Spatial transcriptomics combined with single-nucleus RNA sequencing reveals glial cell heterogeneity in the human spinal cord.

ABSTRACT: Glial cells play crucial roles in regulating physiological and pathological functions, including sensation, the response to infection and acute injury, and chronic neurodegenerative disorders. Glial cells include astrocytes, microglia, and oligodendrocytes in the central nervous system, and satellite glial cells and Schwann cells in the peripheral nervous system. Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models, few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord. Here, we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes, microglia, and oligodendrocytes in the human spinal cord. To explore the conservation and divergence across species, we compared these findings with those from mice. In the human spinal cord, astrocytes, microglia, and oligodendrocytes were each divided into six distinct transcriptomic subclusters. In the mouse spinal cord, astrocytes, microglia, and oligodendrocytes were divided into five, four, and five distinct transcriptomic subclusters, respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice. Additionally, we detected sex differences in gene expression in human spinal cord glial cells. Specifically, in all astrocyte subtypes, the levels of NEAT1 and CHI3L1 were higher in males than in females, whereas the levels of CST3 were lower in males than in females. In all microglial subtypes, all differentially expressed genes were located on the sex chromosomes. In addition to sex-specific gene differences, the levels of MT-ND4, MT2A, MT-ATP6, MT-CO3, MT-ND2, MT-ND3, and MT-CO2 in all spinal cord oligodendrocyte subtypes were higher in females than in males. Collectively, the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cord-related illnesses, including chronic pain, amyotrophic lateral sclerosis, and multiple sclerosis.

Intermediate aminophenol enables hectogram-scale synthesis of highly bright red carbon quantum dots under ambient conditions.

Carbon quantum dots (C-dots) have developed into potential nanomaterials for lighting, catalysis and bioimaging because of their excellent optical properties and good biocompatibility. However, it is still a challenge to produce efficient red emitting carbon quantum dots (R-C-dots) due to their obscure formation mechanism. This work offered a method to reveal the formation process from the precursor o-phenylenediamine (o-PDA) to R-C-dots. Different from traditional hydrothermal reactions, R-C-dots were synthesized at relatively low temperature and ambient pressure. The pre-oxidation intermediate aminophenol played an important role in the synthesis of R-C-dots, which further cross-linked and polymerized with o-PDA in an acid environment to form R-C-dots. The obtained R-C-dots had a photoluminescence quantum yield of up to 33.26% and excellent two-photon fluorescence properties. A white light-emitting diode (WLED) based on R-C-dots as the red phosphor exhibited standard white light CIE color coordinates of (0.33, 0.33) with a correlated color temperature of 5342 K and a high color rendering index (CRI) of 94.5. The obtained rendering index is the highest value among WLEDs with color coordinates of (0.33, 0.33) based on C-dots. This work provides a new perspective for the controllable large-scale synthesis of red C-dots.

Network Pharmacology Based Elucidation of Molecular Mechanisms of Laoke Formula for Treatment of Advanced Non-Small Cell Lung Cancer.

OBJECTIVE: To explore the specific pharmacological molecular mechanisms of Laoke Formula (LK) on treating advanced non-small cell lung cancer (NSCLC) based on clinical application, network pharmacology and experimental validation. METHODS: Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of Chinese medicine (CM) treatment in 296 patients with NSCLC in Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2015. The compounds of LK were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the corresponding targets were performed from Swiss Target Prediction. NSCLC-related targets were obtained from Therapeutic Target Database and Comparative Toxicogenomics Database. Key compounds and targets were identified from the compound-target-disease network and protein-protein interaction (PPI) network analysis, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were used to predict the potential signaling pathways involved in the treatment of advanced NSCLC with LK. The binding affinities between key ingredients and targets were further verified using molecular docking. Finally, A549 cell proliferation and migration assay were used to evaluate the antitumor activity of LK. Western blot was used to further verify the expression of key target proteins related to the predicted pathways. RESULTS: Kaplan-Meier survival analysis showed that the overall survival of the CM group was longer than that of the non-CM group (36 months vs. 26 months), and COX regression analysis showed that LK treatment was an independent favorable prognostic factor (P=0.027). Next, 97 components and 86 potential targets were included in the network pharmacology, KEGG and GO analyses, and the results indicated that LK was associated with proliferation and apoptosis. Moreover, molecular docking revealed a good binding affinity between the key ingredients and targets. In vitro, A549 cell proliferation and migration assay showed that the biological inhibition effect was more obvious with the increase of LK concentration (P<0.05). And decreased expressions of nuclear factor κB1 (NF-κB1), epidermal growth factor receptor (EGFR) and AKT serine/threonine kinase 1 (AKT1) and increased expression of p53 (P<0.05) indicated the inhibitory effect of LK on NSCLC by Western blot. CONCLUSION: LK inhibits NSCLC by inhibiting EGFR/phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, NFκB signaling pathway and inducing apoptosis, which provides evidence for the therapeutic mechanism of LK to increase overall survival in NSCLC patients.

