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1.
Neural Netw ; 176: 106349, 2024 May 03.
Article En | MEDLINE | ID: mdl-38723310

Generalized Person Re-Identification (GReID) aims to develop a model capable of robust generalization across unseen target domains, even with training on a limited set of observed domains. Recently, methods based on the Attack-Defense mechanism are emerging as a prevailing technology to this issue, which treats domain transformation as a type of attack and enhances the model's generalization performance on the target domain by equipping it with a defense module. However, a significant limitation of most existing approaches is their inability to effectively model complex domain transformations, largely due to the separation of attack and defense components. To overcome this limitation, we introduce an innovative Interactive Attack-Defense (IAD) mechanism for GReID. The core of IAD is the interactive learning of two models: an attack model and a defense model. The attack model dynamically generates directional attack information responsive to the current state of the defense model, while the defense model is designed to derive generalizable representations by utilizing a variety of attack samples. The training approach involves a dual process: for the attack model, the aim is to increase the challenge for the defense model in countering the attack; conversely, for the defense model, the focus is on minimizing the effects instigated by the attack model. This interactive framework allows for mutual learning between attack and defense, creating a synergistic learning environment. Our diverse experiments across datasets confirm IAD's effectiveness, consistently surpassing current state-of-the-art methods, and using MSMT17 as the target domain in different protocols resulted in a notable 13.4% improvement in GReID task average Rank-1 accuracy. Code is available at: https://github.com/lhf12278/IAD.

2.
Mol Biol Rep ; 51(1): 632, 2024 May 09.
Article En | MEDLINE | ID: mdl-38724827

BACKGROUND: MicroRNAs (miRNAs) play critical roles in the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs), but the mechanism by which miRNAs indirectly modulate osteogenesis remains unclear. Here, we explored the mechanism by which miRNAs indirectly modulate gene expression through histone demethylases to promote bone regeneration. METHODS AND RESULTS: Bioinformatics analysis was performed on hBMSCs after 7 days of osteogenic induction. The differentially expressed miRNAs were screened, and potential target mRNAs were identified. To determine the bioactivity and stemness of hBMSCs and their potential for bone repair, we performed wound healing, Cell Counting Kit-8 (CCK-8), real-time reverse transcription quantitative polymerase chain reaction (RT‒qPCR), alkaline phosphatase activity, alizarin red S (ARS) staining and radiological and histological analyses on SD rats with calvarial bone defects. Additionally, a dual-luciferase reporter assay was utilized to investigate the interaction between miR-26b-5p and ten-eleven translocation 3 (TET3) in human embryonic kidney 293T cells. The in vitro and in vivo results suggested that miR-26b-5p effectively promoted the migration, proliferation and osteogenic differentiation of hBMSCs, as well as the bone reconstruction of calvarial defects in SD rats. Mechanistically, miR-26b-5p bound to the 3' untranslated region of TET3 mRNA to mediate gene silencing. CONCLUSIONS: MiR-26b-5p downregulated the expression of TET3 to increase the osteogenic differentiation of hBMSCs and bone repair in rat calvarial defects. MiR-26b-5p/TET3 crosstalk might be useful in large-scale critical bone defects.


Bone Regeneration , Cell Differentiation , Dioxygenases , Mesenchymal Stem Cells , MicroRNAs , Osteogenesis , Rats, Sprague-Dawley , Skull , MicroRNAs/genetics , MicroRNAs/metabolism , Animals , Mesenchymal Stem Cells/metabolism , Humans , Osteogenesis/genetics , Cell Differentiation/genetics , Rats , Skull/pathology , Skull/metabolism , Female , Bone Regeneration/genetics , Dioxygenases/genetics , Dioxygenases/metabolism , Cell Proliferation/genetics , HEK293 Cells
3.
Res Sq ; 2024 May 03.
Article En | MEDLINE | ID: mdl-38746161

