Small-molecule fluorescent probes for bioactive species in inflammatory disease: arthritis, pneumonia and hepatitis.

Inflammation as an adaptive response underlies a wide variety of physiological and pathological processes. The progression of inflammation is closely intertwined with various bioactive molecules. To dissect the biological mechanisms and physiopathological functions of these molecules, exploitation of versatile detection mean is of great importance. Fluorescence imaging technique has been widely employed to track bioactive species in living systems. As a result, many small-molecule fluorescent probes for bioactive species in inflammatory disease have been developed. However, this interesting and frontier topic hasn't been systematically categorized. Therefore, in this review, we have generalized the construction strategies and biological imaging applications of small-molecule fluorescent probes for various bioactive species, including reactive oxygen/nitrogen/sulfur species, enzyme, mainly in arthritis, pneumonia and hepatitis. Moreover, the future challenges in constructing novel fluorescent probes for inflammatory disease are also present. This review will facilitate the comprehension of superior fluorescent probes for active molecules associated with inflammation.

Long Non-Coding RNA MALAT1 Decreases the Sensitivity of Resistant Glioblastoma Cell Lines to Temozolomide.

BACKGROUND/AIM: Multidrug resistance (MDR) is largely responsible for the failure of chemotherapy. The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript (MALAT1) has been reported to be closely related to tumor biology. In the present study, whether MALAT1 contributes to the resistance of glioblastoma cell lines to temozolomide (TMZ) was investigated. METHODS: The glioblastoma cell lines U251 and U87 were exposed to increasing concentrations of TMZ to generate TMZ-resistant colonies (the U251/TMZ and U87/TMZ cell lines). The expression levels of MALAT1 and proteins related to epithelial-mesenchymal transition (EMT) were detected by real-time PCR and western blot, respectively. After the transfection of si-MALAT1 or pcDNA-MALAT1, cell viability, mRNA expression of MDR-associated proteins (MDR1, MRP5 and LRP1), and protein expression of EMT related proteins (ZEB1, Snail and SLUG) were evaluated. RESULTS: The expression of MALAT1 was upregulated in the U251/TMZ and U87/TMZ cell lines compared to that in U251 and U87 cell lines, respectively. The treatment of si-MALAT1 decreased MDR1, MRP5, and LRP1 expression, enhanced cell sensitivity to TMZ, and downregulated ZEB1 protein expression, whereas pcDNA-MALAT1 had the opposite effects. However, the effects of si-MALAT1 on MDR -associated protein expression, cell viability, and EMT status were reversed by the transfection of pcDNA-ZEB1, and the effects of pcDNA-MALAT1 were reversed by the transfection of si-ZEB1. In vivo, MALAT1 overexpression enhanced tumors' TMZ resistance and upregulated ZEB1 expression. CONCLUSION: MALAT1 decreased the sensitivity of resistant glioma cell lines to TMZ by regulating ZEB1.

Environmental Circadian Disruption Worsens Neurologic Impairment and Inhibits Hippocampal Neurogenesis in Adult Rats After Traumatic Brain Injury.

Circadian rhythms modulate many physiologic processes and behaviors. Therefore, their disruption causes a variety of potential adverse effects in humans and animals. Circadian disruption induced by constant light exposure has been discovered to produce pathophysiologic consequences after brain injury. However, the underlying mechanisms that lead to more severe impairment and disruption of neurophysiologic processes are not well understood. Here, we evaluated the effect of constant light exposure on the neurobehavioral impairment and survival of neurons in rats after traumatic brain injury (TBI). Sixty adult male Sprague-Dawley rats were subjected to a weight-drop model of TBI and then exposed to either a standard 12-/12-h light/dark cycle or a constant 24-h light/light cycle for 14 days. Our results showed that 14 days of constant light exposure after TBI significantly worsened the sensorimotor and cognitive deficits, which were associated with decreased body weight, impaired water and food intake, increased cortical lesion volume, and decreased neuronal survival. Furthermore, environmental circadian disruption inhibited cell proliferation and newborn cell survival and decreased immature cell production in rats subjected to the TBI model. We conclude that circadian disruption induced by constant light exposure worsens histologic and neurobehavioral impairment and inhibits neurogenesis in adult TBI rats. Our novel findings suggest that light exposure should be decreased and circadian rhythm reestablished in hospitalized TBI patients and that drugs and strategies that maintain circadian rhythm would offer a novel therapeutic option.

