The effect of simulation of sectional human anatomy using ultrasound on students' learning outcomes and satisfaction in echocardiography education: a pilot randomized controlled trial.

BACKGROUND: Effective teaching methods are needed to improve students' abilities in hand-eye coordination and understanding of cardiac anatomy in echocardiography education. Simulation devices have emerged as innovative teaching tools and exhibited distinctive advantages due to their ability to provide vivid and visual learning experiences. This study aimed to investigate the effect of simulation of sectional human anatomy using ultrasound on students' learning outcomes and satisfaction in echocardiography education. METHODS: The study included 18 first-year clinical medical students with no prior echocardiography training. After randomization, they underwent a pre-test to assess basic knowledge. Following this, the students were divided into two groups: traditional teaching (traditional group) and simulation of sectional human anatomy using ultrasound (digital group). Each group received 60 min of instruction. Post-tests were assigned to students at two different time points: immediately after the lecture, and one week later (referred to as post-tests 1, and 2). In addition, anonymous questionnaires were distributed to students after class to investigate their satisfaction with teaching. RESULTS: Both groups showed significant improvement in their scores on post-test 1 compared to pre-test (traditional group: from 33.1 ± 8.8 to 48.1 ± 13.1, P = 0.034 vs. digital group: from 35.0 ± 6.7 to 58.0 ± 13.2, P = 0.008). However, there were no significant differences between the two groups in several post-test comparisons. Student satisfaction ratings revealed that the digital group experienced significantly greater satisfaction in areas such as subject interest, teaching style, course alignment, and interaction compared to the traditional group. Additionally, 80% of the digital group strongly endorsed the use of simulation of sectional human anatomy using ultrasound for echocardiography teaching, highlighting its effectiveness. CONCLUSIONS: Simulation of sectional human anatomy using ultrasound may improve students' understanding of echocardiography and satisfaction with the course. Our study provides evidence supporting the use of simulation teaching devices in medical education. Further research is needed to explore the long-term impact of this teaching method on students' learning outcomes and its integration into the medical curriculum. TRIAL REGISTRATION: http://www.chictr.org.cn (registration number: ChiCTR2300074015, 27/07/2023).

Small extracellular vesicles of organoid-derived human retinal stem cells remodel Müller cell fate via miRNA: A novel remedy for retinal degeneration.

Remodeling retinal Müller glial fate, including gliosis inhibition and pro-reprogramming, represents a crucial avenue for treating degenerative retinal diseases. Stem cell transplantation exerts effects on modulating retinal Müller glial fate. However, the optimized stem cell products and the underlying therapeutic mechanisms need to be investigated. In the present study, we found that retinal progenitor cells from human embryonic stem cell-derived retinal organoids (hERO-RPCs) transferred extracellular vesicles (EVs) into Müller cells following subretinal transplantation into RCS rats. Small EVs from hERO-RPCs (hERO-RPC-sEVs) were collected and were found to delay photoreceptor degeneration and protect retinal function in RCS rats. hERO-RPC-sEVs were taken up by Müller cells both in vivo and in vitro, and inhibited gliosis while promoting early dedifferentiation of Müller cells. We further explored the miRNA profiles of hERO-RPC-sEVs, which suggested a functional signature associated with neuroprotection and development, as well as the regulation of stem cell and glial fate. Mechanistically, hERO-RPC-sEVs might regulate the fate of Müller cells by miRNA-mediated nuclear factor I transcription factors B (NFIB) downregulation. Collectively, our findings offer novel mechanistic insights into stem cell therapy and promote the development of EV-centered therapeutic strategies.

Correlation of preoperative frailty with postoperative delirium and one-year mortality in Chinese geriatric patients undergoing noncardiac surgery: Study protocol for a prospective observational cohort study.

