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1.
Carbohydr Res ; 541: 109167, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38823063

ABSTRACT

This paper describes a mild and efficient catalytic deprotection method for isopropylidene ketals and benzylidene acetals using AcOH/H2O/DME(1,2-Dimethoxyethane). The method effectively removes ketal and acetal protecting groups from 2-deoxyglycosides which are prone to hydrolysis under acidic conditions. Moreover, it enables the selective removal of the terminal ketal over an internal one.

2.
Endocr Res ; : 1-7, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830240

ABSTRACT

BACKGROUND: As the high-risk stage of diabetes, the role of prediabetes in the development of hepatocellular carcinoma (HCC) remains unclear. To address this knowledge gap, we undertook a meta-analysis to investigate the potential association between the prediabetic stage and HCC. METHODS: In this study, two independent investigators conducted a comprehensive search for relevant articles published up until May 2023 in several databases, including PubMed, Web of Science, Medline, EMBASE, and Google Scholar. The results were then summarized using STATA 12.0 software. RESULTS: Our analysis included a total of 6 cohort studies involving 1,490,752 participants, as well as 1 case-control study with 220 participants. The research aimed to examine the association between prediabetes and the risk of HCC. Our meta-analysis revealed that prediabetes was significantly associated with an elevated risk of HCC (odds ratio (OR)/relative risk (RR) = 1.25, 95% confidence interval (CI) 1.06 to 1.48, I2 = 57.2%, p = 0.012), using a random-effects model. Moreover, four cohort studies, encompassing 1,362,847 participants, explored the relationship between prediabetes and HCC mortality. The meta-analysis showed that prediabetes was associated with a higher mortality rate of HCC, also utilizing a random-effects model (hazard ratio (HR) = 1.36, 95% CI 1.02 to 1.81, I2 = 55.8%, p = 0.060). CONCLUSIONS: Overall, our findings highlight a significant association between prediabetes and an increased risk of HCC and suggest that prediabetes may also contribute to higher mortality rates among HCC patients.

3.
Adv Healthc Mater ; : e2304477, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38709914

ABSTRACT

Immunotherapy based on nanoplatforms is a promising approach to treat cancer and infectious diseases, and it has achieved considerable progress in clinical practices. Cell membrane-based nanoplatforms endow nanoparticles with versatile characteristics, such as half-life extension, targeting ability, and immune-system regulation. However, monotypic cell membrane usually fails to provoke strong immune response for immunotherapy while maintaining good biosafety. The integration of different cell-membrane types provides a promising approach to construct multifunctional nanoplatforms for improved immunotherapeutic efficacy by enhancing immunogenicity or targeting function, evading immune clearance, or combining with other therapeutic modalities. In this review, the design principles, preparation strategies, and applications of hybrid cell membrane-based nanoplatforms for cancer and infection immunotherapy are first discussed. Furthermore, the challenges and prospects for the potential clinical translation of hybrid cell membrane-based nanoplatforms are discussed.

4.
Acta Pharmacol Sin ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750074

ABSTRACT

Hypoxia-ischemia (HI) is one of the main causes of neonatal brain injury. Mitophagy has been implicated in the degradation of damaged mitochondria and cell survival following neonatal brain HI injury. Pleckstrin homology-like domain family A member 1 (PHLDA1) plays vital roles in the progression of various disorders including the regulation of oxidative stress, the immune responses and apoptosis. In the present study we investigated the role of PHLDA1 in HI-induced neuronal injury and further explored the mechanisms underlying PHLDA1-regulated mitophagy in vivo and in vitro. HI model was established in newborn rats by ligation of the left common carotid artery plus exposure to an oxygen-deficient chamber with 8% O2 and 92% N2. In vitro studies were conducted in primary hippocampal neurons subjected to oxygen and glucose deprivation/-reoxygenation (OGD/R). We showed that the expression of PHLDA1 was significantly upregulated in the hippocampus of HI newborn rats and in OGD/R-treated primary neurons. Knockdown of PHLDA1 in neonatal rats via lentiviral vector not only significantly ameliorated HI-induced hippocampal neuronal injury but also markedly improved long-term cognitive function outcomes, whereas overexpression of PHLDA1 in neonatal rats via lentiviral vector aggravated these outcomes. PHLDA1 knockdown in primary neurons significantly reversed the reduction of cell viability and increase in intracellular reactive oxygen species (ROS) levels, and attenuated OGD-induced mitochondrial dysfunction, whereas overexpression of PHLDA1 decreased these parameters. In OGD/R-treated primary hippocampal neurons, we revealed that PHLDA1 knockdown enhanced mitophagy by activating FUNDC1, which was abolished by FUNDC1 knockdown or pretreatment with mitophagy inhibitor Mdivi-1 (25 µM). Notably, pretreatment with Mdivi-1 or the knockdown of FUNDC1 not only increased brain infarct volume, but also abolished the neuroprotective effect of PHLDA1 knockdown in HI newborn rats. Together, these results demonstrate that PHLDA1 contributes to neonatal HI-induced brain injury via inhibition of FUNDC1-mediated neuronal mitophagy.

