Apolipoprotein A-I Binding Protein Inhibits the Formation of Infantile Hemangioma through Cholesterol-Regulated Hypoxia-Inducible Factor 1α Activation.

Infantile hemangioma (IH) is the most frequent vascular tumor of infancy with unclear pathogenesis; disordered angiogenesis is considered to be involved in its formation. Apolipoprotein A-I binding protein (AIBP)-also known as NAXE (NAD [P]HX epimerase)-a regulator of cholesterol metabolism, plays a critical role in the pathological angiogenesis of mammals. In this study, we found that AIBP had much lower expression levels in both tissues from patients with IH and hemangioma endothelial cells (HemECs) than in adjacent normal tissues and human dermal vascular endothelial cells, respectively. Knockout of NAXE by CRISPR-Cas9 in HemECs enhanced tube formation and migration, and NAXE overexpression impaired tube formation and migration of HemECs. Interestingly, AIBP suppressed the proliferation of HemECs in hypoxia. We then found that reduced expression of AIBP correlated with increased hypoxia-inducible factor 1α levels in tissues from patients with IH and HemECs. Further mechanistic investigation demonstrated that AIBP disrupted hypoxia-inducible factor 1α signaling through cholesterol metabolism under hypoxia. Notably, AIBP significantly inhibited the development of IH in immunodeficient mice. Furthermore, using the validated mouse endothelial cell (ie, EOMA cells) and Naxe-/- mouse models, we demonstrated that both endogenous AIBP from tumors and AIBP in the tumor microenvironment limit the formation of hemangioma. These findings suggested that AIBP was a player in the pathogenesis of IH and could be a potential pharmacological target for treating IH.

NF-κB: a mediator that promotes or inhibits angiogenesis in human diseases?

The nuclear factor of κ-light chain of enhancer-activated B cells (NF-κB) signaling pathway, which is conserved in invertebrates, plays a significant role in human diseases such as inflammation-related diseases and carcinogenesis. Angiogenesis refers to the growth of new capillary vessels derived from already existing capillaries and postcapillary venules. Maintaining normal angiogenesis and effective vascular function is a prerequisite for the stability of organ tissue function, and abnormal angiogenesis often leads to a variety of diseases. It has been suggested that NK-κB signalling molecules under pathological conditions play an important role in vascular differentiation, proliferation, apoptosis and tumourigenesis by regulating the transcription of multiple target genes. Many NF-κB inhibitors are being tested in clinical trials for cancer treatment and their effect on angiogenesis is summarised. In this review, we will summarise the role of NF-κB signalling in various neovascular diseases, especially in tumours, and explore whether NF-κB can be used as an attack target or activation medium to inhibit tumour angiogenesis.

Spatial genetic patterns and distribution dynamics of Begonia grandis (Begoniaceae), a widespread herbaceous species in China.

Introduction: Begonia L., one of the 10 largest plant genera, contains over 2,100 species, most of which have a very limited distribution range. Understanding the spatial genetic structure and distribution dynamics of a widespread species in this genus will contribute to clarifying the mechanism responsible for Begonia speciation. Methods: In this study, we used three chloroplast DNA markers (ndhF-rpl32, atpI-atpH, and ndhA intron), coupled with species distribution modeling (SDM), to investigate the population genetic structure and distribution dynamics of Begonia grandis Dryand., the species of Begonia with the widest distribution in China. Results: Thirty-five haplotypes from 44 populations clustered into two groups, and haplotype divergence began in the Pleistocene (1.75 Mya). High genetic diversity (H d = 0.894, H T = 0.910), strong genetic differentiation (F ST = 0.835), and significant phylogeographical structure (G ST/N ST = 0.848/0.917, P < 0.05) were observed. The distribution range of B. grandis migrated northwards after the last glacial maximum, but its core distribution area remained stable. Discussion: Combined, the observed spatial genetic patterns and SDM results identified the Yunnan-Guizhou Plateau, the Three Gorges region, and the Daba Mountains as potential refugia of B. grandis. BEAST-derived chronogram and haplotype network analysis do not support the Flora Reipublicae Popularis Sinicae and Flora of China for subspecies classification based on morphological characteristics. Our results support the hypothesis that population-level allopatric differentiation may be an important speciation process for the Begonia genus and a key contributor to its rich diversity.

Benchmark dataset for clot detection in ischemic stroke vessel-based imaging: CODEC-IV.

