Targeting CD8+ T cells with natural products for tumor therapy: Revealing insights into the mechanisms.

BACKGROUND: Despite significant advances in cancer immunotherapy over the past decades, such as T cell-engaging chimeric antigen receptor (CAR)-T cell therapy and immune checkpoint blockade (ICB), therapeutic failure resulting from various factors remains prevalent. Therefore, developing combinational immunotherapeutic strategies is of great significance for improving the clinical outcome of cancer immunotherapy. Natural products are substances that naturally exist in various living organisms with multiple pharmacological or biological activities, and some of them have been found to have anti-tumor potential. Notably, emerging evidences have suggested that several natural compounds may boost the anti-tumor effects through activating immune response of hosts, in which CD8+ T cells play a pivotal role. METHODS: The data of this review come from PubMed, Web of Science, Google Scholar, and ClinicalTrials (https://clinicaltrials.gov/) with the keywords "CD8+ T cell", "anti-tumor", "immunity", "signal 1", "signal 2", "signal 3", "natural products", "T cell receptor (TCR)", "co-stimulation", "co-inhibition", "immune checkpoint", "inflammatory cytokine", "hesperidin", "ginsenoside", "quercetin", "curcumin", "apigenin", "dendrobium officinale polysaccharides (DOPS)", "luteolin", "shikonin", "licochalcone A", "erianin", "resveratrol", "procyanidin", "berberine", "usnic acid", "naringenin", "6-gingerol", "ganoderma lucidum polysaccharide (GL-PS)", "neem leaf glycoprotein (NLGP)", "paclitaxel", "source", "pharmacological activities", and "toxicity". These literatures were published between 1993 and 2023. RESULTS: Natural products have considerable advantages as anti-tumor drugs based on the various species, wide distribution, low price, and few side effects. This review summarized the effects and mechanisms of some natural products that exhibit anti-tumor effects via targeting CD8+ T cells, mainly focused on the three signals that activate CD8+ T cells: TCR, co-stimulation, and inflammatory cytokines. CONCLUSION: Clarifying the role and underlying mechanism of natural products in cancer immunotherapy may provide more options for combinational treatment strategies and benefit cancer therapy, to shed light on identifying potential natural compounds for improving the clinical outcome in cancer immunotherapy.

Upadacitinib for refractory ulcerative colitis with primary nonresponse to infliximab and vedolizumab: A case report.

BACKGROUND: Many patients with ulcerative colitis (UC) do not respond well to, or tolerate conventional and biological therapies. There is currently no consensus on the treatment of refractory UC. Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib, a small-molecule drug, is effective and safe for treating UC. However, no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab. CASE SUMMARY: We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus, in addition to dizziness. The patient had recurrent disease after receiving mesalazine, prednisone, azathioprine, infliximab and vedolizumab over four years. Based on the endoscopic findings and pathological biopsy, the patient was diagnosed with refractory UC. In particular, the patient showed primary nonresponse to infliximab and vedolizumab. Based on the patient's history and recurrent disease, we decided to administer upadacitinib. During hospitalisation, the patient was received upadacitinib under our guidance. Eight weeks after the initiation of upadacitinib treatment, the patient's symptoms and endoscopic findings improved significantly. No notable adverse reactions have been reported to date. CONCLUSION: Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.

DFMG decreases angiogenesis to uphold plaque stability by inhibiting the TLR4/VEGF pathway in mice.

