The oxidized phospholipid PGPC impairs endothelial function by promoting endothelial cell ferroptosis via FABP3.

Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of phospholipid oxidation play a key role in atherosclerosis. 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) is a phospholipid oxidation product present in atherosclerotic lesions. It remains unclear whether PGPC causes atherosclerosis by inducing endothelial cell ferroptosis. In this study, human umbilical vein endothelial cells (HUVECs) were treated with PGPC. Intracellular levels of ferrous iron, lipid peroxidation, superoxide anions (O2•-), and glutathione were detected, and expression of fatty acid binding protein-3 (FABP3), glutathione peroxidase 4 (GPX4), and CD36 were measured. Additionally, the mitochondrial membrane potential (MMP) was determined. Aortas from C57BL6 mice were isolated for vasodilation testing. Results showed that PGPC increased ferrous iron levels, the production of lipid peroxidation and O2•-, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.

Crystallographic and biochemical analyses of a far-red allophycocyanin to address the mechanism of the super-red-shift.

Far-red absorbing allophycocyanins (APC), identified in cyanobacteria capable of FRL photoacclimation (FaRLiP) and low-light photoacclimation (LoLiP), absorb far-red light, functioning in energy transfer as light-harvesting proteins. We report an optimized method to obtain high purity far-red absorbing allophycocyanin B, AP-B2, of Chroococcidiopsis thermalis sp. PCC7203 by synthesis in Escherichia coli and an improved purification protocol. The crystal structure of the trimer, (PCB-ApcD5/PCB-ApcB2)3, has been resolved to 2.8 Å. The main difference to conventional APCs absorbing in the 650-670 nm range is a largely flat chromophore with the co-planarity extending, in particular, from rings BCD to ring A. This effectively extends the conjugation system of PCB and contributes to the super-red-shifted absorption of the α-subunit (λmax = 697 nm). On complexation with the ß-subunit, it is even further red-shifted (λmax, absorption = 707 nm, λmax, emission = 721 nm). The relevance of ring A for this shift is supported by mutagenesis data. A variant of the α-subunit, I123M, has been generated that shows an intense FR-band already in the absence of the ß-subunit, a possible model is discussed. Two additional mechanisms are known to red-shift the chromophore spectrum: lactam-lactim tautomerism and deprotonation of the chromophore that both mechanisms appear inconsistent with our data, leaving this question unresolved.

Gut microbiota modulation: a narrative review on a novel strategy for prevention and alleviation of ovarian aging.

The global rise in life expectancy corresponds with a delay in childbearing age among women. Ovaries, seen as the chronometers of female physiological aging, demonstrate features of sped up aging, evidenced by the steady decline in both the quality and quantity of ovarian follicles from birth. The multifaceted pathogenesis of ovarian aging has kindled intensive research interest from the biomedical and pharmaceutical sectors. Novel studies underscore the integral roles of gut microbiota in follicular development, lipid metabolism, and hormonal regulation, forging a nexus with ovarian aging. In this review, we outline the role of gut microbiota in ovarian function (follicular development, oocyte maturation, and ovulation), compile and present gut microbiota alterations associated with age-related ovarian aging. We also discuss potential strategies for alleviating ovarian aging from the perspective of gut microbiota, such as fecal microbiota transplantation and probiotics.

Appraisal of evidence reliability and applicability of Paxlovid as treatment for SARS-COV-2 infection: A systematic review.

