Prediction of hematologic toxicity in luminal type breast cancer patients receiving neoadjuvant chemotherapy using CT L1 level skeletal muscle index.

This study aims to explore the correlation between the CT-L1 and L3 body composition parameters and analyze the relationship between L1 body composition and hematologic toxicity in luminal-type breast cancer patients undergoing neoadjuvant chemotherapy. Data from 140 luminal-type breast cancer patients who underwent surgical treatment after neoadjuvant chemotherapy were analyzed retrospectively. Spearman analysis was used to assess the correlation between CT-L1 and CT-L3 body composition parameters pre-neoadjuvant chemotherapy. Additionally, univariate and multivariate logistic regression analyses were performed to identify factors influencing hematologic toxicity. CT-L1 body composition parameters were positively correlated with CT-L3 body composition parameters in 34 patients. Severe hematological toxicity occurred in 46 cases among the patient cohort. A skeletal muscle index (SMI) of < 32.91 cm2/m2, initial tumor size ≥ 3.335 cm, and a glucose-to-neutrophil ratio (GLR) ≥ 2.88 were identified as independent risk factors for severe hematologic toxicity during neoadjuvant chemotherapy in luminal-type breast cancer patients. The sample size in this study is small, and the predictive capacity of GLR in hematologic toxicity requires further research for comprehensive validation. CT-L1 analysis represents a viable alternative to CT-L3 analysis for body composition assessment. Patients with a low skeletal muscle index were more prone to experiencing severe hematologic toxicity during neoadjuvant chemotherapy.

BF3 complexing phosphate/phosphonate ionic liquids: synthesis, characterization and thermophysical properties.

A new group of BF3 complexing phosphate/phosphonate ionic liquids (ILs) [Emim][X(BF3)2] (X = dimethyl phosphate, diethyl phosphate, methyl phosphonate, and ethyl phosphonate) were synthesized and characterized. Key thermophysical properties of the new complex ionic liquids, including density, viscosity, conductivity, surface tension, solid-liquid phase transition, and thermal stability were determined and compared with those of [Emim][X]. Some other important thermophysical properties such as isobaric thermal expansion coefficient, molecular volume, standard molar entropy, and lattice potential energy were obtained from measured density data, and the free volume was estimated by a linear equation presented in this article, while critical temperature, normal boiling temperature, and enthalpy of vaporization were estimated from measured surface tension and density data. Furthermore, Fragility study shows that [Emim][X(BF3)2] could be considered as metallic glass-forming liquids, while [Emim][X] could be considered as extremely fragile liquids. The ionicity of [Emim][X(BF3)2] was predicted by Walden rule, and the result shows that these ILs fit well with Walden law. The key features of these complex ILs are their extremely low glass transition (-95.33~-98.46 ℃) without melting, considerably low viscosities (33.876~58.117 mPa·s), and high values of free volume fraction (comparable to [Omim][BF4], [Emim][NTf2], and [Emim][TCB]).

Survival Analysis of Patients Undergoing Intraoperative Contrast-enhanced Ultrasound in the Surgical Treatment of Malignant Glioma.

OBJECTIVE: Complete resection of malignant gliomas is often challenging. Our previous study indicated that intraoperative contrast-enhanced ultrasound (ICEUS) could aid in the detection of residual tumor remnants and the total removal of brain lesions. This study aimed to investigate the survival rates of patients undergoing resection with or without the use of ICEUS and to assess the impact of ICEUS on the prognosis of patients with malignant glioma. METHODS: A total of 64 patients diagnosed with malignant glioma (WHO grade HI and IV) who underwent surgery between 2012 and 2018 were included. Among them, 29 patients received ICEUS. The effects of ICEUS on overall survival (OS) and progression-free survival (PFS) of patients were evaluated. A quantitative analysis was performed to compare ICEUS parameters between gliomas and the surrounding tissues. RESULTS: The ICEUS group showed better survival rates both in OS and PFS than the control group. The univariate analysis revealed that age, pathology and ICEUS were significant prognostic factors for PFS, with only age being a significant prognostic factor for OS. In multivariate analysis, age and ICEUS were significant prognostic factors for both OS and PFS. The quantitative analysis showed that the intensity and transit time of microbubbles reaching the tumors were significantly different from those of microbubbles reaching the surrounding tissue. CONCLUSION: ICEUS facilitates the identification of residual tumors. Age and ICEUS are prognostic factors for malignant glioma surgery, and use of ICEUS offers a better prognosis for patients with malignant glioma.

