Au@Pt nanoparticles-based signal-enhanced lateral flow immunoassay for ultrasensitive naked-eye detection of SARS-CoV-2.

With SARS-CoV-2 N protein as a model target, a signal-enhanced LFIA based on Au@Pt nanoparticles (NPs) as labels is proposed. This Au@Pt NPs combined the distinguished localized surface plasma resonance (LSPR) effect of Au NPs and the ultrahigh peroxidase-like catalytic activity of Pt NPs. Au@Pt NPs could trigger substrate chromogenic reaction, generating a color signal orders of magnitude darker than their intrinsic color. In the detection, after the coloration of the strips, 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2 were added, and a dark blue chelate (OxTMB) was produced soon, enhancing the band color significantly. After the signal amplification, the naked-eye detection limit for N protein reached 40 pg/mL. The detection sensitivity enhanced more than 1000 times than that without signal amplification. Compared with mainstream LFIA requiring complex readout instruments, the Au@Pt-based LFIA achieved a comparable sensitivity using naked eyes detection. This point is crucial, especially for unprofessional users or low-resource areas. Hence, this signal-enhanced LFIA may serve as a sensitive, cost-effective, and user-friendly detection method. It can shorten the testing window period and help identify early infections.

An intramolecular charge transfer based fluorescent probe for imaging of OCl.

The discovery and utilization of new fluorescent chromophore is indispensable to exploit high performance probes for biological research. Stokes shift is one of the most important properties of chromophore accounting for super-resolution fluorescence imaging. Intramolecular charge transfer (ICT) is one of the fundamental mechanisms for fluorescence that accompanied by large Stokes shifts. Based on the conformational changes between ground and excited states, ICT models can be divided into two types: conformation-steady ICT, whose conformation remains unchanged, and conformation-changeable ICT, which is characterized by the rotation of the chromophore around an axis upon excitation. Herein, we report a new chromophore whose donor and acceptor parts took a butterfly geometry with a dihedral angle of 21° in ground state and a planar conformation upon photo excitation. The bent conformation might be ascribed to the extra conjugated double bond, which made the coplanarity of the chromophore in ground state get worse. The chromophore shows a remarkable Stokes shift over 150 nm and a high fluorescence quantum yieldof 0.62. The limit of detection is 41 nM, which enabled the imaging of basal as well as induced OCl- in different cells. Moreover, the pronounced spectroscopic properties ensure the in vivo monitoring of OCl- in arthritic mice. This finding would shed light on the exploitation of small molecule probes based on new fluorescence chromophore for precise biological imaging.

Engineered bacterium-metal-organic framework biohybrids for boosting radiotherapy with multiple effects.

Hypoxia and lactate-overexpressed tumor microenvironment always lead to poor therapeutic effect of radiotherapy. Here, platinum nanoparticles-embellished hafnium metal-organic framework (Hf-MOF-Pt NPs) were elaborately integrated with Shewanella oneidensis MR-1 (SO) to construct an engineered biohybrid platform (SO@Hf-MOF-Pt) for enhancing radiotherapy. Benefiting from the tumor-targeting and metabolic respiration characteristics of SO, SO@Hf-MOF-Pt could enrich in tumor sites and continuously metabolize the overexpressed lactate, which specifically downregulated the expression of hypoxia-inducible factor (HIF-1α), thereby relieving the radiosuppressive tumor microenvironment to some extent. Moreover, SO@Hf-MOF-Pt would react with tumor-overexpressed hydrogen peroxide (H2O2) to generate oxygen (O2) and further inhibit the expression of HIF-1α, resulting in the downregulation of lactate dehydrogenase (LDHA) and subsequently reducing the lactate production. Under these multiple cascaded effects, the radiosuppressive tumor microenvironment was significantly reshaped, thus potentiating the radiosentization of SO@Hf-MOF-Pt and remarkably amplifying the therapeutic outcomes of radiotherapy. The designed biohybrid SO@Hf-MOF-Pt represented promising prospects in sensitizing radiotherapy via bacterium-based metabolic regulation.

The contributory role of GSK3ß in hypertension exacerbating atherosclerosis by regulating the OMA1/PGC1α pathway.

