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1.
J Am Chem Soc ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39255449

ABSTRACT

Dynamic twisting crystals, combining the features of dynamic crystals and twisting crystals, promise advanced applications in targeted drug delivery, biosensors, microrobots, and spiral optoelectronics. However, the determination of dynamic twisting crystals with specific directions remains a formidable challenge in practical applications. Herein, based on organic-inorganic hybrid metal halide (OIHMH) single crystals, we have realized the chirality-induced macroscopic twisting of single crystals driven by a thermo-induced topochemical dehydration reaction. These crystals exhibit molecular-chirality-induced twisting upon heating, along with reversals in their linear chiroptical circular dichroism and nonlinear chiroptical second harmonic generation circular dichroism. Such an induced twisting has been attributed to the alteration of the helical arrangement of chiral cation post-topochemical dehydration. The feasibility of tuning the macroscopic twisting of OIHMH single crystals and the switching in their linear and nonlinear chiroptical properties might open up new avenues for developing dynamic crystals for microactuating and optoelectronic applications.

2.
Plant Commun ; : 101130, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39257006

ABSTRACT

Cotton, an intriguing plant species shaped by polyploidization, evolution, and domestication, holds particular interest due to the complex mechanisms governing fiber traits across its two subgenomes. However, the regulatory elements or transcriptional networks between subgenomes during fiber elongation remain elusive. Here, we analyzed 1,462 cotton fiber samples to reconstruct gene expression regulatory networks influencing fiber cell elongation. Inter-subgenomic eQTLs largely dictate gene transcription, with a notable tendency for the D subgenome to regulate A subgenome eGenes. This regulation showcases synchronized homoeologous gene expression driven by colocalized eQTLs and divergent patterns that diminish genetic correlations, thus leading to preferential expression in the A and D subgenomes. Hotspot456 emerged as a key regulator of fiber initiation and elongation, and artificial selection of trans-eQTLs in hotspot456 positively regulating KCS1 has facilitated cell elongation. To elucidate the roles of trans-eQTL in improved fiber breeding, experimentation confirmed the inhibition of GhTOL9 by a specific trans-eQTL via GhWRKY28, which negatively impacts fiber elongation. We propose a model where the GhWRKY28-GhTOL9 module, through the Endosomal Sorting Complex Required for Transport pathway, regulates this process. This research significantly advances our understanding of cotton's evolutionary, domestication processes, and the intricate regulatory mechanisms underlying significant plant traits.

3.
Chin J Dent Res ; 27(3): 203-213, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39221981

ABSTRACT

OBJECTIVE: To investigate the biological regulatory function of Gremlin1 (GREM1) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) in dental pulp stem cells (DPSCs), and determine the underlying molecular mechanism involved. METHODS: Alkaline phosphatase (ALP) activity, alizarin red staining, scratch migration assays and in vitro and in vivo osteo-/dentinogenic marker detection of bone-like tissue generation in nude mice were used to assess osteo-/dentinogenic differentiation. Coimmunoprecipitation and polypeptide microarray assays were employed to detect the molecular mechanisms involved. RESULTS: The data revealed that knockdown of GREM1 promoted ALP activity, mineralisation in vitro and the expression of osteo-/dentinogenic differentiation markers and enhanced osteo-/ dentinogenesis of DPSCs in vivo. GREM1 bound to YWHAH in DPSCs, and the binding site was also identified. Knockdown of YWHAH suppressed the osteo-/dentinogenesis of DPSCs in vitro, and overexpression of YWHAH promoted the osteo-/dentinogenesis of DPSCs in vitro and in vivo. CONCLUSION: Taken together, the findings highlight the critical roles of GREM1-YWHAH in the osteo-/dentinogenesis of DPSCs.


