Treatment of intracranial aneurysms with pipeline embolization device: a single-center experience.

Background: Endovascular therapy is the primary treatment modality for intracranial aneurysms (IA). The objective of this study was to assess the effectiveness and safety of a pipeline embolization device (PED) for the treatment of IA. Methods: This retrospective study was conducted at a single center. Data were collected for all patients who underwent PED treatment at the Fourth Affiliated Hospital of Xinjiang Medical University between December 2018 and January 2022. Clinical characteristics, aneurysm-related characteristics, treatment details, and clinical and imaging outcomes were collected and analyzed. Results: A total of 60 consecutive patients with 60 IAs were treated with a PED. The mean age of the participants was 61.8 years, with 53% being female. The average size of the aneurysms was 14.7 mm, with 54 located in the anterior circulation and six in the posterior circulation. The median last follow-up time was 13.0 months (range, 11-24 months). All patients underwent final digital subtraction angiography (DSA) for angiographic follow-up, and 50 aneurysms (83.3%) were completely occluded. The overall complication rate was 3.3%, and there were no reported mortalities. Among the 12 cases of ruptured aneurysms, all of which underwent adjunctive coil embolization, the complete occlusion rate was 91.7% with a complication rate of 16.6% [ischemic complication and modified Rankin scale (mRS) deteriorated]. In the 6 cases of posterior circulation aneurysms (2 in the basilar artery), 5 cases achieved complete occlusion and 1 case achieved near-complete occlusion, with no reported complications or mortality. Conclusions: The use of PEDs appears to be an effective treatment option for IA, demonstrating high occlusion rates and low complication rates. While the application of PEDs for the treatment of ruptured aneurysms did not increase the risk of secondary aneurysm rupture, caution is still warranted due to a higher complication rate. In the treatment of aneurysms of the vertebrobasilar artery using PEDs, this study achieved favorable efficacy outcomes without complications nor patient mortality. However, further studies are needed to validate these findings.

Fabrication and characterization of anthocyanin-loaded double Pickering emulsions stabilized by ß-cyclodextrin.

Anthocyanins, one of the important water-soluble pigments, are sensitive to environmental factors, which limits the application of anthocyanins in food field. In order to overcome this limitation, double Pickering emulsions stabilized by ß-cyclodextrin were developed. The optimum preparation conditions of the emulsions were determined firstly and the performance and structure of emulsions were investigated. Results showed that the optimum preparation conditions of emulsions were the ratio of (W1/O): W2 = 6:4 and 4 % ß-cyclodextrin concentration. Optical microscope and confocal laser scanning microscope results confirmed that ß-cyclodextrin adsorbed onto the surface of droplets forming stable double Pickering emulsions structure. In vitro gastrointestinal digestion experiments proved that double Pickering emulsions played a controlled-release effect in the small intestine. Rheological analysis proved that the emulsions exhibited elastic properties and demonstrated shear thinning behavior. The emulsions showed excellent stability under centrifugation and thermal conditions. These findings will promote anthocyanins' application in daily diet.

Endovascular re-canalization for symptomatic non-acute intracranial large artery occlusion: a single-center retrospective study.