Atherosclerosis is closely related to endothelial dysfunction and hypertension. GSK3ß is a critical regulator in atherosclerosis. This study was carried out to investigate the effects of GSK3ß on hypertension exacerbating atherosclerosis in vitro and in vivo. L-NAME + HFD-ApoE-/- mice were used for this study for 12 weeks, and their endothelial dysfunction and inflammation were analyzed. Oil red O and H&E staining revealed that treatment with LiCl, an inhibitor of GSK3ß, reduced atherosclerotic lesions and lipid accumulation. The levels of lipid homeostasis and oxidation stress were attenuated following LiCl administration. LiCl-treated ApoE-/- mice showed lowered blood pressure. LiCl also suppressed the expressions of Drp1, Bax, ICAM1, VCAM1 and TNF-α compared to HFD + L-NAME induced mice and oxLDL + L-NAME-treated Human aorta endothelial cell line(HAECs). LiCl treatment increased the expressions of MFN2 and Bcl2. Mitotracker-red, MitoSOX and JC-1 staining indicated that LiCl treatment reduced mitochondrial division and ROS production, increased mitochondrial ΔΨm compared to oxLDL + L-NAME-treated HAECs. The expression of OMA1 was decreased by LiCl treatment, while PGC1α expression was increased. In HAECs, we found that OMA1 knockdown increased mitochondrial function and the expression of PGC1α. We also demonstrated LiCl increased OMA1 ubiquitination compared with the Control group, thus decreased OMA1 expression. Furthermore, siOMA1 antagonized the increased protein expressions of ICAM1, VCAM1, TNF-α, Bax and Drp1, decreased the protein expressions of Bcl2 and MFN2 by siPGC1α. Taken together, we demonstrated that GSK3ß could play a contributory role in hypertension exacerbating atherosclerosis by regulating the OMA1/PGC1α pathway and inhibiting mitochondrial function.

Insights of Expression Profile of Chemokine Family in Inflammatory Bowel Diseases and Carcinogenesis.

Chemokines are integral components of the immune system and deeply involved in the pathogenesis and progression of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although a considerable amount of transcriptome data has been accumulated on these diseases, most of them are limited to a specific stage of the disease. The purpose of this study is to visually demonstrate the dynamic changes in chemokines across various stages of bowel diseases by integrating relevant datasets. Integrating the existing datasets for IBD and CRC, we compare the expression changes of chemokines across different pathological stages. This study collected 11 clinical databases from various medical centers around the world. Patients: Data of patient tissue types were classified into IBD, colorectal adenoma, primary carcinoma, metastasis, and healthy control according to the publisher's annotation. The expression changes in chemokines in various pathological stages are statistically analyzed. The chemokines were clustered by different expression patterns. The chemokine family was clustered into four distinct expression patterns, which correspond to varying expression changes in different stages of colitis and tumor development. Certain chemokines and receptors associated with inflammation and tumorigenesis have been identified. Furthermore, it was confirmed that the 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model and the azoxymethane (AOM)/ dextran sulfate sodium (DSS)-induced colon cancer model shows stronger correlations with the clinical data in terms of chemokine expression levels. This study paints a panoramic picture of the expression profiles of chemokine families at multiple stages from IBD to advanced colon cancer, facilitating a comprehensive understanding of the regulation patterns of chemokines and guiding the direction of drug development. This study provides researchers with a clear atlas of chemokine expression in the pathological processes of inflammatory bowel disease and colon cancer.

FBXO11 Mediates Ubiquitination of ZEB1 and Modulates Epithelial-to-Mesenchymal Transition in Lung Cancer Cells.

Epithelial-to-mesenchymal transition (EMT) affects the invasion and migration of cancer cells. Here, we show that FBXO11 recognizes and promotes ubiquitin-mediated degradation of ZEB1. There is a strong association between FBXO11 and ZEB1 in non-small cell lung cancer (NSLC) in a clinical database. FBXO11 interacts with ZEB1, a core inducer of EMT. FBXO11 leads to increased ubiquitination and proteasomal degradation of ZEB1. Depletion of endogenous FBXO11 causes ZEB1 protein accumulation and EMT in A549 and H1299 cells, while overexpression of FBXO11 reduces ZEB1 protein abundance and cellular invasiveness. Importantly, the depletion of ZEB1 suppresses the increased migration and invasion of A549 and H1299 cells promoted by the depletion of FBXO11. The same results are shown in xenograft tumors. High FBXO11 expression is associated with a favorable prognosis in NSLC. Collectively, our study demonstrates that FBXO11 modulates EMT by mediating the stability of ZEB1 in lung cancer cells.