Subject(s)
Cell Differentiation , Dental Pulp , Intercellular Signaling Peptides and Proteins , Osteogenesis , Stem Cells , Dental Pulp/cytology , Dental Pulp/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Humans , Animals , Stem Cells/metabolism , Osteogenesis/genetics , Mice , 14-3-3 Proteins/metabolism , 14-3-3 Proteins/genetics , Dentinogenesis/genetics , Mice, Nude , Cells, Cultured
4.
Ecol Evol ; 14(9): e70260, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39247167

ABSTRACT

For decades, many marine animals have been considered to exhibit cosmopolitan or transoceanic distribution. This situation is prevalent in Asia, where many species were collected and named by American or European experts in the 1700s to early 1900s. Using the windowpane oysters Placuna-a small genus of bivalves with five recognized species-we show that careful analysis is required to reassess the validity of these species. Currently, only two species of Placuna (P. placenta and P. ephippium) widely reported in the Indo-Pacific region have been recorded from Chinese coastal waters. Here, we described two new species of Placuna from China. Placuna vitream sp. nov. can be distinguished from P. placenta by its larger ridge angle. Phylogenetic analysis using five gene fragments fully supported that P. vitream sp. nov. is a sister to the specimen from Singapore identified as P. placenta and more distant from other Placuna species with available molecular data. Besides, based on subfossil shells, we describe Placuna aestuaria sp. nov. that differs from its congeneric species by its broad hinge, medium ridge angle, and nearly straight ridges. Finally, we suggest a combination of hinge structure and ridge angle that can be used for identifying Placuna species and preparing a key to this genus. Our findings of two new species expand the diversity of Placuna and prompt reassessment of the many presumably widely distributed marine species in Asia.

5.
Sci Total Environ ; 952: 175877, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39226951

ABSTRACT

Infertility has gradually become a global health concern, and evidence suggests that exposure to environmental endocrine-disrupting chemicals (EDCs) represent one of the key causes of infertility. Benzo(a)pyrene (BaP) is a typical EDC that is widespread in the environment. Previous studies have detected BaP in human urine, semen, cervical mucus, oocytes and follicular fluid, resulting in reduced fertility and irreversible reproductive damage. However, the mechanisms underlying the effects of gestational BaP exposure on offspring fertility in male mice have not been fully explored. In this study, pregnant mice were administered BaP at doses of 0, 5, 10 and 20 mg/kg/day via gavage from Days 7.5 to 12.5 of gestation. The results revealed that BaP exposure during pregnancy disrupted the structural integrity of testicular tissue, causing a disorganized arrangement of spermatogenic cells, compromised sperm quality, elevated levels of histone modifications and increased apoptosis in the testicular tissue of F1 male mice. Furthermore, oxidative stress was also increased in the testicular tissue of F1 male mice. BaP activated the AhR/ERα signaling pathway, affected H3K4me3 expression and induced apoptosis in testicular tissue. AhR and Cyp1a1 were overexpressed, and the expression of key molecules in the antioxidant pathway, including Keap1 and Nrf2, was reduced. The combined effects of these molecules led to apoptosis in testicular tissues, damaging and compromising sperm quality. This impairment in testicular cells further contributed to compromised testicular tissues, ultimately impacting the reproductive health of F1 male mice.

6.
Vet Parasitol ; 331: 110296, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39217762

ABSTRACT

Coccidiosis is an important parasitic disease that has serious adverse effects on the global poultry industry. The mechanism by which the pathogenic factors of Eimeria tenella damage host cells is unknown. Some kinases from the rhoptry compartment can regulate apoptosis of host cells. This study focused on revealing the role and critical nodes of E. tenella rhoptry protein (EtROP) 38 in controlling the apoptosis of host cells via the P38 mitogen-activated protein kinase (MAPK) signaling pathway. The cells were treated with EtROP38 protein, siRNA p38MAPK, or both. The rate of infection, apoptosis, and the dynamic changes in the expression and activation of key factor genes of the P38MAPK signaling pathway in host cells infected with E. tenella were measured. The results showed that the addition of EtROP38 and/or knockdown of the host cells p38 gene reduced the apoptosis rate of cecal epithelial cells (CECS), decreased the mRNA expressions of p38, p53, c-myc, c-fos, and c-jun and increased the expression of p65, decreased the protein expressions of c-myc, c-fos, and c-jun, decreased the p38 protein phosphorylation level, and increased the p65 protein phosphorylation level in CECS. When E. tenella was inoculated for 4-96 h, the addition of Et ROP38 and/or host cell p38 knockdown both increased the infection rate of host cells, and this effect was more pronounced with the addition of EtROP38 with the host cell p38 knockdown. These observations indicate that E. tenella can inhibits the activation of the p38MAPK signaling pathway in host cells via EtROP38, which suppresses apoptosis in host cells.


