[Reconstruction from CT truncated data based on dual-domain transformer coupled feature learning].

OBJECTIVE: To propose a CT truncated data reconstruction model (DDTrans) based on projection and image dualdomain Transformer coupled feature learning for reducing truncation artifacts and image structure distortion caused by insufficient field of view (FOV) in CT scanning. METHODS: Transformer was adopted to build projection domain and image domain restoration models, and the long-range dependency modeling capability of the Transformer attention module was used to capture global structural features to restore the projection data information and enhance the reconstructed images. We constructed a differentiable Radon back-projection operator layer between the projection domain and image domain networks to enable end-to-end training of DDTrans. Projection consistency loss was introduced to constrain the image forwardprojection results to further improve the accuracy of image reconstruction. RESULTS: The experimental results with Mayo simulation data showed that for both partial truncation and interior scanning data, the proposed DDTrans method showed better performance than the comparison algorithms in removing truncation artifacts at the edges and restoring the external information of the FOV. CONCLUSION: The DDTrans method can effectively remove CT truncation artifacts to ensure accurate reconstruction of the data within the FOV and achieve approximate reconstruction of data outside the FOV.

[Prevalence of Echinococcus infections in small rodents in Yushu City, Qinghai Province in 2023].

OBJECTIVE: To investigate the prevalence of Echinococcus infections in small rodents around human residential areas in Yushu City, Qinghai Province in 2023, so as to provide insights into precision echinococcosis control. METHODS: One or two quadrats, each measuring 50 m × 50 m, were randomly assigned in Shanglaxiu Township and Longbao Township, Yushu City, Qinghai Province on June 2023, respectively, and 300 plate-type mouse traps, each measuring 12.0 cm × 6.5 cm, were assigned in each quadrat. Small rodents were captured during the period between 10 : 00 and 18 : 00 each day for 4 days. Then, all captured small rodents were identified and dissected, and liver specimens with suspected Echinococcus infections were subjected to pathological examinations. The Echinococcus cytochrome c oxidase 1 (cox1) gene was amplified using PCR assay, and the sequence of the amplified product was aligned to that was recorded in the GenBank to characterize the parasite species. In addition, a phylogenetic tree of Echinococcus was generated based on the cox1 gene sequence using the neighbor-joining method. RESULTS: A total of 236 small rodents were captured in Shanglaxiu and Longbao townships, Yushu City, including 65 Qinghai voles and 51 plateau pikas in Shanglaxiu Township, and 62 Qinghai voles and 58 plateau pikas in Longbao Township, and there was no significant difference in the constituent ratio of small rodents between the two townships (χ2 = 0.294, P > 0.05). Seven plateau pikas and 12 Qinghai voles were suspected to be infected with Echinococcus by dissection, and pathological examinations showed unclear structure of hepatic lobules and disordered hepatocyte arrangement in livers of small rodents suspected of Echinococcus infections. PCR assay identified E. shiquicus DNA in 7 Qinghai voles, which were all captured from Shanglaxiu Township. Phylogenetic analysis showed that the cox1 gene sequence of Echinococcus in small rodents was highly homologous to the E. shiquicus cox1 gene sequence reported previously. CONCLUSIONS: Plateau pika and Qinghai vole were predominant small rodents around human residential areas in Yushu City, Qinghai Province in 2023, and E. shiquicus infection was detected in Qinghai voles.

The gendered behaviors displayed by Disney protagonists.

