Sephin1 enhances integrated stress response and autophagy to alleviate myocardial ischemia-reperfusion injury in mice.

OBJECTIVE: Integrated stress response (ISR) is activated to promote cell survival by maintaining the phosphorylation of eukaryotic translation initiation factor 2 (eIF2α). We investigated whether Sephin1 enhances ISR and attenuates myocardial ischemia-reperfusion (MIR) injury. METHODS: Male C57BL/6 J mice were injected with Sephin1 (2 mg/kg,i.p.) 30 min before surgery to establish a model of MIR with 45 min ischemia and 180 min reperfusion. In vitro, the H9C2 cell line with hypoxia-reoxygenation (H/R) was used to simulate MIR. Myocardial injury was evaluated by echocardiography, histologic observation after staining with TTC and H&E and electron microscopy. ISR, autophagy and apoptosis in vivo and in vitro were evaluated by immunoblotting, immunohistochemistry, immunofluorescence, and flow cytometry, respectively. Global protein synthesis was determined using a non-radioactive SUnSET Assay based on the puromycin method. Autophinib, an autophagy-specific inhibitor, was used to investigate the correlation between autophagy and apoptosis in the presence of Sephin1. RESULTS: In vivo, Sephin1 significantly reduced myocardial injury and improved the cardiac function in MIR mice. Sephin1 administration prolonged ISR, reduced cell apoptosis, and promoted autophagy. In vitro, Sephin1 increased the number of stress granules (SGs) and autophagic vesicles, enhanced ISR and related protein synthesis suppression, and reduced cell apoptosis. Autophinib partly reversed autophagosome formation and apoptosis in H9c2 cells. CONCLUSIONS: Sephin1 enhances ISR and related protein synthesis suppression, ameliorates myocardial apoptosis, and promotes autophagy during MIR stress. Sephin1 could act as a noval ISR enhancer for managing acute myocardial ischemia disease.

Oxygen-Activated Boron Nitride for Selective Photocatalytic Coupling of Methanol to Ethylene Glycol.

The controllable photocatalytic C-C coupling of methanol to produce ethylene glycol (EG) is a highly desirable but challenging objective for replacing the current energy-intensive thermocatalytic process. Here, we develop a metal-free porous boron nitride catalyst that demonstrates exceptional selectivity in the photocatalytic production of EG from methanol under mild conditions. Comprehensive experiments and calculations are conducted to thoroughly investigate the reaction mechanism, revealing that the OB3 unit in the porous BN plays a critical role in the preferential activation of C-H bond in methanol to form ⋅CH2OH via a concerted proton-electron transfer mechanism. More prominent energy barriers are observed for the further dehydrogenation of the ⋅CH2OH intermediate on the OB3 unit, inhibiting the formation of some other by-products during the catalytic process. Additionally, a small downhill energy barrier for the coupling of ⋅CH2OH in the OB3 unit promotes the selective generation of EG. This study provides valuable insights into the underlying mechanisms and can serve as a guide for the design and optimization of photocatalysts for efficient and selective EG production under mild conditions.

Exploring Preclinical Experiments with Different Fat Types for Autologous Fat Grafting.

BACKGROUND: Autologous fat transplantation has been a cornerstone of tissue regeneration for decades. However, there is no standardized selection system or criteria for fat graft selection, often relying heavily on the surgeon's experience. OBJECTIVES: This study aimed to investigate various types of fat derivatives, both in vitro and in vivo at the same condition. METHODS: We collected traditional fat granules of different sizes and SVF-gel, evaluating the viability of ADSCs isolated from them and their performance after grafting into mice. RESULTS: Large fat granules exhibited more complete adipocyte structures, and the isolated ADSCs demonstrated superior differentiation, proliferation, and secretion capacities. They also showed excellent volume retention after 12 weeks. In contrast, ADSCs isolated from SVF-gel displayed lower vitality. However, grafts from SVF-gel exhibited the highest volume maintenance rate among the four groups after 12 weeks, closely resembling normal adipose tissue and displaying significant vascularization. Compared to large fat granule and SVF-gel group, medium and small fat granule grafts exhibited lower volume retention and less angiogenesis. CONCLUSIONS: Through preclinical studies, the flexible clinical use of different fat grafts can be tailored to their unique characteristics. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The analyses of the complete mitochondrial genomes of three crabs revealed novel gene rearrangements and phylogenetic relationships of Brachyura.

