Reversing the directionality of reactions between non-oxidative pentose phosphate pathway and glycolytic pathway boosts mycosporine-like amino acid production in Saccharomyces cerevisiae.

BACKGROUND: Mycosporine-like amino acids (MAAs) are a class of strongly UV-absorbing compounds produced by cyanobacteria, algae and corals and are promising candidates for natural sunscreen components. Low MAA yields from natural sources, coupled with difficulties in culturing its native producers, have catalyzed synthetic biology-guided approaches to produce MAAs in tractable microbial hosts like Escherichia coli, Saccharomyces cerevisiae and Corynebacterium glutamicum. However, the MAA titres obtained in these hosts are still low, necessitating a thorough understanding of cellular factors regulating MAA production. RESULTS: To delineate factors that regulate MAA production, we constructed a shinorine (mycosporine-glycine-serine) producing yeast strain by expressing the four MAA biosynthetic enzymes from Nostoc punctiforme in Saccharomyces cerevisiae. We show that shinorine is produced from the pentose phosphate pathway intermediate sedoheptulose 7-phosphate (S7P), and not from the shikimate pathway intermediate 3-dehydroquinate (3DHQ) as previously suggested. Deletions of transaldolase (TAL1) and phosphofructokinase (PFK1/PFK2) genes boosted S7P/shinorine production via independent mechanisms. Unexpectedly, the enhanced S7P/shinorine production in the PFK mutants was not entirely due to increased flux towards the pentose phosphate pathway. We provide multiple lines of evidence in support of a reversed pathway between glycolysis and the non-oxidative pentose phosphate pathway (NOPPP) that boosts S7P/shinorine production in the phosphofructokinase mutant cells. CONCLUSION: Reversing the direction of flux between glycolysis and the NOPPP offers a novel metabolic engineering strategy in Saccharomyces cerevisiae.

Network meta-analysis of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults.

OBJECTIVE: To compare the outcomes associated with the use of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults. METHODS: We searched eight electronic databases from database inception to July 11, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the treatment of chronic constipation. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of the evidence was assessed using the Confidence in Network Meta-Analysis framework. The analysis was conducted using R version 4.3.0. RESULTS: Out of the 37 RCTs, a total of 21 different types of interventions were reported, involving 3,903 patients. This NMA demonstrated that both prebiotics and synbiotics resulted in an increase in frequency of stool movements per week. Compared to placebo, lactulose (Mean difference [MD] = 3.39, 95% Confdence interval [CI] [1.13, 5.65], moderate certainty), mix2 (consisting of Lactulose and Bacillus coagulans) (MD = 3.63, 95% CI [1.37, 5.89], moderate certainty), mix6 (consisting of Lactulose and Bifidobacterium coagulans) (MD = 4.30, 95% CI [1.04, 7.54], low certainty), and mix7 (consisting of Lactulose, Bifidobacterium subtilis, and Enterococcus faecium) (MD = 4.58, 95% CI [1.35, 7.78], moderate certainty) exhibited a significant effect. Notably, mix7 demonstrated the highest probability of being the most effective intervention (94.8%). Furthermore, when compared to L. plantarum, four probiotics and two synbiotics showed significant advantages in the Patient Assessment of Constipation Symptoms (PAC-SYM) score. L. reuteri (MD = -13.74, 95% CI [-22.20, -4.66], very low certainty) exhibited a significant effect in improving the Patient Assessment of Constipation Quality of Life (PAC-QoL) score. In terms of safety, there were no statistically significant differences between the intervention and control groups in all adverse event analyses. CONCLUSIONS: Moderate to very low evidence supports the use of lactulose and synbiotics to increase the number of weekly stool movements in patients, particularly highlighting the significant impact of synbiotics in increasing the number of weekly stool movements in patients with constipation. The use of L. paracasei showed improvements in PAC-SYM scores, while L. reuteri demonstrated enhancements in PAC-QoL scores.

Clinical spectrum, over 12-year follow-up and experience of SGLT2 inhibitors treatment on patients with glycogen storage disease type Ib: a single-center retrospective study.

BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment. RESULTS: In this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients. CONCLUSION: Empagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested.

DUSP22 Ameliorates Endothelial-to-Mesenchymal Transition in HUVECs through Smad2/3 and MAPK Signaling Pathways.

