Microglia-derived exosomes selective sorted by YB-1 alleviate nerve damage and cognitive outcome in Alzheimer's disease.

BACKGROUND: Neuroinflammation is a characteristic pathological change of Alzheimer's Diseases (AD). Microglia have been reported to participate in inflammatory responses within the central nervous system. However, the mechanism of microglia released exosome (EXO) contribute to communication within AD microenvironment remains obscure. METHODS: The interaction between microglia and AD was investigated in vitro and in vivo. RNA-binding protein immunoprecipitation (RIP) was used to investigate the mechanisms of miR-223 and YB-1. The association between microglia derived exosomal YB-1/miR-223 axis and nerve cell damage were assessed using Western blot, immunofluorescence, RT-PCR, ELISA and wound healing assay. RESULTS: Here, we reported AD model was responsible for the M1-like (pro-inflammatory) polarization of microglia which in turn induced nerve cell damage. While M2-like (anti-inflammatory) microglia could release miR-223-enriched EXO which reduced neuroinflammation and ameliorated nerve damage in AD model in vivo and in vitro. Moreover, YB-1 directly interacted with miR-223 both in cell and EXO, and participated in microglia exosomal miR-223 loading. CONCLUSION: These results indicate that anti-inflammatory microglia-mediated neuroprotection form inflammatory damage involves exporting miR-223 via EXO sorted by YB-1. Consequently, YB-1-mediated microglia exosomal sorting of miR-223 improved the nerve cell damage repair, representing a promising therapeutic target for AD.

Progression of enlarged perivascular spaces contributes to occurrence of silent lacunar infarction in the elderly.

INTRODUCTION: This study aims to assess the effect of enlarged perivascular spaces (EPVS) in patients using the methods of scale score and 3D volume quantification and to determine whether EPVS progression is related to the occurrence of silent lacunar infarction (SLI). METHOD: Three hundred sixty-seven elderly patients with EPVS were screened by MRI on the day of admission and 2 years later; 295 patients were included in the final study, among which 136 patients had EPVS with SLI (EL); and 159 patients had EPVS without SLI (EOL). Both scale score and 3D volume quantification method were used to evaluate EPVS. The 295 patients were divided into three groups based on EPVS progression state: Group 1 (no progression), Group 2 (0-50% EPVS progression), and Group 3 (≥ 50% EPVS progression). Multiple logistic regression analysis was used to analyze the risk of occurrence of SLI. RESULTS: The EPVS scores and ΔEPVS scores were not significantly different between the EL and EOL groups (p > 0.05). EPVS volumes and their progression were significantly higher in EL compared with EOL (p < 0.001). The incidence of SLI was increased in Groups 2 and 3 compared with those in Group 1, and the trend test showed statistically significant (p = 0.032). Multiple logistic regression analysis showed that the risk of occurrence of SLI was significantly increased in Group 2 (OR 2.24; p = 0.024) and Group 3 (OR 3.31; p = 0.037) versus that in Group 1. CONCLUSION: 3D volume quantification allows for a more sensitive assessment of EPVS changes, and the progression of EPVS volume may contribute to the occurrence of SLI.

Improvement in Corrosion Resistance and Interfacial Contact Resistance Properties of 316L Stainless Steel by Coating with Cr, Ti Co-Doped Amorphous Carbon Films in the Environment of the PEMFCs.

In order to obtain films with high corrosion resistance and excellent interfacial contact resistance (ICR) on 316L stainless steel used for bipolar plates in proton-exchange membrane fuel cells (PEMFCs), Cr, Ti co-doped amorphous carbon films were prepared on 316L stainless steel. The preparation method for the coating was magnetron sputtering. The doping amount of the Ti element was controlled by a Cr target and a Ti target current. The change in the structure and properties of the coating after the change from Cr single-element doping to Cr and Ti co-doping was studied. The change rule of the structure and properties of the coating from Cr single-element doping to Cr and Ti co-doping was studied. An increase in the Ti content led to a decreased grain boundary, a flatter surface, and a higher sp2-hybridized carbon content. TiC and CrC nanocrystals were formed in the amorphous carbon structure together. The amorphous carbon films doped with Cr and Ti simultaneously achieved a low ICR and high corrosion resistance compared with single-Cr-doped amorphous carbon. The enhanced corrosion resistance was attributed to the decreasing grain boundary, the formation of the TiC crystal structure, and the smaller grain size. The best performance was obtained at a Ti target current of 2A. Compared with bare 316L stainless steel, the corrosion resistance of Cr, Ti co-doped amorphous carbon (Icorr = 5.7 × 10-8 A/cm2, Ti-2 sample) was greatly improved. Because Ti doping increased the content of sp2-hybridized carbon in the coating, the contact resistance of the coating decreased. Moreover, the interfacial contact resistance was 3.1 mΩ·cm2 in the Ti-2 sample, much lower than that of bare 316L stainless steel. After the potentiostatic polarization test, the coating still had excellent conductivity.