Tumor Exosomal ENPP1 Hydrolyzes cGAMP to Inhibit cGAS-STING Signaling.

To evade immune surveillance, tumor cells express ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) on the surface of their membrane, which degrades extracellular cyclic GMP-AMP (cGAMP), thereby inhibiting the cyclic GMP-AMP synthase (cGAS) stimulator of interferon gene (STING) DNA-sensing pathway. To fully understand this tumor stealth mechanism, it is essential to determine whether other forms of ENPP1 with hydrolytic cGAMP activity also are present in the tumor microenvironment to regulate this innate immune pathway. Herein, it is reported that various tumor-derived exosomes carry ENPP1, and can hydrolyze synthetic 2'3'-cGAMP and endogenous 2'3'-cGAMP produced by cells to inhibit cGAS-STING pathway in immune cells. Moreover, tumor exosomal ENPP1 also can hydrolyze 2'3'-cGAMP bound to LL-37 (an effective transporter of 2'3'-cGAMP) to inhibit STING signaling. Furthermore, high expression of ENPP1 in exosomes is observed isolated from human breast and lung cancer tissue, and tumor exosomal ENPP1 inhibited the immune infiltration of CD8+ T cells and CD4+ T cells. The results elucidate the essential function of tumor exosomal ENPP1 in the cGAS-STING pathway, furthering understanding of the crosstalk between the tumor cells and immune system.

Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. METHODS: Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS: A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. CONCLUSIONS: The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.

In Situ Detection of Nucleic Acids in Extracellular Vesicles via Membrane Fusion.

Extracellular vesicles (EVs) carry diverse biomolecules (e. g., nucleic acids, proteins) for intercellular communication, serving as important markers for diseases. Analyzing nucleic acids derived from EVs enables non-invasive disease diagnosis and prognosis evaluation. Membrane fusion, a fundamental cellular process wherein two lipid membranes merge, facilitates cell communication and cargo transport. Building on this natural phenomenon, recent years have witnessed the emergence of membrane fusion-based strategies for the detection of nucleic acids within EVs. These strategies entail the encapsulation of detection probes within either artificial or natural vesicles, followed by the induction of membrane fusion with EVs to deliver probes. This innovative approach not only enables in situ detection of nucleic acids within EVs but also ensures the maintenance of structural integrity of EVs, thus preventing nucleic acid degradation and minimizing the interference from free nucleic acids. This concept categorizes approaches into universal and targeted membrane fusion strategies, and discusses their application potential, and challenges and future prospects.

Relationship between fatty acid intake and aging: a Mendelian randomization study.

