Hypomethylated leptin receptor reduces cerebral ischaemia-reperfusion injury by activating the JAK2/STAT3 signalling pathway.

OBJECTIVE: To investigate the cerebroprotective effects of leptin in vitro and in vivo via the Janus kinase-2 (JAK2)/transcription factor signal transducer and activators of transcription-3 (STAT3) pathway and leptin receptors (LEPR). METHODS: The study used the cellular oxygen-glucose deprivation (OGD) model in PC12 cells and the middle cerebral artery occlusion (MCAO) rat model of cerebral ischaemia-reperfusion injury (CIRI) to assess changes in gene expression and protein levels following leptin pretreatment. The methylated DNA immunoprecipitation (MeDIP) assay measured DNA methylation levels. RESULTS: The optimal leptin concentration for exerting neuroprotective effects against ischaemia-reperfusion injury in PC12 cells was 200 ng/ml in vitro, but excessive leptin diminished this effect. Leptin pretreatment in the MCAO rat model demonstrated a similar effect to previously reported leptin administration post-CIRI. In addition to regulating the expression of inflammation-related cytokines, Western blot analysis showed that leptin pretreatment upregulated BCL-2 and downregulated caspase 3 levels. The MeDIP analysis demonstrated that DNA methylation regulated LEPR gene expression in the MCAO rat model when leptin pretreatment was used. CONCLUSION: Exogenous leptin might bind to extra-activated LEPR by reducing the methylation level of the LEPR gene promoter region, which leads to an increase in phosphorylated JAK2/STAT3 and apoptotic signalling pathways.

Stemness subtypes in lower-grade glioma with prognostic biomarkers, tumor microenvironment, and treatment response.

Our research endeavors are directed towards unraveling the stem cell characteristics of lower-grade glioma patients, with the ultimate goal of formulating personalized treatment strategies. We computed enrichment stemness scores and performed consensus clustering to categorize phenotypes. Subsequently, we constructed a prognostic risk model using weighted gene correlation network analysis (WGCNA), random survival forest regression analysis as well as full subset regression analysis. To validate the expression differences of key genes, we employed experimental methods such as quantitative Polymerase Chain Reaction (qPCR) and assessed cell line proliferation, migration, and invasion. Three subtypes were assigned to patients diagnosed with LGG. Notably, Cluster 2 (C2), exhibiting the poorest survival outcomes, manifested characteristics indicative of the subtype characterized by immunosuppression. This was marked by elevated levels of M1 macrophages, activated mast cells, along with higher immune and stromal scores. Four hub genes-CDCA8, ORC1, DLGAP5, and SMC4-were identified and validated through cell experiments and qPCR. Subsequently, these validated genes were utilized to construct a stemness risk signature. Which revealed that Lower-Grade Glioma (LGG) patients with lower scores were more inclined to demonstrate favorable responses to immune therapy. Our study illuminates the stemness characteristics of gliomas, which lays the foundation for developing therapeutic approaches targeting CSCs and enhancing the efficacy of current immunotherapies. By identifying the stemness subtype and its correlation with prognosis and TME patterns in glioma patients, we aim to advance the development of personalized treatments, enhancing the ability to predict and improve overall patient prognosis.

Phosphorus-Doping Enables the Superior Durability of a Palladium Electrocatalyst towards Alkaline Oxygen Reduction Reactions.

The sluggish kinetics of oxygen reduction reactions (ORRs) require considerable Pd in the cathode, hindering the widespread of alkaline fuel cells (AFCs). By alloying Pd with transition metals, the oxygen reduction reaction's catalytic properties can be substantially enhanced. Nevertheless, the utilization of Pd-transition metal alloys in fuel cells is significantly constrained by their inadequate long-term durability due to the propensity of transition metals to leach. In this study, a nonmetallic doping strategy was devised and implemented to produce a Pd catalyst doped with P that exhibited exceptional durability towards ORRs. Pd3P0.95 with an average size of 6.41 nm was synthesized by the heat-treatment phosphorization of Pd nanoparticles followed by acid etching. After P-doping, the size of the Pd nanoparticles increased from 5.37 nm to 6.41 nm, and the initial mass activity (MA) of Pd3P0.95/NC reached 0.175 A mgPd-1 at 0.9 V, slightly lower than that of Pd/C. However, after 40,000 cycles of accelerated durability testing, instead of decreasing, the MA of Pd3P0.95/NC increased by 6.3% while the MA loss of Pd/C was 38.3%. The durability was primarily ascribed to the electronic structure effect and the aggregation resistance of the Pd nanoparticles. This research also establishes a foundation for the development of Pd-based ORR catalysts and offers a direction for the future advancement of catalysts designed for practical applications in AFCs.

