Targeting Neuronal GPR65 With Delayed BTB09089 Treatment Improves Neurorehabilitation Following Ischemic Stroke.

BACKGROUND: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown. METHODS: Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65-/-) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65-/- and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting. RESULTS: BTB09089 significantly promoted motor outcomes in WT but not in GPR65-/- mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65-/- mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65-/- mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65-/- mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice. CONCLUSIONS: Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.

Establishment of a humanized mouse model using steady-state peripheral blood-derived hematopoietic stem and progenitor cells facilitates screening of cancer-targeted T-cell repertoires.

Background: Cancer-targeted T-cell receptor T (TCR-T) cells hold promise in treating cancers such as hematological malignancies and breast cancers. However, approaches to obtain cancer-reactive TCR-T cells have been unsuccessful. Methods: Here, we developed a novel strategy to screen for cancer-targeted TCR-T cells using a special humanized mouse model with person-specific immune fingerprints. Rare steady-state circulating hematopoietic stem and progenitor cells were expanded via three-dimensional culture of steady-state peripheral blood mononuclear cells, and then the expanded cells were applied to establish humanized mice. The human immune system was evaluated according to the kinetics of dendritic cells, monocytes, T-cell subsets, and cytokines. To fully stimulate the immune response and to obtain B-cell precursor NAML-6- and triple-negative breast cancer MDA-MB-231-targeted TCR-T cells, we used the inactivated cells above to treat humanized mice twice a day every 7 days. Then, human T cells were processed for TCR ß-chain (TRB) sequencing analysis. After the repertoires had been constructed, features such as the fraction, diversity, and immune signature were investigated. Results: The results demonstrated an increase in diversity and clonality of T cells after treatment. The preferential usage and features of TRBV, TRBJ, and the V-J combination were also changed. The stress also induced highly clonal expansion. Tumor burden and survival analysis demonstrated that stress induction could significantly inhibit the growth of subsequently transfused live tumor cells and prolong the survival of the humanized mice. Conclusions: We constructed a personalized humanized mouse model to screen cancer-targeted TCR-T pools. Our platform provides an effective source of cancer-targeted TCR-T cells and allows for the design of patient-specific engineered T cells. It therefore has the potential to greatly benefit cancer treatment.

FRAX486, a PAK inhibitor, overcomes ABCB1-mediated multidrug resistance in breast cancer cells.

The overexpression of P-glycoprotein (P-gp/ABCB1) is a leading cause of multidrug resistance (MDR). Hence, it is crucial to discover effective pharmaceuticals that counteract ABCB1-mediated multidrug resistance. FRAX486 is a p21-activated kinase (PAK) inhibitor. The objective of this study was to investigate whether FRAX486 can reverse ABCB1-mediated multidrug resistance, while also exploring its mechanism of action. The CCK8 assay demonstrated that FRAX486 significantly reversed ABCB1-mediated multidrug resistance. Furthermore, western blotting and immunofluorescence experiments revealed that FRAX486 had no impact on expression level and intracellular localization of ABCB1. Notably, FRAX486 was found to enhance intracellular drug accumulation and reduce efflux, resulting in the reversal of multidrug resistance. Docking analysis also indicated a strong affinity between FRAX486 and ABCB1. This study highlights the ability of FRAX486 to reverse ABCB1-mediated multidrug resistance and provides valuable insights for its clinical application.

Shellfish CO2 excretion is modulated by seawater carbonate chemistry but largely independent of pCO2.

