Integrative bioinformatics analysis of miRNA and mRNA expression profiles and identification of associated miRNA-mRNA network in intracranial aneurysms.

Background: Intracranial aneurysms (IAs) represent protrusions in the vascular wall, with their growth and wall thinning influenced by various factors. These processes can culminate in the rupture of the aneurysm, leading to subarachnoid hemorrhage (SAH). Unfortunately, over half of the patients prove unable to withstand SAH, succumbing to adverse outcomes despite intensive therapeutic interventions, even in premier medical facilities. This study seeks to discern the pivotal microRNAs (miRNAs) and genes associated with the formation and progression of IAs. Methods: The investigation gathered expression data of miRNAs (from GSE66240) and mRNAs (from GSE158558) within human aneurysm tissue and superficial temporal artery (STA) samples, categorizing them into IA and normal groups. This classification was based on the Gene Expression Omnibus (GEO) database. Results: A total of 70 differentially expressed microRNAs (DEMs) and 815 differentially expressed mRNAs (DEGs) were pinpointed concerning IA. Subsequently, a miRNA-mRNA network was constructed, incorporating 9 significantly upregulated DEMs and 211 significantly downregulated DEGs. Simultaneously, functional enrichment and pathway analyses were conducted on both DEMs and DEGs. Through protein-protein interaction (PPI) network analysis and functional enrichment, 9 significantly upregulated DEMs (hsa-miR-188-5p, hsa-miR-590-5p, hsa-miR-320b, hsa-miR-423-5p, hsa-miR-140-5p, hsa-miR-486-5p, hsa-miR-320a, hsa-miR-342-3p, and hsa-miR-532-5p) and 50 key genes (such as ATP6V1G1, KBTBD6, VIM, PA2G4, DYNLL1, METTL21A, MDH2, etc.) were identified, suggesting their potential significant role in IA. Among these genes, ten were notably negatively regulated by at least two key miRNAs. Conclusions: The findings of this study provide valuable insights into the potential pathogenic mechanisms underlying IA by elucidating a miRNA-mRNA network. This comprehensive approach sheds light on the intricate interplay between miRNAs and genes, offering a deeper understanding of the molecular dynamics involved in IA development and progression.

Risk Factors for Cerebral Hyperperfusion Syndrome After Combined Revascularization in Adult Patients with Moyamoya Disease.

BACKGROUND: Cerebral hyperperfusion syndrome (CHS) is known as a complication after bypass surgery for Moyamoya disease (MMD). However, the incidence of CHS has not been accurately reported, and there is no consensus on the risk factors associated with it. AIM: The aim of this study was to determine the risk factors associated with postoperative CHS after surgical combined revascularization used to treat adult patients with MMD. OBJECTIVE: To assess the frequency and characteristics of CHS in patients with MMD after revascularization operations. METHODS: Patients who received combined revascularization from Jan 2021 to Nov 2022 were retrospectively reviewed. Preoperative clinical characteristics and radiographic features were recorded. Postoperative CHS after surgery were examined. Multivariate logistic regression analyses were performed to identify the risk factors for CHS. RESULTS: A total of 133 patients (141 hemispheres) were included in this study. Postoperative CHS were observed in 28 hemispheres (19.8%), including focal cerebral hyperperfusion syndrome (FCHS) in 20 hemispheres (14.2%), hemorrhage in 4 (2.8%) hemispheres, seizures in 4 (2.8%) hemispheres. The results of multivariate logistic regression analysis indicated that preoperative hypertension (OR 4.705, 95% CI 1.323 ~ 12.554, p = 0.014), cerebral hemorrhage onset (OR 5.390, 95% CI 1.408 ~ 20.642, p = 0.014) and higher Hct level (OR 1.171, 95% CI 1.051 ~ 1.305, p = 0.004) were significantly associated with CHS after combined revascularization. CONCLUSIONS: Preoperative hypertension, cerebral hemorrhage onset, and higher Hct level were independent risk factors for CHS after combined revascularization.

Outcomes after superficial temporal artery-middle cerebral artery anastomosis combined with multiple burr hole surgery and dural inversion synangiosis for moyamoya disease in adults.