Background: Managing patients with symptomatic non-acute intracranial large artery occlusion (SNA-ILAO) poses a significant challenge due to the high morbidity and risk of recurrent critical ischemic events, even with standard medical therapy. This unique subgroup of patients requires specialized attention. The aim of this study is to evaluate the feasibility and safety of endovascular interventional recanalization for SNA-ILAO. Methods: We retrospectively collected data of patients with SNA-ILAO who underwent endovascular interventional therapy at the Fourth Affiliated Hospital of Xinjiang Medical University from 2018 to 2021. The collected data included clinical demography, imaging data, treatment details, and prognosis. Follow-up imaging assessments were conducted for the patients, and descriptive statistics were performed. Results: A total of 24 patients were enrolled, with a majority being male (58.3%) and a mean age of 62.0±9.3 years. The pre-treatment median modified Rankin scale (mRS) and the National Institutes of Health Stroke Scale (NIHSS) scores at baseline were 3 and 1, respectively. The most common occlusion location was the middle cerebral artery (MCA), including M1 (70.8%), M2 (20.8%), and M3 (4.7%). Successful recanalization was achieved in all 24 patients, with 21 cases (87.5%) achieving thrombolysis in cerebral infarction (TICI) 3 reperfusion and the remaining 3 cases (12.5%) achieving TICI 2b reperfusion. Asymptomatic intracranial hemorrhage (ICH) occurred in 2 patients (8.3%). During the first 30-day clinical follow-up, none of these patients experienced any recurrent cerebral ischemic events. During the 29.5-month follow-up period for vessel imaging, only 12.5% (3/24) of patients who had follow-up imaging experienced re-stenosis. Conclusions: Endovascular recanalization is a potentially safe and effective procedure for patients with SNA-ILAO. However, it is important to note that there is still a non-negligible rate of complications associated with this treatment. Therefore, exercising caution and implementing strict controls when administering this procedure is crucial.

Metabolic engineering of oleaginous yeast in the lipogenic phase enhances production of nervonic acid.

Insufficient biosynthesis efficiency during the lipogenic phase can be a major obstacle to engineering oleaginous yeasts to overproduce very long-chain fatty acids (VLCFAs). Taking nervonic acid (NA, C24:1) as an example, we overcame the bottleneck to overproduce NA in an engineered Rhodosporidium toruloides by improving the biosynthesis of VLCFAs during the lipogenic phase. First, evaluating the catalytic preferences of three plant-derived ketoacyl-CoA synthases (KCSs) rationally guided reconstructing an efficient NA biosynthetic pathway in R. toruloides. More importantly, a genome-wide transcriptional analysis endowed clues to strengthen the fatty acid elongation (FAE) module and identify/use lipogenic phase-activated promoter, collectively addressing the stagnation of NA accumulation during the lipogenic phase. The best-designed strain exhibited a high NA content (as the major component in total fatty acid [TFA], 46.3%) and produced a titer of 44.2 g/L in a 5 L bioreactor. The strategy developed here provides an engineering framework to establish the microbial process of producing valuable VLCFAs in oleaginous yeasts.

The Effect of Intramolecular Hydrogen Bonds on the Rotational Barriers of the Biaryl C-C Axis.

Axially chiral compounds are attracting more attention recently. Although hydrogen bonds are reported as a vital weak force that influences the properties of compounds, the effect of intramolecular hydrogen bonds on the atropisomerization of the Caryl -Caryl single bonds has not yet been well quantitatively investigated. Here, a series of axially chiral biaryl compounds were synthesized to study the effect of hydrogen bonds on the rotational barriers of the biaryl C-C axis. Experimental studies demonstrated that the rotational barrier of hydrogen bonding biaryl 9 was significantly lower (46.7 kJ mol-1 ) than biaryl 10 without hydrogen bonds. Furthermore, theoretical studies revealed that the intramolecular hydrogen bond stabilized the transition state (TS) of tri-ortho-substituted biaryl 9, relieving the steric repulsion in the TS. We believe that this study will provide chemists with a deeper understanding of the atropisomerization process of axially chiral biaryl compounds.

Engineering Escherichia coli to produce aromatic chemicals from ethylene glycol.

Microbial overproduction of aromatic chemicals has gained considerable industrial interest and various metabolic engineering approaches have been employed in recent years to address the associated challenges. So far, most studies have used sugars (mostly glucose) or glycerol as the primary carbon source. In this study, we used ethylene glycol (EG) as the main carbon substrate. EG could be obtained from the degradation of plastic and cellulosic wastes. As a proof of concept, Escherichia coli was engineered to transform EG into L-tyrosine, a valuable aromatic amino acid. Under the best fermentation condition, the strain produced 2 g/L L-tyrosine from 10 g/L EG, outperforming glucose (the most common sugar feedstock) in the same experimental conditions. To prove the concept that EG can be converted into different aromatic chemicals, E. coli was further engineered with a similar approach to synthesize other valuable aromatic chemicals, L-phenylalanine and p-coumaric acid. Finally, waste polyethylene terephthalate (PET) bottles were degraded using acid hydrolysis and the resulting monomer EG was transformed into L-tyrosine using the engineered E. coli, yielding a comparable titer to that obtained using commercial EG. The strains developed in this study should be valuable to the community for producing valuable aromatics from EG.

