Probucol mitigates high-fat diet-induced cognitive and social impairments by regulating brain redox and insulin resistance.

Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects.

Analysis of weighted gene co-expression networks and clinical validation identify hub genes and immune cell infiltration in the endometrial cells of patients with recurrent implantation failure.

Background: About 10% of individuals undergoing in vitro fertilization encounter recurrent implantation failure (RIF), which represents a worldwide social and economic concern. Nevertheless, the critical genes and genetic mechanisms underlying RIF are largely unknown. Methods: We first obtained three comprehensive microarray datasets "GSE58144, GSE103465 and GSE111974". The differentially expressed genes (DEGs) evaluation, enrichment analysis, as well as efficient weighted gene co-expression network analysis (WGCNA), were employed for distinguishing RIF-linked hub genes, which were tested by RT-qPCR in our 30 independent samples. Next, we studied the topography of infiltration of 22 immune cell subpopulations and the association between hub genes and immune cells in RIF using the CIBERSORT algorithm. Finally, a novel ridge plot was utilized to exhibit the potential function of core genes. Results: The enrichment of GO/KEGG pathways reveals that Herpes simplex virus 1 infection and Salmonella infection may have an important role in RIF. After WGCNA, the intersected genes with the previous DEGs were obtained using both variance and association. Notably, the subsequent nine hub genes were finally selected: ACTL6A, BECN1, SNRPD1, POLR1B, GSK3B, PPP2CA, RBBP7, PLK4, and RFC4, based on the PPI network and three different algorithms, whose expression patterns were also verified by RT-qPCR. With in-depth analysis, we speculated that key genes mentioned above might be involved in the RIF through disturbing endometrial microflora homeostasis, impairing autophagy, and inhibiting the proliferation of endometrium. Furthermore, the current study revealed the aberrant immune infiltration patterns and emphasized that uterine NK cells (uNK) and CD4+ T cells were substantially altered in RIF endometrium. Finally, the ridge plot displayed a clear and crucial association between hub genes and other genes and key pathways. Conclusion: We first utilized WGCNA to identify the most potential nine hub genes which might be associated with RIF. Meanwhile, this study offers insights into the landscape of immune infiltration status to reveal the underlying immune pathogenesis of RIF. This may be a direction for the next study of RIF etiology. Further studies would be required to investigate the involved mechanisms.

Cu-phen Coordination Enabled Selective Electrocatalytic Reduction of CO2 to Methane.

Manipulation of selectivity in the catalytic electrochemical carbon dioxide reduction reaction (eCO2RR) poses significant challenges due to inevitable structure reconstruction. One approach is to develop effective strategies for controlling reaction pathways to gain a deeper understanding of mechanisms in robust CO2RR systems. In this work, by precise introduction of 1,10-phenanthroline as a bidentate ligand modulator, the electronic property of the copper site was effectively regulated, thereby directing selectivity switch. By modification of [Cu3(btec)(OH)2]n, the use of [Cu2(btec)(phen)2]n·(H2O)n achieved the selectivity switch from ethylene (faradaic efficiency (FE) = 41%, FEC2+ = 67%) to methane (FECH4 = 69%). Various in situ spectroscopic characterizations revealed that [Cu2(btec)(phen)2]n·(H2O)n promoted the hydrogenation of *CO intermediates, leading to methane generation instead of dimerization to form C2+ products. Acting as a delocalized π-conjugation scaffold, 1,10-phenanthroline in [Cu2(btec)(phen)2]n·(H2O)n helps stabilize Cuδ+. This work presents a novel approach to regulate the coordination environment of active sites with the aim of selectively modulating the CO2RR.

Multimodal Dual-Embedding Networks for Malware Open-Set Recognition.