This study aimed to clarify the beneficial effect and the clinical application value of Paxlovid in the treatment of coronavirus disease-19 (COVID-19) through a systematic review. Databases including PubMed, Cochrane Library, Chinese Clinical Trial Registry, and ClinicalTrials.gov were systematically searched for interventional or observational studies on the efficacy and safety of Paxlovid in the treatment of SARS-COV-2. The relative and absolute effect sizes for the outcomes were calculated based on the data reported in the original intervention literature. The external applicability of the evidence was analysed in terms of clinical application scenarios, patient willingness, and cost utility. One interventional and three observational studies were conducted. Four studies published in 2022, had participation sample sizes ranging 1780-109,254. Based on the randomised controlled trial data, the risk of all-cause mortality, all-cause death, and hospitalisation was significantly reduced in the Paxlovid group. Serious adverse events were reduced during the study. Based on observational studies, Paxlovid can significantly reduce the risk of death and hospitalisation in older patients with COVID-19 (moderate certainty) and improve in-hospital disease progression, composite disease progression, and viral load (low certainty). Paxlovid did not improve the outcomes of death and hospitalisation (low certainty) in patients aged <65 years. As per the economic utility analysis, the economic cost of reducing one death dramatically decreased with increasing age. Early use of Paxlovid in the older adult population with COVID-19 is beneficial. However, in the setting of limited resources, Paxlovid should be prioritised for older patients.

Clinicopathological characteristics and diagnostic accuracy of BRAF mutations in ameloblastoma: A Bayesian network analysis.

OBJECTIVE: This Bayesian network meta-analysis was performed to analyze the associations between clinicopathological characteristics and BRAF mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy. MATERIALS AND METHODS: Four electronic databases were searched from 2010 to 2024. The search terms used were specific to BRAF and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of BRAF mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation. RESULTS: A total of 937 AM patients from 20 studies were included. The pooled prevalence of BRAF mutations in AM patients was 72%. According to the Bayesian network analysis, BRAF mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2-4.5), mandible site (OR, 3.6; 95% CrI: 2.7-5.2), and unicystic (OR, 1.6; 95% CrI: 1.1-2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups. CONCLUSIONS: The incidence, risk, and diagnostic accuracy of BRAF mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis.

CT-based radiomics analysis of different machine learning models for differentiating gnathic fibrous dysplasia and ossifying fibroma.

OBJECTIVE: In this study, our aim was to develop and validate the effectiveness of diverse radiomic models for distinguishing between gnathic fibrous dysplasia (FD) and ossifying fibroma (OF) before surgery. MATERIALS AND METHODS: We enrolled 220 patients with confirmed FD or OF. We extracted radiomic features from nonenhanced CT images. Following dimensionality reduction and feature selection, we constructed radiomic models using logistic regression, support vector machine, random forest, light gradient boosting machine, and eXtreme gradient boosting. We then identified the best radiomic model using receiver operating characteristic (ROC) curve analysis. After combining radiomics features with clinical features, we developed a comprehensive model. ROC curve and decision curve analysis (DCA) demonstrated the models' robustness and clinical value. RESULTS: We extracted 1834 radiomic features from CT images, reduced them to eight valuable features, and achieved high predictive efficiency, with area under curves (AUC) exceeding 0.95 for all the models. Ultimately, our combined model, which integrates radiomic and clinical data, displayed superior discriminatory ability (AUC: training cohort 0.970; test cohort 0.967). DCA highlighted its optimal clinical efficacy. CONCLUSION: Our combined model effectively differentiates between FD and OF, offering a noninvasive and efficient approach to clinical decision-making.

[Mechanism of Puerariae Thomsonii Radix in treatment of mild dyslipidemia: based on clinical metabolomics and proteomics].

This study aims to explore the potential metabolic pathways and targets of Puerariae Thomsonii Radix in the clinical treatment of mild dyslipidemia. UPLC-Q-TOF-MS and EASY-nLC-timsTOF-Pro2 were employed to perform metabolomic and proteomic analyses of the plasma samples collected from the patients with mild dyslipidemia at baseline and after 12 weeks of treatment with Puerariae Thomsonii Radix. The multivariate statistical analysis was carried out for comparison between groups, and the correlation analysis was performed for the metabolites and proteins closely related to mild dyslipidemia with the blood lipid indexes. The possible pathways and targets for mitigating mild dyslipidemia were screened out by the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. The results showed that 56 differential metabolites and 78 differential proteins in the plasma of patients were associated with Puerariae Thomsonii Radix treatment. In addition, changes were detected for the proteins or metabolites(ApoB-100, 9,10-DHOME, GAPDH, PGK1, PGAM1, ENO1, etc.) involved in lipoprotein, lipid, and glucose metabolism and the proteins or metabolites(oxidized phospholipid, PLA2G7, LTA4H, etc.) related to inflammation and oxidative stress. Puerariae Thomsonii Radix may down-regulate the overexpression of ApoB-100, activate the peroxisome proliferator-activated receptor α/γ(PPARα/γ), promote the catabolism of fat and glycerol, and alleviate the oxidative stress mediated by oxidized phospholipids and leukotriene B4(LTB4) in the treatment of mild dyslipidemia.

