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1.
Front Pharmacol ; 15: 1399460, 2024.
Article in English | MEDLINE | ID: mdl-38983920

ABSTRACT

Herb compatibility is the soul of traditional Chinese Medicine prescriptions. Coptidis rhizoma (CR) (Coptis chinensis Franch., Coptis deltoidea C.Y.Cheng et Hsiao, or Coptis teeta Wall.; family Ranunculaceae), is a well-known herb. The bitter and cold nature of CR can irritate the spleen and stomach, and certain ingredients in CR may trigger allergic reactions. Herb combinations can help alleviate the side effects caused by CR. Through data analysis and literature research, there are many herbs combined with CR have a high frequency, but only a few are currently used as formulae in clinical practice. The results showed that these six herb pairs are usually widely studied or used as prescriptions in the clinic. This paper describes the six herb pairs from the key traditional uses, changes in bioactive constituents, and compatibility effects, especially with Euodiae fructus (family Rutaceae), Scutellariae radix (family Lamiaceae), Magnoliae Officinalis cortex (family Magnoliaceae), Glycyrrhizae radix et rhizoma (family Fabaceae), Ginseng radix et rhizoma (family Araliaceae), and Aucklandiae radix (family Asteraceae), and found that herbs are more effective when used in combination. Therefore, it is feasible to establish some methods to study herb pairs comprehensively from different perspectives. This paper aims to provide the latest and most comprehensive information on the six herb pairs and summarize the pattern of CR compatibility effects. It aims to attract more attention, and further experimental studies will be conducted to investigate and evaluate the effects of herb pairs containing CR. These data can also provide valuable references for researchers and also provide more possibilities for future applications in clinical practice and new drug development.

2.
IEEE Trans Med Imaging ; PP2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949933

ABSTRACT

Radiology report generation (RRG) is crucial to save the valuable time of radiologists in drafting the report, therefore increasing their work efficiency. Compared to typical methods that directly transfer image captioning technologies to RRG, our approach incorporates organ-wise priors into the report generation. Specifically, in this paper, we propose Organ-aware Diagnosis (OaD) to generate diagnostic reports containing descriptions of each physiological organ. During training, we first develop a task distillation (TD) module to extract organ-level descriptions from reports. We then introduce an organ-aware report generation module that, for one thing, provides a specific description for each organ, and for another, simulates clinical situations to provide short descriptions for normal cases. Furthermore, we design an auto-balance mask loss to ensure balanced training for normal/abnormal descriptions and various organs simultaneously. Being intuitively reasonable and practically simple, our OaD outperforms SOTA alternatives by large margins on commonly used IU-Xray and MIMIC-CXR datasets, as evidenced by a 3.4% BLEU-1 improvement on MIMIC-CXR and 2.0% BLEU-2 improvement on IU-Xray.

3.
Clin Oral Investig ; 28(7): 406, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38949690

ABSTRACT

OBJECTIVES: This study aimed to develop and validate a predictive nomogram for diagnosing radicular grooves (RG) in maxillary lateral incisors (MLIs), integrating demographic information, anatomical measurements, and Cone Beam Computed Tomography (CBCT) data to diagnose the RG in MLIs based on the clinical observation before resorting to the CBCT scan. MATERIALS AND METHODS: A retrospective cohort of orthodontic patients from the School and Hospital of Stomatology, Wuhan University, was analyzed, including demographic characteristics, photographic anatomical assessments, and CBCT diagnoses. The cohort was divided into development and validation groups. Univariate and multivariate logistic regression analyses identified significant predictors of RG, which informed the development of a nomogram. This nomogram's performance was validated using receiver operating characteristic analysis. RESULTS: The study included 381 patients (64.3% female) and evaluated 760 MLIs, with RG present in 26.25% of MLIs. The nomogram incorporated four significant anatomical predictors of RG presence, demonstrating substantial predictive efficacy with an area under the curve of 0.75 in the development cohort and 0.71 in the validation cohort. CONCLUSIONS: A nomogram for the diagnosis of RG in MLIs was successfully developed. This tool offers a practical checklist of anatomical predictors to improve the diagnostic process in clinical practice. CLINICAL RELEVANCE: The developed nomogram provides a novel, evidence-based tool to enhance the detection and treatment planning of MLIs with RG in diagnostic and therapeutic strategies.


