Alterations in Blood Methylome as Potential Epigenetic Biomarker in Sporadic Parkinson's Disease.

OBJECTIVE: To characterize DNA methylation (DNAm) differences between sporadic Parkinson's disease (PD) and healthy control (HC) individuals enrolled in the Parkinson's Progression Markers Initiative (PPMI). METHODS: Using whole blood, we characterized longitudinal differences in DNAm between sporadic PD patients (n = 196) and HCs (n = 86) enrolled in PPMI. RNA sequencing (RNAseq) was used to conduct gene expression analyses for genes mapped to differentially methylated cytosine-guanine sites (CpGs). RESULTS: At the time of patient enrollment, 5,178 CpGs were differentially methylated (2,683 hypermethylated and 2,495 hypomethylated) in PD compared to HC. Of these, 579 CpGs underwent significant methylation changes over 3 years. Several differentially methylated CpGs were found near the cytochrome P450 family 2 subfamily E member 1 (CYP2E1) gene. Additionally, multiple hypermethylated CpGs were associated with the N-myc downregulated gene family member 4 (NDRG4) gene. RNA-Seq analyses showed 75 differentially expressed genes in PD patients compared to controls. An integrative analysis of both differentially methylated sites and differentially expressed genes revealed 20 genes that exhibited hypomethylation concomitant with overexpression. Additionally, 1 gene, cathepsin H (CTSH), displayed hypermethylation that was associated with its decreased expression. INTERPRETATION: We provide initial evidence of alterations in DNAm in blood of PD patients that may serve as potential epigenetic biomarker of disease. To evaluate the significance of these changes throughout the progression of PD, additional profiling at longer intervals and during the prodromal stages of disease will be necessary. ANN NEUROL 2024;95:1162-1172.

IL-13 and IL-13-induced periostin levels are specifically decreased in patients following endoscopic sinus surgery for chronic rhinosinusitis.

BACKGROUND: Type 2 (T2) inflammation plays a pathogenic role in chronic rhinosinusitis (CRS). The effects of endoscopic sinus surgery (ESS) on T2 inflammation are unknown. OBJECTIVE: The aim of this study was to compare T2 inflammatory biomarkers from middle meatal (MM) mucus for distinguishing patients with CRS from CRS-free patients, identifying major phenotypes (CRS without nasal polyps [CRSsNP] and CRS with nasal polyps [CRSwNP]), assessing endotypic change, and establishing cross-sectional and longitudinal outcomes in patients undergoing ESS. METHODS: MM mucus samples were collected from patients with CRSsNP and patients with CRSwNP before and 6 to 12 months after ESS and compared with samples from CRS-free control patients. T2 biomarkers were evaluated both continuously and using threshold-based definitions of T2 endotype to identify relationships with patient-reported (based on the 22-Item Sinonasal Outcomes Test and Chronic Rhinosinusitis Patient-Reported Outcomes Measure) and clinician-reported (radiographic and endoscopic) severity. Linear mixed models were developed to analyze clinical variables associated with T2 biomarker levels. RESULTS: A total of 154 patients with CRS (89 with CRSsNP and 65 with CRSwNP) were enrolled, with a mean interval of 9 months between ESS and follow-up. An analysis of pre-ESS MM mucus samples revealed elevated levels of T2 mediators in patients with CRSwNP versus in patients with CRSsNP and CRS-free controls. Temporally stable correlations between levels of IL-13 and IL-5, levels of periostin and complement 5a, and levels of eosinophil cationic protein (ECP) and eotaxin-3 were observed. On this basis and on the basis of pathologic significance, levels of IL-13, periostin and ECP were further analyzed. After ESS, levels of IL-13 and periostin decreased significantly, whereas ECP levels remained unchanged. Across pre- and post-ESS evaluation, the T2 endotype was associated with radiographic severity but did not predict outcomes. CRSwNP status and African American race were associated with higher levels of IL-13 and periostin, whereas ECP level was higher in patients undergoing extensive surgery. CONCLUSION: ESS decreased levels of IL-13 and periostin in the middle meatus. T2 inflammation after ESS was correlated with patient- and clinician-reported severity across phenotypes. Pre-ESS T2 inflammation did not predict post-ESS outcomes.