Endothelial-to-mesenchymal transition (EndMT) is the process by which endothelial cells lose their endothelial properties and acquire mesenchymal characteristics. Dual-specific protein phosphatase 22 (DUSP22) inactivates various protein kinases and transcription factors by dephosphorylating serine/threonine residues: hence, it plays a key role in many diseases. The aim of this study was to explore the functional role of DUSP22 in EndMT. In the transforming growth factor-ß-induced EndMT model in human umbilical vein endothelial cells (HUVECs), we observed a downregulation of DUSP22 expression. This DUSP22 deficiency could aggravate EndMT. Conversely, the overexpression of DUSP22 could ameliorate EndMT. We used signaling pathway inhibitors to verify our results and found that DUSP22 could regulate EndMT through the smad2/3 and the mitogen-activated protein kinase (MAPK) signaling pathways. In summary, DUSP22 ameliorates EndMT in HUVECs in vitro through the smad2/3 and MAPK signaling pathways.

Iron(III) and BF3·OEt2-Promoted O-Transfer Reaction of N-Aryl-α,ß-Unsaturated Nitrones to Prepare Difluoroboron ß-Ketoiminates.

We described an iron(III) and BF3·OEt2-promoted oxygen transfer reaction of N-aryl-α,ß-unsaturated nitrones to prepare various N,O-difluoroboron ß-ketoiminates in good yields ranging from 24% to 87%. Control experiments revealed that the enaminone was the vital intermediate for the formation of N,O-difluoroboron ß-ketoiminates, and iron(III) combined with BF3·OEt2 played as cocatalyst to promote the oxygen transfer reaction through intramolecular cyclization and N-O bond cleavage. More importantly, an estrone-derived N,O-difluoroboron ß-ketoiminate was easily prepared in 40% yield from estrone in four steps.

[Value of the human chorionic gonadotropin stimulation test in the diagnosis of disorder of sexual development in children]. / äººç»’æ¯›è†œä¿ƒæ€§è ºæ¿€ç´ æ¿€å‘è¯•éªŒåœ¨æ€§å‘è‚²å¼‚å¸¸å„¿ç«¥ä¸­çš„è¯Šæ–­ä½œç”¨è¯„ä¼°.

OBJECTIVES: To investigate the value of the human chorionic gonadotropin (hCG) stimulation test in the diagnosis of disorder of sexual development (DSD) in children. METHODS: A retrospective analysis was conducted on 132 children with DSD. According to the karyotype, they were divided into three groups: 46,XX group (n=10), 46,XY group (n=87), and sex chromosome abnormality group (n=35). The above groups were compared in terms of sex hormone levels before and after hCG stimulation test, and the morphological manifestation of the impact of testicular tissue on the results of the hCG stimulation test was analyzed. RESULTS: There was no significant difference in the multiple increase of testosterone after stimulation among the three groups (P>0.05). In the 46,XY group, the children with 5α-reductase type 2 deficiency had a testosterone-to-dihydrotestosterone ratio higher than that of the 46,XY DSD children with other causes. Morphological analysis showed that DSD children with testicular tissue demonstrated a significantly higher multiple increase in testosterone after stimulation compared to children without testicular tissue (P<0.05). CONCLUSIONS: The hCG stimulation test has an important value in assessing the presence and function of testicular interstitial cells in children with different types of DSD, and it is recommended to perform the hCG stimulation test for DSD children with unclear gonadal type.

Melanoma differentiation-associated protein 5 prevents cardiac hypertrophy via apoptosis signal-regulating kinase 1-c-Jun N-terminal kinase/p38 signaling.