6.
Org Biomol Chem ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775030

ABSTRACT

Metabolic glycoengineering provides a powerful tool to label proteins with chemical tags for cell imaging and protein enrichment. The structures of per-O-acetylation on unnatural sugars facilitate membrane permeability and increase cellular uptake and are widely used for metabolic glycan labeling. However, unexpected S-glyco modification was discovered via a non-enzymatic reaction with protein cysteines, which was initially conducted with the hydrolysis of anomeric acetate by esterase. Herein, we synthesized a series of GalNAz derivatives that were protected with various lengths of short-chain fatty acid, including acetate, propionate, butyrate, valerate and pivalate, to detect differences in labeling efficiencies and occurrence of S-glyco modification. Our results demonstrate that all the GalNAz derivatives could effectively label proteins in HeLa cells, except the pivalate group. Of note, But4GalNAz exhibited excellent labeling abilities compared with Ac4GalNAz from the results for western blot, flow cytometry and confocal laser scanning microscopy. Moreover, the results for the S-glyco-modification assay by western blot and chemoproteomic analysis indicated that But4GalNAz generated negligible unexpected labeling signals compared to Ac4GalNAz. Our study uncovers the distinct labeling efficiency of different protected groups on unnatural sugars, which provides an alternative strategy to explore novel glycan probes.

7.
Int J Med Robot ; 20(3): e2634, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38767083

ABSTRACT

BACKGROUND: Reducing the annotation burden is an active and meaningful area of artificial intelligence (AI) research. METHODS: Multiple datasets for the segmentation of two landmarks were constructed based on 41 257 labelled images and 6 different microsurgical scenarios. These datasets were trained using the multi-stage transfer learning (TL) methodology. RESULTS: The multi-stage TL enhanced segmentation performance over baseline (mIOU 0.6892 vs. 0.8869). Besides, Convolutional Neural Networks (CNNs) achieved a robust performance (mIOU 0.8917 vs. 0.8603) even when the training dataset size was reduced from 90% (30 078 images) to 10% (3342 images). When directly applying the weight from one certain surgical scenario to recognise the same target in images of other scenarios without training, CNNs still obtained an optimal mIOU of 0.6190 ± 0.0789. CONCLUSIONS: Model performance can be improved with TL in datasets with reduced size and increased complexity. It is feasible for data-based domain adaptation among different microsurgical fields.


Subject(s)
Microsurgery , Neural Networks, Computer , Humans , Microsurgery/methods , Artificial Intelligence , Image Processing, Computer-Assisted/methods , Algorithms , Otorhinolaryngologic Surgical Procedures/methods , Machine Learning , Surgery, Computer-Assisted/methods , Anatomic Landmarks
8.
J Med Chem ; 67(10): 8296-8308, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38739678

ABSTRACT

Platinum-drug-based chemotherapy in clinics has achieved great success in clinical malignancy therapy. However, unpredictable off-target toxicity and the resulting severe side effects in the treatment are still unsolved problems. Although metabolic glycan labeling-mediated tumor-targeted therapy has been widely reported, less selective metabolic labeling in vivo limited its wide application. Herein, a novel probe of B-Ac3ManNAz that is regulated by reactive oxygen species in tumor cells is introduced to enhance the recognition and cytotoxicity of DBCO-modified oxaliplatin(IV) via bioorthogonal chemistry. B-Ac3ManNAz was synthesized from Ac4ManNAz by incorporation with 4-(hydroxymethyl) benzeneboronic acid pinacol ester (HBAPE) at the anomeric position, which is confirmed to be regulated by ROS and could robustly label glycans on the cell surface. Moreover, N3-treated tumor cells could enhance the tumor accumulation of DBCO-modified oxaliplatin(IV) via click chemistry meanwhile reduce the off-target distribution in normal tissue. Our strategy provides an effective metabolic precursor for tumor-specific labeling and targeted cancer therapies.