UDP-Glucose/P2Y14 Receptor Signaling Exacerbates Neuronal Apoptosis After Subarachnoid Hemorrhage in Rats.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a severe subtype of stroke with poor outcomes. Abnormal glucose metabolism often occurs after SAH, but the strict control of blood glucose levels is not always beneficial. This study aimed to investigate the contribution of uridine diphosphate glucose (UDP-G), an intermediate of glucose/glycogen metabolism, and its receptor P2Y14 (P2Y purinoceptor 14) to SAH pathology and explored the potential targeted treatments in rats. METHODS: A total of 218 Sprague-Dawley male rats were used. SAH was induced by endovascular perforation. Brain expressions of P2Y14, uridine diphosphate glucose (UDP-G), and its converting enzyme UGP2 (UDP-G pyrophosphorylase-2) were evaluated. Exogenous UDP-G or selective P2Y14 inhibitor was administered intranasally at 1 hour after SAH to explore their potential effects. Intranasal Ugp2 or P2ry14 siRNA was delivered 24 hours before SAH for mechanistic evaluation. Primary neuron culture and hemoglobin stimulation were used as in vitro model of SAH. Post-SAH evaluation included liquid chromatography-mass spectrometry measurement of brain endogenous UDP-G level, neurobehavioral assessments, Western blotting, immunohistochemistry, TUNEL staining, and Nissl staining. RESULTS: There was an acute elevation of endogenous brain UDP-G and UGP2 after SAH, and P2Y14 was expressed in neurons. Although P2Y14 inhibitor decreased neurological dysfunction, neuronal apoptosis, and proapoptotic molecules, exogenous UDP-G exacerbated these outcomes at 24 hours after SAH. Early inhibition of P2Y14 preserved long-term neuronal survival in the hippocampus, amygdala, and cortex with improved neurocognition and depressive-like behavior. In addition, in vivo knockdown of Ugp2- and P2ry14-reduced neurological deficits and proapoptotic molecules at 24 hours after SAH, and furthermore in vitro knockdown of P2ry14-reduced apoptosis in hemoglobin stimulated primary neuron. CONCLUSIONS: These findings suggest a detrimental role of brain UDP-G/P2Y14 signaling in SAH, as a part of glucose metabolic pathology at the tissue level. P2Y14 inhibitor 4-[4-(4-piperidinyl)phenyl]-7-[4-(trifluoromethyl)phenyl]-2-naphthalenecarboxylic acid hydrochloride may serve as a potential therapeutic target in treating patients with SAH.

PEDF-34 attenuates neurological deficit and suppresses astrocyte-dependent neuroinflammation by modulating astrocyte polarization via 67LR/JNK/STAT1 signaling pathway after subarachnoid hemorrhage in rats.

BACKGROUND: Reactive astrocytes participate in various pathophysiology after subarachnoid hemorrhage (SAH), including neuroinflammation, glymphatic-lymphatic system dysfunction, brain edema, BBB disruption, and cell death. Astrocytes transform into two new reactive phenotypes with changed morphology, altered gene expression, and secretion profiles, termed detrimental A1 and beneficial A2. This study investigates the effect of 67LR activation by PEDF-34, a PEDF peptide, on neuroinflammation and astrocyte polarization after the experimental SAH. METHODS: A total of 318 male adult Sprague-Dawley rats were used in experiments in vivo, of which 272 rats were subjected to the endovascular perforation model of SAH and 46 rats underwent sham surgery. 67LR agonist (PEDF-34) was administrated intranasally 1 h after SAH. 67LR-specific inhibitor (NSC-47924) and STAT1 transcriptional activator (2-NP) were injected intracerebroventricularly 48 h before SAH. Short- and long-term neurological tests, brain water content, immunostaining, Nissl staining, western blot, and ELISA assay were performed. In experiments in vitro, primary astrocyte culture with hemoglobin (Hb) stimulation was used to mimic SAH. The expression of the PEDF-34/67LR signaling pathway and neuro-inflammatory cytokines were assessed using Western blot, ELISA, and immunohistochemistry assays both in vivo and in vitro. RESULTS: Endogenous PEDF and 67LR expressions were significantly reduced at 6 h after SAH. 67LR was expressed in astrocytes and neurons. Intranasal administration of PEDF-34 significantly reduced brain water content, pro-inflammatory cytokines, and short-term and long-term neurological deficits after SAH. The ratio of p-JNK/JNK and p-STAT1/STAT1 and the expression of CFB and C3 (A1 astrocytes marker), significantly decreased after PEDF-34 treatment, along with fewer expression of TNF-α and IL-1ß at 24 h after SAH. However, 2-NP (STAT1 transcriptional activator) and NSC-47924 (67LR inhibitor) reversed the protective effects of PEDF-34 in vivo and in vitro by promoting A1 astrocyte polarization with increased inflammatory cytokines. CONCLUSION: PEDF-34 activated 67LR, attenuating neuroinflammation and inhibiting astrocyte A1 polarization partly via the JNK/STAT1 pathway, suggesting that PEDF-34 might be a potential treatment for SAH patients.

High-resolution extracellular pH imaging of liver cancer with multiparametric MR using Deep Image Prior.