Mechanistic insights into Suanzaoren Decoction's improvement of cardiac contractile function in anxiety-induced cardiac insufficiency.

ETHNOPHARMACOLOGICAL RELEVANCE: According to traditional Chinese medicine, Anxiety-induced cardiac blood insufficiency leads to palpitations and restlessness. Suanzaoren Decoction (SD) is effective in replenishing blood and promoting blood circulation. Clinical practice has shown that it has a better therapeutic effect on cardiac insufficiency. However, its mechanism of action is still unclear. AIM OF THE STUDY: The study aims to determine the mechanism by which SD treats chronic restraint stress (CRS)-induced anxiety-induced cardiac insufficiency (ACI). MATERIALS AND METHODS: SD was orally administered to mice with CRS-induced ACI. Firstly, we constructed an anxiety model in mice by CRS. Subsequently, SD was investigated to assess cardiac function and pathological changes through echocardiography, H&E staining, and Masson staining. Thirdly, the function of sympathetic and parasympathetic nerves was evaluated using enzyme-linked immunosorbent assay (ELISA) and enzyme activity assays. Network pharmacology and molecular docking were employed to predict potential targets for SD treatment of cardiac insufficiency. CaMKII expression was scrutinized utilizing publicly accessible databases. CaMKII was identified as a target through immunohistochemistry and Western Blot analysis in mouse hearts. Finally, the therapeutic mechanism of SD was confirmed in injured cardiomyocytes via Western Blot and quantitative PCR. RESULTS: SD exerted anxiolytic effects by increasing the frequency of entries into and the duration spent in open arms while reducing the time spent in the light chamber and increasing the number of transitions between light and dark chambers. Additionally, it mitigated cardiac insufficiency, as evidenced by the enhancement of left ventricular ejection fraction (LVEF) and attenuation of cardiomyocyte damage and inflammatory infiltration. However, SD did not alleviate the elevated norepinephrine (NE) and decreased Acetylcholine (Ach) in anxiety states. To investigate the mechanism of action of SD, we constructed a Drug-Component-Target-Disease network, identifying 13 potential active compounds. Additionally, leveraging bioinformatics analysis and molecular docking targeting heart diseases characterized by clinical left ventricular ejection fraction (LVEF), we focused on the CaMKII target. The ability of SD to modulate CaMKII expression and phosphorylation in the mouse heart was investigated using immunohistochemistry and Western blotting. SD was found to alleviate NE-injured cardiomyocytes by modulating the Ca2+/CaMKII/MEF2 and GATA4 pathways. CONCLUSION: SD is a potential formula for the treatment of chronic restraint stress (CRS)-induced ACI that ameliorates cardiomyocyte injury and improves cardiac function. Its efficacy is associated with the inhibition of the Ca2+/CaMKII/MEF2 and GATA4 signaling pathways.

Identification and Validation of IFI44 as a Novel Biomarker for Primary Sjögren's Syndrome.

Background: Primary Sjögren's syndrome (pSS) is an autoimmune condition marked by lymphocyte infiltration in the exocrine glands. Our study aimed to identify a novel biomarker for pSS to improve its diagnosis and treatment. Methods: The gene expression profiles of pSS were obtained from the Gene Expression Omnibus (GEO) database. The specific differentially expressed genes (DEGs) were screened by the Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), and Recursive Feature Elimination with Support Vector Machines (SVM-RFE). A biomarker was picked out based on correlation and diagnostic performance, the connection between the biomarker and clinical traits and immune infiltrating cells was explored, and the biomarker's protein expression level in the serum of pSS patients was detected by enzyme-linked immunosorbent assay (ELISA). The competitive endogenous RNA (ceRNA) network regulated by the biomarker was predicted to verify the reliability of the biomarker in diagnosing pSS. Results: IFI44, XAF1, GBP1, EIF2AK2, IFI27, and IFI6 showed prominent diagnostic ability, with the high accuracy (AUC = 0.859) and significance (R ≥ 0.8) of IFI44 within the training dataset. IFI44 strongly exhibited a negative correlation with resting NK cells, macrophages M0, and eosinophils, and a positive correlation with activated dendritic cells, naive B cells, and activated CD4 memory T cells. Furthermore, IFI44 was significantly positively correlated with clinical traits such as IgG, SSA, SSB, ANA, and ESSDAI, with its protein expression level in the serum of pSS patients being notably elevated compared to controls (p < 0.001). Finally, the ceRNA regulatory network showed that hsa-miR-944, hsa-miR-9-5p, hsa-miR-126-5p, and hsa-miR-335-3p were significantly targeted IFI44, suggesting that IFI44 may serve as a dependable biomarker for pSS. Conclusion: In this study, we dug out IFI44 as a biomarker for pSS, systematically studied the potential regulatory mechanism of IFI44, and verified its reliability as a biomarker for pSS.