Four species of shellfish, blue mussel (Mytilus galloprovincialis), Pacific abalone (Haliotis discus hannai), zhikong scallops (Chlamys farreri), and Pacific oyster (Crassostrea gigas), were exposed to decoupled carbonate system variables to investigate the impacts of different seawater carbonate parameters on the CO2 excretion process of mariculture shellfish. Six experimental groups with two levels of seawater pH (pH 8.1 and pH 7.7) and three levels of total alkalinity (TA = 1000, 2300, and 3600 µmol/kg, respectively) were established, while pH 8.1 and TA = 2300 µmol/kg was taken as control. Results showed that the CO2 excretion rates of these tested shellfish were significantly affected by the change in carbonate chemistry (P < 0.05). At the same TA level, animals incubated in the acidified group (pH 7.7) had a lower CO2 excretion rate than those in the control group (pH 8.1). In comparison, at the same pH level, the CO2 excretion rate increased when seawater TA level was elevated. No significant correlation between the CO2 excretion rate and seawater pCO2 levels (P > 0.05) was found; however, a significant correlation (P < 0.05) between CO2 excretion rate and TA-DIC (the difference between total alkalinity and dissolved inorganic carbon) was observed. Blue mussel has a significantly higher CO2 excretion rate than the other three species in the CO2 excretions per unit mass of soft parts, with no significant difference observed among these three species. However, in terms of CO2 excretion rate per unit mass of gills, abalone has the highest CO2 excretion rate, while significant differences were found between each species. Our studies indicate that the CO2 buffering capacity impacts the CO2 excretion rate of four shellfish species largely independent of pCO2. Since CO2 excretion is related to acid-base balancing, the results imply that the effects of other carbonate parameters, particularly the CO2 buffering capacity, should be studied to fully understand the mechanism of how acidification affects shellfish. Besides, the species difference in gill to soft parts proportion may contribute to the species difference in responding to ocean acidification.

Flexible ureteroscopic incision and drainage or laparoscopic unroofing for the parapelvic renal cysts: A systematic review and meta­analysis.

The aim of the present study was to compare flexible ureteroscopy and laparoscopy in the treatment of peripelvic renal cysts, so as to determine the best treatment method for patients with peripelvic renal cysts. A systematic search of the PubMed, EMBASE, Cochrane Library, CONAHL, Clinicaltrials.gov, Google Scholar, CNKI and WanFang DATA databases was conducted for articles published over 22 years (December 1980-December 2022) using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. By searching the database, a total of 594 studies were found, of which eight were analyzed as evidence. A total of 394 patients were included in the present study. Of these, 193 were treated laparoscopically and 201 were treated by flexible ureteroscopy. In terms of analysis results, radiation reexamination after laparoscopic therapy had a higher success rate. Ureteroscopy has advantages in the time spent in the operation, the amount of blood lost during the operation, the time to recover the anal exhaust after the operation and the length of postoperative hospital stay. There were no significant difference in postoperative recurrence or complications between the two surgical methods. After comprehensive analysis, it was considered that flexible ureteroscopy has more advantages in the treatment of peripelvic renal cyst, which is mainly manifested in the duration of operation, the total amount of blood loss during operation, the interval of recovery of anal exhaust after operation and the total length of postoperative hospital stay. It is worth further exploration and promotion.

Phylogenomics, taxonomy and morphological characters of the Microdochiaceae (Xylariales, Sordariomycetes).

Species of the family Microdochiaceae (Xylariales, Sordariomycetes) have been reported from worldwide, and collected from different plant hosts. The proposed new genus and two new species, viz., Macroidriella gen. nov., M.bambusae sp. nov. and Microdochiumaustrale sp. nov., are based on multi-locus phylogenies from a combined dataset of ITS rDNA, LSU, RPB2 and TUB2 with morphological characteristics. Microdochiumsinense has been collected from diseased leaves of Phragmitesaustralis and this is the first report of the fungus on this host plant. Simultaneously, we annotated 10,372 to 11,863 genes, identified 4,909 single-copy orthologous genes, and conducted phylogenomic analysis based on genomic data. A gene family analysis was performed and it will expand the understanding of the evolutionary history and biodiversity of the Microdochiaceae. The detailed descriptions and illustrations of species are provided.

Environment-responsive dendrobium polysaccharide hydrogel embedding manganese microsphere as a post-operative adjuvant to boost cascaded immune cycle against melanoma.