Noninvasive extracellular pH (pHe) mapping with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) using MR spectroscopic imaging (MRSI) has been demonstrated on 3T clinical MR scanners at 8 × 8 × 10 mm3 spatial resolution and applied to study various liver cancer treatments. Although pHe imaging at higher resolution can be achieved by extending the acquisition time, a postprocessing method to increase the resolution is preferable, to minimize the duration spent by the subject in the MR scanner. In this work, we propose to improve the spatial resolution of pHe mapping with BIRDS by incorporating anatomical information in the form of multiparametric MRI and using an unsupervised deep-learning technique, Deep Image Prior (DIP). Specifically, we used high-resolution T 1 , T 2 , and diffusion-weighted imaging (DWI) MR images of rabbits with VX2 liver tumors as inputs to a U-Net architecture to provide anatomical information. U-Net parameters were optimized to minimize the difference between the output super-resolution image and the experimentally acquired low-resolution pHe image using the mean-absolute error. In this way, the super-resolution pHe image would be consistent with both anatomical MR images and the low-resolution pHe measurement from the scanner. The method was developed based on data from 49 rabbits implanted with VX2 liver tumors. For evaluation, we also acquired high-resolution pHe images from two rabbits, which were used as ground truth. The results indicate a good match between the spatial characteristics of the super-resolution images and the high-resolution ground truth, supported by the low pixelwise absolute error.

Effect of Peptide-Polymer Host-Guest Electrostatic Interactions on Self-Assembling Peptide Hydrogels Structural and Mechanical Properties and Polymer Diffusivity.

Peptide-based supramolecular hydrogels are an attractive class of soft materials for biomedical applications when biocompatibility is a key requirement as they exploit the physical self-assembly of short self-assembling peptides avoiding the need for chemical cross-linking. Based on the knowledge developed through our previous work, we designed two novel peptides, E(FKFE)2 and K(FEFK)2, that form transparent hydrogels at pH 7. We characterized the phase behavior of these peptides and showed the clear link that exists between the charge carried by the peptides and the physical state of the samples. We subsequently demonstrate the cytocompatibility of the hydrogel and its suitability for 3D cell culture using 3T3 fibroblasts and human mesenchymal stem cells. We then loaded the hydrogels with two polymers, poly-l-lysine and dextran. When polymer and peptide fibers carry opposite charges, the size of the elemental fibril formed decreases, while the overall level of fiber aggregation and fiber bundle formation increases. This overall network topology change, and increase in cross-link stability and density, leads to an overall increase in the hydrogel mechanical properties and stability, i.e., resistance to swelling when placed in excess media. Finally, we investigate the diffusion of the polymers out of the hydrogels and show how electrostatic interactions can be used to control the release of large molecules. The work clearly shows how polymers can be used to tailor the properties of peptide hydrogels through guided intermolecular interactions and demonstrates the potential of these new soft hydrogels for use in the biomedical field in particular for delivery or large molecular payloads and cells as well as scaffolds for 3D cell culture.

Constructing a Stable Built-In Electric Field in Bi/Bi2Te3 Nanowires for Electrochemical CO2 Reduction Reaction.

Electrochemically converting carbon dioxide (CO2) into valuable fuels and renewable chemical feedstocks is considered a highly promising approach to achieve carbon neutrality. In this work, a robust interfacial built-in electric field (BEF) has been successfully designed and created in Bi/Bi2Te3 nanowires (NWs). The Bi/Bi2Te3 NWs consistently maintain over 90% Faradaic efficiency (FE) within a wide potential range (-0.8 to -1.2 V), with HCOOH selectivity reaching 97.2% at -1.0 V. Moreover, the FEHCOOH of Bi/Bi2Te3 NWs can still reach 94.3% at a current density of 100 mA cm-2 when it is used as a cathode electrocatalyst in a flow-cell system. Detailed in situ experiments confirm that the presence of interfacial BEF between Bi and Bi/Bi2Te3 promotes the formation of *OHCO intermediates, thus facilitating the production of HCOOH species. DFT calculations show that Bi/Bi2Te3 NWs increase the formation energies of H* and *COOH while reducing the energy barrier for *OCHO formation, thus achieving a bidirectional optimization of intermediate adsorption. This work provides a feasible scheme for exploring electrocatalytic reaction intermediates by using the BEF strategy.

Differences of clinical phenotype between familial and sporadic Crohn's disease in East China.

PURPOSE: Family history is one of the strongest risk factors for inflammatory bowel diseases (IBD) while studies about the clinical phenotype of familial IBD are limited. This study aimed to compare the phenotypic features of familial Crohn's disease (CD) with sporadic CD. METHODS: Familial CD was defined as CD patients having one or more first, second, third, fourth degree, or above relatives with CD. Sporadic CD patients hospitalized during the same period were matched 1:3 by age and gender. Differences in clinical characteristics, phenotype distribution, extraintestinal manifestations, and complications at diagnosis, as well as treatment regimen and surgery, were compared between familial and sporadic CD. RESULTS: The familial CD was associated with a higher rate of past appendectomy history (P = 0.009), more intestinal perforation at onset (P = 0.012), more MRI results of anal lesion (P = 0.023), and gastrointestinal perforation (P = 0.040) at diagnosis, higher rate of past intestinal surgery history (P = 0.007), more number of intestinal surgeries (P = 0.037), longer duration of follow-up (P = 0.017), lower rate of taking biologicals for current maintenance (P = 0.043), lower tendency to upgrade to biologicals during follow-up (P = 0.013), higher possibility to experience gastrointestinal obstruction (P = 0.047), and abdominal abscess during follow-up (P = 0.045). CONCLUSION: Familial CD is associated with a more aggressive clinical phenotype.