Wharton's Jelly Transplantation Improves Neurologic Function in a Rat Model of Traumatic Brain Injury.

Traumatic brain injury (TBI), which can lead to disability, dysfunction, and even death, is a prominent health problem worldwide. Effective therapy for this serious and debilitating condition is needed. Human umbilical cord matrix, known as Wharton's jelly (WJ), provides a natural, interface scaffold that is enriched in mesenchymal stem cells. In this study, we tested the efficacy of WJ tissue transplantation in a weight-drop model of TBI in rats. WJ tissue was cultured and transplanted into the injury site 24 h after TBI. The modified neurologic severity score, body weight, brain edema, and lesion volume were evaluated at various time points after TBI. Cognitive behavior was assessed by the novel object recognition test and the Morris water maze test. Expression of brain-derived neurotrophic factor (BDNF) in the perilesional brain area was measured at day 14 after TBI. We found that WJ tissue transplantation lessened TBI-induced brain edema (day 3), reduced lesion volume (day 28), improved neurologic function (days 21-28), and promoted memory and cognitive recovery. Additionally, expression of BDNF mRNA and protein was higher in WJ tissue-treated rats than in sham-operated or vehicle-treated rats. These data suggest that WJ tissue transplantation can reduce TBI-induced brain injury and may have therapeutic potential for the treatment of TBI.

Probing the symmetries of the Dirac Hamiltonian with axially deformed scalar and vector potentials by similarity renormalization group.

Symmetry is an important and basic topic in physics. The similarity renormalization group theory provides a novel view to study the symmetries hidden in the Dirac Hamiltonian, especially for the deformed system. Based on the similarity renormalization group theory, the contributions from the nonrelativistic term, the spin-orbit term, the dynamical term, the relativistic modification of kinetic energy, and the Darwin term are self-consistently extracted from a general Dirac Hamiltonian and, hence, we get an accurate description for their dependence on the deformation. Taking an axially deformed nucleus as an example, we find that the self-consistent description of the nonrelativistic term, spin-orbit term, and dynamical term is crucial for understanding the relativistic symmetries and their breaking in a deformed nuclear system.

METTL14-mediated HOXA5 m6A modification alleviates osteoporosis via promoting WNK1 transcription to suppress NLRP3-dependent macrophage pyroptosis.

Background: Osteoporosis is a commonly diagnosed metabolic bone disease. NLRP3 inflammasome activation and pyroptosis are observed during osteoporosis. However, the mechanism by which NLRP3-mediated pyroptosis contributes to osteoporosis remains largely undefined. Methods: Ovariectomized (OVX) mice were employed as an in vivo model of osteoclastogenesis. H&E staining and micro-CT detected the histological changes and bone parameters in the femur tissues. RANKL-treated macrophages were used as the in vitro model of osteoclastogenesis, and LPS/ATP treatment was used as the macrophage pyroptosis model. The cytotoxicity, cytokine secretion and caspase-1 activity were assessed by LDH release assay, ELISA and flow cytometry, respectively. The osteoclast formation ability was detected by TRAP staining. qRT-PCR, IHC and Western blotting detected the expression and localization of METTL14, pyroptosis-related or osteoclast-specific molecules in femur tissues or macrophages. Mechanistically, MeRIP assessed the m6A modification of HOXA5. Luciferase and ChIP assays were employed to detect the direct association between HOXA5 and WNK1 promoter in macrophages. Results: METTL14, HOXA5 and WNK1 were decreased in OVX mice, which was associated with pyroptosis. METTL14 or HOXA5 overexpression suppressed macrophage-osteoclast differentiation and pyroptosis, along with the upregulation of WNK1. METTL14-mediated m6A modification stabilized HOXA5 mRNA and increased its expression, and HOXA5 regulated WNK1 expression via direct binding to its promoter. Functional studies showed that WNK1 knockdown counteracted METTL14- or HOXA5-suppressed pyroptosis and macrophage-osteoclast differentiation. In OVX mice, overexpression of METTL14 or HOXA5 alleviated osteoporosis via suppressing WNK1-dependent NLRP3 signaling. Conclusion: METTL14-mediated HOXA5 m6A modification increased its expression, thereby inducing WNK1 expression and suppressing NLRP3-dependent pyroptosis to alleviate osteoporosis. The combination of METTL14 or HOXA5 agonist with pyroptosis targeted therapy may be a promising therapeutic approach for osteoporosis. The Translational Potential of this Article·: •METTL14 or HOXA5 overexpression suppressed macrophage-osteoclast differentiation and pyroptosis in macrophages.·â€¢METTL14-mediated m6A modification stabilized HOXA5 mRNA and increased its expression.•HOXA5 regulated WNK1 expression via direct binding to its promoter.•Silencing of WNK1 reversed METTL14- or HOXA5-suppressed pyroptosis and macrophageosteoclast differentiation.·â€¢METTL14 or HOXA5 overexpression alleviated osteoporosis via suppressing WNK1-dependent NLRP3 signaling in OVX mice.