BACKGROUND: Brachyura crab is the largest branch of Decapoda crustacean. Phylogenetic relationships within Brachyura remain controversial to be investigated. The mitochondrial genome (mitogenome) is an important molecular marker for studying the phylogenetic relationships of Brachyura. METHODS AND RESULTS: To understand the phylogeny of Brachyura, the three complete mitogenomes from Charybdis annulata, Leptodius exaratus, and Spider crab were sequenced and annotated. Their full length was 15,747, 15,716, and 16,608 bp long, respectively. The first two crabs both contained 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes and a control region. However, Spider crab contained 13 PCGs, two rRNA genes, 25 tRNA genes and a control region. The mitogenomes of each of the three crabs exhibited high AT content (67.8%, 69.1%, and 70.8%), with negative AT skews (-0.014, - 0.028, and - 0.017) and GC skews (-0.269, - 0.286, and - 0.341). The gene order of C. annulata was identical to the ancestor of Brachyura. Compared with the ancestor of Brachyura, L. exaratus exhibited the gene rearrangements of Val (V)-rrnS-control region, and Spider crab had the four copies of Lys (K). Phylogenetic analyses indicated that C. annulata belonged to Portunidae family, Portunoidea superfamilies, L. exaratus belonged to Xanthidae family, Xanthoidea superfamilies, and Spider crab belonged to Mithracidae family, Majoidea superfamilies. Phylogenetic analyses showed that the two species (Somanniathelphusa boyangensis and Huananpotamon lichuanense) belonging to the Potamoidea were sister groups to the Thoracotremata, thus supporting the conclusion that Heterotremata is polyphyletic. CONCLUSION: The results of this study enriched the crab mitogenome database and enabled us to better understand the phylogenetic relationships of Brachyura.

Sensitivity analysis of operation parameters of the salt cavern under long-term gas injection-production.

Injection-production operation parameters, the minimum injection gas pressure (IGP: operation pressure), IGP interval, minimum IGP residence time, and injection-production cycle of the underground salt rock gas storage under long-term operation, affect not only the capacity and working ability of a salt cavern but also be crucial to the safety and stability of the surrounding rock. A 3D geo-mechanical model of the salt cavern is established to study the stability of the storage in the operation period. The deformation, expansion safety factor, volume shrinkage, and plastic zone are comprehensively considered for predicting the feasibility and stability of the salt cavern. The stability of the surrounding rock of the cavern with different injection-production parameters and the impact of each parameter on the stability of the cavern during operating are systematically investigated. The results indicate that the displacement, the expansion coefficient of the surrounding rock, and the volume shrinkage rate of the salt cavern reduces significantly with the increment of IGP interval and minimum IGP, while they increases with raising the minimum IGP residence time and injection-production cycle. With the continuous operation of the cavity, the displacement and the volume shrinkage rate enhances significantly year by year with the augment of operation parameters, moreover, their value show a fluctuating upward trend with the alternation of the gas injection and the production. The volume of the plastic zone is enlarged with the increment of the IGP interval, minimum IGP, and injection-production cycle, while it reduces with the extension of the minimum IGP residence time. The variation becomes remarkably with the augment of parameters. The sensitivity coefficients of each injection-production operation parameter are ranked, from large to small, as follows: IGP interval, minimum IGP, minimum IGP residence time, injection-production cycle. The results can offer beneficial reference for effectively optimize the injection-production parameters, so as to provide technical guidance for ensuring the stability of the storage and meeting requirements for the storage capacity.

Antiviral CD8+ T-cell immune responses are impaired by cigarette smoke and in COPD.