Objective: Several forms of cerebral revascularization have been carried out to treat moyamoya disease, however, the existing methods are accompanied by a variety of complications. In this study, the authors aimed to evaluate the clinical and angiographic outcomes of a new surgical procedure: superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis combined with multiple burr hole (MBH) surgery and dural inversion synangiosis for the treatment of moyamoya disease in adults. Methods: Patients treated for moyamoya disease from August 2019 to July 2021 were retrospectively reviewed. Clinical data, including perioperative complications and follow-up outcomes, were noted. Preoperative and postoperative angiograms were compared, and the diameters of the frontal branch of the superficial temporal artery (F-STA), the deep temporal artery (DTA), the distal superficial temporal artery (STA) before the bifurcation and the middle meningeal artery (MMA) were measured on preoperative and postoperative angiograms. Meanwhile, a Matsushima score was assigned from postoperative angiograms. Results: This study included 66 patients (67 hemispheres). During the follow-up period, a median of 18 (IQR, 13-21) months, no stroke or death occurred in any of the patients. The clinical outcomes were excellent in 27 patients (40.9%), good in 34 patients (51.6%), fair in 4 patients (6.0%), and poor in 1 patient (1.5%); the overall rate of favorable clinical outcomes (excellent and good) was 92.5%. The modified Rankin Scale (mRS) score was significantly improved at follow-up (P < 0.001). There were 41 hemispheres imaged by cerebral angiography after the operation, at a median postoperative interval of 9 (IQR, 8-12) months; among them, 34 (82.9%) hemispheres had Matsushima scores of grade A and grade B. The average postoperative diameters in the STA, DTA and MMA were increased significantly in 41 hemispheres at follow-up (P < 0.001). Sixteen (24.2%) patients suffered from perioperative complications, including focal hyperperfusion syndrome (HS) in 8 (12.2%) patients, cerebral infarction in 3 (4.5%) patients (including one case accompanied by wound infection), cerebral hemorrhage in 2 (3.0%) patients, seizures in 2 (3.0%) patients, and subdural effusion in 1 (1.5%) patient. Conclusions: The procedure of STA-MCA anastomosis combined with MBH surgery and dural inversion synangiosis may be a safe and effective treatment for adult patients with moyamoya disease.

Flows and connections of metabolic nodes in Beijing-Tianjin-Hebei Region and its cities: A study at two scales.

The metabolic processes of cities and their embedded regions have received great attention, but it is still unclear how the metabolic processes change at the scale from cities to urban agglomerations. In view of the lack of multi-scale research in the field of urban metabolism, this study took Beijing-Tianjin-Hebei region, one of the urban agglomerations with largest economic scales in China, as a case to construct metabolic network models at two scales of city and urban agglomeration. The material transfers between nodes were calculated, and the connection degree index was put forward in the ecological network analysis to quantify the influence of a single node on the network when multi-level transfers were considered. On this basis, the similarities and differences of metabolic nodes at the two scales were analyzed. The results showed that nearly 97% of the volume of material transfers in the urban agglomeration was concentrated within the cities, among which the transfer volumes of Tangshan, Handan, and Shijiazhuang were more than 600 Mt. Manufacturing and environment were the major contributors to material transfers. The connection degrees of nodes had both commonness and differences at the two scales. In general, the connection degrees at the urban scale were relatively homogeneous, while their difference was large at the urban agglomeration scale. The connection degrees of nodes in Langfang were prominent at the urban agglomeration scale. The connection degrees of environment and manufacturing ranked top 3 at both scales. Meanwhile, the connection degree of energy conversion at the urban scale was relatively high, while its influence was replaced by mining sector at the urban agglomeration scale. The analysis of material metabolic nodes in Beijing-Tianjin-Hebei region can provide theoretical supports to position the key points in the process of material utilization in the cities or the urban agglomeration, and help to identify the breakthrough points for subsequent regulatory.

Ultrastable Zinc Anode by Simultaneously Manipulating Solvation Sheath and Inducing Oriented Deposition with PEG Stability Promoter.

Aqueous zinc-ion batteries are a low-cost and safe energy storage system, but suffer from detrimental side reactions and Zn dendrites due to the strong interactions between Zn2+ and water molecules in the electrolytes, and random Zn2+ deposition on the anode surface. Here, an electrolyte involving a dual-functional additive of polyethylene glycol (PEG) to bypass these issues is reported. The electrolyte can not only tailor the solvation sheath of Zn2+ but also enable favorably oriented deposition of Zn2+ on the anode surface. The dendrite-free Zn anode in Zn//Zn cells is obtained with high Columbic efficiency (98.8%) and long cycling lifespan (1500 h), six times longer than that of electrolyte without PEG at 0.25 mA cm-2 . What is more, the excellent cycling stability of the prepared batteries (Zn//V2 O5 ·1.6 H2 O) suggests that the developed tailoring strategy may propel a promising pathway for stabilizing Zn metal anodes.

