The association of isocarbophos and isofenphos with different types of glucose metabolism: The role of inflammatory cells.

To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.

Genome-wide identification and expression analysis of calmodulin and calmodulin-like genes in passion fruit (Passiflora edulis) and their involvement in flower and fruit development.

BACKGROUND: The calmodulin (CaM) and calmodulin-like (CML) proteins play regulatory roles in plant growth and development, responses to biotic and abiotic stresses, and other biological processes. As a popular fruit and ornamental crop, it is important to explore the regulatory mechanism of flower and fruit development of passion fruit. RESULTS: In this study, 32 PeCaM/PeCML genes were identified from passion fruit genome and were divided into 9 groups based on phylogenetic analysis. The structural analysis, including conserved motifs, gene structure and homologous modeling, illustrates that the PeCaM/PeCML in the same subgroup have relative conserved structural features. Collinearity analysis suggested that the expansion of the CaM/CML gene family likely took place mainly by segmental duplication, and the whole genome replication events were closely related with the rapid expansion of the gene group. PeCaM/PeCMLs were potentially required for different floral tissues development. Significantly, PeCML26 had extremely high expression levels during ovule and fruit development compared with other PeCML genes, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. The co-presence of various cis-elements associated with growth and development, hormone responsiveness, and stress responsiveness in the promoter regions of these PeCaM/PeCMLs might contribute to their diverse regulatory roles. Furthermore, PeCaM/PeCMLs were also induced by various abiotic stresses. This work provides a comprehensive understanding of the CaM/CML gene family and valuable clues for future studies on the function and evolution of CaM/CML genes in passion fruit. CONCLUSION: A total of 32 PeCaM/PeCML genes were divided into 9 groups. The PeCaM/PeCML genes showed differential expression patterns in floral tissues at different development stages. It is worth noting that PeCML26, which is highly homologous to AtCaM2, not only interacts with multiple BBR-BPC TFs, but also has high expression levels during ovule and fruit development, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. This research lays the foundation for future investigations and validation of the potential function of PeCaM/PeCML genes in the growth and development of passion fruit.

Pathogenesis of depression and the potential for traditional Chinese medicine treatment.

Depression is a prevalent mental disorder that significantly diminishes quality of life and longevity, ranking as one of the primary causes of disability globally. Contemporary research has explored the potential pathogenesis of depression from various angles, encompassing genetics, neurotransmitter systems, neurotrophic factors, the hypothalamic-pituitary-adrenal axis, inflammation, and intestinal flora, among other contributing factors. In addition, conventional chemical medications are plagued by delayed onset of action, persistent adverse effects, and restricted therapeutic efficacy. In light of these limitations, the therapeutic approach of traditional Chinese medicine (TCM) has gained increasing recognition for its superior effectiveness. Numerous pharmacological and clinical studies have substantiated TCM's capacity to mitigate depressive symptoms through diverse mechanisms. This article attempts to summarize the mechanisms involved in the pathogenesis of depression and to describe the characteristics of herbal medicines (including compounded formulas and active ingredients) for the treatment of depression. It further evaluates their effectiveness by correlating with the multifaceted pathogenesis of depression, thereby furnishing a reference for future research endeavors.

Programmable Chemical Evolution with Natural/non-natural Building Blocks.

Non-natural building blocks (BBs) present a vast reservoir of chemical diversity for molecular recognition and drug discovery. However, leveraging evolutionary principles to efficiently generate bioactive molecules with a larger number of diverse BBs poses challenges within current laboratory evolution systems. Here, we introduce programmable chemical evolution (PCEvo) by integrating chemoinformatic classification and high-throughput array synthesis/screening. PCEvo initiates evolution by constructing a diversely combinatorial library to create ancestral molecules, streamlines the molecular evolution process and identifies high-affinity binders within 2-4 cycles. By employing PCEvo with 108 BBs and exploring >10^17 chemical space, we identify bicyclic peptidomimetic binders against targets SAR-CoV-2 RBD and Claudin18.2, achieving nanomolar affinity. Remarkably, Claudin18.2 binders selectively stain gastric adenocarcinoma cell lines and patient samples. PCEvo achieves expedited evolution in a few rounds, marking a significant advance in utilizing non-natural building blocks for rapid chemical evolution applicable to targets with or without prior structural information and ligand preference.