Pathological cardiac hypertrophy (CH) is driven by maladaptive changes in myocardial cells in response to pressure overload or other stimuli. CH has been identified as a significant risk factor for the development of various cardiovascular diseases, ultimately resulting in heart failure. Melanoma differentiation-associated protein 5 (MDA5), encoded by interferon-induced with helicase C domain 1 (IFIH1), is a cytoplasmic sensor that primarily functions as a detector of double-stranded ribonucleic acid (dsRNA) viruses in innate immune responses; however, its role in CH pathogenesis remains unclear. Thus, the aim of this study was to examine the relationship between MDA5 and CH using cellular and animal models generated by stimulating neonatal rat cardiomyocytes with phenylephrine and by performing transverse aortic constriction on mice, respectively. MDA5 expression was upregulated in all models. MDA5 deficiency exacerbated myocardial pachynsis, fibrosis, and inflammation in vivo, whereas its overexpression hindered CH development in vitro. In terms of the underlying molecular mechanism, MDA5 inhibited CH development by promoting apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, thereby suppressing c-Jun N-terminal kinase/p38 signaling pathway activation. Rescue experiments using an ASK1 activation inhibitor confirmed that ASK1 phosphorylation was essential for MDA5-mediated cell death. Thus, MDA5 protects against CH and is a potential therapeutic target.

Comparison of effectiveness and safety of lasmiditan and CGRP-antagonists for the acute treatment of migraine in adults: systematic review and network meta-analysis of randomised trials.

OBJECTIVE: To compare the outcomes associated with the use of lasmiditan, rimegepant, ubrogepant, and zavegepant for the acute management of migraine headaches. METHODS: We searched four electronic databases from database inception to August 31, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the acute treatment of migraine. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of evidence using the CINeMA approach. We conducted frequentist network meta-analyses (NMA) to summarise the evidence. Data were analyzed using R-4.3.1. RESULTS: A total of 18 eligible studies including 10 different types of interventions with 22,429 migraine patients were included. NMA results showed that compared to ubrogepant (25 mg and 50 mg) and zavegepant, lasmiditan (100 mg and 200 mg) exhibits an elevated probability of achieving pain relief within a 2-hour interval. Similarly, relative to zavegepant, rimegepant (75 mg) and ubrogepant (50 mg and 100 mg) demonstrate an enhanced likelihood of sustaining pain relief over a 24-hour period. Furthermore, in contrast to ubrogepant (25 mg) and lasmiditan (50 mg), rimegepant (75 mg) presents a heightened probability of achieving freedom from photophobia within 2 h. Regarding safety, lasmiditan carries the highest risk of adverse events, which are associated with an increased incidence of adverse effects, including dizziness, somnolence, asthenia, paresthesia, and fatigue. CONCLUSIONS: In this NMA, a spectrum of evidence ranging from very low to high levels underscores the favorable efficacy and tolerability of rimegepant 75 mg and ubrogepant 100 mg, positioning them as potential candidates for the acute management of migraine. Concurrently, lasmiditan (100 mg and 200 mg) exhibits notable efficacy, albeit accompanied by an increased susceptibility to adverse events. These findings should still be approached with caution, primarily due to the intrinsic limitations associated with indirect comparisons.

Synthesis of 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-b]quinazolinones through a cyclized dearomatization and trichloromethylation cascade strategy.

A variety of 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-b]quinazolinones were prepared in moderate to good yields with high regioselectivity through intramolecular 6-endo-dig cyclization and trichloromethylation of N3-alkynyl-2-pyridinyl-tethered quinazolinones in chloroform. Mechanistic studies revealed that chloroform might serve as a trichloromethyl anion precursor. Furthermore, the reaction could be easily performed on gram scales and an estrone-derived 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-b]quinazolinone was prepared over five steps. The present method features broad substrate scope, good functional group tolerance, new dearomatization of pyridine rings, and chloroform as the trichloromethylation reagent.

Defining Bacterial RNA-RNA Interactomes Using CLASH.

Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial pathogen accounting for high mortality rates among infected patients. Transcriptomic regulation by small RNAs (sRNAs) has been shown to regulate networks promoting antibiotic resistance and virulence in S. aureus. Yet, the biological role of most sRNAs during MRSA host infection remains unknown. To fill this gap, in collaboration with the lab of Jai Tree, we performed comprehensive RNA-RNA interactome analyses in MRSA using CLASH under conditions that mimic the host environment. Here we present a detailed version of this optimized CLASH (cross-linking, ligation, and sequencing of hybrids) protocol we recently developed, which has been tailored to explore the RNA interactome in S. aureus as well as other Gram-positive bacteria. Alongside, we introduce a compilation of helpful Python functions for analyzing folding energies of putative RNA-RNA interactions and streamlining sRNA and mRNA seed discovery in CLASH data. In the accompanying computational demonstration, we aim to establish a standardized strategy to evaluate the likelihood that observed chimeras arise from true RNA-RNA interactions.