Subject(s)
Apoptosis , Chickens , Eimeria tenella , p38 Mitogen-Activated Protein Kinases , Eimeria tenella/physiology , Animals , p38 Mitogen-Activated Protein Kinases/metabolism , p38 Mitogen-Activated Protein Kinases/genetics , Poultry Diseases/parasitology , Protozoan Proteins/metabolism , Protozoan Proteins/genetics , Coccidiosis/parasitology , Coccidiosis/veterinary , MAP Kinase Signaling System , Epithelial Cells/parasitology , Cecum/parasitology , Signal Transduction
7.
PLoS One ; 19(9): e0304332, 2024.
Article in English | MEDLINE | ID: mdl-39240822

ABSTRACT

BACKGROUND: From 2004 onwards, the Chinese government has freely offered complimentary Chinese herbal medicine (CHM) to Chinese HIV/AIDS patients, alongside the prescribed first line therapy of highly active antiretroviral therapy (HAART). Thus, we aimed to explore the effectiveness and safety of CHM for patients with HIV/AIDS. METHODS: The data from the Guangxi pilot database and antiviral treatment sites database have been respectively developed into two datasets in this prospective cohort real-world study, the CHM combined HAART group (the integrated group) and the HAART group. A 1:1 propensity score matching (PSM) was performed and the longitudinal data were analyzed using a generalized estimating equation (GEE) model with an autocorrelation matrix and log link function attached to the Gamma distribution. RESULTS: A final sample of 629 patients, 455 and 174 in the integrated group and HAART group respectively, were obtained from the full dataset. As covariates for PSM, gender, age, baseline CD4+ and CD4+/ CD8+ were assessed based on the results of the logistic regression analyses. Following PSM, 166 pairs from the full dataset were matched successfully, with 98 pairs in the baseline CD4+ > 200 subgroup, and 55 pairs in the baseline CD4+ ≤ 200 subgroup. In the full dataset, HAART group achieved higher CD4+ count (OR = 1.119, 95%CI [1.018, 1.230]) and CD4+/CD8+ ratio (OR = 1.168, 95%CI [1.045, 1.305]) than the integrated group, so did in the CD4+ > 200 subgroup. For the CD4+ ≤ 200 subgroup, the CD4+ (OR = 0.825, 95%CI [0.694, 0.980]) and CD4+/CD8+ (OR = 0.826, 95%CI [0.684, 0.997]) of the integrated group were higher than those of the HAART group. The safety outcomes showed that there were no significant differences in BUN, ALT and AST levels between the groups but Cr showed significantly higher levels in HAART groups of all three datasets. CONCLUSIONS: Compared to HAART alone, CHMs combined with HAART had better effects in improving the immune function of HIV/AIDS in patients with baseline CD4+ count ≤ 200. The results of the two subgroups are in opposite directions, and chance does not explain the apparent subgroup effect. A study with larger sample size and longer follow-up period is warranted in order to increase study credibility.


Subject(s)
Antiretroviral Therapy, Highly Active , Drugs, Chinese Herbal , HIV Infections , Propensity Score , Humans , Male , Female , Drugs, Chinese Herbal/therapeutic use , HIV Infections/drug therapy , Adult , China/epidemiology , Middle Aged , CD4 Lymphocyte Count , Prospective Studies
8.
J Cosmet Dermatol ; 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39240125