Identification of a Novel Activated NK-Associated Gene Score Associated with Diagnosis and Biological Therapy Response in Ulcerative Colitis.

INTRODUCTION: Natural killer (NK) cells are associated with the pathogenesis of ulcerative colitis (UC); however, their precise contributions remain unclear. The present study aimed to investigate the diagnostic value of the activated NK-associated gene (ANAG) score in UC and evaluate its predictive value in response to biological therapy. METHODS: Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, differentially expressed genes (DEGs) were screened by the "Batch correction" and "Robust rank aggregation" (RRA) methods. The immune infiltration landscape was estimated using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. DEGs that correlated with activated NK cells were identified as activated NK-associated genes (ANAGs). Protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression were used to screen key ANAGs and establish an ANAG score. The expression levels of the four key ANAGs were validated in human samples by real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence. The potential therapeutic drugs for UC were identified using the DSigDB database. Through scRNA-seq data analysis, the cell scores based on the ANAGs were calculated by "AddModuleScore" and "AUCell." RESULTS: Immune infiltration analysis revealed a higher abundance of activated NK cells in noninflamed UC tissues (ssGSEA, p < 0.001; CIBERSORT, p < 0.01). Fifty-four DEGs correlated with activated NK cells were identified as ANAGs. The ANAG score was established using four key ANAGs (SELP, TIMP1, MMP7, and ABCG2). The ANAG scores were significantly higher in inflamed tissues (p < 0.001) and in biological therapy nonresponders (NR) tissues before treatment (golimumab, p < 0.05; ustekinumab, p < 0.001). The ANAG score demonstrated an excellent diagnostic value (AUC = 0.979). Patients with higher ANAG scores before treatment were more likely to experience a lack of response to golimumab or ustekinumab (golimumab, p < 0.05; ustekinumab, p < 0.001). CONCLUSION: This study established a novel ANAG score with the ability to precisely diagnose UC and distinguish the efficacy of biological treatment.

Periods of low renal perfusion pressure are associated with acute kidney injury following paediatric cardiac surgery.

INTRODUCTION: Acute kidney injury is associated with worse outcomes after cardiac surgery. The haemodynamic goals to ameliorate kidney injury are not clear. Low post-operative renal perfusion pressure has been associated with acute kidney injury in adults. Inadequate oxygen delivery may also cause kidney injury. This study evaluates pressure and oximetric haemodynamics after paediatric cardiac surgery and their association with acute kidney injury. MATERIALS AND METHODS: Retrospective case-control study at a children's hospital. Patients were < 6 months of age who underwent a Society of Thoracic Surgery-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery categories ≥ 3. Low renal perfusion pressure was time and depth below several tested thresholds. The primary outcome was serum creatine-defined acute kidney injury in the first 7 days. RESULTS: Sixty-six patients (median age 8 days) were included. Acute kidney injury occurred in 36%. The time and depth of renal perfusion pressure < 42 mmHg in the first 24 hours was greater in acute kidney injury patients (94 versus 35 mmHg*minutes of low renal perfusion pressure/hour, p = 0.008). In the multivariable model, renal perfusion pressure < 42 mmHg was associated with acute kidney injury (aOR: 2.07, 95%CI: 1.25-3.82, p = 0.009). Mean arterial pressure, central venous pressure, and measures of inadequate oxygen delivery were not associated with acute kidney injury. CONCLUSION: Periods of low renal perfusion pressure (<42 mmHg) in the first 24 post-operative hours are associated with acute kidney injury. Renal perfusion pressure is a potential modifiable target that may mitigate the impact of acute kidney injury after paediatric cardiac surgery.

Fabrication and Application of Ag@SiO2/Au Core-Shell SERS Composite in Detecting Cu2+ in Water Environment.

A sensitive and simple method for detecting Cu2+ in the water source was proposed by using surface-enhanced Raman scattering spectroscopy (SERS) based on the Ag@SiO2/Au core-shell composite. The Ag@SiO2 SERS tag was synthesized by a simple approach, in which Ag nanoparticles were first embedded with Raman reporter PATP and next coated with a SiO2 shell. The Ag@SiO2 nanoparticles had strong stability even in a high-concentration salty solution, and there were no changes to their properties and appearance within one month. The Ag@SiO2/Au composite was fabricated through a controllable self-assemble process. L-cysteine was decorated on the surface of a functionalized Ag@SiO2/Au composite, as the amino and carboxyl groups of it can form coordinate covalent bond with Cu2+, which shows that the Ag@SiO2/Au composite labelled with L-cysteine has excellent performance for the detection of Cu2+ in aqueous media. In this study, the SERS detection of Cu2+ was carried out using Ag@SiO2 nanoparticles, and the limit of detection (LOD) as low as 0.1 mg/L was achieved.