A new scheme of global feature management improved the performance and stability of radiomics model: a study based on CT images of acute brainstem infarction.

OBJECTIVE: The performance and stability of radiomics model caused by dimension reduction remain being confronted with major challenges. In this study, we aimed to propose a new scheme of global feature management independent of dimension reduction to improve it. METHODS: The non-contrast computed tomography (NCCT) images of acute brainstem infarction (ABI) from two medical centers were used as test and validation sets. A new scheme was constructed based on global feature management, and the traditional scheme dependent on dimension reduction was used as control. The radiomic features of NCCT images were extracted in Matlab R2013a. The performance of prediction model was evaluated by the generalized linear model (GLM) and multivariate logistic regression. And, the stability of radiomics model was evaluated with the difference of area under curve (AUC) between the test and validation sets. RESULTS: Compared with the traditional scheme, the new scheme presented a similar detection performance (AUC: 0.875 vs. 0.883), yet a better performance in predicting prognosis (AUC: 0.864, OR = 0.917, p = 0.021 vs. AUC:0.806, OR = 0.972, p = 0.007). All these results were well verified in an independent validation set. Moreover, the new scheme showed stronger stability in both the detection model (ΔAUC: 0.013 vs. 0.039) and prediction model (ΔAUC = 0.004 vs. 0.044). CONCLUSION: Although there might be several limitations, this study proved that the scheme of global feature management independent of dimension reduction could be a powerful supplement to the radiomics methodology. KEY POINTS: • The new scheme (Swavelet) presented similar detection performances for ABI with the traditional scheme. • A better predictive performance for END was found in the new scheme (Swavelet) compared with the traditional scheme. • Stronger model stability was found in both the detection and prediction models based on the new scheme.

Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression.

BACKGROUND: Neuroinflammation is an important component mechanism in the development of depression. Exosomal transfer of MDD-associated microRNAs (miRNAs) from neurons to microglia might exacerbate neuronal cell inflammatory injury. RESULTS: By sequence identification, we found significantly higher miR-9-5p expression levels in serum exosomes from MDD patients than healthy control (HC) subjects. Then, in cultured cell model, we observed that BV2 microglial cells internalized PC12 neuron cell-derived exosomes while successfully transferring miR-9-5p. MiR-9-5p promoted M1 polarization in microglia and led to over releasing of proinflammatory cytokines, such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which exacerbated neurological damage. Furthermore, we identified suppressor of cytokine signaling 2 (SOCS2) as a direct target of miR-9-5p. Overexpression of miR-9-5p suppressed SOCS2 expression and reactivated SOCS2-repressed Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways. Consistently, we confirmed that adeno-associated virus (AAV)-mediated overexpression of miR-9-5p polarized microglia toward the M1 phenotype and exacerbated depressive symptoms in chronic unpredictable mild stress (CUMS) mouse mode. CONCLUSION: MiR-9-5p was transferred from neurons to microglia in an exosomal way, leading to M1 polarization of microglia and further neuronal injury. The expression and secretion of miR-9-5p might be novel therapeutic targets for MDD.

Real-world data on breast pathologic complete response and disease-free survival after neoadjuvant chemotherapy for hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer: a multicenter, retrospective study in China.