The aim of this study was to elucidate the specific mechanism through which 7-difluoromethoxy-5,4'-dimethoxygenistein (DFMG) inhibits angiogenesis in atherosclerosis (AS) plaques, given its previously observed but poorly understood inhibitory effects. In vitro, a model using Human Umbilical Vein Endothelial (HUVEC-12) cells simulated the initial lesion in the atherosclerotic pathological process, specifically oxidative stress injury, by exposing cells to 30 µmol/L LPC. Additionally, an AS mouse model was developed in ApoE knockout mice through a 16-week period of high-fat feeding. DFMG demonstrated a reduction in tubule quantities in the tube formation assay and neovascularization induced by oxidative stress-damaged endothelial cells in the chicken embryo chorioallantoic membrane assay. Furthermore, DFMG decreased lipid levels in the blood of ApoE knockout mice with AS, along with a decrease in atherosclerotic plaques and neovascularizations in the aortic arch and descending aorta of AS animal models. DFMG treatment upregulated microRNA140 (miR-140) expression and suppressed VEGF secretion in HUVEC-12 cells. These effects were counteracted by Toll-like receptor 4 (TLR4) overexpression in HUVEC-12 cells subjected to oxidative injury or in a mouse model of AS. Dual-luciferase reporter assays demonstrated that miR-140 directly targeted TLR4. Immunohistochemical assay findings indicated a significant inverse relationship between miR-140 expression and TLR4 expression in ApoE knockout mice subjected to a high-fat diet. The study observed a close association between DFMG inhibitory effects on angiogenesis and plaque stability in AS, and the inhibition of the TLR4/NF-κB/VEGF signaling pathway, negatively regulated by miR-140.

ROS-responsive sprayable hydrogel as ROS scavenger and GATA6+ macrophages trap for the prevention of postoperative abdominal adhesions.

Postoperative abdominal adhesions are a common clinical problem after surgery and can cause many serious complications. Current most commonly used antiadhesion products are less effective due to their short residence time and focus primary on barrier function. Herein, we developed a sprayable hydrogel barrier (sHA-ADH/OHA-E) with self-regulated drug release based on ROS levels at the trauma site, to serve as a smart inflammatory microenvironment modulator and GATA6+ macrophages trap for non-adherent recovery from abdominal surgery. Sulfonated hyaluronic acid (HA) conjugates modified with adipic dihydrazide (sHA-ADH), and oxidized HA conjugates grafted with epigallocatechin-3-gallate (EGCG) via ROS-cleavable boronate bonds (OHA-E) were synthesized. sHA-ADH/OHA-E hydrogel was facilely fabricated within 5 s after simply mixing sHA-ADH and OHA-E through forming dynamic covalent acylhydrazones. With good biocompatibility, appropriate mechanical strength, tunable shear-thinning, self-healing, asymmetric adhesion, and reasonable in vivo retention time, sHA-ADH/OHA-E hydrogel meets the requirements of a perfect physical barrier. Intriguingly, sulfonic acid groups endowed the hydrogel with satisfactory anti-fibroblast and macrophage attachment capability, and were demonstrated for the first time to act as polyanion traps to prevent GATA6+ macrophages aggregation. Importantly, EGCG could be intelligently released by ROS triggering to alleviate oxidative stress and promote proinflammatory M1 macrophage polarize to antiinflammatory M2 phenotype. Further, the fibrinolytic system balance was restored to reduce fibrosis. Thanks to the above advantages, the sHA-ADH/OHA-E hydrogel exhibited excellent anti-adhesion effects in a rat sidewall defect-cecum abrasion model and is expected to be a promising and clinically translatable antiadhesion barrier.

Enhanced SLC35B2/SAV1 sulfation axis promotes tumor growth by inhibiting Hippo signaling in HCC.

BACKGROUND AND AIMS: Protein tyrosine sulfation (PTS) is a common posttranslational modification that regulates a variety of physiological and pathological processes. However, the role of PTS in cancer remains poorly understood. The goal of this study was to determine whether and how PTS plays a role in HCC progression. APPROACH AND RESULTS: By mass spectrometry and bioinformatics analysis, we identified SAV1 as a novel substrate of PTS in HCC. Oxidative stress upregulates the transcription of SLC35B2, a Golgi-resident transporter of sulfate donor 3'-phosphoadenosine 5'-phosphosulfate, leading to increased sulfation of SAV1. Sulfation of SAV1 disrupts the formation of the SAV1-MST1 complex, resulting in a decrease of MST1 phosphorylation and subsequent inactivation of Hippo signaling. These molecular events ultimately foster the growth of HCC cells both in vivo and in vitro. Moreover, SLC35B2 is a novel transcription target gene of the Hippo pathway, constituting a positive feedback loop that facilitates HCC progression under oxidative stress. CONCLUSIONS: Our findings reveal a regulatory mechanism of the SLC35B2/SAV1 sulfation axis in response to oxidative stress, highlighting its potential as a promising therapeutic target for HCC.