Subject(s)
Cone-Beam Computed Tomography , Incisor , Maxilla , Nomograms , Humans , Female , Male , Incisor/diagnostic imaging , Retrospective Studies , Cone-Beam Computed Tomography/methods , Adolescent , Maxilla/diagnostic imaging , Tooth Root/diagnostic imaging , Child , China
4.
Nature ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961296

ABSTRACT

One-dimensional (1D) interacting electrons are often described as a Luttinger liquid1-4 having properties that are intrinsically different from those of Fermi liquids in higher dimensions5,6. In materials systems, 1D electrons exhibit exotic quantum phenomena that can be tuned by both intra- and inter-1D-chain electronic interactions, but their experimental characterization can be challenging. Here we demonstrate that layer-stacking domain walls (DWs) in van der Waals heterostructures form a broadly tunable Luttinger liquid system, including both isolated and coupled arrays. We have imaged the evolution of DW Luttinger liquids under different interaction regimes tuned by electron density using scanning tunnelling microscopy. Single DWs at low carrier density are highly susceptible to Wigner crystallization consistent with a spin-incoherent Luttinger liquid, whereas at intermediate densities dimerized Wigner crystals form because of an enhanced magneto-elastic coupling. Periodic arrays of DWs exhibit an interplay between intra- and inter-chain interactions that gives rise to new quantum phases. At low electron densities, inter-chain interactions are dominant and induce a 2D electron crystal composed of phased-locked 1D Wigner crystal in a staggered configuration. Increased electron density causes intra-chain fluctuation potentials to dominate, leading to an electronic smectic liquid crystal phase in which electrons are ordered with algebraical correlation decay along the chain direction but disordered between chains. Our work shows that layer-stacking DWs in 2D heterostructures provides opportunities to explore Luttinger liquid physics.

5.
Inorg Chem ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38984385

ABSTRACT

Efficient CO oxidation at ambient or low temperatures is essential for environmental purification and selective CO oxidation in H2, yet achieving this remains a challenge with current methodologies. In this research, we extensively evaluated the catalytic performance of phosphotungstic acid (PTA)-supported 11 M1/PTA single-atom catalysts (SACs) using density functional theory calculations across both gas phase and 12 common solvents. The Rh1/PTA, Pd1/PTA, and Pt1/PTA systems exhibit moderate CO adsorption energies, facilitating the feasibility of oxygen vacancy formation. Remarkably, the Pd1/PTA and Pt1/PTA catalysts exhibited negligible energy barriers and demonstrated exceptionally high catalytic rates, with values reaching up to (1 × 1010)11, markedly exceeding the threshold for room temperature reactions, set at 6.55 × 108. This phenomenon is attributed to a transition from the high-energy barrier processes of oxygen dissociation in O2 and N-O bond dissociation in N2O to the more efficient dissociation of H2O2. Orbital analysis and charge variations at metal sites throughout the reaction process provide deeper insights into the role of the three metal catalytic sites in CO activation. Our findings not only reveal key aspects of SACs in facilitating CO oxidation at low temperatures but also provide valuable insights for future catalytic reaction mechanism studies and environmental applications.