Rapid and Sensitive Detection of Verticillium dahliae from Soil Using LAMP-CRISPR/Cas12a Technology.

Cotton Verticillium wilt is mainly caused by the fungus Verticillium dahliae, which threatens the production of cotton. Its pathogen can survive in the soil for several years in the form of microsclerotia, making it a destructive soil-borne disease. The accurate, sensitive, and rapid detection of V. dahliae from complex soil samples is of great significance for the early warning and management of cotton Verticillium wilt. In this study, we combined the loop-mediated isothermal amplification (LAMP) with CRISPR/Cas12a technology to develop an accurate, sensitive, and rapid detection method for V. dahliae. Initially, LAMP primers and CRISPR RNA (crRNA) were designed based on a specific DNA sequence of V. dahliae, which was validated using several closely related Verticillium spp. The lower detection limit of the LAMP-CRISPR/Cas12a combined with the fluorescent visualization detection system is approximately ~10 fg/µL genomic DNA per reaction. When combined with crude DNA-extraction methods, it is possible to detect as few as two microsclerotia per gram of soil, with the total detection process taking less than 90 min. Furthermore, to improve the method's user and field friendliness, the field detection results were visualized using lateral flow strips (LFS). The LAMP-CRISPR/Cas12a-LFS system has a lower detection limit of ~1 fg/µL genomic DNA of the V. dahliae, and when combined with the field crude DNA-extraction method, it can detect as few as six microsclerotia per gram of soil, with the total detection process taking less than 2 h. In summary, this study expands the application of LAMP-CRISPR/Cas12a nucleic acid detection in V. dahliae and will contribute to the development of field-deployable diagnostic productions.

Endovascular treatment of intracranial dural arteriovenous fistulas with Onyx: A consecutive series of 62 patients from a single-center.

OBJECTIVE: Intracranial intracranial dural arteriovenous fistulas (DAVFs) are mainly treated with an endovascular approach and various embolic agents. The aim of this study was to investigate the efficacy and safety of Onyx embolization in the treatment of DAVFs and characterize the factors as sociated with complete obliteration. METHODS: This retrospective study was based on 62 patients with DAVFs who underwent endovascular treatment with Onyx alone or in combination with coils at our institution. Clinical and imaging data were collected and analyzed. RESULTS: A total of 62 patients with 64 DAVFs were treated with endovascular embolization. The most common primary symptom was ophthalmological signs with a rate of 37.1%. Cognard type III was the most commonly seen subtype (32.8%). The immediate complete occlusion and follow-up rate was 92.2% and 93.5%, respectively. Transvenous balloon-assisted sinus protection was used in 12 patients (18.8%). The pressure cooker technique was used in eight patients (12.5%). Complications were seen in five patients including intracerebral hemorrhage (n = 2), venous thrombotic events (n = 2), and glued microcatheter (n = 1). CONCLUSIONS: Endovascular Onyx alone or in combination with coils embolization is a safe and effective therapy for DAVFs. Favorable angiographic and clinical outcomes can be achieved using different endovascular approaches. Transvenous balloon-assisted sinus protection and the pressure cooker technique may help achieve complete occlusion of DAVFs.

Association between lead and circulating markers of inflammation among traffic enforcers in Metro Manila, Philippines: the MMDA traffic enforcer's health study.