Panoptic elucidation of algicidal mechanism of Raoultella sp. S1 against the Microcystis aeruginosa by TMT quantitative proteomics.

Harmful algal blooms (HABs) due to eutrophication are becoming a serious ecological disaster worldwide, threatening human health and the optimal balance of aquatic ecosystems. The traditional approaches to eradicate HABs yield several drawbacks in practical application, while microbial algicidal technology is garnering mounting recognition due to its high efficiency, eco-friendliness, and low cost. In our previous study, we isolated a bacterium strain Raoultella sp. S1 from eutrophic water with high efficiency of algicidal properties. This study further investigated the flocculation and inactivation efficiency of S1 on Microcystis aeruginosa at different eutrophic stages by customizing the algal cell densities. The supernatant extract of S1 strain exhibited remarkable flocculation and inactivation effects against low (1 × 106 cell/mL)and medium (2.7 × 106 cell/mL)concentrations of algal cells, but unexceptional for higher densities. The results further revealed that algal cells at low and medium counts manifested a more apparent antioxidant defense response, while the photosynthetic efficiency and relative electron transport rate were considerably reduced within 24 h. TEM observations confirmed the disruption of thylakoid membranes and cell structure of algal cells by algicidal substances. Moreover, TMT proteomics revealed alterations in protein metabolic pathways of algal cells during the flocculation and lysis stages at the molecular biological level. This signified that the disruption of the photosynthetic system is the core algicidal mechanism of S1 supernatant. In contrast, the photosynthetic metabolic pathways in the HABs were significantly upregulated, increasing the energy supply for the NADPH dehydrogenation process and the upregulation of ATPases in oxidative phosphorylation. Insufficient energy provided by NADPH resulted in a dwindled electron transport rate, stagnation of carbon fixation in dark reactions, and blockage of light energy conversion into chemical energy. Nonetheless, carbohydrate metabolism (gluconeogenesis and glycolysis) proteins were down-regulated and hampered DNA replication and repair. This study aided in unveiling the bacterial management of eutrophication by Raoultella sp. S1 and further arrayed the proteomic mechanism of algal apoptosis.

Magnetite-equipped algal-rich sediments for microbial fuel cells: Remediation of sediment organic matter pollution and mechanisms of remote electron transfer.

Using the bio-electrochemical methods for the restoration of high algae sediments is full of potential and challenges. How to promote extracellular electron transfer (EET) process in microbial fuel cells (MFC) is the key bottleneck. The study had explored the potential application of magnetite on accelerating electron transfer for improving the output of MFC and sediment pollution remediation. The results indicated that the organic matter degradation rate showed a remarkable increase of 27.45 %, and the voltage output was approximately 1.68 times higher compared to the MFC configured with regular sediment. Abundant electroactive bacteria (EABs), such as Geobacter and Burkholderiaceae, and fermentative bacteria were responsible for these results, accompanied by the enhanced fluorescence of humic substances (HS), increased concentration and activity of cytochrome C (25.05 % and 21.12 %), as well as elevated extracellular polymeric substance content. Moreover, the intrinsic EET mechanisms among Fe-oxides, HS, and EABs were explored. According to the electrochemical analysis and substance transformation, the EET process involved four stages: magnetite-enhanced direct electron transfer via strong conductivity, iron respiration mediating electron transfer to the electrode, the model quinone substance acting as an electron shuttle facilitating EET and iron reduction, and iron cycling mediating electron transfer. This study provides an effective strategy for pollution remediation in algal-rich sediment, which was beneficial for the harmless treatment and resource utilization of both algae and sediment, simultaneously.