Non-targeted metabolomics analysis of fermented traditional Chinese medicine and its impact on growth performance, serum biochemistry, and intestinal microbiome of weaned lambs.

Fermented traditional Chinese medicines (TCMs) have been identified as a low-cost and promising feed additive to to alleviate weaning stress in young livestock and poultry effectively. This study investigated the impact of probiotic fermentation on the metabolite content of BanQi (Radix Isatidis and Astragalus membranaceus) extract while also examined the effects of both fermented-BanQi (FBQ) and unfermented-BanQi (UBQ) on growth performance, serum biochemistry, intestinal villi, and gut microbiota in weaned lambs. This study demonstrated that compared with UBQ, FBQ contained significantly higher levels of free amino acids (e.g., phenylalanine and isoleucine), short peptides (e.g., Val-Leu-Pro-Val-Pro-Gln and Gly-Leu), and the active ingredients (e.g., vindesine and reserpine) (P < 0.05). The addition of FBQ to the diet significantly increased the final body weight and average daily gain of weaned lambs (P < 0.05). In addition, FBQ significantly increased the total protein level in the serum and the villus length of the jejunum and ileum in lambs, while significantly reduced the levels of aspartate aminotransferase (AST) and urea (P < 0.05). Sequencing of the intestinal flora showed that FBQ improved the diversity of intestinal flora and promoted the enrichment of beneficial bacteria in the lamb intestine, such as Mogibacterium and Butyrivibrio, compared to NC or UBQ groups (P < 0.05). Fermentation with Bacillus subtilis can enhance the content of free amino acids, peptides, and active ingredients in BanQi extract, making it an effective method to improve the efficacy of traditional Chinese medicine. Adding FBQ to the diet can improve the growth performance of weaned lambs, and its mechanism may be related to increasing the height of intestinal villi and increasing the diversity of intestinal flora.

Top 100 most-cited articles on pediatric anesthesia from 1990 to 2023.

Pediatric anesthesia presents greater challenges than does adult anesthesia. This bibliometric analysis aimed to analyze the top 100 most cited articles to be better understand the hot spots and prospects in pediatric anesthesia. Articles and reviews related to pediatric anesthesia were retrieved from the Web of Science Core Collection from 1990 to 2023. A bibliometric analysis of the top 100 most cited articles was also performed using information such as topics, author names, countries, institutions, publication years, and journals. A total of 32 831 articles were identified, with a total of 32 230 citations for the top 100 articles. The peak period for pediatric anesthesia research was from 2005 to 2009. The USA has emerged as the most active country in pediatric anesthesia research. Major journals published included Anesthesia and Analgesia, Anesthesiology, and Pediatrics, underscoring their authority in the field. Clinical studies on the top 100 most cited articles have focused on different stages of the perioperative period, the use of different anesthetic agents, and adverse outcomes in pediatric patients. The current study conducted a bibliometric analysis of the top 100 most cited articles in the field of pediatric anesthesia. Such insights are valuable for identifying research hot spots, assessing academic impact and collaboration in pediatric anesthesia, and guiding future research directions.

Exploring molecular mechanisms of exercise on metabolic syndrome: a bibliometric and visualization study using CiteSpace.

Objective: To investigate the molecular mechanisms through which exercise influences metabolic syndrome (MS) and identify key research trends and collaborative networks using bibliometric and visualization techniques. Methods: We conducted a systematic literature search using the Web of Science Core Collection for articles published from 2014 to 2023. Using CiteSpace, we performed a bibliometric analysis of 562 eligible papers, generating visual knowledge maps to identify prevailing patterns, popular subjects, and emerging trends in the literature. Results: The study reveals that exercise mitigates MS by reversing high-fat diet-induced abdominal obesity, reducing lipid accumulation and inflammation, enhancing insulin sensitivity, and improving cardiovascular function. Key molecular pathways include PPAR-γ/CPT-1/MCAD signaling, AMPK activation, and nitric oxide production. The USA leads in research output, with significant contributions from American institutions. Collaboration among researchers is limited, highlighting the need for more extensive and high-quality research initiatives. Conclusions: Regular, moderate-to-high-intensity exercise is crucial for managing MS. Exercise activates beneficial molecular pathways, improving metabolic health and cardiovascular function. Future research should focus on expanding collaborations and exploring novel molecular targets to enhance the therapeutic potential of exercise in metabolic syndrome management.