Microglia are involved in regulating histamine-dependent and non-dependent itch transmissions with distinguished signal pathways.

Although itch and pain have many similarities, they are completely different in perceptual experience and behavioral response. In recent years, we have a deep understanding of the neural pathways of itch sensation transmission. However, there are few reports on the role of non-neuronal cells in itch. Microglia are known to play a key role in chronic neuropathic pain and acute inflammatory pain. It is still unknown whether microglia are also involved in regulating the transmission of itch sensation. In the present study, we used several kinds of transgenic mice to specifically deplete CX3CR1+ microglia and peripheral macrophages together (whole depletion), or selectively deplete microglia alone (central depletion). We observed that the acute itch responses to histamine, compound 48/80 and chloroquine were all significantly reduced in mice with either whole or central depletion. Spinal c-fos mRNA assay and further studies revealed that histamine and compound 48/80, but not chloroquine elicited primary itch signal transmission from DRG to spinal Npr1- and somatostatin-positive neurons relied on microglial CX3CL1-CX3CR1 pathway. Our results suggested that microglia were involved in multiple types of acute chemical itch transmission, while the underlying mechanisms for histamine-dependent and non-dependent itch transmission were different that the former required the CX3CL1-CX3CR1 signal pathway.

Confirmation of eosinophilic sialodochitis by terminal duct biopsy.

OBJECTIVE: To analyse the histopathological features of eosinophilic sialodochitis by using terminal duct biopsy. METHODS: Sixty-five patients with suspected eosinophilic sialodochitis and four with chronic obstructive sialadenitis were prospectively enrolled. Clinical features, laboratory tests and sialograms were comparatively analysed. Terminal duct biopsy of the parotid or submandibular glands was performed concomitantly with endoscopy-assisted duct dilatation to determine the histopathological features of eosinophilic sialodochitis. RESULTS: Based on eosinophil quantification, the samples of suspected patients were scored as 'definite', 'highly suspected' and 'negative' in 26 (40%), 15 (23.1%) and 24 (36.9%) cases, respectively. Gland types and peripheral blood eosinophil counts were significantly different among these three groups. The proportions of itching glands, mucus plug exudations and elevated immunoglobulin E levels were higher in the 'definite' group than in the other two groups; however, the intergroup differences were insignificant. The primary pathological features of eosinophilic sialodochitis were abundant eosinophils and lymphocytes infiltrated around the duct, degranulation of eosinophils, extensive fibrosis and scattered mastocytes. Periductal eosinophils were not found in cases of chronic obstructive sialadenitis. CONCLUSION: Our findings suggest that terminal duct biopsy is safe and valuable for the pathological confirmation of eosinophilic sialodochitis, and can be used simultaneously with endoscopy-assisted duct dilatation.

Low-dose phthalates promote breast cancer stem cell properties via the oncogene ΔNp63α and the Sonic hedgehog pathway.