Current gene therapy for Duchenne muscular dystrophy (DMD) utilizes adeno-associated virus (AAV) to deliver miniaturized dystrophin (micro-dystrophin or µDys), which does not provide full protection for striated muscles as it lacks many important functional domains within full-length (FL) dystrophin. Here we develop a triple vector system to deliver FL-dystrophin into skeletal and cardiac muscles. We rationally split FL-dystrophin into three fragments (N, M, and C) linked to two orthogonal pairs of split intein, allowing efficient, unidirectional assembly of FL-dystrophin. The three fragments packaged in myotropic AAV (MyoAAV4A) restore FL-dystrophin expression in both skeletal and cardiac muscles in male mdx 4cv mice. Dystrophin-glycoprotein complex components are also restored in the sarcolemma of dystrophic muscles. MyoAAV4A-delivered FL-dystrophin significantly improves muscle histopathology, contractility, and overall strength comparable to µDys, but unlike µDys, it also restores defective ERK signaling in heart. The FL-dystrophin gene therapy therefore promises to offer superior protection for DMD.

4.
Materials (Basel) ; 17(9)2024 Apr 24.
Article En | MEDLINE | ID: mdl-38730782

Bimetallic composites have a wide range of application prospects in various industries. Different bonding temperatures, as one of the influencing factors, directly affect the bonding effectiveness as well as the performance and application of the materials. Using metallurgical bonding techniques ensures a strong bond at the interface of bimetallic materials, resulting in high-quality composite pipe billets. This paper describes an Incoloy825/P110 steel bimetal composite material made by the solid-liquid composite method. By utilizing ProCAST 14.5 software for simulation and deriving theoretical formulas, an initial range of temperatures for bimetallic preparation has been tentatively determined. And this temperature range will be utilized for on-site experiments to prepare bimetallic samples. After the preparation process is completed, samples will be selected. The influence of the external mold temperature on the interface bonding of Incoloy825/P110 steel solid-liquid composite material is studied using an ultra-depth three-dimensional morphology microscope and a scanning electron microscope. Through research, the optimal preheating temperature range for the solid-liquid composite outer mold of Incoloy825/P110 bimetallic composite material has been determined. The casting temperature of the inner mold has a significant impact on the interface bonding of this bimetal composite material. As the casting temperature of the inner mold increases, the interface thickness gradually increases. At lower temperatures, the interface thickness is lower and the bonding is poorer. At higher temperatures, melting may occur, leading to coarse grains at the interface. When the temperatures of the inner and outer molds are within a certain range, a new phase appears at the interface. Indeed, it increases the strength of the interface bonding. Due to co-melting of the bimetal near the interface, element migration occurs, resulting in increased Ni and Cr content at the interface and enhanced corrosion resistance.

5.
Int J Biol Macromol ; 269(Pt 2): 132216, 2024 May 08.
Article En | MEDLINE | ID: mdl-38729483

Agricultural by-products of sesame are promising bioresources in food processing. This study extracted lignin from the by-products of sesame oil production, namely, the capsules and straw of black and white sesame. Using acid, alkali, and ethanol methods, 12 distinct lignins were obtained to prepare biochar, aiming to investigate both the structural characteristics of lignin-based biochar (LBB) and its ability to remove benzo[a]pyrene (BaP) from sesame oil. The results showed that white sesame straw was the most suitable raw material for preparing biochar. In terms of the preparation method, acid-extracted lignin biochar was more effective in removing BaP than alkaline or ethanol methods. Notably, WS-1LB (white sesame straw acid-extracted lignin biochar) exhibited the highest BaP adsorption efficiency (91.44 %) and the maximum specific surface area (1065.8187 m2/g), characterized by porous structures. The pseudo 2nd and Freundlich models were found to be the best fit for the adsorption kinetics and isotherms of BaP on LBB, respectively, suggesting that a multilayer adsorption process was dominant. The high adsorption of LBB mainly resulted from pore filling. This study provides an economical and highly efficient biochar adsorbent for the removal of BaP in oil.

