with some cancers, but the role of FKBP5 in CRC is not clear. The present study aimed to reveal the relationship between FKBP5 and CRC and to uncover the roles of FK506 in CRC. In total, 96 CRC patients were recruited. Survival analysis was conducted using the Kaplan-Meier method and COX regression analyses. Bioinformatics analyses were performed to explore the functions of FKBP5. The mechanisms of FKBP5 and the roles of FK506 in CRC progression were clarified by immunohistochemistry, MTS, scratch assay, transwell and flow cytometric analyses via in vitro and in vivo experiments. FKBP5 was overexpressed in 77 cancer tissues compared to that in matched normal tissues, and the overall survival rate of these patients was relatively shorter. Bioinformatics analyses showed that FKBP5 regulates proliferation, invasion, migration, epithelial-mesenchymal transition and nuclear factor-kappa B (NF-κB) signaling. The upregulation or downregulation of FKBP5 dramatically increases or decreases the proliferation, invasion and migration abilities of CRC cells. The expression of NF-κB, inhibitor B kinase α, matrix metalloproteinase-2 and metalloproteinase-9 positively correlated with FKBP5. FK506 inhibits the progression of CRC via the FKBP5/NF-κB signaling pathway. Our study identified a regulatory role for FKBP5 in CRC progression. Therefore, targeting FKBP5 may provide a novel treatment approach for CRC. FK506 can inhibit the progression of CRC by restraining the FKBP5/NF-κB signaling pathway and is expected to become a new drug for the treatment of CRC.

FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection.

The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in ß cells. This upregulation increases both insulin secretion and susceptibility of ß cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

The feasibility and clinical significance of lateral approach thyroidectomy.

BACKGROUND: By comparing the three lateral approaches to thyroidectomy, the feasibility and clinical effects were analyzed, and the advantages of the lateral approach were summarized. METHODS: From January 2022 to January 2023, 52 patients with thyroid cancer admitted to our department were selected and subjected to Lateral approach for thyroidectomy. Among them, 31 patients underwent thyroidectomy via the supraclavicular approach, 13 patients underwent endoscopic thyroidectomy via the subclavicular approach, and 8 patients underwent endoscopic thyroidectomy via the axillary approach. The basic conditions, surgical conditions, complications, postoperative pain scores and postoperative satisfaction of patients in the three approach surgery groups were recorded and analyzed. RESULTS: There were no significant differences among the three approach groups in terms of patient characteristics, number of central lymph node dissections, intraoperative blood loss, postoperative drainage volume, duration of drainage tube placement, length of hospital stay, postoperative pain, satisfaction, and complications. However, the operation time was longest in the subclavicular approach group, followed by the axillary approach group, and shortest in the supraclavicular approach group. The total hospitalization cost was highest in the axillary approach group, followed by the subclavicular approach group, and lowest in the supraclavicular approach group. CONCLUSION: The lateral approach for thyroidectomy is deemed a safe and effective method. The three different approach paths gradually increase in length, allowing for the accumulation of anatomical experience. This approach has a shorter learning curve for clinical doctors and is a favorable choice for patients seeking aesthetic benefits.

Angiosarcoma of the breast: A review.

Breast angiosarcoma is a rare and highly aggressive malignancy with a poor prognosis. It can occur spontaneously or be associated with factors such as radiation therapy or chronic lymphedema. The etiology and pathogenesis of this disease are still unclear, the clinical symptoms and imaging findings lack specificity, and the pathological morphology is diverse, which is easy to be confused with other diseases. There is no clear guideline for surgical treatment. Although the optimal surgical approach remains unclear, the ultimate goal is surgical excision with optimal margins, which remains the primary method of treatment. In clinical practice, the choice of the surgical approach should be made by considering the tumor size, pathological type, and patient preferences. In clinical practice, the selection of surgical methods should be carried out with comprehensive consideration of tumor size, pathological types and patients' wishes. There is no clear consensus on whether radiotherapy and chemotherapy should be carried out after surgery, and its optimal program and efficacy are uncertain. This article reviews the etiology, clinical manifestations, pathological features, imaging findings, treatment, prognosis and other aspects of breast angiosarcoma, so as to strengthen clinicians' overall understanding of this disease and avoid missed diagnosis and misdiagnosis.

Spatiotemporal transcriptome atlas reveals the regional specification of the developing human brain.