PURPOSE: Several epidemiological studies have linked lead (Pb) exposure to induced oxidative stress and the promotion of inflammatory response. We performed a within-subjects study (repeated measures study) to evaluate the relationship between the concentration of blood lead (B-Pb) and toenail lead (T-Pb) and circulating markers of inflammation. METHODS: We evaluated the associations between B-Pb concentrations and T-Pb concentrations and circulating markers of inflammation, soluble intracellular adhesion molecule-1 (s-ICAM-1), soluble vascular adhesion molecule-1 (s-VCAM-1), and high-sensitivity C-reactive protein (hs-CRP) on 158 traffic enforcers from the Metropolitan Manila Development Authority (MMDA) traffic enforcer's health study. Linear mixed-effects models with random subject-specific intercepts were fitted to estimate the association between B-Pb and T-Pb exposure and circulating markers of inflammation, adjusting for confounding factors. RESULTS: Traffic enforcers were middle-aged men (89.4%) with a mean age (± SD) of 37.1 years ± 8.9 years and had a total of 293 valid markers of inflammation measurements. B-Pb concentration was related to increased hs-CRP levels. A 10% increase in B-Pb was associated with a 5.7% increase in hs-CRP level [95% confidence interval (95% CI): 1.3-10.1]. However, B-Pb was not associated with s-ICAM-1 and s-VCAM-1. Furthermore, no associations were observed between T-Pb and all the circulating markers of inflammation. CONCLUSIONS: Low-level B-Pb may increase hs-CRP among traffic enforcers. Moreover, the study suggests that Pb via the oxidative and inflammation pathways may have an essential role in the development of cardiovascular disease. Furthermore, MMDA and the Department of Labor and Employment can use our study's findings as evidence to conduct routine screening of blood heavy metals, especially Pb, among MMDA and other traffic enforcers as part of their yearly medical examination.

Clinical Outcomes On Tubridge Flow Diverter in Treatmenting Intracranial Aneurysms: a Retrospective Multicenter Registry Study.

PURPOSE: In China, the application of nitinol Tubridge flow diverter (TFD) has become popular for treating intracranial aneurysms (IAs). In this study, we investigated the safety outcomes of the application of TFD for treating IAs in real-world scenarios. METHODS: We retrospectively analyzed aneurysms treated with TFD in 235 centers throughout China between April 2018 and April 2020. The primary endpoint was the event-free survival rate at 12 months, defined as the occurrence of morbidity (spontaneous rupture, intraparenchymal hemorrhage (IPH), ischemic stroke, and permanent cranial neuropathy) or death. Univariate and multivariate analyses were performed to assess the risk factors. A good outcome was defined as a modified Rankin Score (mRS) of 0-2. RESULTS: We included 1281 unruptured aneurysms treated with TFD. The overall neurological morbidity and death rates after 12 months were 5.4 and 2.8%, respectively. Ischemic strokes were the most common complication (4.2%, P < 0.001). Cranial neuropathy, IPH, and spontaneous rupture occurred in 0.3%, 0.3%, and 0.5% of aneurysms, respectively. Univariate and multivariate analyses indicated that the male gender, older age, larger aneurysm diameter, and aneurysm located on BA were the independent risk factors for neurologic events. Aneurysm located on BA was the independent risk factor for ischemic strokes. Most patients (1222) had access to the mRS, and 93.2% of them achieved good outcomes. CONCLUSION: Treatment of IAs with TFD was associated with low morbidity and mortality, most of which were ischemic events. Large posterior aneurysms might be associated with a higher complication rate. TRIAL REGISTRATION: Retrospectively registered.

Identifying individualized prognostic signature and unraveling the molecular mechanism of recurrence in early-onset colorectal cancer.

BACKGROUND: The incidence and mortality of early-onset colorectal cancer (EOCRC; < 50 years old) is increasing worldwide, with a high recurrence rate. The inherent heterogeneity of EOCRC makes its treatment challenging. Hence, to further understand the biology and reveal the molecular mechanisms of EOCRC, a recurrence risk signature is needed to guide clinical management. METHODS: Based on the relative expression orderings (REOs) of genes in each sample, a prognostic signature was developed and validated utilizing multiple independent datasets. The underlying molecular mechanisms between distinct prognostic groups were explored via integrative analysis of multi-omics data. RESULTS: The prognostic signature consisting of 6 gene pairs (6-GPS) could predict the recurrence risk for EOCRC at the individual level. High-risk EOCRC classified by 6-GPS showed a poor prognosis but a good response to adjuvant chemotherapy. Moreover, high-risk EOCRC was characterized by epithelial-mesenchymal transition (EMT) and enriched angiogenesis, and had higher mutation burden, immune cell infiltration, and PD-1/PD-L1 expression. Furthermore, we identified four genes associated with relapse-free survival in EOCRC, including SERPINE1, PECAM1, CDH1, and ANXA1. They were consistently differentially expressed at the transcriptome and proteome levels between high-risk and low-risk EOCRCs. They were also involved in regulating cancer progression and immune microenvironment in EOCRC. Notably, the expression of SERPINE1 and ANXA1 positively correlated with M2-like macrophage infiltration. CONCLUSION: Our results indicate that 6-GPS can robustly predict the recurrence risk of EOCRC, and that SERPINE1, PECAM1, CDH1, and ANXA1 may serve as potential therapeutic targets. This study provides valuable information for the precision treatment of EOCRC.