BACKGROUND: The data in the real-world setting on breast pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for hormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+, HER2-) breast cancer (BC) is limited. The present study aims to screen for some predictors and investigate the prognostic significance of breast pCR after NAC in HR+, HER2- BC in China. METHODS: This was a multicenter, retrospective study. In this study, three hundred eighty-four HR+, HER2- BC patients who received NAC were enrolled between 2010 and 2016 from Shanghai Jiaotong University Breast Cancer Database (SJTU-BCDB). These patients were dichotomized according to the presence of breast pCR after NAC. Logistic analysis was used to screen for predictors associated with breast pCR. Kaplan-Meier (K-M) curve and a propensity score matching (PSM) analysis were performed to compare the disease-free survival (DFS) between the two groups. Cox regression was used to analyze the prognostic significance of breast pCR on DFS in HR+, HER2- BC. A nomogram model was established to predict the probability of DFS at 1, 3, and 5 years after NAC. RESULTS: Fifty-seven patients (14.8%) achieved breast pCR. Univariate analysis showed that tumor size, estrogen receptor (ER), progesterone receptor (PR), and Ki67 were associated with breast pCR. Further, multivariate analysis showed that tumor size, PR, and Ki67 remained statistically significant. K-M curves showed a statistical difference between the breast pCR and non-pCR groups before PSM (p = 0.047), and a more significant difference was shown after PSM (p = 0.033). Cox regression after PSM suggested that breast pCR, adjuvant ET, clinical T stage, and Ki67 status were the significant predictive factors for DFS in HR+, HER2- BC patients. The adjusted hazards ratio (aHR) for breast pCR was 0.228 (95% CI, 0.070~0.739; p = 0.014), for adjuvant endocrine therapy was 0.217 (95% CI, 0.059~0.801; p = 0.022), for Ki67 was 1.027 (95% CI, 1.003~1.052; p = 0.027), for cT stages 2 and 3 compared with 1, the values were 1.331 (95% CI, 0.170~10.389), and 4.699 (95% CI, 0.537~41.142), respectively (p = 0.043). A nomogram was built based on these significant predictors, providing an integrated probability of DFS at 1, 3, and 5 years. The values of area under the receiver operating characteristic (ROC) curve (AUC) were 0.967, 0.991, and 0.787, at 1 year, 3 years, and 5 years, respectively, demonstrating the ability of the nomogram to predict the DFS. CONCLUSIONS: This real-world study demonstrates that tumor size, PR, and Ki67 were independent predictive factors for breast pCR in HR+, HER2- BC. Breast pCR after NAC was an independent predictor for DFS in HR+, HER2- patients, regardless of a change in nodes. Furthermore, the nomogram built in our study could predict the probability of individualized DFS in HR+, HER2- BC patients.

Clinicopathological study of gastric schwannoma and review of related literature.

BACKGROUND: This study aimed to investigate the clinical features, diagnostic criteria, treatment options, and prognosis of patients with gastric schwannoma (GS). METHODS: We collected the clinical data of all patients pathologically diagnosed with GS in Zhejiang Provincial People's Hospital from May 2012 to October 2021. RESULTS: A total of 26 cases of GS were analyzed clinicopathologically, where the sizes of the tumor were found to be in the range of 1-6 cm (mean: 3.16 cm, median: 3.05 cm). A computed tomography (CT) scan analysis revealed that most masses were either moderately progressive or uniformly enhanced. According to ultrasound gastroscopy results, most of them were hypoechoic masses. There were 23 cases of surgery and three cases of endoscopic submucosal tumor dissection. Immunohistochemistry demonstrated that S100 was positive in 26 patients, immunomarker SOX10 was positive in five, whereas CD34, CD117, and SMA were negative in most patients. CK (Pan), Dog-1, and Desmin were also found negative. All 26 cases were followed up after the conclusion of the study where no evidence of recurrence or metastasis was observed. CONCLUSIONS: GS is a unique form of peripheral schwannoma. The diagnosis of this type of tumor depends on the pathology and immunohistochemistry of the individual. The key to treating this type of tumor is endoscopy and surgery. Follow up and related literature review showed that GS was a benign tumor with little possibility of malignant transformation.

Abnormalities in FGF family members and their roles in modulating depression-related molecules.

The role of the fibroblast growth factor (FGF) system in depression has received considerable attention in recent years. To understand the role of this system, it is important to identify the specific members of the FGF family that have been implicated and the various mechanisms that they modulated. Here, we review the role of FGFs in depression and integrate evidence from clinical and basic research. These data suggest that changes in the FGF family are involved in depression and possibly in a wider range of psychiatric disorders. We analyse the abnormalities of FGF family members in depression and their roles in modulating depression-related molecules. The role of the FGF family in depression and related disorders needs to be studied in more detail.