BACKGROUND: The omnipresence of human phthalate (PAE) exposure is linked to various adverse health issues, including breast cancer. However, the effects of low-dose PAE exposure on breast cancer stem cells (BCSCs) and the underlying mechanism remain unexplored. METHODS: BCSCs from breast cancer cell lines (MDA-MB-231 and MCF-7) were enriched using a tumorsphere formation assay. Gene and protein expression was detected by measurement of quantitative real-time reverse transcription PCR, western blot, and immunofluorescence assays. Transient transfection assays were used to evaluate the involvement of Gli1, a signaling pathway molecule and ΔNp63α, an oncogene in influencing the PAE-induced characteristics of BCSCs. RESULTS: PAE (butylbenzyl phthalate, BBP; di-butyl phthalate, DBP; di-2-ethylhexyl phthalate, DEHP) exposure of 10-9 M significantly promoted the tumorsphere formation ability in BCSCs. Breast cancer spheroids with a 10-9 M PAE exposure had higher levels of BCSC marker mRNA and protein expression, activated sonic hedgehog (SHH) pathway, and increased mRNA and protein levels of an oncogene, ΔNp63α. Furthermore, suppression of the SHH pathway attenuated the effects of PAEs on BCSCs. And the overexpression of ΔNp63α enhanced PAE-induced characteristics of BCSCs, while low expression of ΔNp63α inhibited the promotion effects of PAEs on BCSCs and the SHH pathway. CONCLUSION: Low-dose PAE exposure promoted the stem cell properties of BCSCs in a ΔNp63α- and SHH-dependent manner. The influence of low-dose exposure of PAEs and its relevance for the lowest observed effect concentrations requires further investigation, and the precise underlying mechanism needs to be further explored.

DBDMH-Promoted Methylthiolation in DMSO: A Metal-Free Protocol to Methyl Sulfur Compounds with Multifunctional Groups.

Organic thioethers play an important role in the discovery of drugs and natural products. However, the green synthesis of organic sulfide compounds remains a challenging task. The convenient and efficient synthesis of 5-alkoxy-3-halo-4-methylthio-2(5H)-furanones from DMSO is performed via the mediation of 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), affording a facile route for the sulfur-functionalization of 3,4-dihalo-2(5H)-furanones under transition metal-free conditions. This new approach has demonstrated the functionalization of non-aromatic Csp2-X-type halides with unique structures containing C-X, C-O, C=O and C=C bonds. Compared with traditional synthesis methods using transition metal catalysts with ligands, this reaction has many advantages, such as the lower temperature, the shorter reaction time, the wide substrate range and good functional group tolerance. Notably, DMSO plays multiple roles, and is simultaneously used as an odorless methylthiolating reagent and safe solvent.

[Application of Deep Learning in Differential Diagnosis of Ameloblastoma and Odontogenic Keratocyst Based on Panoramic Radiographs].

Objective To evaluate the accuracy of different convolutional neural networks (CNN),representative deep learning models,in the differential diagnosis of ameloblastoma and odontogenic keratocyst,and subsequently compare the diagnosis results between models and oral radiologists. Methods A total of 1000 digital panoramic radiographs were retrospectively collected from the patients with ameloblastoma (500 radiographs) or odontogenic keratocyst (500 radiographs) in the Department of Oral and Maxillofacial Radiology,Peking University School of Stomatology.Eight CNN including ResNet (18,50,101),VGG (16,19),and EfficientNet (b1,b3,b5) were selected to distinguish ameloblastoma from odontogenic keratocyst.Transfer learning was employed to train 800 panoramic radiographs in the training set through 5-fold cross validation,and 200 panoramic radiographs in the test set were used for differential diagnosis.Chi square test was performed for comparing the performance among different CNN.Furthermore,7 oral radiologists (including 2 seniors and 5 juniors) made a diagnosis on the 200 panoramic radiographs in the test set,and the diagnosis results were compared between CNN and oral radiologists. Results The eight neural network models showed the diagnostic accuracy ranging from 82.50% to 87.50%,of which EfficientNet b1 had the highest accuracy of 87.50%.There was no significant difference in the diagnostic accuracy among the CNN models (P=0.998,P=0.905).The average diagnostic accuracy of oral radiologists was (70.30±5.48)%,and there was no statistical difference in the accuracy between senior and junior oral radiologists (P=0.883).The diagnostic accuracy of CNN models was higher than that of oral radiologists (P<0.001). Conclusion Deep learning CNN can realize accurate differential diagnosis between ameloblastoma and odontogenic keratocyst with panoramic radiographs,with higher diagnostic accuracy than oral radiologists.