Corrigendum to "Active components of Dengzhan Shengmai ameliorate cognitive impairment by facilitating hippocampal long-term potentiation via the NMDA receptor-mediated Ca2+/CaMKII pathway" [J. Pharm. Anal. 14 (2024) 435-438].

[This corrects the article DOI: 10.1016/j.jpha.2023.09.016.].

Solvothermal Preparation of Crystal Seeds and Anisotropy-Controlled Growth of Silver Nanoplates.

We synthesized silver nanoplates using the solvothermal method and, for the first time, placed them as crystal seeds in a water-based growth solution, thereby successfully achieving the large-scale production of silver nanoplates. The synthesis method enabled independent control of the lateral size and vertical size of the silver nanoplates. More specifically, the lateral size could be adjusted within the range of 565 nm-1.682 µm, while the vertical size was achieved by introducing Cl- as a capping agent and the vertical size was thickened from 18.28 to 40.41 nm.

Effect of α7 nAChR-autophagy axis of deciduous tooth pulp stem cells in regulating IL-1ß in the process of physiological root resorption of deciduous teeth.

Physiological root resorption of deciduous teeth is a normal phenomenon occurring during the developmental stages of children. Previous research has indicated the pivotal role of the inflammatory microenvironment in this process, although the specific mechanisms remain unclear. This study is aimed at elucidating the involvement of the alpha7 nicotinic acetylcholine receptors (α7 nAChR)-autophagy axis in the regulation of the inflammatory microenvironment during physiological root resorption in deciduous teeth. Samples were collected from deciduous teeth at various stages of physiological root resorption, and deciduous dental pulp stem cells (DDPSCs) were isolated and cultured during the mid-phase of root resorption. The findings revealed a substantial infiltration of the pulp of deciduous teeth at the mid-phase of root resorption, characterized by elevated expression levels of α7 nAChR and IL-1ß. Significantly increased IL-1ß and α7 nAChR expressions were observed in DDPSCs during the mid-phase of root resorption, with α7 nAChR demonstrating a regulatory effect on IL-1ß. Moreover, evidence suggested that mechanical stress may act as a trigger, regulating autophagy and IL-1 expression via α7 nAChR. In conclusion, mechanical stress was identified as a regulator of autophagy in DDPSCs through α7 nAChR, influencing the expression of IL-1ß and contributing to the formation of the inflammatory microenvironment. This mechanism plays a crucial role in the physiological root resorption of deciduous teeth. KEY MESSAGES: The pulp of deciduous teeth at mid-phase of root resorption was heavily infiltrated with high expression of α7nAChR and IL-1ß. α7 nAChR acts as an initiating factor to regulate IL-1ß through autophagy in DDPSCs. Mechanical stress can regulate autophagy of DDPSCs through α7 nAChR and thus affect IL-1ß expression and inflammatory microenvironment formation in physiological root resorption in deciduous teeth.

Telehealth Availability for Mental Health Care During and After the COVID-19 Public Health Emergency.

