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1.
Plant Commun ; : 101076, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39228128

ABSTRACT

Cytokinins (CKs) are one of important classes of plant hormones essential for plant growth and development. The TATA-box binding protein-associated factor 12b (TAF12b) is involved in cytokinin (CK) signaling, but its molecular and biochemical mechanisms remain unclear. In this study, TAF12b of Nicotiana benthamiana (NbTAF12b) was found to mediate CK response by directly interacting with type-B response regulators (B-RRs), which are positive regulators of CK signaling, and inhibiting their transcriptional activities. The co-factor specifically facilitated the proteasomal degradation of non-phosphorylated B-RRs by recruiting the KMD family of F-box proteins. Such interactions between TAF12b and B-RRs also occur in other plant species. Genetic transformation experiments further showed that overexpression of NbTAF12b attenuates the CK-hypersensitive phenotype conferred by NbRR1 overexpression. Taken together, these results suggest a conserved mechanism that TAF12b negatively regulates CK responses through promoting 26S proteasome-mediated degradation of B-RRs degradation in multiple plant species, which provides novel insights into the regulatory network of CK signaling in plants.

2.
J Asian Nat Prod Res ; : 1-17, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39317172

ABSTRACT

As a kind of glycoside, pentacyclic triterpenoid saponins have good biological activities, such as anticancer, antibacterial, antiviral and hypoglycemic effects [1]. In this paper, twenty-four pentacyclic triterpenoid derivatives, including twelve monosaccharide derivatives, were designed and synthesized. The anticancer effect and antibacterial activities of all compounds were evaluated. It is noteworthy that compound UA-2b has the strongest inhibitory effect on the growth of A549, Hela and HepG2 cancer cells (IC50 = 5.37 ± 0.22 µM, 5.82 ± 0.25 µM and 5.47 ± 0.06 µM, respectively). Compounds OA-2b, OA-6a, OA-6b, UA-2b and UA-6a have the best activity against Escherichia coli 1924 (MIC = 16 µg/ml).

3.
J Am Chem Soc ; 146(38): 26427-26434, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39241233

ABSTRACT

Realizing topological transformation through supramolecular fusion is particularly challenging, as the self-assembly of disparate components often results in the orthogonal assembly of building blocks into distinct structures rather than the formation of a heteroleptic architecture. This study introduces a topological transformation, transitioning from a figure-eight knot (41 knot) to a Solomon link (412 link) through a supramolecular fusion process. By employing two structurally similar amino acid ligands (L1 and L3) of varying lengths as bridge ligands, we obtained figure-eight knot 1 and a molecular tweezer-like compound 3 when individually complexed with binuclear Cp*Rh acceptor B1. Our results revealed that subtle modifications to bridge ligands can lead to dramatic changes in their structures and recognition properties. Moreover, we successfully achieved the targeted formation of a heteroleptic Solomon link 4 by blending figure-eight knot 1 and compound 3 in a 1:1 ratio without the need for templates. This procedure effortlessly converted the 41 knot into a 412 link, thus marking a significant advancement in the topological transformation. This work not only marks the construction of the first heteroleptic Solomon link comprising two distinct metallamacrocycles but also demonstrates a process of supramolecular fusion-based topological transformation involving three distinct topological structures.

4.
Curr Res Food Sci ; 9: 100849, 2024.
Article in English | MEDLINE | ID: mdl-39319110

ABSTRACT

In this experiment, five metal ions (K+, Mg2+, Al3+, Ga3+, and Sn4+) were utilized as copigments to investigate their copigmentation processes with cyanidin-3-O-glucoside (C3OG) in simulated fruit wine solutions. The color characteristics were analyzed using Glories and CIELAB methods, and the copigmentation effects were determined spectrophotometrically. Thermodynamic parameters, including the equilibrium constant (K) and standard Gibbs free energy (ΔG°), were calculated to comprehend the binding affinity between metal ions and C3OG. Ultra-fast femtosecond spectroscopy was employed to monitor the photoinduced electron transfer process between C3OG and cations. Theoretical calculations were also conducted to support experimental findings. The results revealed that the presence of metal ions significantly enhanced the color intensity of C3OG in simulated fruit wine solutions. Higher valency cations, particularly Sn4+, Ga3+, and Al3+, exhibited superior copigmentation effects, resulting in significant bathochromic and hyperchromic changes. Thermodynamic analysis confirmed that the interaction between C3OG and metal ions was spontaneous and exothermic. Ultra-fast femtosecond spectroscopy demonstrated that electron transfer from C3OG to metal ions occurred, with the efficiency of transfer being dependent on valency. Theoretical calculations corroborated the experimental results by highlighting the role of metal ions in stabilizing C3OG/metal complexes through electron transfer. The findings presented in this study contribute to a more comprehensive understanding of pigment/metal complexes and the underlying chemistry behind fruit wine color. Furthermore, it advances the theoretical foundation of copigmentation and broadens its applications in the beverage industry.