Previous research suggests that the portrayal of male and female protagonists in Disney animations may be changing over time. The current study examined the portrayal of gendered behaviors displayed within some of Disney's most successful animated feature length films, including those beyond the Disney princess franchise. Extending the scope of the Disney animated films analyzed was important because both young girls and young boys report little personal interest in male characters within the Disney princess animations. This suggests that it is important to look beyond the Disney princess franchise to understand the gendered behaviors displayed by potentially influential male Disney protagonists. The current study also considered a greater number of masculine and feminine behaviors as well as some gender-neutral traits which had yet to be incorporated. A quantitative content analysis of 39 Disney protagonists from films released between 1937 and 2021 was conducted. The results revealed that male and female protagonists were statistically higher in feminine than masculine traits. Female protagonists from the earliest animations were the most feminine. However, there was no statistical difference in the gendered portrayals of females in the animations released in the 1990s and those released from 2009 to 2021 suggesting some continued stereotyping in females' profiles. Alternatively, male characters were more feminine relatively consistently across time-points. This study concludes that Disney is persistently portraying stereotyped female protagonists, and this could have implications on young females' behavioral profiles. However, the extent to which feminine traits are being celebrated when displayed by male protagonists needs to be examined, as well as the potential relationship between such messages and boys' behaviors and children's conceptualizations of gender more broadly.

[The effect of the AIM2 inflammasome in noise-induced cognitive dysfunction in rats].

Objective: To explore the effect of the absent in melanoma 2 (AIM2) -mediated neuroinflammation in noise-induced cognitive dysfunction in rats. Methods: In April 2023, sixteen male Wistar rats were randomly divided into control group and noise group, with 8 rats in each group. The rats in the noise group were placed in 50 cm×50 cm×40 cm transparent boxes and exposed to 100 dB (A) white noise with a sound pressure level of 100 dB (A) (4 h/d for 30 d) . At the same time, rats in the control group were kept in similar boxes with environmental noise less than 60 dB (A) . After 30 days of noise exposure, the Morris water maze experiment was applied to test the learning and memory abilities of the rats; the pathological morphology of hippocampal tissues was observed by Hematoxylin-Eosin (HE) staining. Western blot was used to detect the protein expression levels of AIM2, cysteinyl aspartate specific proteinase-1 (caspase-1) , apoptosis-associated speck-like protein (ASC) , interleukin-1ß (IL-1ß) , IL-18, ionic calcium-binding articulation molecule-1 (Iba-1) , and glial fibrillary acidic protein (GFAP) . The expression of both Iba-1 and GFAP in hippocampal tissue was assessed by immunohistochemical staining. The co-localization of AIM2 with Iba-1 or GFAP was determined by immunofluorescence double staining. Results: Compared with the control group, the escape latency of rats in the noise group was increased by 16.29 s, 17.71 s, and 20.26 s on days 3, 4, and 5, respectively. On day 6, the noise-exposed rats spent shorter time in the target quadrant and had fewer times in crossing the platform[ (7.25±2.27) s and (1.13±0.64) times] than the control group[ (15.64±3.99) s and (4.25±2.12) times] (P<0.05) . After noise exposure, hippocampal neurons of rats displayed marked nuclear hyperchromatic and pyknosis phenomenon. The noise-exposed rats had higher numbers of both microglia and astrocytes (27.00±2.65 and 43.33±5.51) in the DG area of the hippocampus relative to the control group (14.67±3.06 and 20.00±4.58) (P<0.05) . Moreover, the glial cells in the noise group had larger cell cytosol with more and thicker branches. The protein expression levels of inflammatory cytokines Cleaved-IL-1ß and Cleaved-IL-18 in the hippocampus of rats in the noise group (1.55±0.19 and 1.74±0.12) were significantly higher than the control group (1.00±0.11 and 1.00±0.13) (P<0.05) . After noise exposure, the protein expression levels of AIM2, Cleaved-Caspase-1 and ASC (1.19±0.09, 1.34±0.07 and 1.14±0.01) were higher than the control group (1.00±0.07, 1.00±0.14 and 1.00±0.06) and differences between the two groups were statistically significant (P<0.05) . A significant increase in the number of cells co-localizing AIM2 with Iba-1 or GFAP in the noise group (28.67±4.04 and 40.67±5.13) compared with the control group (15.67±4.04 and 17.67±3.79) , and statistically significant differences were observed between the two groups (P<0.05) . Conclusion: Noise exposure may activate the AIM2 inflammasome in hippocampal glial cells of rats, releasing excessive inflammatory cytokines and causing neuroinflammation that damages neurons.