Importance: Telehealth services expanded rapidly during the COVID-19 public health emergency (PHE). Objective: To evaluate changes in availability of telehealth services at outpatient mental health treatment facilities (MHTFs) throughout the US during and after the COVID-19 PHE. Design, Setting, and Participants: In this cohort study, callers posing as prospective clients contacted a random sample of 1404 MHTFs drawn from the Substance Abuse and Mental Health Services Administration's Behavioral Health Treatment Locator from December 2022 to March 2023 (wave 1 [W1]; during PHE). From September to November 2023 (wave 2 [W2]; after PHE), callers recontacted W1 participants. Analyses were conducted in January 2024. Main Outcomes and Measures: Callers inquired whether MHTFs offered telehealth (yes vs no), and, if yes, whether they offered (1) audio-only telehealth (vs audio and video); (2) telehealth for therapy, medication management, and/or diagnostic services; and (3) telehealth for comorbid alcohol use disorder (AUD). Sustainers (offered telehealth in both waves), late adopters (did not offer telehealth in W1 but did in W2), nonadopters (did not offer telehealth in W1 or W2), and discontinuers (offered telehealth in W1 but not W2) were all compared. Results: During W2, 1001 MHTFs (86.1%) were successfully recontacted. A total of 713 (71.2%) were located in a metropolitan county, 151 (15.1%) were publicly operated, and 935 (93.4%) accepted Medicaid as payment. The percentage offering telehealth declined from 799 (81.6%) to 765 (79.0%) (odds ratio [OR], 0.84; 95% CI, 0.72-1.00; P < .05). Among MHTFs offering telehealth, a smaller percentage in W2 offered audio-only telehealth (369 [49.3%] vs 244 [34.1%]; OR, 0.53; 95% CI, 0.44-0.64; P < .001) and telehealth for comorbid AUD (559 [76.3%] vs 457 [66.5%]; OR, 0.62; 95% CI, 0.50-0.76; P < .001) compared with W1. In W2, MHTFs were more likely to report telehealth was only available under certain conditions for therapy (141 facilities [18.0%] vs 276 [36.4%]; OR, 2.62; 95% CI, 1.10-3.26; P < .001) and medication management (216 facilities [28.0%] vs 304 [41.3%]; OR, 1.81; 95% CI, 1.48-2.21; P < .001). A total of 684 MHTFs (72.0%) constituted sustainers, 94 (9.9%) were discontinuers, 106 (11.2%) were nonadopters, and 66 (7.0%) were late adopters. Compared with sustainers, discontinuers were less likely to be private for-profit (adjusted OR [aOR], 0.28; 95% CI, 0.11-0.68) or private not-for-profit (aOR, 0.26; 95% CI, 0.14-0.48) after adjustment for facility and area characteristics. Conclusions and Relevance: Based on this longitudinal cohort study of 1001 MHTFs, telehealth availability has declined since the PHE end with respect to scope and modality of services, suggesting targeted policies may be necessary to sustain telehealth access.

Overexpression of AcWRKY31 Increases Sensitivity to Salt and Drought and Improves Tolerance to Mealybugs in Pineapple.

Pineapple is a globally significant tropical fruit, but its cultivation faces numerous challenges due to abiotic and biotic stresses, affecting its quality and quantity. WRKY transcription factors are known regulators of stress responses, however, their specific functions in pineapple are not fully understood. This study investigates the role of AcWRKY31 by overexpressing it in pineapple and Arabidopsis. Transgenic pineapple lines were obtained using Agrobacterium-mediated transformation methods and abiotic and biotic stress treatments. Transgenic AcWRKY31-OE pineapple plants showed an increased sensitivity to salt and drought stress and an increased resistance to biotic stress from pineapple mealybugs compared to that of WT plants. Similar experiments in AcWRKY31-OE, AtWRKY53-OE, and the Arabidopsis Atwrky53 mutant were performed and consistently confirmed these findings. A comparative transcriptomic analysis revealed 5357 upregulated genes in AcWRKY31-OE pineapple, with 30 genes related to disease and pathogen response. Notably, 18 of these genes contained a W-box sequence in their promoter region. A KEGG analysis of RNA-Seq data showed that upregulated DEG genes are mostly involved in translation, protein kinases, peptidases and inhibitors, membrane trafficking, folding, sorting, and degradation, while the downregulated genes are involved in metabolism, protein families, signaling, and cellular processes. RT-qPCR assays of selected genes confirmed the transcriptomic results. In summary, the AcWRKY31 gene is promising for the improvement of stress responses in pineapple, and it could be a valuable tool for plant breeders to develop stress-tolerant crops in the future.

Hydroxychloroquine blood concentrations and effects in Chinese patients with IgA nephropathy.