A Polymer/Graphene Composite Cathode with Active Carbonyls and Secondary Amine Moieties for High-Performance Aqueous Zn-Organic Batteries Involving Dual-Ion Mechanism.

Aqueous zinc-ion batteries (AZIBs) are regarded as one of the most promising alternative technology to lithium-ion batteries on account of their low flammability and cost-benefits. Among various cathode materials in AZIBs, environment-friendly and sustainable organic electrode materials stand out owing to their structural diversity and tunability. However, their limited rate capability and cycle stability remain the obstacles to their further application in AZIBs. Herein, a mixed cathode design strategy including polymerization and carbon materials hybridization is adopted to assemble high-rate and durable AZIBs. Specifically, a polymer/graphene composite cathode with active carbonyls and secondary amine moieties is prepared to construct high-performance aqueous Zn-organic batteries. Furthermore, a hybrid energy storage mechanism involving dual-ion mechanism is confirmed by various ex situ characterization techniques, providing promising battery chemistry. Thus, this work opens up a new path to high performance AZIBs through a rational cathode design.

Electrochemical Injection Oxygen Vacancies in Layered Ca2Mn3O8 for Boosting Zinc-Ion Storage.

Manganese-based compounds have emerged as attractive cathode materials for zinc-ion batteries owing to their high operating voltage, large specific capacity, and no pollution. However, the structural collapse and sluggish kinetics of manganese-based compounds are major obstacles that hinder their practical applications. Here, a kind of novel layered Ca2Mn3O8 with a low ion diffusion barrier and high structural stability has been achieved through an electrochemical charging process with in situ injecting oxygen vacancies. This greatly increases the electrochemical active area and improves the Zn ions diffusion coefficient by 2 orders of magnitude, which significantly enhances the reaction kinetics, pseudocapacitance properties, and capacity. As a result, the cathode containing oxygen vacancies present an impressive reversible capacity of 368 mAh g-1, an unprecedented energy density of 512 Wh kg-1, and superior capacity retention of 92.3% at a high current density of 5 A g-1 after 3000 cycles. This work unveils an effective method for vacancy regulation of electrode materials, paving a new way to improve the electrochemical performance of zinc-ion batteries.

Superior-Performance Aqueous Zinc-Ion Batteries Based on the In Situ Growth of MnO2 Nanosheets on V2CTX MXene.

Mn-based aqueous zinc-ion batteries (ZIBs) are promising candidate for large-scale rechargeable energy storage because of easy fabrication, low cost, and high safety. Nevertheless, the commercial application of Mn-based cathode is hindered by the challenging issues of low rate capability and poor cyclability. Herein, a manganese-vanadium hybrid, K-V2C@MnO2 cathode, featured with MnO2 nanosheets uniformly formed on a V2CTX MXene surface, is elaborately designed and synthesized by metal-cation intercalation and following in situ growth strategy. Benefiting from the hybrid structure with high conductivity, abundant active sites, and the synergistic reaction of Mn2+ electrodeposition and inhibited structural damage of MnO2, K-V2C@MnO2 shows excellent electrochemical performance for aqueous ZIBs. Specifically, it presents the high specific capacity of 408.1 mAh g-1 at 0.3 A g-1 and maintains the specific capacity of 119.2 mAh g-1 at a high current density of 10 A g-1 in a long-term cycle of up to 10000 cycles. It is superior to almost all reported Mn-based cathodes for ZIBs in the aqueous electrolyte. The superior electrochemical performance suggests that the Mn-based cathode materials designed in this work can be a rational approach to be applied for high-performance ZIBs cathodes.

LINC00662 sponges miR-107 accelerating the invasiveness and proliferation of glioma cells.