Subject(s)
Antineoplastic Agents , Oxaliplatin , Polysaccharides , Prodrugs , Reactive Oxygen Species , Prodrugs/chemistry , Prodrugs/pharmacology , Prodrugs/chemical synthesis , Oxaliplatin/pharmacology , Oxaliplatin/chemistry , Humans , Reactive Oxygen Species/metabolism , Polysaccharides/chemistry , Polysaccharides/metabolism , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Mice , Cell Line, Tumor , Mice, Inbred BALB C , Mice, Nude
9.
Sci Adv ; 10(14): eadk9754, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38578994

ABSTRACT

The lack of bacterial-targeting function in antibiotics and their prophylactic usage have caused overuse of antibiotics, which lead to antibiotic resistance and inevitable long-term toxicity. To overcome these issues, we develop neutrophil-bacterial hybrid cell membrane vesicle (HMV)-coated biofunctional lipid nanoparticles (LNP@HMVs), which are designed to transport antibiotics specifically to bacterial cells at the infection site for the effective treatment and prophylaxis of bacterial infection. The dual targeting ability of HMVs to inflammatory vascular endothelial cells and homologous Gram-negative bacterial cells results in targeted accumulation of LNP@HMVs in the site of infections. LNP@HMVs loaded with the antibiotic norfloxacin not only exhibit enhanced activity against planktonic bacteria and bacterial biofilms in vitro but also achieve potent therapeutic efficacy in treating both systemic infection and lung infection. Furthermore, LNP@HMVs trigger the activation of specific humoral and cellular immunity to prevent bacterial infection. Together, LNP@HMVs provide a promising strategy to effectively treat and prevent bacterial infection.


Subject(s)
Bacterial Infections , Nanoparticles , Humans , Endothelial Cells , Bacterial Infections/drug therapy , Bacterial Infections/prevention & control , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Liposomes
10.
Front Med (Lausanne) ; 11: 1337669, 2024.
Article in English | MEDLINE | ID: mdl-38651056

ABSTRACT

The tracheal Y-shaped stent is mainly used for the treatment of critical patients with airway stenosis or esophagotracheal fistula near carina. A novel method for precise implantation of Y-shaped tracheal stents was developed using double-lumen endotracheal intubation and flexible bronchoscopy. This approach aims to address the limitations associated with X-ray or rigid bronchoscopy guidance, such as operational difficulties and the risk of inaccurate stent placement leading to implantation failure or suffocation. With this new technique, 13 tracheal Y-shaped stents were successfully implanted. This method shows promise in reducing the complexity of stent implantation and facilitating timely treatment for patients in need. Additionally, it has the potential to update current operating standards and guidelines for this procedure.

11.
Proc Natl Acad Sci U S A ; 121(16): e2315123121, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38602915

ABSTRACT

Pulmonary arterial hypertension (PAH) is characterized by stenosis and occlusions of small pulmonary arteries, leading to elevated pulmonary arterial pressure and right heart failure. Although accumulating evidence shows the importance of interleukin (IL)-6 in the pathogenesis of PAH, the target cells of IL-6 are poorly understood. Using mice harboring the floxed allele of gp130, a subunit of the IL-6 receptor, we found substantial Cre recombination in all hematopoietic cell lineages from the primitive hematopoietic stem cell level in SM22α-Cre mice. We also revealed that a CD4+ cell-specific gp130 deletion ameliorated the phenotype of hypoxia-induced pulmonary hypertension in mice. Disruption of IL-6 signaling via deletion of gp130 in CD4+ T cells inhibited phosphorylation of signal transducer and activator of transcription 3 (STAT3) and suppressed the hypoxia-induced increase in T helper 17 cells. To further examine the role of IL-6/gp130 signaling in more severe PH models, we developed Il6 knockout (KO) rats using the CRISPR/Cas9 system and showed that IL-6 deficiency could improve the pathophysiology in hypoxia-, monocrotaline-, and Sugen5416/hypoxia (SuHx)-induced rat PH models. Phosphorylation of STAT3 in CD4+ cells was also observed around the vascular lesions in the lungs of the SuHx rat model, but not in Il6 KO rats. Blockade of IL-6 signaling had an additive effect on conventional PAH therapeutics, such as endothelin receptor antagonist (macitentan) and soluble guanylyl cyclase stimulator (BAY41-2272). These findings suggest that IL-6/gp130 signaling in CD4+ cells plays a critical role in the pathogenesis of PAH.