Identification of a new gene signature for prognostic evaluation in cervical cancer: based on cuproptosis-associated angiogenesis and multi-omics analysis.

Patients with recurrent or metastatic cervical cancer are in urgent need of novel prognosis assessment or treatment approaches. In this study, a novel prognostic gene signature was discovered by utilizing cuproptosis-related angiogenesis (CuRA) gene scores obtained through weighted gene co-expression network analysis (WGCNA) of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. To enhance its reliability, the gene signature was refined by integrating supplementary clinical variables and subjected to cross-validation. Meanwhile, the activation of the VEGF pathway was inferred from an analysis of cell-to-cell communication, based on the expression of ligands and receptors in cell transcriptomic datasets. High-CuRA patients had less infiltration of CD8 + T cells and reduced expression of most of immune checkpoint genes, which indicated greater difficulty in immunotherapy. Lower IC50 values of imatinib, pazopanib, and sorafenib in the high-CuRA group revealed the potential value of these drugs. Finally, we verified an independent prognostic gene SFT2D1 was highly expressed in cervical cancer and positively correlated with the microvascular density. Knockdown of SFT2D1 significantly inhibited ability of the proliferation, migration, and invasive in cervical cancer cells. CuRA gene signature provided valuable insights into the prediction of prognosis and immune microenvironment of cervical cancer, which could help develop new strategies for individualized precision therapy for cervical cancer patients.

Genome-wide identification and characterization of NAC transcription factor family members in Trifolium pratense and expression analysis under lead stress.

BACKGROUND: The NAC TF family is widely involved in plant responses to various types of stress. Red clover (Trifolium pratense) is a high-quality legume, and the study of NAC genes in red clover has not been comprehensive. The aim of this study was to analyze the NAC gene family of red clover at the whole-genome level and explore its potential role in the Pb stress response. RESULTS: In this study, 72 TpNAC genes were identified from red clover; collinearity analysis showed that there were 5 pairs of large fragment replicators of TpNAC genes, and red clover was found to be closely related to Medicago truncatula. Interestingly, the TpNAC genes have more homologs in Arabidopsis thaliana than in soybean (Glycine max). There are many elements in the TpNAC genes promoters that respond to stress. Gene expression analysis showed that all the TpNAC genes responded to Pb stress. qRT-PCR showed that the expression levels of TpNAC29 and TpNAC42 were significantly decreased after Pb stress. Protein interaction network analysis showed that 21 TpNACs and 23 other genes participated in the interaction. In addition, the TpNAC proteins had three possible 3D structures, and the secondary structure of these proteins were mainly of other types. These results indicated that most TpNAC members were involved in the regulation of Pb stress in red clover. CONCLUSION: These results suggest that most TpNAC members are involved in the regulation of Pb stress in red clover. TpNAC members play an important role in the response of red clover to Pb stress.

Optic neuropathy in high myopia: Glaucoma or high myopia or both?

Due to the increasing prevalence of high myopia around the world, structural and functional damages to the optic nerve in high myopia has recently attracted much attention. Evidence has shown that high myopia is related to the development of glaucomatous or glaucoma-like optic neuropathy, and that both have many common features. These similarities often pose a diagnostic challenge that will affect the future management of glaucoma suspects in high myopia. In this review, we summarize similarities and differences in optic neuropathy arising from non-pathologic high myopia and glaucoma by considering their respective structural and functional characteristics on fundus photography, optical coherence tomography scanning, and visual field tests. These features may also help to distinguish the underlying mechanisms of the optic neuropathies and to determine management strategies for patients with high myopia and glaucoma.

Oxidative Stress Promotes Liver Cancer Metastasis via RNF25-Mediated E-Cadherin Protein Degradation.