Rationale: Surgical resection is a primary treatment for solid tumors, but high rates of tumor recurrence and metastasis post-surgery present significant challenges. Manganese (Mn2+), known to enhance dendritic cell-mediated cancer immunotherapy by activating the cGAS-STING pathway, has potential in post-operative cancer management. However, achieving prolonged and localized delivery of Mn2+ to stimulate immune responses without systemic toxicity remains a challenge. Methods: We developed a post-operative microenvironment-responsive dendrobium polysaccharide hydrogel embedded with Mn2+-pectin microspheres (MnP@DOP-Gel). This hydrogel system releases Mn2+-pectin microspheres (MnP) in response to ROS, and MnP shows a dual effect in vitro: promoting immunogenic cell death and activating immune cells (dendritic cells and macrophages). The efficacy of MnP@DOP-Gel as a post-surgical treatment and its potential for immune activation were assessed in both subcutaneous and metastatic melanoma models in mice, exploring its synergistic effect with anti-PD1 antibody. Result: MnP@DOP-Gel exhibited ROS-responsive release of MnP, which could exert dual effects by inducing immunogenic cell death of tumor cells and activating dendritic cells and macrophages to initiate a cascade of anti-tumor immune responses. In vivo experiments showed that the implanted MnP@DOP-Gel significantly inhibited residual tumor growth and metastasis. Moreover, the combination of MnP@DOP-Gel and anti-PD1 antibody displayed superior therapeutic potency in preventing either metastasis or abscopal brain tumor growth. Conclusions: MnP@DOP-Gel represents a promising drug-free strategy for cancer post-operative management. Utilizing this Mn2+-embedding and ROS-responsive delivery system, it regulates surgery-induced immune responses and promotes sustained anti-tumor responses, potentially increasing the effectiveness of surgical cancer treatments.

Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma: A population-based study.

BACKGROUND: Gastric signet ring cell carcinoma (GSRC) represents a specific subtype of gastric cancer renowned for its contentious epidemiological features, treatment principles, and prognostic factors. AIM: To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC (LAGSRC) after surgery. METHODS: The annual rates of GSRC incidence and mortality, covering the years 1975 to 2019, were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software. The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates. The Cox regression model was used to explore the independent prognostic factors for overall survival (OS). The risk factors extracted were used to establish a prognostic nomogram. RESULTS: The overall incidence of GSRC increased dramatically between 1975 and 1998, followed by a significant downward trend in incidence after 1998. In recent years, there has been a similarly optimistic trend in GSRC mortality rates. The trend in GSRC showed discrepancies based on age and sex. Receiver operating characteristic curves, calibration curves, and decision curve analysis for 1-year, 3-year, and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram. The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system. CONCLUSION: The model we established can aid clinicians in the early prognostication of LAGSRC patients, resulting in improved clinical outcomes by modifying management strategies and patient health care.

Bone Marrow Mesenchymal Stem Cell-Derived Nanovesicles Containing H8 Improve Hepatic Glucose and Lipid Metabolism and Exert Ameliorative Effects in Type 2 Diabetes.

Purpose: Nanovesicles (NVs) derived from bone mesenchymal stem cells (BMSCs) as drug delivery systems are considered an effective therapeutic strategy for diabetes. However, its mechanism of action remains unclear. Here, we evaluated the efficacy and molecular mechanism of BMSC-derived NVs carrying the curcumin analog H8 (H8-BMSCs-NVs) on hepatic glucose and lipid metabolism in type 2 diabetes (T2D). Subjects and Methods: Mouse BMSCs were isolated by collagenase digestion and H8-BMSCs-NVs were prepared by microvesicle extrusion. The effects of H8-BMSCs-NVs on hepatic glucose and lipid metabolism were observed in a T2D mouse model and a HepG2 cell insulin resistance model. To evaluate changes in potential signaling pathways, the PI3K/AKT/AMPK signaling pathway and expression levels of G6P and PEPCK were assessed by Western blotting. Results: H8-BMSCs-NVs effectively improved lipid accumulation in liver tissues and restored liver dysfunction in T2D mice. Meanwhile, H8-BMSCs-NVs effectively inhibited intracellular lipid accumulation in the insulin resistance models of HepG2 cells. Mechanistic studies showed that H8-BMSCs-NVs activated the PI3K/AKT/AMPK signaling pathway and decreased the expression levels of G6P and PEPCK. Conclusion: These findings demonstrate that H8-BMSCs-NVs improved hepatic glucose and lipid metabolism in T2D mice by activating the PI3K/AKT/AMPK signaling pathway, which provides novel evidence suggesting the potential of H8-BMSCs-NVs in the clinically treatment of T2D patients.

The evolution of calcified anaerobic granular sludge bed informs the deep insight into its agglomeration process.