6.
Mol Cell ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38955180

ABSTRACT

During implantation, embryos undergo an unpolarized-to-polarized transition to initiate postimplantation morphogenesis. However, the underlying molecular mechanism is unknown. Here, we identify a transient transcriptional activation governing embryonic morphogenesis and pluripotency transition during implantation. In naive pluripotent embryonic stem cells (ESCs), which represent preimplantation embryos, we find that the microprocessor component DGCR8 can recognize stem-loop structures within nascent mRNAs to sequester transcriptional coactivator FLII to suppress transcription directly. When mESCs exit from naive pluripotency, the ERK/RSK/P70S6K pathway rapidly activates, leading to FLII phosphorylation and disruption of DGCR8/FLII interaction. Phosphorylated FLII can bind to transcription factor JUN, activating cell migration-related genes to establish poised pluripotency akin to implanting embryos. Resequestration of FLII by DGCR8 drives poised ESCs into formative pluripotency. In summary, we identify a DGCR8/FLII/JUN-mediated transient transcriptional activation mechanism. Disruption of this mechanism inhibits naive-poised-formative pluripotency transition and the corresponding unpolarized-to-polarized transition during embryo implantation, which are conserved in mice and humans.

7.
Foods ; 13(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38890944

ABSTRACT

A long-term intake of a high-fat and high-fructose diet (HFFD), even a high-fat, high-fructose but low-protein diet (HFFD + LP), could cause obesity associated with cognitive impairments. In the present study, rats were subjected to a normal diet (ND), an HFFD diet, an HFFD + LP diet, and an HFFD with kidney bean protein (KP) diet for 8 weeks to evaluate the effect of KP on HFFD- or HFFD + LP-induced obesity and cognitive impairment. The results demonstrated that compared with the HFFD diet, KP administration significantly decreased the body weight by 7.7% and the serum Angiotensin-Converting Enzyme 2 (ACE-2) and Insulin-like Growth Factor 1 (IGF-1) levels by 14.4% and 46.8%, respectively (p < 0.05). In addition, KP suppressed HFFD-induced cognitive impairment, which was evidenced by 8.7% less time required to pass the water maze test. The 16s RNA analysis of the colonic contents showed that the relative abundance of Bifidobacterium, Butyricimonas, and Alloprevotella was increased by KP by 5.9, 44.2, and 79.2 times. Additionally, KP supplementation primarily affected the choline metabolic pathway in the liver, and the synthesis and functional pathway of neurotransmitters in the brain, thereby improving obesity and cognitive function in rats.

8.
Cell ; 187(13): 3284-3302.e23, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38843832

ABSTRACT

The cleavage of zygotes generates totipotent blastomeres. In human 8-cell blastomeres, zygotic genome activation (ZGA) occurs to initiate the ontogenesis program. However, capturing and maintaining totipotency in human cells pose significant challenges. Here, we realize culturing human totipotent blastomere-like cells (hTBLCs). We find that splicing inhibition can transiently reprogram human pluripotent stem cells into ZGA-like cells (ZLCs), which subsequently transition into stable hTBLCs after long-term passaging. Distinct from reported 8-cell-like cells (8CLCs), both ZLCs and hTBLCs widely silence pluripotent genes. Interestingly, ZLCs activate a particular group of ZGA-specific genes, and hTBLCs are enriched with pre-ZGA-specific genes. During spontaneous differentiation, hTBLCs re-enter the intermediate ZLC stage and further generate epiblast (EPI)-, primitive endoderm (PrE)-, and trophectoderm (TE)-like lineages, effectively recapitulating human pre-implantation development. Possessing both embryonic and extraembryonic developmental potency, hTBLCs can autonomously generate blastocyst-like structures in vitro without external cell signaling. In summary, our study provides key criteria and insights into human cell totipotency.


Subject(s)
Cell Differentiation , Spliceosomes , Animals , Humans , Mice , Blastocyst/metabolism , Blastocyst/cytology , Blastomeres/metabolism , Blastomeres/cytology , Cellular Reprogramming , Embryonic Development/genetics , Germ Layers/metabolism , Germ Layers/cytology , Pluripotent Stem Cells/metabolism , Pluripotent Stem Cells/cytology , RNA Splicing , Spliceosomes/metabolism , Totipotent Stem Cells/metabolism , Totipotent Stem Cells/cytology , Zygote/metabolism , Cells, Cultured , Models, Molecular , Protein Structure, Tertiary , Genome, Human , Single-Cell Analysis , Growth Differentiation Factor 15/chemistry , Growth Differentiation Factor 15/genetics , Growth Differentiation Factor 15/metabolism , Epigenomics , Cell Lineage
9.
Int J Biol Macromol ; 273(Pt 1): 133080, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38866284