Outcomes of posterior sheath supplementation with Vicryl mesh in TAR-a single-center study.

INTRODUCTION: In the Transversus Abdominis Release (TAR) procedure, ideally, the posterior sheath is completely reapproximated to establish an interface isolating the polypropylene mesh from visceral contents. When primary closure of the posterior sheath is unachievable, Vicryl mesh is commonly used to supplement the posterior sheath closure and an uncoated polypropylene mesh is placed superficial to the Vicryl mesh. The long-term implications of utilizing Vicryl mesh as an antiadhesive barrier are poorly understood. In this study, we aimed to assess our outcomes when utilizing Vicryl mesh to supplement the posterior sheath defects when placed underneath polypropylene mesh in patients undergoing posterior component separation. METHODS: Adult patients who underwent VHR with concurrent TAR procedure with a permanent synthetic mesh and posterior sheath supplementation with Vicryl mesh in the Cleveland Clinic Center for Abdominal Core Health between January 2014 and December 2022 were queried retrospectively from a prospectively collected database in the Abdominal Core Health Quality Collaborative. We evaluated 30-day wound morbidity, perioperative complications, long-term mesh-related complications, and pragmatic hernia recurrence. RESULTS: 53 patients who underwent TAR procedure with posterior sheath supplementation using Vicryl mesh and had a minimum 12-month follow-up were identified. Of the 53 patients, 94.3% presented with recurrent hernias, 73.6% had a midline hernia, 7.5% had a flank hernia, and 18.9% had concurrent parastomal hernia. The mean hernia width was 24.9 cm (± 8.8 cm). No Vicryl mesh-related operative complications were identified in our study, with no instances of mesh erosion, fistulas, or interventions for small bowel obstruction. Skin necrosis requiring reoperations was observed in three patients (5.7%), leading to permanent mesh excision in two cases (3.8%) without intraabdominal visceral involvement. Throughout the 12-month follow-up, 23 incidences (43.4%) of surgical site occurrences (SSOs) and surgical site occurrences requiring procedural intervention (SSOPI) were documented. CONCLUSIONS: Our findings suggest that posterior sheath supplementation with Vicryl mesh is a feasible approach to achieve posterior sheath closure in challenging abdominal wall reconstruction cases. Given the absence of notable mesh-related complications and a similar hernia recurrence rate to cases without posterior sheath supplementation, Vicryl mesh can be used to safely achieve posterior sheath closure in complex reconstructions with insufficient native tissue.

Exploring Putative Causal Associations between Diet and Periodontal Disease Susceptibility.

INTRODUCTION: Dietary factors may play an important role in periodontal health. However, current evidence from observational studies remains inconclusive. OBJECTIVE: This study aimed to investigate the causal relationships between dietary exposures and periodontal disease risks using Mendelian randomization analysis. METHODS: Large-scale genome-wide association study summary statistics for 20 dietary factors were obtained from the MRC-IEU consortium. Multivariable and univariable 2-sample Mendelian randomization analyses were performed to assess the causal effects of each dietary exposure on 6 periodontal outcomes, including gingivitis and periodontitis. RESULTS: Genetically predicted higher dried fruit intake was significantly associated with reduced risks of acute gingivitis (odds ratio [OR]: 0.02; 95% confidence interval [CI]: 0.00-0.42; P = 0.01) and bleeding gums (OR: 0.96; 95% CI: 0.93-0.99; P = 0.01). Higher fresh fruit and water intake showed protective effects against chronic gingivitis (OR: 0.18; 95% CI: 0.04-0.91; P = 0.04 and OR: 0.15; 95% CI: 0.04-0.53; P = 0.00) and bleeding gums (OR: 0.95; 95% CI: 0.92-0.981; P = 0.00 and OR: 0.98; 95% CI: 0.96-0.99; P = 0.02). Alcohol intake frequency and processed meat intake were risk factors for bleeding gums (OR: 1.01; 95% CI: 1.00-1.02; P = 0.01 and OR: 1.05; 95% CI: 1.01-1.08; P = 0.00) and painful gums (OR: 1.01; 95% CI: 1.00-1.01; P = 0.00 and OR: 1.02; 95% CI: 1.01-1.03; P = 0.00). Most of the causal relationships between genetic predisposition to the specified dietary factors and periodontal diseases remained statistically significant (P < 0.05) after adjusting for genetic risks associated with dentures, smoking, and type 2 diabetes in multivariable Mendelian randomization models. CONCLUSIONS: The findings suggest potential protective effects of higher fruit and water intake against gingivitis and other periodontal problems, while alcohol and processed meat intake may increase the risks of periodontal disease. Our study provides preliminary causal evidence on the effects of diet on periodontal health and could inform prevention strategies targeting dietary habits to improve oral health. KNOWLEDGE TRANSFER STATEMENT: This study suggests that fruit and water intake may protect against periodontal disease, while alcohol and processed meats increase risk, informing dietary guidelines to improve oral health.