Loss of E-cadherin (ECAD) is required in tumor metastasis. Protein degradation of ECAD in response to oxidative stress is found in metastasis of hepatocellular carcinoma (HCC) and is independent of transcriptional repression as usually known. Mechanistically, protein kinase A (PKA) senses oxidative stress by redox modification in its ß catalytic subunit (PRKACB) at Cys200 and Cys344. The activation of PKA kinase activity subsequently induces RNF25 phosphorylation at Ser450 to initiate RNF25-catalyzed degradation of ECAD. Functionally, RNF25 repression induces ECAD protein expression and inhibits HCC metastasis in vitro and in vivo. Altogether, these results indicate that RNF25 is a critical regulator of ECAD protein turnover, and PKA is a necessary redox sensor to enable this process. This study provides some mechanistic insight into how oxidative stress-induced ECAD degradation promotes tumor metastasis of HCC.

The Impact of high-performance work system perceived by medical staff on job satisfaction: the mediating role of self-efficacy.

As the mainstay of healthcare, the job satisfaction of medical staff deserves attention. This study aimed to explore the correlation between the perception of the high-performance work system (P-HPWS) and job satisfaction of medical staff in public hospitals and to further investigate the mediating effect of self-efficacy. From November 2019 to January 2020, a cross-sectional survey on working doctors and nurses was conducted in five tertiary public hospitals in China. A total of 520 participants were surveyed. The P-HPWS, job satisfaction, and self-efficacy were assessed using the 25-item self-administered scale, six-item job satisfaction questionnaire, and the General Self-Efficacy Scale, respectively. Linear regression and mediation effects models were used to identify the associations between primary variables. The results showed a significant positive correlation between P-HPWS and job satisfaction (P < 0.01), while self-efficacy played a mediating role between P-HPWS and job satisfaction. This finding reveals the benefits of improving employees' P-HPWS and self-efficacy on their job satisfaction, and that hospitals can improve their management systems by implementing and refining HPWS.

HSPA8 Activates Wnt/ß-Catenin Signaling to Facilitate BRAF V600E Colorectal Cancer Progression by CMA-Mediated CAV1 Degradation.

BRAF V600E attracts wide attention in the treatment of colorectal cancer (CRC) as stratifying and predicting a refractory classification of CRC. Recent evidence indicates that Wnt/ß-catenin signaling is broadly activated and participates in the refractoriness of BRAF V600E CRC, but the underlying molecular mechanism needs to be elucidated. Here, heat shock 70 kDa protein 8 (HSPA8), an essential regulator in chaperone-mediated autophagy (CMA), is identified as a potential therapeutic target for advanced BRAF V600E CRC. These results show that HSPA8 is transcriptionally upregulated in BRAF V600E CRC, which promotes CMA-dependent degradation of caveolin-1 (CAV1) to release ß-catenin into the nucleus and thus activates the Wnt/ß-catenin pathway, contributing to metastasis and progression of BRAF V600E CRC. Of note, HSPA8 directly interacts with the KIFSN motif on CAV1, the interaction can be enhanced by p38 MAPK-mediated CAV1 S168 phosphorylation. Furthermore, pharmacological targeting HSPA8 by VER155008 exhibits synergistic effects with BRAF inhibitors on CRC mouse models. In summary, these findings discover the important role of the HSPA8/CAV1/ß-catenin axis in the development of refractory BRAF V600E CRC and highlight HSPA8 as a predictive biomarker and therapeutic target in clinical practice.

Presence of meaning in life and meaning confusion mediate the effects of adverse childhood experiences on mental health among university students.

Few studies have explored meaning in life as a mediator between adverse childhood experiences (ACEs) and mental health. This study examined the protective and risk factors associated with meaning in life, as they mediate the effect of ACEs on mental health. The sample was 293 university students in Hong Kong (mean age = 21 years). The results of analyses based on three-wave longitudinal data and structural equation modeling demonstrated that the presence of meaning mediated the negative association between ACEs and happiness, and that meaning confusion mediated the positive association between ACEs and depression and anxiety. This study provides evidence that the presence of meaning may play a protective role and that meaning confusion may be a risk factor for the effects of ACEs on mental health. This study's results have implications for the development of prevention and intervention strategies to alleviate the detrimental impact of ACEs and promote mental health in young adults.