Effect of optical fiber end face scratches on laser-induced damage threshold.

The scratches on the fiber end face can enhance the local electrical field, which lowers the damage threshold. The damage mechanism of a high-energy laser is investigated. The effect of scratches on the electric field is simulated by the finite difference time domain (FDTD) solution. The results show that the depth of the scratch has a greater ability to influence the electric field than the width, and multiple scratches have a stronger modulation than a single scratch. In calculation, the damage threshold of the scratch-free end face is 0.456J/c m 2 when the incident light electric field intensity is 50M V/c m, compared to 0.345J/c m 2 in the presence of the scratch on the end face.

Ovarian Tumor Domain-Containing 7B Attenuates Pathological Cardiac Hypertrophy by Inhibiting Ubiquitination and Degradation of Krüppel-Like Factor 4.

BACKGROUND: Cardiac hypertrophy (CH) is a well-established risk factor for many cardiovascular diseases and a primary cause of mortality and morbidity among older adults. Currently, no pharmacological interventions have been specifically tailored to treat CH. OTUD7B (ovarian tumor domain-containing 7B) is a member of the ovarian tumor-related protease (OTU) family that regulates many important cell signaling pathways. However, the role of OTUD7B in the development of CH is unclear. Therefore, we investigated the role of OTUD7B in CH. METHODS AND RESULTS: OTUD7B knockout mice were used to assay the role of OTUD7B in CH after transverse aortic coarctation surgery. We further assayed the specific functions of OTUD7B in isolated neonatal rat cardiomyocytes. We found that OTUD7B expression decreased in hypertrophic mice hearts and phenylephrine-stimulated neonatal rat cardiomyocytes. Furthermore, OTUD7B deficiency exacerbated transverse aortic coarctation surgery-induced myocardial hypertrophy, abnormal cardiac function, and fibrosis. In cardiac myocytes, OTUD7B knockdown promoted phenylephrine stimulation-induced myocardial hypertrophy, whereas OTUD7B overexpression had the opposite effect. An immunoprecipitation-mass spectrometry analysis showed that OTUD7B directly binds to KLF4 (Krüppel-like factor 4). Additional molecular experiments showed that OTUD7B impedes KLF4 degradation by inhibiting lysine residue at 48 site-linked ubiquitination and suppressing myocardial hypertrophy by activating the serine/threonine kinase pathway. CONCLUSIONS: These results demonstrate that the OTUD7B-KLF4 axis is a novel molecular target for CH treatment.

Synthesis of Spirooxindole-1,2-oxazinan-5-ones through 2,2,2-Trifluoroethanol Promoted [3 + 3] Cycloaddition of N-Vinyl Oxindole Nitrones and Oxyallyl Cations.

A variety of spirooxindole-1,2-oxazinan-5-one derivatives were prepared in moderate to excellent yields through 2,2,2-trifluoroethanol (TFE)-promoted [3 + 3] cycloaddition of N-vinyl oxindole nitrones with oxyallyl cations generated from α-tosyloxy ketones under mild reaction conditions. Mechanistic studies revealed that [3 + 3] cycloaddition might involve two possible reaction pathways, including direct [3 + 3] cycloaddition of N-vinyl oxindole ntirones with oxyallyl cations, or the addition of TFE to N-vinyl oxindole nitrones, sequential addition to oxyallyl cations, elimination, and cyclization. The present method features mild reaction conditions, broad substrate scope, good functional group tolerance, easy gram scalable preparation, and new applications of TFE.

Discovery adductomics provides a comprehensive portrait of tissue-, age- and sex-specific DNA modifications in rodents and humans.