BACKGROUND: Virus infections drive COPD exacerbations and progression. Antiviral immunity centres on the activation of virus-specific CD8+ T-cells by viral epitopes presented on major histocompatibility complex (MHC) class I molecules of infected cells. These epitopes are generated by the immunoproteasome, a specialised intracellular protein degradation machine, which is induced by antiviral cytokines in infected cells. METHODS: We analysed the effects of cigarette smoke on cytokine- and virus-mediated induction of the immunoproteasome in vitro, ex vivo and in vivo using RNA and Western blot analyses. CD8+ T-cell activation was determined in co-culture assays with cigarette smoke-exposed influenza A virus (IAV)-infected cells. Mass-spectrometry-based analysis of MHC class I-bound peptides uncovered the effects of cigarette smoke on inflammatory antigen presentation in lung cells. IAV-specific CD8+ T-cell numbers were determined in patients' peripheral blood using tetramer technology. RESULTS: Cigarette smoke impaired the induction of the immunoproteasome by cytokine signalling and viral infection in lung cells in vitro, ex vivo and in vivo. In addition, cigarette smoke altered the peptide repertoire of antigens presented on MHC class I molecules under inflammatory conditions. Importantly, MHC class I-mediated activation of IAV-specific CD8+ T-cells was dampened by cigarette smoke. COPD patients exhibited reduced numbers of circulating IAV-specific CD8+ T-cells compared to healthy controls and asthmatics. CONCLUSION: Our data indicate that cigarette smoke interferes with MHC class I antigen generation and presentation and thereby contributes to impaired activation of CD8+ T-cells upon virus infection. This adds important mechanistic insight on how cigarette smoke mediates increased susceptibility of smokers and COPD patients to viral infections.

Ultra-Highly Active Ni-Doped MOF-5 Heterogeneous Catalysts for Ethylene Dimerization.

Here, an ultra-highly active Ni-MOF-5 catalyst with high Ni loading for ethylene dimerization is reported. The Ni-MOF-5 catalysts are synthesized by a facile one-pot co-precipitation method at room temperature, where Ni2+ replaces Zn2+ in MOF-5. Unlike Zn2+ with tetrahedral coordination in MOF-5, Ni2+ is coordinated with extra solvent molecules except for four-oxygen from the framework. After removing coordinated solvent molecules, Ni-MOF-5 achieves an ethylene turnover frequency of 352 000 h-1 , corresponding to 9040 g of product per gram of catalyst per hour, at 35 °C and 50 bar, far exceeding the activities of all reported heterogeneous catalysts. The high Ni loading and full exposure structure account for the excellent catalytic performance. Isotope labeling experiments reveal that the catalytic process follows the Cossee-Arlman mechanism, rationalizing the high activity and selectivity of the catalyst. These results demonstrate that Ni-MOF-5 catalysts are very promising for industrial catalytic ethylene dimerization.

Increased level of exosomal miR-20b-5p derived from hypothermia-treated microglia promotes neurite outgrowth and synapse recovery after traumatic brain injury.

Mild hypothermia has been proven to inhibit microglia activation after TBI. Exosomal microRNA derived from microglia played a critical role in promoting neurite outgrowth and synapse recovery. Here, we aimed to investigate the role of microRNAs in microglial exosomes after hypothermia treatment on neuronal regeneration after TBI. For in vitro study, stretch-injured neurons were co-cultured with microglial exosomes. For in vivo study, C57BL/6 mice were under controlled cortical impact and injected with microglial exosomes. The results showed that MG-LPS-EXOHT increased the number of dendrite branches and total length of dendrites both in vitro and in vivo, elevated the expression levels of PSD-95 and GluR1 in stretch-injured neurons, and increased spine density in the pericontusion region. Moreover, MG-LPS-EXOHT improved motor function and motor coordination. A high-throughput sequencing showed that miR-20b-5p was upregulated in MG-LPS-EXOHT. Elevating miR-20b-5p promoted neurite outgrowth and synapse recovery of injured neurons both in vitro and in vivo. Following mechanistic study demonstrated that miR-20b-5p might promote neurite outgrowth and synapse recovery by directly targeting PTEN and activating PI3K-AKT pathway. In conclusion, mild hypothermia could modify the microRNA prolife of exosomes derived from LPS activated BV2 cells. Furthermore, high level of microglial exosomal miR-20b-5p induced by mild hypothermia could transfer into injured neurons and promote neurite outgrowth and synapse recovery after TBI via activating the PI3K-AKT pathway by suppressing PTEN expression.

AI-assisted Method for Efficiently Generating Breast Ultrasound Screening Reports.