ABSTRACT

In the intricate web of ecological relationships, pollinators such as the Italian honeybee (Apis mellifera) play a crucial role in maintaining biodiversity and agricultural productivity. This study focuses on the interactions between three neonicotinoid compounds and the honeybee's chemosensory protein 3 (CSP3), a key player in their olfactory system. Employing advanced spectroscopic techniques and molecular modeling, we explore the binding dynamics and conformational changes in CSP3 upon exposure to these pesticides. The research reveals that all three neonicotinoids considerably quench CSP3's fluorescence through a dynamic and static mixing mechanism, indicating a strong binding affinity, predominantly driven by hydrophobic interactions. UV-visible absorption, synchronous fluorescence, and 3D fluorescence spectra support slight changes in the microenvironment around the aromatic amino acids of CSP3. Circular dichroism spectra indicate a reduction in CSP3's α-helix content, suggesting structural alterations. Molecular docking and dynamics simulations further elucidate the binding modes and stability of these interactions, highlighting the role of specific amino acids in CSP3's binding cavity. Findings provide critical insights into molecular mechanisms by which neonicotinoids may impair honeybee chemosensory function, offering implications for designing safer pesticides and understanding the broader ecological impact of these chemicals on pollinator health.


Subject(s)
Insect Proteins , Molecular Docking Simulation , Molecular Dynamics Simulation , Neonicotinoids , Animals , Bees/drug effects , Bees/chemistry , Neonicotinoids/chemistry , Insect Proteins/chemistry , Insect Proteins/metabolism , Protein Binding , Structure-Activity Relationship , Models, Molecular , Spectrometry, Fluorescence , Spectrum Analysis , Circular Dichroism
10.
NPJ Parkinsons Dis ; 10(1): 111, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834646

ABSTRACT

A new Parkinson's disease (PD) subtyping model has been recently proposed based on the initial location of α-synuclein inclusions, which divides PD patients into the brain-first subtype and the body-first subtype. Premotor RBD has proven to be a predictive marker of the body-first subtype. We found compared to PD patients without possible RBD (PDpRBD-, representing the brain-first subtype), PD patients with possible premotor RBD (PDpRBD+, representing the body-first subtype) had lower Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (MDS UPDRS-III) score (p = 0.022) at baseline but presented a faster progression rate (p = 0.009) in MDS UPDRS-III score longitudinally. The above finding indicates the body-first subtype exhibited a faster disease progression in motor impairments compared to the brain-first subtype and further validates the proposed subtyping model.

11.
BMC Med Inform Decis Mak ; 24(1): 176, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38907208

ABSTRACT

BACKGROUND: Patient-reported outcome (PRO) is a distinct and indispensable dimension of clinical characteristics and recent advances have made remote PRO measurement possible. Sex difference in PRO of Parkinson's disease (PD) is hardly extensively researched. METHODS: A smartphone-based self-management platform, offering remote PRO measurement for PD patients, has been developed. A total of 1828 PD patients, including 1001 male patients and 827 female patients, were enrolled and completed their PRO submission through this platform. RESULTS: Sex differences in PROs have been identified. The female group had a significantly lower height, weight, and body mass index (BMI) than the male group (P < 0.001). For motor symptoms, a higher proportion of patients reporting dyskinesia was observed in the female group. For non-motor symptoms, there is a higher percentage (P < 0.001) as well as severity (P = 0.016) of depression in the female group. More male patients reported hyposmia, lisp, drooling, dysuria, frequent urination, hypersexuality, impotence, daytime sleepiness, and apathy than females (P < 0.05). In contrast, more female patients reported headache, palpation, body pain, anorexia, nausea, urinal incontinence, anxiety, insomnia (P < 0.05) than males. CONCLUSIONS: We provide evidence for sex differences in PD through the data collected from our platform. These results highlighted the importance of gender in clinical decision-making, and also support the feasibility of remote PRO measurement through a smartphone-based self-management platform in patients with PD.