Psychological interventions to pregnancy-related complications in patients with post-traumatic stress disorder: a scoping review.

OBJECTIVE: This scoping review sought to investigate the association between pregnancy-related complications and post-traumatic stress disorder (PTSD) among postpartum women, then summarize effective psychological interventions for pregnancy-related PTSD or sub-PTSD. METHOD: Publications in English and Chinese were searched in PubMed, Embase, Cochrane, ISI Web of Science, China National Knowledge Infrastructure (CNKI), and WanFang databases using the subject headings of "Stress Disorders, Post-Traumatic", "Pregnant Women", and "psychotherapy". To ensure that as many relevant studies are incorporated as possible, free terms such as prenatal, postnatal, perinatal and gestation were also used. Intervention studies and related cases published by July 1st, 2023, were also searched. RESULTS: Twenty-one articles (including 3,901 mothers) were included in this review. Evidence showed that typical psychological interventions exhibited great effect, and family support programs, peer support, online yoga, and music therapy were also effective in reducing risk and improving the psychological well-being of the studied population. CONCLUSION: Fetal abnormalities, miscarriage, premature birth, infants with low birth weights, hypertension, pre-eclampsia, HELLP syndrome, and hyperemesis gravidarum are associated with an increased risk of PTSD. Moreover, high-risk pregnant women may benefit from psychological interventions such as cognitive behavioral therapy (CBT). It may also be feasible and well-accepted for music therapy and exposure therapy to lessen the intensity of PTSD in mothers.

CPPF++: Uncertainty-Aware Sim2Real Object Pose Estimation by Vote Aggregation.

Object pose estimation constitutes a critical area within the domain of 3D vision. While contemporary state-of-the-art methods that leverage real-world pose annotations have demonstrated commendable performance, the procurement of such real training data incurs substantial costs. This paper focuses on a specific setting wherein only 3D CAD models are utilized as a priori knowledge, devoid of any background or clutter information. We introduce a novel method, CPPF++, designed for sim-to-real category-level pose estimation. This method builds upon the foundational point-pair voting scheme of CPPF, reformulating it through a probabilistic view. To address the challenge posed by vote collision, we propose a novel approach that involves modeling the voting uncertainty by estimating the probabilistic distribution of each point pair within the canonical space. Furthermore, we augment the contextual information provided by each voting unit through the introduction of N-point tuples. To enhance the robustness and accuracy of the model, we incorporate several innovative modules, including noisy pair filtering, online alignment optimization, and a tuple feature ensemble. Alongside these methodological advancements, we introduce a new category-level pose estimation dataset, named DiversePose 300. Empirical evidence demonstrates that our method significantly surpasses previous sim-to-real approaches and achieves comparable or superior performance on novel datasets. Our code is available on https://github.com/qq456cvb/CPPF2.

Astrocytes modulate a specific paraventricular thalamus-prefrontal cortex projection to enhance consciousness recovery from anesthesia.