BACKGROUND: To Frailty is associated with postoperative delirium (POD) but is rarely assessed in patients undergoing noncardiac surgery. In this study, the correlation between preoperative frailty and POD, one-year mortality will be investigated in noncardiac Chinese geriatric surgery patients. METHODS: This study is a prospective, observational, cohort study conducted at a single center with Chinese geriatric patients. Patients who undergo noncardiac surgery and are older than 70 years will be included. A total of 536 noncardiac surgery patients will be recruited from the First Affiliated Hospital of Shandong First Medical University for this study. The Barthel Index (BI) rating will be used to assess the patient's ability to carry out everyday activities on the 1st preoperative day. The modified frailty index (mFI) will be used to assess frailty. Patients in the nonfrailty group will have an mFI < 0.21, and patients in the frailty group will have an mFI ≥ 0.21. The primary outcome is the incidence of POD. Three-Minute Diagnostic Interview for CAM-defined Delirium (3D-CAM) will be conducted twice daily during the 1st-7th postoperative days, or just before discharge. The secondary outcomes will include one-year mortality, in-hospital cardiopulmonary events, infections, acute renal injury, and cerebrovascular events. DISCUSSION: This study will clarify the correlation of preoperative frailty with POD and one-year all-cause mortality in Chinese geriatric patients undergoing noncardiac surgery. Can preoperative frailty predict POD or one-year mortality? In the face of China's serious aging social problems, this result may have important clinical value for the surgical treatment of geriatric patients. TRIAL REGISTRATION: This protocol has been registered with ClinicalTrials. Gov on 12 January 2022 (https://clinicaltrials.gov/ct2/show/NCT05189678).

Promotive actions of lncRNA EBLN3P involved in cervical cancer progression via interacting with miR-29c-3p and TAF15 to modify RCC2.

BACKGROUND: Cervical cancer is a common cancer that seriously affects women's health globally. The key roles of long non-coding RNAs (lncRNAs) in the onset and development of cervical cancer have attracted much attention. Our study aims to uncover the roles of lncRNA EBLN3P and miR-29c-3p and the mechanisms by which EBLN3P and miR-29c-3p regulate malignancy in cervical cancer. METHODS: Tumor and adjacent normal tissues were collected from cervical cancer patients, and the expression of EBLN3P and miR-29c-3p were analyzed via RT-qPCR. The capacities of proliferation, migration, and invasion were assessed using CCK-8, wound healing and transwell assays. The interaction among EBLN3P, miR-29c-3p and TAF15 was determined by luciferase, RNA immunoprecipitation and RNA pull-down assays, respectively. A subcutaneous tumor xenograft mouse model was established to evaluate the functional role of EBLN3P in vivo. RESULTS: The interaction and reciprocal negative regulation between EBLN3P and miR-29c-3p were uncovered in cervical cancer cells. Likewise, EBLN3P and miR-29c-3p expression patterns in tumor tissues presented a negative association. EBLN3P knockdown weakened cell proliferation, migration and invasion, but these effects were abrogated by miR-29c-3p depletion. Mechanistically, ALKBH5 might impaired EBLN3P stability to reduce its expression. EBLN3P functioned as a competing endogenous RNA (ceRNA) for miR-29c-3p to relieve its suppression of RCC2. Besides, EBLN3P enhanced RCC2 mRNA stability via interacting with TAF15. Furthermore, silencing of EBLN3P repressed the tumor growth in mice. CONCLUSION: Altogether, lncRNA EBLN3P positively regulates RCC2 expression via competitively binding to miR-29c-3p and interacting with TAF15, thereby boosting proliferation, migration, and invasion of cervical cancer cells.

Oxygen enrichment mediated by calcium peroxide loaded gelatin methacrylate hydrogel eradicates periodontal biofilms.