Mendelian Randomization Analysis Reveals Causal Factors behind Alzheimer's Disease Risk: Evidence, Opportunities, and Challenges.

Alzheimer's disease and its comorbidities pose a heavy disease burden globally, and its treatment remains a major challenge. Identifying the protective and risk factors for Alzheimer's disease, as well as its possible underlying molecular processes, can facilitate the development of interventions that can slow its progression. Observational studies and randomized controlled trials have provided some evidence regarding potential risk factors for Alzheimer's disease; however, the results of these studies vary. Mendelian randomization is a novel epidemiological methodology primarily used to infer causal relationships between exposures and outcomes. Many Mendelian randomization studies have identified potential causal relationships between Alzheimer's disease and certain diseases, lifestyle habits, and biological exposures, thus providing valuable data for further mechanistic studies and the development and implementation of clinical prevention strategies. However, the results and data from Mendelian randomization studies must be interpreted based on comprehensive evidence. Moreover, the existing Mendelian randomization studies on the epidemiology of Alzheimer's disease have some limitations that are worth exploring. Therefore, the aim of this review was to summarize the available evidence on the potential protective and risk factors for Alzheimer's disease by assessing published Mendelian randomization studies on Alzheimer's disease, and to provide new perspectives on the etiology of Alzheimer's disease.

Hepatotoxicity of Antibiotics and Antifungals and Their Safe Use in Hepatic Impairment.

Idiosyncratic drug-induced liver injury (DILI) is a rare and unpredictable form of hepatotoxicity. While its clinical course is usually benign, cases leading to liver transplantation or death can occur. Based on modern prospective registries, antimicrobials including antibiotics and antifungals are frequently implicated as common causes. Amoxicillin-clavulanate ranks as the most common cause for DILI in the Western World. Although the absolute risk of hepatotoxicity of these agents is low, as their usage is quite high, it is not uncommon for practitioners to encounter liver injury following the initiation of antibiotic or antifungal therapy. In this review article, mechanisms of hepatoxicity are presented. The adverse hepatic effects of well-established antibiotic and antifungal agents are described, including their frequency, severity, and pattern of injury and their HLA risks. We also review the drug labeling and prescription guidance from regulatory bodies, with a focus on individuals with hepatic impairment.

Brassica napus BnaA09.MYB52 enhances seed coat mucilage accumulation and tolerance to osmotic stress during seed germination in Arabidopsis thaliana.