18F-FDG uptake velocity but not uptake level is associated with progression of carotid plaque.

OBJECTIVES: The objective of this study was to evaluate whether baseline 18F-fluorodeoxyglucose (FDG) uptake is associated with carotid plaque progression. METHODS: A total of 156 subjects with carotid plaque were enrolled and underwent carotid magnetic resonance imaging (MRI) (at baseline and the 12-month follow-up) and positron emission tomography-computed tomography (PET-CT) (baseline). Carotid plaque progression was evaluated by two indices (the incidence of plaque progression and percentage of plaque increase) with three-dimensional (3D) imaging, while the 18F-FDG uptake was evaluated by the 18F-FDG uptake levels and 18F-FDG uptake velocity. The association between plaque progression and 18F-FDG uptake was investigated by the trend test and multivariate logistic regression analysis. RESULTS: Of the 156 subjects, 80 (51.3%) showed carotid plaque progression during the 12-month follow-up. Firstly, no association was found between 18F-FDG uptake levels and plaque progression. Secondly, significant differences in the incidence of plaque progression were observed among the groups with different uptake velocities, showing a significant decreasing trend ranging from high to intermediate to low (p = 0.002, trend test). After adjusting for covariates, an adequate prediction of the 18F-FDG uptake velocity for the incidence of plaque progression was revealed (OR = 0.682, p < 0.05). In addition, no association was found between the 18F-FDG uptake velocity and the percentage of plaque increase in the subjects with plaque progression (p = 0.757, trend test). CONCLUSIONS: Our findings suggest 18F-FDG uptake velocity is independently associated with the incidence of carotid plaque progression. Additionally, the 18F-FDG uptake velocity, as another important parameter of PET-CT, warrants further study in future clinical research. KEY POINTS: • The18F-FDG uptake levels were not associated with the carotid plaque progression. • The18F-FDG uptake velocity could predict the incidence of carotid plaque progression. • The18F-FDG uptake velocity with related factors warrants more attention in future clinical research.

Synthesis and Characterization of Ru-MOFs on Microelectrode for Trace Mercury Detection.

Mercury ions (Hg2+) pollution in the water environment can cause serious harm to human health. Trace Hg2+ detection is of vital importance for environmental monitoring. Herein, we report a novel design of Ru-MOFs modified gold microelectrode for Hg2+ determination. Ru-MOFs are synthesized directly by the cathodic method on gold microelectrode, with the covered area accurately controlled. Cathodic synthesized Ru-MOFs show good conductivity and are suitable to be used as the electrode surface material directly. The synergy of the pre-deposition process and the adsorption process of Ru-MOFs can effectively improves the performance of the sensor. The results show good linearity (R2 = 0.996) from 0.1 ppb to 5 ppb, with a high sensitivity of 0.583 µA ppb-1 mm-2. The limit of detection is found to be 0.08 ppb and the test process is within 6 min. Most importantly, the senor has a good anti-interference ability and the recoveries are satisfactory. This miniature electrochemical sensor has the potential for on-site detection of trace mercury in the field.

Temporal changes in Lycium barbarum fruit separation force and hardness during selective harvesting.

Lycium barbarum, a plant belonging to the Solanaceae family, is widely used in China due to its abundant nutritional value. Although the current mechanized harvesting method of L. barbarum has effectively minimized production expenses, it continues to have the challenge of inconsistent quality of the produced L. barbarum. The objective of this paper is to evaluate the correlation of the separating force and hardness concerning the timing of harvesting, maturity, and variety. Thus, the optimal time for harvesting ripe L. barbarum can be determined to enhance the quality of selectively mechanized harvesting of this fruit. The experiment was conducted in a L. barbarum plantation located in Qinghai Province during the 2023 harvest period. Two occasions were studied focusing on the primary cultivars Ningqi No. 1 and Ningqi No. 7, examining the three ripening stages of L. barbarum harvested at various times throughout the day. The finding of this study showed that the separation force and hardness of L. barbarum fruits were influenced by the harvesting time, the fruit variety, and the level of maturity. The optimal timing for harvesting different types of L. barbarum varies. It was observed that Ningqi No.1 was best to be harvested in the late afternoon and evening (17:00-21:00), whereas Ningqi No.7 was most suitable to be harvested in the morning (7:00-9:00).