Subject(s)
Parkinson Disease , Patient Reported Outcome Measures , Self-Management , Smartphone , Humans , Parkinson Disease/therapy , Male , Female , Pilot Projects , Cross-Sectional Studies , Middle Aged , Aged , Sex Factors , Mobile Applications
12.
Bioact Mater ; 37: 459-476, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38698920

ABSTRACT

Magnesium phosphate bone cements (MPC) have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability. However, their poor porosity and permeability limit osteogenic cell ingrowth and vascularization, which is critical for bone regeneration. In the current study, we constructed a novel hierarchically-porous magnesium phosphate bone cement by incorporating extracellular matrix (ECM)-mimicking electrospun silk fibroin (SF) nanofibers. The SF-embedded MPC (SM) exhibited a heterogeneous and hierarchical structure, which effectively facilitated the rapid infiltration of oxygen and nutrients as well as cell ingrowth. Besides, the SF fibers improved the mechanical properties of MPC and neutralized the highly alkaline environment caused by excess magnesium oxide. Bone marrow stem cells (BMSCs) adhered excellently on SM, as illustrated by formation of more pseudopodia. CCK8 assay showed that SM promoted early proliferation of BMSCs. Our study also verified that SM increased the expression of OPN, RUNX2 and BMP2, suggesting enhanced osteogenic differentiation of BMSCs. We screened for osteogenesis-related pathways, including FAK signaing, Wnt signaling and Notch signaling, and found that SM aided in the process of bone regeneration by suppressing the Notch signaling pathway, proved by the downregulation of NICD1, Hes1 and Hey2. In addition, using a bone defect model of rat calvaria, the study revealed that SM exhibited enhanced osteogenesis, bone ingrowth and vascularization compared with MPC alone. No adverse effect was found after implantation of SM in vivo. Overall, our novel SM exhibited promising prospects for the treatment of critical-sized bone defects.

13.
Front Microbiol ; 15: 1353940, 2024.
Article in English | MEDLINE | ID: mdl-38721596

ABSTRACT

Introduction: An increasing number of studies have demonstrated the pivotal role of microbiota changes in the onset, progression, diagnosis, treatment, and prognosis of lung adenocarcinoma (LUAD). However, a comprehensive analysis of intratumoral microbiome variation across distinct LUAD stages has not been performed. The aim of this study was to identify the microbial markers that significantly vary during tumor stage of LUAD. Methods: Here, we used the cancer genome atlas (TCGA) database to comprehensively compare and analyze the differences in microbial composition between 267 patients with early and 224 patients with advanced LUAD. In order to determine the best biomarkers, we used the random forest (RF) model and found that the microbial markers have a certain ability in predicting the stage of LUAD. Results: We found that there were certain differences in the microbiome of patients with LUAD at different stages, especially in the tumor tissues of patients with advanced LUAD, whose co-abundance network was significantly more complex. We also found that five bacterial biomarkers (Pseudoalteromonas, Luteibacter, Caldicellulosiruptor, Loktanella, and Serratia) were correlated with LUAD stage, among which Pseudoalteromonas, Luteibacter, Caldicellulosiruptor, and Serratia were significantly overexpressed in patients with advanced LUAD. In particular, after integrating the biomarkers of mRNA, we achieved an area under the curve (AUC) of 0.70. Discussion: Our study revealed the microbial profile of patients with LUAD and the intrinsic pathogenic mechanism between the microbiome and the disease, and established a multi-omics model to determine LUAD tumor stage.