BACKGROUND: Hydroxychloroquine (HCQ) is recommended for Chinese patients with immunoglobulin A nephropathy (IgAN). However, the relationship between HCQ blood concentration and the therapeutic effect for IgAN has not yet been defined. This study investigates the optimal and efficacious range of HCQ blood concentrations in Chinese patients with IgAN. METHODS: Seventy-three patients with biopsy-proven IgAN who were at risk of progression were included in this study. Thirty-eight patients with IgAN were treated with HCQ plus an optimized renin-angiotensin-aldosterone system inhibitor (RAASi), and thirty-five patients received only RAASi. Blood HCQ concentration and 24-h proteinuria were examined at three and six months after treatment. RESULTS: The baseline proteinuria levels were comparable between the RAASi and HCQ groups. The HCQ group had lower 24-h proteinuria than the RAASi group three months after treatment, though the difference was not significant (p = 0.38). After six months, the median proteinuria level was significantly lower in the HCQ group than in the RAASi group (p < 0.05). The percentage reduction in 24-h proteinuria in the HCQ group was greater than that in the RAASi group at three (p < 0.05) and six months (p < 0.05). Hydroxychlorquine blood concentration and efficacy were positively correlated at three months (r = 0.428, p < 0.05) and six months (r = 0.48, p < 0.05). Moreover, the optimal blood concentration of HCQ for three-month efficacy was 418.96 ng/mL and that for six-month efficacy was 582.48 ng/mL. No serious adverse events were reported during HCQ treatment. CONCLUSIONS: Hydroxyhloroquine safely reduces proteinuria in Chinese patients with IgAN. The efficacy of HCQ is positively correlated with its blood concentration.

Evolution and Functional Differentiation of the C-terminal Motifs of FtsZs During Plant Evolution.

Filamentous temperature-sensitive Z (FtsZ) is a tubulin-like GTPase that is highly conserved in bacteria and plants. It polymerizes into a ring at the division site of bacteria and chloroplasts and serves as the scaffold protein of the division complex. While a single FtsZ is present in bacteria and cyanobacteria, there are two subfamilies, FtsZ1 and FtsZ2 in the green lineage, and FtsZA and FtsZB in red algae. In Arabidopsis thaliana, the C-terminal motifs of AtFtsZ1 (Z1C) and AtFtsZ2-1 (Z2C) display distinct functions in the regulation of chloroplast division. Z1C exhibits weak membrane-binding activity, whereas Z2C engages in the interaction with the membrane protein AtARC6. Here, we provide evidence revealing the distinct traits of the C-terminal motifs of FtsZ1 and FtsZ2 throughout the plant evolutionary process. In a range of plant species, the C-terminal motifs of FtsZ1 exhibit diverse membrane-binding properties critical for regulating chloroplast division. In chlorophytes, the C-terminal motifs of FtsZ1 and FtsZ2 exhibit both membrane-binding and protein interaction functions, which are similar to those of cyanobacterial FtsZ and red algal FtsZA. During the transition from algae to land plants, the functions of the C-terminal motifs of FtsZ1 and FtsZ2 exhibit differentiation. FtsZ1 lost the function of interacting with ARC6 in land plants, and the membrane-binding activity of FtsZ2 was lost in ferns. Our findings reveal the functional differentiation of the C-terminal motifs of FtsZs during plant evolution, which is critical for chloroplast division.

Cu-Doping Layered Double Hydroxides Nanozyme Integrated with Nitric Oxide Donor for Enhanced Antioxidant Therapy in Retinopathy.

