The role of small dense LDL-C/large buoyant LDL-C ratio as an independent risk factor in patients with type 2 diabetes mellitus and metabolic syndrome

Dyslipidemia plays a key role in metabolic syndrome (MS), intricately linked to type 2 diabetes mellitus (T2DM). This study aimed to investigate the differences in low-density lipoprotein cholesterol (LDL-C) subfraction levels between T2DM and T2DM with MS, and identify the risk factors associated with the disease. A total of 246 individuals diagnosed with T2DM, including 144 T2DM patients with MS, and 147 healthy subjects were recruited. All participants underwent a comprehensive clinical evaluation. Lipoprotein subfraction analysis was performed using the Lipoprint LDL system. Multivariate logistic regression analysis revealed that several lipid markers, including triglyceride (TG), LDL-C, large buoyant LDL-C (lbLDL-C), small dense LDL-C (sdLDL-C), LDLC2-5, and sdLDL-C/lbLDL-C ratio, were identified as independent risk factors for T2DM. Additionally, TG, sdLDL-C, LDLC-4, LDLC-5, and sdLDL-C/lbLDL-C ratio were found to be independent risk factors for T2DM with MS. Furthermore, the results of the receiver operating characteristic (ROC) curves demonstrated that sdLDL-C, LDLC-4, LDLC-3, and sdLDL-C/lbLDL-C ratio exhibited excellent predictive performance for the risk of T2DM (AUC > 0.9). The sdLDL-C/lbLDL-C ratio emerges as a shared independent risk factor for T2DM and MS complications. Furthermore, sdLDL-C/lbLDL-C ratio, along with LDL-4 and LDL-3, exhibits noteworthy predictive capabilities for T2DM.

Knowledge mapping of paediatric fever-a visual analysis based on CiteSpace.

Objective: This study aimed to analyse the research hotspots and frontiers in the field of paediatric fever between 2013 and 2023. Methods: The included articles were visually analysed using CiteSpace 6.1.R6 software. Results: A total of 2,662 Chinese-language articles and 1,456 English-language articles were included in the study. Based on the Chinese literature, research groups were identified represented by Xinmin Li, Jinling Hong and Hongshuang Luo. Based on the English literature, research groups were formed represented by Henriette Moll, Santiago Mintegi and Elizabeth Alpern. Tianjin University of Traditional Chinese Medicine was the institution with the largest number of publications in the Chinese literature, and the Centers For Disease Control And Prevention was the institution with the largest number of publications in the English literature. The research on paediatric fever mainly focused on mechanism exploration, green treatment and clinical management. Conclusion: Several relatively stable research groups have been formed. Future studies on the differential diagnosis, rational drug use, standardised management and clinical practice guidelines for paediatric fever are needed.

Synthesis and Characterization of a Novel PET Tracer for Noninvasive Evaluation of FGL1 Status in Tumors.

Fibrinogen-like protein 1 (FGL1) is a potential novel immune checkpoint target for malignant tumor diagnosis and therapy. Accurate detection of FGL1 levels in tumors via noninvasive PET imaging might be beneficial for managing the disease. To achieve this, multiple FGL1-targeting peptides (FGLP) were designed, and a promising candidate, 68Ga-NOTA-FGLP2, was identified through a high-throughput screening approach using microPET imaging of 68Ga-labeled peptides. Subsequent in vitro cell experiments showed that uptake values of 68Ga-NOTA-FGLP2 in FGL1 positive Huh7 tumor cells were significantly higher than those in FGL1 negative U87 MG tumor cells. Further microPET imaging showed that the Huh7 xenografts were clearly visualized with a favorable contrast. ROI analysis showed that the uptake values of the tracer in Huh7 xenografts were 2.63 ± 0.07% ID/g at 30 min p.i.. After treatment with an excess of unlabeled FGLP2, the tumor uptake significantly decreased to 0.54 ± 0.05% ID/g at 30 min p.i.. Moreover, the uptake in U87 MG xenografts was 0.44 ± 0.06% ID/g at the same time point. The tracer was excreted mainly through the renal system. 18F-FDG PET imaging was also performed in mice bearing Huh7 and U87 MG xenografts, respectively. However, there was no significant difference in the uptake between the tumors with different FGL1 expressions. Preclinical data indicated that 68Ga-NOTA-FGLP2 might be a suitable radiotracer for in vivo noninvasive visualization of tumors with abundant expression of FGL1. Further investigation of 68Ga-NOTA-FGLP2 for tumor diagnosis and therapy is undergoing.