5.
Healthcare (Basel) ; 12(18)2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39337223

ABSTRACT

BACKGROUND: Identifying mediators between obesity-related traits and lower respiratory tract infections (LRTIs) would inform preventive and therapeutic strategies to reduce the burden of LRITs. We aimed to recognize whether lung function and inflammatory factors mediate their associations. METHODS: We conducted a two-step, two-sample Mendelian randomization (MR) analysis. Two-sample MR was performed on (1) obesity-related traits (i.e., body mass index [BMI], waist circumference [WC], and waist-to-hip ratio [WHR]) and LRTIs (i.e., acute bronchitis, acute bronchiolitis, bronchiectasis, influenza, and pneumonia), (2) obesity-related traits and potential mediators, and (3) potential mediators and LRTIs. Next, two-step MR was applied to infer whether the mediation effects exist. RESULTS: We found that C-reactive protein (CRP), interleukin-6 (IL-6), and forced expiratory volume in the first second (FEV1) mediated 32.59% (95% CI: 17.90%, 47.27%), 7.96% (95% CI: 1.79%, 14.14%), and 4.04% (95% CI: 0.34%, 7.74%) of the effect of BMI on pneumonia, and they mediated 26.90% (95% CI: 13.98%, 39.83%), 10.23% (95% CI: 2.72%, 17.73%), and 4.67% (95% CI: 0.25%, 9.09%) of the effect of WC on pneumonia, respectively. Additionally, CRP, forced vital capacity (FVC), and FEV1 mediated 18.66% (95% CI: 8.70%, 28.62%), 8.72% (95% CI: 1.86%, 15.58%), and 8.41% (95% CI: 2.77%, 14.06%) of the effect of BMI on acute bronchitis, and they mediated 19.96% (95% CI: 7.44%, 32.48%), 12.19% (95% CI: 2.00%, 22.39%), and 12.61% (95% CI: 2.94%, 22.29%) of the effect of WC on acute bronchitis, respectively. CONCLUSIONS: Health interventions linked to reducing inflammation and maintaining normal lung function could help mitigate the risk of obesity-related LRTIs.

6.
Int J Ophthalmol ; 17(9): 1707-1716, 2024.
Article in English | MEDLINE | ID: mdl-39296563

ABSTRACT

AIM: To analyze the spectrum of isolated pathogens and antibiotic resistance for ocular infections within 5y at two tertiary hospitals in east China. METHODS: Ocular specimen data were collected from January 2019 to October 2023. The pathogen spectrum and positive culture rate for different infection location, such as keratitis, endophthalmitis, and periocular infections, along with antibiotic resistance were analyzed. RESULTS: We included 2727 specimens, including 827 (30.33%) positive cultures. A total of 871 strains were isolated, 530 (60.85%) bacterial and 341 (39.15%) fungal strains were isolated. Gram-positive cocci (GPC) were the most common ocular pathogens. The most common bacterial isolates were Staphylococcus epidermidis (25.03%), Staphylococcus aureus (7.46%), Streptococcus pneumoniae (4.59%), Corynebacterium macginleyi (3.44%), and Pseudomonas aeruginosa (3.33%). The most common fungal genera were Fusarium spp. (12.74%), Aspergillus spp. (6.54%), and Scedosporium spp. (5.74%). Staphylococcus epidermidis strains showed more than 50% resistance to fluoroquinolones. Streptococcus pneumoniae and Corynebacterium macginleyi showed more than 90% resistance to erythromycin. The percentage of bacteria showing multidrug resistance (MDR) significantly decreased (χ 2=17.44, P=0.002). CONCLUSION: GPC are the most common ocular pathogens. Corynebacterium macginleyi, as the fourth common bacterium, may currently be the local microbiological feature of east China. Fusarium spp. is the most common fungus. More than 50% of the GPC are resistant to fluoroquinolones, penicillins, and macrolides. However, the proportion of MDR strains has been reduced over time.

