Shizukaol C alleviates trimethylamine oxide-induced inflammation through activating Keap1-Nrf2-GSTpi pathway in vascular smooth muscle cell.

BACKGROUND: Cardiovascular disease is one of the main causes of global mortality, and there is an urgent need for effective treatment strategies. Gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) promotes the development of cardiovascular diseases, and shizukaol C, a natural sesquiterpene isolated from Chloranthus multistachys with various biological activities, might exhibit beneficial role in preventing TMAO-induced vascular inflammation. PURPOSE: The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of shizukaol C on TMAO-induced vascular inflammation. METHODS: The effect and underlying mechanism of shizukaol C on TMAO-induced adhesion molecules expression, bone marrow-derived macrophages (BMDM) adhesion to VSMC were evaluated by western blot, cell adhesion assay, co-immunoprecipitation, immunofluorescence assay, and quantitative Real-Time PCR, respectively. To verify the role of shizukaol C in vivo, TMAO-induced vascular inflammation model were established using guidewire-induced injury on mice carotid artery. Changes in the intima area and the expression of GSTpi, VCAM-1, CD68 were examined using haematoxylin-eosin staining, and immunofluorescence assay. RESULTS: Our data demonstrated that shizukaol C significantly suppressed TMAO-induced adhesion molecule expression and the bone marrow-derived macrophages (BMDM) adhesion in vascular smooth muscle cells (VSMC). Mechanically, shizukaol C inhibited TMAO-induced c-Jun N-terminal kinase (JNK)-nuclear factor-kappa B (NF-κB)/p65 activation, and the JNK inhibition was dependent on the shizukaol C-mediated glutathione-S-transferase pi (GSTpi) expression. By further molecular docking and protein-binding analysis, we demonstrated that shizukaol C directly binds to Keap1 to induce Nrf2 nuclear translocation and upregulated GSTpi expression. Consistently, our in vivo experiment showed that shizukaol C elevated the expression level of GSTpi in carotid arteries and alleviates TMAO-induced vascular inflammation. CONCLUSION: Shizukaol C exerts anti-inflammatory effects in TMAO-treated VSMC by targeting Keap1 and activating Nrf2-GSTpi signaling and resultantly inhibits the downstream JNK-NF-κB/p65 activation and VSMC adhesion, and alleviates TMAO-induced vascular inflammation in vivo, suggesting that shizukaol C may be a potential drug for treating TMAO-induced vascular diseases.

Effect of CHST11, a novel biomarker, on the biological functionalities of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor, and the role of carbohydrate sulfotransferase 11 (CHST11) in this cancer remains unclear. Here, by using bioinformatics methods, we comprehensively analyzed the relationship between CHST11 and clinical significance, immune infiltration, functional enrichment, m6A methylation, and protein-protein interaction networks. We found that CHST11 expression was significantly higher in ccRCC samples than in normal tissues. Additionally, CHST11 levels correlated with the clinicopathological features of ccRCC patients and functioned as a prognostic factor for patient survival. Functional analysis revealed the involvement of CHST11 in metabolic pathways. Immune infiltration and m6A methylation analysis suggested the association of CHST11 with immune cell abundance in the tumor microenvironment and specific methylation patterns in ccRCC. The in vitro analysis of the clinical samples and ccRCC cell lines demonstrated that the overexpression of CHST11 promotes ccRCC cell proliferation, migration, and invasion, while its suppression has the opposite effect. Thus, CHST11 may play a remarkable role in the occurrence and progression of ccRCC. Functionally, CHST11 promotes the aggressiveness of ccRCC cells. These findings provide insights into the role of CHST11 in ccRCC progression.Registry and the Registration No. of the study/trial: No. 2021K034.

Effect of 24†h glucose fluctuations on 30-day and 1-year mortality in patients with acute myocardial infarction: an analysis from the MIMIC-III database.