Evaluating the quality of home care in community health service centres: A machine learning approach.

AIMS: The aim of the study is to develop a model using a machine learning approach that can effectively identify the quality of home care in communities. DESIGN: A cross-sectional design. METHODS: In this study, we evaluated the quality of home care in 170 community health service centres between October 2022 and February 2023. The Home Care Service Quality Questionnaire was used to collect information on home care structure, process and outcome quality. Then, an intelligent and comprehensive evaluation model was developed using a convolutional neural network, and its performance was compared with random forest and logistic regression models through various performance indicators. RESULTS: The convolutional neural network model was built upon seven variables, which encompassed the qualification of home nursing staff, developing and practicing emergency plan to cope with different emergency rescues in home environment, being equipped with medication and supplies for first aid according to specific situations, assessing nutrition condition of home patients, allocation of the number of home nursing staff, cases of new pressure ulcers and patient satisfaction rate. Remarkably, the convolutional neural network model demonstrated superior performance, outperforming both the random forest and regression models. CONCLUSION: The successful development and application of the convolutional neural network model highlight its ability to leverage data from community health service centres for rapid and accurate grading of home care quality. This research points the way to home care quality improvement. IMPACT: The model proposed in this study, coupled with the aforementioned factors, is expected to enhance the accuracy and efficiency of a comprehensive evaluation of home care quality. It will also help managers to take purposeful measures to improve the quality of home care. REPORTING METHOD: The reporting of this study (Observational, cross-sectional study) conforms to the STROBE statement. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The application of this model has the potential to contribute to the advancement of high-quality home care, particularly in lower-middle-income communities.

Regulation of TMEM100 expression by epigenetic modification, effects on proliferation and invasion of esophageal squamous carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy with a high morbidity and mortality rate. TMEM100 has been shown to be suppressor gene in a variety of tumors, but there are no reports on the role of TMEM100 in esophageal cancer (EC). AIM: To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion. METHODS: Firstly, we found the expression of TMEM100 in EC through The Cancer Genome Atlas database. The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis. We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification. To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100. Finally, we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases (MAPK) pathway. RESULTS: In the present study, by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects. Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC. Then, we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells [quantitative real-time PCR (qRT-PCR) and western blotting]. Subsequently, we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells (qRT-PCR and western blotting). Overexpression of TMEM100 also inhibited proliferation, invasion and migration of ESCC cells (cell counting kit-8 and clone formation assays). Next, by enrichment analysis, we found that the gene set was significantly enriched in the MAPK signaling pathway. The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting. CONCLUSION: TMEM100 is a suppressor gene in ESCC, and its low expression may lead to aberrant activation of the MAPK pathway. Promoter methylation may play a key role in regulating TMEM100 expression.