Malware open-set recognition (MOSR) is an emerging research domain that aims at jointly classifying malware samples from known families and detecting the ones from novel unknown families, respectively. Existing works mostly rely on a well-trained classifier considering the predicted probabilities of each known family with a threshold-based detection to achieve the MOSR. However, our observation reveals that the feature distributions of malware samples are extremely similar to each other even between known and unknown families. Thus, the obtained classifier may produce overly high probabilities of testing unknown samples toward known families and degrade the model performance. In this article, we propose the multi \ modal dual-embedding networks, dubbed MDENet, to take advantage of comprehensive malware features from different modalities to enhance the diversity of malware feature space, which is more representative and discriminative for down-stream recognition. Concretely, we first generate a malware image for each observed sample based on their numeric features using our proposed numeric encoder with a re-designed multiscale CNN structure, which can better explore their statistical and spatial correlations. Besides, we propose to organize tokenized malware features into a sentence for each sample considering its behaviors and dynamics, and utilize language models as the textual encoder to transform it into a representable and computable textual vector. Such parallel multimodal encoders can fuse the above two components to enhance the feature diversity. Last, to further guarantee the open-set recognition (OSR), we dually embed the fused multimodal representation into one primary space and an associated sub-space, i.e., discriminative and exclusive spaces, with contrastive sampling and ρ -bounded enclosing sphere regularizations, which resort to classification and detection, respectively. Moreover, we also enrich our previously proposed large-scaled malware dataset MAL-100 with multimodal characteristics and contribute an improved version dubbed MAL-100 + . Experimental results on the widely used malware dataset Mailing and the proposed MAL-100 + demonstrate the effectiveness of our method.

Diagnostic accuracy of thoracic CT to differentiate transudative from exudative pleural effusion prior to thoracentesis.

BACKGROUND: Computed tomography (CT) scan is commonly performed for pleural effusion diagnostis in the clinic. However, there are limited data assessing the accuracy of thoracic CT for the separation of transudative from exudative effusions. The study aimed to determine the diagnostic value of thoracic CT in distinguishing transudates from exudates in patients with pleural effusion. METHODS: This is a two-center retrospective analysis of patients with pleural effusion, a total of 209 patients were included from The First Affiliated Hospital of Henan University of Science and Technology as the derivation cohort (Luoyang cohort), and 195 patients from the First Affiliated Hospital of Zhengzhou University as the validation cohort (Zhengzhou cohort). Patients who underwent thoracic CT scan followed by diagnostic thoracentesis were enrolled. The optimal cut-points of CT value in pleural fluid (PF) and PF to blood CT value ratio for predicting a transudative vs. exudative pleural effusions were determined in the derivation cohort and further verified in the validation cohort. RESULTS: In the Derivation (Luoyang) cohort, patients with exudates had significantly higher CT value [13.01 (10.01-16.11) vs. 4.89 (2.31-9.83) HU] and PF to blood CT value ratio [0.37 (0.27-0.53) vs. 0.16 (0.07-0.26)] than those with transudates. With a cut-off value of 10.81 HU, the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CT value were 0.85, 88.89%, 68.90%, 43.96%, and 95.76%, respectively. The optimum cut-value for PF to blood CT value ratio was 0.27 with AUC of 0.86, yielding a sensitivity of 61.11%, specificity of 86.36%, PPV of 78.57%, and NPV of 73.08%. These were further verified in the Validation (Zhengzhou) cohort. CONCLUSIONS: CT value and PF to blood CT value ratio showed good differential abilities in predicting transudates from exudates, which may help to avoid unnecessary thoracentesis.

First report on female monozygotic twins discordant for congenital nephrogenic diabetes insipidus.