BACKGROUND: Observational studies have previously shown a possible link between fatty acids and aging-related diseases, raising questions about its health implications. However, the causal relationship between the two remains uncertain. METHODS: Univariable and multivariable Mendelian randomization (MR) was used to analyze the relationship between five types of fatty acids-polyunsaturated fatty acid (PUFA), monounsaturated fatty acid (MUFA), saturated fatty acid (SFA), Omega-6 fatty acid (Omega-6 FA), and Omega-3 fatty acid (Omega-3 FA) and three markers of aging: telomere length (TL), frailty index (FI), and facial aging (FclAg). The primary approach for Mendelian randomization (MR) analysis involved utilizing the inverse variance weighted (IVW) method, with additional supplementary methods employed. RESULTS: Univariate MR analysis revealed that MUFA, PUFA, SFA, and Omega-6 fatty acids were positively associated with TL (MUFA OR: 1.019, 95% CI: 1.006-1.033; PUFA OR: 1.014, 95% CI: 1.002-1.026; SFA OR: 1.016, 95% CI: 1.002-1.031; Omega-6 FAs OR=1.031, 95% CI: 1.006-1.058). PUFA was also associated with a higher FI (OR: 1.033, 95% CI: 1.009-1.057). In multivariate MR analysis, after adjusting for mutual influences among the five fatty acids, MUFA and PUFA were positively independently associated with TL (MUFA OR: 1.1508, 95% CI = 1.0724-1.2350; PUFA OR: 1.1670, 95% CI = 1.0497-1.2973, while SFA was negatively correlated (OR: 0.8005, 95% CI: 0.7045-0.9096). CONCLUSIONS: Our research presents compelling evidence of a causal association between certain fatty acids and indicators of the aging process. In particular, MUFA and PUFA may play a role in slowing down the aging process, while SFAs may contribute to accelerated aging. These findings could have significant implications for dietary recommendations aimed at promoting healthy aging.

Investigation of the mutual crosstalk between ER stress and PI3K/AKT/mTOR signaling pathway in iron overload-induced liver injury in chicks.

Iron is an essential element for the normal functioning of living organisms, but excessive iron deposition can lead to organ damage. This study aims to investigate the interaction between the endoplasmic reticulum stress signaling pathway and the PI3K/AKT/mTOR signaling pathway in liver injury induced by iron overload in chicks. Rspectively, 150 one-day-old broilers were divided into three groups and supplemented with 50 (C), 500 (E1), and 1000 (E2) mg ferrous sulfate monohydrate/kg in the basal diet. Samples were taken after continuous feeding for 14 days. The results showed that iron overload could upregulate the levels of ALT and AST. Histopathological examination revealed bleeding in the central vein of the liver accompanied by inflammatory cell infiltration. Hoechst staining showed that the iron overload group showed significant bright blue fluorescence, and ultrastructural observations showed chromatin condensation as well as mitochondrial swelling and cristae disorganization in the iron overload group. RT-qPCR and Western blot results showed that iron overload upregulated the expression of Bax, Caspase-3, Caspase-9, GRP78, GRP94, P-PERK, ATF4, eIF2α, IRE1, and ATF6, while downregulating the expression of Bcl-2 and the PI3K/AKT/mTOR pathway. XBP-1 splicing experiment showed significant splicing of XBP-1 gene after iron overload. PCA and correlation analysis suggested a potential association between endoplasmic reticulum stress, the PI3K/AKT/mTOR signaling pathway, and liver injury in chicks. In summary, iron overload can induce cell apoptosis and liver injury by affecting endoplasmic reticulum stress and the PI3K/AKT/mTOR signaling pathway.

The BMAL1/HIF2A heterodimer modulates circadian variations of myocardial injury.

Acute myocardial infarction stands as a prominent cause of morbidity and mortality worldwide1-6. Clinical studies have demonstrated that the severity of cardiac injury following myocardial infarction exhibits a circadian pattern, with larger infarct sizes and poorer outcomes in patients experiencing morning onset myocardial infarctions7-14. However, the molecular mechanisms that govern circadian variations of myocardial injury remain unclear. Here, we show that BMAL114-20, a core circadian transcription factor, orchestrates diurnal variability in myocardial injury. Unexpectedly, BMAL1 modulates circadian-dependent cardiac injury by forming a transcriptionally active heterodimer with a non-canonical partner, hypoxia-inducible factor 2 alpha (HIF2A)6,21-23, in a diurnal manner. Substantiating this finding, we determined the cryo-EM structure of the BMAL1/HIF2A/DNA complex, revealing a previously unknown capacity for structural rearrangement within BMAL1, which enables the crosstalk between circadian rhythms and hypoxia signaling. Furthermore, we identified amphiregulin (AREG) as a rhythmic transcriptional target of the BMAL1/HIF2A heterodimer, critical for regulating circadian variations of myocardial injury. Finally, pharmacologically targeting the BMAL1/HIF2A-AREG pathway provides effective cardioprotection, with maximum efficacy when aligned with the pathway's circadian trough. Our findings not only uncover a novel mechanism governing the circadian variations of myocardial injury but also pave the way for innovative circadian-based treatment strategies, potentially shifting current treatment paradigms for myocardial infarction.