ABSTRACT

OBJECTIVE: The primary aim of this systematic review and meta-analysis was to synthesize and compare the clinical efficacy of intense pulsed light (IPL) and pulsed-dye laser (PDL) therapies for the management of rosacea. METHODS: The literatures were searched in the Web of Science, PubMed, Embase, and Cochrane Library databases to identify relevant studies investigating the use of IPL and PDL for the treatment of rosacea. Screening of the retrieved articles and data extraction were performed as per the pre-established inclusion and exclusion criteria. The primary outcome measures evaluated in this meta-analysis included clearance rates, erythema scores, and pain scores. RESULTS: The meta-analysis incorporated data from four studies involving a total of 141 participants. The meta-analysis did not reveal a statistically significant difference between IPL and PDL in the rate of achieving greater than 50% clearance (RR = -0.07, 95% CI: -0.19, 0.05). However, the IPL group demonstrated a significantly higher rate of clearance exceeding 75% compared to the PDL group (RR = -0.13, 95% CI: -0.23, -0.04). The change in erythema index, a key measure of rosacea severity, was similar between the two treatment modalities (SMD = -0.15, 95% CI: -0.55, 0.26). Interestingly, the PDL group reported a notably lower VAS pain score than the IPL group (SMD = 1.54, 95% CI: 0.08, 3.00). CONCLUSION: Either PDL or IPL appears to be effective modalities for the management of rosacea. IPL exhibits a slight advantage in achieving a higher rate of substantial (>75%) clearance, while PDL may be preferable for patients with lower tolerance for post-treatment discomfort. However, the existing literature directly comparing these two laser/light-based therapies is limited, warranting further well-designed, large-scale studies to establish the optimal treatment algorithm for this chronic inflammatory skin condition.

9.
Curr Neuropharmacol ; 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39248058

ABSTRACT

Germinal matrix-intraventricular hemorrhage (GM-IVH) is a detrimental neurological complication that occurs in preterm infants, especially in babies born before 32 weeks of gestation and in those with a very low birth weight. GM-IVH is defined as a rupture of the immature and fragile capillaries located in the subependymal germinal matrix zone of the preterm infant brain, and it can lead to detrimental neurological sequelae such as posthemorrhagic hydrocephalus (PHH), cerebral palsy, and other cognitive impairments. PHH following GM-IVH is difficult to treat in the clinic, and no levelone strategies have been recommended to pediatric neurosurgeons. Several cellular and molecular mechanisms of PHH following GM-IVH have been studied in animal models, but no effective pharmacological strategies have been used in the clinic. Thus, a comprehensive understanding of molecular mechanisms, potential pharmacological strategies, and surgical management of PHH is urgently needed. The present review presents a synopsis of the pathogenesis, diagnosis, and cellular and molecular mechanisms of PHH following GM-IVH and explores pharmacological strategies and surgical management.

10.
J Org Chem ; 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39250179

ABSTRACT

Aryl 2-pyridyl esters could efficiently undergo cross-electrophile couplings with aryl bromides with the aid of magnesium as a reducing metal in the absence of a transition-metal catalyst, leading to the unsymmetrical diaryl ketones in modest to good yields with wide functionality compatibility. In addition, the reaction could be easily scaled up and applied in the late-stage modification of biologically active molecules. Preliminary mechanistic study showed that the coupling reaction presumably proceeds through the in situ formation of arylmagnesium reagents as key intermediates.

11.
Chem Commun (Camb) ; 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39246022

ABSTRACT

We have developed a phosphine catalyzed asymmetric [3+2] cyclization of 3-oxetanone derived MBH carbonates with activated methyleneoxindole, to construct oxetane dispirooxindole skeletons. Diastereodivergent synthesis was realized via the control of the phosphine catalyst. The (-)-DIOP provides the syn diastereoisomers, while the spiro phosphine (R)-SITCP achieves the anti-epimers.