The prevalence of retinal neovascular diseases necessitates novel treatments beyond current therapies like laser surgery or anti-VEGF treatments, which often carry significant side effects. A novel therapeutic approach is introduced using copper-containing layered double hydroxides (Cu-LDH) nanozymes integrated with nitric oxide-releasing molecules (GSHNO), forming Cu-LDH@GSHNO aimed at combating oxidative stress within the retinal vascular system. Combination of synthetic chemistry and biological testing, Cu-LDH@GSHNO are synthesized, characterized, and assessed for curative effect in HUVECs and an oxygen-induced retinopathy (OIR) mouse model. The results indicate that Cu-LDH@GSHNO demonstrates SOD-CAT cascade catalytic ability, accompanied with GSH and nitric oxide-releasing capabilities, which significantly reduces oxidative cell damage and restores vascular function, presenting a dual-function strategy that enhances treatment efficacy and safety for retinal vascular diseases. The findings encourage further development and clinical exploration of nanozyme-based therapies, promising a new horizon in therapeutic approaches for managing retinal diseases driven by oxidative stress.

Antithrombotic therapy at discharge and prognosis in patients with chronic coronary syndrome and atrial fibrillation who underwent PCI: a real-world study.

BACKGROUND: This study aimed to describe the status of antithrombotic therapy at discharge and prognosis in patients with atrial fibrillation (AF) and chronic coronary syndrome (CCS) who underwent percutaneous coronary intervention (PCI). METHODS: This was an observational, prospective study. The primary endpoint was major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke/transient ischemic attach (TIA), systemic embolism or ischemia-driven revascularization. Bleeding events were collected according to the Thrombolysis in Myocardial Infarction (TIMI) criteria. RESULTS: Between 2017 and 2019, a cohort of 516 patients (mean age 66, [SD 9], of whom 18.4% were female) with AF and CCS who underwent PCI were evaluated, with a median followed-up time of 36 months (Interquartile range: 22-45). MACE events occurred in 13.0% of the patients, while the TIMI bleeding events were observed in 17.4%. Utilization of TAT (triple antithrombotic therapy) (P < 0.001) and oral anticoagulation (OAC) therapy (P < 0.001) increased through years. History of heart failure (HF) (Hazard ratio [HR], 1.744; 95% confidence interval [CI], 1.011-3.038) and TAT (HR, 2.708; 95%CI, 1.653-4.436) had independent associations with MACE events. OAC (HR, 10.378; 95%CI, 6.136-17.555) was identified as a risk factor for bleeding events. A higher creatine clearance (HR, 0.986; 95%CI, 0.974-0.997) was associated with a lower incidence of bleeding events. CONCLUSIONS: Antithrombotic therapy has been improved among patients with AF and CCS who underwent PCI these years. History of HF and TAT were independently associated with MACE events. Higher creatine clearance was protective factor of bleeding events, while OAC was a risk factor for TIMI bleeding events.

Selectively T cell phosphorylation activation of azvudine in the thymus tissue with immune protection effect.

Thymus is the important immune organ, responsible for T cell development and differentiation. The lower circulating T counts have been observed in patients who died from COVID-19 compared with survivors. Azvudine, also known as FNC, is a thymus-homing anti-SARS-CoV-2 drug in treating COVID-19 patients. In this study, single-cell transcriptome, proteomics, and parallel reaction monitoring (PRM) were applied to insight into the activation process of FNC in rat and SARS-CoV-2 rhesus monkey thymus. The results indicated that thymic immune cells possess a robust metabolic capacity for cytidine-analogue drugs such as FNC. Key enzymes involved in the FNC phosphorylation process, such as Dck, Cmpk1, and Nme2, were highly expressed in CD4+ T cells, CD8+ T cells, and DP (CD4+ CD8+) cells. Additionally, FNC could upregulate multiple phosphorylated kinases in various cell types while downregulating the phosphatases, phosphoribosyl transferases, and deaminases, respectively. The robust phosphorylation capacity of the thymus for cytidine analogue drug FNC, and the activation effect of FNC on the NAs metabolism system potentially contribute to its enrichment in the thymus and immune protection effect. This suggests that it is crucial to consider the expression level of phosphorylation kinases when evaluating NA drug properties, as an important factor during antiviral drug design.

Cholinergic nucleus degeneration and its association with gait impairment in Parkinson's disease.