Conduction and validation of a novel prognostic signature in cervical cancer based on the necroptosis characteristic genes via integrating of multiomics data.

The significance of necroptosis in recurrent or metastatic cervical cancer remains unclear. In this study, we utilized various bioinformatics methods to analyze the cancer genome atlas (TCGA) data, gene chip and the single-cell RNA-sequencing (scRNA seq) data. And a necroptosis-related genes signature for prognostic assessment of patients with cervical cancer was constructed successfully. Survival analysis, receiver operating characteristic (ROC) curve, the support vector machine recursive feature elimination (SVM-RFE) algorithm and random forest analysis were performed to validate this signature. Patients in TCGA-CESC cohort were grouped into "high-necroptosis score (H-NCPS)" vs "low-necroptosis score (L-NCPS)" subgroups based on the median of necroptosis score of each patient. Analyses of the tumor microenvironment manifested "H-NCPS" patients associated with lower degree of immune infiltration. Through the utilization of survival analysis, cell communication, and Gene Set Enrichment Analysis (GSEA), PGK1 was determined to be the pivotal gene within the 9-gene signature associated with necroptosis. The high expression of PGK1 in cervical cancer cells was confirmed through the utilization of quantitative real-time polymerase chain reaction (RT-qPCR) and the human protein atlas (HPA). In the interim, PGK1 prompted the transition of M1 macrophages to M2 macrophages and influenced the occurrence and development of necroptosis. In conclusion, the 9-gene signature developed from necroptosis-related genes has shown significant predictive capabilities for the prognosis of cervical cancer, offered valuable guidance for individualized and targeted treatment approaches for patients.

Effect of Elevated Progesterone Levels on hCG Trigger Day on Clinical Pregnancy Outcome in Short-Acting GnRHa Downregulated Cycles.

Background: Previous studies suggested higher serum progesterone (P) levels were strongly associated with a lower clinical pregnancy rate (CPR) for in vitro fertilization-embryo transfer (IVF-ET). However, the effect of increased serum P levels on the day of human chorionic gonadotropin (hCG) administration on clinical outcomes in short-acting gonadotropin-releasing hormone agonist (GnRHa) downregulated IVF-ET cycles remains unclear. Methods: We conducted a retrospective cohort study from January 2017 to December 2021, which included a total of 1664 patients receiving their first short-acting GnRHa IVF-ET cycles at our reproductive medicine centre of Nanjing Drum Tower Hospital. The smooth curve fitting and interaction analysis were employed to analyse the association between the CPR and the serum P levels with different embryo types (cleavage-stage embryo or blastocyst). In addition, total cycles were grouped according to different P levels on the trigger day of hCG administration for further analysis. Results: The CPR of patients with increased serum P level (higher than 1.5 ng/mL) on the hCG day did not decrease. A smoothing curve fitting showed that the CPR did not change obviously with the increase in serum P levels. Subgroup analysis of different types of embryos transferred showed that no correlation was observed between the CPR and serum P levels on the day of hCG administration in cleavage-stage embryo transfer cycles. However, the CPR of patients receiving blastocyst transfer showed a downward trend with the increase in serum P levels. At the same time, an interaction analysis also confirmed that the CPR of blastocyst transfer was more likely to be affected by elevated serum P levels on the hCG day. Conclusion: In the luteal phase short-acting GnRHa downregulated IVF-ET cycles, the elevated serum P levels on the hCG day did not affect the CPR of cleavage-stage embryo transfer but reduced the CPR of blastocyst transfer.

Classification of diabetic maculopathy based on optical coherence tomography images using a Vision Transformer model.