Seed coat mucilage plays an important role in promoting seed germination under adversity. Previous studies have shown that Arabidopsis thaliana MYB52 (AtMYB52) can positively regulate seed coat mucilage accumulation. However, the role of Brassica napus MYB52 (BnaMYB52) in accumulation of seed coat mucilage and tolerance to osmotic stress during seed germination remains largely unknown. We cloned the BnaA09.MYB52 coding domain sequence from B. napus cv ZS11, identified its conserved protein domains and elucidated its relationship with homologues from a range of plant species. Transgenic plants overexpressing BnaA09.MYB52 in the A. thaliana myb52-1 mutant were generated through Agrobacterium-mediated transformation and used to assess the possible roles of BnaA09.MYB52 in accumulation of seed coat mucilage and tolerance to osmotic stress during seed germination. Subcellular localization and transcriptional activity assays demonstrated that BnaA09.MYB52 functions as a transcription factor. RT-qPCR results indicate that BnaA09.MYB52 is predominantly expressed in roots and developing seeds of B. napus cv ZS11. Introduction of BnaA09.MYB52 into myb52-1 restored thinner seed coat mucilage in this mutant to levels in the wild type. Consistently, expression levels of three key genes participating in mucilage formation in developing seeds of myb52-1 were also restored to wild type levels by overexpressing BnaA09.MYB52. Furthermore, BnaA09.MYB52 was induced by osmotic stress during seed germination in B. napus, and ectopic expression of BnaA09.MYB52 successfully corrected sensitivity of the myb52-1 mutant to osmotic stress during seed germination. These findings enhance our understanding of the functions of BnaA09.MYB52 and provide a novel strategy for future B. napus breeding.

Risk factor analysis and nomogram construction in patients with distant metastatic prostate cancer at different PSA levels: a study based on the SEER database.

OBJECTIVE: Prostate cancer (PCa) is the most common malignant tumor in the male genitourinary system. Once PCa has metastasized, it is very difficult to cure. The purpose of this study was to investigate the prognostic risk factor analysis of patients with different prostate-specific antigen (PSA) levels in distant metastatic PCa. At the same time, we construct effective models for predicting the survival rate of prostate cancer patients. PATIENTS AND METHODS: Data on prostate cancer patients with the presence of distant metastases were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. PCa patients with distant metastases were categorized into two groups based on PSA levels, one with PSA <20 ng/mL and the other with PSA ≥20 ng/mL. Univariate and multivariate COX regression analyses were used to identify independent factors affecting the prognosis of the patients. A nomogram was constructed using the independent prognostic factors, and the results were evaluated using calibration curves, timeROC curves, and Kaplan-Meier curves. RESULTS: In the PSA <20 ng/mL group, there were a total of 1,832 patients. COX regression analysis showed that age, marital status, N stage, grade, Gleason score, and medical household income inflation were independent prognostic factors for overall survival (OS) in patients. In addition, we found that age, marital status, N stage, bone metastasis, grade, and Gleason score were independent prognostic factors for cancer-specific survival (CSS) in patients. In the PSA ≥20 ng/mL group, there were a total of 5,314 patients. It was found that age, ethnicity, marital status, bone metastasis, first malignant primary indicator, grade, Gleason score, and medical household income inflation were patients' independent prognostic factors for OS. For CSS, we found that age, ethnicity, marital status, T stage, radiotherapy, bone metastasis, Gleason score, and Median household income inflation were independent prognostic factors. Constructing a nomogram can accurately predict the prognosis of this group of patients. CONCLUSIONS: We found different independent prognostic factors for different PSA levels in patients with distant metastatic PCa. A new nomogram was constructed to predict OS and CSS in patients, which helps in clinical-assisted decision-making.

[Use of the ETV6/RUNX1 probe to verify the performance of the fluorescence in situ hybridization probe before clinical detection].

Objective: To explore the standardized performance of a FISH probe before clinical detection. Methods: The probe sensitivity and specificity of ETV6/RUNX1 were analyzed via interphase and metaphase FISH in 20 discarded healthy bone marrow samples. The threshold system of the probe was established using an inverse beta distribution, and an interpretation standard was established. Finally, a parallel-controlled polymerase chain reaction detection study was conducted on 286 bone marrow samples from patients at our hospital. The clinical sensitivity, specificity, and diagnostic coincidence rate of ETV6/RUNX1 FISH detection were analyzed, and the diagnostic consistency of the two methods was analyzed by the kappa test. Results: The probe sensitivity and specificity of the ETV6/RUNX1 probe were 98.47% and 100%, respectively. When 50, 100, and 200 cells were counted, the typical positive signal pattern cutoffs were 5.81%, 2.95%, and 1.49%, respectively, and the atypical positive signal pattern cutoffs were 13.98%, 9.75%, and 6.26%, respectively. The clinical sensitivity of FISH was 96.1%, clinical specificity was 99.6%, diagnostic coincidence rate was 99.00%, diagnostic consistency test kappa value was 0.964, and P value was <0.001. Conclusion: For FISH probes without a national medical device registration certificate, standardized performance verification and methodology performance verification can be performed using laboratory developed test verification standards to ensure a reliable and accurate reference basis for clinical diagnosis and treatment.