BACKGROUND: Ultrasound is one of the preferred choices for early screening of dense breast cancer. Clinically, doctors have to manually write the screening report, which is time-consuming and laborious, and it is easy to miss and miswrite. AIM: We proposed a new pipeline to automatically generate AI breast ultrasound screening reports based on ultrasound images, aiming to assist doctors in improving the efficiency of clinical screening and reducing repetitive report writing. METHODS: AI efficiently generated personalized breast ultrasound screening preliminary reports, especially for benign and normal cases, which account for the majority. Doctors then make simple adjustments or corrections based on the preliminary AI report to generate the final report quickly. The approach has been trained and tested using a database of 4809 breast tumor instances. RESULTS: Experimental results indicate that this pipeline improves doctors' work efficiency by up to 90%, greatly reducing repetitive work. CONCLUSION: Personalized report generation is more widely recognized by doctors in clinical practice than non-intelligent reports based on fixed templates or options to fill in the blanks.

Correction of breast asymmetry by autologous fat grafting with the aid of 3D laser-scanning technology.

BACKGROUND: Currently, the lack of clinically accurate measurement and evaluation methods for breast asymmetry has considerably limited the use of autologous fat grafting in the correction of breast asymmetry. OBJECTIVE: This study calculated the volume difference in the bilateral breasts by three-dimensional (3D) laser scanning technology, established a bridge between digitalization and surgery to guide the correction of breast asymmetry by autologous fat grafting, and evaluated the surgical effect. METHODS: In the experimental group (3D group), the measurement range was defined by standardized methods, the algorithm to calculate the volume difference in the bilateral breasts was determined by the established software instructions, and the volume of intraoperative autologous fat grafting was guided by personalized data. In the control group, the volume of intraoperative autologous fat grafting was determined based on the surgeon's visual assessment and surgical experience. RESULTS: The volume difference in the bilateral breasts was less at 12 months after surgery (P < 0.05), the satisfaction of patients was higher (P < 0.05), and the reoperation rate was lower (P < 0.05). The incidence of postoperative complications was low in both groups (P > 0.05). CONCLUSIONS: 3D laser scanning technology can be used as a bridge between digitalization and surgery to significantly improve the surgical effect of autologous fat grafting in the correction of breast asymmetry, with high patient satisfaction and high clinical application value.

Interaction between A-kinase anchoring protein 5 and protein kinase A mediates CaMKII/HDAC signaling to inhibit cardiomyocyte hypertrophy after hypoxic reoxygenation.

We reported that A-kinase anchoring protein 5 (AKAP5) played a role in cardiomyocyte apoptosis after hypoxia-reoxygenation (H/R). The role of AKAP5 in cardiomyocyte hypertrophy has not been fully elucidated. Herein we investigated whether AKAP5 regulates cardiomyocyte hypertrophy through calcium/calmodulin-dependent protein kinase II (CaMKII). After H/R, deficiency of AKAP5 in H9C2 cardiomyocytes and neonatal rat cardiac myocytes activated CaMKII and stimulated cardiomyocyte hypertrophy. AKAP5 upregulation limited this. Low expression of AKAP5 increased CaMKII interaction with histone deacetylases 4/5 (HDAC4/5) and increased nuclear export of HDAC4/5. In addition, AKAP5 interactions with protein kinase A (PKA) and phospholamban (PLN) were diminished. Moreover, the phosphorylation of PLN was decreased, and intracellular calcium increased. Interference of this process with St-Ht31 increased CaMKII signaling, decreased PLN phosphorylation and promoted post-H/R cell hypertrophy. And PKA-anchoring deficient AKAP5ΔPKA could not attenuate hypoxia-reoxygenation-induced cardiomyocyte hypertrophy, but AKAP5 could. Altogether, AKAP5 downregulation exacerbated H/R-induced hypertrophy in cardiomyocytes. This was due to, in part, to less in AKAP5-PKA interaction and the accumulation of intracellular Ca2+ with a subsequent increase in CaMKII activity.

Predictive value of the presence of Prevotella and the ratio of Porphyromonas gingivalis to Prevotella in saliva for esophageal squamous cell carcinoma.