Biosynthesis of geranate via isopentenol utilization pathway in Escherichia coli.

Isoprenoids are a large family of natural products with diverse structures, which allow them to play diverse and important roles in the physiology of plants and animals. They also have important commercial uses as pharmaceuticals, flavoring agents, fragrances, and nutritional supplements. Recently, metabolic engineering has been intensively investigated and emerged as the technology of choice for the production of isoprenoids through microbial fermentation. Isoprenoid biosynthesis typically originates in plants from acetyl-coA in central carbon metabolism, however, a recent study reported an alternative pathway, the isopentenol utilization pathway (IUP), that can provide the building blocks of isoprenoid biosynthesis from affordable C5 substrates. In this study, we expressed the IUP in Escherichia coli to efficiently convert isopentenols into geranate, a valuable isoprenoid compound. We first established a geraniol-producing strain in E. coli that uses the IUP. Then, we extended the geraniol synthesis pathway to produce geranate through two oxidation reactions catalyzed by two alcohol/aldehyde dehydrogenases from Castellaniella defragrans. The geranate titer was further increased by optimizing the expression of the two dehydrogenases and also parameters of the fermentation process. The best strain produced 764 mg/L geranate in 24 h from 2 g/L isopentenols (a mixture of isoprenol and prenol). We also investigated if the dehydrogenases could accept other isoprenoid alcohols as substrates.

Hypoxia-elicited cardiac microvascular endothelial cell-derived exosomal miR-210-3p alleviate hypoxia/reoxygenation-induced myocardial cell injury through inhibiting transferrin receptor 1-mediated ferroptosis.

OBJECTIVE: Ferroptosis is a novel mode of non-apoptotic cell death induced by build-up of toxic lipid peroxides (lipid-ROS) in an iron dependent manner, which is a key event in ischemia/reperfusion (I/R)-induced cardiomyocytes damages. Studies indicated that ischemic preconditioning with cardiac microvascular endothelial cells (CMECs) protected against I/R-induced cardiomyocytes damages. However, the role of hypoxia-conditioned CMECs-derived Exo (H-exo) in I/R cardiomyocytes damages remains largely unclear. Therefore, the objective of this study was to explore the role and underlying mechanisms of H-exo in hypoxia/reoxygenation(H/R)-induced H9C2 cells damages. METHODS: The rat CMECs were subjected to hypoxia or normoxia culture and Exo was subsequently collected and identified. H-exo or normoxia-conditioned CMECs-derived Exo (N-exo) were administered to H9C2 cells with H/R. To evaluate the therapeutic effect of H-exo and H-exo on H/R-induced H9C2 cells damages, cell proliferation was detected by CCK-8 assay and Edu staining, and ferroptosis process were evaluated by iron ion concentration, lipid reactive oxygen species (ROS) level, malondialdehyde (MDA) level, glutathione peroxidase (GSH-Px) level, and the protein expression of ferroptosis markers. Mechanically, we utilized the RT-qPCR to identify the expression of candidate miR-210-3p in N-exo and H-exo. Bioinformatics combined with dual luciferase reporter assay disclosed the downstream molecular mechanism of miR-210-3p. RESULTS: The results indicated that both H-exo and N-exo significantly facilitated cell proliferation, increased GSH-Px levels and ferroptosis marker (GPX4) protein levels, and reduced iron ion concentration, lipid ROS level, MDA levels and ferroptosis markers (ACSL4 and PTGS2) protein levels in H/R-treated H9C2 cells. More importantly, the therapeutic effect of H-exo was significantly better than that of N-exo. Mechanistically, the results of RT-qPCR revealed significant enrichment of miR-210-3p in H-exo compared with N-exo. The miR-210-3p delivered by H-exo inhibited TFR expression by directly interacting with TFR mRNA, resulting in the promotion of cell proliferation and the attenuation of cell ferroptosis in H/R-treated H9C2 cells. CONCLUSION: All these data demonstrated that H-exo derived miR-210-3p facilitated the proliferation of myocardial cells in H/R-treated H9C2 cells by suppressing TFR-mediated ferroptosis, which provided new methods to treat H/R-induced myocardial injury.