The low oxygen environment of the periodontal pocket favors pathogenic anaerobes' growth, biofilm formation, and quick recurrence after periodontal treatment. In contrast, oxygen is detrimental to anaerobes, such as Porphyromonas gingivalis (P. gingivalis), since they lack a complete anti-oxidation mechanism to detoxify the oxygen challenge. Therefore, consistently feeding pathogenic anaerobes with abundant oxygen would be an effective strategy to combat them. Here, we reported injectable oxygen-generating hydrogels as oxygen mediators to alleviate the local anaerobic environment and eliminate periodontal pathogens. Gelatin methacrylate (GelMA) hydrogels loaded with calcium peroxide (CPO) possessed excellent injectability and exhibited burst releases of oxygen within 24 h with a 40 % oxygen tension peak. CPO-GelMA hydrogels with CPO concentrations of 5, 10, and 15 % reduced 60, 99, and 89.9 % viable P. gingivalis, respectively. Five percentage CPO-GelMA hydrogel downregulated gingipain and fimA gene expression in P. gingivalis without resistance development. Moreover, the CPO-GelMA hydrogels remarkably prevented biofilm formation and eradicated both monospecies and multispecies bacterial biofilms. In conclusion, CPO-GelMA hydrogels exert remarkable antimicrobial and antibiofilm effects on subgingival biofilms, providing a promising strategy for periodontal treatment.

Potential role of modulating autophagy levels in sensorineural hearing loss.

In recent years, extensive research has been conducted on the pathogenesis of sensorineural hearing loss (SNHL). Apoptosis and necrosis have been identified to play important roles in hearing loss, but they cannot account for all hearing loss. Autophagy, a cellular process responsible for cell self-degradation and reutilization, has emerged as a significant factor contributing to hearing loss, particularly in cases of autophagy deficiency. Autophagy plays a crucial role in maintaining cell health by exerting cytoprotective and metabolically homeostatic effects in organisms. Consequently, modulating autophagy levels can profoundly impact the survival, death, and regeneration of cells in the inner ear, including hair cells (HCs) and spiral ganglion neurons (SGNs). Abnormal mitochondrial autophagy has been demonstrated in animal models of SNHL. These findings indicate the profound significance of comprehending autophagy while suggesting that our perspective on this cellular process holds promise for advancing the treatment of SNHL. Thus, this review aims to clarify the pathogenic mechanisms of SNHL and the role of autophagy in the developmental processes of various cochlear structures, including the greater epithelial ridge (GER), SGNs, and the ribbon synapse. The pathogenic mechanisms of age-related hearing loss (ARHL), also known as presbycusis, and the latest research on autophagy are also discussed. Furthermore, we underscore recent findings on the modulation of autophagy in SNHL induced by ototoxic drugs. Additionally, we suggest further research that might illuminate the complete potential of autophagy in addressing SNHL, ultimately leading to the formulation of pioneering therapeutic strategies and approaches for the treatment of deafness.

Multi-Semantic Decoding of Visual Perception with Graph Neural Networks.

Constructing computational decoding models to account for the cortical representation of semantic information plays a crucial role in understanding visual perception. The human visual system processes interactive relationships among different objects when perceiving the semantic contents of natural visions. However, the existing semantic decoding models commonly regard categories as completely separate and independent visually and semantically and rarely consider the relationships from prior information. In this work, a novel semantic graph learning model was proposed to decode multiple semantic categories of perceived natural images from brain activity. The proposed model was validated on the functional magnetic resonance imaging data collected from five normal subjects while viewing 2750 natural images comprising 52 semantic categories. The results showed that the Graph Neural Network-based decoding model achieved higher accuracies than other deep neural network models. Moreover, the co-occurrence probability among semantic categories showed a significant correlation with the decoding accuracy. Additionally, the results suggested that semantic content organized in a hierarchical way with higher visual areas was more closely related to the internal visual experience. Together, this study provides a superior computational framework for multi-semantic decoding that supports the visual integration mechanism of semantic processing.

Effect of the new video laryngeal mask airway SaCoVLM on airway management in lateral laparoscopic urological surgery: A single center randomized controlled trial.