BACKGROUND: The contribution of cholinergic degeneration to gait disturbance in Parkinson's disease (PD) is increasingly recognized, yet its relationship with dopaminergic-resistant gait parameters has been poorly investigated. We investigated the association between comprehensive gait parameters and cholinergic nucleus degeneration in PD. METHODS: This cross-sectional study enrolled 84 PD patients and 69 controls. All subjects underwent brain structural magnetic resonance imaging to assess the gray matter density (GMD) and volume (GMV) of the cholinergic nuclei (Ch123/Ch4). Gait parameters under single-task (ST) and dual-task (DT) walking tests were acquired using sensor wearables in PD group. We compared cholinergic nucleus morphology and gait performance between groups and examined their association. RESULTS: PD patients exhibited significantly decreased GMD and GMV of the left Ch4 compared to controls after reaching HY stage > 2. Significant correlations were observed between multiple gait parameters and bilateral Ch123/Ch4. After multiple testing correction, the Ch123/Ch4 degeneration was significantly associated with shorter stride length, lower gait velocity, longer stance phase, smaller ankle toe-off and heel-strike angles under both ST and DT condition. For PD patients with HY stage 1-2, there were no significant degeneration of Ch123/4, and only right side Ch123/Ch4 were corrected with the gait parameters. However, as the disease progressed to HY stage > 2, bilateral Ch123/Ch4 nuclei showed correlations with gait performance, with more extensive significant correlations were observed in the right side. CONCLUSIONS: Our study demonstrated the progressive association between cholinergic nuclei degeneration and gait impairment across different stages of PD, and highlighting the potential lateralization of the cholinergic nuclei's impact on gait impairment. These findings offer insights for the design and implementation of future clinical trials investigating cholinergic treatments as a promising approach to address gait impairments in PD.

Diffuse large B-cell lymphoma with central nervous system symptoms during the maintenance therapy of acute lymphoblastic leukemia: a case report and literature review.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) secondary to acute lymphoblastic leukemia (ALL) is a rare disease with poor prognosis, usually attributed to delayed diagnosis. To date, only four cases of ALL developing DLBCL have been reported, while none of them exhibiting central nervous system (CNS) symptoms. CASE DESCRIPTION: Here, we report an unusual case of a 15-year-old boy diagnosed with ALL and treated based on the SCCLG-ALL 2016 protocol. While he was receiving maintenance treatment, the patient developed dizziness and vomiting. An Epstein-Barr virus (EBV)-positive DLBCL with CNS involvement was diagnosed from inguinal lymph nodes biopsy, EBV DNA tests and head magnetic resonance imaging (MRI). Meanwhile, a dramatic decrease of immune cells and immunoglobulin was detected in the occurrence of DLBCL. He received therapy based on SCCCG-NHL-2017 protocol immediately after the diagnosis. CONCLUSIONS: We present the first retrospective report of four cases of non-Hodgkin lymphoma (NHL) secondary to ALL between 1990 and 2022. The pathogenesis of secondary DLBCL may be related to infection, immunodeficiency, genetic susceptibility, and treatment. Thus, the detection of EBV DNA during the full course of ALL therapy and genetic tests were needed in the occurrence of secondary DLBCL. Given to the rare rate and insufficient treatment experience, longer follow-up and enough sample size are needed.

In Vitro and In Vivo Evaluation of Lactoferrin-Modified Liposomal Etomidate with Enhanced Brain-Targeting Effect for General Anesthesia.

Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage forms having been reported for this drug, formulation types are very limited in clinical practice, and brain-targeted formulations for this central nervous system (CNS) drug have been rarely reported. Moreover, studies on the biocompatibility, toxicity, and anesthetic effects of the etomidate preparations in vivo were inadequate. The present study was to develop lactoferrin-modified liposomal etomidate (Eto-lip-LF) for enhanced drug distribution in the brain and improved anesthetic effects. Eto-lip-LF had good stability for storage and hemocompatibility for intravenous injection. Compared with the non-lactoferrin-containing liposomes, the lactoferrin-modified liposomes had notably enhanced brain-targeting ability in vivo, which was probably realized by the binding of transferrin with the transferrin and lactoferrin receptors highly distributed in the brain. Eto-lip-LF had a therapeutic index of about 25.3, higher than that of many other general anesthetics. Moreover, compared with the commercial etomidate emulsion, Eto-lip-LF could better achieve rapid onset of general anesthesia and rapid recovery from anesthesia, probably due to the enhanced drug delivery to the brain. The above results demonstrated the potential of this lactoferrin-modified liposomal etomidate to become an alternative preparation for clinical general anesthesia.