We present an annotated dataset for the purposes of creating a benchmark in Artificial Intelligence for automated clot detection. While there are commercial tools available for automated clot detection on computed tomographic (CT) angiographs, they have not been compared in a standardized manner whereby accuracy is reported on a publicly available benchmark dataset. Furthermore, there are known difficulties in automated clot detection - namely, cases where there is robust collateral flow, or residual flow and occlusions of the smaller vessels - and it is necessary to drive an initiative to overcome these challenges. Our dataset contains 159 multiphase CTA patient datasets, derived from CTP and annotated by expert stroke neurologists. In addition to images where the clot is marked, the expert neurologists have provided information about clot location, hemisphere and the degree of collateral flow. The data is available on request by researchers via an online form, and we will host a leaderboard where the results of clot detection algorithms on the dataset will be displayed. Participants are invited to submit an algorithm to us for evaluation using the evaluation tool, which is made available at together with the form at https://github.com/MBC-Neuroimaging/ClotDetectEval.

Risk factors of hemorrhagic transformation in acute ischaemic stroke: A systematic review and meta-analysis.

Background: Hemorrhagic transformation (HT) following reperfusion therapies for acute ischaemic stroke often predicts a poor prognosis. This systematic review and meta-analysis aims to identify risk factors for HT, and how these vary with hyperacute treatment [intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT)]. Methods: Electronic databases PubMed and EMBASE were used to search relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) were estimated. Results: A total of 120 studies were included. Atrial fibrillation and NIHSS score were common predictors for any intracerebral hemorrhage (ICH) after reperfusion therapies (both IVT and EVT), while a hyperdense artery sign (OR = 2.605, 95% CI 1.212-5.599, I 2 = 0.0%) and number of thrombectomy passes (OR = 1.151, 95% CI 1.041-1.272, I 2 = 54.3%) were predictors of any ICH after IVT and EVT, respectively. Common predictors for symptomatic ICH (sICH) after reperfusion therapies were age and serum glucose level. Atrial fibrillation (OR = 3.867, 95% CI 1.970-7.591, I 2 = 29.1%), NIHSS score (OR = 1.082, 95% CI 1.060-1.105, I 2 = 54.5%) and onset-to-treatment time (OR = 1.003, 95% CI 1.001-1.005, I 2 = 0.0%) were predictors of sICH after IVT. Alberta Stroke Program Early CT score (ASPECTS) (OR = 0.686, 95% CI 0.565-0.833, I 2 =77.6%) and number of thrombectomy passes (OR = 1.374, 95% CI 1.012-1.866, I 2 = 86.4%) were predictors of sICH after EVT. Conclusion: Several predictors of ICH were identified, which varied by treatment type. Studies based on larger and multi-center data sets should be prioritized to confirm the results. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=268927, identifier: CRD42021268927.

Pharmacodynamics of Dracorhodin Perchlorate and Its Inflammation-Targeting Emulsion Gel for Wound Healing.

The mechanism of dracorhodin perchlorate for the repair of rat skin wounds was investigated. In order to screen a more favorable drug delivery system for wound repair, the therapeutic effect of dracorhodin perchlorate inflammation-targeted emulsion gel was compared with that of non-targeted emulsion gel on rat wounds. Compared with non-targeted emulsion gels, inflammation-targeted emulsion gels had a better transdermal penetration and lower potentials (-51.6 mV and -17.1 mV, respectively). The recovery of the wound from the dracorhodin perchlorate inflammation targeted emulsion gel group was better than that of the dracorhodin perchlorate inflammation non-targeted emulsion gel group and the positive drug group. Compared with the no-target emulsion gel group, the bFGF expression on day 7 and the EGF expression on day 14 in the targeted emulsion group showed 45.5% and 49.9% improvement, respectively. Pathological tissue slices showed that the epidermis, dermis, and basal layer inflammatory cells in the inflammation-targeted emulsion gel group and non-targeted emulsion gel group were significantly reduced, the granulation tissue proliferation was obvious, and the inflammation-targeted emulsion gel group was more effective. The results proved that dracorhodin perchlorate had a repairing effect on rat skin wounds, and its mechanism might be related to the promotion of the expression of EGF and bFGF in tissues.

Metabolic network changes during skotomorphogenesis in Arabidopsis thaliana mutant (atdfb-3).