6.
Front Psychiatry ; 15: 1349989, 2024.
Article En | MEDLINE | ID: mdl-38742128

Objective: Although extensive structural and functional abnormalities have been reported in schizophrenia, the gray matter volume (GMV) covariance of the amygdala remain unknown. The amygdala contains several subregions with different connection patterns and functions, but it is unclear whether the GMV covariance of these subregions are selectively affected in schizophrenia. Methods: To address this issue, we compared the GMV covariance of each amygdala subregion between 807 schizophrenia patients and 845 healthy controls from 11 centers. The amygdala was segmented into nine subregions using FreeSurfer (v7.1.1), including the lateral (La), basal (Ba), accessory-basal (AB), anterior-amygdaloid-area (AAA), central (Ce), medial (Me), cortical (Co), corticoamygdaloid-transition (CAT), and paralaminar (PL) nucleus. We developed an operational combat harmonization model for 11 centers, subsequently employing a voxel-wise general linear model to investigate the differences in GMV covariance between schizophrenia patients and healthy controls across these subregions and the entire brain, while adjusting for age, sex and TIV. Results: Our findings revealed that five amygdala subregions of schizophrenia patients, including bilateral AAA, CAT, and right Ba, demonstrated significantly increased GMV covariance with the hippocampus, striatum, orbitofrontal cortex, and so on (permutation test, P< 0.05, corrected). These findings could be replicated in most centers. Rigorous correlation analysis failed to identify relationships between the altered GMV covariance with positive and negative symptom scale, duration of illness, and antipsychotic medication measure. Conclusion: Our research is the first to discover selectively impaired GMV covariance patterns of amygdala subregion in a large multicenter sample size of patients with schizophrenia.

7.
ACS Nano ; 18(19): 12412-12426, 2024 May 14.
Article En | MEDLINE | ID: mdl-38693619

Glycans play vital roles in nearly all life processes of multicellular organisms, and understanding these activities is inseparable from elucidating the biological significance of glycans. However, glycan research has lagged behind that of DNA and protein due to the challenges posed by structural heterogeneity and isomerism (i.e., structures with equal molecular weights) the lack of high-efficiency structural analysis techniques. Nanopore technology has emerged as a sensitive single-molecule biosensor, shining a light on glycan analysis. However, a significant number of glycans are small and uncharged, making it challenging to elicit identifiable nanopore signals. Here we introduce a R-binaphthyl tag into glycans, which enhances the cation-π interaction between the derivatized glycan molecules and the nanopore interface, enabling the detection of neutral glycans with an aerolysin nanopore. This approach allows for the distinction of di-, tri-, and tetrasaccharides with monosaccharide resolution and has the potential for group discrimination, the monitoring of enzymatic transglycosylation reactions. Notably, the aerolysin mutant T240R achieves unambiguous identification of six disaccharide isomers, trisaccharide and tetrasaccharide linkage isomers. Molecular docking simulations reveal that multiple noncovalent interactions occur between residues R282, K238, and R240 and the glycans and R-binaphthyl tag, significantly slowing down their translocation across the nanopore. Importantly, we provide a demonstration of the kinetic translocation process of neutral glycan isomers, establishing a solid theoretical foundation for glycan nanopore analysis. The development of our technology could promote the analysis of glycan structural isomers and has the potential for nanopore-based glycan structural determination and sequencing.


Bacterial Toxins , Nanopores , Polysaccharides , Pore Forming Cytotoxic Proteins , Polysaccharides/chemistry , Bacterial Toxins/chemistry , Bacterial Toxins/genetics , Pore Forming Cytotoxic Proteins/chemistry , Pore Forming Cytotoxic Proteins/genetics , Molecular Docking Simulation , Mutation
8.
Reprod Sci ; 2024 May 20.
Article En | MEDLINE | ID: mdl-38767769