Increasing evidence revealed that the aberrant expression of long non-coding RNAs (lncRNAs) has been implicated in tumorigenesis. However, the role and mechanisms of LINC00662 in glioma have not been elucidated. Here, we show that upregulation of LINC00662 expression in glioma is associated with advanced clinical features and poor prognosis. Our results from loss-of-function assays suggest that LINC00662 silencing suppresses the proliferative and invasive abilities of glioma cells. In vivo, glioma growth was inhibited by depletion of LINC00662 in nude mice. Mechanistically, LINC00662 directly interacts with miR-107. The High-mobility group box 1 protein (HMGB1) is a known target of miR-107. Moreover, rescue assays reveal that HMGB1 overexpression (or miR-107 inhibition) reverses the glioma growth inhibition caused by LINC00662 knockdown. In conclusion, our results indicate that LINC00662 acts as an oncogene in glioma by modulating the miR-107/HMGB1 axis, suggesting that LINC00662 could be a novel therapeutic target for glioma treatment.

Growth Differentiation Factor 5 Improves Neurogenesis and Functional Recovery in Adult Mouse Hippocampus Following Traumatic Brain Injury.

The aim of this study was to investigate the therapeutic effect of growth differentiation factor 5 (GDF-5) on traumatic brain injury (TBI) in mice. We utilized a controlled cortical impact to establish a mouse TBI model, and then stereotaxically administered 25 or 100 ng GDF-5 into the bilateral hippocampal dentate gyrus (DG) of each of the animals. Seven days after the injury, some of the animals were sacrificed for immunohistochemical and immunofluorescence examination of 5-bromo-2'-deoxyuridine (BrdU), Sox-2, doublecortin (DCX) and phosphorylated cAMP response element binding protein (p-CREB). Dendrite quantification was also performed using DCX positive cells. Activation of newborn neurons was assessed 35 days after the injury. The remaining animals were subjected to open field, Y maze and contextual fear conditioning tests 2 months after TBI. As a result, we found that post-injury stereotaxical administration of GDF-5 can improve neural stem cell proliferation and differentiation in the DG of the hippocampus, evidenced by the increase in BrdU, Sox-2, and DCX-labeled cells, as well as the improvement in dendrite arborization and newborn neuron activation in response to GDF-5 treatment. Mechanistically, these effects of GDF-5 may be mediated by the CREB pathway, manifested by the recovery of TBI-induced dephosphorylation of CREB upon GDF-5 administration. Behavioral tests further verified the effects of GDF-5 on improving cognitive and behavioral dysfunction after TBI. Collectively, these results reveal that direct injection of GDF-5 into the hippocampus can stimulate neurogenesis and improve functional recovery in a mouse TBI model, indicating the potential therapeutic effects of GDF-5 on TBI.

The 37-kDa laminin receptor precursor regulates the malignancy of human glioma cells.

Glioma is one of the most common brain tumors and one of the most aggressive cancers. Although extensive progress has been made regarding to the diagnosis and treatment, the mortality in glioma patients is still high. Therefore, finding new therapeutic targets to the glioma is critical to the advancement in cancer treatment. Recently, the 37-kDa laminin receptor precursor (37LRP) was reported to play important roles in occurrence of some types of cancer, indicating that this molecule may function as a key regulator in the tumor migration and metastasis. However, there is still no report to elucidate the correlation between 37LRP expression and glioma genesis and development. In this study, we found the higher expression of 37LRP in the glioma cells compared with the normal brain cells. We also indicated that the downregulation of 37LRP could affect the glioma biomarker expression and also weaken the proliferative, migratory, and metastatic capacity of glioma cells in vitro. Furthermore, 37LRP silencing inhibited the glioma tumor growth in vivo. Collectively, these data demonstrated that 37LRP regulates the metastasis of glioma cells in vitro and tumor growth in vivo, suggesting that 37LRP may function as a potential molecular target in the glioma treatment.

Metabolic coupling of two small-molecule thiols programs the biosynthesis of lincomycin A.