There are few pertinent studies about the application of laryngeal mask airways (LMAs) in lateral decubitus surgery. Therefore, the aim of our study was to evaluate the effects of lateral position and pneumoperitoneum on oropharyngeal leak pressure (OLP) and ventilation efficiency for the LMA SaCoVLM. Patients undergoing elective retroperitoneal laparoscopic urological surgery were randomized 1:1 to the Supreme group or SaCoVLM group. The primary outcome was the OLP with LMA insertion. The secondary outcomes were the first-attempt success rate, insertion time, adjustment times, gastric tube success rate, LMA alignment accuracy, LMA removal time, regurgitation or aspiration, LMA blood staining, and incidence of adverse events 24 h after surgery. We recruited 70 patients to complete the study. Regardless of lateral position and pneumoperitoneum, the OLP was greater in the SaCoVLM group (n = 35) than in the Supreme group (n = 35), with a median difference of 4-7 cmH2O. The first-attempt success rate of the SaCoVLM group was higher than that of the Supreme group (91.4% vs. 77.1%, risk ratio (RR): 1.19; 95% CI 0.96 to 1.46, P = 0.188). Thus, in the lateral position with pneumoperitoneum, although the new video LMA SaCoVLM has a higher OLP than the LMA Supreme, both devices provide sufficient ventilation efficiency.

Machine Learning for Early Prediction of Major Adverse Cardiovascular Events After First Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction: Retrospective Cohort Study.

BACKGROUND: The incidence of major adverse cardiovascular events (MACEs) remains high in patients with acute myocardial infarction (AMI) who undergo percutaneous coronary intervention (PCI), and early prediction models to guide their clinical management are lacking. OBJECTIVE: This study aimed to develop machine learning-based early prediction models for MACEs in patients with newly diagnosed AMI who underwent PCI. METHODS: A total of 1531 patients with AMI who underwent PCI from January 2018 to December 2019 were enrolled in this consecutive cohort. The data comprised demographic characteristics, clinical investigations, laboratory tests, and disease-related events. Four machine learning models-artificial neural network (ANN), k-nearest neighbors, support vector machine, and random forest-were developed and compared with the logistic regression model. Our primary outcome was the model performance that predicted the MACEs, which was determined by accuracy, area under the receiver operating characteristic curve, and F1-score. RESULTS: In total, 1362 patients were successfully followed up. With a median follow-up of 25.9 months, the incidence of MACEs was 18.5% (252/1362). The area under the receiver operating characteristic curve of the ANN, random forest, k-nearest neighbors, support vector machine, and logistic regression models were 80.49%, 72.67%, 79.80%, 77.20%, and 71.77%, respectively. The top 5 predictors in the ANN model were left ventricular ejection fraction, the number of implanted stents, age, diabetes, and the number of vessels with coronary artery disease. CONCLUSIONS: The ANN model showed good MACE prediction after PCI for patients with AMI. The use of machine learning-based prediction models may improve patient management and outcomes in clinical practice.

A copula-based method of risk prediction for autonomous underwater gliders in dynamic environments.

Autonomous underwater gliders (AUGs) are effective platforms for oceanic research and environmental monitoring. However, complex underwater environments with uncertainties could pose the risk of vehicle loss during their missions. It is therefore essential to conduct risk prediction to assist decision making for safer operations. The main limitation of current studies for AUGs is the lack of a tailored method for risk analysis considering both dynamic environments and potential functional failures of the vehicle. Hence, this study proposed a copula-based approach for evaluating the risk of AUG loss in dynamic underwater environments. The developed copula Bayesian network (CBN) integrated copula functions into a traditional Bayesian belief network (BBN), aiming to handle nonlinear dependencies among environmental variables and inherent technical failures. Specifically, potential risk factors with causal effects were captured using the BBN. A Gaussian copula was then employed to measure correlated dependencies among identified risk factors. Furthermore, the dependence analysis and CBN inference were performed to assess the risk level of vehicle loss given various environmental observations. The effectiveness of the proposed method was demonstrated in a case study, which considered deploying a Slocum G1 Glider in a real water region. Risk mitigation measures were provided based on key findings. This study potentially contributes a tailored tool of risk prediction for AUGs in dynamic environments, which can enhance the safety performance of AUGs and assist in risk mitigation for decision makers.