Ninety percent of congenital nephrogenic diabetes insipidus (NDI) are X-linked inherited and are caused by mutations in the vasopressin type 2 receptor gene (AVPR2). Most affected individuals are males. Only sporadic female cases have been reported. Here, we first reported a female monozygotic twin with discordant phenotypes for NDI carrying a missense variant c.845T>C (p.Leu282Pro) in exon 4 of AVPR2. Intracellular cAMP concentrations in COS7 cells transfected with AVPR2-L282P were significantly decreased by about 60% compared with those in wild-type AVPR2 plasmid transfected cells, suggesting this variation was pathogenic. The X-inactivation pattern was investigated in peripheral leukocytes and urine sediments in both the unaffected and affected pair. Results showed that the affected pair had a skewed X chromosome inactivation (XCI) pattern in urine sediments and a random XCI pattern in leukocytes, while the unaffected pair showed a random XCI pattern both in leukocytes and urine sediments. This was the first report of monozygotic twins who developed different phenotypes of NDI. Our study suggested that the development of NDI symptoms is more closely associated with the XCI pattern in urine sediments compared with the XCI pattern in peripheral leukocytes. Analysis of XCI in peripheral leukocytes may not be enough to explore possible mechanisms.

Maimendong and Qianjinweijing Tang combined with cisplatin suppressed lung cancer through targeting lncRNA-p21.

ETHNOPHARMACOLOGICAL RELEVANCE: Maimendong and Qianjinweijing Tang (Jin formula) is a traditional Chinese medicine formula that has been proven effective in the treatment of lung cancer in long-term clinical practice. AIM OF THE STUDY: To evaluate the anti-tumor effects of Jin formula combined with cisplatin (JIN + DDP) in vivo and in vitro, as well as to explore the role of long non-coding RNA (lncRNA) in the anti-lung cancer mechanism of its action. MATERIALS AND METHODS: A Lewis lung cancer model was established in C57 BL/6 mice to study the in vivo anti-tumor effect of Jin formula combined with cisplatin. TUNEL staining and western blot were applied to study the effects of Jin formula combined cisplatin on apoptosis. The in vitro anti-cancer function of Jin formula combined with cisplatin was explored by cell viability assay, flow cytometry, wound healing assay and transwell assay. The changes in lncRNA expression profiles were determined by lncRNA microarray, and the differentially expressed lncRNA-p21 was verified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. The expression differences of lncRNA-p21 in tumor and normal tissues were analyzed by bioinformatics, and the expression differences of lncRNA-p21 in tumor cells and normal cells were detected by qRT-PCR. The role of lncRNA-p21 in the anti-cancer effect of Jin formula combined cisplatin was investigated by knockdown or overexpression of lncRNA-p21 and a series of cell experiments. The expression of MAPK pathway-related proteins was analyzed by western blot. RESULTS: Jin formula combined with cisplatin (JIN + DDP) can suppress tumor growth and promote apoptosis in Lewis lung cancer mouse model. LncRNA-p21 was significantly up-regulated in the JIN and JIN + DDP groups, and the expression of lncRNA-p21 in lung cancer tissues and cells was lower than that in normal tissues and cells. In vitro, JIN + DDP significantly induced apoptosis and inhibited the proliferation, migration, and invasion of H460 and H1650 lung cancer cells. The above effects can be enhanced by the overexpression of lncRNA-p21 and eliminated by knock-down of lncRNA-p21. Further studies revealed that JIN + DDP inhibited the expression of mitogen-activated protein kinase (MAPK) pathway-related proteins, whereas knock-down of lncRNA-p21 abrogated the inhibition of the MAPK signaling pathway. CONCLUSIONS: This study showed that Jin formula combined with cisplatin could effectively inhibit the progression of lung cancer partially through targeting lncRNA-p21.

Increased expression of ficolin-1 is associated with airway obstruction in asthma.