A Novel Extensible Continuum Robot with Growing Motion Capability Inspired by Plant Growth for Path-Following in Transoral Laryngeal Surgery.

This article presents a novel extensible continuum robot (ECR) with growing motion capability for improved flexible access in transoral laryngeal procedures. The robot uses an extensible continuum joint with a staggered V-shaped notched structure as the backbone, driven by the pushing and pulling of superelastic Nitinol rods. The notched structure is optimized to achieve a wide range of extension/contraction and bending motion for the continuum joint. The successive and uniform deflection of the notches provides the continuum joint with excellent constant curvature bending characteristics. The bidirectional rod-driven approach expands the robot's extension capabilities with both pushing and pulling operations, and the superelasticity of the driving rods preserves the robot's bending performance. The ECR significantly increases motion dexterity and reachability through its variable length, which facilitates collision-free access to deep lesions by following the anatomy. To further exploit the advantages of the ECR in path-following for flexible access, a growing motion approach inspired by the plant growth process has been proposed to minimize the path deviation error. Characterization experiments are conducted to verify the performances of the proposed ECR. The extension ratio achieves up to 225.92%, and the average distal positioning error and hysteresis error values are 2.87% and 0.51% within the ±120° bending range. Compared with the typical continuum robot with a fixed length, the path-following deviation of this robot is reduced by more than 58.30%, effectively reducing the risk of collision during access. Phantom experiments validate the feasibility of the proposed concept in flexible access procedures.

A review on the role of RNA methylation in aging-related diseases.

Senescence is the underlying mechanism of organism aging and is robustly regulated at the post-transcriptional level. This regulation involves the chemical modifications, of which the RNA methylation is the most common. Recently, a rapidly growing number of studies have demonstrated that methylation is relevant to aging and aging-associated diseases. Owing to the rapid development of detection methods, the understanding on RNA methylation has gone deeper. In this review, we summarize the current understanding on the influence of RNA modification on cellular senescence, with a focus on mRNA methylation in aging-related diseases, and discuss the emerging potential of RNA modification in diagnosis and therapy.

Identification of SV2C and DENR as Key Biomarkers for Parkinson's Disease Based on Bioinformatics, Machine Learning, and Experimental Verification.

The objective of this study is to investigate the potential biomarkers and therapeutic target genes for Parkinson's disease (PD). We analyzed four datasets (GSE8397, GSE20292, GSE20163, GSE20164) from the Gene Expression Omnibus database. We employed weighted gene co-expression network analysis and differential expression analysis to select genes and perform functional analysis. We applied three algorithms, namely, random forest, support vector machine recursive feature elimination, and least absolute shrinkage and selection operator, to identify hub genes, perform functional analysis, and assess their clinical diagnostic potential using receiver operating characteristic (ROC) curve analysis. We employed the xCell website to evaluate differences in the composition patterns of immune cells in the GEO datasets. We also collected serum samples from PD patients and established PD cell model to validate the expression of hub genes using enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction. Our findings identified SV2C and DENR as two hub genes for PD and decreased in PD brain tissue compared with controls. ROC analysis showed effectively value of SV2C and DENR to diagnose PD, and they were downregulated in the serum of PD patients and cell model. Functional analysis revealed that dopamine vesicle transport and synaptic vesicle recycling are crucial pathways in PD. Besides, the differences in the composition of immune cells, especially basophils and T cells, were discovered between PD and controls. In summary, our study identifies SV2C and DENR as potential biomarkers for diagnosing PD and provides a new perspective for exploring the molecular mechanisms of PD.

Synapse-Related Serum and P300 Biomarkers Predict the Occurrence of Mild Cognitive Impairment in Depression.