Endometriosis (EM) is a common gynecologic condition that often leads to infertility in women of reproductive age. Cell adhesion molecule 2 (CADM2) is involved in maintaining cell adhesion and polarity, as well as suppressing tumors. However, the role and mechanism of CADM2 in endometriosis is unclear. Therefore, this study evaluated the expression levels of CADM2 and epithelial-mesenchymal transition (EMT)-related marker proteins (E-cadherin, α-SMA, and N-cadherin). Compared to normal endometrial tissue, CADM2 was expressed at low levels in ectopic endometrial tissue from patients with EM. We performed clone formation assays, wound healing assays, and Transwell cell invasion assays to investigate the effects of CADM2 on the biological behavior of endometriosis epithelial cells (11Z) and ectopic endometrial stromal cells (EESCs). The growth, migration, and invasion abilities of these cells were significantly inhibited by overexpression of CADM2. The results were reversed after the knockdown of CADM2. Finally, western blotting (WB) was utilized to detect the effect of CADM2 on EMT in endometriosis cells. CADM2 inhibited EMT in endometriosis cells. In conclusion, our study suggests that CADM2 is a negative regulator of endometriosis development and may inhibit endometriosis development by suppressing EMT.

9.
BMC Psychiatry ; 24(1): 352, 2024 May 10.
Article En | MEDLINE | ID: mdl-38730288

BACKGROUND: To explore the demographic and clinical features of current depressive episode that discriminate patients diagnosed with major depressive disorder (MDD) from those with bipolar I (BP-I) and bipolar II (BP-II) disorder who were misdiagnosed as having MDD . METHODS: The Mini-International Neuropsychiatric Interview (MINI) assessment was performed to establish DSM-IV diagnoses of MDD, and BP-I and BP-II, previously being misdiagnosed as MDD. Demographics, depressive symptoms and psychiatric comorbidities were compared between 1463 patients with BP-I, BP-II and MDD from 8 psychiatric settings in mainland China. A multinomial logistic regression model was performed to assess clinical correlates of diagnoses. RESULTS: A total of 14.5% of the enrolled patients initially diagnosed with MDD were eventually diagnosed with BP. Broad illness characteristics including younger age, higher prevalence of recurrence, concurrent dysthymia, suicidal attempts, agitation, psychotic features and psychiatric comorbidities, as well as lower prevalence of insomnia, weight loss and somatic symptoms were featured by patients with BP-I and/or BP-I, compared to those with MDD. Comparisons between BP-I and BP-II versus MDD indicated distinct symptom profiles and comorbidity patterns with more differences being observed between BP-II and MDD, than between BP-I and MDD . CONCLUSION: The results provide evidence of clinically distinguishing characteristics between misdiagnosed BP-I and BP- II versus MDD. The findings have implications for guiding more accurate diagnoses of bipolar disorders.


Bipolar Disorder , Comorbidity , Depressive Disorder, Major , Diagnostic Errors , Humans , Bipolar Disorder/diagnosis , Bipolar Disorder/epidemiology , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/epidemiology , Male , Female , Adult , Diagnostic Errors/statistics & numerical data , Middle Aged , China/epidemiology , Young Adult , Diagnostic and Statistical Manual of Mental Disorders
10.
J Drugs Dermatol ; 23(5): 353-359, 2024 05 01.
Article En | MEDLINE | ID: mdl-38709701

BACKGROUND: Medical aesthetic procedures for facial antiaging with laser and energy-based devices (EBDs) are rapidly increasing, but standards integrating skincare before, during, and after these treatments are lacking. The algorithm for integrated skin care for facial antiaging treatment with EBDs aims to stimulate healing, reduce downtime, and improve comfort and treatment outcomes. METHODS: A panel of 8 global physicians employed a modified Delphi method and reached a consensus on the algorithm integrating skincare based on the best available evidence, the panel's clinical experience, and opinions. RESULTS: The algorithm has a pretreatment (starts 2 - 4 weeks before the procedure) and treatment (day of treatment) section, followed by care after the procedure (0 - 7 days) and follow-up care (1 - 4 weeks after the procedure or ongoing). Applying a broad-spectrum sunscreen with an SPF 50 or higher, combined with protective measures such as wearing a wide-brimmed hat and sunglasses, is recommended to protect the face from sun exposure. Dyschromia is a significant concern for those with skin of color (SOC). Clinicians may recommend skincare using a gentle cleanser and moisturizer containing vitamins C and E, retinoid, or other ingredients such as niacinamide, kojic acid, licorice root extract, azelaic acid, and tranexamic acid, depending on the patient's facial skin condition. CONCLUSION: Medical aesthetic procedures for facial antiaging with EBDs integrating skincare or topical treatments may improve outcomes and patient satisfaction. Topical antioxidants and free radical quenchers can combat photodamage and may offer a safe alternative to topical hydroquinone.  J Drugs Dermatol. 2024;23(5):353-359.     doi:10.36849/JDD.8092.