Chrysin mitigated neuropathic pain and peripheral sensitization in knee osteoarthritis rats by repressing the RAGE/PI3K/AKT pathway regulated by HMGB1.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic progressive osteoarthropathy. Chrysin's anti-KOA action has been demonstrated, however more research is needed to understand how chrysin contributes to KOA. METHODS: LPS/ATP-induced macrophages transfected with or without HMGB1 overexpression underwent 5 µg/mL chrysin. The cell viability and macrophage pyroptosis were examined by cell counting kit-8 and flow cytometer. In vivo experiments, rats were injected with 1 mg monosodium iodoacetate by the infrapatellar ligament of the bilateral knee joint to induce KOA. The histological damage was analyzed by Safranin O/Fast Green staining and hematoxylin and eosin staining. The PWT, PWL and inflammatory factors were analyzed via Von-Frey filaments, thermal radiometer and ELISA. Immunofluorescence assay examined the expressions of CGRP and iNOS. The levels of HMGB1/RAGE-, NLRP3-, PI3K/AKT- and neuronal ion channel-related markers were examined by qPCR and western blot. RESULTS: Chrysin alleviated macrophage pyroptosis by inhibiting HMGB1 and the repression of chrysin on HMGB1/RAGE pathway and ion channel activation was reversed by overexpressed HMGB1. HMGB1 facilitated neuronal ion channel activation through the RAGE/PI3K/AKT pathway. Chrysin could improve the pathological injury of knee joints in KOA rats. Chrysin suppressed the HMGB1-regulated RAGE/PI3K/AKT pathway, hence reducing KOA damage and peripheral sensitization. CONCLUSION: Chrysin mitigated neuropathic pain and peripheral sensitization in KOA rats by repressing the RAGE/PI3K/AKT pathway modulated by HMGB1.

Olfactory dysfunction and long-term trajectories of sleep disorders among early Parkinson's disease: findings from a longitudinal cohort.

BACKGROUND: Previous studies have suggested a connection between impaired olfactory function and an increased risk of rapid eye movement sleep behavior disorder (RBD) in individuals diagnosed with Parkinson's disease (PD). However, there is a gap in knowledge regarding the potential impact of olfactory dysfunction on the long-term patterns of sleep disorders among early PD patients. METHODS: Data from the Parkinson's Progression Markers Initiative program included 589 participants with assessments of sleep disorders using the Epworth Sleepiness Scale (ESS) and RBD Screening Questionnaire (RBDSQ). Olfactory dysfunction at baseline was measured using the University of Pennsylvania Smell Identification Test. Trajectories of sleep disorders over a 5-year follow-up were identified using group-based trajectory modeling, and the relationship between olfactory dysfunction and sleep disorder trajectories was examined through binomial logistic regression. RESULTS: Two distinct trajectories of sleep disorders over the 5-year follow-up period were identified, characterized by maintaining a low or high ESS score and a low or high RBDSQ score. An inversion association was observed between olfactory function measures and trajectories of excessive daytime sleepiness (EDS) (odds ratio [OR]=0.97, 95% confidence interval [CI] 0.95, 1.00, P=0.038), after controlling for potential covariates. Similarly, olfactory function showed a significant association with lower trajectories of probable RBD (pRBD) (OR=0.96, 95% CI 0.94, 0.98, P=0.001) among early PD individuals. Consistent findings were replicated across alternative analytical models. CONCLUSIONS: Our findings indicated that olfactory dysfunction was associated with unfavorable long-term trajectories of sleep disorders among early Parkinson's disease.

Low functional redundancy revealed high vulnerability of the subtropical evergreen broadleaved forests to environmental change.

Anthropogenic-induced environmental changes threaten forest ecosystems by reducing their biodiversity and adaptive capacity. Understanding the sensitivity of ecosystem function to loss of diversity is vital in designing conservation strategies and maintaining the resilience of forest ecosystems in a changing world. Here, based on unique combinations of ten functional traits (termed as functional entities; FEs), we quantified the metrics of functional redundancy (FR) and functional vulnerability (FV) in 250 forest plots across five locations in subtropical evergreen broadleaved forests. We then examined the potential impacts of species loss on functional diversity in subtropical forest communities along environmental gradients (climate and soil). Results showed that the subtropical forests displayed a low level of functional redundancy (FR < 2). Over 75 % of the FEs in these subtropical forest communities were composed of only one species, with rare species emerging as pivotal contributors to these vulnerable FEs. The number of FEs and functional redundancy both increased with the rise in species richness, but functional vulnerability decreased with increasing species richness. Climatic factors, especially mean diurnal range, played crucial roles in determining the functions that the forest ecosystem delivers. Under variable temperature conditions, species in each plot were packed into a few FEs, leading to higher functional redundancy and lower functional vulnerability. These results highlighted that rare species contribute significantly to ecosystem functions and the highly diverse subtropical forest communities could show more insurance effects against species loss under stressful environmental conditions.