Low-molecular-mass thiols in organisms are well known for their redox-relevant role in protection against various endogenous and exogenous stresses. In eukaryotes and Gram-negative bacteria, the primary thiol is glutathione (GSH), a cysteinyl-containing tripeptide. In contrast, mycothiol (MSH), a cysteinyl pseudo-disaccharide, is dominant in Gram-positive actinobacteria, including antibiotic-producing actinomycetes and pathogenic mycobacteria. MSH is equivalent to GSH, either as a cofactor or as a substrate, in numerous biochemical processes, most of which have not been characterized, largely due to the dearth of information concerning MSH-dependent proteins. Actinomycetes are able to produce another thiol, ergothioneine (EGT), a histidine betaine derivative that is widely assimilated by plants and animals for variable physiological activities. The involvement of EGT in enzymatic reactions, however, lacks any precedent. Here we report that the unprecedented coupling of two bacterial thiols, MSH and EGT, has a constructive role in the biosynthesis of lincomycin A, a sulfur-containing lincosamide (C8 sugar) antibiotic that has been widely used for half a century to treat Gram-positive bacterial infections. EGT acts as a carrier to template the molecular assembly, and MSH is the sulfur donor for lincomycin maturation after thiol exchange. These thiols function through two unusual S-glycosylations that program lincosamide transfer, activation and modification, providing the first paradigm for EGT-associated biochemical processes and for the poorly understood MSH-dependent biotransformations, a newly described model that is potentially common in the incorporation of sulfur, an element essential for life and ubiquitous in living systems.

Polyhydroxy cyclohexanols from a Dendrodochium sp. fungus associated with the sea cucumber Holothuria nobilis Selenka.

Four cyclohexanol analogues, dendrodochols A-D (1-4), were isolated from a Dendrodochium sp. fungus associated with the sea cucumber Holothuria nobilis Selenka collected from the South China Sea. The structures were elucidated by means of detailed spectroscopic analysis. The absolute configurations were assigned using a solution TDDFT/ECD calculation approach and the modified Mosher's method. In an in vitro bioassay, these compounds exhibited no growth inhibition activity against the A549 and MG63 cell lines. Dendrodochols 1 and 3 exhibited modest antifungal activity against Candida strains, Cryptococcus neoformans, and Trichophyton rubrum, whereas 2 and 4 showed no activity against the tested strains.

Structure, absolute configuration, and conformational study of 12-membered macrolides from the fungus Dendrodochium sp. associated with the sea cucumber Holothuria nobilis Selenka.

Dendrodolides A-M (1-13), 13 new 12-membered macrolides, were isolated from Dendrodochium sp., a fungus associated with the sea cucumber Holothuria nobilis Selenka, which was collected from the South China Sea. The structures of the dendrodolides were elucidated by means of detailed spectroscopic analysis and X-ray single-crystal diffraction. The absolute configurations were assigned using the modified Mosher method, exciton-coupled circular dichroism (ECCD), electronic solution and solid-state circular dichroism (ECD) supported by time-dependent density functional theory (TDDFT) ECD calculations, and X-ray analysis. A detailed conformational analysis of the 13 derivatives indicated that the conformation of the flexible macrolide ring plays a decisive role in their chiroptical properties. Thus, it is highly recommended to apply advanced levels of theory and to avoid simple comparison of ECD spectra to determine the absolute configurations of these derivatives. In an in vitro bioassay, compounds 1-5, 7-9, 11, and 12 exhibited different levels of growth inhibitory activity against SMMC-7721 and HCT116 cells. This is the first report of 12-membered macrolides from the fungus of the genus Dendrodochium . The coisolation of four pairs of epimers is extremely interesting and indicates the complexity of ß-ketoreductase stereospecificity in the biosynthesis of enigmatic iterative fungal polyketides.

Inhibition of heat shock protein response enhances PS-341-mediated glioma cell death.

BACKGROUND: Previous study indicated that PS-341 induces cell death via JNK pathway in vitro in glioma. However, suppressing proteasome complex by PS-341 may induce expression of heat shock proteins (HSPs), which confer potential protection against cellular stress. In this study, we explored whether induction of HSPs could impair PS-341-induced cell death and whether inhibition of HSPs could enhance cell damage induced by PS-341 in glioma cells. METHODS: HSP expression in glioma cells was modulated by HSP inhibitor, sublethal heat, or knockdown of heat shock factor1 (HSF1), then PS-341-induced cell damage was examined by different methods. Similar experiments were also performed in HSF1+/+ and HSF1-/- cells. HSP70 expression and HSF1 nuclear localization were compared between glioma and normal brain tissues. RESULTS: HSP level was upregulated mediated by HSF1 when glioma cells were treated with PS-341. PS-341-mediated cell damage could be significantly augmented by HSP inhibition. Furthermore, HSP70 expression and HSF1 nuclear localization were much more abundant in gliomas than in normal brain tissues. CONCLUSIONS: Our results demonstrated that HSP70 impaired cell death induced by PS-341 in glioma cells. Administration of PS-341 in combination with either HSP70 inhibitor or HSF1 knockdown may act as a new approach to treatment of glioma.