BACKGROUND: The activated complement cascade is involved in asthmatic airway inflammation. Ficolins are essential for innate immunity and can activate the complement lectin pathway. Despite this, the significance of ficolins in asthma has yet to be determined. This study aimed to explore the presence of ficolins in individuals with asthma and to determine the relationship between ficolins and clinical characteristics. METHODS: For the study, 68 asthmatic patients and 30 healthy control subjects were recruited. Enzyme-linked immunosorbent assay was used to determine plasma ficolin-1, ficolin-2, and ficolin-3 concentrations both before and after inhaled corticosteroid (ICS) therapy. Further, the associations of plasma ficolin-1 level with pulmonary function and asthma control questionnaire (ACQ) score were examined in the asthma patients. RESULTS: Patients with asthma exhibited significantly elevated plasma ficolin-1 levels (median, 493.9 ng/mL; IQR, 330.2-717.8 ng/mL) in comparison to healthy controls (median, 330.6 ng/mL; IQR, 233.8-371.1 ng/mL). After ICS treatment, plasma ficolin-1 (median, 518.1 ng/mL; IQR, 330.2-727.0 ng/mL) in asthmatic patients was significantly reduced (median, 374.7 ng/mL; IQR, 254.8-562.5 ng/mL). Additionally, ficolin-1 expressions in plasma were significantly correlated with pulmonary function parameters and ACQ score in asthmatic patients. Asthma patients with higher plasma ficolin-1 levels demonstrated poorer lung function than those with lower plasma ficolin-1 levels. CONCLUSIONS: The results revealed that asthmatic patients had higher plasma ficolin-1 concentrations, which decreased after ICS treatment and were linked to their lung function, implying a potential involvement of ficolin-1 in asthma pathogenesis.

Pathogenic Nocardia amamiensis infection: A rare case report and literature review.

Background: To date, only six cases of Nocardia amamiensis infection have been reported, including two ocular cases, three pulmonary cases, and one disseminated case. However, no Nocardia amamiensis pulmonary infection cases have been reported in immunocompetent patients without structural pulmonary disease. This study describes a rare case and provides a detailed review of all previous cases. Methods: A pulmonary infection caused by Nocardia amamiensis in a 64-year-old man with low-grade fever, night sweats, and weight loss was reported. All previously reported cases of Nocardia amamiensis infection were searched and reviewed. Results: The pathogen was identified as Nocardia amamiensis using bronchoalveolar lavage fluid (BALF) mNGS, and the current case was successfully treated with trimethoprim-sulfamethoxazole (ST) monotherapy. mNGS and 16S rRNA PCR are standard tests to identify Nocardia.Conclusion: mNGS has high diagnostic performance for Nocardia amamiensis. Further studies are needed to clarify the clinical characteristics and explore more effective treatment protocols for this rare pathogen.

Astragaloside IV attenuates lipopolysaccharide induced liver injury by modulating Nrf2-mediated oxidative stress and NLRP3-mediated inflammation.

Aims and objectives: Sepsis-associated liver injury is a common public health problem in intensive care units. Astragaloside IV (AS-IV) is an active component extracted from the Chinese herb Astragalus membranaceus, and has been shown to have anti-oxidation, anti-inflammation, and anti-apoptosis properties. The research aimed to investigate the protective effect of AS-IV in lipopolysaccharide (LPS)-induced liver injury. Methods: Male C57BL/6 wild-type mice (6-8 week-old) were intraperitoneally injected with 10 mg/kg LPS for 24 h and AS-IV (80 mg/kg) 2 h before the LPS injection. Biochemical and histopathological analyses were carried out to assess liver injury. The RT-qPCR analyzed the mRNA expression of IL-1ß, TNF-α, and IL-6. The mRNA and protein expression of SIRT1, nuclear Nrf2, Nrf2, and HO-1 were measured by Western blotting. Results: Serum alanine/aspartate aminotransferases (ALT/AST) analysis, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were showed that AS-IV protected against LPS-induced hepatotoxicity. The protection afforded by AS-IV was confirmed by pathological examination of the liver. Pro-inflammatory cytokines, including interleukin- 1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6), were observed to be reversed by AS-IV after exposure to LPS. Western blot analysis demonstrated that AS-IV enhanced the expression levels of Sirtuin 1 (SIRT1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1). Conclusions: AS-IV protects against LPS-induced Liver Injury and Inflammation by modulating Nrf2-mediated oxidative stress and NLRP3-mediated inflammation.

Spinel-Derived Formation and Amorphization of Bimetallic Oxyhydroxides for Efficient Electrocatalytic Biomass Oxidation.