The regulatory effect of the anterior cingulate cortex on helping behavior in juvenile social isolation model mice.

Social isolation during adolescence negatively impacts the development of adult social behaviors. However, the exact link between social experiences during adolescence and social behaviors in adulthood is not fully understood. In the present study, we investigated how isolation during juvenility affects harm avoidance behavior in a mouse model of juvenile social isolation. We found that mice subjected to social isolation as juveniles display atypical harm avoidance behaviors and that neurons in the anterior cingulate cortex are involved in these abnormal behaviors. Furthermore, we discovered that the chemogenetic activation of anterior cingulate cortex pyramidal neurons can rescue impaired harm-avoidance behaviors in these mice. Our findings provide valuable insights into the potential mechanisms underlying the impact of social experiences on behavior and brain function. Understanding how social isolation during crucial developmental periods can lead to alterations in behavior opens up new avenues for exploring therapeutic interventions for neuropsychiatric disorders characterized by impaired prosocial behaviors.

Notopterygium incisum roots extract (NRE) alleviates neuroinflammation pathology in Alzheimer's disease through TLR4-NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Notopterygium incisum Ting ex H. T. Chang, also called 'Qianghuo', is a distinct umbelliferae plant in China. The rhizomes and roots of Notopterygium incisum have long been used to treat headaches, colds, analgesia and rheumatoid arthritis. It is a main traditional Chinese medicine in Qianghuo Yufeng Decoction, which was used to treat diseases such as liver and kidney insufficiency, mental paralysis and dementia. AIM OF THIS STUDY: As the most common dementia, Alzheimer's disease (AD) has a complicated pathogenesis. So far, there is no effective drug to prevent its pathological process. Previous research has shown that Notopterygium incisum root extract (NRE) may inhibit the release of Aß and the activation of tau in mice with AD. However, the effect of NRE on the pathological process of neuroinflammation is still unclear. MATERIALS AND METHODS: We determined the pro-inflammatory cytokines levels in BV2 cells exposed to LPS/Aß42 after treated with NRE. APP/PS1 and LPS-induced C57BL/6 neuroinflammatory mice were given NRE for 8 weeks and 5 days respectively to detect the pathological changes of neuroinflammation. RESULTS: The findings showed that NRE had a notable inhibitory effect on the levels of TNF-α and IL-1ß in BV2 cells induced by LPS/Aß42. The results of in vivo experiments show that following NRE treatment, there was a notable decrease in the number of activated microglia in the hippocampus of APP/PS1 mice as indicated by immunofluorescence results. Sholl analysis showed that microglia branches increased in NRE group, indicating that M1 microglia activation was inhibited. In the mice model injected with LPS in the tail vein, PCR and Western Blot results confirmed the anti-inflammatory effect of NRE, Nissl staining showed the protective effect of NRE on neurons, and immunofluorescence results also indicated that the activation of M1 microglia was inhibited. CONCLUSION: These results suggest that long term oral administration of NRE may inhibit neuroinflammation in the progression of AD.

Bibliometric Analysis of TREM2 (2001-2022): Trends, Hotspots and Prospects in Human Disease.

Background: Triggering receptor expressed in myeloid cells 2 (TREM2), a transmembrane receptor, has garnered extensive research attention due to its pivotal role in the diagnosis and treatment of various diseases. Despite the abundance of studies on its function, there is a gap in comprehensive analysis and summarization of the current state of this research field. Methods: Articles and reviews related to TREM2 were retrieved from the Web of Science Core Collection (WOSCC) on October 1, 2023. A bibliometric analysis of TREM2 was conducted using CiteSpace, VOSviewer and Bibliometrix (R package). Results: A total of 1,502 articles, spanning from 2001 to 2022, met the search criteria. The number of publications and citations has increased steadily over the years. The United States and China are the most active countries in TREM2 research, with the University of Washington as the leading research institution. The most influential journal in the field is Neurology of Aging. The predominant research areas include molecular, biology and immunology. Alzheimer's disease, microglia, variants, and inflammation are significant keywords. Emerging directions such as metabolism and tumor microenvironment have recently gained attention in numerous studies. Conclusion: The current study utilizes bibliometric analysis software and visual graphics to intuitively highlight TREM2-related hotspots, trends, and prospects in human disease. Such insights are valuable for scholars seeking a deeper understanding of TREM2-related research progress, enabling a focused approach to its application in human disease.