The metabolic networks underlying skotomorphogenesis in seedlings remain relatively unknown. On the basis of our previous study on the folate metabolism in seedlings grown in darkness, the plastidial folylpolyglutamate synthetase gene (AtDFB) T-DNA insertion Arabidopsis thaliana mutant (atdfb-3) was examined. Under the nitrate-sufficient condition, the mutant exhibited deficient folate metabolism and hypocotyl elongation, which affected skotomorphogenesis. Further analyses revealed changes to multiple intermediate metabolites related to carbon and nitrogen metabolism in the etiolated atdfb-3 seedlings. Specifically, the sugar, polyol, and fatty acid contents decreased in the atdfb-3 mutant under the nitrate-sufficient condition, whereas the abundance of various organic acids and amino acids increased. In response to nitrate-limited stress, multiple metabolites, including sugars, polyols, fatty acids, organic acids, and amino acids, accumulated more in the mutant than in the wild-type control. The differences in the contents of multiple metabolites between the atdfb-3 and wild-type seedlings decreased following the addition of exogenous 5-F-THF under both nitrogen conditions. Additionally, the mutant accumulated high levels of one-carbon metabolites, such as Cys, S-adenosylmethionine, and S-adenosylhomocysteine, under both nitrogen conditions. Thus, our data demonstrated that the perturbed folate metabolism in the atdfb-3 seedlings, which was caused by the loss-of-function mutation to AtDFB, probably altered carbon and nitrogen metabolism, thereby modulating skotomorphogenesis. Furthermore, the study findings provide new evidence of the links among folate metabolism, metabolic networks, and skotomorphogenesis.

Humanization of Yeasts for Glycan-Type End-Products.

Yeasts are often considered microorganisms for producing human therapeutic glycosylated end-products at an industrial scale. However, the products with non-humanized glycans limited their usage. Therefore, various methods to develop humanized glycosylated end-products have been widely reported in yeasts. To make full use of these methods, it is necessary to summarize the present research to find effective approaches to producing humanized products. The present research focuses on yeast species selection, glycosyltransferase deletion, expression of endoglycosidase, and expression of proteins with galactosylated and or sialylated glycans. Nevertheless, the yeasts will have growth defects with low bioactivity when the key enzymes are deleted. It is necessary to express the corresponding repairing protein. Compared with N-glycosylation, the function of yeast protein O-glycosylation is not well-understood. Yeast proteins have a wide variety of O-glycans in different species, and it is difficult to predict glycosylation sites, which limits the humanization of O-glycosylated yeast proteins. The future challenges include the following points: there are still many important potential yeasts that have never been tried to produce glycosylated therapeutic products. Their glycosylation pathway and related mechanisms for producing humanized glycosylated proteins have rarely been reported. On the other hand, the amounts of key enzymes on glycan pathways in human beings are significantly more than those in yeasts. Therefore, there is still a challenge to produce a large body of humanized therapeutic end-products in suitable yeast species, especially the protein with complex glycans. CRISPR-Cas9 system may provide a potential approach to address the important issue.

[Research progress of multidisciplinary team co-management models for geriatric hip fracture treatment].

OBJECTIVE: To summarize the research progress of multidisciplinary team (MDT) co-management models in the clinical treatment of geriatric hip fractures. METHODS: The literature about types and characteristics of MDT for geriatric hip fracture treatment were extensively reviewed, and the advantages of its clinical application were analysed and summarised. Finally, the MDT model and characteristics of geriatric hip fracture in the Zhongda Hospital affiliated to Southeast University were introduced in detail. RESULTS: Clinical models of MDT are diverse and have their own characteristics, and MDT can shorten the length of stay and waiting time before operation, reduce the incidence of internal complications, save labor costs, and reduce patient mortality. CONCLUSION: The application of MDT in the treatment of geriatric hip fracture has achieved remarkable results, which provides an optimal scheme for the treatment of geriatric hip fracture.

Highly selective visual sensing of copper based on fluorescence enhanced glutathione-Au nanoclusters.

A blue emission glutathione stabilized Au nanoclusters prepared by an Au/Histidine complex with ligand-exchanges method was used for sensing of copper ions. We found that the glutathione stabilized Au NCs which has fluorescence emission hundred times higher than the Au/Histidine complex and has a highly selective fluorescence quenching response to copper ion. Other common metal ions, such as mercury, lead, iron and zinc, which could obviously quench or enhance the fluorescence of Au/Histidine complex, do not interfere the sensing of copper using glutathione stabilized Au nanocluster. The possible quenching mechanism and the dynamic quenching process for copper detection were also discussed. The results indicated that copper in the range from 0.5 to 300.0µM could be linearly detected and the detection could be finished quickly in 5min. A visual detection method for copper ion that may be used to fast warn copper pollution in waters by naked eyes observation was also be developed using the glutathione stabilized Au NCs probe.

[Research progress in treatment of femoral neck fracture in the elderly].