[A low- dose CT reconstruction algorithm across different scanners based on federated feature learning].

OBJECTIVE: To propose a low-dose CT reconstruction algorithm across different scanners based on federated feature learning (FedCT) to improve the generalization of deep learning models for multiple CT scanners and protect data privacy. METHODS: In the proposed FedCT framework, each client is assigned an inverse Radon transform-based reconstruction model to serve as a local network model that participates in federated learning. A projection- domain specific learning strategy is adopted to preserve the geometry specificity in the local projection domain. Federated feature learning is introduced in the model, which utilizes conditional parameters to mark the local data and feed the conditional parameters into the network for encoding to enhance the generalization of the model in the image domain. RESULTS: In the cross-client, multi-scanner, and multi-protocol low-dose CT reconstruction experiments, FedCT achieved the highest PSNR (+2.8048, +2.7301, and +2.7263 compared to the second best federated learning method), the highest SSIM (+0.0009, +0.0165, and +0.0131 in the same comparison), and the lowest RMSE (- 0.6687, - 1.5956, and - 0.9962). In the ablation experiment, compared with the general federated learning strategy, the model with projection-specific learning strategy showed an average improvement by 1.18 on Q1 of the PSNR and an average decrease by 1.36 on Q3 of the RMSE on the test set. The introduction of federated feature learning in FedCT further improved the Q1 of the PSNR on the test set by 3.56 and reduced the Q3 of the RMSE by 1.80. CONCLUSION: FedCT provides an effective solution for collaborative construction of CT reconstruction models, which can enhance model generalization and further improve the reconstruction performance on global data while protecting data privacy.

Enhancing gestational diabetes mellitus risk assessment and treatment through GDMPredictor: a machine learning approach.

BACKGROUND: Gestational diabetes mellitus (GDM) is a serious health concern that affects pregnant women worldwide and can lead to adverse pregnancy outcomes. Early detection of high-risk individuals and the implementation of appropriate treatment can enhance these outcomes. METHODS: We conducted a study on a cohort of 3467 pregnant women during their pregnancy, with a total of 5649 clinical and biochemical records collected. We utilized this dataset as our training dataset to develop a web server called GDMPredictor. The GDMPredictor utilizes advanced machine learning techniques to predict the risk of GDM in pregnant women. We also personalize treatment recommendations based on essential biochemical indicators, such as A1MG, BMG, CysC, CO2, TBA, FPG, and CREA. Our assessment of GDMPredictor's effectiveness involved training it on the dataset of 3467 pregnant women and measuring its ability to predict GDM risk using an AUC and auPRC. RESULTS: GDMPredictor demonstrated an impressive level of precision by achieving an AUC score of 0.967. To tailor our treatment recommendations, we use the GDM risk level to identify higher risk candidates who require more intensive care. The GDMPredictor can accept biochemical indicators for predicting the risk of GDM at any period from 1 to 24 weeks, providing healthcare professionals with an intuitive interface to identify high-risk patients and give optimal treatment recommendations. CONCLUSIONS: The GDMPredictor presents a valuable asset for clinical practice, with the potential to change the management of GDM in pregnant women. Its high accuracy and efficiency make it a reliable tool for doctors to improve patient outcomes. Early identification of high-risk individuals and tailored treatment can improve maternal and fetal health outcomes http://www.bioinfogenetics.info/GDM/ .