Algorithms , Patient Satisfaction , Skin Aging , Skin Care , Humans , Skin Aging/drug effects , Skin Care/methods , Delphi Technique , Treatment Outcome , Face , Laser Therapy/methods , Sunscreening Agents/administration & dosage
11.
Heliyon ; 10(9): e30712, 2024 May 15.
Article En | MEDLINE | ID: mdl-38765131

Objectives: We aimed to evaluate and compare the diagnostic performance of RNA-mNGS and DNA-mNGS workflow in bacterial pneumonia, fungal pneumonia and tuberculosis. Methods: A total of 134 cases suspected pneumonia undergoing both DNA and RNA based mNGS of bronchoalveolar lavage fluid (BALF) and also traditional etiological examination were evaluated retrospectively.Sensitivity, specificity, PPV, NPV and accuracy rate of DNA and RNA based mNGS were estimated. Results: In the diagnosis performance of bacterial pathogens in LRTIs,the specificity of RNA-mNGS was higher than that of DNA-mNGS(82.3 % vs. 61.9 %, P < 0.01). There was no significant difference of sensitivity between the two process(71.4 % vs. 85.7 %, P = 0.375).In the diagnosis performance of fungal pathogens in LRTIs,the specificity of RNA-mNGS was higher than that of DNA-mNGS (72.3 % vs. 27.3 %,p < 0.001). There was no significant difference of sensitivity between the two process(96.5 % vs. 98.8 %,p = 0.125).In the diagnosis performance of tuberculosis in LRTIs,the sensitivity of DNA-mNGS was higher than that of RNA-mNGS (91.7 % vs. 33.3 %,p = 0.016),the specificity was similar in the two process (100 %). Conclusions: RNA-mNGS may reduced the misdiagnosis rate of bacterial and fungal pathogens in LRTIs.Compared to RNA-mNGS, DNA-mNGS may could improve the diagnostic rate of tuberculosis.

12.
Pharm Biol ; 62(1): 456-471, 2024 Dec.
Article En | MEDLINE | ID: mdl-38773737

CONTEXT: The mechanisms of Traditional Chinese Medicine (TCM) Guizhi-Gancao Decoction (GGD) remain unknown. OBJECTIVE: This study explores the mechanisms of GGD against cardiac hypertrophy. MATERIALS AND METHODS: Network pharmacology analysis was carried out to identify the potential targets of GGD. In vivo experiments, C57BL/6J mice were divided into Con, phenylephrine (PE, 10 mg/kg/d), 2-chloroadenosine (CADO, the stable analogue of adenosine, 2 mg/kg/d), GGD (5.4 g/kg/d) and GGD (5.4 g/kg/d) + CGS15943 (a nonselective adenosine receptor antagonist, 4 mg/kg/d). In vitro experiments, primary neonatal rat cardiomyocytes (NRCM) were divided into Con, PE (100 µM), CADO (5 µM), GGD (10-5 g/mL) and GGD (10-5 g/mL) + CGS15943 (5 µM). Ultrasound, H&E and Masson staining, hypertrophic genes expression and cell surface area were conducted to verify the GGD efficacy. Adenosine receptors (ADORs) expression were tested via real-time polymerase chain reaction (PCR), western blotting and immunofluorescence analysis. RESULTS: Network pharmacology identified ADORs among those of the core targets of GGD. In vitro experiments demonstrated that GGD attenuated PE-induced increased surface area (with an EC50 of 5.484 × 10-6 g/mL). In vivo data shown that GGD attenuated PE-induced ventricular wall thickening. In vitro and in vivo data indicated that GGD alleviated PE-induced hypertrophic gene expression (e.g., ANP, BNP and MYH7/MYH6), A1AR over-expression and A2aAR down-expression. Moreover, CADO exerts effects similar to GGD, whereas CGS15943 eliminated most effects of GGD. DISCUSSION AND CONCLUSIONS: Our findings suggest the mechanism by which GGD inhibits cardiac hypertrophy, highlighting regulation of ADORs as a potential therapeutic strategy for HF.