Furanonyl amino acid derivatives as hemostatic drugs: design, synthesis and hemostasis performance.

Using 3,4-dihalo-2(5H)-furanones and easily available hemostatic drugs, such as tranexamic acid (TA), 4-aminomethylbenzoic acid (ABA), aminocaproic acid (AA) as starting materials, serial multi-functional molecules 2(5H)-furanonyl amino acids are designed by the combination of different pharmacophores, and successfully synthesized by a transition metal-free Michael addition-elimination reaction. The reaction is carried out under mild conditions with ethanol-dichloromethane as solvent and only stirring at room temperature for 24 h, and the yield can be up to 91%. All products are well characterized by infrared spectroscopy (IR), nuclear magnetic resonance (NMR), high-resolution mass spectra (HRMS). Ten typical target compounds among them are selected out for the experiments of hemostasis performance by the evaluation of in vitro clot formation model and liver hemorrhage model. The test results show that, their hemostasis effect is better than the original drugs. Especially the target compound G, a TA derivative from 5-borneoloxy-3,4-dibromo-2(5H)-furanone, has the best hemostasis effect among all the tested compounds. These obtained target molecules are expected to be used as multi-functional hemostatic drugs.

Orthokeratinized odontogenic cysts: A clinicopathologic study of 159 cases and molecular evidence for the absence of PTCH1 mutations.

BACKGROUND: Orthokeratinized odontogenic cyst (OOC), a newly designated entity of odontogenic cysts, is an intraosseous jaw cyst that is entirely or predominantly lined by orthokeratinized squamous epithelium. The aim of this study was to report a large series of OOC to substantiate its clinicopathologic profiles and to investigate PTCH1 mutations in OOCs. METHOD: The clinicopathologic features of 167 OOCs from 159 patients were analyzed and the immunohistochemical expression of markers related to cell differentiation and proliferation was evaluated. Furthermore, PTCH1 mutations were analyzed in 14 fresh samples of OOC. RESULTS: OOCs occurred mostly in the third and fourth decades (60.4%) with a male predilection (66.7%). The lesions developed more often in the mandible than maxilla, primarily in the posterior mandible and ramus. Eight patients (5.0%) showed multiple locations of either bilateral posterior mandible (n = 6) or both the maxilla and mandible. Radiographically, the majority of OOCs (91.2%) showed a well-demarcated, unilocular radiolucency with 14 multilocular cases (8.8%). A follow-up of 131 patients (123 treated by enucleation with or without marsupialization and eight by peripheral ostectomy) revealed no recurrence during an average period of 4.56 years after surgery. Immunohistochemistry indicated lower proliferative activity and a varying epithelial differentiation pattern in OOC compared with odontogenic keratocysts (OKC). No PTCH1 mutation was detected, except for three known single nucleotide polymorphisms. CONCLUSION: The clinicopathological and molecular differences between OOC and OKC justified their separation, and unlike OKCs, OOCs did not harbor PTCH1 mutations, suggesting different pathogenesis underlying these two jaw cysts.

[Chemical pattern recognition of Atractylodes chinensis from different producing areas and establishment of quantitative analysis of multi-components by single marker (QAMS) method for four components].

This study established the fingerprint and combined it with chemical pattern recognition to evaluate the quality of Atractylodes chinensis samples from different producing areas and then employed the quantitative analysis of multi-components by single marker(QAMS) method to verify the feasibility and applicability of the established method in the quality evaluation of A. chinensis. The fingerprints of A. chinensis samples were constructed via high performance liquid chromatography(HPLC) to evaluate the inter-batch consistency. With the quality control component atractylodin as the internal reference, the relative correction factors(RCFs) were established for atractylenolide Ⅰ, atractylenolide Ⅲ, and ß-eudesmol and the content of the four components was calculated. The external standard method was used to verify the accuracy of QAMS method. The quality of A. chinensis was further evaluated by similarity analysis, clustering analysis, and principal component analysis. The fingerprints of 13 batches of samples were calibrated with 21 common peaks, and 4 common peaks were identified with the similarities all above 0.9. The RCFs established with atractylodin as the internal reference represented good reproducibility under different experimental conditions. Specifically, the RCFs of atractylenolide Ⅰ, atractylenolide Ⅲ, and ß-eudesmol in A. chinensis were 2.091, 4.253, and 6.010, respectively. QAMS and ESM showed no significant difference in the results, indicating that the QAMS method established in this study was stable and reliable. Thus, HPLC fingerprint combined with QAMS can be used for the quality evaluation of A. chinensis, providing a basis for comprehensive and rapid quality evaluation of A. chinensis.