Case report: Clinical features of pediatric acute myeloid leukemia presenting with cardiac tamponade: a case series study and literature review.

Objective: This study aims to elucidate the clinical features observed in cases of pediatric acute myeloid leukemia (AML) initially presenting with cardiac tamponade and to share treatment experiences. Materials and methods: Five pediatric patients were initially diagnosed with AML accompanied by cardiac myeloid sarcoma (MS). The diagnosis was established by examining our hospital records and reviewing pertinent literature from 1990 to July 2023, accessible through MEDLINE/PubMed. We comprehensively assessed the clinical characteristics and treatment modalities employed for these patients. Result: Five pediatric patients presented with acute symptoms, including shortness of breath, malaise, cough, and fever, leading to their hospitalization. Physical examination revealed irritability, hypoxia, tachypnea, tachycardia, and hypotension. Initial detection utilized chest X-ray or echocardiogram, leading to subsequent diagnoses based on pericardial effusion and/or bone marrow examination. Two patients received chemotherapy at the time of initial diagnosis, one with cytarabine and etoposide, and the other with cytarabine and cladribine. Post-treatment, their bone marrow achieved remission, and over a 2.5-year follow-up, their cardiac function remained favorable. Unfortunately, the remaining three patients succumbed within two weeks after diagnosis, either due to receiving alternative drugs or without undergoing chemotherapy. Conclusion: This is the first and largest case series of pediatric AML patients with cardiac MS, manifesting initially with cardiac tamponade. It highlights the rarity and high mortality associated with this condition. The critical factors for reducing mortality include identifying clinical manifestations, conducting thorough physical examinations, performing echocardiography promptly, initiating early and timely pericardial drainage, and avoiding cardiotoxic chemotherapy medications.

High-Coverage UHPLC-MS/MS Analysis of 67 Mycotoxins in Plasma for Male Infertility Exposure Studies.

Mycotoxins are a class of exogenous metabolites that are major contributors to foodborne diseases and pose a potential threat to human health. However, little attention has been paid to trace mycotoxin co-exposure situations in vivo. To address this, we devised a novel analytical strategy, both highly sensitive and comprehensive, for quantifying 67 mycotoxins in human plasma samples. This method employs isotope dilution mass spectrometry (IDMS) for approximately 40% of the analytes and utilizes internal standard quantification for the rest. The mycotoxins were classified into three categories according to their physicochemical properties, facilitating the optimization of extraction and detection parameters to improve analytical performance. The lowest limits of detection and quantitation were 0.001-0.5 µg/L and 0.002-1 µg/L, respectively, the intra-day precision ranged from 1.8% to 11.9% RSD, and the intra-day trueness ranged from 82.7-116.6% for all mycotoxins except Ecl, DH-LYS, PCA, and EnA (66.4-129.8%), showing good analytical performance of the method for biomonitoring. A total of 40 mycotoxins (including 24 emerging mycotoxins) were detected in 184 plasma samples (89 from infertile males and 95 from healthy males) using the proposed method, emphasizing the widespread exposure of humans to both traditional and emerging mycotoxins. The most frequently detected mycotoxins were ochratoxin A, ochratoxin B, enniatin B, and citrinin. The incidence of exposure to multiple mycotoxins was significantly higher in infertile males than in healthy subjects, particularly levels of ochratoxin A, ochratoxin B, and citrinin, which were significantly increased. It is necessary to carry out more extensive biological monitoring to provide data support for further study of the relationship between mycotoxins and male infertility.