Probucol mitigates high-fat diet-induced cognitive and social impairments by regulating brain redox and insulin resistance.

Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects.

The effect of fecal microbiota transplantation on antibiotic-associated diarrhea and its impact on gut microbiota.

BACKGROUND: Antibiotic-associated diarrhea (AAD) refers to symptoms of diarrhea that cannot be explained by other causes after the use of antibiotics. AAD is thought to be caused by a disruption of intestinal ecology due to antibiotics. Fecal Microbiota Transplantation (FMT) is a treatment method that involves transferring microbial communities from the feces of healthy individuals into the patient's gut. METHOD: We selected 23 AAD patients who received FMT treatment in our department. Before FMT, we documented patients' bowel movement frequency, abdominal symptoms, routine blood tests, and inflammatory markers, and collected fecal samples for 16S rRNA sequencing to observe changes in the intestinal microbiota. Patients' treatment outcomes were followed up 1 month and 3 months after FMT. RESULTS: Out of the 23 AAD patients, 19 showed a clinical response to FMT with alleviation of abdominal symptoms. Among them, 82.61% (19/23) experienced relief from diarrhea, 65% (13/20) from abdominal pain, 77.78% (14/18) from abdominal distension, and 57.14% (4/7) from bloody stools within 1 month after FMT. Inflammatory markers IL-8 and CRP significantly decreased after FMT, but there were no noticeable changes in WBC, IL-6, and TNF-α before and after transplantation. After FMT, the abundance of Bacteroides and Faecalibacterium increased in patients' fecal samples, while the abundance of Escherichia-Shigella and Veillonella decreased. CONCLUSION: FMT has a certain therapeutic effect on AAD, and can alleviate abdominal symptoms and change the intestinal microbiota of patients.

The Glucose-Succinate Pathway: A Crucial Anaerobic Metabolic Pathway in the Scallop Chlamys farreri Experiencing Heat Stress.

Recently, the increase in marine temperatures has become an important global marine environmental issue. The ability of energy supply in marine animals plays a crucial role in avoiding the stress of elevated temperatures. The investigation into anaerobic metabolism, an essential mechanism for regulating energy provision under heat stress, is limited in mollusks. In this study, key enzymes of four anaerobic metabolic pathways were identified in the genome of scallop Chlamys farreri, respectively including five opine dehydrogenases (CfOpDHs), two aspartate aminotransferases (CfASTs) divided into cytoplasmic (CfAST1) and mitochondrial subtype (CfAST2), and two phosphoenolpyruvate carboxykinases (CfPEPCKs) divided into a primitive type (CfPEPCK2) and a cytoplasmic subtype (CfPEPCK1). It was surprising that lactate dehydrogenase (LDH), a key enzyme in the anaerobic metabolism of the glucose-lactate pathway in vertebrates, was absent in the genome of scallops. Phylogenetic analysis verified that CfOpDHs clustered according to the phylogenetic relationships of the organisms rather than substrate specificity. Furthermore, CfOpDHs, CfASTs, and CfPEPCKs displayed distinct expression patterns throughout the developmental process and showed a prominent expression in muscle, foot, kidney, male gonad, and ganglia tissues. Notably, CfASTs displayed the highest level of expression among these genes during the developmental process and in adult tissues. Under heat stress, the expression of CfASTs exhibited a general downregulation trend in the six tissues examined. The expression of CfOpDHs also displayed a downregulation trend in most tissues, except CfOpDH1/3 in striated muscle showing significant up-regulation at some time points. Remarkably, CfPEPCK1 was significantly upregulated in all six tested tissues at almost all time points. Therefore, we speculated that the glucose-succinate pathway, catalyzed by CfPEPCK1, serves as the primary anaerobic metabolic pathway in mollusks experiencing heat stress, with CfOpDH3 catalyzing the glucose-opine pathway in striated muscle as supplementary. Additionally, the high and stable expression level of CfASTs is crucial for the maintenance of the essential functions of aspartate aminotransferase (AST). This study provides a comprehensive and systematic analysis of the key enzymes involved in anaerobic metabolism pathways, which holds significant importance in understanding the mechanism of energy supply in mollusks.