7.
Int Immunopharmacol ; 142(Pt B): 113183, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39298815

ABSTRACT

Children all over the world suffer from atopic dermatitis (AD), a prevalent condition that impairs their health. Corticosteroids, which have long-term negative effects, are frequently used to treat AD. There has been a growing body of research on the gut microbiota's function in AD. Nevertheless, the function and underlying mechanisms of fecal microbiota transplantation (FMT) in AD children remain to be established. Therefore, in order to assess the preventive effects of FMT treatment on AD and investigate the mechanisms, we constructed an ovalbumin (OVA)-induced juvenile mouse AD model in this investigation. This study explored the role and mechanism of FMT treatment in AD through 16S RNA sequencing, pathological histological staining, molecular biology, and Flow cytometry. Results demonstrated that the FMT treatment improved the gut microbiota's diversity and composition, bringing it back to a level similar to that of a close donor. Following FMT treatment, OVA-specific antibodies were inhibited, immunoglobulin (Ig) E production was decreased, the quantity of mast cells and eosinophils was decreased, and specific inflammatory markers in the skin and serum were decreased. Further mechanistic studies revealed that FMT treatment induced CD103+ DCs and programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression in skin-draining lymph nodes and promoted Treg production to induce immune tolerance and suppress skin inflammation. Meanwhile, changes in the gut microbiota were substantially correlated with Th2 cytokines, OVA-specific antibodies, and PD-L1/PD-1. In conclusion, FMT regulates the Th1/Th2 immunological balance and the gut microbiota. It may also inhibit AD-induced allergy responses through the PD-L1/PD-1 pathway, and providing a unique idea and possibly a fresh approach to the treatment of AD.

8.
Article in English | MEDLINE | ID: mdl-39299559

ABSTRACT

OBJECTIVES: Simnotrelvir is a small molecule highly specific 3C-like protease inhibitor for anti-SARS-CoV-2 and was approved as a combination drug with ritonavir (simnotrelvir/ritonavir) in China. Simnotrelvir is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), and a weak inhibitor of CYP3A. Ritonavir is a substrate and inhibitor of CYP3A and an inhibitor of P-gp. Hence, the drug-drug interaction (DDI) potential of simnotrelvir/ritonavir should be investigated. METHODS: This DDI study was an open-label, fixed-sequence, two-period Phase I clinical trial in Chinese healthy adult subjects, divided into 3 cohorts, including simnotrelvir/ritonavir co-administrated with a strong CYP3A and P-gp inhibitor (itraconazole) and inducer (rifampicin), and with a specific CYP3A substrate (midazolam). RESULTS: The results demonstrated that compared to administration of simnotrelvir/ritonavir alone, the co-administration with itraconazole increased the geometric least-square mean ratio (GMR) of the expose (AUC0-t) of simnotrelvir by 25% (GMR 125%, 90% confidence interval (CI) 114% - 137%), whereas co-administration with rifampicin significantly decreased the AUC0-t of simnotrelvir by 81.5% (GMR 18.5%, 90% CI 16.4% - 20.9%). Notably, simnotrelvir/ritonavir increased the AUC0-t of midazolam by 16.69-fold (GMR 1769%, 90% CI 1551% - 2018%). The co-administration of simnotrelvir/ritonavir and rifampicin caused the increased amount and severity of treatment-emergent adverse events, especially hepatotoxicity. CONCLUSIONS: The co-administration of simnotrelvir/ritonavir with CYP3A and P-gp inhibitors can be safely used, while the co-administration with CYP3A and P-gp strong inducer should be avoided to minimize the risk of under-exposure. Co-administration of midazolam with simnotrelvir/ritonavir increased systemic exposure of midazolam. GOV IDENTIFIER: NCT05665647.