Background: It is recognized that patients' blood glucose fluctuates over time during acute disease episodes, especially during the outbreak of cardiovascular events, regardless of the presence of an abnormal blood glucose profile prior to admission to the hospital. Glucose fluctuations in patients with acute myocardial infarction (AMI) in the intensive care unit (ICU) are currently not adequately monitored and studied. We focused on blood glucose fluctuation values within 24 h of admission to assess their association with 30-day and 1-year mortality. Methods: Data of patients with AMI aged 18 years or older from the Critical Care Medical Information Marketplace database III V1.4 were available for analysis in this research. Glucose data were obtained by measurement. A total of 390 of them were treated with PCI. The principal consequence was 30-day and 1-year mortality in patients with AMI. The effect of different glucose fluctuations within 24 h of admission on mortality was predicted by constructing a multivariate Cox regression model with four model adjustments and Kaplan-Meier survival curves. Additionally, we performed curve-fitting analyses to show the correlation between blood glucose fluctuations and risk of death. Results: We selected 1,699 AMI patients into our study through screening. The included population was categorized into three groups based on the tertiles of blood glucose fluctuation values within 24 h of admission to the ICU. The three groups were <25 mg/dl, 25-88 mg/dl and >88 mg/dl. By cox regression analysis, the group with the highest blood glucose fluctuation values (>88 mg/dl) had the most significant increase in 30-day and 1-year mortality after excluding confounding factors (30-day mortality adjusted HR = 2.11; 95% CI = 1.49-2.98 p < 0.001; 1-year mortality adjusted HR = 1.83; 95% CI = 1.40-2.39 p < 0.001). As demonstrated by the Kaplan-Meier survival curves, the group with the greatest fluctuations in blood glucose has the worst 30-day and 1-year prognosis. Conclusions: The extent of glucose fluctuations in patients with AMI in the first 24 h after ICU admission is an essential predictor as to 30-day as well as 1-year mortality. When blood glucose fluctuates more than 88 mg/dl within 24 h, mortality increases significantly with the range of blood glucose fluctuations.

Clinical and pathological features of pilomatrixoma in children: a retrospective study.

Introduction Pilomatrixoma is a benign skin neoplasm that is common in children and is often misdiagnosed. This study aimed to summarize the clinical and pathological features of pilomatrixoma in children. Methods Data on demographic information, clinical and pathological features, diagnosis, and treatment of 171 patients with pilomatrixoma from Shenzhen Baoan Women's and Children's Hospital were collected and analyzed retrospectively. Results The mean age of the patients was 5.7 (standard deviation (SD) = 3.9) year-old, and there were two age peaks (≤1 year-old, 5-11 years old) and two age valleys (2-4 years old, ≥ 12 years old). The mean disease course was 9.3 (SD = 14.1) months, 69.0%, 86.5%, and 95.3% of the patients' disease course in 6 months, 12 months, and 24 months, respectively. The mean tumor volume is 0.6 (SD = 1.0) cm3, 81.3% of the patients' tumor volume ≤ 1.0 cm3. Tumors were distributed sequentially in the head and neck (77.2%), upper limbs (12.9%), trunk (7.6%), and lower limbs (2.3%). The correct rates of clinical and ultrasonic diagnosis were 50.9% and 38.6%, respectively. The two most common pathological features of pilomatrixoma were shadow cells (99.4%) and basaloid cells (94.7%). There were no significant differences in age, disease course, or tumor volume between the male and female patients (P > 0.05). The age and tumor volume of the patients in different body parts were significantly different (P1 = 3.10E-05 and P2 = 5.60E-05, respectively). The correlation between the disease course and tumor volume was positively significant (P ≤ 0.05). There was a significantly correlation between the disease course and tumor volume in patients with tumors at upper limbs (P = 0.03). Conclusion The age of children with pilomatrixoma presented two peaks and two valleys. Most patients had disease courses in 24 months and with tumor volumes ≤ 1.0 cm3. The correct rates of clinical and ultrasonic diagnosis were relatively low. The head and neck are the most common distribution sites of pilomatrixoma, shadow cells and basaloid cells are the most common pathological features. The tumor volume is positively correlated with disease course in patients with pilomatrixoma.

Regulating Surface-Passivator Binding Priority for Efficient Perovskite Light-Emitting Diodes.