Transcriptional patterns of the cortical Morphometric Inverse Divergence in first-episode, treatment-naïve early-onset schizophrenia.

Early-onset Schizophrenia (EOS) is a profoundly progressive psychiatric disorder characterized by both positive and negative symptoms, whose pathogenesis is influenced by genes, environment and brain structure development. In this study, the MIND (Morphometric Inverse Divergence) network was employed to explore the relationship between morphological similarity and specific transcriptional expression patterns in EOS patients. This study involved a cohort of 187 participants aged between 7 and 17 years, consisting of 97 EOS patients and 90 healthy controls (HC). Multiple morphological features were used to construct the MIND network for all participants. Furthermore, we explored the associations between MIND network and brain-wide gene expression in EOS patients through partial least squares (PLS) regression, shared genetic predispositions with other psychiatric disorders, functional enrichment of PLS weighted genes, as well as transcriptional signature assessment of cell types, cortical layers, and developmental stages. The MIND showed similarity differences in the orbitofrontal cortex, pericalcarine cortex, lingual gyrus, and multiple networks in EOS patients compared to HC. Moreover, our exploration revealed a significant overlap of PLS2 weighted genes linking to EOS-related MIND differences and the dysregulated genes reported in other psychiatric diseases. Interestingly, genes correlated with MIND changes (PLS2-) exhibited a significant enrichment not only in metabolism-related pathways, but also in specific astrocytes, cortical layers (specifically layer I and III), and posterior developmental stages (late infancy to young adulthood stages). However, PLS2+ genes were primarily enriched in synapses signaling-related pathways and early developmental stages (from early-mid fetal to neonatal early infancy) but not in special cell types or layers. These findings provide a novel perspective on the intricate relationship between macroscopic morphometric structural abnormalities and microscopic transcriptional patterns during the onset and progression of EOS.

DGW1, encoding an hnRNP-like RNA binding protein, positively regulates grain size and weight by interacting with GW6 mRNA.

Grain size and weight determine rice yield. Although numerous genes and pathways involved in regulating grain size have been identified, our knowledge of post-transcriptional control of grain size remains elusive. In this study, we characterize a rice mutant, decreased grain width and weight 1 (dgw1), which produces small grains. We show that DGW1 encodes a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family protein and preferentially expresses in developing panicles, positively regulating grain size by promoting cell expansion in spikelet hulls. Overexpression of DGW1 increases grain weight and grain numbers, leading to a significant rise in rice grain yield. We further demonstrate that DGW1 functions in grain size regulation by directly binding to the mRNA of Grain Width 6 (GW6), a critical grain size regulator in rice. Overexpression of GW6 restored the grain size phenotype of DGW1-knockout plants. DGW1 interacts with two oligouridylate binding proteins (OsUBP1a and OsUBP1b), which also bind the GW6 mRNA. In addition, the second RRM domain of DGW1 is indispensable for its mediated protein-RNA and protein-protein interactions. In summary, our findings identify a new regulatory module of DGW1-GW6 that regulates rice grain size and weight, providing important insights into the function of hnRNP-like proteins in the regulation of grain size.

Sstr2 Defines the Cone Differentiation-Competent Late-Stage Retinal Progenitor Cells in the Developing Mouse Retina.