Different functional regions of brain are fundamental for basic neurophysiological activities. However, the regional specification remains largely unexplored during human brain development. Here, by combining spatial transcriptomics (scStereo-seq) and scRNA-seq, we built a spatiotemporal developmental atlas of multiple human brain regions from 6-23 gestational weeks (GWs). We discovered that, around GW8, radial glia (RG) cells have displayed regional heterogeneity and specific spatial distribution. Interestingly, we found that the regional heterogeneity of RG subtypes contributed to the subsequent neuronal specification. Specifically, two diencephalon-specific subtypes gave rise to glutamatergic and GABAergic neurons, whereas subtypes in ventral midbrain were associated with the dopaminergic neurons. Similar GABAergic neuronal subtypes were shared between neocortex and diencephalon. Additionally, we revealed that cell-cell interactions between oligodendrocyte precursor cells and GABAergic neurons influenced and promoted neuronal development coupled with regional specification. Altogether, this study provides comprehensive insights into the regional specification in the developing human brain.

PIWI-interacting RNA expression regulates pathogenesis in a Caenorhabditis elegans model of Lewy body disease.

PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that regulate gene expression, yet their molecular functions in neurobiology are unclear. While investigating neurodegeneration mechanisms using human α-syn(A53T)Tg and AßTg;α-syn(A53T)Tg pan-neuronal overexpressing strains, we unexpectedly observed dysregulation of piRNAs. RNAi screening revealed that knock down of piRNA biogenesis genes improved thrashing behavior; further, a tofu-1 gene deletion ameliorated phenotypic deficits in α-syn(A53T)Tg and AßTg;α-syn(A53T)Tg transgenic strains. piRNA expression was extensively downregulated and H3K9me3 marks were decreased after tofu-1 deletion in α-syn(A53T)Tg and AßTg;α-syn(A53T)Tg strains. Dysregulated piRNAs targeted protein degradation genes suggesting that a decrease of piRNA expression leads to an increase of degradation ability in C. elegans. Finally, we interrogated piRNA expression in brain samples from PD patients. piRNAs were observed to be widely overexpressed at late motor stage. In this work, our results provide evidence that piRNAs are mediators in pathogenesis of Lewy body diseases and suggest a molecular mechanism for neurodegeneration in these and related disorders.

Spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium.

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.

Evolution of the Microstructure and Mechanical Performance of As-Sprayed and Annealed Silicon Coating on Melt-Infiltrated Silicon Carbide Composites.

In this study, silicon coating was deposited on melt-infiltrated SiC composites using atmospheric plasma spraying and then annealed at 1100 and 1250 °C for 1-10 h to investigate the effect of annealing on the layer. The microstructure and mechanical properties were evaluated using scanning electron microscopy, X-ray diffractometry, transmission electron microscopy, nano-indentation, and bond strength tests. A silicon layer with a homogeneous polycrystalline cubic structure was obtained without phase transition after annealing. After annealing, three features were observed at the interface, namely ß-SiC/nano-oxide film/Si, Si-rich SiC/Si, and residual Si/nano-oxide film/Si. The nano-oxide film thickness was ≤100 nm and was well combined with SiC and silicon. Additionally, a good bond was formed between the silicon-rich SiC and silicon layer, resulting in a significant bond strength improvement from 11 to >30 MPa.

Low-Grade Ductal Carcinoma in situ Within a Fibroadenoma of the Breast: A Rare Case Report and Review of the Literature.

Background: Ductal carcinoma in situ within a breast fibroadenoma is a rare malignancy with an incidence of only 0.02-0.125%. Imaging of low-grade ductal carcinoma in situ within a breast fibroadenoma shows no specific presentation. Therefore, pathology and immunohistochemistry are required for definitive diagnosis. Surgery is currently considered to be an effective treatment. There is no uniform clinical standard for postoperative adjuvant radiotherapy. Case Summary: A 60-year-old female patient underwent excisional biopsy on October 19, 2022. Pathology and immunohistochemistry confirmed the diagnosis of low-grade ductal carcinoma in situ within the fibroadenoma. Subsequently, breast-conserving surgery and sentinel lymph node biopsy were performed under general anesthesia with tracheal intubation, and no cancer metastasis was observed in the sentinel lymph nodes or incisional margins. Conclusion: Low-grade ductal carcinoma in situ within a breast fibroadenoma is an extremely rare malignancy, and clinicians should be familiar with its clinicopathological features and treatment methods. Multidisciplinary joint treatment is recommended to maximize the benefits to patients.

Multilayer brain network modeling and dynamic analysis of juvenile myoclonic epilepsy.