9.
Medicine (Baltimore) ; 103(36): e39464, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39252309

ABSTRACT

To more accurately diagnose and treat patients with different subtypes of thyroid cancer, we constructed a diagnostic model related to the iodine metabolism of THCA subtypes. THCA expression profiles, corresponding clinicopathological information, and single-cell RNA-seq were downloaded from TCGA and GEO databases. Genes related to thyroid differentiation score were obtained by GSVA. Through logistic analyses, the diagnostic model was finally constructed. DCA curve, ROC curve, machine learning, and K-M analysis were used to verify the accuracy of the model. qRT-PCR was used to verify the expression of hub genes in vitro. There were 104 crossover genes between different TDS and THCA subtypes. Finally, 5 genes (ABAT, CHEK1, GPX3, NME5, and PRKCQ) that could independently predict the TDS subpopulation were obtained, and a diagnostic model was constructed. ROC, DCA, and RCS curves exhibited that the model has accurate prediction ability. K-M and subgroup analysis results showed that low model scores were strongly associated with poor PFI in THCA patients. The model score was significantly negatively correlated with T cell follicular helper. In addition, the diagnostic model was significantly negatively correlated with immune scores. Finally, the results of qRT-PCR corresponded with bioinformatics results. This diagnostic model has good diagnostic and prognostic value for THCA patients, and can be used as an independent prognostic indicator for THCA patients.


Subject(s)
Iodine , Thyroid Neoplasms , Humans , Thyroid Neoplasms/genetics , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/pathology , Computational Biology/methods , Female , Male , Machine Learning , Middle Aged , Thyroid Gland/pathology , Thyroid Gland/metabolism , ROC Curve , Cell Differentiation , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism
10.
Nat Commun ; 15(1): 7713, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39231979

ABSTRACT

Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.


Subject(s)
CD8-Positive T-Lymphocytes , Chemokine CXCL13 , Immunotherapy , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Single-Cell Analysis , Tertiary Lymphoid Structures , Humans , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/immunology , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/metabolism , Tertiary Lymphoid Structures/immunology , Tertiary Lymphoid Structures/genetics , Chemokine CXCL13/metabolism , Chemokine CXCL13/genetics , Immunotherapy/methods , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/immunology , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/therapy , Gene Expression Profiling , Disease Progression , Transcriptome , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Prognosis , Fibroblasts/metabolism , Fibroblasts/immunology
11.
Br J Cancer ; 131(7): 1126-1136, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39164491

ABSTRACT

BACKGROUND: Neoadjuvant immunotherapy is under intensive investigation for esophageal squamous cell carcinoma (ESCC). This study assesses the efficacy and immune response of neoadjuvant immunochemotherapy (nICT) in ESCC. METHODS: In this phase II trial (ChiCTR2100045722), locally advanced ESCC patients receiving nICT were enrolled. The primary endpoint was the pathological complete response (pCR) rate. Multiplexed immunofluorescence, RNA-seq and TCR-seq were conducted to explore the immune response underlying nICT. RESULTS: Totally 42 patients were enrolled, achieving a 27.0% pCR rate. The 1-year, 2-year DFS and OS rates were 89.2%, 64.4% and 97.3%, 89.2%, respectively. RNA-seq analysis highlighted T-cell activation as the most significantly enriched pathway. The tumour immune microenvironment (TIME) was characterised by high CD4, CD8, Foxp3, and PD-L1 levels, associating with better pathological regression (TRS0/1). TIME was categorised into immune-infiltrating, immune-tolerant, and immune-desert types. Notably, the immune-infiltrating type and tertiary lymphoid structures correlated with improved outcomes. In the context of nICT, TIM-3 negatively influenced treatment efficacy, while elevated TIGIT/PD-1 expression post-nICT correlated positively with CD8+ T cell levels. TCR-seq identified three TCR rearrangements, underscoring the specificity of T-cell responses. CONCLUSIONS: Neoadjuvant camrelizumab plus chemotherapy is effective for locally advanced, resectable ESCC, eliciting profound immune response that closely associated with clinical outcomes.


Subject(s)
Antibodies, Monoclonal, Humanized , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Neoadjuvant Therapy , Tumor Microenvironment , Humans , Female , Male , Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Squamous Cell Carcinoma/immunology , Esophageal Squamous Cell Carcinoma/pathology , Middle Aged , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/immunology , Esophageal Neoplasms/pathology , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Tumor Microenvironment/immunology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Aged , Treatment Outcome , Adult , Immunotherapy/methods
12.
Org Biomol Chem ; 22(36): 7500-7517, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39189805

ABSTRACT

Axially chiral C2-arylquinoline has been successfully constructed via asymmetric heteroannulation of alkynes catalyzed by chiral phosphoric acid with high yield and high enantioselectivity. Inspired by this intriguing work, theoretical calculations have been carried out, and the detailed reaction mechanism has been elaborated, in which the whole reaction can be divided into steps including hydrogen transfer, C-N bonding, annulation reaction and the final dehydration processes. The initial hydrogen-transfer reaction has two possible pathways, while the subsequent C-N bonding process has eight possible pathways. Then, after the annulation reaction and the final dehydration processes, the major product and byproduct were formed. QTAIM and IGMH analyses were used to illustrate the role of weak intermolecular interactions in the catalytic process, and the distortion/interaction and EDA analyses provided a deeper understanding of the origin of enantioselectivity. The calculated results are consistent with the experimental results. This work would provide valuable insights into asymmetric reactions catalyzed by chiral phosphoric acid.