Endovascular embolization for basal ganglia and thalamic arteriovenous malformations.

Background: Basal ganglia and thalamic arteriovenous malformations (AVMs) represent a special subset of malformations. Due to the involvement of vital brain structures and the specifically fine and delicate angioarchitecture of these lesions, it presents unique therapeutic challenges and technical difficulties that require thorough treatment planning, individualized treatment strategies, and advanced techniques for good clinical outcome. Method: In this study, we presented a series of ruptured basal ganglia and thalamic AVMs embolized via a transarterial, transvenous or combined approach. Herein, we summarized our treatment experience and clinical outcomes to further evaluate the effectiveness and safety of endovascular embolization for these AVMs as well as the indications, therapy strategies, and techniques of embolization procedures. Results: Twelve patients with basal ganglia and thalamus AVMs were included in the study. Their average age was 23.83 ± 16.51 years (range, 4-57 years) with a female predominance of 67% at presentation. The AVMs were located in the thalamus in 3 (25%) patients, in the basal ganglia in 3 (25%) patients, and in both sites of the brain in 6 (50%) patients. There were 5 AVMs located on the left side and 7 on the right. The mean nidus diameter was 3.32 ± 1.43 cm (range 1.3-6.1 cm). According to the Spetzler-Martin grading classification, 4 (33.3%) brain AVMs were Grade III, 7 (58.3%) were Grade IV, and 1 (8.3%) was Grade V. All of them presented with bleeding at admission: four of these patients presented with an intracerebral hemorrhage (ICH), 8 ICH in combination with intraventricular hemorrhage (IVH), and no patient with subarachnoid hemorrhage (SAH). Among these patients treated with endovascular embolization, 7 patients were treated by the transarterial approach, 4 patients transvenous approach, and 1 patient underwent the combined approach. A single embolization procedure was performed in 6 patients (50%) and the other 6 cases (50%) were treated in a staged manner with up to three procedures. Procedure-related complications occurred only in two patient (16.7%). Complete AVM obliteration was obtained in 7 patients (58.3%), and partial obliteration was in 4 patients (33.3%). Overall, good or excellent outcomes were obtained in 7 patients (58.3%), and poor functional outcome was observed in 5 patients (41.7%) at the last follow-up. All survived patients achieved anatomic stabilization and there was no postoperative bleeding or recurrence in the follow-up. Conclusion: The management of the basal ganglia and thalamic AVMs is a great challenge, which needs multimodal individualized treatment to improve the chances of radiographic cure and good outcomes. Endovascular therapy is safe and effective in the treatment of cerebral AVMs particularly for deep-seated AVMs such as the basal ganglia and thalamus. Our results demonstrate a high rate of anatomic obliteration with an acceptable rate of complications in the endovascular treatment of these vasculopathies via a transarterial approach or a transvenous approach.

ICGA combined with EP monitoring in microclipping of cerebral aneurysms.