OBJECTIVE: To introduce the research progress of conservative treatment, internal fixation, hip arthroplasty, and multidisciplinary team (MDT) modes in the treatment of femoral neck fracture in the elderly. METHODS: By consulting domestic and foreign literature in recent years, the characteristics and application of various treatment methods and new treatment modes for femoral neck fracture in the elderly were summarized and analyzed. RESULTS: The elderly non-displaced femoral neck fracture should be treated surgically, and conservative treatment has a high risk of secondary displacement. The displaced fracture should be operated as soon as possible. There is no difference in long-term functional outcome between hemiarthroplasty and total hip arthroplasty. Hemiarthroplasty has less intraoperative blood loss, shorter operation time, and is suitable for the elderly patients with poor basic condition. Total hip arthroplasty is suitable for the elderly patients with better basic condition and higher demand of life quality. MDT can effectively reduce preoperative waiting time and length of stay, reduce the incidence of medical complications, improve the nutritional status of patients, and reduce the mortality of patients. CONCLUSION: Significant results have been achieved in the treatment of femoral neck fractures in the elderly by methods such as internal fixation, hip arthroplasty, and MDT.

Step-wise pterional combined epidural and subdural approach to clip large carotid-ophthalmic segment aneurysms.

BACKGROUND: Microsurgical clipping of large ophthalmic-carotid artery (OA) aneurysms is technically challenging. Among the reported approaches, pterional combined epidural and subdural approach is one of the efficient choices. METHOD: We have applied this approach to treat a 33-year old female patient with a left large OA aneurysm. The step-wise technical details of this approach are reported. CONCLUSION: We show that it is a safe way to clip large OA aneurysms through a step-wise pterional combined epidural and subdural approach, which could make a clear anatomy and a confident manipulation.

Alkyl hydroperoxide reductase is important for oxidative stress resistance and symbiosis in Azorhizobium caulinodans.

Reactive oxygen species (ROS) are not only toxic products of oxygen from aerobic metabolism or stress but also signalling molecules involved in the development of the legume-Rhizobium symbiosis. To assess the importance of alkyl hydroperoxide reductase (AhpCD) in the nitrogen-fixating bacterium Azorhizobium caulinodans, we investigated the phenotypes of the ∆ahpCD strain with regards to ROS resistance and symbiotic interactions with Sesbania rostrata. The ∆ahpCD strain was notably more sensitive than its parent strain to hydrogen peroxide (H2O2) but not to two organic peroxides, in the early log phase. The expression of ahpCD was not controlled by a LysR-type transcriptional activator either in vitro or in vivo. The catalase activity of the ∆ahpCD strain was affected at a relatively low level of H2O2 stress. Furthermore, the ∆ahpCD strain induced a reduced number of stem nodules in S. rostrata with lowering of nitrogenase activity. These data suggest that A. caulinodans AhpCD is not only important for H2O2 detoxification in vitro but also critical for symbiosis with S. rostrata. Functional analysis of AhpCD is worth investigating in other rhizobia to gain a comprehensive view of its contributions to ROS defence and symbiotic association with legumes.

Double-barrel STA to proximal MCA bypass and proximal parent artery occlusion for a fusiform superior clinoidal ICA aneurysm.

BACKGROUND: Blood flow replacement and parent artery occlusion are alternative treatments of complex fusiform superior clinoidal ICA aneurysms. While double-barrel STA to proximal MCA bypass is a conventional approach among these reported bypass algorithms, its technical details remain underexplored. METHOD: We have applied the double-barrel STA to proximal MCA bypass and parent artery occlusion to treat a 45-year-old female patient with a right fusiform superior clinoidal ICA aneurysm. The technical nuances of this approach are reported. CONCLUSION: We show that double-barrel STA to proximal MCA bypass and proximal parent artery occlusion can be alternative treatments of complex fusiform superior clinoidal ICA aneurysms.

Chicken Egg White-stabilized Au Nanoclusters for Selective and Sensitive Detection of Hg(II).

In this paper, chicken egg white purchased from a local market without further purification was directly used to prepare fluorescent gold nanoclusters through a one-step, simple, fast and green synthesis approach for analytical purposes. The as-prepared chicken egg white stabilized gold nanocluster probe has strong red fluorescence emission, which can be quenched by mercury ions and copper ions sensitively. By using an ethylenediaminetetraacetate (EDTA) masking method, mercury ions in the range from 0.60 to 10 µM can be linearly detected with the limit of detection (LOD, 3σ) of 0.510 µM in the presence of equivalent copper ions. Since the preparation of a chicken egg white stabilized gold nanocluster probe is fast, easy and cheap, this selective analytical method for mercury pollution monitoring in environmental waters may be widely used in daily life by ordinary people.