Replacing the oxygen evolution reaction (OER) with water-assisted oxidation of organic molecules represents a promising approach for achieving sustainable electrochemical biomass utilization. Among numerous OER catalysts, spinels have received substantial attention due to their manifold compositions and valence states, yet their application in biomass conversions remains rare. Herein, a series of spinels were investigated for the selective electrooxidation of furfural and 5-hydroxymethylfurfural, two model substrates for versatile value-added chemical products. Spinel sulfides universally exhibit superior catalytic performance compared to that of spinel oxides, and further investigations show that the replacement of oxygen with sulfur led to the complete phase transition of spinel sulfides into amorphous bimetallic oxyhydroxides during electrochemical activation, serving as the active species. Excellent values of conversion rate (100%), selectivity (100%), faradaic efficiency (>95%), and stability were achieved via sulfide-derived amorphous CuCo-oxyhydroxide. Furthermore, a volcano-like correlation was established between their BEOR and OER activities based on an OER-assisted organic oxidation mechanism.

KOH-Enabled Axial-Oxygen Coordinated Ni Single-Atom Catalyst for Efficient Electrocatalytic CO2 Reduction.

Precise control of the coordination structure of metal centers is an ideal approach to achieve reasonable selectivity, activity, and stability in the electrochemical reduction of CO2 . In this work, the KOH activation strategy for preparation of hierarchically porous material containing Ni single-atoms with axial-oxygen coordination is reported. Spectroscopic measurements reveal the multiple roles of KOH as oxygen source, pore-making reagent and promoter for the formation of key phthalocyanine structure. It exhibits superior surface area (1801 m2  g-1 ) and electrocatalytic performance (Faradaic efficiency of 94%, Turnover frequency of 11 362 h-1 ). Notably, KOH-enabled architecture with abundant pores benefits the anchoring of Ni atoms and mass transfer for high activity and selectivity. Density functional theory calculations suggest that the axial-oxygen ligand can promote the electronic delocalization of the Ni site for facilitating the *COOH formation and *CO desorption to efficiently produce CO.

Influence of microplastics on microbial anaerobic detoxification of chlorophenols.

Microplastics (MPs) can absorb halogenated organic compounds and transport them into marine anaerobic zones. Microbial reductive dehalogenation is a major process that naturally attenuates organohalide pollutants in anaerobic environments. Here, we aimed to determine the mechanisms through which MPs affect the microbe-mediated marine halogen cycle by incubating 2,4,6-trichlorophenol (TCP) dechlorinating cultures with various types of MPs. We found that TCP was dechlorinated to 4-chlorophenol in biotic control and polypropylene (PP) cultures, but essentially terminated at 2,4-dichlorophenol in polyethylene (PE) and polyethylene terephthalate (PET) cultures after incubation for 20 days. Oxygen-containing functional groups such as peroxide and aldehyde were enriched on PE and PET after incubation and corresponded to elevated levels of intracellular reactive oxygen species (ROS) in the microorganisms. Adding PE or PET to the cultures exerted limited effects on hydrogenase and ATPase activities, but delayed the expression of the gene encoding reductive dehalogenase (RDase). Considering the limited changes in the microbial composition of the enriched cultures, these findings suggested that microbial dechlorination is probably affected by MPs through the ROS-induced inhibition of RDase synthesis and/or activity. Overall, our findings showed that extensive MP pollution is unfavorable to environmental xenobiotic detoxification.

Conservative Novelty Synthesizing Network for Malware Recognition in an Open-Set Scenario.