Cardiomegaly , Drugs, Chinese Herbal , Mice, Inbred C57BL , Myocytes, Cardiac , Network Pharmacology , Phenylephrine , Animals , Drugs, Chinese Herbal/pharmacology , Phenylephrine/pharmacology , Cardiomegaly/drug therapy , Cardiomegaly/chemically induced , Mice , Male , Rats , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology , Myocytes, Cardiac/metabolism , Rats, Sprague-Dawley , Cells, Cultured , Disease Models, Animal , Medicine, Chinese Traditional/methods
13.
Theranostics ; 14(7): 2757-2776, 2024.
Article En | MEDLINE | ID: mdl-38773982

Background: Cancer cells are capable of evading clearance by macrophages through overexpression of anti-phagocytic surface proteins known as "don't eat me" signals. Monoclonal antibodies that antagonize the "don't-eat-me" signaling in macrophages and tumor cells by targeting phagocytic checkpoints have shown therapeutic promises in several cancer types. However, studies on the responses to these drugs have revealed the existence of other unknown "don't eat me" signals. Moreover, identification of key molecules and interactions regulating macrophage phagocytosis is required for tumor therapy. Methods: CRISPR screen was used to identify genes that impede macrophage phagocytosis. To explore the function of Vtn and C1qbp in phagocytosis, knockdown and subsequent functional experiments were conducted. Flow cytometry were performed to explore the phagocytosis rate, polarization of macrophage, and immune microenvironment of mouse tumor. To explore the underlying molecular mechanisms, RNA sequencing, immunoprecipitation, mass spectrometry, and immunofluorescence were conducted. Then, in vivo experiments in mouse models were conducted to explore the probability of Vtn knockdown combined with anti-CD47 therapy in breast cancer. Single-cell sequencing data from the Gene Expression Omnibus from The Cancer Genome Atlas database were analyzed. Results: We performed a genome-wide CRISPR screen to identify genes that impede macrophage phagocytosis, followed by analysis of cell-to-cell interaction databases. We identified a ligand-receptor pair of Vitronectin (Vtn) and complement C1Q binding protein (C1qbp) in tumor cells or macrophages, respectively. We demonstrated tumor cell-secreted Vtn interacts with C1qbp localized on the cell surface of tumor-associated macrophages, inhibiting phagocytosis of tumor cells and shifting macrophages towards the M2-like subtype in the tumor microenvironment. Mechanistically, the Vtn-C1qbp axis facilitated FcγRIIIA/CD16-induced Shp1 recruitment, which reduced the phosphorylation of Syk. Furthermore, the combination of Vtn knockdown and anti-CD47 antibody effectively enhanced phagocytosis and infiltration of macrophages, resulting in a reduction of tumor growth in vivo. Conclusions: This work has revealed that the Vtn-C1qbp axis is a new anti-phagocytic signal in tumors, and targeting Vtn and its interaction with C1qbp may sensitize cancer to immunotherapy, providing a new molecular target for the treatment of triple-negative breast cancer.