Mechanisms of exercise intervention in type 2 diabetes: a bibliometric and visualization analysis based on CiteSpace.

Objective: Type 2 diabetes (T2D) is a common chronic metabolic disease, and its prevalence is increasing globally. Exercise is crucial for T2D management, yet many aspects of its mechanisms remain unclear. This study employs CiteSpace to reveal research hotspots and frontier issues in exercise intervention for T2D. Method: A literature review spanning from January 1, 2013 to December 31, 2022, was conducted using the Web of Science Core Collection (WoSCC), with keywords including "exercise," "type 2 diabetes," and "mechanisms." We analyzed network diagrams generated by CiteSpace, which depicted relationships among countries, authors, and keywords. Results: This study includes 1,210 English papers from 555 journals, affiliated with 348 institutions across 80 countries/regions. Notably, the United States, China, and the United Kingdom account for nearly half of all publications. The University of Copenhagen leads in publication volume, followed by Harvard Medical School and the University of Colorado. Key authors include Kirwan, John P (Case Western Reserve University), Malin, Steven K (Rutgers University), and Pedersen, Bente Klarlund (University of Copenhagen). Based on co-occurrence analysis of keywords, it is evident that terms such as "disease," "glucagon-like peptide 1," and "cardiovascular risk factor" exhibit high intermediary centrality. Conclusion: The analysis highlights ongoing investigations into molecular mechanisms, such as ß-cell function enhancement, exerkines, and epigenetic mechanisms. Emerging areas include exercise response heterogeneity, circadian rhythm regulation, transcription factors, neurotrophic factors, and mitochondrial function. Future studies should prioritize understanding interactions between different exercise mechanisms and optimizing exercise prescriptions for T2D. Exercise prescriptions are crucial for effective interventions. Collaboration between countries and institutions is essential to understand the influences of different genetic backgrounds and environmental factors. Currently, a combination of aerobic and resistance training is considered the optimal form of exercise. However, considering time efficiency, high-intensity interval training (HIIT) has gained widespread attention and research due to its ability to achieve similar exercise effects in a shorter duration. Additionally, circadian rhythm regulation may affect the exercise outcomes of diabetic individuals at different times of the day, particularly concerning the specific types, doses, and intensities used for precision intervention in T2D.

Comparison Between Esketamine and Alfentanil for Hysteroscopy: A Prospective, Double-Blind, Randomized Controlled Trial.

Purpose: This study aimed to establish the 95% effective dose (ED95) of esketamine in combination with propofol for hysteroscopy and then to evaluate its efficacy and safety profile. Patients and Methods: This prospective, double-blind, randomized controlled trial consisted of two cohorts. In cohort 1, 45 women aged 18-65 years undergoing hysteroscopy were randomly assigned to either group E (esketamine + propofol) or group A (alfentanil + propofol). Dixon's up-and-down method was used to determine the ED95 of esketamine and alfentanil. In cohort 2, 86 patients were randomized to group E and group A, with the calculated ED95 dose of the study drugs used for induction. The success rate of anesthesia using the ED95% dose, along with parameters related to anesthesia induction, recovery, and adverse events were also recorded. Results: The ED95 of esketamine was 0.254 mg/kg (95% CI: 0.214-1.004), while that of alfentanil was 9.121 µg/kg (95% CI: 8.479-13.364). The anesthesia success rate was 93.0% in group E and 95.2% in group A (p = 0.664). After resuscitation, both groups achieved a 100% success rate. The induction time was significantly shorter in group E (60.0 [55.0-70.0] s) compared to group A (67.0 [61.0-79.3] s) (p = 0.006). Group E had lower rates of respiratory depression (p < 0.001), hypoxia (p = 0.006), minimum perioperative SpO2 (p = 0.010), and hypotension (p = 0.001). Esketamine had less effect on respiratory rate, heart rate, mean blood pressure, and end-tidal carbon dioxide compared to alfentanil (all p < 0.001). There were no significant differences in postoperative pain between the two groups. Conclusion: This study determined the ED 95 dose of esketamine for intravenous general anesthesia during hysteroscopy. Esketamine showed less respiratory and hemodynamic depression, as well as fewer adverse effects compared to alfentanil. Esketamine is an ideal anesthetic agent compared to alfentanil for hysteroscopic anesthesia. Trial Registration: www.chictr.org.cn, (ChiCTR2300077283); registered November 3, 2023.