A Cholecystokinin Analogue Ameliorates Cognitive Deficits and Regulates Mitochondrial Dynamics via the AMPK/Drp1 Pathway in APP/PS1 Mice.

BACKGROUND: There are no drugs on the market that can reverse or slow Alzheimer's disease (AD) progression. A protease-resistant Cholecystokinin (CCK) analogue used in this study is based on the basic structure of CCK, which further increases the stability of the peptide fragment and prolongs its half-life in vivo. We observed a neuroprotective effect of CCK-8L in APPswe/PS1dE9 (APP/PS1) AD mice. However, its corresponding mechanisms still need to be elucidated. OBJECTIVE: This study examined CCK-8L's neuroprotective effects in enhancing cognitive impairment by regulating mitochondrial dynamics through AMPK/Drp1 pathway in the APP/PS1 AD mice. METHODS: Behavioural tests are applied to assess competence in cognitive functions. Transmission electron microscopy (TEM) was performed to observe the ultrastructure of mitochondria of hippocampal neurons, Immunofluorescent staining was employed to assay for Aß1-42, APP, Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and dynamin-related protein1 (Drp1). CRISPR/Cas9 was utilized for targeted knockout of the CCKB receptor (CCKBR) in the mouse APP/PS1 hippocampal CA1 region. A model of lentiviral vector-mediated overexpression of APP in N2a cells was constructed. RESULTS: In vivo, experiments revealed that CCK analogue and liraglutide significantly alleviated cognitive deficits in APP/PS1 mice, reduced Aß1-42 expression, and ameliorated l damage, which is associated with CCKBR activation in the hippocampal CA1 region of mice. In vitro tests showed that CCK inhibited mitochondrial fission and promoted fusion through AMPK/Drp1 pathway. CONCLUSIONS: CCK analogue ameliorates cognitive deficits and regulates mitochondrial dynamics by activating the CCKB receptor and the AMPK/Drp1 pathway in AD mice.

A comprehensive analysis of essential meiotic endonuclease 1 to prognosis and immune infiltration in kidney renal clear cell carcinoma.

OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is the most common type of cancer, and its molecular pathogenesis is unclear. In this study, we investigated the prognostic value of essential meiotic endonuclease 1 (EME1) in kidney renal clear cell carcinoma (KIRC). MATERIALS AND METHODS: We downloaded the RNA-Seq expression of 526 KIRC tissues and 72 normal tissues from the TCGA database and the corresponding clinical data. The gene expression profiles associated with four clear cell renal cell carcinomas were downloaded from the GEO database for analysis. The expression of EME1 in clear renal cell carcinoma and its correlation with the clinical baseline data were analyzed. Kaplan-Meier survival curve analysis was performed to assess the relationship between EME1 and patient survival. Enrichment analysis was performed to elucidate the possible functions of EME1. We also analyzed the relationship between the EME1 expression and immune infiltration through TIMER2.0 and TISIDB online databases as well as the relationship between EME1 and common immune checkpoints. RESULTS: EME1 was identified as a risk factor for overall survival in clear cell renal cell carcinoma with a hazard ratio of 3.201 (95% confidence interval: 2.430-4.215; p < 0.001). EME1 was highly expressed in KIRC compared to that in normal tissues (p < 0.001) and in the worse TNM stages and late stages (stage 3/4) (p < 0.001). High EME1 expression was strongly associated with the advanced T stage (p = 0.003), advanced N stage (p = 0.002), and advanced M stage (p = 0.006). Research data on KIRC were simultaneously collected and analyzed from the GEO database, including GSE40435, GSE53000, GSE68417, and GSE53757. EME1 predicted the survival status in KIRC patients (AUC = 0.62). We further established a nomogram including the correlation between the high and low EME1 expression, and EME1 was found to contribute to the prediction of the probability of patient survival with a c-index = 0.796. Kaplan-Meier analysis revealed a lower likelihood of survival with a high EME1 expression (p < 0.001). In addition, further bioinformatics analysis suggested that EME1 may be associated with the extent of immune infiltration in KIRC. CONCLUSIONS: An increased expression of EME1 in KIRC is thus associated with advanced clinicopathological features, possibly acting as a potential biomarker of poor prognosis in KIRC.