CD47 Antigen , Macrophages , Phagocytosis , Animals , Mice , Humans , Macrophages/metabolism , Macrophages/immunology , CD47 Antigen/metabolism , CD47 Antigen/genetics , Female , Cell Line, Tumor , Tumor Microenvironment/immunology , Tumor Microenvironment/drug effects , Cell Communication , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/immunology , Breast Neoplasms/genetics , Signal Transduction/drug effects , Mice, Inbred BALB C , Carrier Proteins , Mitochondrial Proteins
14.
J Agric Food Chem ; 72(20): 11321-11330, 2024 May 22.
Article En | MEDLINE | ID: mdl-38714361

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a crucial target enzyme in albino herbicides. The inhibition of HPPD activity interferes with the synthesis of carotenoids, blocking photosynthesis and resulting in bleaching and necrosis. To develop herbicides with excellent activity, a series of 3-hydroxy-2-(6-substituted phenoxynicotinoyl)-2-cyclohexen-1-one derivatives were designed via active substructure combination. The title compounds were characterized via infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopies, and high-resolution mass spectrometry. The structure of compound III-17 was confirmed via single-crystal X-ray diffraction. Preliminary tests demonstrated that some compounds had good herbicidal activity. Crop safety tests revealed that compound III-29 was safer than the commercial herbicide mesotrione in wheat and peanuts. Moreover, the compound exhibited the highest inhibitory activity against Arabidopsis thaliana HPPD (AtHPPD), with a half-maximal inhibitory concentration of 0.19 µM, demonstrating superior activity compared with mesotrione (0.28 µM) in vitro. A three-dimensional quantitative structure-activity relationship study revealed that the introduction of smaller groups to the 5-position of cyclohexanedione and negative charges to the 3-position of the benzene ring enhanced the herbicidal activity. A molecular structure comparison demonstrated that compound III-29 was beneficial to plant absorption and conduction. Molecular docking and molecular dynamics simulations further verified the stability of the complex formed by compound III-29 and AtHPPD. Thus, this study may provide insights into the development of green and efficient herbicides.


4-Hydroxyphenylpyruvate Dioxygenase , Arabidopsis , Drug Design , Enzyme Inhibitors , Herbicides , Molecular Docking Simulation , Herbicides/chemistry , Herbicides/pharmacology , Herbicides/chemical synthesis , 4-Hydroxyphenylpyruvate Dioxygenase/antagonists & inhibitors , 4-Hydroxyphenylpyruvate Dioxygenase/chemistry , 4-Hydroxyphenylpyruvate Dioxygenase/metabolism , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Arabidopsis/drug effects , Arabidopsis/growth & development , Structure-Activity Relationship , Molecular Structure , Ketones/chemistry , Ketones/pharmacology , Ketones/chemical synthesis , Cyclohexanones/chemistry , Cyclohexanones/pharmacology , Cyclohexanones/chemical synthesis , Triticum/chemistry , Arabidopsis Proteins/antagonists & inhibitors , Arabidopsis Proteins/chemistry , Arabidopsis Proteins/metabolism
15.
J Nat Med ; 78(3): 633-643, 2024 Jun.
Article En | MEDLINE | ID: mdl-38704807

Hepatocellular carcinoma (HCC) is a malignant tumor with extremely high mortality. The tumor microenvironment is the "soil" of its occurrence and development, and the inflammatory microenvironment is an important part of the "soil". Bile acid is closely related to the occurrence of HCC. Bile acid metabolism disorder is not only directly involved in the occurrence and development of HCC but also affects the inflammatory microenvironment of HCC. Yinchenhao decoction, a traditional Chinese medicine formula, can regulate bile acid metabolism and may affect the inflammatory microenvironment of HCC. To determine the effect of Yinchenhao decoction on bile acid metabolism in mice with HCC and to explore the possible mechanism by which Yinchenhao decoction improves the inflammatory microenvironment of HCC by regulating bile acid metabolism, we established mice model of orthotopic transplantation of hepatocellular carcinoma. These mice were treated with three doses of Yinchenhao decoction, then liver samples were collected and tested. Yinchenhao decoction can regulate the disorder of bile acid metabolism in liver cancer mice. Besides, it can improve inflammatory reactions, reduce hepatocyte degeneration and necrosis, and even reduce liver weight and the liver index. Taurochenodeoxycholic acid, hyodeoxycholic acid, and taurohyodeoxycholic acid are important molecules in the regulation of the liver inflammatory microenvironment, laying a foundation for the regulation of the liver tumor inflammatory microenvironment based on bile acids. Yinchenhao decoction may improve the inflammatory microenvironment of mice with HCC by ameliorating hepatic bile acid metabolism.