Spatio-temporal evolution and driving factors of new urbanization in central China based on multi-source data.

Urbanization is an inevitable outcome of the development of human society to a certain stage, and it is also an irreversible pattern of the concentration degree of human society. Based on multi-source data such as remote sensing images, ecological environment and socio-economic data, the evaluation index system of new urbanization is constructed from multi-dimensions of population, economy, society, space and ecology. To explore the spatio temporal evolution and driving factors of urbanization in 80 prefecture-level cities in central China from 2013 to 2021 by using entropy method, spatial autocorrelation model and geographic detector. The results show that: (1) The level of new urbanization continues to grow, with the average value rising from 0.1562 in 2013 to 0.2557 in 2021, and the regional differences are obvious, forming a circle structure with Wuhan, Zhengzhou and other provincial capitals as the center and weakening radiation to surrounding cities. (2) The agglomeration of ecological urbanization is significant, and the agglomeration trend is gradually enhanced. The high-high agglomeration areas tend to Xinzhou City, most prefecture-level cities in Hubei Province and some prefecture-level cities in Southern Hunan Province, while the low-low agglomeration areas tend to Changzhi City, most prefecture level cities in Henan Province and some prefecture-level cities in Northern Anhui Province. (3) The night light index, total retail sales of consumer goods, investment in fixed assets, proportion of built-up areas and urban economic density are the main driving factors affecting the level of new urbanization. (4) The interaction of driving factors shows double factor enhancement and nonlinear enhancement effects.

Soil ecoenzyme activities coupled with soil properties and plant biomass strongly influence the variation in soil organic carbon components in semi-arid degraded wetlands.

Wetland degradation can induce alterations in plant biomass, soil properties, and soil ecoenzyme activities, consequently influencing soil organic carbon components. Despite extensive investigations into the relationships among plant characteristics, soil properties, and soil organic carbon components, the enzymatic mechanisms underlying changes in soil organic carbon components, particularly the impact and contribution of ecoenzyme activities, remain poorly understood. This study compared the soil organic carbon components at a depth of 0-20 cm in wetlands in the semi-arid western Songnen Plain under different degradation levels and explored plant biomass, soil properties, and soil ecoenzyme activities. The results showed that the soil total organic carbon, labile organic carbon, and recalcitrant organic carbon contents in the degraded wetlands were generally lower than those in the non-degraded wetlands. Furthermore, the soil nutrient contents and soil ß-1,4-glucosidase, L-leucine aminopeptidase, and acid phosphatase activities were also lower in the degraded wetlands than in the non-degraded wetlands. Vector analysis of enzymatic stoichiometry revealed that wetland degradation did not increase microbial carbon limitation. The soil organic carbon components showed significant positive correlations with plant biomass, soil water content, soil total nitrogen, soil total phosphorus, as well as soil ecoenzyme activities. Variation partitioning analysis revealed that plant biomass, soil properties, soil ecoenzyme activities collectively accounted for 78.5 % variation in soil organic carbon components, among which plant biomass, soil properties, soil ecoenzyme activities, and their interactions explaining 4.2 %, 8.0 %, 7.9 %, and 24.5 % of the variation, respectively. Therefore, the impact of soil ecoenzyme activities and soil properties on soil organic carbon component changes was greater than that of plant biomass, with the interaction of these three factors playing a crucial role in soil organic carbon formation. This study provides a theoretical basis for scientifically evaluating the carbon sink function of degraded wetland soil and preserving the wetland soil carbon pool.