12.
Cell Death Dis ; 15(9): 642, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39227585

ABSTRACT

Paired immunoglobin-like type 2 receptor beta (PILRB) mainly plays a crucial role in regulating innate immunity, but whether PILRB is involved in cancer is poorly understood. Here, we report that PILRB potentiates the PI3K/AKT pathway to drive gastric tumorigenesis by binding and stabilizing IRS4, which could hyperactivate the PI3K/AKT pathway. Firstly, the levels of PILRB are upregulated in human gastric cancer (GC) specimens and associated with poor prognosis in patients with GC. In addition, our data show that PILRB promotes cell proliferation, colony formation, cell migration and invasion in GC cells in vitro and in vivo. Mechanistically, PILRB recruits the deubiquitination enzymes OTUB1 to IRS4 and relieves K48-linked ubiquitination of IRS4, protecting IRS4 protein from proteasomal-mediated degradation and subsequent activation of the PI3K/AKT pathway. Importantly, the levels of PILRB are positively correlated with IRS4 in GC specimens. Meanwhile, we also found that PILRB reprogrammed cholesterol metabolism by altering ABCA1 and SCARB1 expression levels, and PILRB-expression confers GC cell resistance to statin treatment. Taken together, our findings illustrate that the oncogenic role of PILRB in gastric tumorigenesis, providing new insights into the regulation of PI3K/AKT signaling in GC and establishing PILRB as a biomarker for simvastatin therapy resistance in GC.


Subject(s)
Carcinogenesis , Cholesterol , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/metabolism , Stomach Neoplasms/genetics , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Animals , Cholesterol/metabolism , Carcinogenesis/metabolism , Carcinogenesis/pathology , Carcinogenesis/genetics , Cell Line, Tumor , Mice , Mice, Nude , Cell Proliferation , Neoplasm Metastasis , Cell Movement , Male , Mice, Inbred BALB C
14.
Nature ; 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39232164

ABSTRACT

Histopathology image evaluation is indispensable for cancer diagnoses and subtype classification. Standard artificial intelligence methods for histopathology image analyses have focused on optimizing specialized models for each diagnostic task1,2. Although such methods have achieved some success, they often have limited generalizability to images generated by different digitization protocols or samples collected from different populations3. Here, to address this challenge, we devised the Clinical Histopathology Imaging Evaluation Foundation (CHIEF) model, a general-purpose weakly supervised machine learning framework to extract pathology imaging features for systematic cancer evaluation. CHIEF leverages two complementary pretraining methods to extract diverse pathology representations: unsupervised pretraining for tile-level feature identification and weakly supervised pretraining for whole-slide pattern recognition. We developed CHIEF using 60,530 whole-slide images spanning 19 anatomical sites. Through pretraining on 44 terabytes of high-resolution pathology imaging datasets, CHIEF extracted microscopic representations useful for cancer cell detection, tumour origin identification, molecular profile characterization and prognostic prediction. We successfully validated CHIEF using 19,491 whole-slide images from 32 independent slide sets collected from 24 hospitals and cohorts internationally. Overall, CHIEF outperformed the state-of-the-art deep learning methods by up to 36.1%, showing its ability to address domain shifts observed in samples from diverse populations and processed by different slide preparation methods. CHIEF provides a generalizable foundation for efficient digital pathology evaluation for patients with cancer.

15.
Ying Yong Sheng Tai Xue Bao ; 35(6): 1590-1598, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-39235017

ABSTRACT

Soil organic matter serves as a crucial indicator for soil quality. Albic soil, characterized by a barrier layer, exhibits limitations in organic matter content, which can adversely affect crop growth and development. To elucidate the impact of deep mixing of various organic materials on the redistribution of organic matter in the surface soil of albic soil could provide theoretical and technical insights for establishing suitable plough layers for albic soil in Northeast China. We conducted a two-year positioning experiment in Shuangyashan, Heilongjiang Province with five treatments, conventional shallow tillage (0-15 cm, CK), inversion tillage (0-35 cm) without or with straw return (T35 and T35+S), inversion tillage with cattle manure (T35+M) and cattle manure plus maize straw (T35+S+M). The results showed that soil fertilization via deep mixing of organic materials to a depth of 35 cm significantly increased maize yield in albic soil, with the T35+S+M treatment demonstrating the most pronounced effect, yielding an average production of 2934.76 kg·hm-2. Compared to CK, the T35 treatment resulted in a significant 8.4% decrease in organic matter content in the tillage layer, a significant 7.6% increase in organic matter in the sub-tillage layer, and a relative richness degree of soil organic matter in the sub-tillage layer increased by 17.5%. Deep mixed return of organic materials following deep ploughing markedly increased organic matter content of the plough layer, with organic matter conversion ranging from 16.3% to 31.0%. In comparison to the T35 treatment, there was no significant increase in soil organic matter content in the T35+S tillage layer and sub-tillage layer. Conversely, soil organic matter content increased by 4.6% and 6.9% in the T35+M and T35+S+M treatments, with corresponding increase of 11.2% and 15.4% in sub-tillage layer, respectively. Additionally, the soil organic matter richness index in sub-tillage layer increased by 2.5% and 5.1%, respectively. There was a significant positive correlation between organic matter content in the entire plough layer and maize yield, with a contribution rate of 17.5%. Therefore, the utilization of organic fertilizer or a combination of organic fertilizer and straw deep mixing can quickly fertilize albic soil by increasing soil organic matter content in both the whole tillage layer (0-35 cm) and the sub-tillage layer (15-35 cm).