PURPOSE: To develop a Vision Transformer model to detect different stages of diabetic maculopathy (DM) based on optical coherence tomography (OCT) images. METHODS: After removing images with poor quality, a total of 3319 OCT images were extracted from the Eye Center of the Renmin Hospital of Wuhan University and randomly split the images into training and validation sets in a 7:3 ratio. All macular cross-sectional scan OCT images were collected retrospectively from the eyes of DM patients from 2016 to 2022. One of the OCT stages of DM, including early diabetic macular oedema (DME), advanced DME, severe DME and atrophic maculopathy, was labelled on the collected images, respectively. A deep learning (DL) model based on Vision Transformer was trained to detect four OCT grading of DM. RESULTS: The model proposed in our paper can provide an impressive detection performance. We achieved an accuracy of 82.00%, an F1 score of 83.11%, an area under the receiver operating characteristic curve (AUC) of 0.96. The AUC for the detection of four OCT grading (ie, early DME, advanced DME, severe DME and atrophic maculopathy) was 0.96, 0.95, 0.87 and 0.98, respectively, with an accuracy of 90.87%, 89.96%, 94.42% and 95.13%, respectively, a precision of 88.46%, 80.31%, 89.42% and 87.74%, respectively, a sensitivity of 87.03%, 88.18%, 63.39% and 89.42%, respectively, a specificity of 93.02%, 90.72%, 98.40% and 96.66%, respectively and an F1 score of 87.74%, 84.06%, 88.18% and 88.57%, respectively. CONCLUSION: Our DL model based on Vision Transformer demonstrated a relatively high accuracy in the detection of OCT grading of DM, which can help with patients in a preliminary screening to identify groups with serious conditions. These patients need a further test for an accurate diagnosis, and a timely treatment to obtain a good visual prognosis. These results emphasised the potential of artificial intelligence in assisting clinicians in developing therapeutic strategies with DM in the future.

Prediction of nonlayered oxide monolayers as flexible high-κ dielectrics with negative Poisson's ratios.

During the last two decades, two-dimensional (2D) materials have been the focus of condensed matter physics and material science due to their promising fundamental properties and (opto-)electronic applications. However, high-κ 2D dielectrics that can be integrated within 2D devices are often missing. Here, we propose nonlayered oxide monolayers with calculated exfoliation energy as low as 0.39 J/m2 stemming from the ionic feature of the metal oxide bonds. We predict 51 easily or potentially exfoliable oxide monolayers, including metals and insulators/semiconductors, with intriguing physical properties such as ultra-high κ values, negative Poisson's ratios and large valley spin splitting. Among them, the most promising dielectric, GeO2, exhibits an auxetic effect, a κ value of 99, and forms type-I heterostructures with MoSe2 and HfSe2, with a band offset of ~1 eV. Our study opens the way for designing nonlayered 2D oxides, offering a platform for studying the rich physics in ultra-thin oxides and their potential applications in future information technologies.

Optic Nerve Head Abnormalities in Nonpathologic High Myopia and the Relationship With Visual Field.

PURPOSE: To describe the optic nerve head (ONH) abnormalities in nonpathologic highly myopic eyes based on swept-source optical coherence tomography (OCT) and the relationship with visual field (VF). DESIGN: Secondary analysis from a longitudinal cohort study. METHODS: Highly myopic patients without myopic maculopathy of category 2 or higher were enrolled. All participants underwent a swept-source OCT examination focused on ONH. We differentiated between 3 major types (optic disc morphologic abnormality, papillary/peripapillary tissue defect, and papillary/peripapillary schisis) and 12 subtypes of ONH abnormalities. The prevalence and characteristics of ONH abnormalities and the relationship with VF were analyzed. RESULTS: A total of 857 participants (1389 eyes) were included. Among the 1389 eyes, 91.86%, 68.61%, and 34.92% of them had at least 1, 2, or 3 ONH abnormalities, respectively, which corresponded to 29.55%, 31.79%, and 35.67% of VF defects, respectively. Among the 12 subtypes of the 3 major types, peripapillary hyperreflective ovoid mass-like structure, visible retrobulbar subarachnoid space, and prelaminar schisis were the most common, respectively. Perimetric defects corresponding to OCT abnormalities were more commonly found in eyes with peripapillary retinal detachment, peripapillary retinoschisis, and peripapillary hyperreflective ovoid mass-like structure. Glaucoma-like VF defects were more common in eyes with deep optic cups (28.17%) and with optic disc pit/pit-like change (18.92%). CONCLUSIONS: We observed and clarified the ONH structural abnormalities in eyes with nonpathologic high myopia. These descriptions may be helpful to differentiate changes in pathologic high myopia or glaucoma.