In ovo injection of AZD6244 suppresses feather follicle development by the inhibition of ERK and Wnt/ß-catenin pathways in goose embryos (Anser cygnoides).

1. Feathers are an important product from poultry, and the state of feather growth and development plays an important role in their economic value.2. In total, 120 eggs were selected for immunoblotting and immunolocalisation experiments of ERK and ß-catenin proteins in different developmental stages of goose embryos. The ERK protein was highly expressed in the early stage of goose embryo development, while ß-catenin protein was highly expressed in the middle stage of embryo development.3. The 120 eggs were divided into four treatment groups, including an uninjected group (BLANK), a group injected with 100 µl of cosolvent (CK), a group injected with 100 µl of AZD6244 containing cosolvent in a dose of 5 mg/kg AZD6244 containing cosolvent (AZD5) and a group injected with 100 µl of AZD6244 containing cosolvent in a dose of 15 mg/kg AZD6244 containing cosolvent (AZD15). The eggs were injected on the ninth day of embryonic development (E9). Samples were collected at E21.5 to observe feather width, feather follicle diameter, ERK and Wnt/ß-catenin pathway protein expression.4. The AZD5 and AZD15 doses were within the embryonic safety range compared to the BLANK and CK groups and had no significant effect on the survival rate and weight at the inflection point, but significantly reduced the feather width and feather follicle diameter (p < 0.05). The AZD6244 treatment inhibited ERK protein phosphorylation levels and blocked the Wnt/ß-catenin pathway, which in turn significantly down-regulated the expression levels of FZD4, ß-catenin, TCF4 and LEF1 (p < 0.05), with an inhibitory effect in the AZD15 group being more significant. The immunohistochemical results of ß-catenin and p-ERK were consistent with Western blot results.5. The small molecule inhibitor AZD6244 regulated the growth and development of feather follicles in goose embryos by the ERK and Wnt/ß-catenin pathways.

The Impact of Testosterone on Alzheimer's Disease Are Mediated by Lipid Metabolism and Obesity: A Mendelian Randomization Study.

BACKGROUND: To investigate the causal relationship between testosterone (BT) levels and Alzheimer's disease (AD) risk and to quantify the role of obesity and lipid metabolism as potential mediators. METHODS: We used a two-sample, two-step MR to determine:1) the causal effect of BT levels on AD; 2) the causal effect of two lipid metabolites, obesity and LDLc on AD; and 3) the mediating effects of these metabolites. Pooled data for BT levels and lipid metabolism were obtained from the UK Biobank. AD data were obtained from the Alzheimer's Disease Project International Genomics Consortium, FinnGen Consortium, and UK Biobank study. Effect estimates from external genome-wide association study (GWAS) pooled statistics were obtained using inverse variance-weighted (IVW) MR analysis. RESULTS: Higher levels of BT were associated with a reduced risk of AD (odds ratio [OR] 0.9992, 95% CI 0.9985-0.9998, P = 0.019), and there was a negative correlation with LDLc (OR 0.9208, 95% CI 0.8569-0.9895, P = 0.024) and obesity class 2 (OC2) (OR 0.7445, 95% CI 0.5873-0.9437, P = 0.014). Conversely, there was a positive correlation between LDLc (OR 1.0014, 95% CI 1.0000-1.0029, P = 0.043) and OC2 (OR 1.0005, 95% CI 1.0001-1.0009, P = 0.003) and AD. Mediation analysis showed that the indirect effect of BT levels on AD was achieved through LDLc and OC2, which accounted for 17% and 17% of the total effect, respectively. CONCLUSION: Our study identified a causal role of BT levels in LDLc and OC2. BT levels may affect AD through LDLc and OC2 metabolic processes.