14.
Inorg Chem ; 63(19): 8977-8987, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38690714

ABSTRACT

Integration of hydrogen evolution with the oxidation of organic substances in one electrochemical system is highly desirable. However, achieving selective oxidation of organic substances in the integrated system is still highly challenging. In this study, a phosphorylated NiMoO4 nanoneedle-like array was designed as the catalytic active electrode for the integration of highly selective electrochemical dehydrogenation of tetrahydroisoquinolines (THIQs) with hydrogen production. The leaching of anions, including MoO42- and PO43-, facilitates the reconstruction of the catalyst. As a result, nickel oxyhydroxides with the doping of PO43- and richness of defects are in situ formed. In situ Raman and density functional theory calculations have shown that the high catalytic activity is attributed to the in situ formed PO43- involved NiOOH substance. In the dehydrogenation process, the involved C-H bond but not the N-H bond is first destroyed. A two-electrode system was then fabricated with the optimized electrode that shows a benchmark current density of 10 mA cm-2 at 1.783 V, providing a yield of 70% for dihydroisoquinolines. A robust stability was also shown for this integrated electrochemical system. The understanding of the reconstruction behavior and the achievement of selective dehydrogenation will provide some hints for electrochemical synthesis.

15.
Database (Oxford) ; 20242024 May 28.
Article in English | MEDLINE | ID: mdl-38805752

ABSTRACT

Mechanical aspects of tissues and cells critically influence a myriad of biological processes and can substantially alter the course of diverse diseases. The emergence of diverse methodologies adapted from physical science now permits the precise quantification of the cellular forces and the mechanical properties of tissues and cells. Despite the rising interest in tissue and cellular mechanics across fields like biology, bioengineering and medicine, there remains a noticeable absence of a comprehensive and readily accessible repository of this pertinent information. To fill this gap, we present MechanoBase, a comprehensive tissue and cellular mechanics database, curating 57 480 records from 5634 PubMed articles. The records archived in MechanoBase encompass a range of mechanical properties and forces, such as modulus and tractions, which have been measured utilizing various technical approaches. These measurements span hundreds of biosamples across more than 400 species studied under diverse conditions. Aiming for broad applicability, we design MechanoBase with user-friendly search, browsing and data download features, making it a versatile tool for exploring biomechanical attributes in various biological contexts. Moreover, we add complementary resources, including the principles of popular techniques, the concepts of mechanobiology terms and the cellular and tissue-level expression of related genes, offering scientists unprecedented access to a wealth of knowledge in this field of research. Database URL: https://zhanglab-web.tongji.edu.cn/mechanobase/ and https://compbio-zhanglab.org/mechanobase/.


Subject(s)
Databases, Factual , Humans , Biomechanical Phenomena , Animals
16.
Adv Sci (Weinh) ; 11(26): e2403227, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38704731

ABSTRACT

To effectively treat osteoarthritis (OA), the existing inflammation must be reduced before the cartilage damage can be repaired; this cannot be achieved with a single type of extracellular vesicles (EVs). Here, a hydrogel complex with logic-gates function is proposed that can spatiotemporally controlled release two types of EVs: interleukin 10 (IL-10)+ EVs to promote M2 polarization of macrophage, and SRY-box transcription factor 9 (SOX9)+ EVs to increase cartilage matrix synthesis. Following dose-of-action screening, the dual EVs are loaded into a matrix metalloporoteinase 13 (MMP13)-sensitive self-assembled peptide hydrogel (KM13E) and polyethylene glycol diacrylate/gelatin methacryloyl-hydrogel microspheres (PGE), respectively. These materials are mixed to form a "microspheres-in-gel" KM13E@PGE system. In vitro, KM13E@PGE abruptly released IL-10+ EVs after 3 days and slowly released SOX9+ EVs for more than 30 days. In vivo, KM13E@PGE increased the CD206+ M2 macrophage proportion in the synovial tissue and decreased the tumor necrosis factor-α and IL-1ß levels. The aggrecan and SOX9 expressions in the cartilage tissues are significantly elevated following inflammation subsidence. This performance is not achieved using anti-inflammatory or cartilage repair therapy alone. The present study provides an injectable, integrated delivery system with spatiotemporal control release of dual EVs, and may inspire logic-gates strategies for OA treatment.