Cholinium Pyridinolate Ionic Pair-Catalyzed Fixation of CO2 into Cyclic Carbonates.

A halide-free ionic pair organocatalyst was proposed for the cycloaddition of CO2 into epoxide reactions. Cholinium pyridinolate ionic pairs with three different substitution positions were designed. Under conditions of temperature of 120 °C, pressure of 1 MPa CO2, and catalyst loading of 5 mol %, the optimal catalyst cholinium 4-pyridinolate ([Ch]+[4-OP]-) was employed. After a reaction time of 12 h, styrene oxide was successfully converted into the corresponding cyclic carbonate, and its selectivity was improved to 90%. A series of terminal epoxides were converted into cyclic carbonates within 12 h, with yields ranging from 80 to 99%. The proposed mechanism was verified by 1H NMR and 13C NMR titrations. Cholinium cations act as a hydrogen bond donor to activate epoxides, and pyridinolate anions combine with carbon dioxide to form intermediate carbonate anions that attack epoxides as nucleophiles and lead to ring opening. In summary, a halide-free ionic pair organocatalyst was designed and the catalytic mechanism in the cycloaddition of CO2 into epoxides reactions was proposed.

Protective effect of trehalose sugar on amyloid-membrane interactions using BLM electrophysiology.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by dementia and memory loss in the elderly population. The amyloid-ß peptide (Aß) is one of the main pathogenic factors in AD and is known to cause damage to neuronal cellular membranes. There is no cure currently available for AD, and new approaches, including preventive strategies, are highly desirable. In this work, we explore the possibility of protecting neuronal membranes from amyloid-induced damage with naturally existing sugar trehalose. Trehalose has been shown to protect plant cellular membranes in extreme conditions and modify Aß misfolding. We hypothesize that trehalose can protect the neuronal membrane from amyloid toxicity. In this work, we studied the protective effect of trehalose against Aß1-42-induced damage in model lipid membranes (DPPC/POPC/cholesterol) using atomic force microscopy and black lipid membrane electrophysiology. Our results demonstrate that Aß1-42 damaged membranes and led to ionic current leakage across these membranes due to the formation of various defects and pores. The presence of trehalose reduced the ion current across membranes caused by Aß1-42 peptide damage, thus efficiently protecting the membranes. These findings suggest that the trehalose sugar can potentially be useful in protecting neuronal membranes against amyloid toxicity in AD.

Cuproptosis associated cytoskeletal destruction contributes to podocyte injury in chronic kidney disease.

The podocyte cytoskeleton determines the stability of podocyte structure and function, and their imbalance plays a pathogenic role in podocyte diseases. However, the underlying mechanism of podocyte cytoskeleton damage is not fully understood. Here, we investigate the specific role of cuproptosis in inducing podocyte cytoskeleton injury. In vitro and in vivo studies, exposure to high levels of copper and adriamycin (ADR) caused significant increases in copper concentration in intracellular and renal tissue. Moreover, excessive accumulation of copper induced cuproptosis, resulting in the destruction of the podocyte cytoskeleton. However, inhibition of copper accumulation to reduce cuproptosis also significantly alleviated the damage of podocyte cytoskeleton. In addition, inhibition of cuproptosis mitigated ADR-induced mitochondrial damage as well as the production of reactive oxygen species and depolarization of mitochondrial membrane potential, and restored ATP synthesis. Among the transcriptome sequencing data, the difference of CXCL5 was the most significant. Both high copper and ADR exposure can cause up-regulation of CXCL5, and CXCL5 deletion inhibits the occurrence of cuproptosis, thereby alleviating the podocyte cytoskeleton damage. This suggests that CXCL5 may act upstream of cuproptosis that mediates podocyte cytoskeleton damage. In conclusion, cuproptosis induced by excessive copper accumulation may induce podocyte cytoskeleton damage by promoting mitochondrial dysfunction, thereby causing podocyte injury. This indicates that cuproptosis plays an important role in the pathogenesis of podocyte injury and provides a basis for seeking potential targets for the treatment of chronic kidney disease.