Efficacy of intermittent iron supplementation in children with mild iron-deficiency anemia. / å„¿ç«¥è½»åº¦ç¼ºé“æ€§è´«è¡€é—´æ­‡è¡¥é“ç–—æ³•çš„æœ‰æ•ˆæ€§ç ”ç©¶.

OBJECTIVES: To study the efficacy of intermittent iron supplementation in children with mild iron-deficiency anemia. METHODS: A total of 147 children with mild iron-deficiency anemia were enrolled in this prospective study. They were divided into an intermittent iron supplementation group (n=83) and a conventional iron supplementation group (n=64). The levels of hemoglobin were measured before treatment and after 1 and 3 months of treatment. The treat response rate and the incidence rate of adverse drug reactions were compared between the two groups. RESULTS: Both groups had a significant increase in the level of hemoglobin after iron supplementation (P<0.05). After 1 month of treatment, the conventional iron supplementation group had a significantly higher treatment response rate than the intermittent iron supplementation group (61% vs 42%, P<0.05). After 3 months of treatment, there was no significant difference in the treatment response between the two groups (86% vs 78%, P>0.05). The incidence rate of adverse drug reactions in the conventional iron supplementation group was significantly higher than that in the intermittent iron supplementation group (25% vs 8%, P<0.05). CONCLUSIONS: For children with mild iron-deficiency anemia, although intermittent iron supplementation is inferior to conventional iron supplementation in the short-term efficacy, there is no significant difference in the long-term efficacy between the two methods, and compared with conventional iron supplementation, intermittent iron supplementation can reduce the incidence of adverse drug reactions, alleviate family financial burdens, and improve treatment compliance of children, thus holding promise for clinical application.

The role of lyases, NblA and NblB proteins and bilin chromophore transfer in restructuring the cyanobacterial light-harvesting complex‡.

Phycobilisomes are large light-harvesting complexes attached to the stromal side of thylakoids in cyanobacteria and red algae. They can be remodeled or degraded in response to changing light and nutritional status. Both the core and the peripheral rods of phycobilisomes contain biliproteins. During biliprotein biosynthesis, open-chain tetrapyrrole chromophores are attached covalently to the apoproteins by dedicated lyases. Another set of non-bleaching (Nb) proteins has been implicated in phycobilisome degradation, among them NblA and NblB. We report in vitro experiments with lyases, biliproteins and NblA/B which imply that the situation is more complex than currently discussed: lyases can also detach the chromophores and NblA and NblB can modulate lyase-catalyzed binding and detachment of chromophores in a complex fashion. We show: (i) NblA and NblB can interfere with chromophorylation as well as chromophore detachment of phycobiliprotein, they are generally inhibitors but in some cases enhance the reaction; (ii) NblA and NblB promote dissociation of whole phycobilisomes, cores and, in particular, allophycocyanin trimers; (iii) while NblA and NblB do not interact with each other, both interact with lyases, apo- and holo-biliproteins; (iv) they promote synergistically the lyase-catalyzed chromophorylation of the ß-subunit of the major rod component, CPC; and (v) they modulate lyase-catalyzed and lyase-independent chromophore transfers among biliproteins, with the core protein, ApcF, the rod protein, CpcA, and sensory biliproteins (phytochromes, cyanobacteriochromes) acting as potential traps. The results indicate that NblA/B can cooperate with lyases in remodeling the phycobilisomes to balance the metabolic requirements of acclimating their light-harvesting capacity without straining the overall metabolic economy of the cell.