Background: Imbalance of oral salivary microbiota has been linked to the pathogenesis of a variety of systemic diseases, and oral bacterial species have been shown to be useful biomarkers for systemic diseases.This study aimed to characterize the alterations of oral microbiota in patients with esophageal squamous cell carcinoma (ESCC) and to evaluate the diagnostic performance of oral microbial biomarkers for ESCC. Methods: The relative abundance of flora in saliva samples was analyzed by 16S rDNA sequencing, and differences in the species present in samples from ESCC patients and healthy controls (HCs) were identified by analyzing species diversity and performing LEfSe analysis. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic performance of the characteristic bacteria individually and in combination. Results: Differences in bacterial diversity indexes were observed for the saliva of ESCC patients versus HCs (P<0.05), but principal coordinate analysis did not detect a significant difference in the composition of oral microbiota between ESCC patients and HCs (P>0.05). LEfSe analysis showed that Leptotrichia, Porphyromonas (Pg), Streptococcus, Rothia, Lactobacillus and Peptostreptococcus were more abundant in ESCC patient saliva than in HC saliva, whereas Haemophilus, Alloprevotella (All), Prevotella_7, Prevotella (Pre), Prevotella_6, Pasteurellaceae and Pasteurellales were significantly less abundant in ESCC patient saliva (P<0.05). From ROC curve analysis, Pg could detect ESCC with an area under the ROC curve (AUC) of 0.599, sensitivity of 62.2%, and specificity of 70%, whereas the ratio of Pg/Pre had an AUC of 0.791, sensitivity of 93.3%, and specificity of 62.3%. Moreover, the combination of the Pg/Pre and Pg/All ratios showed further improved diagnostic performance for ESCC (AUC=0.826) and even good sensitivity and specificity for the diagnosis of early ESCC (68.2% and 86%, respectively; AUC=0.786). Conclusion: This study shows that Pg in saliva can be used as a characteristic marker of ESCC, and the ratios of Pg/Pre and Pg/All offered significantly improved diagnostic performance, especially for early ESCC.

Salivary microbiota may predict the presence of esophageal squamous cell carcinoma.

The aim is to explore the predictive value of salivary bacteria for the presence of esophageal squamous cell carcinoma (ESCC). Saliva samples were obtained from 178 patients with ESCC and 101 healthy controls, and allocated to screening and verification cohorts, respectively. In the screening phase, after saliva DNA was extracted, 16S rRNA V4 regions of salivary bacteria were amplified by polymerase chain reaction (PCR) with high-throughput sequencing. Highly expressed target bacteria were screened by Operational Taxonomic Units clustering, species annotation and microbial diversity assessment. In the verification phase, the expression levels of target bacteria identified in the screening phase were verified by absolute quantitative PCR (Q-PCR). Receiver operating characteristic (ROC) curves were plotted to investigate the predictive value of target salivary bacteria. LEfSe analysis revealed higher proportions of Fusobacterium, Streptococcus and Porphyromonas, and Q-PCR assay showed significantly higher numbers of Streptococcus salivarius, Fusobacterium nucleatum and Porphyromonas gingivalis in patients with ESCC, when compared with healthy controls (all P < 0.05). The areas under the ROC curves for Streptococcus salivarius, Fusobacterium nucleatum, Porphyromonas gingivalis and the combination of the three bacteria for predicting patients with ESCC were 69%, 56.5%, 61.8% and 76.4%, respectively. The sensitivities corresponding to cutoff value were 69.3%, 22.7%, 35.2% and 86.4%, respectively, and the matched specificity were 78.4%, 96.1%, 90.2% and 58.8%, respectively. These highly expressed Streptococcus salivarius, Fusobacterium nucleatum and Porphyromonas gingivalis in the saliva, alone or in combination, indicate their predictive value for ESCC.

Hadamard-Encoded Synthetic Transmit Aperture Imaging for Improved Lateral Motion Estimation in Ultrasound Elastography.