Objective: It is indisputable that the functional connectivity of the brain network in juvenile myoclonic epilepsy (JME) patients is abnormal. As a mathematical extension of the traditional network model, the multilayer network can fully capture the fluctuations of brain imaging data with time, and capture subtle abnormal dynamic changes. This study assumed that the dynamic structure of JME patients is abnormal and used the multilayer network framework to analyze the change brain community structure in JME patients from the perspective of dynamic analysis. Methods: First, functional magnetic resonance imaging (fMRI) data were obtained from 35 JME patients and 34 healthy control subjects. In addition, the communities of the two groups were explored with the help of a multilayer network model and a multilayer community detection algorithm. Finally, differences were described by metrics that are specific to the multilayer network. Results: Compared with healthy controls, JME patients had a significantly lower modularity degree of the brain network. Furthermore, from the level of the functional network, the integration of the default mode network (DMN) and visual network (VN) in JME patients showed a significantly higher trend, and the flexibility of the attention network (AN) also increased significantly. At the node level, the integration of seven nodes of the DMN was significantly increased, the integration of five nodes of the VN was significantly increased, and the flexibility of three nodes of the AN was significantly increased. Moreover, through division of the core-peripheral system, we found that the left insula and left cuneus were core regions specific to the JME group, while most of the peripheral systems specific to the JME group were distributed in the prefrontal cortex and hippocampus. Finally, we found that the flexibility of the opercular part of the inferior frontal gyrus was significantly correlated with the severity of JME symptoms. Conclusion: Our findings indicate that the dynamic community structure of JME patients is indeed abnormal. These results provide a new perspective for the study of dynamic changes in communities in JME patients.

Prenatal alcohol exposure enhanced alcohol preference and susceptibility to PTSD in a sex-dependent manner through the synaptic HCN1 channel.

BACKGROUND: Prenatal alcohol exposure (PAE) adversely affects the neurobiological and behavioral functions of offspring. Increasing evidence indicates that alcohol-use disorders and post-traumatic stress disorder (PTSD) commonly co-occur. Enhanced function of hyperpolarization-activated gated channel 1 (HCN1) may be involved in the pathogenesis of PTSD. This study aimed to explore the effect of PAE on fear extinction, spontaneous recovery, alcohol preference, and function of HCN1 channels in offspring of both sexes. METHODS: The PAE model was established with a 20 % (m/V) ethanol solution, and offspring were treated with 0.5, 1, and 2 µg/mL ZD7288 to block the HCN1 channel. Behavioral tests were used to detect the mental state and fear of extinction of the mice. Western blot was used to detect HCN1 expression in the synaptosomes. The BDNF/TrkB-pmTOR pathway was also examined. RESULTS: ZD7288 administration ameliorated PAE-induced impairment of fear extinction and depression-like behavior. ZD7288 administration also alleviated PAE-induced inhibition of the HCN1 channel in the prefrontal cortex (PFC) and the BDNF/TrkB-pmTOR pathway in the hippocampus of offspring. In addition, the therapeutic effect of ZD7288 in males was better than that in females. CONCLUSIONS: Overall, these results suggest that PAE enhances alcohol preference and susceptibility to PTSD through synaptic HCN1 channels in the PFC. In addition, ZD7288 may be a promising candidate for preventing alcohol-associated PTSD-like syndrome, particularly in males. LIMITATIONS: The effects of ZD7288 were only studied in PAE animals and not in healthy animals.

Angiosarcoma of the breast with hypofibrinogenemia: A rare case report and review of the literature.

Background: Breast angiosarcoma is a rare malignant tumor, accounting for approximately 0.04% of all breast malignancies. Angiosarcoma of the breast with hypofibrinogenemia is even rarer and has not been described in man. Breast angiosarcoma is associated with high metastatic potential and poor prognosis, and there is no specific manifestation in imaging. At present, surgery is considered to be the only effective treatment. There is no unified standard for postoperative adjuvant radiotherapy and chemotherapy. Case Presentation: A 30-year-old female patient underwent left breast mass resection under local anesthesia on May 22, 2014. Postoperative pathology showed a vasogenic tumor. On November 10, 2017, she visited us again due to left breast swelling and pain during lactation, and underwent breast mass puncture. She was diagnosed with breast hematoma and fibrinogen reduction. On November 14, 2017, mastectomy was performed under tracheal intubation and general anesthesia, and the fibrinogen gradually returned to normal after surgery. Pathological examination showed a hemangiosarcoma with hematoma formation in the left breast. According to the pathological findings and after comprehensive evaluation, the patient underwent modified radical mastectomy for left breast cancer and right axillary sentinel lymph node biopsy on December 5, 2017. The patient died on January 28, 2018 due to rupture and hemorrhage of liver cancer and hemorrhagic shock. Conclusion: Breast angiosarcoma with hypofibrinogenemia is a rare and highly aggressive malignancy. Clinicians should be familiar with its clinicopathological features and diagnostic criteria. Multidisciplinary approach is recommended to benefit the patients.