Current anesthetic theory is mostly based on neurons and/or neuronal circuits. A role for astrocytes also has been shown in promoting recovery from volatile anesthesia, while the exact modulatory mechanism and/or the molecular target in astrocytes is still unknown. In this study, by animal models in male mice and electrophysiological recordings in vivo and in vitro, we found that activating astrocytes of paraventricular thalamus (PVT) and/or knocking down PVT astrocytic Kir4.1 promoted the consciousness recovery from sevoflurane anesthesia. Single-cell RNA sequencing of PVT reveals two distinct cellular subtypes of glutamatergic neurons: PVT GRM and PVT ChAT neurons. Patch-clamp recording results proved astrocytic Kir4.1-mediated modulation of sevoflurane on PVT mainly worked on PVT ChAT neurons, which projected mainly to the mPFC. In summary, our findings support the novel conception that there is a specific PVT-prefrontal cortex projection involved in consciousness recovery from sevoflurane anesthesia, which mediated by the inhibition of sevoflurane on PVT astrocytic Kir4.1 conductance.Significance Statement How volatile anesthetics work is not fully understood. Here, we demonstrate that the commonly used volatile anesthetic sevoflurane can inhibit astrocytic Kir4.1 conductance in PVT, which enhances neuronal firing of PVT neurons. Additionally, by single-cell sequencing, cholinergic neurons in the PVT (PVT ChAT ) are the neuronal substrates for astrocytic modulation in volatile anesthesia, which directly project to prefrontal cortex. Behaviorally, the modulation of astrocytes on PVT ChAT promotes electroencephalogram (EEG) transition of prefrontal cortex; and then accelerates emergence from sevoflurane anesthesia. In summary, this study is the first to identify that astrocytic Kir4.1 in wakeful nuclei is involved in consciousness recovery from volatile anesthetics, as well as the subcellular mechanism.

Ascorbate peroxidase catalyses synthesis of protocatechualdehyde from p-hydroxybenzaldehyde in Lycoris aurea.

Protocatechualdehyde is a plant natural phenolic aldehyde and an active ingredient with important bioactivities in traditional Chinese medicine. Protocatechualdehyde is also a key intermediate in the synthesis of Amaryllidaceae alkaloids for supplying the C6-C1 skeleton. However, the biosynthesis of protocatechualdehyde in plants remains obscure. In this study, we measured the protocatechualdehyde contents in the root, bulb, scape and flower of the Amaryllidaceae plant Lycoris aurea (L'Hér.) Herb., and performed the correlation analysis between the protocatechualdehyde contents and the transcriptional levels of the phenolic oxidization candidate protein encoding genes. We found that a novel ascorbate peroxidase encoded by the contig_24999 in the L. aurea transcriptome database had potential role in the biosynthesis of protocatechualdehyde. The LauAPX_24999 gene was then cloned from the cDNA of the scape of L. aurea. The transient expression of LauAPX_24999 protein in Arabidopsis protoplasts demonstrated that LauAPX_24999 protein was localized in the cytoplasm, thus belonging to Class II L-ascorbate peroxidase. Subsequently, LauAPX_24999 protein was heterogenously expressed in Escherichia coli, and identified that LauAPX_24999 biosynthesized protocatechualdehyde from p-hydroxybenzaldehyde using L-ascorbic acid as the electron donor. The protein structure modelling and molecular docking indicated that p-hydroxybenzaldehyde could access to the active pocket of LauAPX_24999 protein, and reside at the δ-edge of the heme group while L-ascorbic acid binds at the γ-heme edge. To our knowledge, LauAPX_24999 is the first enzyme discovered in plants able to biosynthesize protocatechualdehyde from p-hydroxybenzaldehyde, and offers a competent enzyme resource for the biosynthesis of Amaryllidaceae alkaloids via synthetic biology.

The cumulative impact of temperature and nitrogen availability on the potential nitrogen fixation and extracellular polymeric substances secretion by Dolichospermum.

Nitrogen-fixing cyanobacteria not only cause severe blooms but also play an important role in the nitrogen input processes of lakes. The production of extracellular polymeric substances (EPS) and the ability to fix nitrogen from the atmosphere provide nitrogen-fixing cyanobacteria with a competitive advantage over other organisms. Temperature and nitrogen availability are key environmental factors in regulating the growth of cyanobacteria. In this study, Dolichospermum (formerly known as Anabaena) was cultivated at three different temperatures (10 °C, 20 °C, and 30 °C) to examine the impact of temperature and nitrogen availability on nitrogen fixation capacity and the release of EPS. Initially, confocal laser scanning microscopy (CLSM) and the quantification of heterocysts at different temperatures revealed that lower temperatures (10 °C) hindered the differentiation of heterocysts under nitrogen-deprived conditions. Additionally, while heterocysts inhibited the photosynthetic activity of Dolichospermum, the secretion of EPS was notably affected by nitrogen limitation, particularly at 30 °C. Finally, real-time quantitative polymerase chain reaction (qPCR) was used to measure the expression of nitrogen-utilizing genes (ntcA and nifH) and EPS synthesis-related genes (wzb and wzc). The results indicated that under nitrogen-deprived conditions, the expression of each gene was upregulated, and there was a significant correlation between the upregulation of nitrogen-utilizing and EPS synthesis genes (P < 0.05). Our findings suggested that Dolichospermum responded to temperature variation by affecting the formation of heterocysts, impacting its potential nitrogen fixation capacity. Furthermore, the quantity of EPS released was more influenced by nitrogen availability than temperature. This research enhances our comprehension of interconnections between nitrogen deprivation and EPS production under the different temperatures.