Cerebral aneurysm is one of the common cerebrovascular diseases in neurosurgery, and rupture of cerebral aneurysm is the most important cause of spontaneous subarachnoid hemorrhage. How to precisely clip the aneurysm has been a topic worth discussing, so the authors explore the value of ICGA combined with electrophysiological monitoring in the microclipping of cerebral aneurysms. Using the method of retrospective analysis of cases, 661 patients with cerebral aneurysms admitted to the Department of Neurosurgery, Zhongnan Hospital of Wuhan University, from 2021.8 to 2022.10 were studied, 390 patients with aneurysm clipping were included, and patients with Hunt-Hess classification ≥ 4 were excluded, and whether to use ICGA combined with EP in microclipping of the ruptured and unruptured aneurysm in pterional approach was investigated at the time of discharge, respectively. The MRS and total hospital days were compared to investigate the value of ICGA combined with EP in the microclipping of cerebral aneurysms. All 390 patients enrolled in the group had successful aneurysm clipping, 178 patients were screened for ruptured aneurysm pterional approach and 120 patients for unruptured aneurysm pterional approach access; the MRS at discharge was significantly lower in the ICGA combined with EP group than in the no-EP group for ruptured aneurysm pterional approach microclipping (p < 0.001), and the mean number of days in hospital was significantly lower (p < 0.01). Patients in the ICGA combined with EP group in microclipping of unruptured aneurysms with pterional approach also had significantly lower MRS at discharge compared with patients in the ICGA alone group (p < 0.001), with no statistically significant difference in the mean number of days in hospital (p = 0.09). In open cerebral aneurysm microclipping, ICGA combined with EP monitoring for both ruptured and unruptured aneurysms can effectively reduce the false-negative rate of ICGA, significantly reduce the incidence of postoperative neurological deficits, and shorten the total hospital stay to some extent. ICGA combined with EP monitoring may be an effective means to reduce the rate of false clipping of the penetrating vessels and to avoid stenosis or occlusion of the aneurysm-carrying artery and is worth promoting in microclipping of cerebral aneurysms except for Hunt-Hess ≥ 4.

A comparison of Atlas and Leo Baby stents-assisted coiling of intracranial aneurysms with small parent vessels.

Some studies have reported the efficacy and safety of the Atlas stent and the Leo Baby stent-assisted coiling (SAC) of intracranial aneurysms arising from small cerebral vessels. The authors aimed to compare the clinical performance of the Atlas and the Leo Baby stents in small parent arteries. Methods and materials: Between January 2019 and November 2022, 56 patients at our centre were treated using either Atlas or Leo Baby SAC of intracranial aneurysms arising from small parent vessels (<2 mm). The clinical and angiographic imaging data of the two cohorts were retrospectively collected and comparatively analyzed. Results: A total of 56 patients were included in this study. Thirty-two patients were treated with the Atlas SAC, and 24 patients were treated with the Leo Baby SAC. The mean age of the Atlas stent cohort was older, and the mean aneurysm size was smaller than the Leo Baby stent. The immediate complete occlusion rate was 68.6% in the Atlas stent cohort and 62.5% in the Leo Baby stent cohort. The mean angiographic follow-up time for Atlas stent cohort was 8.9±2.5 months, and the final aneurysm complete occlusion rate was 81.0%. The mean follow-up time for Leo Baby stent cohort was 18.9±6.0 months, and the final aneurysm complete occlusion rate was 83.3%. Conclusions: At the final follow-up, the Atlas or the Leo baby stent SAC of intracranial aneurysms with small parent vessels resulted in favourable angiographic results and clinical outcomes, with a low rate of associated complications.

Hybrid surgery recanalization for high-level chronic internal carotid artery occlusion.

Objective: Although endovascular recanalization is considered a more effective treatment for chronic internal carotid artery occlusion (CICAO), the success rate of complex CICAO remains inadequate. We present hybrid surgery (carotid endarterectomy combined with carotid stenting) for complex CICAO and explore the influential factors and effects of hybrid surgery recanalization. Methods: We retrospectively analyzed the clinical, imaging, and follow-up data of 22 patients with complex CICAO treated by hybrid surgery at the Zhongnan Hospital of Wuhan University from December 2016 to December 2020. We also summarize the technical points related to hybrid surgery recanalization. Results: A total of 22 patients with complex CICAO underwent hybrid surgery recanalization. There were no postoperative deaths in all patients after hybrid surgery recanalization. Nineteen patients successfully underwent recanalization with a success rate of 86.4% and three cases with a failure rate of 13.6%. Patients were divided into success and failure groups. Significantly different radiographic classification of lesions was observed between the success group and the failure group (P = 0.019). The rates of CICAO with reverse ophthalmic artery blood flow in the internal carotid artery (ICA) preoperatively were 94.7% in the success group and 33.3% in the failure group (P = 0.038). Three cases of hybrid surgery recanalization failure were transferred for EC-IC bypass and had good neurological recovery. Postoperative average KPS scores of the 19 patients were improved compared to the preoperative ones (P < 0.001). Conclusion: Hybrid surgery for complex CICAO is safe and effective with a high recanalization rate. The recanalization rate is related to whether the occluded segment surpasses the ophthalmic artery.

Epigenetic analysis in a murine genetic model of Gulf War illness.