We study the challenging task of malware recognition on both known and novel unknown malware families, called malware open-set recognition (MOSR). Previous works usually assume the malware families are known to the classifier in a close-set scenario, i.e., testing families are the subset or at most identical to training families. However, novel unknown malware families frequently emerge in real-world applications, and as such, require recognizing malware instances in an open-set scenario, i.e., some unknown families are also included in the test set, which has been rarely and nonthoroughly investigated in the cyber-security domain. One practical solution for MOSR may consider jointly classifying known and detecting unknown malware families by a single classifier (e.g., neural network) from the variance of the predicted probability distribution on known families. However, conventional well-trained classifiers usually tend to obtain overly high recognition probabilities in the outputs, especially when the instance feature distributions are similar to each other, e.g., unknown versus known malware families, and thus, dramatically degrade the recognition on novel unknown malware families. To address the problem and construct an applicable MOSR system, we propose a novel model that can conservatively synthesize malware instances to mimic unknown malware families and support a more robust training of the classifier. More specifically, we build upon the generative adversarial networks to explore and obtain marginal malware instances that are close to known families while falling into mimical unknown ones to guide the classifier to lower and flatten the recognition probabilities of unknown families and relatively raise that of known ones to rectify the performance of classification and detection. A cooperative training scheme involving the classification, synthesizing and rectification are further constructed to facilitate the training and jointly improve the model performance. Moreover, we also build a new large-scale malware dataset, named MAL-100, to fill the gap of lacking a large open-set malware benchmark dataset. Experimental results on two widely used malware datasets and our MAL-100 demonstrate the effectiveness of our model compared with other representative methods.

Overexpression of hypoxia-inducible factor 1α and excessive vascularization in the peri-implantation endometrium of infertile women with chronic endometritis.

Objective: Chronic endometritis (CE) contributes to impaired endometrial receptivity and is closely associated with poor in vitro fertilization (IVF) outcomes. However, the mechanisms underlying CE are unclear. Here, we investigated the role of the hypoxic microenvironment and endometrial vascularization in the peri-implantation endometrium of infertile women with CE. Methods: This retrospective study involved 15 fertile women and 77 infertile patients diagnosed with CE based on CD138+ ≥1/10 high-power fields (HPFs). The CE patients were divided into Group 1 (CD138+ 1-4/10 HPFs, 53 cases) and Group 2 (CD138+ ≥5/10 HPFs, 24 cases). The expression levels of hypoxia-inducible factor 1α (HIF1α), vascular endothelial growth factor A (VEGFA), and vascular endothelial growth factor receptor 2 (VEGFR2) in peri-implantation endometrium were assessed by qRT-PCR and western blot analyses. Spatial levels of HIF1α, VEGFA, and VEGFR2 in various endometrial compartments was determined using immunohistochemistry and H-score analysis. Microvascular density (MVD) was determined using CD34 staining and scored using Image J. Finally, we used qRT-PCR to assess changes in the expression of HIF1α, VEGFA, and VEGFR2 in CE patients after treatment with first-line antibiotics. Results: Relative to Group 1 and control group, during the implantation window, protein and mRNA levels of HIF1α, VEGFA, and VEGFR2 were markedly high in Group 2 (P<0.05). H-score analysis showed that HIF1α, VEGFA, and VEGFR2 in the luminal, glandular epithelium, and stromal compartments were markedly elevated in Group 2, comparing to control group and Group 1 (P<0.05). Moreover, markedly elevated MVD levels were observed in Group 2. Notably, the above indexes did not differ significantly in the control group versus Group 1. Treatment with antibiotics significantly suppressed the endometrial HIF1α and VEGFA levels in CE-cured patients. Conclusions: Here, we for the first time report the upregulation of HIF1α, VEGFA, and VEGFR2, as well as excessive endometrial vascularization in the peri-implantation endometrium of CE patients. Our findings offer new insights into reduced endometrial receptivity in CE-associated infertility.

Ninj2 regulates Schwann cells development by interfering laminin-integrin signaling.