Cone cell death is a characteristic shared by various retinal degenerative disorders, such as cone-rod dystrophy, Stargardt disease, achromatopsia, and retinitis pigmentosa. This leads to conditions like color blindness and permanently impaired visual acuity. Stem cell therapy focused on photoreceptor replacement holds promise for addressing these conditions. However, identifying surface markers that aid in enriching retinal progenitor cells (RPCs) capable of differentiating into cones remains a complex task. In this study, we employed single-cell RNA sequencing to scrutinize the transcriptome of developing retinas in C57BL/6J mice. This revealed the distinctive expression of somatostatin receptor 2 (Sstr2), a surface protein, in late-stage RPCs exhibiting the potential for photoreceptor differentiation. In vivo lineage tracing experiments verified that Sstr2+ cells within the late embryonic retina gave rise to cones, amacrine and horizontal cells during the developmental process. Furthermore, Sstr2+ cells that were isolated from the late embryonic mouse retina displayed RPC markers and exhibited the capability to differentiate into cones in vitro. Upon subretinal transplantation into both wild-type and retinal degeneration 10 (rd10) mice, Sstr2+ cells survived and expressed cone-specific markers. This study underscores the ability of Sstr2 to enrich late-stage RPCs primed for cone differentiation to a large extent. It proposes the utility of Sstr2 as a biomarker for RPCs capable of generating cones for transplantation purposes.

Extracellular vesicles from organoid-derived human retinal progenitor cells prevent lipid overload-induced retinal pigment epithelium injury by regulating fatty acid metabolism.

Retinal degeneration (RD), a group of diseases leading to irreversible vision loss, is characterised by retinal pigment epithelium (RPE) or retinal neuron damage and loss. With fewer risks of immune rejection and tumorigenesis, stem cell-secreted extracellular vesicles (EVs) offer a new cell-free therapeutic paradigm for RD, which remains to be investigated. Human retinal organoid-derived retinal progenitor cells (hERO-RPCs) are an easily accessible and advanced cell source for RD treatment. However, hERO-RPCs-derived EVs require further characterisation. Here, we compared the characteristics of EVs from hERO-RPCs (hRPC-EVs) with those of human embryonic stem cell (hESC)-derived EVs (hESC-EVs) as controls. Based on in-depth proteomic analysis, we revealed remarkable differences between hRPC-EVs and hESC-EVs. A comparison between EVs and their respective cells of origin demonstrated that the protein loading of hRPC-EVs was more selective than that of hESC-EVs. In particular, hESC-EVs were enriched with proteins related to angiogenesis and cell cycle, whereas hRPC-EVs were enriched with proteins associated with immune modulation and retinal development. More importantly, compared with that of hESC-EVs, hRPC-EVs exhibited a lower correlation with cell proliferation and a unique capacity to regulate lipid metabolism. It was further confirmed that hRPC-EVs potentially eliminated lipid deposits, inhibited lipotoxicity and oxidative stress, and enhanced phagocytosis and survival of oleic acid-treated ARPE-19 cells. Mechanistically, hRPC-EVs are integrated into the mitochondrial network of oleic acid-treated ARPE-19 cells, and increased the level of mitochondrial fatty acid ß-oxidation-related proteins. Thus, organoid-derived hRPC-EVs represent a promising source of cell-free therapy for RD, especially for blinding diseases related to abnormal lipid metabolism in RPE cells.

A review of the research progress on Pinellia ternata (Thunb.) Breit.: Botany, traditional uses, phytochemistry, pharmacology, toxicity and quality control.