Of the nearly 1 million military personnel who participated in the 1990-1991 Gulf War, between 25% and 35% became ill with what now is referred to as Gulf War Illness (GWI) by the Department of Defense. Symptoms varied from gastrointestinal distress to lethargy, memory loss, inability to concentrate, depression, respiratory, and reproductive problems. The symptoms have persisted for 30 years in those afflicted but the basis of the illness remains largely unknown. Nerve agents and other chemical exposures in the war zone have been implicated but the long-term effects of these acute exposures have left few if any identifiable signatures. The major aim of this study is to elucidate the possible genomic basis for the persistence of symptoms, especially of the neurological and behavioral effects. To address this, we performed a whole genome epigenetic analysis of the proposed cause of GWI, viz., exposure to organophosphate neurotoxicants combined with high circulating glucocorticoids in two inbred mouse strains, C57BL/6J and DBA/2J. The animals received corticosterone in their drinking water for 7 days followed by injection of diisopropylfluorophosphate, a nerve agent surrogate. Six weeks after DFP injection, the animals were euthanized and medial prefrontal cortex harvested for genome-wide DNA methylation analysis using high-throughput sequencing. We observed 67 differentially methylated genes, notably among them, Ttll7, Akr1c14, Slc44a4, and Rusc2, all related to different symptoms of GWI. Our results support proof of principle of genetic differences in the chronic effects of GWI-related exposures and may reveal why the disease has persisted in many of the now aging Gulf War veterans.

Endovascular Treatment of a Traumatic Carotid Cavernous Fistula Concomitant with Intracranial Pseudoaneurysm by Flow Diverter, 2-Dimensional Operative Video.

Traumatic carotid cavernous fistulas (TCCFs) and traumatic intracranial pseudoaneurysms are uncommon vascular anomalies associated with head trauma.1,2 Detachable balloons, covered stents, or liquid embolic agents can be used to treat TCCFs in some conditions.3,4 TCCF concomitant with pseudoaneurysm is an extremely rare occurrence in the literature.5,6 In Video 1, we present a unique case of a TCCF concomitant with a giant pseudoaneurysm of the posterior communicating segment of the left internal carotid artery in a young patient. Both lesions were successfully managed with an endovascular treatment using a Tubridge flow diverter (MicroPort Medical Company, Shanghai, China), coils, and Onyx 18 (Medtronic, Bridgeton, Missouri, USA). No neurologic complications occurred due to the procedures. Six-month follow-up angiography illustrated complete resolution of fistula and pseudoaneurysm. This video shows a new treatment method for TCCF concomitant with a pseudoaneurysm. The patient consented to the procedure.

Efficiency of endovascular management with a combination of Onyx and coils for direct and indirect carotid cavernous fistula treatment: Experience of a single center.

BACKGROUND: To evaluate the safety and efficacy of endovascular treatment with a combination of Onyx and coils for carotid cavernous fistulas (CCFs), and to characterize the factors associated with clinical and angiographic outcomes for direct and indirect CCFs. METHODS: This retrospective study included 31 patients with CCF treated with an endovascular procedure between December 2017 and March 2022. RESULTS: Direct and indirect CCFs were found in 14 (45.2%) and 17 (54.8%) cases, respectively. Direct CCFs included eleven traumatic carotid cavernous fistulas. The most common symptom on admission was chemosis, which was seen in 17 (54.8%) patients. Eight (25.7%) cases were treated by the transarterial approach. Fourteen (45.2%) cases were treated using the femoral vein-inferior petrosal sinus approach. Seven (22.6%) were treated by direct puncture of the superior ophthalmic vein. Two (6.5%) were treated by the femoral vein-facial vein approach. Immediate complete occlusion and follow-up rates were 93.5% and 96.7%, respectively. Twenty-nine (96.7%) patients experienced an improvement in their symptoms at clinical follow-up. Chemosis was significantly improved or resolved in 15 patients. Ophthalmoplegia was improved or resolved in 10 patients. Visual impairment was improved in 6 patients. Proptosis was improved or resolved in 5 patients. One case (3.2%) experienced procedure-related complication presented with transient oculomotor nerve palsy. In univariate subgroup analysis, use of balloon, treatment approach, and history of head trauma were significantly different between the direct and indirect CCF groups. CONCLUSIONS: Endovascular treatment with a combination of Onyx and coils is a safe and effective therapy for CCFs. In this study, the transarterial approach was a favorable option for embolization of direct CCFs. In contrast, the transvenous approach may be the first choice of treatment for indirect CCFs.