13.
Se Pu ; 42(8): 731-739, 2024 Aug.
Article in Chinese | MEDLINE | ID: mdl-39086241

ABSTRACT

Edible plant oils are a key component of the daily human diet, and the quality and safety of plant oils are related to human health. Perfluorinated and polyfluoroalkyl substances (PFASs) are pollutants that can contaminate plant oil through the processing of raw materials or exposure to materials containing these substances. Thus, establishing a sensitive and accurate analytical method for the determination of PFASs is critical for ensuring the safety of plant oils. In this study, a method based on acetonitrile extraction and solid phase extraction purification combined with ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS) was developed for the simultaneous determination of 21 PFASs, including perfluorocarboxylic acids, perfluoroalkyl sulfonic acids, and fluorotelomer sulfonic acids, in edible plant oils. The chromatographic conditions and MS parameters were optimized, and the influences of the extraction solvents and purification method were systematically studied. Plant oil samples were directly extracted with acetonitrile and purified using a weak anion-exchange (WAX) column. The 21 target PFASs were separated on a reversed-phase C18 chromatographic column and detected using a triple quadrupole mass spectrometer with an electrospray ionization source. The mass spectrometer was operated in negative-ion mode. The target compounds were analyzed in multiple reaction monitoring (MRM) mode and quantified using an internal standard method. The results demonstrated that the severe interference observed during the detection of PFASs in the co-extracted substances was completely eliminated after the extraction mixture was purified using a WAX column. The 21 target PFASs showed good linearity in their corresponding ranges, with correlation coefficients greater than 0.995. The limits of detection (LODs) and limits of quantification (LOQs) of the method were in the range of 0.004-0.015 and 0.015-0.050 µg/kg, respectively. The recoveries ranged from 95.6% to 115.8%, with relative standard deviations (RSDs) in the range of 0.3%-10.9% (n=9). The established method is characterized by simple sample pretreatment, good sensitivity, high immunity to interferences, and good stability, rendering it suitable for the rapid analysis and accurate determination of typical PFASs in edible plant oils.


Subject(s)
Fluorocarbons , Food Contamination , Plant Oils , Tandem Mass Spectrometry , Chromatography, High Pressure Liquid/methods , Fluorocarbons/analysis , Tandem Mass Spectrometry/methods , Food Contamination/analysis , Plant Oils/chemistry , Plant Oils/analysis
14.
Autophagy ; : 1-18, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39189526

ABSTRACT

Severe fever with thrombocytopenia syndrome is an emerging viral hemorrhagic fever caused by a tick-borne bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), with a high case fatality. We previously found that SFTSV nucleoprotein (NP) induces macroautophagy/autophagy to facilitate virus replication. However, the role of NP in antagonizing host innate immunity remains unclear. Mitophagy, a selected form of autophagy, eliminates damaged mitochondria to maintain mitochondrial homeostasis. Here, we demonstrate that SFTSV NP triggers mitophagy to degrade MAVS (mitochondrial antiviral signaling protein), thereby blocking MAVS-mediated antiviral signaling to escape the host immune response. Mechanistically, SFTSV NP translocates to mitochondria by interacting with TUFM (Tu translation elongation factor, mitochondrial), and mediates mitochondrial sequestration into phagophores through interacting with LC3, thus inducing mitophagy. Notably, the N-terminal LC3-interacting region (LIR) motif of NP is essential for mitophagy induction. Collectively, our results demonstrated that SFTSV NP serves as a novel virulence factor, inducing TUFM-mediated mitophagy to degrade MAVS and evade the host immune response.Abbreviation: 3-MA: 3-methyladenine; ACTB: actin beta; co-IP: co-immunoprecipitation; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole, dihydrochloride; DMSO: dimethyl sulfoxide; FCCP: carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone; GFP: green fluorescent protein; HTNV: Hantan virus; IAV: influenza A virus; IFN: interferon; LAMP1: lysosomal associated membraneprotein 1; LIR: LC3-interacting region; MAP1LC3B/LC3B: microtubule associatedprotein 1 light chain 3 beta; MAVS: mitochondrial antiviral signaling protein; Mdivi-1: mitochondrial division inhibitor 1; MOI: multiplicity of infection; MT-CO2/COXII: mitochondrially encoded cytochrome C oxidase II; NP: nucleoprotein; NSs: nonstructural proteins; poly(I:C): polyinosinic:polycytidylic acid; RIGI: RNA sensor RIG-I; RLR: RIGI-like receptor; SFTSV: severe fever withthrombocytopenia syndrome virus; TCID50: 50% tissue culture infectiousdose; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20:translocase of outer mitochondrial membrane 20; TUFM: Tu translation elongationfactor, mitochondrial.