Ethnopharmacological relevance: Pinellia ternata (Thunb.) Breit. is a well-known perennial herb that is used in traditional medicine in China, Japan and Korea. It's drawing worldwide interests in medicinal applications owing such as anti-diarrhea, lipid-lowering, anti-tumor, anti-cough, expectorant, anti-gastric ulcer, etc. Aim of the study: This review aims to provide useful information on the botany, traditional uses, phytochemistry, pharmacology, toxicity and quality control of Pinellia ternata to help increase its efficiency. In addition, this review will discuss the future research trends and development prospects of this plant. Materials and methods: Data was obtained through a systematic search of published literature and online databases such as Google Scholar, Web of Science, PubMed, Science Direct, and Sci-Finder. The botanical names were confirmed using the World Flora Online and chemical structures were drawn using the ChemBio Draw Ultra Version 19.0 Software. Results: Pinellia ternata is distributed in regions of China and other areas. Pinellia ternata and its compound preparations can be used for cough, vomiting, gastric ulcer and other diseases. Approximately 212 chemical constituents have been isolated from Pinellia ternata, including alkaloids, volatile oils, amino acids, organic acids, flavonoids, cerebrosides, phenylpropanoids and other compounds. Considerable pharmacological experiments in vitro and in vivo have demonstrated that Pinellia ternata possessed antitumor effect, antitussive effects, antiasthmatic effects, increasing resistance to gastric ulcer, and antidiarrheal effect. However, these extracts can also lead to various toxicities such as irritant toxicity, cardiotoxicity, hepatotoxicity and embryonic toxicity. Considerable experiments have demonstrated that different processing methods and suitable compatibility with other herbs can effectively reduce the toxicities and increase the efficiency of Pinellia ternata. Conclusions: Pinellia ternata is an ancient herbal medicine with a broad spectrum of pharmacological activities that has been used for thousands of years in China. Future studies should perform an in-depth analyses of the pharmacokinetics and mechanisms of toxicity of Pinellia ternata. Quality standards should be developed to correspond to the various application methods to ensure the efficacy of drugs in actual treatment.

Associations of serum DNA methylation levels of chemokine signaling pathway genes with mild cognitive impairment (MCI) and Alzheimer's disease (AD).

OBJECTIVE: To investigate the associations of serum DNA methylation levels of chemokine signaling pathway genes with Alzheimer's disease (AD) and mild cognitive impairment (MCI) in elderly people in Xinjiang, China, and to screen out genes whose DNA methylation could distinguish AD and MCI. MATERIALS AND METHODS: 37 AD, 40 MCI and 80 controls were included in the present study. DNA methylation assay was done using quantitative methylation-specific polymerase chain reaction (qMSP). Genotyping was done using Sanger sequencing. RESULTS: DNA methylation levels of ADCY2, MAP2K1 and AKT1 were significantly different among AD, MCI and controls. In the comparisons of each two groups, AKT1 and MAP2K1's methylation was both significantly different between AD and MCI (p < 0.05), whereas MAP2K1's methylation was also significantly different between MCI and controls. Therefore, AKT1's methylation was considered as the candidate serum marker to distinguish AD from MCI, and its association with AD was independent of APOE ε4 allele (p < 0.05). AKT1 hypermethylation was an independent risk factor for AD and MAP2K1 hypomethylation was an independent risk factor for MCI in logistic regression analysis (p < 0.05). CONCLUSION: This study found that the serum of AKT1 hypermethylation is related to AD independently of APOE ε4, which was differentially expressed in the Entorhinal Cortex of the brain and was an independent risk factor for AD. It could be used as one of the candidate serum markers to distinguish AD and MCI. Serum of MAP2K1 hypomethylation is an independent risk factor for MCI.

Cortical structural changes of morphometric similarity network in early-onset schizophrenia correlate with specific transcriptional expression patterns.

BACKGROUND: This study aimed to investigate the neuroanatomical subtypes among early-onset schizophrenia (EOS) patients by exploring the association between structural alterations and molecular mechanisms using a combined analysis of morphometric similarity network (MSN) changes and specific transcriptional expression patterns. METHODS: We recruited 206 subjects aged 7 to 17 years, including 100 EOS patients and 106 healthy controls (HC). Heterogeneity through discriminant analysis (HYDRA) was used to identify the EOS subtypes within the MSN strength. The differences in morphometric similarity between each EOS subtype and HC were compared. Furthermore, we examined the link between morphometric changes and brain-wide gene expression in different EOS subtypes using partial least squares regression (PLS) weight mapping, evaluated genetic commonalities with psychiatric disorders, identified functional enrichments of PLS-weighted genes, and assessed cellular transcriptional signatures. RESULTS: Two distinct MSN-based EOS subtypes were identified, each exhibiting different abnormal MSN strength and cognitive functions compared to HC. The PLS1 score mapping demonstrated anterior-posterior gradients of gene expression in EOS1, whereas inverse distributions were observed in EOS2 cohorts. Genetic commonalities were identified in autistic disorder and adult schizophrenia with EOS1 and inflammatory bowel diseases with EOS2 cohorts. The EOS1 PLS1- genes (Z < -5) were significantly enriched in synaptic signaling-related functions, whereas EOS2 demonstrated enrichments in virtual infection-related pathways. Furthermore, the majority of observed associations with EOS1-specific MSN strength differences contributed to specific transcriptional changes in astrocytes and neurons. CONCLUSIONS: The findings of this study provide a comprehensive analysis of neuroanatomical subtypes in EOS, shedding light on the intricate relationships between macrostructural and molecular aspects of the EOS disease.