Background: Cognitive impairment is one of the common concomitant symptoms of depression. The aims of the present study were to predict the occurrence of mild cognitive impairment (MCI) in patients with depression. Methods: In this study, 217 patients with depression were recruited. Demographic data, serum indices and ERP indices from all participants were collected in the baseline period. The participants were followed for one year, and data from 200 patients were included in final analysis. Patients with depression were divided into those with MCI group (DWM group; n=145) and those without MCI (DWOM group; n=55). Data from the DWM group and the DWOM group were used to construct a logistic regression model, and a receiver operating characteristic (ROC) curve was drawn. Another 72 patients were used to validate the accuracy of our model. Results: Compared with DWOM individuals, DWM individuals were more likely to live alone (P<0.05), had lower baseline serum levels of brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and fibroblast growth factor 22 (FGF22) (P<0.05), and exhibited higher baseline latencies of P300, mismatch negativity (MMN), and N200 (P<0.05). Baseline serum BDNF and FGF22 levels, along with the P300 latency, were selected to construct the regression model using logistic regression. The regression equation was [Formula: see text], and the combination of the 3 indices yielded an area under the ROC curve (AUC) of 0.790 and a predictive accuracy of 0.806. Conclusion: The logistic regression model and ROC curves based on serum BDNF and FGF22 levels and the P300 latency could provide a more effective means to predict the occurrence of MCI in patients with depression.

Cadmium contamination decreased bacterial network complexity and stability in coastal reclamation areas.

Cadmium(Cd) contamination can exert significantly adverse effects on soil microbiota in reclaimed areas, however, its effects on bacterial network structure are still limitedly understood. Here we collected soil samples from typical reclaimed wetlands (RW) and ditch wetlands (DW) in coastal reclamation areas and examined the effects of Cd contamination on the bacterial network complexity and stability. The results showed that the bacterial networks were destabilized by the Cd contamination, while bacteria in DW soils showed robust invulnerability characterized by higher node constancy and compositional stability compared with RW soils. Soil bacteria resisted Cd stress by forming a network with intensive connections in the module but sparser connections among the modules. Especially, network modularity was higher in DW soils than in RW soils, but made it more vulnerable to nodes removal. In addition, Cd contamination promoted bacterial positive cohesion but decreased negative cohesion in RW soils. Flavobacteriaceae, Xanthomonadaceae, and Alcaligenaceae were identified as core phylotypes, which played pivotal roles in regulating interspecies interactions due to higher contributions to cohesion and significant correlations with soil nutrients. The findings of this work indicate the changes of bacterial network structure and the indispensable role of core phylotypes in regulating interactions and maintaining network sustainability under Cd contamination.

A New Species of the Genus Pseudocalotes (Squamata: Agamidae) from Southwest Yunnan, China.

In this study, a new species of the genus Pseudocalotes is described from Yingjiang County, Dehong Dai and Jingpo Autonomous Prefecture, Yunnan Province, China, based on four female specimens. It can be distinguished from its congeners by the following combination of characters: (1) interoculabials 3 or 4; (2) canthals 5-7; (3) cicrcumorbitals 8-11; (4) 1 scale between rostral and nasal; (5) interparietal 1; (6) superciliaries 4-6; (7) supralabials 6-7, the 1st in contact with the nasal; (8) infralabials 6-8; (9) transverse gular fold and antehumeral fold present; (10) 2-3 enlarged scales between eye and ear; (11) nuchal crest single, consists of 3-5 erected spines; (12) dorsal crest row single, discontinuous and low, located between two keeled, parallel and enlarged scale rows; (13) enlarged postrictals absent; (14) scales around midbody 53-62, dorsal body scales heterogenous in size and shape; (15) midventrals smaller than dorsals; (16) subdigital scales on the 4th finger 20-26, and on the 4th toe 24-29; (17) dorsal background coloration light taupe with four irregular brown patches along the middle of dorsal; (18) inner lips wathet, tongue aurantiacus, throat bluish black. The population from Yingjiang County was nested within a highly supported lineage, formed a sister taxon with P. kakhienensis (SH 97/UFB 100) and according to the p-distance, the new species differed from its congeners by 14.5% to 35.2% for NADH dehydrogenase subunit 2 (ND2) and 15.5% to 25.0% for NADH dehydrogenase subunit 4 (ND4).

A new species of the genus Hebius (Squamata, Natricidae) from Yunnan, China.