15.
Article in English | MEDLINE | ID: mdl-39090455

ABSTRACT

Autism spectrum disorder (ASD) is a neurodevelopmental disorder; the prevalence of which has been on the rise with unknown causes. Alterations in the gut-brain axis have been widely recognized in ASD patients, and probiotics are considered to potentially benefit the rescuing of autism-like behaviors. However, the effectiveness and mechanisms of multiple probiotics on zebrafish models are still not clearly revealed. This study aims to use the germ-free (GF) and conventionally raised (CR) AB wild-type zebrafish and the mutant Tbr1b-/- and Katnal2-/- lines as human-linked ASD animal models to evaluate the effects of multiple probiotics on mitigating developmental and behavioral defects. Results showed that the addition of probiotics increased the basic important developmental indexes, such as body length, weight, and survival rate of treated zebrafish. Moreover, the Lactobacillus plantarum and Lactobacillus rhamnosus affected the behavior of CR zebrafish by increasing their mobility, lowering the GF zebrafish manic, and mitigating transgenic zebrafish abnormal behavior. Moreover, the expression levels of key genes related to gamma-aminobutyric acid (GABA), dopamine (DA), and serotonin (5-HT) as important neuropathways to influence the appearance and development of autism-related disorders, including gad1b, tph1a, htr3a, th, and slc6a3, were significantly activated by some of the probiotics' treatment at some extent. Taken together, this study indicates the beneficial effects of different probiotics, which may provide a novel understanding of probiotic function in related diseases' therapy.

16.
World J Gastrointest Oncol ; 16(8): 3716-3722, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39171176

ABSTRACT

BACKGROUND: Aggressive fibromatosis (AF), also known as desmoid tumor or desmoid-type fibromatosis, is a rare soft tissue neoplasm that can occur in almost any part of the body. Although it is a benign disease, AF is aggressive and infiltrative and has a high recurrence rate after surgery. Common sites for intra-abdominal AF are the small bowel mesentery, retroperitoneum, and pelvis. AF in the colon is extremely rare. CASE SUMMARY: Here, we report the first case of sigmoid colon AF, which was accidentally discovered in a 27-year-old woman during laparoscopic myomectomy. Computed tomography confirmed a slightly enhanced mass in the sigmoid colon. Subsequent colonoscopy did not reveal a mass in the colonic lumen, but a suspected external compress was found in the sigmoid colon. Surgical disease involving a gastrointestinal stromal tumor was suspected. The patient underwent laparoscopic exploration, and sigmoidectomy with a negative margin was performed to excise the mass. Postoperative immunohistochemistry revealed that the mass was an AF. The patient recovered well and was recurrence-free at the 30-month follow-up without adjuvant therapy. CONCLUSION: AF should be considered in the differential diagnosis of subepithelial colon masses. Radical resection alone can achieve good outcomes.