The Advancements and Prospects of Nervonic Acid Production.

Nervonic acid (NA) is a monounsaturated very long-chain fatty acid (VLCFA) and has been identified with critical biological functions in medical and health care for brain development and injury repair. Yet, the approaches to producing NA from the sources of plants or animals continue to pose challenges to meet increasing market demand, as they are generally associated with high costs, a lack of natural resources, a long life cycle, and low production efficiency. The recent technological advance in metabolic engineering allows us to precisely engineer oleaginous microbes to develop high-content NA-producing strains, which has the potential to provide a possible solution to produce NA on a commercial fermentation scale. In this Review, the biosynthetic pathway, natural sources, and metabolic engineering of NA are summarized. The strategies of metabolic engineering that could be adopted to modify oleaginous yeast to produce NA are discussed in detail, providing the prospecting views for the microbial cells producing NA.

CCL3 Promotes Proliferation of Colorectal Cancer Related with TRAF6/NF-κB Molecular Pathway.

Chemokine C-C motif chemokine ligand 3 (CCL3) plays an important role in the invasion and metastasis of malignant tumors. For developing new therapeutic targets and antitumor drugs, the effect of chemokine CCL3 and the related cytokine network on colorectal cancer should be investigated. This study used cell, tissue, and animal experiments to prove that CCL3 is highly expressed in colorectal cancer and confirmed that CCL3 can promote the proliferation of cancer cells, and its expression is closely related to TRAF6/NF-κB molecular pathway. In addition, protein chip technology was used to examine colorectal cancer tissue samples and identify the key factors of chemokine CCL3 and the toll-like receptors/nuclear factor-κB (TLR/NF-κB) pathway in cancer and metastatic lymph nodes. Furthermore, the lentiviral vector technology was employed for transfection to construct interference and overexpression cell lines. The experimental results reveal the mechanism of CCL3 and TNF receptor-associated factor 6 (TRAF6)/NF-κB pathway-related factors and their effects on the proliferation of colon cancer cells. Finally, the expression and significance of CCL3 in colorectal cancer tissues and its correlation with clinical pathology were studied by immunohistochemistry. Also, the results confirmed that CCL3 and C-C motif chemokine receptor 5 (CCR5) were expressed in adjacent tissues, colorectal cancer tissues, and metastatic cancer. The expression level was correlated with the clinical stage and nerve invasion. The expression of chemokine CCL3 and receptor CCR5 was positively correlated with the expression of TRAF6 and NF-κB and could promote the proliferation, invasion, and migration of colorectal cancer cells through TRAF6 and NF-κB.

Intrinsically unidirectional chemically fuelled rotary molecular motors.

Biological systems mainly utilize chemical energy to fuel autonomous molecular motors, enabling the system to be driven out of equilibrium1. Taking inspiration from rotary motors such as the bacterial flagellar motor2 and adenosine triphosphate synthase3, and building on the success of light-powered unidirectional rotary molecular motors4-6, scientists have pursued the design of synthetic molecular motors solely driven by chemical energy7-13. However, designing artificial rotary molecular motors operating autonomously using a chemical fuel and simultaneously featuring the intrinsic structural design elements to allow full 360° unidirectional rotary motion like adenosine triphosphate synthase remains challenging. Here we show that a homochiral biaryl Motor-3, with three distinct stereochemical elements, is a rotary motor that undergoes repetitive and unidirectional 360° rotation of the two aryl groups around a single-bond axle driven by a chemical fuel. It undergoes sequential ester cyclization, helix inversion and ring opening, and up to 99% unidirectionality is realized over the autonomous rotary cycle. The molecular rotary motor can be operated in two modes: synchronized motion with pulses of a chemical fuel and acid-base oscillations; and autonomous motion in the presence of a chemical fuel under slightly basic aqueous conditions. This rotary motor design with intrinsic control over the direction of rotation, simple chemical fuelling for autonomous motion and near-perfect unidirectionality illustrates the potential for future generations of multicomponent machines to perform mechanical functions.