Lateral motion estimation has been a challenge in ultrasound elastography mainly due to the low resolution, low sampling frequency, and lack of phase information in the lateral direction. Synthetic transmit aperture (STA) can achieve high resolution due to two-way focusing and can beamform high-density image lines for improved lateral motion estimation with the disadvantages of low signal-to-noise ratio (SNR) and limited penetration depth. In this study, Hadamard-encoded STA (Hadamard-STA) is proposed for the improvement of lateral motion estimation in elastography, and it is compared with STA and conventional focused wave (CFW) imaging. Simulations, phantom, and in vivo experiments were conducted to make the comparison. The normalized root mean square error (NRMSE) and the contrast-to-noise ratio (CNR) were calculated as the evaluation criteria in the simulations. The results show that, at a noise level of -10 dB and an applied strain of -1% (compression), Hadamard-STA decreases the NRMSEs of lateral displacements by 46.92% and 35.35%, decreases the NRMSEs of lateral strains by 52.34% and 39.75%, and increases the CNRs by 9.70 and 9.75 dB compared with STA and CFW, respectively. In the phantom experiments performed on a heterogeneous tissue-mimicking phantom, the sum of squared differences (SSD) between the reference and the motion-compensated RF data, and the CNR were calculated as the evaluation criteria. At an applied strain of -1.80%, Hadamard-STA is found to decrease the SSDs by 20.91% and 30.99% and increase the CNRs by 14.15 and 24.66 dB compared with STA and CFW, respectively. In the experiments performed on a breast phantom, Hadamard-STA achieves better visualization of the breast inclusion with a clearer boundary between the inclusion and the background than STA and CFW. The in vivo experiments were performed on a patient with a breast tumor, and the tumor could also be better visualized with a more homogeneous background in the strain image obtained by Hadamard-STA than by STA and CFW. These results demonstrate that Hadamard-STA achieves a substantial improvement in lateral motion estimation and maybe a competitive method for quasi-static elastography.

Comparing Tumor Cell Invasion and Myeloid Cell Composition in Compatible Primary and Relapsing Glioblastoma.

Glioblastoma (GBM) recurrence after treatment is almost inevitable but addressing this issue with adequate preclinical models has remained challenging. Here, we introduce a GBM mouse model allowing non-invasive and scalable de-bulking of a tumor mass located deeply in the brain, which can be combined with conventional therapeutic approaches. Strong reduction of the GBM volume is achieved after pharmacologically inducing a tumor-specific cell death mechanism. This is followed by GBM re-growth over a predictable timeframe. Pharmacological de-bulking followed by tumor relapse was accomplished with an orthotopic mouse glioma model. Relapsing experimental tumors recapitulated pathological features often observed in recurrent human GBM, like increased invasiveness or altered immune cell composition. Orthotopic implantation of GBM cells originating from biopsies of one patient at initial or follow-up treatment reproduced these findings. Interestingly, relapsing GBM of both models contained a much higher ratio of monocyte-derived macrophages (MDM) versus microglia than primary GBM. This was not altered when combining pharmacological de-bulking with invasive surgery. We interpret that factors released from viable primary GBM cells preferentially attract microglia whereas relapsing tumors preponderantly release chemoattractants for MDM. All in all, this relapse model has the capacity to provide novel insights into clinically highly relevant aspects of GBM treatment.

Assessment of neovascularization of carotid artery atherosclerotic plaques using superb microvascular imaging: a comparison with contrast-enhanced ultrasound imaging and histology.