17.
Sci Rep ; 14(1): 18530, 2024 08 09.
Article in English | MEDLINE | ID: mdl-39122793

ABSTRACT

To gain a deeper understanding of the flowering pattern and reproductive characteristics of Epimedium sagittatum, to enrich the research on the flower development of E. sagittatum and its reproductive regulation, and to screen the methods suitable for the rapid detection of pollen viability of E. sagittatum and to promote its cross-breeding. The characteristics of its flower parts were observed, recorded and measured, and the pollen viability of E. sagittatumwas determined by five methods, including TTC staining, I2-KI staining, red ink staining, peroxidase method and in vitro germination method. The flowering process of E. sagittatum can be divided into five stages: calyx dehiscence, bract spathe, petal outgrowth, pollen dispersal, and pollination and withering. The results of I2-KI staining and peroxidase method were significantly higher than those of other methods; the in vitro germination method was intuitive and accurate, but the operation was complicated and time-consuming; the red ink staining method was easy to operate and had obvious staining effect, and the results were the closest to those of the in vitro germination method; and it was found that the pollen of E. sagittatum was not as effective as the in vitro germination method at the bud stamen stage, the flower stigma and the flower bud. It was also found that the pollen viability and germination rate of E. sagittatum pollen were higher in the three periods of bud spitting, petal adductor and pollen dispersal. Comparing the five methods, the red ink staining method was found to be a better method for the rapid detection of pollen viability; the best pollination periods of E. sagittatum were the bud stamen stage, petal adductor stage, and pollen dispersal stage of flowers at the peak of bloom. This study on the flowering and fruiting pattern of E. sagittatum, and the related mechanism of sexual reproduction, can be used as a reference for the next step of research on the breeding of E. sagittatum.


Subject(s)
Epimedium , Flowers , Germination , Pollen , Flowers/growth & development , Pollen/growth & development , Germination/physiology , Pollination
18.
J Integr Neurosci ; 23(8): 143, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39207076

ABSTRACT

Alzheimer's disease (AD) is recognized as the leading cause of dementia, imposing a significant economic toll on society. Despite the emergence of novel therapeutic approaches for AD, their efficacy and safety mandates further validation through rigorous clinical trials. In this context, hypertension (HTN) has garnered considerable attention as an amendable risk factor for AD. Research indicates that hypertension during midlife is associated with an elevated risk of AD in later years, influencing both the onset and progression of the disease. Nevertheless, the relationship between AD and hypertension in the later stages of life remains a subject of debate. Moreover, the consequences of blood pressure reduction on cognitive function, along with the optimal pharmacological interventions and therapeutic thresholds for hypertension, have emerged as pivotal areas of inquiry. This review synthesizes findings on epidemiology, neuroimaging, and biomarkers, and the effects of antihypertensive medications to elucidate the link between hypertension and cognitive performance. We particularly investigate how hypertension and AD are related by plasma sulfide dysregulation, offering possible indicators for future diagnosis and therapy.


Subject(s)
Alzheimer Disease , Hypertension , Neuroimaging , Humans , Alzheimer Disease/physiopathology , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/metabolism , Hypertension/physiopathology , Hypertension/complications , Neuroimaging/methods , Brain/diagnostic imaging , Brain/physiopathology , Brain/metabolism
19.
Article in English | MEDLINE | ID: mdl-39067514

ABSTRACT

OBJECTIVES: To evaluate posaconazole (POS) gastro-resistant tablets for preventing invasive fungal disease (IFD) in haematopoietic stem cell transplantation (HSCT) patients and analyse POS plasma concentrations. METHODS: A single-arm trial was designed with a historical cohort as a control. Patients aged 13 years and older undergoing HSCT at the HSCT Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences between December 2020 and May 2022 were enrolled, prospectively taking POS gastro-resistant tablets orally from day 1 to day 90 post-transplant and monitoring plasma concentrations. We also identified a retrospective cohort treated with alternative antifungal prophylaxis between January 2018 and December 2020, matched using propensity score methods. The primary outcome was the cumulative incidence of IFD at day 90 post-transplant. RESULTS: The prospective study involved 144 patients receiving POS gastro-resistant tablets for IFD prevention, contrasting with 287 patients receiving non-POS tablets. By day 90 post-transplant, the POS tablet group exhibited a significantly lower cumulative incidence of IFD (2.81%; 95% CI, 0.09-5.50% vs. 7.69%; 95% CI, 4.60-10.78%; p 0.044). Adverse events were comparable between the groups with liver changes in 33/144 (22.92%) vs. 84/287 (29.27%) (p 0.162), and renal injuries in 15/144 (10.41%) vs. 37/287 (12.89%) (p 0.457). Mean POS plasma concentrations on days 4, 8, 15, and 22 post-administration were 930.97 ng/mL, 1143.97 ng/mL, 1569.8 ng/mL, and 1652.57 ng/mL, respectively. DISCUSSION: Patients administered POS gastro-resistant tablets for antifungal prophylaxis experienced a lower cumulative incidence of IFD. POS plasma concentrations in HSCT patients stabilized by day 15 of medication.

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