Fractalkine Enhances Hematoma Resolution and Improves Neurological Function via CX3CR1/AMPK/PPARγ Pathway After GMH.

BACKGROUND: Hematoma clearance has been a proposed therapeutic strategy for hemorrhagic stroke. This study investigated the impact of CX3CR1 (CX3C chemokine receptor 1) activation mediated by r-FKN (recombinant fractalkine) on hematoma resolution, neuroinflammation, and the underlying mechanisms involving AMPK (AMP-activated protein kinase)/PPARγ (peroxisome proliferator-activated receptor gamma) pathway after experimental germinal matrix hemorrhage (GMH). METHODS: A total of 313 postnatal day 7 Sprague Dawley rat pups were used. GMH was induced using bacterial collagenase by a stereotactically guided infusion. r-FKN was administered intranasally at 1, 25, and 49 hours after GMH for short-term neurological evaluation. Long-term neurobehavioral tests (water maze, rotarod, and foot-fault test) were performed 24 to 28 days after GMH with the treatment of r-FKN once daily for 7 days. To elucidate the underlying mechanism, CX3CR1 CRISPR, or selective CX3CR1 inhibitor AZD8797, was administered intracerebroventricularly 24 hours preinduction of GMH. Selective inhibition of AMPK/PPARγ signaling in microglia via intracerebroventricularly delivery of liposome-encapsulated specific AMPK (Lipo-Dorsomorphin), PPARγ (Lipo-GW9662) inhibitor. Western blot, Immunofluorescence staining, Nissl staining, Hemoglobin assay, and ELISA assay were performed. RESULTS: The brain expression of FKN and CX3CR1 were elevated after GMH. FKN was expressed on both neurons and microglia, whereas CX3CR1 was mainly expressed on microglia after GMH. Intranasal administration of r-FKN improved the short- and long-term neurobehavioral deficits and promoted M2 microglia polarization, thereby attenuating neuroinflammation and enhancing hematoma clearance, which was accompanied by an increased ratio of p-AMPK (phosphorylation of AMPK)/AMPK, Nrf2 (nuclear factor erythroid 2-related factor 2), PPARγ, CD36 (cluster of differentiation 36), CD163 (hemoglobin scavenger receptor), CD206 (the mannose receptor), and IL (interleukin)-10 expression, and decreased CD68 (cluster of differentiation 68), IL-1ß, and TNF (tumor necrosis factor) α expression. The administration of CX3CR1 CRISPR or CX3CR1 inhibitor (AZD8797) abolished the protective effect of FKN. Furthermore, selective inhibition of microglial AMPK/PPARγ signaling abrogated the anti-inflammation effects of r-FKN after GMH. CONCLUSIONS: CX3CR1 activation by r-FKN promoted hematoma resolution, attenuated neuroinflammation, and neurological deficits partially through the AMPK/PPARγ signaling pathway, which promoted M1/M2 microglial polarization. Activating CX3CR1 by r-FKN may provide a promising therapeutic approach for treating patients with GMH.

Surgical versus nonsurgical treatment selection patterns among Asian American patients with pelvic floor disorders: a matched cohort study.

INTRODUCTION AND HYPOTHESIS: The objective was to determine if Asian racial identity was associated with the selection of surgical versus nonsurgical treatments for pelvic floor disorders (PFDs). Secondarily, we aimed to determine if there were other demographic or clinical characteristics associated with treatment selection patterns. METHODS: This was a retrospective matched cohort study that examined new patient visits (NPVs) of Asian patients at an academic urogynecology practice in Chicago, IL, USA. We included NPVs with primary diagnoses of anal incontinence, mixed urinary incontinence, stress urinary incontinence, overactive bladder, or pelvic organ prolapse. We identified Asian patients with self-identified racial identity recorded in the electronic medical records. Every Asian patient was age matched to white patients in a 1:3 ratio. The primary outcome was surgical versus nonsurgical treatment selection for their primary PFD diagnosis. Comparison of demographic and clinical variables between the two groups and multivariate logistic regression models were performed. RESULTS: A total of 53 Asian patients and 159 white patients were included in this analysis. Asian patients were less likely to be English speaking (92% vs 100%, p=0.004), endorse history of anxiety (17% vs 43%, p<0.001), and report history of any pelvic surgery (15% vs 34%, p=0.009) than white patients. When controlling for race, age, history of anxiety, depression, prior pelvic surgery, sexual activity, Pelvic Organ Prolapse Distress Inventory, Colorectal-Anal Distress Inventory, and Urinary Distress Inventory scores, Asian racial identity (adjusted odds ratio 0.36 [95% CI 0.14-0.85]) was independently associated with decreased likelihood of choosing surgical treatments for PFDs. CONCLUSIONS: Asian patients with PFDs were less likely than white patients to undergo surgical treatment for their PFDs despite similar demographic and clinical characteristics.