Upregulation of α enolase (ENO1) crotonylation in colorectal cancer and its promoting effect on cancer cell metastasis.

Lysine crotonylation (Kcr) is a newly identified protein translational modification and is involved in major biological processes including glycolysis, but its role in colorectal cancer (CRC) is unknown. Here, we found that the Kcr of α enolase (ENO1) was significantly elevated in human CRC tissues compared with the paratumoral tissues. CREB-binding protein (CBP) functioned as a crotonyltranferase of ENO1, and SIRT2 was involved in the decrotonylation of ENO1. Using quantitative mass spectrometry for crotonylomics analysis, we further found that K420 was the main Kcr site of ENO1 and ENO1 K420 Kcr promoted the growth, migration, and invasion of CRC cells in vitro by enhancing the activity of ENO1 and regulating the expression of tumor-associated genes. Our study reveals an important mechanism by which ENO1 regulates CRC through crotonylation.

The evidence of a macrophage barrier in the xenotransplantation of human hematopoietic stem cells to severely immunodeficient rats.

BACKGROUND: The human-to-rat hematopoietic stem cell transplantation (HSCT) model is rare, unlike its human-to-mouse counterpart. The rat models are desired, especially in areas of physiology, toxicology, and pharmacology. In addition to lymphocytes, macrophages are also considered to be important for xenotransplantation. We generated a rat xenotransplantation model to prove the role of macrophages as a xenotransplantation barrier. METHODS: Immunodeficiency in SRG rats, which are Sprague-Dawley (SD) rats lacking Rag2 and Il2rg, was confirmed by flow cytometry and spleen immunostaining. Human umbilical cord blood was collected after scheduled cesarean section at the University of Tsukuba Hospital. Cord blood mononuclear cells (CB-MNCs) were transplanted into the SRG rats administered several injections of clodronate liposome (CL), which cause macrophage depletion. Survival of human cells was observed by flow cytometry. Rat macrophage phagocytosis assay was performed to check the species-specific effects of rat macrophages on injected human/rat blood cells. RESULTS: SRG rats were deficient in T/B/NK cells. Without CL pretreatment, human CB-MNCs were removed from SRG rats within 7 hours after transplantation. The rats pretreated with CL could survive after transplantation. Prolonged survival for more than 4 weeks was observed only following a one-time CL injection. Rat macrophages had a species-specific potential for the phagocytosis of human blood cells in vivo. CONCLUSION: In human-to-rat HSCT, the short period of early macrophage control, leading to macrophage immunotolerance, is important for engraftment. The generated model can be useful for the creation of future xenotransplantation models or other clinical research.

Synthesis of N-2(5H)-furanonyl sulfonyl hydrazone derivatives and their biological evaluation in vitro and in vivo activity against MCF-7 breast cancer cells.

A series of (E)-N-2(5H)-furanonyl sulfonyl hydrazone derivatives have been rationally designed and efficiently synthesized by one-pot reaction with good yields for the first time. This green approach with wide substrate range and good selectivity can be achieved at room temperature in a short time in the presence of metal-free catalyst. The cytotoxic activities against three human cancer cell lines of all newly obtained compounds have been evaluated by MTT assay. Among them, compound 5 k exhibits high cytotoxic activity against MCF-7 human breast cancer cells with an IC50 value of 14.35 µM. The cytotoxic mechanism may involve G2/M phase arrest pathway, which is probably caused by activating DNA damage. Comet test and immunofluorescence results show that compound 5 k can induce DNA damage in time- and dose-dependent manner. Importantly, 5 k also can effectively inhibit the proliferation of MCF-7 cells and angiogenesis in the zebrafish xenograft model. It is potential to further develop N-2(5H)-furanonyl sulfonyl hydrazone derivatives as potent drugs for breast cancer treatment with higher cytotoxic activity by modifying the structure of the compound.