Calcium-induced agglomeration of anaerobic granular sludge bed (AGSB) has become a critical factor in performance decline of calcified anaerobic reactors. However, the agglomeration process of AGSB and the underlying mechanisms remain unclear and elusive. This study delved into the evolution of calcified AGSB, and four typical states of normal AGSB (Nor-AGSB), calcified dispersed AGSB (Dis-AGSB), calcified dimeric AGSB (Dim-AGSB), and calcified polymeric AGSB (Pol-AGSB) were characterized. It was found that the minimum transport velocity of Dis-AGSB was 3.14-3.79 times higher than that of Nor-AGSB, and surpassed both the superficial velocity and the bubble-induced wake velocity. This led to the sedimentation of AGS at the bottom of reactor, resulting in stable contacts with each other. Solid fillers between AGS, namely cement, were observed within Dim-AGSB and Pol-AGSB, and could be classified as tightly- and loosely- bonded cement (T- and L-cement). Further analysis revealed that T-cement was rich in extracellular polymeric substances and intertwining pili/flagella, serving as the primary driving force for robust inter-AGS adhesion. While the L-cement was primarily in the form of calcite precipitation, and blocked the convective mass transfer pathways in Pol-AGSB, leading to the decreased convective mass transfer capacity. The critical distance between calcite and AGS was further revealed as 5.33 nm to form stable initial adhesion. Consequently, the agglomeration mechanism involving the evolution of AGSB was proposed as calcium-induced sedimentation, calcium-induced adhesion, and calcium-induced stasis in order. This study is expected to offer deep insight into the calcium-induced agglomeration especially from the overlooked perspective of AGSB, and provides feasible control strategies to manage the pressing calcification issues in engineering applications.

Nano/micro flexible fiber and paper-based advanced functional packaging materials.

Recently, fiber-based and functional paper food packaging has garnered significant attention for its versatility, excellent performance, and potential to provide sustainable solutions to the food packaging industry. Fiber-based food packaging is characterized by its large surface area, adjustable porosity and customizability, while functional paper-based food packaging typically exhibits good mechanical strength and barrier properties. This review summarizes the latest research progress on food packaging based on fibers and functional paper. Firstly, the raw materials used for preparing fiber and functional paper, along with their physical and chemical properties and roles in food packaging, were discussed. Subsequently, the latest advancements in the application of fiber and paper materials in food packaging were introduced. This paper also discusses future research directions and potential areas for improvement in fiber and functional paper food packaging to further enhance their effectiveness in ensuring food safety, quality, and sustainability.

Ultra-efficient peroxymonosulfate utilization and trichloroethylene degradation in heterogeneous catalytic system guided by sheet-like Cu2MnO4 nanoparticles: The role of Cu(III)-O species and free radicals.

Synthesizing cubic spinel Cu2MnO4 with nanosheet structure (SCMO) aimed to construct a "non-radical-mediated radical-oxidative reaction", for increasing PMS utilization efficiency, and solving the defects of SO4•- and •OH through indirect PMS activation by electron transfer process. Compared with box-like Cu2MnO4 (11.1%, 0.0035 min-1) and ordinary Cu2MnO4 nanoparticles (21.3%, 0.0070 min-1), SCMO/PMS showed excellent trichloroethylene removal (98.8%, 0.1577 min-1). The pivotal role of Cu(III) was determined based on EPR analysis, quenching experiments, chemical probe experiments, hydrogen temperature-programmed reduction and Raman spectroscopy analysis, in-situ FTIR and Raman analyses. In brief, the interaction between PMS and SCMO could produce surface-bonded reactive complexes and the subsequent breaking of O-O bond in the sub-stable structure allowed the conversion of Cu(II) to Cu(III), which in turn facilitates the generation of •OH and SO4•-. The density functional theory (DFT) calculations provided supporting evidence for the electron donor role of SCMO and the increase of the electron acceptance capacity of PMS. SCMO/PMS system showed good resistance and degradation efficiency to complex composition and combined pollutants in actually contaminated groundwater, respectively. However, the coexistence of high concentrations of arsenic could significantly affect SCMO performance due to their adsorption on -OH groups, which still need in-depth study.

Percutaneous coronary intervention leads to microplastics entering the blood: Interventional devices are a major source.