Exploratory mixed methods study on care-seeking behaviors of Asian Americans with pelvic floor symptoms.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate whether younger age was associated with noncare-seeking behavior among Asian Americans with pelvic floor symptoms, and secondarily, to explore multilevel factors that may contribute to noncare-seeking behavior in this population. METHODS: We performed a concurrent mixed methods study and heterogeneously sampled Asian Americans with urinary incontinence, urgency-frequency, vaginal bulge, or anal incontinence. We stratified the participants into two groups, care seekers vs noncare seekers. Using Anderson's model as the main framework, we administered validated questionnaires and conducted semi-structured interviews to explore factors associated with care-seeking behaviors. RESULTS: Seventy-eight surveys and 20 interviews were completed and analyzed. Most participants reported urinary leakage (67%), followed by urinary urgency-frequency (50%), anal incontinence (18%), and vaginal bulge (17%). The mean age of the study cohort was 46.1 ± 16.2 years. We found noncare seekers to be younger and with an increased proportion of lifetime spent in the USA than care seekers. When controlling for age, proportion of lifetime spent in the USA, symptom severity, and individual-level resources, both younger age and increased proportion of lifetime spent in USA remained independently associated with noncare-seeking behavior. From qualitative data, we found that noncare seekers often experienced anti-Asian racism across workplace, neighborhoods, and health care settings. Additionally, noncare seekers also reported symptom minimization and decreased self-efficacy when coping with their pelvic floor symptoms. CONCLUSIONS: We found that one's age and proportion of lifetime spent in the USA may affect the extent of exposure to anti-Asian racism that is associated with symptom minimization, increased perceived barrier, and noncare-seeking behavior.

Blood inflammatory biomarkers predict in-hospital pneumonia after endovascular treatment of aneurysm in patients with aneurysmal subarachoid hemorrhage.

The systemic inflammatory response index (SIRI) is a well-known marker of systemic inflammation reflecting the body's inflammatory/immune state. The study aimed to evaluate the relationship between the SIRI on admission and aneurysmal subarachnoid hemorrhage (aSAH)-associated pneumonia and compare with other currently used bio-markers. We reviewed 562 successive patients with aneurysmal SAH who underwent endovascular treatment between January 2019 and September 2021. ASAH-associated pneumonia was diagnosed using the modified Centers for Disease Control and Prevention criteria. The SIRI on admission was calculated as monocyte count × neutrophil count / lymphocyte count. Multiple logistic regression models were used for data analysis. A total of 158 (28.11%) patients developed aSAH-associated pneumonia. Using the Multiple logistic regression analysis, a notable dose-response association was found between the elevated SIRI (fourth quartile) and aSAH-associated pneumonia (adjusted odds ratio = 6.759; 95% confidence interval [CI], 3.280-13.930; p < 0.001 [p for trend < 0.001]). The SIRI (0.701, 95% CI: 0.653-0.749) presented a higher area under the curve (AUC) than systemic immune- inflammation index (SII) (0.669, 95% CI: 0.620-0.718) (p = 0.089); neutrophil-to-lymphocyte ratio (NLR) (0.665, 95% CI: 0.616-0.714) (p = 0.035) and platelet-lymphocyte ratio (PLR) (0.587, 95% CI: 0.534-0.641) (p < 0.001). A higher SIRI on admission was associated with aSAH-associated pneumonia, which may guide further clinical trials of prophylactic antibiotic therapy.

Association between higher systemic immune inflammation index (SII) and deep vein thrombosis (DVT) in patients with aneurysmal subarachnoid hemorrhage (aSAH) after endovascular treatment.