Subject(s)
Hypertension, Pulmonary , Interleukin-6 , Animals , Mice , Rats , CD4-Positive T-Lymphocytes/pathology , Cytokine Receptor gp130/genetics , Hypertension, Pulmonary/genetics , Hypertension, Pulmonary/pathology , Hypoxia/pathology , Interleukin-6/genetics , Pulmonary Artery/pathology
12.
Behav Neurosci ; 138(2): 85-93, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38661668

ABSTRACT

Rodent behavioral studies have largely focused on male animals, which has limited the generalizability and conclusions of neuroscience research. Working with humans and rodents, we studied sex effects during interval timing that requires participants to estimate an interval of several seconds by making motor responses. Interval timing requires attention to the passage of time and working memory for temporal rules. We found no differences between human females and males in interval timing response times (timing accuracy) or the coefficient of variance of response times (timing precision). Consistent with prior work, we also found no differences between female and male rodents in timing accuracy or precision. In female rodents, there was no difference in interval timing between estrus and diestrus cycle stages. Because dopamine powerfully affects interval timing, we also examined sex differences with drugs targeting dopaminergic receptors. In both female and male rodents, interval timing was delayed after administration of sulpiride (D2-receptor antagonist), quinpirole (D2-receptor agonist), and SCH-23390 (D1-receptor antagonist). By contrast, after administration of SKF-81297 (D1-receptor agonist), interval timing shifted earlier only in male rodents. These data illuminate sex similarities and differences in interval timing. Our results have relevance for rodent models of both cognitive function and brain disease by increasing representation in behavioral neuroscience. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Time Perception , Female , Male , Animals , Time Perception/physiology , Time Perception/drug effects , Humans , Sex Characteristics , Dopamine/metabolism , Rats , Receptors, Dopamine D2/metabolism , Sulpiride/pharmacology , Quinpirole/pharmacology , Dopamine Agonists/pharmacology , Dopamine Agonists/administration & dosage , Dopamine Antagonists/pharmacology , Dopamine Antagonists/administration & dosage , Adult , Reaction Time/drug effects , Reaction Time/physiology , Benzazepines/pharmacology , Young Adult , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D1/antagonists & inhibitors , Memory, Short-Term/physiology , Memory, Short-Term/drug effects
13.
Neurosci Lett ; 831: 137790, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38670522

ABSTRACT

OBJECTIVE: To explore degree centrality (DC) abnormalities in ischemic stroke patients and determine whether these abnormalities have potential value in understanding the pathological mechanisms of ischemic stroke patients. METHODS: Sixteen ischemic stroke patients and 22 healthy controls (HCs) underwent resting state functional magnetic resonance imaging (rs-fMRI) scanning, and the resulting data were subjected to DC analysis. Then we conducted a correlation analysis between DC values and neuropsychological test scores, including Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). Finally, extracted the abnormal DC values of brain regions and defined them as features for support vector machine (SVM) analysis. RESULTS: Compared with HCs, ischemic stroke patients showed increased DC in the bilateral supplementary motor area, and median cingulate and paracingulate gyri and decreased DC in the left postcentral gyrus, right calcarine fissure and surrounding cortex, lingual gyrus, and orbital parts of the right superior frontal gyrus and bilateral cuneus. Correlation analyses revealed that DC values in the right lingual gyrus, calcarine fissure and surrounding cortex, and orbital parts of the right superior frontal gyrus were positively correlated with the MMSE scores. The SVM classification of the DC values achieved an area under the curve (AUC) of 0.93, an accuracy of 89.47%. CONCLUSION: Our research results indicate that ischemic stroke patients exhibit abnormalities in the global connectivity mechanisms and patterns of the brain network. These abnormal changes may provide neuroimaging evidence for stroke-related motor, visual, and cognitive impairments, contribute to a deeper comprehension of the underlying pathophysiological mechanisms implicated in ischemic stroke.