A Novel Local Magnetic Fluid Hyperthermia Based on High Gradient Field Guided by Magnetic Particle Imaging.

Magnetic Particle Imaging (MPI)-guided Magnetic Fluid Hyperthermia (MFH) has the potential for widespread utilization, as it allows for the prediction of magnetothermal dosage, real-time visualization of the thermal therapy process, and precise localization of the lesion area. However, the existing MPI-guided MFH (MPI-MFH) method is insensitive to concentration gradients of magnetic nanoparticles (MNPs) and is susceptible to causing damage to normal tissues with high MNP concentrations during MFH treatment, while inadequately heating tumor tissues with lower MNP concentrations. In this work, we established a relationship between MNP concentration and heating efficiency through simulations and phantom measurements, enabling the optimal selection of MFH parameters guided by MPI. Based on these findings, we developed a high-gradient field MPI-MFH method using a fieldfree point (FFP) approach to achieve precise local heating. Phantom experiments and in vivo glioma model experiments were conducted to validate this proposed method. The results demonstrated that the proposed method of MPIMFH can improve the MNP concentration gradient sensitivity to ±1 mg/ml, thereby enabling more effective lesion-site heating without damaging normal tissues. This method not only reduced glioma size effectively but also holds promise for application in various other types of cancers.

Metabolomic analysis reveals biogenic selenium nanoparticles improve the meat quality of thigh muscle in heat-stressed broilers is related to the regulation of ferroptosis pathway.

Heat stress (HS) causes oxidative damage and abnormal metabolism of muscle, thus impairing the meat quality in broilers. Selenium is an indispensable element for enhancing antioxidant systems. In our previous study, we synthesized a novel type of biogenic selenium nanoparticles synthesized with alginate oligosaccharides (SeNPs-AOS), and found that the particle size of Se is 80 nm and the Se content is 8% in the SeNPs-AOS; and dietary 5 mg/kg SeNPs-AOS has been shown to be effective against HS in broilers. However, whether SeNPs-AOS can mitigate HS-induced the impairment of thigh muscle quality in broilers is still unclear. Therefore, the purpose of this study was to investigate the protective effects of dietary SeNPs-AOS on meat quality, antioxidant capacity, and metabolomics of thigh muscle in broilers under HS. A total of 192 twenty-one-day-old Arbor Acres broilers were randomly divided into 4 groups with 6 replicates per group (8 broilers per replicate) according to a 2 × 2 experimental design: thermoneutral group (TN, broilers raised under 23±1.5°C); TN+SeNPs-AOS group (TN group supplemented 5 mg/kg SeNPS-AOS); HS group (broilers raised under 33 ± 2°C for 10 h/d); and HS + SeNPs-AOS group (HS group supplemented 5 mg/kg SeNPS-AOS). The results showed that HS increased the freezing loss, cooking loss, and malondialdehyde (MDA) content of thigh muscle, whereas decreased the total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities, as well as downregulated the mRNA expression of SOD2, CAT, GPX3, nuclear factor erythroid 2-related factor 2 (Nrf2), selenoprotein S (SELENOS), solute carrier family 7 member 11 (SLC7A11), GPX4, and ferroportin 1 (Fpn1) of thigh muscle (P < 0.05). Dietary SeNPS-AOS reduced the b* value, elevated the pH0min value and the activities of T-SOD, GSH-Px, glutathione S-transferase (GST) and the mRNA expression levels of GSTT1, GSTA3, GPX1, GPX3, ferritin heavy polypeptide-1 (FTH1), and Fpn1 of thigh muscle in broilers under HS (P < 0.05). Nontargeted metabolomics analysis identified a total of 79 metabolites with significant differences among the four groups, and the differential metabolites were mainly enriched in 8 metabolic pathways including glutathione metabolism and ferroptosis (P < 0.05). In summary, dietary 5 mg/kg SeNPs-AOS (Se content of 8%) could alleviate HS-induced impairment of meat quality by improving the oxidative damage, metabolic disorders and ferroptosis of thigh muscle in broilers challenged with HS. Suggesting that the SeNPs-AOS may be used as a novel nano-modifier for meat quality in broilers raised in thermal environment.