BACKGROUND: This study aimed to investigate the usefulness of superb microvascular imaging (SMI), a novel non-contrast-enhanced ultrasound technique, in characterizing neovessels within carotid atherosclerotic plaques through comparison with contrast-enhanced ultrasound (CEUS) and histology. METHODS: Patients with carotid plaque were recruited and underwent SMI and CEUS ultrasound imaging of the carotid arteries. The maximum plaque thickness, length, and stenosis of each plaque were measured. Grade of the neovessels was determined by SMI and CEUS, respectively. Grade 0 was defined as no blood flow signal/microbubbles within plaques; grade 1 was defined as moderate blood flow signals/microbubbles confined to the shoulder and/or adventitial side of the plaque; and grade 2 was defined as extensive intraplaque signals/microbubbles. Patients with symptomatic carotid stenosis (stenosis ≥50%) or asymptomatic carotid stenosis (stenosis ≥70%) underwent endarterectomy, and plaque specimens were subjected to immunohistochemical analysis of CD31 expression. The neovessels were quantified by histology. The agreement of SMI with CEUS and histology in characterizing neovessels was analyzed using weighted Kappa statistic and Spearman's correlation analyses. RESULTS: Seventy-eight patients (mean age: 67.3±8.9 years old, 63 males) were recruited. Of these patients, 52 (66.7%) had a unilateral plaque and 26 (33.3%) had bilateral plaques in the carotid arteries. For the 104 carotid plaques detected, the mean plaque thickness and length were 4.3±1.1 and 18.8±6.6 mm, respectively. The prevalence of <50%, 50-69%, and ≥70% stenosis was 43.3%, 24.0%, and 32.7%, respectively. Excellent agreement was found between SMI and CEUS (κ=0.825 at the plaque level; κ=0.820 at the patient level) in evaluating the neovessel grade within the carotid plaques. Of the 25 patients who underwent carotid endarterectomy, a strong correlation (r=0.660, P<0.001) was found between SMI and histology in the evaluation of intraplaque neovessels. SMI had excellent scan-rescan (κ=0.857), intra-reader (κ=0.810), and inter-reader (κ=0.754) agreement in the assessment of intraplaque neovessels. CONCLUSIONS: The SMI technique is capable of reliably characterizing neovessels within carotid atherosclerotic plaques and demonstrates good to excellent agreement with histology and CEUS.

Synthesis of a Boron-Imidazolate Framework Nanosheet with Dimer Copper Units for CO2 Electroreduction to Ethylene.

Fundamental understanding of the dependence between the structure and composition on the electrochemical CO2 reduction reaction (CO2 RR) would guide the rational design of highly efficient and selective electrocatalysts. A major impediment to the deep reduction CO2 to multi-carbon products is the complexity of carbon-carbon bond coupling. The chemically well-defined catalysts with atomically dispersed dual-metal sites are required for these C-C coupling involved processes. Here, we developed a catalyst (BIF-102NSs) that features Cl- bridged dimer copper (Cu2 ) units, which delivers high catalytic activity and selectivity for C2 H4 . Mechanistic investigation verifies that neighboring Cu monomers not only perform as regulator for varying the reaction barrier, but also afford distinct reaction paths compared with isolated monomers, resulting in greatly improved electroreduction performance for CO2 .

TAMEP are brain tumor parenchymal cells controlling neoplastic angiogenesis and progression.

Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor parenchymal cells may promote specific phases of disease progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Notably, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell population, by conditional Sox2-knockout, drastically reduced glioblastoma vascularization and size. Hence, TAMEP emerge as a tumor parenchymal component with a strong impact on glioblastoma progression.

Baicalin Reduces Early Brain Injury after Subarachnoid Hemorrhage in Rats.

OBJECTIVE: To evaluate the effect of baicalin on subarachnoid hemorrhage (SAH) in rats and explore the potential mechanisms. METHODS: Sprague-Dawley rats underwent experimental SAH and received treatment with baicalin at 10 or 50 mg/kg after 2 and 12 h of SAH. Neurological scores, brain water content, Evans-blue extravasation, and levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), myeloperoxidase (MPO), and malondialdehyde (MDA) were measured 24 h after SAH. Expression of nuclear factor erythroid-related factor 2 (Nrf2), NAD(P)H: quinone oxidoreductase 1 (NQO1), matrix metalloproteinase-9 (MMP-9), aquaporin 4 (AQP4), occludin, and zonulaoccludens-1 (ZO-1) were detected in the brain by Western blot. Heme oxygenase-1 (HO-1) was detected by quantitative polymerase chain reaction, and tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were assessed by enzyme-linked immunosorbent assay. RESULTS: Baicalin attenuated EBI 24 h after SAH in rats (P<0.05). Baicalin elevated neurological scores, GSH-Px, SOD, and increased the expression of Nrf2, NQO1, HO-1, occludin, and ZO-1 in SAH rats (P<0.05 or P<0.01). Baicalin reduced MPO, MDA, and the expression of MMP-9, AQP4, TNF-α, and IL-1ß (P<0.05 or P<0.01). CONCLUSION: Baicalin reduced SAH-induced EBI, partially via activation of the Nrf2/HO-1 pathway and inhibition of MMP-9 and AQP4.