Suppressing trap-assisted nonradiative losses through passivators is a prerequisite for efficient perovskite light-emitting diodes (PeLEDs). However, the complex bonding between passivators and perovskites severely suppresses the passivation process, which still lacks comprehensive understanding. Herein, the number, category, and degree of bonds between different functional groups and the perovskite are quantitatively assessed to study the passivation dynamics. Functional groups with high electrostatic potential and large steric hindrance prioritize strong bonding with organic cations and halides on the perfect surface, leading to suppressed coordination with bulky defects. By modulating the binding priorities and coordination capacity, hindrance from the intense interaction with perfect perovskite is significantly reduced, leading to a more direct passivation process. Consequently, the near-infrared PeLED without external light out-coupling demonstrates a record external quantum efficiency of 24.3% at a current density of 42 mA cm-2. In addition, the device exhibits a record-level-cycle ON/OFF switching of 20 000 and ultralong half-lifetime of 1126.3 h under 5 mA cm-2. An in-depth understanding of the passivators can offer new insights into the development of high-performance PeLEDs.

An efficient ß-nucleating agent with high lattice matching rate for plate-like crystallization of polypropylene random copolymer.

It is challenging to naturally produce large amounts of ß-crystals by directly adding a commercial ß-nucleating agent (ß-NA) into polypropylene random copolymer (PPR) at present. In this work, a novel rare earth ß-NA WBN-28 was directly introduced into PPR to prepare ß-PPR with high ß-crystal conversion. The results of differential scanning calorimetry (DSC) and wide-angle X-ray diffraction (WAXD) indicated that it is an efficient ß-NA for PPR. The ß-conversion rate (ß-CR) could surpass 85% when the nucleating agent content was mere 0.05%. With the further increment of nucleating agent, the ß-CR increased gradually, which could reach 89.5% and 86.9% respectively calculated by DSC and WAXD when the addition amount was 0.4%. The incredible high ß-CR delayed the ßα-recrystallization in isothermal crystallization. The fusion peak of α-crystal was unobserved below the isothermal crystallization temperature of 122 °C when the addition amount was more than 0.2%. Furthermore, there was a highly ordered structure in WBN-28 with the periodicity of 12.89 Å, which was approximately twice of the unit cell parameter in the c direction of ß-PP, indicating a high lattice matching rate between them. Intuitively observed by polarizing optical microscope (POM), the crystal grains of the blends with ß-NA were more refined and finally crystallized in a plate-like shape. The forming process of the plate-like ß crystalline regions were proposed by scanning electron microscope (SEM) and POM.

A national-scale assessment of land subsidence in China's major cities.

China's massive wave of urbanization may be threatened by land subsidence. Using a spaceborne synthetic aperture radar interferometry technique, we provided a systematic assessment of land subsidence in all of China's major cities from 2015 to 2022. Of the examined urban lands, 45% are subsiding faster than 3 millimeters per year, and 16% are subsiding faster than 10 millimeters per year, affecting 29 and 7% of the urban population, respectively. The subsidence appears to be associated with a range of factors such as groundwater withdrawal and the weight of buildings. By 2120, 22 to 26% of China's coastal lands will have a relative elevation lower than sea level, hosting 9 to 11% of the coastal population, because of the combined effect of city subsidence and sea-level rise. Our results underscore the necessity of enhancing protective measures to mitigate potential damages from subsidence.

Retinal Ischemic Perivascular Lesion Reflects Cerebral Small Vessel Disease Burden in Single Subcortical Infarction.