Subject(s)
Disease Models, Animal , Extracellular Vesicles , Osteoarthritis , Extracellular Vesicles/metabolism , Osteoarthritis/metabolism , Animals , Hydrogels/chemistry , Macrophages/metabolism , Interleukin-10/metabolism , Humans , SOX9 Transcription Factor/metabolism , Mice , Rats
18.
Chin Med J (Engl) ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816396

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated. METHODS: We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (three each from CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. RESULTS: Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. CONCLUSIONS: Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

19.
Nutrients ; 16(7)2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38613113

ABSTRACT

The implications of soy consumption on human health have been a subject of debate, largely due to the mixed evidence regarding its benefits and potential risks. The variability in responses to soy has been partly attributed to differences in the metabolism of soy isoflavones, compounds with structural similarities to estrogen. Approximately one-third of humans possess gut bacteria capable of converting soy isoflavone daidzein into equol, a metabolite produced exclusively by gut microbiota with significant estrogenic potency. In contrast, lab-raised rodents are efficient equol producers, except for those raised germ-free. This discrepancy raises concerns about the applicability of traditional rodent models to humans. Herein, we designed a gnotobiotic mouse model to differentiate between equol producers and non-producers by introducing synthetic bacterial communities with and without the equol-producing capacity into female and male germ-free mice. These gnotobiotic mice display equol-producing phenotypes consistent with the capacity of the gut microbiota received. Our findings confirm the model's efficacy in mimicking human equol production capacity, offering a promising tool for future studies to explore the relationship between endogenous equol production and health outcomes like cardiometabolic health and fertility. This approach aims to refine dietary guidelines by considering individual microbiome differences.


Subject(s)
Equol , Isoflavones , Humans , Female , Male , Animals , Mice , Disease Models, Animal , Ketones , Phenotype
20.
Heliyon ; 10(8): e27851, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38655360

ABSTRACT

With the increasing focus on Environmental, Social, and Governance (ESG) and Corporate Social Responsibility (CSR) on a global scale, stakeholders expect businesses to transform and enhance social responsibility. Over time, ESG and CSR have developed into vital performance metrics for businesses. Businesses are actively putting improvement measures into place in response to this new paradigm in order to stay competitive in this changing environment. China's dual commitment to CSR and sustainable development is in line with wider objectives, such as resolving issues of pay inequality. In 2012, the China Banking Regulatory Commission (CBRC) unveiled the "Green Credit Guidelines" (GCG), which take corporate governance's environmental considerations into account. These regulations set standards and specifically target high-pollution corporations. Companies may need to restructure their corporate structures and create efficient governance mechanisms in order to comply with these regulations and reduce carbon emissions. This will have an impact on the compensation packages of executives and regular employees. The most important question is how the "GCG" will affect the wage disparity in highly polluting companies. This study examines the 2012 "GCG" and its potential to reduce internal wage disparities, viewing it as a critical element of green financial policy. The paper uses data from Chinese A-share listed companies from 2007 to 2020. Besides, it uses the Difference-in-Differences method to assess the impact of China's GCG, treating its implementation as a quasi-natural experiment and controlling for concurrent policy effects to precisely identify its net impact on corporate carbon emissions and internal wage disparities. The findings show that "GCG" considerably closed internal wage disparities. Furthermore, the "GCG" has a path of guidance, incentives, and punishments that reduce internal wage disparities and promote a more equitable wage distribution within businesses. According to heterogeneity analysis, policies have a greater impact on the wage gap in businesses that are highly dependent on outside funding and have political connection. In order to achieve a compensation balance and meet the objectives of social responsibility and corporate sustainable development, the government should strengthen the complementary effects of green financial policies. The compensation balance in highly polluting companies has important theoretical and practical ramifications. On the one hand, it represents the convergence of income equality, corporate governance, and environmental responsibility. It helps to expand knowledge of sustainable development, fair compensation, and environmental policies. On the other hand, the widening pay disparity between executives and average employees reflects the exacerbation of income inequality in China, which could potentially impact companies' long-term development. Conversely, a well-balanced pay plan can improve worker productivity and motivation while empowering stakeholders to make wise investment choices.

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