Cardiac copper content and its relationship with heart physiology: Insights based on quantitative genetic and functional analyses using BXD family mice.

Background: Copper (Cu) is essential for the functioning of various enzymes involved in important cellular and physiological processes. Although critical for normal cardiac function, excessive accumulation, or deficiency of Cu in the myocardium is detrimental to the heart. Fluctuations in cardiac Cu content have been shown to cause cardiac pathologies and imbalance in systemic Cu metabolism. However, the genetic basis underlying cardiac Cu levels and their effects on heart traits remain to be understood. Representing the largest murine genetic reference population, BXD strains have been widely used to explore genotype-phenotype associations and identify quantitative trait loci (QTL) and candidate genes. Methods: Cardiac Cu concentration and heart function in BXD strains were measured, followed by QTL mapping. The candidate genes modulating Cu homeostasis in mice hearts were identified using a multi-criteria scoring/filtering approach. Results: Significant correlations were identified between cardiac Cu concentration and left ventricular (LV) internal diameter and volumes at end-diastole and end-systole, demonstrating that the BXDs with higher cardiac Cu levels have larger LV chamber. Conversely, cardiac Cu levels negatively correlated with LV posterior wall thickness, suggesting that lower Cu concentration in the heart is associated with LV hypertrophy. Genetic mapping identified six QTLs containing a total of 217 genes, which were further narrowed down to 21 genes that showed a significant association with cardiac Cu content in mice. Among those, Prex1 and Irx3 are the strongest candidates involved in cardiac Cu modulation. Conclusion: Cardiac Cu level is significantly correlated with heart chamber size and hypertrophy phenotypes in BXD mice, while being regulated by multiple genes in several QTLs. Prex1 and Irx3 may be involved in modulating Cu metabolism and its downstream effects and warrant further experimental and functional validations.

Visualization balloon occlusion-assisted technique in the treatment of large or giant paraclinoid aneurysms: A study of 17 cases series.

Objective: Although balloon-assisted techniques are valuable in aneurysm clipping, repeated angiography and fluoroscopy are required to understand the location and shape of the balloon. This study investigated the value of visualization balloon occlusion-assisted techniques in aneurysm hybridization procedures. Methods: We propose a visualization balloon technique that injects methylene blue into the balloon, allowing it to be well visualized under a microscope without repeated angiography. This study retrospects the medical records of 17 large or giant paraclinoid aneurysms treated by a visualization balloon occlusion-assisted technique in a hybrid operating room. Intraoperative surgical techniques, postoperative complications, and immediate and long-term angiographic findings are highlighted. Results: All 17 patients had safe and successful aneurysm clipping surgery with complete angiographic occlusion. Under the microscope, the balloon injected with methylene blue is visible through the arterial wall. The position and shape of the balloon can be monitored in real time without repeated angiography and fluoroscopic guidance. Two cases of intraoperative visualization balloon shift and slip into the aneurysm cavity were detected in time, and there were no cases of balloon misclipping or difficult removal. Of 17 patients, four patients (23.5%) experienced short-term complications, including pulmonary infection (11.8%), abducens nerve paralysis (5.9%), and thalamus hemorrhage (5.9%). The rate of vision recovery among patients with previous visual deficits was 70% (7 of 10 patients). The mean follow-up duration was 32.76 months. No aneurysms or neurological deficits recurred among all patients who completed the follow-up. Conclusion: Our study indicates that microsurgical clipping with the visualization balloon occlusion-assisted technique seems to be a safe and effective method for patients with large or giant paraclinoid aneurysms to reduce the surgical difficulty and simplify the operation process of microsurgical treatment alone.

Satellite estimation of suspended particle types using a backscattering efficiency-based model in the marginal seas.