Ingenious fluorescent probes for biogenic amine and their applications in bioimaging and food spoilage detection.

Food safety issues have received much attention. Biogenic amines are considered important markers of food spoilage. Accurate detection of biogenic amines is important for food quality monitoring. Herein, we developed two coumarin-difluoroboron ß-diketonate hybrid probes, 1 and 2, for detection of amines. Both probes possess large conjugated structures and donor-acceptor-donor configuration, exhibiting solvatochromic effects due to intramolecular charge transfer mechanism. Upon reaction with amines, the boron atom in difluoroboron unit can interact with lone pair electrons of nitrogen atom, thus resulting in significant changes in absorption and fluorescence properties. These probes were successfully utilized to image amine in live cells and liver tissues. Moreover, by photographing probe-loaded food extract supernatant, we establish the relationship between color parameters and food storage time, which can easily indicate food spoilage process. This work and its findings hold promise for providing potential strategies for real-time and convenient detection of food freshness.

The Use of Identified Hypoxia-related Genes to Generate Models for Predicting the Prognosis of Cerebral Ischemia‒reperfusion Injury and Developing Treatment Strategies.

Cerebral ischemia‒reperfusion injury (CIRI) is a type of secondary brain damage caused by reperfusion after ischemic stroke due to vascular obstruction. In this study, a CIRI diagnostic model was established by identifying hypoxia-related differentially expressed genes (HRDEGs) in patients with CIRI. The ischemia‒reperfusion injury (IRI)-related datasets were downloaded from the Gene Expression Omnibus (GEO) database ( http://www.ncbi.nlm.nih.gov/geo ), and hypoxia-related genes in the Gene Cards database were identified. After the datasets were combined, hypoxia-related differentially expressed genes (HRDEGs) expressed in CIRI patients were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the HRDEGs were performed using online tools. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed with the combined gene dataset. CIRI diagnostic models based on HRDEGs were constructed via least absolute shrinkage and selection operator (LASSO) regression analysis and a support vector machine (SVM) algorithm. The efficacy of the 9 identified hub genes for CIRI diagnosis was evaluated via mRNA‒microRNA (miRNA) interaction, mRNA-RNA-binding protein (RBP) network interaction, immune cell infiltration, and receiver operating characteristic (ROC) curve analyses. We then performed logistic regression analysis and constructed logistic regression models based on the expression of the 9 HRDEGs. We next established a nomogram and calibrated the prediction data. Finally, the clinical utility of the constructed logistic regression model was evaluated via decision curve analysis (DCA). This study revealed 9 critical genes with high diagnostic value, offering new insights into the diagnosis and selection of therapeutic targets for patients with CIRI. : Not applicable.

Dissecting lysosomal viscosity fluctuations in live cells and liver tissues with an ingenious NIR fluorescent probe.

Viscosity is a pivotal component in the cell microenvironment, while lysosomal viscosity fluctuation is associated with various human diseases, such as tumors and liver diseases. Herein, a near-infrared fluorescent probe (BIMM) based on merocyanine dyes was designed and synthesized for detecting lysosomal viscosity in live cells and liver tissue. The increase in viscosity restricts the free rotation of single bonds, leading to enhanced fluorescence intensity. BIMM exhibits high sensitivity and good selectivity, and is applicable to a wide pH range. BIMM has near-infrared emission, and the fluorescent intensity shows an excellent linear relationship with viscosity. Furthermore, BIMM possessing excellent lysosomes-targeting ability, and can monitor viscosity changes in live cells stimulated by dexamethasone, lipopolysaccharide (LPS), and nigericin, and differentiate between cancer cells and normal cells. Noticeably, BIMM can accurately analyze viscosity changes in various liver disease models with HepG2 cells, and is successfully utilized to visualize variations in viscosity on APAP-induced liver injury. All the results demonstrated that BIMM is a powerful wash-free tool to monitor the viscosity fluctuations in living systems.