Subject(s)
Brain , Ischemic Stroke , Magnetic Resonance Imaging , Humans , Male , Magnetic Resonance Imaging/methods , Female , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/physiopathology , Middle Aged , Brain/diagnostic imaging , Brain/physiopathology , Aged , Support Vector Machine , Rest , Brain Mapping/methods , Biomarkers
14.
Food Chem ; 450: 139411, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-38653055

ABSTRACT

Fresh strawberries are easily contaminated by microorganisms after picking. Therefore, how to effectively store and keep fresh strawberries has been a hot topic for scientists to study. In this study, we prepared a leaf shaped metal organic framework nanomaterial loaded with quercetin (Quercetin@ZIF-L) at first, which can achieve effective loading of quercetin (96%) within 45 min and has a controlled release effect under acidic conditions. In addition, by cleverly combining satellite graphene oxide @ silver nanoparticles (GO@AgNPs) with slow precipitation performance, Quercetin@ZIF-L/GO@AgNPs nanocomposite film with larger pore size and larger specific surface area was prepared by scraping method. The characterization data of water flux, retention rate, flux recovery rate and water vapor permeability show that the composite film has good physical properties. The experiment of film packaging showed that the fresh life of strawberry could be extended from 3 to 8 days, which significantly improved the storage and freshness cycle of strawberry. At the same time, the metal migration test proved that the residual amount of silver ion in strawberry met the EU standard and zinc ions are beneficial to the health, enriching the types of high-performance fresh-keeping materials and broadening the application.


Subject(s)
Food Packaging , Food Preservation , Fragaria , Graphite , Metal Nanoparticles , Nanocomposites , Quercetin , Silver , Fragaria/chemistry , Silver/chemistry , Nanocomposites/chemistry , Quercetin/chemistry , Metal Nanoparticles/chemistry , Graphite/chemistry , Food Preservation/methods , Food Preservation/instrumentation , Food Packaging/instrumentation , Metal-Organic Frameworks/chemistry , Temperature , Fruit/chemistry
15.
Anal Chem ; 96(19): 7497-7505, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38687987

ABSTRACT

Redox potential plays a key role in regulating intracellular signaling pathways, with its quantitative analysis in individual cells benefiting our understanding of the underlying mechanism in the pathophysiological events. Here, a metal organic framework (MOF)-functionalized SERS nanopotentiometer has been developed for the dynamic monitoring of intracellular redox potential. The approach is based on the encapsulation of zirconium-based MOF (Uio-66-F4) on a surface of gold-silver nanorods (Au-Ag NRs) that is modified with the newly synthesized redox-sensitive probe ortho-mercaptohydroquinone (HQ). Thanks to size exclusion of MOF as the chemical protector, the nanopotentiometer can be adapted to long-term use and possess high anti-interference ability toward nonredox species. Combining the superior fingerprint identification of SERS with the electrochemical activity of the quinone/hydroquinone, the nanopotentiometer shows a reversible redox responsivity and can quantify redox potential with a relatively wide range of -250-100 mV. Furthermore, the nanopotentiometer allows for dynamic visualization of intracellular redox potential changes induced by drugs' stimulation in a high-resolution manner. The developed approach would be promising for offering new insights into the correlation between redox potential and tumor proliferation-involved processes such as oxidative stress and hypoxia.


Subject(s)
Gold , Metal-Organic Frameworks , Oxidation-Reduction , Silver , Zirconium , Metal-Organic Frameworks/chemistry , Humans , Gold/chemistry , Silver/chemistry , Zirconium/chemistry , Spectrum Analysis, Raman , Nanotubes/chemistry , Hydroquinones/chemistry , Metal Nanoparticles/chemistry
16.
Biomaterials ; 309: 122573, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38677222