Establishment and Clinical Application in Stroke of a Serum Copeptin Time-Resolved Fluorescence Immunoassay.

The serum biomarker copeptin, an innovative and stable substitute biomarker of vasopressin, is associated with stroke. Therefore, establishing a highly sensitive time-resolved fluorescence immunoassay for copeptin (copeptin-TRFIA) is helpful to measure stroke and evaluate its value in clinical applications. Double antibody sandwich was used to establish copeptin-TRFIA. The established method was then assessed. Two coated and Eu3+-labeled copeptin monoclonal specific antibodies targeting different antigen epitopes were employed. The serum fluorescence counts of patients with stroke and healthy volunteers were detected by using the well-established copeptin-TRFIA. Serum copeptin levels were measured and analyzed statistically. The actual measurement linearity range of the proposed method was 0.13-44.66 ng/mL. Copeptin-TRFIA had the inter-assay coefficient of variation (CV) of 6.49%-9.08% and the intra-assay CV of 4.75%-7.77%. Patients with cerebral infarction (CI) and intracerebral hemorrhage (ICH) had significantly higher serum copeptin levels than healthy subjects. Copeptin concentrations in the serum of patients with stroke were significantly correlated with the scores of the National Institute for Healthy Stroke Scale (NIHSS) and modified Rankin Scale (mRS). A highly sensitive copeptin-TRFIA was successfully established. Serum copeptin has a certain value in the clinical diagnosis and prognosis of stroke.

Identification and Evolutionary Analysis of the Auxin Response Factor (ARF) Family Based on Transcriptome Data from Caucasian Clover and Analysis of Expression Responses to Hormones.

Caucasian clover (Trifolium ambiguum M. Bieb.) is an excellent perennial plant in the legume family Fabaceae, with a well-developed rhizome and strong clonal growth. Auxin is one of the most important phytohormones in plants and plays an important role in plant growth and development. Auxin response factor (ARF) can regulate the expression of auxin-responsive genes, thus participating in multiple pathways of auxin transduction signaling in a synergistic manner. No genomic database has been established for Caucasian clover. In this study, 71 TaARF genes were identified through a transcriptomic database of Caucasian clover rhizome development. Phylogenetic analysis grouped the TaARFs into six (1-6) clades. Thirty TaARFs contained a complete ARF structure, including three relatively conserved regions. Physical and chemical property analysis revealed that TaARFs are unstable and hydrophilic proteins. We also analyzed the expression pattern of TaARFs in different tissues (taproot, horizontal rhizome, swelling of taproot, rhizome bud and rhizome bud tip). Quantitative real-time RT-PCR revealed that all TaARFs were responsive to phytohormones (indole-3-acetic acid, gibberellic acid, abscisic acid and methyl jasmonate) in roots, stems and leaves. These results helped elucidate the role of ARFs in responses to different hormone treatments in Caucasian clover.

Integrated Transcriptome Analysis of Long Noncoding RNA and mRNA in Developing and Aging Mouse Retina.

Mice have emerged as a widely employed model for investigating various retinal diseases. However, the availability of comprehensive datasets capturing the entire developmental and aging stages of the mouse retina, particularly during the elderly period, encompassing integrated lncRNA and mRNA expression profiles, is limited. In this study, we assembled a total of 18 retina samples from mice across 6 distinct stages of development and aging (5 days, 3 weeks, 6 weeks, 10 weeks, 6 months, and 15 months) to conduct integrated lncRNA and mRNA sequencing analysis. This invaluable dataset offers a comprehensive transcriptomic resource of mRNA and lncRNA expression profiles during the natural progression of retinal development and aging. The discoveries stemming from this investigation will significantly contribute to the elucidation of the underlying molecular mechanisms associated with various retinal diseases, such as congenital retinal dysplasia and retinal degenerative diseases.