DNA damage causes genomic instability underlying many diseases, with traditional analytical approaches providing minimal insight into the spectrum of DNA lesions in vivo. Here we used untargeted chromatography-coupled tandem mass spectrometry-based adductomics (LC-MS/MS) to begin to define the landscape of DNA modifications in rat and human tissues. A basis set of 114 putative DNA adducts was identified in heart, liver, brain, and kidney in 1-26-month-old rats and 111 in human heart and brain by 'stepped MRM' LC-MS/MS. Subsequent targeted analysis of these species revealed species-, tissue-, age- and sex-biases. Structural characterization of 10 selected adductomic signals as known DNA modifications validated the method and established confidence in the DNA origins of the signals. Along with strong tissue biases, we observed significant age-dependence for 36 adducts, including N2-CMdG, 5-HMdC and 8-Oxo-dG in rats and 1,N6-ϵdA in human heart, as well as sex biases for 67 adducts in rat tissues. These results demonstrate the potential of adductomics for discovering the true spectrum of disease-driving DNA adducts. Our dataset of 114 putative adducts serves as a resource for characterizing dozens of new forms of DNA damage, defining mechanisms of their formation and repair, and developing them as biomarkers of aging and disease.

Fishery catch is affected by geographic expansion, fishing down food webs and climate change in Aotearoa, New Zealand.

Historical fishing effort has resulted, in many parts of the ocean, in increasing catches of smaller, lower trophic level species once larger higher trophic level species have been depleted. Concurrently, changes in the geographic distribution of marine species have been observed as species track their thermal affinity in line with ocean warming. However, geographic shifts in fisheries, including to deeper waters, may conceal the phenomenon of fishing down the food web and effects of climate warming on fish stocks. Fisheries-catch weighted metrics such as the Mean Trophic Level (MTL) and Mean Temperature of the Catch (MTC) are used to investigate these phenomena, although apparent trends of these metrics can be masked by the aforementioned geographic expansion and deepening of fisheries catch across large areas and time periods. We investigated instances of both fishing down trophic levels and climate-driven changes in the geographic distribution of fished species in New Zealand waters from 1950-2019, using the MTL and MTC. Thereafter, we corrected for the masking effect of the geographic expansion of fisheries within these indices by using the Fishing-in-Balance (FiB) index and the adapted Mean Trophic Level (aMTL) index. Our results document the offshore expansion of fisheries across the New Zealand Exclusive Economic Zone (EEZ) from 1950-2019, as well as the pervasiveness of fishing down within nearshore fishing stock assemblages. We also revealed the warming of the MTC for pelagic-associated fisheries, trends that were otherwise masked by the depth- and geographic expansion of New Zealand fisheries across the study period.

Bias control approach based on VMD and LIA demodulation of a lithium niobate polarization controller.

A bias control approach is an automatic lock working point algorithm based on variational mode decomposition (VMD) and lock-in amplification (LIA) demodulation for a lithium niobate polarization controller (LNPC). Commonly, the dither voltage applied to the LNPC is much smaller than the bias voltage to avoid the influence of the dither signal on the output light, which reduces the polarization control accuracy of the LNPC. In this paper, we use VMD and LIA, with which the polarization control accuracy of LNPC can be improved, to extract and amplify the dither signal to compensate the drift half-wave of LNPC. The light intensity fluctuations of the output polarized light in vertical or horizontal directions are less than 0.017%.

Ultrahigh bandwidth measuring approach of an I-FOG based on axial magnetic sensitivity.

The bandwidth is one of the key indicators of the interferometric fiber optic gyroscope (I-FOG) in the application with high frequency jitter. The traditional bandwidth measurement equipment, such as the angular vibration table, can only provide angular vibrations of hundreds of hertz and cannot meet the measurement needs of a high bandwidth gyro. We propose an approach, with which a signal of several thousand hertz can be provided and can measure a high bandwidth of I-FOGs. The bandwidth measurement approach is based on the axial magnetic sensitivity. We present the measurement principle, derive the axial magnetic sensitivity expression of the fiber coil in I-FOGs, and demonstrate the bandwidth measuring system. With this system, the bandwidth of an I-FOG is measured and the experimental result shows that the bandwidth is ∼10 kHz. It is proved that this new, to the best of our knowledge, approach is capable of testing the bandwidth of the I-FOG at ultrahigh frequencies.

High-performance Si@C anode for lithium-ion batteries enabled by a novel structuring strategy.