Depression and suicidal ideation among Chinese college students during the COVID-19 pandemic: the mediating roles of chronotype and sleep quality.

BACKGROUND: This study was intended to investigate the correlation between depression and suicidal ideation among Chinese college students during the COVID-19 pandemic and the potential mediating roles of chronotype and sleep quality in this relationship . METHODS: A sample of 4,768 college students was selected from four institutions in Anhui Province, China, and the study was conducted during the COVID-19 pandemic (November to December 2020) using a stratified, cluster, multi-stage sampling method. This study used the two-item Patient Health Questionnaire (PHQ-2) to assess depressive symptoms, the Morningness-Eveningness Questionnaire 19 (MEQ-19) to determine individual sleep chronotypes (i.e., morning or evening preference), and the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep quality. Participants were asked about suicidal ideation. MPLUS 8.3 software was used to analyze the mediating effect of chronotype and sleep quality on the relationship between depression and suicidal ideation. RESULTS: During the COVID-19 pandemic, the prevalence of suicidal ideation among Chinese college students was 5.4%. Depression was inversely correlated with chronotype (beta = - 0.346, P < 0.01) and positively correlated with sleep quality (beta = 0.846, P < 0.001), indicating that students experiencing depressive symptoms were more likely to have a later chronotype and poor sleep quality. A later chronotype (beta = - 0.019, P < 0.05) and poor sleep quality (beta = 0.066, P < 0.01) predicted suicidal ideation. Depression emerged as a direct and significant risk factor for suicidal ideation (effect value = 0.535, 95% confidence interval: 0.449 ~ 0.622). Chronotype and sleep quality were found to have potential mediating effects on the relationship between depression and suicidal ideation; however, the chain-mediating effect of chronotype and sleep quality was not statistically significant. CONCLUSIONS: Our findings suggest that during the COVID-19 pandemic, depression can precipitate suicidal ideation through its influence on sleep chronotype and quality. These compelling findings highlight the urgency of early intervention strategies intended to mitigate suicidal thoughts, particularly among students exhibiting depressive symptoms, who experience disrupted sleep patterns and poor sleep quality.

Hypoxia-induced LAMB2-enriched extracellular vesicles promote peritoneal metastasis in gastric cancer via the ROCK1-CAV1-Rab11 axis.

Peritoneal metastasis is one of the most common risk factors contributing to the poor prognosis of gastric cancer. We previously reported that extracellular vesicles from gastric cancer cells could facilitate peritoneal metastasis. However, their impact on gastric cancer-induced peritoneal metastasis under hypoxic conditions remains unclear. This study aims to elucidate how hypoxia-resistant gastric cancer cell-derived extracellular vesicles affect the peritoneal metastasis of normoxic gastric cancer cells. Proteomic analysis revealed elevated levels of Caveolin1 and Laminin ß2 in hypoxia-resistant gastric cancer cells and their corresponding extracellular vesicles. Importantly, Caveolin1 was found to play a central role in mediating Laminin ß2 sorting into extracellular vesicles derived from hypoxia-resistant gastric cancer cells, and subsequently, extracellular vesicle-associated Laminin ß2 promoted peritoneal metastasis in normoxic gastric cancer cells by activating the AKT pathway. Further investigation confirmed that Caveolin1 activation by Rho-related Coiled-coil kinase 1-mediated phosphorylation of Y14 residue is a key factor facilitating Laminin ß2 sorting into extracellular vesicles. Moreover, Y14 phosphorylated- Caveolin1 enhanced Laminin ß2 sorting by activating Rab11. Finally, our study demonstrated that a combined assessment of plasma extracellular vesicle-associated Caveolin1 and extracellular vesicle-associated Laminin ß2 could provide an accurate predictive tool for peritoneal metastasis occurrence in gastric cancer.