Subject(s)
Agriculture , Fertilizers , Organic Chemicals , Soil , Zea mays , Soil/chemistry , Organic Chemicals/analysis , China , Zea mays/growth & development , Agriculture/methods , Fertilizers/analysis , Manure , Crops, Agricultural/growth & development
16.
Org Lett ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39235126

ABSTRACT

A protocol for the construction of cycloheptatrienes has been developed. 4-(Dimethylamino)pyridine (DMAP) was found to be an efficient catalyst to promote the [4 + 3] annulation between coumalates and γ-alkyl-substituted allenoate or γ-aryl-3-butynoates to deliver a variety of cycloheptatrienes in moderate to good yield with excellent chemoselectivity. The asymmetric version of this annulation was also realized by using bifunctional phosphine catalyst to provide the chiral products with 32-97% ee and 29-64% yield.

17.
J Biophotonics ; : e202400275, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39225054

ABSTRACT

The elasticity of the limbus is crucial for ocular health, yet it remains inadequately explored. This study employs acoustic radiation force optical coherence elastography (ARF-OCE) to evaluate the biomechanical properties of the limbus under varying intraocular pressures. The method was validated using a heterogeneous phantom and subsequently applied to ex vivo porcine limbus samples. Elastic wave velocity at specific locations within the limbus was calculated, and the corresponding Young's modulus values were obtained. Spatial elasticity distribution maps were generated by correlating Young's modulus values with their respective locations in the two-dimensional structural images. The results indicate that ARF-OCE enhances the understanding of limbus biomechanical behavior and holds potential for diagnosing regional variations caused by ocular diseases.

18.
Angew Chem Int Ed Engl ; : e202410519, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39090074

ABSTRACT

Carbon dots (CDs), as a kind of zero-dimensional nanomaterials, have been widely synthesized by bottom-up methods from various precursors. However, the formation mechanism is still unclear and controversial, which also brings difficulty to the regulation of structures and properties. Only some tentative formation processes were postulated by analyzing the products obtained at different reaction times and temperatures. Here, the effect of crosslinking on the formation of carbonized polymer dots (CPDs) is explored. Crosslinking-induced nucleation and carbonization (CINC) is proposed as the driving force for the formation of CPDs. Under hydrothermal synthesis, the precursors are initiated to polymerize and crosslink. The crosslinking brings higher hydrophobicity to generate the hydrophilic/hydrophobic microphase separation, which promotes dehydration and carbonization resulting in the formation of CPDs. Based on the principle of CINC, the influence factors of size are also revealed. Moreover, the dissipative particle dynamics (DPD) simulation is employed to support this formation mechanism. This concept of CINC will bring light to the formation process of CPDs, as well as facilitate the regulation of CPDs' size and photoluminescence.