Impact of lipoprotein(a) and fibrinogen on prognosis in patients with coronary artery disease: A retrospective cohort study.

BACKGROUND: Despite the considerable progress made in preventative methods, medication, and interventional therapies, it remains evident that cardiovascular events (CVEs) continue to be the primary cause of both death and morbidity among individuals diagnosed with coronary artery disease (CAD). OBJECTIVE: To compare the connection between lipoprotein a (Lp[a]), fibrinogen (Fib), and both parameters combined with all-cause mortality to detect their value as prognostic biomarkers. METHODS: This is a retrospective study. Patients diagnosed with CAD between January 2007 and December 2020 at the Guangdong Provincial People's Hospital (China) were involved in the study. 43,367 patients met the eligibility criteria. The Lp(a) and Fib levels were distributed into three tertile groups (low, medium, and high). All of the patients included in the study were followed up for all-cause mortality. Kaplan-Meier and Cox regression were performed to determine the relationship between Lp(a), Fib, and all-cause mortality. A concordance statistics model was developed to detect the impact of Fib and Lp(a) in terms of anticipating poor outcomes in patients with CAD. RESULTS: Throughout a median follow-up of 67.0 months, 6,883 (15.9%) patients died. Participants with high Lp(a) (above 27.60 mg/dL) levels had a significantly higher risk for all-cause mortality than individuals with low Lp(a) levels (below 11.13 mg/dL; adjusted hazard ratio [aHR] 1.219, 95% confidence interval [CI]: 1.141-1.304, p< 0.001). Similarly, patients with high Fib levels (above 4.32 g/L) had a significantly greater risk of developing all-cause mortality compared with those with reduced Fib levels (below 3.41 g/L; aHR 1.415, 95% CI: 1.323-1.514, p< 0.001). Patients with raised Lp(a) and Fib levels had the maximum risk for all-cause mortality (aHR 1.702; 95% CI: 1.558-1.859, p< 0.001). When considered together, Lp(a) and Fib caused a significant elevation of the concordance statistic by 0.009 (p< 0.05), suggesting a higher value for predicting mortality when combining the two indicators. CONCLUSION: High Lp(a) and Fib levels could be used as predictive biomarkers for all-cause mortality in individuals with CAD. The prediction accuracy for all-cause mortality improved after combining the two parameters.

The HHEX-ABI2/SLC17A9 axis induces cancer stem cell-like properties and tumorigenesis in HCC.

Accumulating evidence indicated that HHEX participated in the initiation and development of several cancers, but the potential roles and mechanisms of HHEX in hepatocellular carcinoma (HCC) were largely unclear. Cancer stem cells (CSCs) are responsible for cancer progression owing to their stemness characteristics. We reported that HHEX was a novel CSCs target for HCC. We found that HHEX was overexpressed in HCC tissues and high expression of HHEX was associated with poor survival. Subsequently, we found that HHEX promoted HCC cell proliferation, migration, and invasion. Moreover, bioinformatics analysis and experiments verified that HHEX promoted stem cell-like properties in HCC. Mechanistically, ABI2 serving as a co-activator of transcriptional factor HHEX upregulated SLC17A9 to promote HCC cancer stem cell-like properties and tumorigenesis. Collectively, the HHEX-mediated ABI2/SLC17A9 axis contributes to HCC growth and metastasis by maintaining the CSC population, suggesting that HHEX serves as a promising therapeutic target for HCC treatment.

Prehabilitation of surgical patients: a bibliometric analysis from 2005 to 2023.