One-click device for rapid visualization and extraction of latent evidence through multi-moding light source integration and light-guiding technology.

Visualizing latent evidence at a crime scene has gained popularity in the field of forensic science during the past few years. Thus, this study designs and develops a one-click device for the rapid visualization and extraction of latent evidence through multimodal light source integration and light-guiding technology. Our device exhibits multispectral and angle timing functions for storing the captured evidence images. Furthermore, the geometric registration, feature extraction, feature optimization, and feature integration of the evidence images are processed by a backend system, and the images are then presented. Overall, this study enhances the standard and the technical content of evidence extraction and simplifies the evidence extraction process. In addition to the rapid handling of the scenes captured at a crime scene, the one-click device has other notable advantages, such as fast imaging, portability, being independent of the environmental conditions and the operator's technical capabilities, and zero pollution to ensure the repeatability of material evidence extraction. Compared with the original optical forensics equipment, the spectrum and angle of our system are more extensive.

SMUG1 regulates fat homeostasis leading to a fatty liver phenotype in mice.

Fatty liver diseases are a major health threat across the western world, leading to cirrhosis and premature morbidity and mortality. Recently, a correlation between the base excision repair enzyme SMUG1 and metabolic homeostasis was identified. As the molecular mechanisms remain unknown, we exploited a SMUG1-knockout mouse model to gain insights into this association by characterizing the liver phenotype in young vs old SMUG1-null mice. We observed increased weight and fat content in one-year old animals, with altered activity of enzymes important for fatty acids influx and uptake. Consistently, lipidomic profiling showed accumulation of free fatty acids and triglycerides in SMUG1-null livers. Old SMUG1-knockout mice also displayed increased hepatocyte senescence and DNA damage at telomeres. Interestingly, RNA sequencing revealed widespread changes in the expression of lipid metabolic genes already in three months old animals. In summary, SMUG1 modulates fat metabolism favouring net lipogenesis and resulting in development of a fatty liver phenotype.

Development of a novel MR-conditional microwave needle for MR-guided interventional microwave ablation at 1.5T.

PURPOSE: To develop an MR-conditional microwave needle that generates a spherical ablation zone and clear MRI visibility for MR-guided microwave ablation. METHODS: An MR-conditional microwave needle consisting of zirconia tip and TA18 titanium alloy tube was investigated. The numerical model was created to optimize the needle's geometry and analyze its performance. A geometrically optimized needle was produced using non-magnetic materials based on the electromagnetics simulation results. The needle's mechanical properties were tested per the Chinese pharmaceutical industry standard YY0899-2013. The MRI visibility performance and ablation characteristics of the needle was tested both in vitro (phantom) and in vivo (rabbit) at 1.5T. The RF-induced heating was evaluated in ex vivo porcine liver. RESULTS: The needle's mechanical properties met the specified requirements. The needle susceptibility artifact was clearly visible both in vitro and in vivo. The needle artifact diameter (A) was small in in vivo (Ashaft: 4.96 ± 0.18 mm for T1W-FLASH, 3.13 ± 0.05 mm for T2-weighted fast spin-echo (T2W-FSE); Atip: 2.31 ± 0.09 mm for T1W-FLASH, 2.29 ± 0.08 mm for T2W-FSE; tip location error [TLE]: -0.94 ± 0.07 mm for T1W-FLASH, -1.10 ± 0.09 mm for T2W-FSE). Ablation zones generated by the needle were nearly spherical with an elliptical aspect ratio ranging from 0.79 to 0.90 at 30 W, 50 W for 3, 5, 10 min duration ex vivo ablations and 0.86 at 30 W for 10 min duration in vivo ablations. CONCLUSION: The designed MR-conditional microwave needle offers excellent mechanical properties, reliable MRI visibility, insignificant RF-induced heating, and a sufficiently spherical ablation zone. Further clinical development of MR-guided microwave ablation appears warranted.

Enhanced Grain Refinement and Precipitation of the IEECAPed Mg-Sm-Zn-Zr Alloy by Nd Addition.