Rationale: Myelin sheath is an important structure to maintain normal functions of the nerves. Nerve Injury-Induced Protein 2 (Ninj2) was found upregulated in Schwann cells (SC) upon injury. However, whether and how Ninj2 plays a role in myelination remain unknown. Methods: In this study, we use transmission electron microscope imaging, immunofluorescent imaging, and behavioral tests to show the effects of Ninj2 on myelination and remyelination in peripheral nervous system (PNS) of SC-specific Ninj2 knockout mice (Dhhcre/+;Ninj2fl/fl ). For mechanism studies, we use RNA-Seq analysis to show the Ninj2-related pathways, and co-immunoprecipitation/mass-spectrometry to identify the Ninj2-interacting proteins in SCs. Furthermore, we evaluate the effect of integrin inhibitor GRGDSP during remyelination. Results: Ninj2 negatively regulates SC development. Ninj2-deficient mice exhibit precocious myelination phenotype, as well as the accelerated remyelination process after sciatic nerve injury. Loss of Ninj2 promotes myelination by promoting SC proliferation to augment its population. Mechanistically, Ninj2 interacted with ITGB1 on SC membrane, which inhibits laminin-integrin signaling. Removal of Ninj2 induces the activity of laminin-integrin signaling, resulting in the improved myelination in the Dhhcre/+;Ninj2fl/fl mice. Inhibition of laminin-integrin signaling by integrin inhibitor GRGDSP sufficiently delays the remyelination process in the Dhhcre/+;Ninj2fl/fl mice with sciatic nerve injury. Conclusion: Our study found Ninj2 as a negative regulator in the network controlling myelination in the PNS.

Case Report: Clinical characteristics and genetic analysis of two patients with hereditary hemorrhagic telangiectasia.

Objective: To analyze the clinical features and genetic characteristics of two patients with hereditary hemorrhagic telangiectasia (HHT) and to review the relevant literature. Methods: The clinical data of two HHT patients admitted to the author's hospital between April 2019 and February 2022 were retrospectively analyzed. Meanwhile, the genetic analysis was performed with their consent. Results: The first patient was a 62-year-old woman who had been complaining of shortness of breath and fever for 20 days. Her previous medical history included brain abscess drainage and video-assisted thoracoscopic surgery for a pulmonary hemangioma. A right heart catheterization revealed no pulmonary arterial hypertension, and an abdominal enhanced magnetic resonance imaging revealed multiple arteriovenous malformations in the liver. Her ACVRL1 heterozygous variants were discovered through whole-exon gene testing. The second case involved a 47-year-old woman who had been experiencing chest tightness for the past 2 years. Several years ago, she underwent brain abscess drainage and embolization of a pulmonary arteriovenous fistula. Ultrasound revealed generalized hepatic vascular dilation, and enhanced computed tomography revealed numerous pulmonary venous fistulas scattered in both lungs as well as multiple arteriovenous malformations in the liver. Her whole-exon gene testing revealed that she, like her son, had heterozygous ENG variants. Conclusion: HHT patients may experience infection, bleeding, dyspnea, and other symptoms. Imaging is important in disease diagnosis and management because early detection and treatment can prevent major complications and disability or even death.

Highly Selective Electrocatalytic Oxidation of Amines to Nitriles Assisted by Water Oxidation on Metal-Doped α-Ni(OH)2.

Selective oxidation to synthesize nitriles is critical for feedstock manufacturing in the chemical industry. Current strategies typically involve substitutions of alkyl halides with toxic cyanides or the use of strong oxidation reagents (oxygen or peroxide) under ammoxidation/oxidation conditions, setting considerable challenges in energy efficiency, sustainability, and production safety. Herein, we demonstrate a facile, green, and safe electrocatalytic route for selective oxidation of amines to nitriles under ambient conditions, assisted by the anodic water oxidation on metal-doped α-Ni(OH)2 (a typical oxygen evolution reaction catalyst). By controlling the balance between co-adsorption of the amine molecule and hydroxyls on the catalyst surface, we demonstrate that Mn doping significantly promotes the subsequent chemical oxidation of amines, resulting in Faradaic efficiencies of 96% for nitriles under ≥99% conversion. This anodic oxidation is further coupled with cathodic hydrogen evolution for overall atomic economy and additional green energy production.

Plasma Angiopoietin-2 as a Promising Biomarker for the Prognosis of Acute Pulmonary Embolism.