Microplastics (MPs) is an emerging pollutant potentially harmful to health. Medical practices using plastic devices, such as percutaneous coronary interventions (PCI), may result in MPs entering into the blood. The purpose of this study was to quantify the effect of PCI on microplastic levels in patients' blood. Laser direct infrared (LDIR) was used to detect MPs in the blood of 23 patients before and after PCI. MPs in the water in which devices used in PCI were washed were also examined. The concentration of MPs in the blood was significantly elevated (93.57 ± 35.95 vs. 4.96 ± 3.40 particles/10 mL of blood, P < 0.001) after PCI compared to before, and the increased MPs were polyamide (PA), polyethylene (PE), polyurethane (PU), and polyethylene terephthalate (PET), which was consistent with the types of MPs detected in the device washing water. The maximum diameter of MPs in blood before PCI was 50 µm, whereas after PCI it was 213 µm, and even 336 µm in device washing water. These findings indicated that PCI will cause MPs to enter the blood, and devices used during PCI were a major source, a range of medical practices that use plastic devices may be a new route for MPs to enter the human body.

MCA Parallel Anatomic Scanning MR Imaging-Guided Recanalization of a Chronic Occluded MCA by Endovascular Treatment.

Basi-parallel anatomic scanning has been widely used for assessing the vascular morphology of vertebral basilar arteries. Previous studies have demonstrated its efficacy in evaluating the morphology of the MCA, which we refer to as MCA parallel anatomic scanning MR imaging (MCPAS). In this study, we present our experience with the application of MCPAS in patients with MCA occlusion. Endovascular treatment was performed on the patients with intact MCA morphology visible in on MCPAS, with no intracranial hemorrhage, occlusion, or other complications observed. No severe stenosis or re-occlusion was observed at the 12-month postoperative follow-up. In conclusion, MCPAS is an effective method for assessing the outer contour of an occlusive MCA. Endovascular treatment can be considered a safe and efficient option for patients who show a favorable MCA through MCPAS assessment.

The volatile oil of Hyssopus cuspidatus Boriss. (HVO) ameliorates OVA-induced allergic asthma via inhibiting PI3K/Akt/JNK/P38 signaling pathway and maintaining airway barrier integrity.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyssopus cuspidatus Boriss., a classic Uyghur medicine, is used to treat inflammatory lung diseases such as asthma. But the therapeutic effect and mechanism of the volatile oil of Hyssopus cuspidatus Boriss.(HVO) in asthma therapy remain unclear. AIM OF THE STUDY: We aim to characterize the constituents of HVO, investigate the therapeutic effect in OVA-induced allergic asthmatic mice and further explore the molecular mechanism. MATERIALS AND METHODS: In this study, we applied two-dimensional gas chromatography quadrupole time-of-flight mass spectrometry (GC × GC-QTOF MS) to identify the ingredients of HVO. We established OVA-induced asthmatic model to investigate the therapeutic effect of HVO. To further explore the potential molecular pathways, we used network pharmacology approach to perform GO and KEGG pathways enrichment, and then built an ingredient-target-pathway network to identify key molecular pathways. Finally, LPS-induced RAW 264.7 macrophages and OVA-induced asthmatic model were used to validate the potential signaling pathways. RESULTS: GC × GC-QTOF MS analysis revealed the presence of 123 compounds of HVO. The sesquiterpenes and monoterpenes are the main constituents. The in vivo study indicated that HVO suppressed OVA-induced eosinophilic infiltration in lung tissues, inhibited the elevation of IgE, IL-4, IL-5, and IL-13 levels, downregulated the expressions of phosphorylated PI3K, Akt, JNK and P38, and maintained epithelial barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin. The in vitro study also revealed an inhibition of NO release and downregulation of phosphorylated PI3K, Akt, JNK and P38 levels. CONCLUSION: HVO alleviates airway inflammation in OVA-induced asthmatic mice by inhibiting PI3K/Akt/JNK/P38 signaling pathway and maintaining airway barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin.

Lipocalin-2 induced LDHA expression promotes vascular remodelling in pulmonary hypertension.

Aerobic glycolysis is involved in the pathogenesis of pulmonary hypertension (PH). The mechanisms by which glycolysis is increased and how it contributes to pulmonary vascular remodelling are not yet fully understood. In this study, we demonstrated that elevated lipocalin-2 (LCN2) in PH significantly enhances aerobic glycolysis in human pulmonary artery smooth muscle cells (PASMCs) by up-regulating LDHA expression. Knockout of Lcn2 or having heterozygous LDHA deficiency in mice significantly inhibits the progression of hypoxic PH. Our study reveals that LCN2 stimulates LDHA expression by activating Akt-HIF-1α signalling pathway. Inhibition of Akt or HIF-1α reduces LDHA expression and proliferation of PASMCs. Both Akt and HIF-1α play critical roles in the development of PH and are suppressed in the pulmonary vessels of hypoxic PH mice lacking LCN2. These findings shed light on the LCN2-Akt-HIF1α-LDHA axis in aerobic glycolysis in PH.