Achieving magnesium-rare earth alloys with excellent mechanical properties remains a challenging goal in the aerospace industry. The integrated extrusion and equal channel angular pressing were employed to refine grain and improve the mechanical properties of Mg-xNd-2.0Sm-0.4Zn-0.4Zr alloys. The effect of Nd element on microstructure and mechanical properties of the extruded and subsequently aged alloys were carried out by varying the amount of the Nd element from 0 wt.% to 2.5 wt.%. The optical microscopy results indicated that the grain size was remarkably refined by the addition of Nd element. The grain size decreased from 29.7 µm to 10.9 µm with increasing of the Nd element from 0 wt.% to 2.5 wt.%. The transmission electron microscopy results showed that the nano-scaled basal lamellar precipitates, prismatic lamellar precipitates and granular precipitates were formed in α-Mg matrix. The amount of the precipitates increased significantly by the addition of Nd. Moreover, the strength of the alloys significantly improved with Nd. Superior strength and considerable plasticity were obtained as the content of Nd element reached 2.0 wt.%, while the tensile strength of the Mg-2.0Nd-Sm-Zn-Zr alloy (315 ± 5 MPa) increased by 35.8% with respect to the Nd-free alloy (232 ± 3 MPa).

How time pressure and fingerprint complexity affect fingerprint examiner performance in an Eye Tracking Study.

We conducted two experiments to examine the effects of time pressure and task difficulty on the strategies used and task accuracy during fingerprint examination. In Experiment I, we collected behavior and eye movement data from 31 fingerprint examiners in conditions with and without time pressure. In Experiment II, we used the same procedure but added a task difficulty variable. The results showed that, in contrast to the trials without time pressure, the fingerprint examiners used an observation mode with decreased fixation time and made fewer mistakes (stronger discriminability and higher response criterion) when under time pressure (Experiment I). This pattern was only observed when the task was less difficult. When the task was more difficult (Experiment II), the examiners tended to adopt an observation mode with more fixation counts, and time pressure weakened the accuracy of their performance. In conclusion, time pressure can influence decision-making by affecting the cognitive strategies used during fingerprint examination. And task difficulty has a moderating effect on the influence of time pressure.

The downregulation of NCXs is positively correlated with the prognosis of stage II-IV colon cancer.

PURPOSE: Colon cancer (CC) is a very common gastrointestinal tumor that is prone to invasion and metastasis in the late stage. This study aims to observe the expression of Na+/Ca2+ exchangers (NCXs) and analyze the correlation between NCXs and the prognosis of CC. METHODS: Specimens of 111 stage II-IV CC patients were collected. We used western blotting, qPCR, and immunohistochemical staining to observe the distributions and expression levels of NCX isoforms (NCX1, NCX2, and NCX3) in CC and distal normal tissues. Cox proportional hazards models were used to assess prognostic factors for patients. RESULTS: The expression of NCXs in most tumor specimens was lower than that in normal tissues. The NCX expression levels in tumor tissues from the primary tumor, local lymph node metastasis sites, and distant liver metastasis sites were increasingly significantly lower than those in normal tissues. The results of the Kaplan-Meier survival curves showed that the downregulation of any NCX isoform was closely related to the worse prognosis of advanced CC. CONCLUSION: NCXs can be used as independent prognostic factors for CC. Our research results are expected to provide new targets for the treatment of CC.

Human amyloid beta and α-synuclein co-expression in neurons impair behavior and recapitulate features for Lewy body dementia in Caenorhabditis elegans.

Amyloid ß (Aß), a product of APP, and SNCA (α-synuclein (α-syn)) are two of the key proteins found in lesions associated with the age-related neurodegenerative disorders Alzheimer's disease (AD) and Parkinson's disease (PD), respectively. Previous clinical studies uncovered Aß and α-syn co-expression in the brains of patients, which lead to Lewy body dementia (LBD), a disease encompassing Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). To explore the pathogenesis and define the relationship between Aß and α-syn for LBD, we established a C. elegans model which co-expresses human Aß and α-syn with alanine 53 to threonine mutant (α-syn(A53T)) in pan-neurons. Compared to α-syn(A53T) single transgenic animals, pan-neuronal Aß and α-syn(A53T) co-expression further enhanced the thrashing, egg laying, serotonin and cholinergic signaling deficits, and dopaminergic neuron damage in C. elegans. In addition, Aß increased α-syn expression in transgenic animals. Transcriptome analysis of both Aß;α-syn(A53T) strains and DLB patients showed common downregulation in lipid metabolism and lysosome function genes, suggesting that a decrease of lysosome function may reduce the clearance ability in DLB, and this may lead to the further pathogenic protein accumulation. These findings suggest that our model can recapitulate some features in LBD and provides a mechanism by which Aß may exacerbate α-syn pathogenesis.