BACKGROUND: Retinal ischemic perivascular lesions (RIPLs) are an indicator of ischemia in the middle retina. We aimed to determine the relationship between RIPLs and single subcortical infarction (SSI). We also investigated the differences in cerebral small vessel disease imaging burden between groups with and without RIPLs in SSI. METHODS AND RESULTS: In this case-control study, we enrolled 82 patients with SSI and 72 nonstroke controls. All participants underwent magnetic resonance imaging and swept-source optical coherence tomography/optical coherence tomography angiography. Small vessel disease markers such as lacunes, cerebral microbleeds, white matter hyperintensity, and perivascular spaces were rated on brain imaging. RIPLs were assessed via swept-source optical coherence tomography. Optical coherence tomography angiography was used to measure the superficial vascular complex and deep vascular complex of the retina. After adjusting for risk factors, the presence of RIPLs was significantly associated with SSI (odds ratio [OR], 1.506 [95% CI, 1.365-1.662], P<0.001). Eyes with RIPLs showed lower deep vascular complex density (P=0.035) compared with eyes without RIPLs in patients with SSI. After adjusting for vascular risk factors, the presence of RIPLs in patients with SSI was associated with an increased periventricular white matter hyperintensity burden (ß=0.414 [95% CI, 0.181-0.647], P<0.001) and perivascular spaces-basal ganglia (ß=0.296 [95% CI, 0.079-0.512], P=0.008). CONCLUSIONS: RIPLs are associated with SSI independent of underlying risk factors. The relationship between the presence of RIPLs and small vessel disease markers provides evidence that RIPLs might be an additional indicator of cerebral ischemic changes.

A new preparation method of covalent annular nanodiscs based on MTGase.

The preservation of the native conformation and functionality of membrane proteins has posed considerable challenges. While detergents and liposome reconstitution have been traditional approaches, nanodiscs (NDs) offer a promising solution by embedding membrane proteins in phospholipids encircled by an amphipathic helical protein MSP belt. Nevertheless, a drawback of commonly used NDs is their limited homogeneity and stability. In this study, we present a novel approach to construct covalent annular nanodiscs (cNDs) by leveraging microbial transglutaminase (MTGase) to catalyze isopeptide bond formation between the side chains of terminal amino acids, specifically Lysine (K) and Glutamine (Q). This methodology significantly enhances the homogeneity and stability of NDs. Characterization of cNDs and the assembly of membrane proteins within them validate the successful reconstitution of membrane proteins with improved homogeneity and stability. Our findings suggest that cNDs represent a more suitable tool for investigating interactions between membrane proteins and lipids, as well as for analyzing membrane protein structures.

Exciton polariton condensation from bound states in the continuum at room temperature.

Exciton-polaritons (polaritons) resulting from the strong exciton-photon interaction stimulates the development of novel low-threshold coherent light sources to circumvent the ever-increasing energy demands of optical communications1-3. Polaritons from bound states in the continuum (BICs) are promising for Bose-Einstein condensation owing to their theoretically infinite quality factors, which provide prolonged lifetimes and benefit the polariton accumulations4-7. However, BIC polariton condensation remains limited to cryogenic temperatures ascribed to the small exciton binding energies of conventional material platforms. Herein, we demonstrated room-temperature BIC polariton condensation in perovskite photonic crystal lattices. BIC polariton condensation was demonstrated at the vicinity of the saddle point of polariton dispersion that generates directional vortex beam emission with long-range coherence. We also explore the peculiar switching effect among the miniaturized BIC polariton modes through effective polariton-polariton scattering. Our work paves the way for the practical implementation of BIC polariton condensates for integrated photonic and topological circuits.

Solvent-Induced In(III)-MOFs with Controllable Interpenetration Degree Performing High-Efficiency Separation of CO2/N2 and CO2/CH4.

Herein, three In(III)-based metal-organic frameworks (In-MOFs) with different degrees of interpenetration (DOI), namely In-MOF-1, In-MOF-2, and In-MOF-3, constructed by In3+ and Y-shaped ligands 4,4',4″-s-triazine-2,4,6-triyltribenzoate (H3TATB), are successfully synthesized through the ionothermal/solvothermal method. Subsequently, three novel In-MOFs, including noninterpenetration polycatenation, 2-fold interpenetrated, and 4-fold interpenetrated structure, are employed as the platform for systematically investigating the separation efficiency of CO2/N2, CO2/CH4, and CO2/CH4/N2 mixture gas system. Among them, In-MOF-2 shows the highest CO2 uptake capacities at 298 K and simultaneously possesses the low adsorption enthalpy of CO2 (26.4 kJ/mol at low coverage), a feature desirable for low-energy-cost adsorbent regeneration. The CO2/N2 (v: v = 15/85) selectivity of In-MOF-2 reaches 37.6 (at 298 K and 1 bar), also revealing outstanding selective separation ability from flue gases and purifying natural gas, affording a unique robust separation material as it has moderate DOI and pore size. In-MOF-2 shows exceptional stability and feasibility to achieve reproducibility. Aperture adjustment makes In-MOF-2 a versatile platform for selectively capturing CO2 from flue gases or purifying natural gas.