ABSTRACT

The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) gene editing has attracted extensive attentions in various fields, however, its clinical application is hindered by the lack of effective and safe delivery system. Herein, we reported a cationic micelle nanoparticle composed of cholesterol-modified branched small molecular PEI (PEI-CHO) and biodegradable PEG-b-polycarbonate block copolymer (PEG-PC), denoted as PEG-PC/PEI-CHO/pCas9, for the CRISPR/Cas9 delivery to realize genomic editing in cancer. Specifically, PEI-CHO condensed pCas9 into nanocomplexes, which were further encapsulated into PEG-PC nanoparticles (PEG-PC/PEI-CHO/pCas9). PEG-PC/PEI-CHO/pCas9 had a PEG shell, protecting DNA from degradation by nucleases. Enhanced cellular uptake of PEG-PC/PEI-CHO/pCas9 nanoparticles was observed as compared to that mediated by Lipo2k/pCas9 nanoparticles, thus leading to significantly elevated transfection efficiency after escaping from endosomes via the proton sponge effect of PEI. In addition, the presence of PEG shell greatly improved biocompatibility, and significantly enhanced the in vivo tumor retention of pCas9 compared to PEI-CHO/pCas9. Notably, apparent downregulation of GFP expression could be achieved both in vitro and in vivo by using PEG-PC/PEI-CHO/pCas9-sgGFP nanoparticles. Furthermore, PEG-PC/PEI-CHO/pCas9-sgMcl1 induced effective apoptosis and tumor suppression in a HeLa tumor xenograft mouse model by downregulating Mcl1 expression. This work may provide an alternative paradigm for the efficient and safe genome editing in cancer.


Subject(s)
CRISPR-Cas Systems , Gene Editing , Micelles , Nanoparticles , Gene Editing/methods , Nanoparticles/chemistry , CRISPR-Cas Systems/genetics , Animals , Humans , Neoplasms/therapy , Neoplasms/genetics , Mice, Nude , Mice , Polyethylene Glycols/chemistry , Cell Line, Tumor , Mice, Inbred BALB C , Polymers/chemistry
17.
Elife ; 122024 Apr 08.
Article in English | MEDLINE | ID: mdl-38587455

ABSTRACT

The color pattern of insects is one of the most diverse adaptive evolutionary phenotypes. However, the molecular regulation of this color pattern is not fully understood. In this study, we found that the transcription factor Bm-mamo is responsible for black dilute (bd) allele mutations in the silkworm. Bm-mamo belongs to the BTB zinc finger family and is orthologous to mamo in Drosophila melanogaster. This gene has a conserved function in gamete production in Drosophila and silkworms and has evolved a pleiotropic function in the regulation of color patterns in caterpillars. Using RNAi and clustered regularly interspaced short palindromic repeats (CRISPR) technology, we showed that Bm-mamo is a repressor of dark melanin patterns in the larval epidermis. Using in vitro binding assays and gene expression profiling in wild-type and mutant larvae, we also showed that Bm-mamo likely regulates the expression of related pigment synthesis and cuticular protein genes in a coordinated manner to mediate its role in color pattern formation. This mechanism is consistent with the dual role of this transcription factor in regulating both the structure and shape of the cuticle and the pigments that are embedded within it. This study provides new insight into the regulation of color patterns as well as into the construction of more complex epidermal features in some insects.


Subject(s)
Bombyx , Lepidoptera , Animals , Bombyx/genetics , Drosophila melanogaster/genetics , Pigmentation/genetics , Drosophila , Larva/genetics , Transcription Factors/genetics
18.
Basic Res Cardiol ; 119(2): 261-275, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38436707

ABSTRACT

Myocardial infarction (MI) induces the generation of proinflammatory Ly6Chigh monocytes in the spleen and the recruitment of these cells to the myocardium. CD4+ Foxp3+ CD25+ T-cells (Tregs) promote the healing process after myocardial infarction by engendering a pro-healing differentiation state in myocardial monocyte-derived macrophages. We aimed to study the effects of CD4+ T-cells on splenic myelopoiesis and monocyte differentiation. We instigated MI in mice and found that MI-induced splenic myelopoiesis is abrogated in CD4+ T-cell deficient animals. Conventional CD4+ T-cells promoted myelopoiesis in vitro by cell-cell-contact and paracrine mechanisms, including interferon-gamma (IFN-γ) signalling. Depletion of regulatory T-cells enhanced myelopoiesis in vivo, as evidenced by increases in progenitor cell numbers and proliferative activity in the spleen 5 days after MI. The frequency of CD4+ T-cells-producing factors that promote myelopoiesis increased within the spleen of Treg-depleted mice. Moreover, depletion of Tregs caused a proinflammatory bias in splenic Ly6Chigh monocytes, which showed predominantly upregulated expression of IFN-γ responsive genes after MI. Our results indicate that conventional CD4+ T-cells promote and Tregs attenuate splenic myelopoiesis and proinflammatory differentiation of monocytes.