Efficient removal of 3,6-dichlorocarbazole with Fe0-activated peroxymonosulfate: performance, intermediates and mechanism.

Nowadays, polyhalogenated carbazoles (PHCZs) are a major pollutant that has recently sparked widespread concern. In this work, peroxymonosulfate (PMS) was activated by zero valent iron (Fe0) to remove 3,6-dichlorocarbazole (3,6-CCZ). First, the key parameters influencing 3,6-CCZ degradation (PMS dosage, Fe0 dosage, initial pH, temperature and co-existing ions) were determined. Under the determined optimum conditions, the removal rate of 3,6-CCZ reached 100% within 1.5 h. Sulfate radicals (SO4·-), hydroxyl radicals (OH·), and singlet oxygen (1O2) generated in the reaction were directly identified with 0.1 M 5,5-dimethyl-1-pyrrolidine N-oxide (DMPO) by in-situ electron paramagnetic resonance (EPR) and indirectly identified by radical quenching experiments. The main reactive oxygen species (ROS) were different from most reported hydroxyl radicals (OH·) and sulfate radicals (SO4·-). In this study, it was found that OH· and 1O2 play a major role. Then, fresh and reacted Fe0 were characterized by XRD, SEM, and XPS. Iron corrosion products such as Fe2O3, Fe3O4, and FeOOH were generated. Finally, 3,6-CCZ degradation intermediates were identified by GC-MS and its degradation pathway was speculated. The intermediate pathway confirmed the combined action of (OH·) and (1O2) in 3,6-CCZ removal. This study provides new insight into the activation mechanism of Fe0-activated PMS and the removal mechanism of 3,6-CCZ.Highlights Fe0 is a long-lasting and efficient catalyst of PMS for the degradation of 3,6-CCZ.The key parameters influencing 3,6-CCZ degradation were determined.The degradation pathways of 3,6-CCZ were inferred.OH· and 1O2 were the main ROS in Fe0-activated PMS system.

Microelectrolysis-integrated constructed wetland with sponge iron filler to simultaneously enhance nitrogen and phosphorus removal.

Integrating sponge iron (SI) and microelectrolysis individually into constructed wetlands (CWs) to enhance nitrogen and phosphorus removal are challenged by ammonia (NH4+-N) accumulation and limited total phosphorus (TP) removal efficiency, respectively. In this study, a microelectrolysis-assisted CW using SI as filler surrounding the cathode (e-SICW) was successfully established. Results indicated that e-SICW reduced NH4+-N accumulation and intensified nitrate (NO3--N), the total nitrogen (TN) and TP removal. The concentration of NH4+-N in the effluent from e-SICW was lower than that from SICW in the whole process with 39.2-53.2 % decrease, and as the influent NO3--N concentration of 15 mg/L and COD/N ratio of 3, the removal efficiencies of NO3--N, TN and TP in e-SICW achieved 95.7 ± 1.9 %, 79.8 ± 2.5 % and 98.0 ± 1.3 %, respectively. Microbial community analysis revealed that hydrogen autotrophic denitrifying bacteria of Hydrogenophaga was highly enriched in e-SICW.

A photocatalytic-microbial coupling system for simultaneous removal of harmful algae and enhanced denitrification: Construction, performance and mechanism of action.