Comparative analysis of sipeimine content, metabolome and chloroplast genome in cultivated and wild varieties of Fritillaria taipaiensis.

BACKGROUND: The wild variety Fritillaria taipaiensis E.B (EB) is known for its superior therapeutic effects, but its limited production cannot meet demand. As a result, the cultivated variety F. taipaiensis P. Y. Li (PY) has been widely grown. In this study, we conducted a comprehensive analysis comparing EB and PY in terms of external features, sipeimine content, metabolome and chloroplast genome to differentiate these two varieties. RESULTS: Our research revealed that the petals and pods of EB are green, while those of PY have purple markings. The bulbs of EB contain significantly higher levels of sipeimine compared to those of PY. Metabolomic analysis identified 56 differentially expressed metabolites (DMs), with 23 upregulated and 33 downregulated in EB bulbs. Particularly, 3-hydroxycinnamic acid and secoxyloganin may serve as distinctive DMs. These DMs were associated with 17 KEGG pathways, including pyrimidine metabolism, alanine, aspartate and glutamate metabolism, and galactose metabolism. Differences in the length of the chloroplast genome were primarily observed in the large single-copy (LSC) region, with the largest variation in the trnH-GUC-psbA region. The placement of the trnH gene and the rps gene in proximity to the LSC/IRb boundary differs between EB and PY. CONCLUSION: The results of this study provide valuable insights for the introduction and comprehensive development of wild F. taipaiensis from a scientific perspective. © 2024 Society of Chemical Industry.

Safety and efficacy of magnesium-rich artificial cerebrospinal fluid for subarachnoid hemorrhage.

Objectives: This study aimed to investigate the efficacy of using a newly formulated magnesium-rich artificial cerebrospinal fluid (MACSF) as an alternative to normal saline (NS) for intraoperative irrigation during aneurysm clipping in improving the prognosis of patients with Aneurysmal subarachnoid hemorrhage (aSAH). Methods: Patients with aSAH who underwent intraoperative irrigation with MACSF or NS during the clipping in the First Affiliated Hospital of Xi 'an Jiaotong University from March 2019 to March 2022 were selected as MACSF group and NS group, respectively. The primary prognostic indicators were the incidence of favorable outcomes (mRS 0-2). The secondary outcome measures included cerebral vasospasm (CVS), mortality, total hospital stay, and intensive care unit (ICU) stay. Safety was evaluated based on the occurrence rates of hypermagnesemia, meningitis, and hydrocephalus. Results: Overall, 34 and 37 patients were enrolled in the MACSF and NS groups, respectively. At 90 days after aSAH onset, the proportion of favorable prognosis in the MACSF group was significantly higher than that in the NS group (p = 0.035). The incidence of CVS within 14 days after surgery was significantly lower in the MACSF group than that in the NS group (p = 0.026). The mortality rate in the MACSF group was significantly lower than in the NS group (p = 0.048). The median lengths of hospital stay (p = 0.008) and ICU stay (p = 0.018) were significantly shorter in the MACSF group than in the NS group. No significant differences were observed in safety measures. Conclusion: Using MACSF as an irrigation fluid for aneurysm clipping can significantly improve the 90-day prognosis of patients with aSAH, which may be related to the reduced incidence of CVS. Clinical trial registration: https://www.clinicaltrials.gov, identifier NCT04358445.

Nanoscale Structure of Lipid-Gemini Surfactant Mixed Monolayers Resolved with AFM and KPFM Microscopy.