Role of rs873601 Polymorphisms in Prognosis of Lung Cancer Patients Treated with Platinum-Based Chemotherapy.

BACKGROUND: Lung cancer is still the most lethal malignancy in the world, according to the report of Cancer Statistics in 2021. Platinum-based chemotherapy combined with immunotherapy is the first-line treatment in lung cancer patients. However, the 5-year survival rate is always affected by the adverse reactions and drug resistance caused by platinum-based chemotherapy. DNA damage and repair system is one of the important mechanisms that can affect the response to chemotherapy and clinical outcomes in lung cancer patients. OBJECTIVE: The objective of this study is to find the relationship between the polymorphisms of DNA repair genes with the prognosis of platinum-based chemotherapy in lung cancer patients. PATIENTS AND METHODS: We performed genotyping in 17 single nucleotide polymorphisms (SNPs) of Excision Repair Cross-Complementation group (ERCC) genes and X-ray Repair Cross-Complementing (XRCC) genes of 345 lung cancer patients via Sequenom MassARRAY. We used Cox proportional hazard models, state, and plink to analyze the associations between SNPs and the prognosis of lung cancer patients. RESULTS: We found that the ERCC5 rs873601 was associated with the overall survival time in lung cancer patients treated with platinum-based chemotherapy (p = 0.031). There were some polymorphisms that were related to the prognosis in specific subgroups of lung cancer. Rs873601 showed a great influence on the prognosis of patients more than 55 years, Small Cell Lung Cancer (SCLC), and smoking patients. Rs2444933 was associated with prognosis in age less than 55 years, SCLC, metastasis, and stage III/IV/ED patients. Rs3740051 played an important role in the prognosis of SCLC and metastasis patients. Rs1869641 was involved in the prognosis of SCLC patients. Rs1051685 was related to the prognosis in non-metastasis patients. CONCLUSION: The ERCC5 rs873601 (G>A) was a valuable biomarker for predicting the prognosis in lung cancer patients treated with platinum-based chemotherapy.

Photoredox-Catalyzed Three-Component 1,2-Cyanoalkylpyridylation of Styrenes with Nonredox-Active Cyclic Oximes.

Three-component alkene 1,2-difunctionalizations have emerged as a powerful strategy for rapid buildup of diverse and complex alkylpyridines, but the distal functionalized alkyl radicals for the alkene 1,2-alkylpyridylations were still rare. Herein, we report an example of regioselective three-component 1,2-cyanoalkylpyridylation of feedstock styrenes with accessible nonredox-active cyclic oximes through visible-light photoredox catalysis, providing a series of structurally diverse ß-cyanoalkylated alkylpyridines. This protocol proceeds through a radical relay pathway including the generation of iminyl radicals enabled by phosphoranyl radical-mediated ß-scission, radical transposition through C-C bond cleavage, highly selective radical addition, and precise radical-radical cross-coupling sequence, thus facilitating the regioselective formation of two distinct C-C single bonds in a single-pot operation. This synthetic strategy features mild conditions, broad compatibility of functional groups and substrate scope, diverse product derivatization, and late-stage modification.