19.
Theranostics ; 14(11): 4218-4239, 2024.
Article in English | MEDLINE | ID: mdl-39113799

ABSTRACT

Rationale: The aryl hydrocarbon receptor (AhR) functions in the regulation of intestinal inflammation, but knowledge of the underlying mechanisms in innate immune cells is limited. Here, we investigated the role of AhR in modulating the functions of macrophages in inflammatory bowel disease pathogenesis. Methods: The cellular composition of intestinal lamina propria CD45+ leukocytes in a dextran sulfate sodium (DSS)-induced mouse colitis model was determined by single-cell RNA sequencing. Macrophage pyroptosis was quantified by analysis of lactate dehydrogenase release, propidium iodide staining, enzyme-linked immunosorbent assay, western blot, and flow cytometry. Differentially expressed genes were confirmed by RNA-seq, RT-qPCR, luciferase assay, chromatin immunoprecipitation, and immunofluorescence staining. Results: AhR deficiency mediated dynamic remodeling of the cellular composition of intestinal lamina propria (LP) CD45+ immune cells in a colitis model, with a significant increase in monocyte-macrophage lineage. Mice with AhR deficiency in myeloid cells developed more severe dextran sulfate sodium induced colitis, with concomitant increased macrophage pyroptosis. Dietary supplementation with an AhR pre-ligand, indole-3-carbinol, conferred protection against colitis while protection failed in mice lacking AhR in myeloid cells. Mechanistically, AhR signaling inhibited macrophage pyroptosis by promoting ornithine decarboxylase 1 (Odc1) transcription, to enhance polyamine biosynthesis. The increased polyamine, particularly spermine, inhibited NLRP3 inflammasome assembly and subsequent pyroptosis by suppressing K+ efflux. AHR expression was positively correlated with ODC1 in intestinal mucosal biopsies from patients with ulcerative colitis. Conclusions: These findings suggest a functional role for the AhR/ODC1/polyamine axis in maintaining intestinal homeostasis, providing potential targets for treatment of inflammatory bowel disease.


Subject(s)
Colitis , Dextran Sulfate , Macrophages , Polyamines , Pyroptosis , Receptors, Aryl Hydrocarbon , Receptors, Aryl Hydrocarbon/metabolism , Receptors, Aryl Hydrocarbon/genetics , Animals , Mice , Macrophages/metabolism , Macrophages/immunology , Colitis/metabolism , Colitis/chemically induced , Colitis/pathology , Humans , Polyamines/metabolism , Disease Models, Animal , Mice, Inbred C57BL , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Mice, Knockout , Inflammation/metabolism , Male , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/pathology , Basic Helix-Loop-Helix Transcription Factors
20.
Am J Transl Res ; 16(7): 3316-3325, 2024.
Article in English | MEDLINE | ID: mdl-39114708

ABSTRACT

OBJECTIVES: To investigate the emergency response capabilities of cardiovascular surgical nurses, analyze their correlation with self-efficacy and coping styles, and summarize targeted intervention measures. METHODS: A total of 243 cardiovascular surgical nurses from comprehensive tertiary Grade A hospitals in Jiangsu Province were selected using convenience sampling from October to November 2023. Participants were surveyed using a general information questionnaire, an emergency response capability assessment scale for operating room nurses, a general self-efficacy scale, and a simplified coping style scale. RESULTS: The total scores were 114.77±12.39 for emergency response capability, 2.69±0.58 for self-efficacy, 2.02±0.54 for positive coping style, and 1.16±0.53 for negative coping style. Pearson correlation analysis showed that emergency response capability was positively correlated with self-efficacy and positive coping styles and negatively correlated with negative coping styles (all P<0.05). Optimal scaling regression analysis indicated seven factors; age, years of work, professional level, title, self-efficacy, positive coping style, and negative coping style, which could explain 39.0% of the variation in emergency response capability (all P<0.05). CONCLUSIONS: The emergency response capabilities of cardiovascular surgical nurses are moderately high and closely related to their self-efficacy and coping styles. Emergency rescue training for cardiovascular surgical nurses should aim at enhancing self-efficacy and positive coping styles by, for example, setting clear training goals, focusing on individual differences, fostering of active learning, and stimulating their intrinsic motivation to enhance their emergency response capabilities. These changes will lead to more organized and efficient cardiovascular surgical emergency work.

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