Recently, harmful algal blooms (HABs) have become occurred with increasingly frequency worldwide. High nitrate content is one of the primary causes of eutrophication. Research has shown that photocatalytic materials enhance the effectiveness of microbial denitrification while removing other contaminants, despite some shortcomings. Based on this, we loaded TiO2/C3N4 heterojunctions onto weaveable, flexible carbon fibers and established a novel photocatalytically enhanced microbial denitrification system for the simultaneous removal of harmful algae and Microcystin-LR. We found that 99.35% of Microcystis aeruginosa and 95.34% of MC-LR were simultaneously and effectively removed. Compared to existing denitrification systems, the nitrate removal capacity improved by 72.33%. The denitrifying enzyme activity and electron transport system activity of microorganisms were enhanced by 3.54-3.86 times. Furthermore, the microbial community structure was optimized by the regulation of photogenerated electrons, and the relative abundance of main denitrifying bacteria increased from 50.72% to 66.45%, including Proteobacteria and Bacteroidetes. More importantly, we found that the increased secretion of extracellular polymeric substances by microorganisms may be responsible for the persistence of the reinforcing effect caused by photogenerated electrons in darkness. The higher removal of Microcystis aeruginosa and Microcystin-LR (MC-LR) achieved by the proposed system would reduce the frequency of HAB outbreaks and prevent the associated secondary pollution.

Multimodal evaluation of the bloodstream alteration before and after combined revascularization for Moyamoya disease.

Objective: This study aimed to explore the hemodynamic changes before and after anastomosis in patients with Moyamoya disease (MMD) using multiple models. Methods: We prospectively enrolled 42 MMD patients who underwent combined revascularization. Intraoperative FLOW800 was performed before and after anastomosis, and parameters was collected, including maximum intensity, delay time, rise time, slope, blood flow index, and microvascular transit time (MVTT). Additionally, preoperative and postoperative hemodynamic parameters were measured using color Doppler ultrasonography (CDUS), including peak systolic velocity, end-diastolic velocity, resistance index (RI), pulsatility index (PI), and flow volume. Subsequently, the correlation between FLOW800 and CDUS parameters was explored. Results: A total of 42 participants took part with an average age of 46.5 years, consisting of 19 men and 23 women. The analysis of FLOW800 indicated that both the delay time and rise time experienced a substantial decrease in both the recipient artery and vein. Additionally, the MVTT was found to be significantly reduced after the surgery (5.7 ± 2.2 s vs. 4.9 ± 1.6, p = 0.021). However, no statistically significant differences were observed among the other parameters. Similarly, all postoperative parameters in CDUS hemodynamics exhibited significant alterations in comparison to the preoperative values. The correlation analysis between FLOW800 and CDUS parameters indicated a significant association between MVTT and RI and PI, no significant relationships were found among the other parameters in the two groups. Conclusion: The hemodynamic outcomes of the donor and recipient arteries demonstrated significant changes following bypass surgery. The parameter of time appears to be more precise and sensitive in assessing hemodynamics using FLOW800. Multiple evaluations of hemodynamics could offer substantial evidence for perioperative management.

A thiomorpholine substituted malonyl-coumarin dye for discriminative detection of hydrazine and strong acidity.

Detection of toxic hydrazine and harmful strong acidity is of great importance for survival of organisms. In the present paper, a new thiomorpholine substituted malonyl-coumarin dye was synthesized for discriminative detection of hydrazine and strong acidity. At pH 7.4, the fluorescence at 560 nm decreased and that at 496 nm increased upon reaction with hydrazine, which was used for on-site detection of hydrazine vapor and endogenous hydrazine in live cells. From pH 2.0 to 1.2, the fluorescence at 563 nm increased greatly, which could be ascribed to the PET process from thiomorpholine to malonyl-coumarin. The probe was desirable for discriminative detection of toxic hydrazine and strong acidity.

Risk factors for wound healing complications after revascularization for MMD with complete Y-shaped incision.

Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease that can be treated with revascularization. Surgery increases the risk of poor wound healing (PWH) due to the impact on the blood supply to the flap. We aimed to analyze risk factors for PWH in MMD with a complete Y-shaped incision. A total of 125 patients with MMD were enrolled in this prospective observational study. The wounds were assessed and measured on the third and seventh days after surgery. The mean age of these patients was 43.3 ± 10.0 years. The ratio of male to female was 1:1.3. 15 (12.0%) patients had incision complications. 5 patients (4.0%) had redness; 2 patients (1.6%) had swelling; 2 patients (1.6%) had fat necrosis; 3 patients (2.4%) had incision infection; and 3 patients (2.4%) had flap necrosis. Student's t test showed significant differences in BMI (P = 0.040) and fever time (P = 0.050). The standard chi-squared test showed significant differences in incision infection (P = 0.010), suture mode (P = 0.047), and cutting off large branch vessels in the flap (P < 0.001). Multivariate logistic regression analysis suggested that incision infection (P = 0.026, OR 12.958), using a skin stapler (P = 0.030, OR 4.335), cutting off large branch vessels in the flap (P = 0.009, OR 5.227), and BMI (P = 0.027, OR 1.204) were risk factors. The area under the curve for risk factors for PWH on a receiver operating characteristic curve was 0.853. Incision infection, using a skin stapler, higher BMI, and cutting off large branch vessels in the flap are risk factors for PWH.

Bioinformatics analysis reveals the landscape of immune cell infiltration and novel immune-related biomarkers in moyamoya disease.

Objective: This study aimed to identify immune infiltration characteristics and new immunological diagnostic biomarkers in the cerebrovascular tissue of moyamoya disease (MMD) using bioinformatics analysis. Methods: GSE189993 and GSE141022 were downloaded from the GEO database. Differentially expressed gene and PPI analysis were performed. After performing WGCNA, the most significant module associated with MMD was obtained. Next, functional pathways according to GSEA, GO, and KEGG were enriched for the aforementioned core genes obtained from PPI and WGCNA. Additionally, immune infiltration, using the CIBERSORT deconvolution algorithm, immune-related biomarkers, and the relationship between these genes, was further explored. Finally, diagnostic accuracy was verified with ROC curves in the validation dataset GSE157628. Results: A total of 348 DEGs were screened, including 89 downregulated and 259 upregulated genes. The thistlel module was detected as the most significant module associated with MMD. Functional analysis of the core genes was chiefly involved in the immune response, immune system process, protein tyrosine kinase activity, secretory granule, and so on. Among 13 immune-related overlapping genes, 4 genes (BTK, FGR, PTPN11, and SYK) were identified as potential diagnostic biomarkers, where PTPN11 showed the highest specificity and sensitivity. Meanwhile, a higher proportion of eosinophils, not T cells or B cells, was demonstrated in the specific immune infiltration landscape of MMD. Conclusion: Immune activities and immune cells were actively involved in the progression of MMD. BTK, FGR, PTPN11, and SYK were identified as potential immune diagnostic biomarkers. These immune-related genes and cells may provide novel insights for immunotherapy in the future.

Adipose-derived stem cell-derived extracellular vesicles inhibit neuroblastoma growth by regulating GABBR1 activity through LINC00622-mediated transcription factor AR.

Neuroblastoma (NB) is a huge threat to children's health. Adipose-derived stem cells-derived extracellular vesicles (ADSC-Evs) can regulate tumor progression. This study aimed to identify the role of ADSC-Evs in NB. Following ADSC-Ev isolation and identification, PKH26-labeled ADSC-Evs were cocultured with NB cells to observe the internalization of ADSC-Evs. ADSC-Ev effects on NB cell proliferation, invasion, and migration were assessed. The regulatory molecules related to NB development were predicted. The expressions of and relations among LINC00622, transcriptional factor androgen receptor (AR), and gamma-aminobutyric acid B-type receptor 1 (GABRR1) were detected and verified. LINC00622 was inhibited in ADSCs to evaluate ADSC-Ev effects on NB cells. Xenograft tumor experiment in nude mice was further performed to evaluate the effects of ADSC-Evs-carried LINC00622 on NB in vivo. ADSC-Evs inhibited NB cell proliferation, invasion, and migration. ADSC-Evs increased GABBR1 expression in NB cells. ADSC-Evs-carried LINC00622 mediated AR to promote GABBR1 expression. Silencing LINC00622 in ADSCs weakened the inhibition of ADSC-Evs on NB cell malignant behaviors. ADSC-Evs reduced tumor growth in nude mice, which was restored after inhibiting LINC00622 expression in ADSCs. We highlighted that ADSC-Evs carried LINC00622 into NB cells to inhibit transcription factor AR and promote GABBR1 expression, thus inhibiting NB cell growth.