BACKGROUND: Good preoperative conditions help patients to counteract surgical injury. Prehabilitation is a multimodal preoperative management strategy, including physical, nutritional, psychological, and other interventions, which can improve the functional reserve of patients and enhance postoperative recovery. The purpose of this study is to show the evolution trend and future directions of research related to the prehabilitation of surgical patients. METHODS: The global literature regarding prehabilitation was identified from The Web of Science Core Collection database. Bibliometric methods of the Bibliometrix package of R (version 4.2.1) and VOSviewer were used to analyze publication trends, cooperative networks, study themes, and co-citation relationships in the field. RESULTS: A total of 638 publications were included and the number of publications increased rapidly since 2016, with an average annual growth rate of 41.0%. "Annals of Surgery", "British Journal of Surgery" and "British Journal of Anesthesia" were the most cited journals. Experts from the USA, Canada, the UK, and the Netherlands contributed the most in this field, and an initial cooperative network among different countries and clinical teams was formed. Malnutrition, older patients, frailty, and high-risk patients were the hotspots of recent studies. However, among the top 10 cited articles, the clinical effects of prehabilitation were conflicting. CONCLUSION: This bibliometric review summarized the most influential publications as well as the publication trends and clarified the progress and future directions of prehabilitation, which could serve as a guide for developing evidence-based practices.

Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).

FSCME: A Feature Selection Method Combining Copula Correlation and Maximal Information Coefficient by Entropy Weights.

Feature selection is a critical component of data mining and has garnered significant attention in recent years. However, feature selection methods based on information entropy often introduce complex mutual information forms to measure features, leading to increased redundancy and potential errors. To address this issue, we propose FSCME, a feature selection method combining Copula correlation (Ccor) and the maximum information coefficient (MIC) by entropy weights. The FSCME takes into consideration the relevance between features and labels, as well as the redundancy among candidate features and selected features. Therefore, the FSCME utilizes Ccor to measure the redundancy between features, while also estimating the relevance between features and labels. Meanwhile, the FSCME employs MIC to enhance the credibility of the correlation between features and labels. Moreover, this study employs the Entropy Weight Method (EWM) to evaluate and assign weights to the Ccor and MIC. The experimental results demonstrate that FSCME yields a more effective feature subset for subsequent clustering processes, significantly improving the classification performance compared to the other six feature selection methods. The source codes of the FSCME are available online at https://github.com/CDMBlab/FSCME.

Transcriptomic profiling and gene network analysis revealed regulatory mechanisms of bract development in Bougainvillea glabra.

BACKGROUND: Bracts are important for ornamental plants, and their developmental regulation process is complex; however, relatively little research has been conducted on bracts. In this study, physiological, biochemical and morphological changes in Bougainvillea glabra leaves, leaf buds and bracts during seven developmental periods were systematically investigated. Moreover, transcriptomic data of B. glabra bracts were obtained using PacBio and Illumina sequencing technologies, and key genes regulating their development were screened. RESULTS: Scanning electron microscopy revealed that the bracts develop via a process involving regression of hairs and a color change from green to white. Transcriptome sequencing revealed 79,130,973 bp of transcript sequences and 45,788 transcripts. Differential gene expression analysis revealed 50 expression patterns across seven developmental periods, with significant variability in transcription factors such as BgAP1, BgFULL, BgCMB1, BgSPL16, BgSPL8, BgDEFA, BgEIL1, and BgBH305. KEGG and GO analyses of growth and development showed the involvement of chlorophyll metabolism and hormone-related metabolic pathways. The chlorophyll metabolism genes included BgPORA, BgSGR, BgPPH, BgPAO and BgRCCR. The growth hormone and abscisic acid signaling pathways involved 44 and 23 homologous genes, and coexpression network analyses revealed that the screened genes BgAPRR5 and BgEXLA1 are involved in the regulation of bract development. CONCLUSIONS: These findings improve the understanding of the molecular mechanism of plant bract development and provide important guidance for the molecular regulation and genetic improvement of the growth and development of ornamental plants, mainly ornamental bracts.

Automatic grading of knee osteoarthritis with a plain radiograph radiomics model: combining anteroposterior and lateral images.