Si anode has drawn growing attention because of its features of large specific capacity, low electrochemical potential, and high natural abundance. However, it suffers from severe electrochemical irreversibility due to its large volume change during cycling. In spite of the achievement of improved electrochemical performance after compositing with carbon materials, most of the reported Si/C composite anodes lack a simple preparation process. To obtain a promising Si-based anode material, both simple preparation process and improved performance are necessary. Herein, inspired by the structure of shock proof foam, a novel structure of Si-based composite (Si@FeNO@P), consisting of Si nanoparticles embedded within a highly graphitized Fe3C/Fe3O4 hybrid nanoparticle-interspersed foam-like porous carbon matrix, has been constructed using a simple method, consisting of simple mixing, drying, and carbonization processes. Thus, the well-designed composite structure effectively mitigates issues resulting from volumetric change of the Si during cycle and hence improves its performance significantly. The research results confirm outstanding performance of the Si@FeNO@P anode in the aspects of cycle durability, specific capacity, and rate capability, with 1116.1 (250th cycle), 858.1 (500th cycle), and 503.1 (500th cycle) mA h g-1 at 100, 1000, and 5000 mA g-1, respectively. By comparing the performance and structure of Si@FeNO@P with other control samples, it was substantiated that the outstanding performances of the Si@FeNO@P anode depend on the synergistic effects of the well-designed unique carbon matrix, conductive Fe3C, and Fe3O4-in situ derived metallic Fe nanoparticles during cycling. The outstanding electrochemical performance and simple preparation route make the Si@FeNO@P anode promising for lithium-ion battery applications. This work also gives useful insights into the development of high-performance Si-based anodes with simple practical methods.

Laccase-Induced Gelation of Sugar Beet Pectin-Curcumin Nanocomplexes Enhanced by Genipin Crosslinking.

Research on the use of polysaccharides as hydrophobic bioactive carriers instead of proteins is still scarce. Sugar beet pectin (SBP) contains a small amount of protein and is a potential carrier for loading curcumin. In this work, SBP encapsulation, genipin crosslinking, and laccase-induced gelation were used to develop novel jelly food and improve the stability of curcumin without the incorporation of oil. By mixing the SBP solution (40 mg/mL) with curcumin powder (25 mg/mL SBP solution), an SBP-curcumin complex (SBP-Cur) was fabricated with a loading amount of 32 mg/g SBP, and the solubility of curcumin improved 116,000-fold. Fluorescence spectroscopy revealed that hydrophobic interactions drove the complexation of curcumin and SBP. Crosslinked by genipin (10 mM), SBP-Cur showed a dark blue color, and the gel strength of laccase-catalyzed gels was enhanced. Heating and UV radiation tests suggested that the genipin crosslinking and gelation strategies substantially improved the stability of curcumin. Because of the unique UV-blocking capacity of blue pigment, crosslinked samples retained 20% more curcumin than control samples. With the enhanced stability of curcumin, the crosslinked SBP-curcumin complexes could be a functional food ingredient used in functional drinks, baked food, and jelly food.

Endothelial cell-released extracellular vesicles trigger pyroptosis and vascular inflammation to induce atherosclerosis through the delivery of HIF1A-AS2.

Extracellular vesicles (EVs) possess great potential in the modulation of cardiovascular diseases. Our current work intended to assay the clinical significance of endothelial cell (EC)-derived EVs in atherosclerosis (AS). Expression of HIF1A-AS2, miR-455-5p, and ESRRG in plasma from AS patients and mice and EVs from ox-LDL-treated ECs was measured. Interactions among HIF1A-AS2, miR-455-5p, ESRRG, and NLRP3 were analyzed. Next, EVs were co-cultured with ECs, and ectopic expression and depletion experimentations of HIF1A-AS2, miR-455-5p, ESRRG, and/or NLRP3 were carried out to assay their roles in pyroptosis and inflammation of ECs in AS. At last, the effects of HIF1A-AS2 shuttled by EC-derived EVs on EC pyroptosis and vascular inflammation in AS were verified in vivo. HIF1A-AS2 and ESRRG were highly expressed, while miR-455-5p was poorly expressed in AS. HIF1A-AS2 could sponge miR-455-5p to elevate the expression of ESRRG and NLRP3. Both in vitro and in vivo experiments revealed that ECs-derived EVs carrying HIF1A-AS2 induced the pyroptosis and vascular inflammation of ECs to promote the progression of AS by sponging miR-455-5p via ESRRG/NLRP3. HIF1A-AS2 shuttled by ECs-derived EVs can accelerate the progression of AS by downregulating miR-455-5p and upregulating ESRRG and NLRP3.