Producing aromatic amino acid from corn husk by using polyols as intermediates.

Agricultural biomass remains as one of the commonly found waste on Earth. Although valorisation of these wastes has been studied in detail, the fermentation-based processes still need improvement due to the high cost of hydrolysing enzymes, and the presence of growth inhibitors which constrains the fermentation to produce high-value products. To address these challenges, we developed an integrated process in this study combining abiotic- and bio-catalysis to produce l-tyrosine from corn husk. The first step involved a one-pot hydrolytic hydrogenation tandem reaction without the use of the expensive enzymes, which yielded a mixture of polyols and sugars. Without any purification, these crude hydrolysates can be almost completely utilized by an engineered Escherichia coli strain, which did not exhibit any growth inhibition. The strain produced 0.44 g/L l-tyrosine from 10 g/L crude corn husk hydrolysates, demonstrating the feasibility of converting agricultural biomass into a valuable aromatic amino acid via an integrated process.

Synthesis of Oxygenated Sesquiterpenoids Enabled by Combining Metabolic Engineering and Visible-Light Photocatalysis.

The diversification of natural products to expand biologically relevant chemical space for drug discovery can be achieved by combining complementary bioprocessing and chemical transformations. Herein, genetically engineered Escherichia coli fermentation to produce amorphadiene and valencene was combined with metal-free photocatalysis transformations to further access nootkatone, cis-nootkatol and two hydration derivatives. In fermentation, using a closed, anaerobic condition avoided the use of organic overlay, increased the productivity, and simplified the work-up process. Metal-free photocatalysis hydration and allylic C-H oxidation were designed and implemented to make the whole process greener. It was shown that the anti-Markovnikov selectivity of photocatalyzed alkene hydration could be reversed by stereo-electronic and steric effects existing in complex natural products. The combination of bioprocessing and photocatalysis may provide an efficient and greener way to expand the chemical space for pharmaceutical, flavor and fragrance industry.

para-Selective Radical Trifluoromethylation of Benzamide Derivatives via Iminium Intermediates.

The direct C-H trifluoromethylation of arenes via a radical pathway has attracted considerable attention recently. However, a major challenge of C-H trifluoromethylation is the lack of site-selectivity on the phenyl ring especially para-selectivity. Herein we show a new strategy for para-selective C-H trifluoromethylation of benzamide derivatives using iminium activation. The reaction undergoes a radical-type nucleophilic substitution instead of a radical-type electrophilic substitution owing to iminium activation as a result of lowering the LUMO (lowest unoccupied molecular orbital). A wide range of substrates are compatible with this method giving almost exclusive para-trifluoromethylated products.

Optimization of the Isopentenol Utilization Pathway for Isoprenoid Synthesis in Escherichia coli.

Engineering microbes to produce isoprenoids can be limited by the competition between product formation and cell growth because biomass and isoprenoids are naturally derived from central metabolism. Recently, a two-step synthetic pathway was developed to partially decouple isoprenoid formation from central carbon metabolism. The pathway used exogenously added isopentenols as substrates. In the present study, we systematically optimized this isopentenol utilization pathway in Escherichia coli by comparing enzyme variants from different species, tuning enzyme expression levels, and using a two-stage process. Under the optimal conditions found in this study, ∼300 mg/L lycopene was synthesized from 2 g/L isopentenol in 24 h. The strain could be easily modified to synthesize two other isoprenoid molecules efficiently (248 mg/L ß-carotene or 364 mg/L R-(-)-linalool produced from 2 g/L isopentenol). This study lays a solid foundation for producing agri-food isoprenoids at high titer/productivity from cost-effective feedstocks.