OBJECTIVES: To establish a radiomics-based automatic grading model for knee osteoarthritis (OA) and evaluate the influence of different body positions on the model's effectiveness. MATERIALS AND METHODS: Plain radiographs of a total of 473 pairs of knee joints from 473 patients (May 2020 to July 2021) were retrospectively analyzed. Each knee joint included anteroposterior (AP) and lateral (LAT) images which were randomly assigned to the training cohort and the testing cohort at a ratio of 7:3. First, an assessment of knee OA severity was done by two independent radiologists with Kallgren-Lawrence grading scale. Then, another two radiologists independently delineated the region of interest for radiomic feature extraction and selection. The radiomic classification features were dimensionally reduced and a machine model was conducted using logistic regression (LR). Finally, the classification efficiency of the model was evaluated using receiver operating characteristic curves and the area under the curve (AUC). RESULTS: The AUC (macro/micro) of the model using a combination of AP and LAT (AP&LAT) images were 0.772/0.778, 0.818/0.799, and 0.864/0.879, respectively. The radiomic features from the combined images achieved better classification performance than the individual position image (p < 0.05). The overall accuracy of the radiomic model with AP&LAT images was 0.727 compared to 0.712 and 0.417 for radiologists with 4 years and 2 years of musculoskeletal diagnostic experience. CONCLUSIONS: A radiomic model constructed by combining the AP&LAT images of the knee joint can better grade knee OA and assist clinicians in accurate diagnosis and treatment. CRITICAL RELEVANCE STATEMENT: A radiomic model based on plain radiographs accurately grades knee OA severity. By utilizing the LR classifier and combining AP&LAT images, it improves accuracy and consistency in grading, aiding clinical decision-making, and treatment planning. KEY POINTS: Radiomic model performed more accurately in K/L grading of knee OA than junior radiologists. Radiomic features from the combined images achieved better classification performance than the individual position image. A radiomic model can improve the grading of knee OA and assist in diagnosis and treatment.

Assessing the utility of artificial intelligence throughout the triage outpatients: a prospective randomized controlled clinical study.

Currently, there are still many patients who require outpatient triage assistance. ChatGPT, a natural language processing tool powered by artificial intelligence technology, is increasingly utilized in medicine. To facilitate and expedite patients' navigation to the appropriate department, we conducted an outpatient triage evaluation of ChatGPT. For this evaluation, we posed 30 highly representative and common outpatient questions to ChatGPT and scored its responses using a panel of five experienced doctors. The consistency of manual triage and ChatGPT triage was assessed by five experienced doctors, and statistical analysis was performed using the Chi-square test. The expert ratings of ChatGPT's answers to these 30 frequently asked questions revealed 17 responses earning very high scores (10 and 9.5 points), 7 earning high scores (9 points), and 6 receiving low scores (8 and 7 points). Additionally, we conducted a prospective cohort study in which 45 patients completed forms detailing gender, age, and symptoms. Triage was then performed by outpatient triage staff and ChatGPT. Among the 45 patients, we found a high level of agreement between manual triage and ChatGPT triage (consistency: 93.3-100%, p<0.0001). We were pleasantly surprised to observe that ChatGPT's responses were highly professional, comprehensive, and humanized. This innovation can help patients win more treatment time, improve patient diagnosis and cure rates, and alleviate the pressure of medical staff shortage.

Longevity factor FOXO3a: A potential therapeutic target for age-related ocular diseases.

The forkhead box protein O3 (FOXO3a) belongs to the subgroup O of the forkhead transcription factor family and plays an important role in regulating the aging process by participating in the regulation of various life processes, including cell cycle arrest, apoptosis, autophagy, oxidative stress, and DNA repair. The eye is an organ that is affected by aging earlier. However, the functional role and potential clinical applications of FOXO3a in age-related eye diseases have not received widespread attention and lacked comprehensive and clear clarification. In this review, we demonstrated the relationship between FOXO3a and visual system health, summarized the functional roles of FOXO3a in various eye diseases, and potential ocular-related therapies and drugs targeting FOXO3a in visual system diseases through a review and summary of relevant literature. This review indicates that FOXO3a is an important factor in maintaining the normal function of various tissues in the eye, and is closely related to the occurrence and development of ophthalmic-related diseases. Based on its vital role in the normal function of the visual system, FOXO3a has potential clinical application value in related ophthalmic diseases. At present, multiple molecules and drugs targeting FOXO3a have been reported to have the potential for the treatment of related ophthalmic diseases, but further clinical trials are needed. In conclusion, this review can facilitate us to grasp the role of FOXO3a in the visual system and provide new views and bases for the treatment strategy research of age-related eye diseases.

A chromosome-level genome assembly of Chinese quince (Pseudocydonia sinensis).