The particle composition of suspended matter provides crucial information for a deeper understanding of marine biogeochemical processes and environmental changes. Particulate backscattering efficiency (Qbbe(λ)) is critical to understand particle composition, and a Qbbe(λ)-based model for classifying particle types was proposed. In this study, we evaluated the applicability of the Qbbe(λ)-based model to satellite observations in the shallow marginal Bohai and Yellow Seas. Spatiotemporal variations of the particle types and their potential driving factors were studied. The results showed that the Qbbe(λ) products generated from Moderate Resolution Imaging Spectroradiometer (MODIS) on the satellite Aqua agreed well with the in situ measured values, with determination coefficient, root mean square error, bias, and mean absolute percentage error of 0.76, 0.007, 16.5%, and 31.0%, respectively. This result verifies the satellite applicability of the Qbbe(λ)-based model. Based on long-term MODIS data, we observed evident spatiotemporal variations of the Qbbe(λ), from which distinct particle types were identified. Coastal waters were often dominated by minerals, with high Qbbe(λ) values, though their temporal changes were also observed. In contrast, waters in the offshore regions showed clear changes in particle types, which shifted from organic-dominated with low Qbbe(λ) levels in summer to mineral-dominated with high Qbbe(λ) values in winter. We also observed long-term increasing and decreasing trends in Qbbe(λ) in some regions, indicating a relative increase in the proportions of mineral and organic particles in the past decades, respectively. These spatiotemporal variations of Qbbe(λ) and particle types were probably attributed to sediment re-suspension related to water mixing driven by wind and tidal forcing, and to sediment load associated with river discharge. Overall, the findings of this study may provide valuable proxies for better studying marine biogeochemical processes, material exchanges, and sediment flux.

The Rubber Tree (Heveae brasiliensis) MLO Protein HbMLO12 Promotes Plant Susceptibility to Sustain Infection by a Powdery Mildew Fungus.

Powdery mildew severely affects several important crops and cash plants. Disruption of mildew resistance locus O (MLO) genes elevates resistance against powdery mildew in several plants. However, whether rubber tree (Heveae brasiliensis) MLO proteins are linked to susceptibility remains unknown, owing to technical limitations in the genetic manipulation of this woody plant. A previous study showed that the H. brasiliensis MLO-like protein HbMLO12 demonstrates high amino acid sequence similarity with the known Arabidopsis MLO protein AtMLO12. In this study, we investigated whether HbMLO12 regulates susceptibility to powdery mildew. H. brasiliensis leaves take up exogenously synthesized double-stranded RNAs (dsRNAs), and foliar application of dsRNA homologous to HbMLO12 gene specifically induces HbMLO12 silencing in H. brasiliensis leaf tissues. Notably, HbMLO12 silencing inhibited fungal infection and elevated the immune response during interaction with the rubber tree powdery mildew fungus. Furthermore, the heterologous expression of HbMLO12 suppressed bacterial flg22- and fungal chitin-induced immune responses and enhanced bacterial infection in Arabidopsis. Our study provides evidence that HbMLO12 contributes to susceptibility to powdery mildew. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Tubridge flow diverter alone vs. Tubridge flow diverter and coils for the treatment of intracranial aneurysms: A propensity score matching analysis.

Background: The study was designed to assess the clinical performance of a tubridge flow diverter (TFD) in the treatment of intracranial aneurysms and to compare the efficacy and safety between intracranial aneurysms treated with TFD alone and TFD combined with coiling. Methods: In this retrospective study, patients treated with the TFD alone or TFD combined with coiling between June 2018 to November 2022 were included. The patient demographics, the characteristics of the aneurysm, and the treatment outcomes between the two groups were compared. Propensity score matching was performed to match the variables with a significant difference between groups. Results: In the current study, data from 93 consecutive patients including 104 aneurysms treated with TFD were analyzed. In total, 43 patients with 49 aneurysms were treated with TFD alone, and 50 patients with 55 aneurysms were treated with TFD combined with coiling. Aneurysms in the TFD combined with the coiling group were larger (12.9 ± 8.6 vs. 8.7 ± 8.8 mm, P = 0.016) and more likely to be saccular (92.7% vs. 75.5%, P = 0.027) than in the TFD alone group. No significant difference was observed between the two groups in terms of perioperative complication rate. During the follow-up period, the complete occlusion rate in the TFD combined with the coiling group was higher (80.0% vs. 43.8%, P = 0.001) than in the TFD alone group. These results were further confirmed using a propensity score matching analysis. Conclusion: TFD combined with coiling can be a safe and effective alternative option for the treatment of complex aneurysms. Given the potential risks of these therapeutic modalities, thus very careful consideration is required on an individual patient basis.