A new species of the genus Hebius Thompson, 1913 is described from Yingjiang County, Dehong Dai and Jingpo Autonomous Prefecture, Yunnan Province, China, based on molecular and morphological evidence. It can be distinguished from its congeners by the following set of characters: (1) dorsal scale rows 19-17-17, feebly keeled; (2) ventrals 146-151; (3) nasal complete, nostril in the middle of the nasal; (4) supralabials 9, the fourth to sixth in contact with the eye; (5) infralabials 10-11, the first 5 touching the first pair of chin shields; (6) preoculars 2; (7) postoculars 3; (8) temporals 3, arranged in two rows (1+2); (9) maxillary teeth 31, the last 4 slightly enlarged, without diastema; (10) tail comparatively long, TAL/TL ratio 0.334 in the male; (11) dorsolateral series of irregular orange or ochre yellow blotches, extending from the neck to the posterior part of the tail; and (12) venter pale orange, tips of ventrals with subrectangular black blotches. All Hebius specimens were strongly recovered as monophyletic, in which Hebiustaronensis (Smith, 1940) and Hebiusvenningi (Wall, 1910) were monophyletic as sister to the Yingjiang County specimens. According to the p-distance of cytochrome b, the new species differs from its congeners by 9.7-15.4%.

Inhibition of ADORA3 promotes microglial phagocytosis and alleviates chronic ischemic white matter injury.

BACKGROUND: Adenosine A3 receptor (ADORA3) belongs to the adenosine receptor families and the role of ADORA3 in vascular dementia (VaD) is largely unexplored. The present study sought to determine the therapeutic role of ADORA3 antagonist in a mouse model of VaD. METHODS: The GSE122063 dataset was selected to screen the differential expression genes and pathways between VaD patients and controls. A mouse model of bilateral carotid artery stenosis (BCAS) was established. The cognitive functions were examined by the novel object recognition test, Y maze test, and fear of conditioning test. The white matter injury (WMI) was examined by 9.4 T MRI, western blot, and immunofluorescence staining. The mechanisms of ADORA3-regulated phagocytosis by microglia were examined using qPCR, western blot, dual immunofluorescence staining, and flow cytometry. RESULTS: The expression of ADORA3 was elevated in brain tissues of VaD patients and ADORA3 was indicated as a key gene for VaD in the GSE122063. In BCAS mice, the expression of ADORA3 was predominantly elevated in microglia in the corpus callosum. ADORA3 antagonist promotes microglial phagocytosis to myelin debris by facilitating cAMP/PKA/p-CREB pathway and thereby ameliorates WMI and cognitive impairment in BCAS mice. The therapeutic effect of ADORA3 antagonist was partially reversed by the inhibition of the cAMP/PKA pathway. CONCLUSIONS: ADORA3 antagonist alleviates chronic ischemic WMI by modulating myelin clearance of microglia, which may be a potential therapeutic target for the treatment of VaD.

Echinatin protects from ischemic brain injury by attenuating NLRP3-related neuroinflammation.

BACKGROUND: Microglia-mediated neuroinflammation is the major contributor to the secondary brain injury of ischemic stroke. NLRP3 is one of the major components of ischemia-induced microglial activation. Echinatin, a chalcone found in licorice, was reported to have the activity of anti-inflammation and antioxidant. However, the relative study of echinatin in microglia or ischemic stroke is still unclear. METHODS: We intravenously injected echinatin or vehicle into adult ischemic male C57/BL6J mice induced by 60-min transient middle cerebral artery occlusion (tMCAO). The intraperitoneal injection was performed 4.5 h after reperfusion and then daily for 2 more days. Infarct size, blood brain barrier (BBB) leakage, neurobehavioral tests, and microglial-mediated inflammatory reaction were examined to assess the outcomes of echinatin treatment. LPS and LPS/ATP stimulation on primary microglia were used to explore the underlying anti-inflammatory mechanism of echinatin. RESULTS: Echinatin treatment efficiently decreased the infarct size, alleviated blood brain barrier (BBB) damage, suppressed microglial activation, reduced the production of inflammatory factors (e.g., IL-1ß, IL-6, IL-18, TNF-α, iNOS, COX2), and relieved post-stroke neurological defects in tMCAO mice. Mechanistically, we found that echinatin could suppress the NLRP3 assembly and reduce the production of inflammatory mediators independently of NF-κB and monoamine oxidase (MAO). CONCLUSION: Based on our study, we have identified echinatin as a promising therapeutic strategy for the treatment of ischemic stroke.