A novel nomogram model for lung adenocarcinoma subtypes based on RNA-modification regulatory genes.

Background: In non-small cell lung cancer (NSCLC), lung adenocarcinoma (LUAD) is the most common subtype. RNA modification has become the frontier and hotspot of current tumor research. Results: In this study, 109 genes that regulate RNA modifications were identified according to The Cancer Genome Atlas (TCGA). A differential gene expression analysis identified 46 differentially expressed RNA modification regulatory genes (DERRGs). LUAD samples were stratified into two distinct clusters based on the expression of these DERRGs. A significant correlation was observed between these clusters and patient survival rates, as well as clinical features. Furthermore, a four-DERRG signature (EIF3B, HNRNPC, IGF2BP1, and METTL3) developed using LASSO regression. According to the calculated risk scores from this signature, LUAD patients were categorized into high-risk and low-risk groups. Patients in the low-risk group exhibited a more favorable prognosis. A prognostic nomogram was crafted, integrating the four-DERRGs signature with clinical parameters. The nomogram was revealed that OS, age, clinical stage, immune cell infiltration, and immune checkpoint molecule expression were significantly linked to the OS of LUAD. GSEA analysis found that the DERRGs were primarily regulated immune pathways. Conclusions: This study developed four DERRGs signatures and formulated a nomogram model for precise prognosis estimation in LUAD patients. The study's insights are instrumental for advancing diagnosis, prognosis, and therapeutic strategies for LUAD.

Six-Cyclic Crown Ether-Type Pillar[5]arene: Enhanced Binding Ability to Bispyridinium Derivatives.

A six-cyclic crown ether-type pillar[5]arene was synthesized, and the five ethylene oxide loops were located outside the cavity and not affected by temperature changes which was confirmed by variable-temperature NMR experiment in DMSO-d6 and CDCl3 and 2D 1H-1H NOESY experiment in CDCl3. The six-cyclic pillar[5]-crown also showed greater binding ability of host-guest with bis(pyridinium) derivatives than conventional alkoxy pillar[5]arenes that illustrated through 1H NMR titration spectroscopic experiment in acetone-d6/CDCl3 (1:1) and UV-vis titration experiments in CHCl3 at room temperature. The five benzocrown ethers at the periphery were able to bind metal cations by 1H NMR titration spectroscopic experiment in CD2Cl2/methanol-d4(9:1).

Quantitative Assessment of Acute Intracranial Clot and Collaterals on High Resolution Magnetic Resonance Imaging.

INTRODUCTION: There has been an increasing demand for imaging methods that provide a comprehensive evaluation of intracranial clot and collateral circulation, which are helpful for clinical decision-making and predicting functional outcomes. We aimed to quantitatively evaluate acute intracranial clot burden and collaterals on high-resolution magnetic resonance imaging (HR-MRI). METHODS: We analyzed acute ischemic stroke patients with internal carotid artery or middle cerebral artery occlusion in a prospective multicenter study. The clot burden was scored on a scale of 0-10 based on the clot location on HR-MRI. The collateral score was assigned on a scale of 0-3 using the minimum intensity projection from HR-MRI. Uni- and multivariable logistic regression analyses were performed to assess their correlation with clinical outcome (modified Rankin Scale >2 at 90 days). Thresholds were defined to dichotomize into low and high score groups and predictive performances were assessed for clinical and radiologic outcomes. RESULTS: Ninety-nine patients (mean age of 60.77 ± 11.54 years) were included in the analysis. The interobserver correlation was 0.89 (95% CI: 0.77-0.95) for the clot burden score and 0.78 (95% CI: 0.53-0.90) for the collateral score. Multivariable logistic regression analysis demonstrated that the collateral score (odds ratio: 0.41, 95% CI: 0.19-0.90) was significantly associated with clinical outcomes. A better functional outcome was observed in the group with clot burden scores greater than 7 (p=0.011). A smaller final infarct size and a higher diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score were observed in the group with collateral scores greater than 1 (all p<0.05). CONCLUSIONS: HR-MRI offers a new tool for quantitative assessment of clot burden and collaterals simultaneously in future clinical practices and research endeavors.