Inflammation contributes to deep vein thrombosis (DVT) formation in patients with aSAH after endovascular treatment. The relationship between systemic immune-inflammatory index (SII) as an inflammatory marker and DVT formation remains unclear. Thus, this study aims to evaluate the association between SII and aSAH-associated DVT following endovascular treatment. We enrolled 562 consecutive patients with aSAH after endovascular treatment at three centers from January 2019 to September 2021. The endovascular treatments included simple coil embolization and stent-assisted coil embolization. Deep venous thrombosis (DVT) was assessed by Color Doppler ultrasonography (CDUS). Multivariate logistic regression analysis was used to establish the model. We assessed the association of the SII, neutrophil-to-lymphocyte ratio (NLR), the systemic inflammatory response index (SIRI), platelet-lymphocyte ratio (PLR), and DVT by using restricted cubic spline (RCS). ASAH-associated DVT was found in 136 (24.20%) patients. Based on the multiple logistic regression analysis, the correlation was found between aSAH-associated DVT and elevated SII (fourth quartile) (adjusted odds ratio = 8.20 [95% confidence interval, 3.76-17.92]; p < 0.001 [p for trend < 0.001]), elevated NLR (fourth quartile) (adjusted odds ratio = 6.94 [95% confidence interval, 3.24-14.89]; p < 0.001 [p for trend < 0.001]), elevated SIRI (fourth quartile) (adjusted odds ratio = 4.82 [95% confidence interval, 2.36-9.84]; p < 0.001 [p for trend < 0.001]), and elevated PLR (fourth quartile) (adjusted odds ratio = 5.49 [95% confidence interval, 2.61-11.57]; p < 0.001 [p for trend < 0.001]). The increased SII was correlated with the formation of aSAH-associated DVT after endovascular treatment.

Association of elevated neutrophil-to-lymphocyte ratio with increased intracranial aneurysm stability scores and aneurysm growth.

BACKGROUND AND PURPOSE: Inflammation involves in the progression of intracranial aneurysms (IAs). However, whether the neutrophil-to-lymphocyte ratio (NLR) as an inflammatory marker links to IAs stability is unidentified. This study was performed to assess the association of the NLR with IAs stability. METHODS: We retrospectively reviewed the medical records of patients diagnosed with unruptured IAs from January 2014 to June 2018. According to the quartiles of the NLR, patients with unruptured IAs were categorized into four groups. We evaluated the association between the NLR and IAs stability scores and IAs growth. Multiple logistic regression models were used in the analysis. RESULTS: A significant dose-response association was found between the NLR with IAs stability scores and IAs growth. After adjustment for potential confounders, an elevated NLR (fourth quartile) was associated with increased PHASES score (>5) (adjusted odds ratio [OR], 2.007; 95% confidence interval [CI], 1.361-2.960; p<0.001 [p for trend <0.001]), increased ELAPSS score (>15) (adjusted OR, 1.581; 95% CI, 1.074-2.328; p=0.020 [p for trend =0.001]), increased JAPAN 3-year rupture risk score (>5) (adjusted OR, 1.512; 95% CI, 1.033-2.215; p=0.034 [p for trend <0.001]), and IAs growth (adjusted OR, 16.759; 95% CI, 3.022-92.928; p=0.001 [p for trend <0.001]). CONCLUSION: An elevated NLR was associated with increased IAs stability scores and IAs growth. The association between NLR and IAs stability need further investigate.

Effects of blood lipids and lipid-modifying drugs on intracranial aneurysms.

BACKGROUND AND PURPOSE: We used two-sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid-modifying drugs on intracranial aneurysm (IA). METHODS: Genetic variants for the effects of high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, and triglycerides and targets for lipid-modifying drugs were selected from the genome-wide discovery analyses of the UK Biobank. Summary-level data on IAs were obtained from the International Stroke Genetics Consortium. Univariate and multivariate MR analyses were performed. RESULTS: Univariate MR analyses showed that the HDL-C was negatively correlated with IA (odds ratio [OR] = 0.816, 95% confidence interval [CI] = 0.715-0.932, p = 0.003) and ruptured IA (rIA; OR = 0.775, 95% CI = 0.663-0.906, p = 0.001). The multivariate MR-inverse variance weighted analysis showed that the HDL-C was negatively correlated with IA (OR = 0.655, 95% CI = 0.434-0.988, p = 0.043) and rIA (OR = 0.563, 95% CI = 0.347-0.913, p = 0.02), and the LDL-C was negatively correlated with IA (OR = 0.402, 95% CI = 0.191-0.848, p = 0.017) and rIA (OR = 0.376, 95% CI = 0.160-0.883, p = 0.025). Using genetic proxies of known lipid-modifying drugs, we found that the increased HDL-C with cholesterol ester transfer protein proxies was associated with a decreased risk of rIA (OR = 0.852, 95% CI = 0.747-0.973, p = 0.018), and the decreased LDL-C with 3-hydroxy-3-methylglutaryl-coenzyme A reductase proxies was associated with increased risk of IA (OR = 1.772, 95% CI = 1.080-2.908, p = 0.024) and rIA (OR = 1.856, 95% CI = 1.022-3.371, p = 0.042). CONCLUSIONS: Genetically determined HDL-C and LDL-C reduce the risk of IA and rIA. The effects of different lipid-modifying drugs on IA need to be further investigated.

First Report of Neofusicoccum parvum Causing Leaf Spot on coral trees (Viburnum odoratissimum) in China.