Revealing the effectiveness of technological innovation shocks on CO2 emissions in BRICS: emerging challenges and implications.

The debate on technological innovation shocks and its effect on the environment are of great interest to academicians and environmentalists worldwide. At present, primary focus of this research is to investigate the asymmetric technology shocks and its impact on CO2 emissions for BRICS economies. The linear and non-linear panel ARDL models are applied to compute both short-run and long-run dynamics of technology shocks and CO2 emissions. Asymmetric estimates confer that a positive shock in patents reduces the CO2 emissions by 0.418%, whereas negative shock increases the CO2 emissions by 0.854%. Contrariwise, the trademark positive shock increases the carbon emissions by 0.416% and vice versa. The non-linear analysis provides an opportunity to measure the direction and magnitude of positive and negative shocks in technology on the environmental quality of BRICS economies. Hence, policymakers and environmentalists should devise their strategies by keeping in mind the impacts of positive and negative shocks.

C2 feedstock-based biomanufacturing of value-added chemicals.

Engineering microbes to produce value-added chemicals from C6/C5 sugars sometimes requires long biosynthetic pathways, which causes carbon loss due to involving multiple metabolic branch nodes, leading to a lower product yield. Using C2 feedstocks derived from gaseous, cellulosic, and plastic wastes could establish shorter biosynthetic pathways to produce some target chemicals, for example, acetyl-CoA-derived natural products. Utilizing these waste-derived feedstocks would also contribute to reducing the carbon footprint of the chemical industry. In this review, we highlighted the promising waste-processing technologies that could provide C2 feedstocks that are compatible with microbial fermentation. We also analyzed the recent metabolic engineering works in which the microorganisms/fermentation processes were modified/optimized to utilize acetate, ethanol, or ethylene glycol more efficiently.

A comprehensive review on innovative and advanced stabilization approaches of anthocyanin by modifying structure and controlling environmental factors.

Anthocyanins are pigments abundant in fruits and vegetables, and commonly applied in foods due to attractive colour and health-promoting benefits. However, instability of anthocyanins leads to their easy degradation, reduced bioactivity, and colour fading in food processing, limiting their application and causing economic losses. Stability of anthocyanins depends on their own structures and environmental factors. For structural factors, modification including copigmentation, acylation and biosynthesis is a potential solution to increase anthocyanin stability due to forming stable structures. With regard to environmental factors, encapsulation such as microencapsulation, liposome and nanoparticles has been shown effectively to enhance the stability. We proposed the potential challenges and perspectives for the diversification of anthocyanin-rich products for food application, particularly, introduction of hazards, technical limitations, interaction with other ingredients in food system and exploration of pyranoanthocyanins. The integrated strategies are warranted for improving anthocyanin stabilization for promoting their further application in food industry.

Monoterpenoid biosynthesis by engineered microbes.

Monoterpenoids are C10 isoprenoids and constitute a large family of natural products. They have been used as ingredients in food, cosmetics, and therapeutic products. Many monoterpenoids such as linalool, geraniol, limonene, and pinene are volatile and can be found in plant essential oils. Conventionally, these bioactive compounds are obtained from plant extracts by using organic solvents or by distillation method, which are costly and laborious if high-purity product is desired. In recent years, microbial biosynthesis has emerged as alternative source of monoterpenoids with great promise for meeting the increasing global demand for these compounds. However, current methods of production are not yet at levels required for commercialization. Production efficiency of monoterpenoids in microbial hosts is often restricted by high volatility of the monoterpenoids, a lack of enzymatic activity and selectivity, and/or product cytotoxicity to the microbial hosts. In this review, we summarize advances in microbial production of monoterpenoids over the past 3 years with particular focus on the key metabolic engineering strategies for different monoterpenoid products. We also provide our perspective on the promise of future endeavors to improve monoterpenoid productivity.