Influences of Genetic and Environmental Factors on Chronic Migraine: A Narrative Review.

PURPOSE OF REVIEW: In this narrative review, we aim to summarize recent insights into the complex interplay between environmental and genetic factors affecting the etiology, development, and progression of chronic migraine (CM). RECENT FINDINGS: Environmental factors such as stress, sleep dysfunction, fasting, hormonal changes, weather patterns, dietary compounds, and sensory stimuli are critical triggers that can contribute to the evolution of episodic migraine into CM. These triggers are particularly influential in genetically predisposed individuals. Concurrently, genome-wide association studies (GWAS) have revealed over 100 genetic loci linked to migraine, emphasizing a significant genetic basis for migraine susceptibility. In CM, environmental and genetic factors are of equal importance and contribute to the pathophysiology of the condition. Understanding the bidirectional interactions between these elements is crucial for advancing therapeutic approaches and preventive strategies. This balanced perspective encourages continued research into the complex gene-environment nexus to improve our understanding and management of CM.

The effect of body mass index on short-term outcomes in patients undergoing off-pump coronary artery bypass grafting surgery: a retrospective study from a single cardiovascular center.

OBJECTIVE: This study is designed to investigate the impact of body mass index (BMI) on the short-term outcomes of patients undergoing off-pump coronary artery bypass graft (OPCAB) surgery. METHODS: Data was obtained from 1006 Chinese patients who underwent isolated, primary OPCAB at a high-traffic cardiovascular center during 2020. Subjects were categorized, by BMI, into a low & normal weight (LN) group (BMI < 24 kg/m2), an overweight (OVW) group (24 ≤ BMI < 28 kg/m2), and an obese (OBS) group (BMI ≥ 28 kg/m2). Information pertaining to patients' short-term outcomes (including incidence of mortality and morbidities; duration of postoperative mechanical ventilation; length of stay in the ICU and hospital; postoperative bleeding; etc.) were extracted, and the data from each group were compared. RESULTS: The incidences of in-hospital mortality and morbidities were similar for all three groups. The volume of fluid infusion, postoperative bleeding within 24 h and total bleeding in LN group were higher than those in the OBS group (P < 0.001). The hemoglobin level was lower in the LN group than that in the OBS group (P < 0.001). Duration of mechanical ventilation and length of stay in the ICU in the LN group were longer than those in the OBS group (P < 0.001). CONCLUSIONS: Our results demonstrate that BMI is not significantly related with short-term outcomes in OPCAB patients. However, we suggest that OPCAB patients with low-normal BMI are more susceptible to post-operative blood loss.

Altered N6-Methyladenosine Modification Patterns and Transcript Profiles Contributes to Cognitive Dysfunction in High-Fat Induced Diabetic Mice.

N6-methyladenosine (m6A) constitutes the paramount post-transcriptional modification within eukaryotic mRNA. This modification is subjected to stimulus-dependent regulation within the central nervous system of mammals, being influenced by sensory experiences, learning processes, and injuries. The patterns of m6A methylation within the hippocampal region of diabetes cognitive impairment (DCI) has not been investigated. A DCI model was established by feeding a high-fat diet to C57BL/6J mice. m6A and RNA sequencing was conducted to profile the m6A-tagged transcripts in the hippocampus. Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing analyses yielded differentially m6A-modified and expressed genes in the hippocampus of DCI mice, which were enriched in pathways involving synaptic transmission and axonal guidance. Mechanistic analyses revealed a remarkable change in m6A modification levels through alteration of the mRNA expression of m6A methyltransferases (METTL3 and METTL14) and demethylase (FTO) in the hippocampus of DCI mice. We identified a co-mediated specific RNA regulatory strategy that broadens the epigenetic regulatory mechanism of RNA-induced neurodegenerative disorders associated with metabolic and endocrine diseases.