Introduction: Pseudocydonia sinensis, also known as Chinese quince, is a perennial shrub or small tree highly valued for its edibility and medicinal properties. Method: This study presents the first chromosome-level genome assembly of P. sinensis, achieved using HiFi sequencing and Hi-C scaffolding technology. Results: The assembly resulted in a high-quality genome of 576.39 Mb in size. The genome was anchored to 17 pseudo-chromosomes, with a contig N50 of 27.6 Mb and a scaffold N50 of 33.8 Mb. Comprehensive assessment using BUSCO, CEGMA and BWA tools indicates the high completeness and accuracy of the genome assembly. Our analysis identified 116 species-specific genes, 1196 expanded genes and 1109 contracted genes. Additionally, the distribution of 4DTv values suggests that the most recent duplication event occurred before the divergence of P. sinensis from both Chaenomeles pinnatifida and Pyrus pyrifolia. Discussion: The assembly of this high-quality genome provides a valuable platform for the genetic breeding and cultivation of P. sinensis, as well as for the comparison of the genetic complexity of P. sinensis with other important crops in the Rosaceae family.

Fine-tuning pH sensor H98 by remote essential residues in the hydrogen-bond network of mTASK-3.

TASK-3 generates a background K+ conductance which when inhibited by acidification depolarizes membrane potential and increases cell excitability. These channels sense pH by protonation of histidine residue H98, but recent evidence revealed that several other amino acid residues also contribute to TASK-3 pH sensitivity, suggesting that the pH sensitivity is determined by an intermolecular network. Here we use electrophysiology and molecular modeling to characterize the nature and requisite role(s) of multiple amino acids in pH sensing by TASK-3. Our results suggest that the pH sensor H98 and consequently pH sensitivity is influenced by remote amino acids that function as a hydrogen-bonding network to modulate ionic conductivity. Among the residues in the network, E30 and K79 are the most important for passing external signals near residue S31 to H98. The hydrogen-bond network plays a key role in selectivity or pH sensing in mTASK-3, and E30 and S31 in the network can modulate the conductive properties (E30) or reverse the pH sensitivity and selectivity of the channel (S31). Molecular dynamics simulations and pK1/2 calculation revealed that double mutants involving H98 + S31 primarily regulate the structure stability of the pore selectivity filter and pore loop regions, further strengthen the stability of the cradle suspension system, and alter the ionization state of E30 and K79, thereby preventing pore conformational change that normally occurs in response to varying extracellular pH. These results demonstrate that crucial residues in the hydrogen-bond network can remotely tune the pH sensing of mTASK-3 and may be a potential allosteric regulatory site for therapeutic molecule development.

Treatment of acute basilar artery occlusion by retrograde puncture via the vertebral artery approach: A care-compliant case report.

BACKGROUND: Vertebral artery stump syndrome (VASS) is a cause of acute stroke. Owing to the particularity of the pathogenesis of VASS, interventional treatment of VASS is difficult. Common mechanical thrombectomy approaches include femoral and radial artery approaches. However, conventional approaches may not be suitable for VASS. If effective measures are not taken to open offending vessels in time, this can lead to a high rate of disability. In recent years, no consensus has been reached regarding surgical methods for treating VASS. PATIENT CONCERNS: The patient presented to the emergency department with a 2-hour history of disturbance of consciousness. DIAGNOSIS: After neurological and magnetic resonance imaging examinations, the patient was diagnosed with acute large vessel occlusive posterior circulation cerebral infarction. METHODS: The patient's symptoms were not relieved after intravenous infusion of argatroban (10 mg) at a local hospital. We first attempted to open the occluded vertebral artery through normal approaches but failed. We then punctured the vertebral artery, successfully opened the occluded vertebral artery, and performed mechanical thrombectomy. RESULTS: The patient underwent successful vertebral artery puncture and mechanical thrombectomy, with no evidence of postoperative bleeding or vascular injury at the puncture site. The patient regained consciousness the day after surgery but remained impaired in physical activity. After 4 months of rehabilitation, the patient recovered completely. CONCLUSION: When the conventional approach cannot meet the requirements of mechanical thrombectomy, reverse puncture of the vertebral artery is a feasible surgical method for patients with VASS. However, due to the small number of cases, a series of safety problems such as potential puncture failure, hemorrhage after puncture, and vascular occlusion still need to be further explored.