Drug delivery vehicles composed of lipids and gemini surfactants (GS) are promising in gene therapy. Tuning the composition and properties of the delivery vehicle is important for the efficient load and delivery of DNA fragments (genes). In this paper, we studied novel gene delivery systems composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dipalmitoyl-sn-3-phosphocholine (DPPC), and GS of the type N,N-bis(dimethylalkyl)-α,ω-alkanediammonium dibromide at different ratios. The nanoscale properties of the mixed DOPC-DPPC-GS monolayers on the surface of the gene delivery system were studied using atomic force microscopy (AFM) and Kelvin probe force microscopy (KPFM). We demonstrate that lipid-GS mixed monolayers result in the formation of nanoscale domains that vary in size, height, and electrical surface potential. We show that the presence of GS can impart significant changes to the domain topography and electrical surface potential compared to monolayers composed of lipids alone.

The Selective Removal of Bisphenol A Using a Magnetic Adsorbent Fused with Bisphenol A-Binding Peptides.

The potential of bisphenol A (BPA)-binding peptides fused to magnetic beads is demonstrated as novel adsorbents that are reusable and highly selective for BPA removal from aqueous environments, in which various interfering substances coexist. Magnetic beads harboring peptides (peptide beads) showed a higher BPA removal capacity (8.6 mg/g) than that of bare beads without peptides (2.0 mg/g). The BPA adsorption capacity of peptide beads increased with the number of peptides fused onto the beads, where monomeric, dimeric, or trimeric repeats of a BPA-binding peptide were fused to magnetic beads. The BPA-adsorbing beads were regenerated using a methanol-acetic acid mixture, and after six regeneration cycles, the adsorption capacity remained above 87% of its initial capacity. The selective removal of BPA was confirmed in the presence of BPA analogs with high structural similarity (bisphenol F and bisphenol S) or in synthetic wastewater. The present work is a pioneering study that investigates the selective affinity of peptides to remove specific organics with high selectivity from complex environmental matrices.

Grain transportation and consumption reshapes the α-HCH exposure picture of China.

Socio-economic activities like food trade can increase the uncertainty of human risk of persistent organic pollutants (POPs). We compared the change in model predicted α-hexachlorocyclohexane (α-HCH) cancer risk (CR) with and without grain trade in mainland China. In scenario without grain logistics, α-HCH moved fast away from southern and southeastern China via northward atmospheric transport. However, the grain logistics from northeastern China delivers the α-HCH previously accumulated in northeastern sink back to densely populated areas in recent years, which enhance CR by >50 % in the southern seaboard of China. The northward movement of grain production center and recent grain deficiency in southern provinces induced by dietary pattern changes is identified as the major driving factors of the reversed transport of α-HCH. The finding highlights the potential of socio-economic activities that can otherwise offset the risk reduction effect of the geochemical cycle of POPs.

Tumor-Tailored Ionizable Lipid Nanoparticles Facilitate IL-12 Circular RNA Delivery for Enhanced Lung Cancer Immunotherapy.

The advancement of message RNA (mRNA) -based immunotherapies for cancer is highly dependent on the effective delivery of RNA (Ribonucleic) payloads using ionizable lipid nanoparticles (LNPs). However, the clinical application of these therapies is hindered by variable mRNA expression among different cancer types and the risk of systemic toxicity. The transient expression profile of mRNA further complicates this issue, necessitating frequent dosing and thus increasing the potential for adverse effects. Addressing these challenges, a high-throughput combinatorial method is utilized to synthesize and screen LNPs that efficiently deliver circular RNA (circRNA) to lung tumors. The lead LNP, H1L1A1B3, demonstrates a fourfold increase in circRNA transfection efficiency in lung cancer cells over ALC-0315, the industry-standard LNPs, while providing potent immune activation. A single intratumoral injection of H1L1A1B3 LNPs, loaded with circRNA encoding interleukin-12 (IL-12), induces a robust immune response in a Lewis lung carcinoma model, leading to marked tumor regression. Immunological profiling of treated tumors reveals substantial increments in CD45+ leukocytes and enhances infiltration of CD8+ T cells, underscoring the ability of H1L1A1B3 LNPs to modulate the tumor microenvironment favorably. These results highlight the potential of tailored LNP platforms to advance RNA drug delivery for cancer therapy, broadening the prospects for RNA immunotherapeutics.