Rhizosphere metabolic cross-talk from plant-soil-microbe tapping into agricultural sustainability: Current advance and perspectives.

Rhizosphere interactions from plant-soil-microbiome occur dynamically all the time in the "black microzone" underground, where we can't see intuitively. Rhizosphere metabolites including root exudates and microbial metabolites act as various chemical signalings involving in rhizosphere interactions, and play vital roles on plant growth, development, disease suppression and resistance to stress conditions as well as proper soil health. Although rhizosphere metabolites are a mixture from plant roots and soil microbes, they often are discussed alone. As a rapid appearance of various omics platforms and analytical methods, it offers possibilities and opportunities for exploring rhizosphere interactions in unprecedented breadth and depth. However, our comprehensive understanding about the fine-tuning mechanisms of rhizosphere interactions mediated by these chemical compounds still remain clear. Thus, this review summarizes recent advances systemically including the features of rhizosphere metabolites and their effects on rhizosphere ecosystem, and looks forward to the future research perspectives, which contributes to facilitating better understanding of biochemical communications belowground and helping identify novel rhizosphere metabolites. We also address challenges for promoting the understanding about the roles of rhizosphere metabolites in different environmental stresses.

Environmental Controls on Evapotranspiration and Its Components in a Qinghai Spruce Forest in the Qilian Mountains.

Qinghai spruce forests, found in the Qilian mountains, are a typical type of water conservation forest and play an important role in regulating the regional water balance and quantifying the changes and controlling factors for evapotranspiration (ET) and its components, namely, transpiration (T), evaporation (Es) and canopy interceptions (Ei), of the Qinghai spruce, which may provide rich information for improving water resource management. In this study, we partitioned ET based on the assumption that total ET equals the sum of T, Es and Ei, and then we analyzed the environmental controls on ET, T and Es. The results show that, during the main growing seasons of the Qinghai spruce (from May to September) in the Qilian mountains, the total ET values were 353.7 and 325.1 mm in 2019 and 2020, respectively. The monthly dynamics in the daily variations in T/ET and Es/ET showed that T/ET increased until July and gradually decreased afterwards, while Es/ET showed opposite trends and was mainly controlled by the amount of precipitation. Among all the ET components, T always occupied the largest part, while the contribution of Es to ET was minimal. Meanwhile, Ei must be considered when partitioning ET, as it accounts for a certain percentage (greater than one-third) of the total ET values. Combining Pearson's correlation analysis and the boosted regression trees method, we concluded that net radiation (Rn), soil temperature (Ts) and soil water content (SWC) were the main controlling factors for ET. T was mainly determined by the radiation and soil hydrothermic factors (Rn, photosynthetic active radiation (PAR) and TS30), while Es was mostly controlled by the vapor pressure deficit (VPD), atmospheric precipitation (Pa), throughfall (Pt) and air temperature (Ta). Our study may provide further theoretical support to improve our understanding of the responses of ET and its components to surrounding environments.

Calculation of additional load and deformation of the receiving well enclosure structure caused by shield tunneling.

The bulkhead additional thrust during shield tunneling, the force of friction between shield and soil, and the additional grouting pressure can cause additional stress in the surrounding soil, thereby disturbing existing buildings and structures. However, few studies focused on the disturbance situation when the shield tunneling machine approaches the receiving well. If the additional stress and deformation of the receiving well are too excessive, it could result in the collapse of the receiving well. Based on the two-stage method, this study derived the calculation formula of the additional stress and deformation of the receiving well enclosure structure caused by shield tunneling. Taking a shield machine receiving engineering as the context, this study established a numerical simulation model and compared theoretical calculation, the results of numerical simulation model and on-site monitoring data. Finally, the additional stress of the receiving well is analyzed. The research findings demonstrate that the theoretical prediction results, numerical simulation calculation results, and on-site monitoring data exhibit relatively small calculation errors, which validated the applicability of the theoretical prediction formula and numerical simulation model. As the distance between the shield machine and the receiving well decreases, the disturbance to the receiving well increases sharply. When the distance between the cutter head and the receiving well is less than three times the shield length, it is crucial to enhance the deformation monitoring of the receiving well. The primary factors affecting the additional load and deformation of the receiving well enclosure structure are the force of friction between shield and soil and the additional thrust of the cutterhead. The disturbance caused by the additional grouting pressure on the enclosure structure can be ignored.