Coral trees (Viburnum odoratissimum), as a class of evergreen shrubs, are mainly planted in landscapes in numerous cities in China. During September 2020, the author investigated four major parks in Hefei (Bao Park, Hefei Botanical Garden, Luzhou Park and Peninsula Park) and the campus of Anhui Agricultural University (approximately 0.5 ha) (31°49'21.30″N, 117°13'18.25″E). The results showed that the incidence rate of leaf spot disease reached 60% among approximately 100,000 coral trees planted in these areas. Coral trees begin to show leaf spots in August. In early stages of coral trees infection, the symptoms appeared as small brown spots ranged in length from 2 to 3 millimeters on the leaves. After the disease patches expand and darken, the coral leaves eventually wither and fall, which seriously affects its viewing and admiring value. To identify the fungal pathogen, the five-point sampling method was used to take typical similar leaf samples from 5 regions, and 6 samples were taken from each site, so a total of 150 samples were obtained. Fragments of sample leaves were surface-sterilized with 1% NaClO, plated on potato dextrose agar, and incubated at 25 °C in the dark. A total of 275 strains were obtained from 150 samples. According to the morphological characteristics, 275 strains were purified and divided into four types. Four representative strains (MI1, K1, F1, D1) were selected from four types for further pathogenicity testing and identification. The pathogenicity test was conducted in triplicate by inoculating wounded leaves of 1-year-old potted V. odoratissimum with 20µL of a conidial suspension (106 conidia/mL). The control was inoculated with sterile water. The specimens were placed in a growth chamber while maintaining 90% relative humidity and 28℃. After five days, the characteristic lesions were observed only on inoculated MI1 spore suspension leaves. The same fungus was reisolated from the lesions, thus fulfilling Koch's postulates. The pathogenic fungi accounted for 60% of all strains. Fungal colonies were circular and had abundant white aerial mycelium, and colonies changed from white to pure black after maturity. Conidia were fusiform (16-17×5-6 µm), thin-walled, transparent, and without diaphragms. Molecular identification was performed by partially sequencing the internal transcribed spacer (ITS) gene, the translation elongation Factor 1-alpha(EF1-alpha) gene, and the ß-tubulin (TUB2) gene by using the primers ITS1/ITS4 (White et al. 1990), EF1-728F (Alves et al. 2008)/EF1-986R (Carbone & Kohn 1999), and Bt2a/Bt2b (Glass & Donaldson 1995), respectively. The obtained ITS sequence (MW767713) showed 99% identity with N. parvum CMW28429 (KU997429.1), the EF1-alpha sequence (MZ398261) showed 99% identity with N. parvum isolate A4 (FJ528597.1), and the TUB2 sequence (MZ398260) showed 99% identity with N. parvum isolate BO52 (KU554657.1). By combining the sequences of individual fragments of each fungus in the order ITS, EF1-alpha and TUB2, MEGA 6.0 was used to analyze the sequence of kinship by using the maximum likelihood method, and the repeat value of bootstraps was 1000. A polygenic phylogenetic tree analysis based on multilocus alignment (ITS, EF1-alpha and TUB2) was constructed with some strains of Botryosphaeriaceae species. The results of the phylogenetic tree showed that MI1 and N. parvum clustered into a branch. To our knowledge, this is the first report of N. parvum causing leaf spot on V. odoratissimum in China.

LncRNA LINC00467 acted as an oncogene in esophageal squamous cell carcinoma by accelerating cell proliferation and preventing cell apoptosis via the miR-485-5p/DPAGT1 axis.

BACKGROUND AND AIM: Esophageal carcinoma has been regarded as one of the top 10 common malignancies globally. Esophageal squamous cell carcinoma (ESCC) is an important subtype of esophageal carcinoma with approximately 20% survival rate. Long noncoding RNAs were documented to regulate the occurrence or progression of several tumors. However, neither the biological role nor the molecular mechanism of LINC00467 has been explored. This research is aimed to investigating the regulatory mechanism of LINC00467 in ESCC. METHODS: In this study, a series of experiments including reverse transcription-quantitative polymerase chain reaction, Cell Counting Kit-8, luciferase reporter, western blot, and RNA immunoprecipitation were designed and conducted to explore the potential function and mechanism of LINC00467 in ESCC. RESULTS: According to experimental results, we found out upregulated LINC00467 improved cell proliferation, but hindered cell apoptosis. In mechanism, miR-485-5p was predicted, screened out, and validated to combine with LINC00467, which displayed lower expression in ESCC. Additionally, miR-485-5p negatively regulated and directly targeted DPAGT1. Rescue assays suggested that DPAGT1 amplification was able to recover the influence of LINC00467 deficiency on cell proliferation and apoptosis. Furthermore, knockdown of LINC00467 suppressed tumor growth in vivo. CONCLUSION: We proved that LINC00467 acted as an oncogene in ESCC by accelerating cell proliferation and preventing cell apoptosis via miR-485-5p/DPAGT1 axis. This may provide a potential diagnostic marker for ESCC treatment.