Subject(s)
Monocytes , Myocardial Infarction , Mice , Animals , Monocytes/metabolism , Myelopoiesis , Spleen/metabolism , Myocardial Infarction/metabolism , T-Lymphocytes, Regulatory/metabolism , Interferon-gamma/pharmacology , Mice, Inbred C57BL
19.
BMJ Open ; 14(3): e080826, 2024 Mar 23.
Article in English | MEDLINE | ID: mdl-38521530

ABSTRACT

OBJECTIVE: This study aimed to systematically investigate the relationship between immune-inflammatory indexes with lower urinary tract symptoms (LUTSs). DESIGN: Cross-sectional study. SETTING: National Health and Nutrition Examination Survey (NHANES) (2005-2008). PARTICIPANTS: A total of 2709 men with complete information for immune-inflammatory indexes and LUTSs were included from NHANES 2005-2008. OUTCOMES AND ANALYSES: Automated haematology analysing devices are used to measure blood cell counts, and LUTSs were presented by standard questionnaires. Non-linear and logistic regression analyses were used to estimate their association after adjustment for confounders. RESULTS: Multivariate logistic regression showed that pan-immune-inflammation value (OR (95% CI)=1.60 (1.14 to 2.23)), systemic inflammation response index (SIRI) (OR (95% CI)=1.82 (1.21 to 2.73)), neutrophil/lymphocyte ratio (NLR) (OR (95% CI)=1.81 (1.31 to 2.49)), derived NLR (dNLR) (OR (95% CI)=1.91 (1.35 to 2.70)) and C reactive protein (CRP) (OR (95% CI)=1.71 (1.05 to 2.79)) was positively associated with LUTS. Additionally, composite immune-inflammation markers exhibited a stronger association with LUTS than any single index, with the ORs for high SIRI+high CRP, high NLR+high CRP and high dNLR+high CRP being 2.26, 2.44 and 2.16, respectively (all p<0.05). Furthermore, subgroup analyses revealed that age, smoking status and hypertension have different effects on the relationship between immune-inflammatory markers and LUTS. CONCLUSIONS: This study indicated that high levels of immune-inflammatory markers were associated with an increased risk of clinical LUTS. The combination of CRP with SIRI, NLR and dNLR, respectively, showed a stronger positive correlation with clinical LUTS compared with any single index.


Subject(s)
C-Reactive Protein , Lower Urinary Tract Symptoms , Male , Humans , Nutrition Surveys , Cross-Sectional Studies , C-Reactive Protein/metabolism , Biomarkers , Inflammation , Lower Urinary Tract Symptoms/epidemiology
20.
J Phys Condens Matter ; 36(26)2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38537276

ABSTRACT

2-Propanol and n-hexane are widely used (as) chemical reagents in electronic, pharmaceutical, and chemical industries. An efficient separation of the azeotropic system of 2-propanol-n-hexane is of profound practical significance. By using the conductor-like screening model for real solve (COSMO-RS) predictive model, ionic liquids as extractants for separating the azeotropic system of 2-propanol-n-hexane were evaluated with selectivity coefficients (S) and capacity (C) as the evaluation indexes. Based on the evaluation results, one high-performance extractants named hydroxylamine Cl (C8A19) was selected from 435 kinds of ionic liquids designed by combining 29 kinds of anions and 15 kinds of cations. Moreover, the reliability of the model in predicting the vapor-liquid phase equilibrium behavior of 2-propanol-n-hexane system was verified. Then, the effect of C8A19 on the vapor-liquid phase equilibrium of the 2-propanol-n-hexane system was investigated theoretically and experimentally. The results show that the azeotrope of the system can be broken when the molar fraction of C8A19 is 0.02, denoting that C8A19 can be used for enhanced separation of 2-propanol-n-hexane system. On the basis of the aforementioned study, the selectivity mechanism of the extractant was analyzed from the perspective of microscopic molecular interactions by using the descriptor (σ-profiles) of COSMO-RS. This study provides both theoretical and data support for further designing high-performance ionic liquid extractants and extraction process.

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