Sex differences in mortality and liver-related events in non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND & AIMS: Many systematic reviews explore the association of non-alcoholic fatty liver disease (NAFLD) with mortality, but none of them explores sex-based differences in detail. We aimed to assess whether NAFLD is associated with cause-specific mortality, all-cause mortality, and cancer incidence in both men and women. METHODS: The PubMed, Embase, and Medline databases were searched from inception through April 2023 for eligible studies. We separately pooled relative risks (RRs) for men and women using a random effects model. Subsequently, the RRs and 95% CIs (confidence intervals) in each study were used to calculate the women-to-men ratio of RRs (RRR). Furthermore, subgroup analyses were performed to explore the robustness of outcomes. The random-effects model was employed to conduct sensitivity analyses to determine the impact of specific studies on the overall findings. RESULTS: The meta-analysis included nine cohort studies comprising 557 614 patients with NAFLD were chosen. Women were 44% more likely than men to get cancer among those with NAFLD (RRR: 1.44; 95% CI: 1.02-2.04; p = .039). However, no sex-related differences were observed between NAFLD and all-cause mortality (RRR: 1.06; 95% CI: 0.56-2.01; p = .861), liver-related mortality (RRR: 1.06; 95% CI: 0.02-69.82; p = .977), cardiovascular mortality (RRR: 1; 95% CI: 0.65-1.53; p = .987) and liver cancer (RRR: 0.76; 95% CI: 0.43-1.36; p = .36). CONCLUSIONS: There may be sex variations between NAFLD and the risk of cancer, with the connection being stronger in females than in males.

CO-Assisted Methane Oxidation into Oxygenates over Surface Platinum-Titanium Alloyed Layers.

Methane oxidation using molecular oxygen remains a grand challenge in which the obstacle is not only the activation of methane but also the reaction with oxygen, considering the mismatch of the ground spin states. Herein, we report TiO2-supported Pt nanocrystals (Pt/TiO2) with surface Pt-Ti alloyed layers that directly convert methane into oxygenates by using O2 as the oxidant with the assistance of CO. The oxygenate yield reached 749.8 mmol gPt-1 in a H2O aqueous solution over 0.1% Pt/TiO2 under 31 bar of mixed gas (20:5:6 CH4:CO:O2) at 150 °C for 3 h, while the CH3OH selectivity was 62.3%. On the basis of the control experiments and spectroscopic results, we identified the surface Pt-Ti alloy as the active sites. Moreover, CO promoted the dissociation of O2 on the surface of Pt-Ti alloyed layers and the subsequent activation of CH4 to form oxygenated products.

A group-targeting biosensor for sensitive and rapid detection of quinolones in water samples.

BACKGROUND: Quinolones (QNs) widely exist in the environment due to their wide range of applications and poor metabolic properties, resulting in the generation and spread of resistance genes, posing a potential threat to human health. Traditional analytical methods cannot detect all broad ranges of QNs simultaneously. The development of facile, efficient and reliable method for quantification and assessment of the total QNs is a long-lasting challenge. RESULTS: We hereby provide a simple, sensitive and instantaneous group-targeting biosensor for the detection of total QNs in environmental water samples. The biosensor is based on a group-specific antibodies with high affinity against QNs. Fluorescent labeled antibodies bound to the coated antigen modified on the surface of the transducer, and excited by the evanescent waves. The detected fluorescent signal is inversely proportional to the QNs concentration. This biosensor exhibited excellent performance with detection limits lower than 0.15 µg L-1 for all five QNs variants, and even lower than 0.075 µg L-1 for ciprofloxacin (CIP) and ofloxacin (OFL). Environmental water samples can be detected after simple pretreatment, and all detection steps can be completed in 10 min. The transducer has a high regenerative capacity and shows no significant signal degradation after two hundred detection cycles. The recoveries of QNs in a variety of wastewater range from 105 to 119%, confirming its application potential in the measurement of total QNs in reality. SIGNIFICANCE: The biosensor can realize rapid and sensitive detection of total QNs in water samples by simple pretreatment, which overcomes the disadvantage of the traditional methods that require complex pretreatment and time-consuming, and pave the groundwork for expansive development centered around this technology.