Risk Factor Analysis of Complications and Mortality Following Coil Procedures in Patients with Intracranial Unruptured Aneurysms Using a Nationwide Health Insurance Database.

(1) Background: Unruptured intracranial aneurysm (UIA) occurs in 1-2% of the population and is being increasingly detected. Patients with UIA are treated with close observation, endovascular coiling or surgical clipping. The proportion of endovascular coiling has been rising. However, complications such as cerebral infarction (CI), intracranial hemorrhage (ICRH), and death remain crucial issues after coil treatment. (2) Methods: We analyzed the incidence and risk factors of complications after the use of coil in patients with UIA based on the patients' characteristics. We utilized the Health Insurance Review and Assessment (HIRA) database. Patients treated with coils for UIA between 1 January 2015 and 1 December 2021 were retrospectively analyzed. (3) Results: Of the total 35,140 patients, 1062 developed ICRH, of whom 87 died, with a mortality rate of 8.2%. Meanwhile, 749 patients developed CI, of whom 29 died, with a mortality rate of 3.9%. The overall mortality rate was 1.8%. In a univariate analysis of the risk factors, older age, males, a higher Charlson Comorbidity Index (CCI) score, and diabetes increase the risk of CI. Meanwhile, males with higher CCI scores and hemiplegia or paraplegia show increased ICRH risk. Older age, males and metastatic solid tumors relate to increased mortality risk. (4) Conclusions: This study is significant in that the complications based on the patient's underlying medical condition were analyzed.

Discovery of a Photoaffinity Probe that Captures the Active Conformation of the Cannabinoid CB2 Receptor.

The cannabinoid receptor type 2 (CB2R) is a G protein-coupled receptor with therapeutic potential for the treatment of inflammatory disorders. Fluorescent probes are desirable to study its receptor localization, expression and occupancy. Previously, we have reported a photoaffinity probe LEI-121 that stabilized the inactive conformation of the CB2R. Here, we report the structure-based design of a novel bifunctional probe that captures the active conformation of the CB2R upon irradiation with light. An alkyne handle was incorporated to visualize the receptor using click-chemistry with fluorophore-azides. These probes may hold promise to study different receptor conformations in relation to their cellular localization and function.

The Effects of Daytime Variation on Short-term Outcomes of Patients Undergoing Off-Pump Coronary Artery Bypass Grafting.

OBJECTIVE: To evaluate the effects of time of surgery on the short-term outcomes of patients undergoing off-pump coronary artery bypass grafting (OPCABG). DESIGN: A retrospective cohort study. SETTING: A single large-volume cardiovascular center. PATIENTS: Patients undergoing elective OPCABG between September 2019 and July 2022. INTERVENTIONS: Patients were divided into the following 2 groups according to the start time of surgery: morning (AM group, before 11 AM) and afternoon (PM group, after 11 AM). Propensity-score matching (PSM) with a 1:1 matching ratio was used to create comparable cohorts. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the composite incidence of mortality and morbidities during hospitalization. Secondary endpoints included postoperative bleeding and transfusion, mechanical ventilation duration (MVD), and lengths of stay (LOS) in the intensive care unit (ICU) and hospital. From a consecutive series of 1,039 patients, PSM yielded 317 well-matched pairs. There was no difference in the composite incidence of in-hospital mortality and morbidities between the AM and PM groups (16.4% v 17.4%, p = 0.832). However, patients in the PM group were associated with less postoperative blood loss over the first 24 hours (470 v 540 mL, p = 0.002), decreased MVD (14 v 16 hours, p < 0.001), and shorter LOS in ICU (46 v 68 hours, p = 0.002) compared to patients in AM group. CONCLUSIONS: The current study suggested a lack of relevance regarding the time of surgery with in-hospital mortality and morbidities in patients undergoing OPCABG.