BACKGROUND: Endothelial damage is one of the pathogenic conditions of acute pulmonary embolism (APE). The essential role of angiogenin, ribonuclease A family, member 2 (Ang-2) in APE remains unclear. This study aimed to investigate the predictive value of Ang-2 in the clinical outcomes of patients with APE. METHODS: Plasma Ang-2 levels were measured by an enzyme-linked immunosorbent assay kit using a DuoSet methodology in 118 APE patients and 53 healthy controls. Baseline data relevant to mortality over time were obtained from hospital databases or by patient's follow-up (median follow-up time: 25.0 ± 13.2 months). The main outcome was all-cause mortality. RESULTS: Plasma Ang-2 level was significantly higher in APE patients than in healthy controls (p < 0.001). Patients dying during the first 30 days presented higher baseline levels of Ang-2 than the survivors (p < 0.001). Patients dying during the follow-up also showed higher baseline levels of Ang-2 than the survivors (p < 0.001). The multi-variable logistic regression analysis showed that the N-terminal propeptide of B-type natriuretic peptide (NT-proBNP) [odds ratio (OR): 19.8; 95% CI: 1.5 - 255.8; p = 0.022] and Ang-2 (OR: 9.9; 95% CI: 1.4 - 70.5; p = 0.022) emerged as independent predictors of the 30-day mortality. Furthermore, the multivariable Cox's regression identified plasma Ang-2 [hazards ratio (HR): 1.35; 95% CI: 1.10 - 1.66; p = 0.004] as an independent predictor of long-term mortality in patients with APE. CONCLUSIONS: A high circulating level of Ang-2 can be considered as an independent predictor for the poor outcome of APE and may serve as a biomarker for the risk stratification in patients with APE.

Exosomes derived from the blood of patients with sepsis regulate apoptosis and aerobic glycolysis in human myocardial cells via the hsa­miR­1262/SLC2A1 signaling pathway.

Myocardial injury occurs in the majority of patients with sepsis and is associated with early mortality. MicroRNAs (miRs) transported by exosomes have been implicated in numerous diseases, such as tumors, acute myocardial infarction and cardiovascular disease. Human serum albumin (hsa)­miR­1262 has been shown to serve a role in sepsis; however, its role in exosomes isolated from patients with sepsis and septic myocardial injury remains unclear. In the present study, serum exosomes were isolated via ultracentrifugation. Solute carrier family 2 member 1 (SLC2A1), an essential mediator in energy metabolism, was silenced and overexpressed in the human myocardial AC16 cell line using lentiviral plasmids containing either SLC2A1­targeting short interfering RNAs or SLC2A1 cDNA, respectively. Cell apoptosis was analyzed using flow cytometry, and the extracellular acidification rate and oxygen consumption rate of AC16 cells were determined using an XFe24 Extracellular Flux Analyzer. Furthermore, the dual­luciferase reporter assay was used to evaluate the interaction between hsa­miR­1262 and SLC2A1. Finally, reverse transcription­quantitative PCR and western blotting were used to evaluate gene and protein expression levels, respectively. Exosomes isolated from the blood of patients with sepsis (Sepsis­exo) markedly reduced aerobic glycolysis activity, but significantly promoted the apoptosis of human AC16 cells in a time­dependent manner. Moreover, Sepsis­exo significantly increased hsa­miR­1262 expression levels, but significantly decreased SLC2A1 mRNA expression levels in a time­dependent manner. Bioinformatics analysis indicated that hsa­miR­1262 bound to the 3' untranslated region of SLC2A1 to negatively regulate its expression. The silencing of SLC2A1 promoted apoptosis and suppressed glycolysis in AC16 cells, whereas SLC2A1 overexpression resulted in the opposite effects. Therefore, the present study demonstrated that exosomes derived from patients with sepsis may inhibit glycolysis and promote the apoptosis of human myocardial cells through exosomal hsa­miR­1262 via its target SLC2A1. These findings highlighted the importance of the hsa­miR­1262/SLC2A1 signaling pathway in septic myocardial injury and provided novel insights into therapeutic strategies for septic myocardial depression.