Simultaneous production of algal biomass and lipid by heterotrophic cultivation of linoleic acid-rich oleaginous microalga Chlorella sorokiniana using high acetate dosage.

The low-cost carbon source, acetate, was utilized to feed a linoleic acid-rich Chlorella sorokiniana for microalgal biomass and lipid accumulation. Remarkably high tolerance capability to high acetate dosage up to 30 g/L was observed, with heterotrophy being the preferred trophic mode for algal growth and lipogenesis when supplemented 20 g/L acetate. Transcriptome analysis revealed a marked activation of pathways involved in acetate bioconversion and lipogenesis upon exposure to high-level of acetate. However, the enhancement of photorespiration inhibited photosynthesis, which ultimately led to a decrease in biomass and lipid under mixotrophy. Heterotrophic acetate-feeding generated more superior amino acid profiling of algal biomass and a predominant linoleic acid content (50 %). Heterotrophic repeat fed-batch strategy in 5 L fermenter significantly increased the growth performance and lipid titer, with the highest levels achieved being 23.4 g/L and 7.0 g/L, respectively. This work provides a viable approach for bio-products production through acetate-based heterotrophic algal cultivation.

The role of foam cells in spinal cord injury: challenges and opportunities for intervention.

Spinal cord injury (SCI) results in a large amount of tissue cell debris in the lesion site, which interacts with various cytokines, including inflammatory factors, and the intrinsic glial environment of the central nervous system (CNS) to form an inhibitory microenvironment that impedes nerve regeneration. The efficient clearance of tissue debris is crucial for the resolution of the inhibitory microenvironment after SCI. Macrophages are the main cells responsible for tissue debris removal after SCI. However, the high lipid content in tissue debris and the dysregulation of lipid metabolism within macrophages lead to their transformation into foamy macrophages during the phagocytic process. This phenotypic shift is associated with a further pro-inflammatory polarization that may aggravate neurological deterioration and hamper nerve repair. In this review, we summarize the phenotype and metabolism of macrophages under inflammatory conditions, as well as the mechanisms and consequences of foam cell formation after SCI. Moreover, we discuss two strategies for foam cell modulation and several potential therapeutic targets that may enhance the treatment of SCI.

Iridium-Catalyzed Asymmetric Hydrogenation of Heteroaromatics with Multiple N Atoms via Substrate Activation: An Entry to 4,5,6,7-Tetrahydropyrazolo[1,5-a]pyrimidine-3-carbonitrile Core of a Potent BTK Inhibitor.

The chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine is the key core skeleton of potent Bruton's tyrosine kinase (BTK) inhibitor Zanubrutinib, and the catalyst-controlled asymmetric hydrogenation of planar multinuclear pyrimidine heteroarenes with multiple N atoms could provide an efficient route toward its synthesis. Owing to the strong aromaticity and poisoning effect toward chiral transition metal catalyst, asymmetric hydrogenation of pyrazolo[1,5-a]pyrimidines with multiple nitrogen atoms is still a challenge for synthesizing the chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]-pyrimidine. Herein, an efficient iridium-catalyzed asymmetric hydrogenation of pyrazolo[1,5-a]pyrimidines has been developed using substrate activation strategy, with up to 99% ee. The decagram scale synthesis further demonstrated the potential and promise of this procedure in the synthesis of Zanubrutinib. In addition, a mechanistic study indicated that the hydrogenation starts with 1,2-hydrogenation.