Bile Acids and Salts , Carcinoma, Hepatocellular , Drugs, Chinese Herbal , Liver Neoplasms , Tumor Microenvironment , Animals , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Mice , Bile Acids and Salts/metabolism , Tumor Microenvironment/drug effects , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Male , Liver/drug effects , Liver/metabolism , Liver/pathology , Inflammation/drug therapy , Inflammation/metabolism
16.
Int J Biol Macromol ; 268(Pt 1): 131619, 2024 May.
Article En | MEDLINE | ID: mdl-38692998

The plant cell wall is a complex, heterogeneous structure primarily composed of cellulose, hemicelluloses, and lignin. Exploring the variations in these three macromolecules over time is crucial for understanding wood formation to enhance chemical processing and utilization. Here, we comprehensively analyzed the chemical composition of cell walls in the trunks of Pinus tabulaeformis using multiple techniques. In situ analysis showed that macromolecules accumulated gradually in the cell wall as the plant aged, and the distribution pattern of lignin was opposite that of polysaccharides, and both showed heterogenous distribution patterns. In addition, gel permeation chromatography (GPC) results revealed that the molecular weights of hemicelluloses decreased while that of lignin increased with age. Two-dimensional heteronuclear single quantum coherence nuclear magnetic resonance (2D-HSQC NMR) analysis indicated that hemicelluloses mainly comprised galactoglucomannan and arabinoglucuronoxylan, and the lignin types were mainly comprised guaiacyl (G) and p-hydroxyphenyl (H) units with three main linkage types: ß-O-4, ß-ß, and ß-5. Furthermore, the C-O bond (ß-O-4) signals of lignin decreased while the C-C bonds (ß-ß and ß-5) signals increased over time. Taken together, these findings shed light on wood formation in P. tabulaeformis and lay the foundation for enhancing the processing and use of wood and timber products.


Cell Wall , Cellulose , Lignin , Pinus , Polysaccharides , Lignin/chemistry , Pinus/chemistry , Cell Wall/chemistry , Polysaccharides/chemistry , Cellulose/chemistry , Molecular Weight , Trees/chemistry , Magnetic Resonance Spectroscopy/methods , Wood/chemistry
17.
Dalton Trans ; 53(20): 8716-8721, 2024 May 21.
Article En | MEDLINE | ID: mdl-38711354

Immobilization of imidazole molecules as proton carriers into MOFs to facilitate proton conduction is a general strategy for developing high proton conductive materials. Herein, we designed two imidazole substituted phthalic acid ligands and constructed two novel MOFs, {[Zr6(OH)16(H3L1)4]Cl8·20H2O}n [Zr-MOF; H3L1 = 2-(1H-imidazol-4-yl) methylaminoterephthalic acid] and {Gd(HCOO)(H2L2)2}n [Gd-MOF; H3L2 = 5-(1H-imidazol-4-yl)methylaminoisophthalic acid] and fully studied their porous nature, stability and water-assisted proton conduction. The resulting Zr-MOF exhibits a high proton conductivity of 1.82 × 10-2 S cm-1 at 98% RH and 80 °C, while Gd-MOF has a proton conductivity of 3.01 × 10-3 S cm-1 at 98% RH and 60 °C.

18.
J Am Heart Assoc ; 13(10): e032856, 2024 May 21.
Article En | MEDLINE | ID: mdl-38726896

BACKGROUND: We aimed to investigate the association of characteristics of lenticulostriate artery (LSA) morphology and parental atheromatous disease (PAD) with single subcortical infarction (SSI) and to explore whether the LSA morphology is correlated with proximal plaque features in asymptomatic PAD. METHODS AND RESULTS: Patients with acute SSI were prospectively enrolled and classified as large- and small-SSI groups. The clinical data and imaging features of LSA morphology (branches, length, dilation, and tortuosity) and middle cerebral artery plaques (normalized wall index, remodeling index, enhancement degree, and hyperintense plaques) were evaluated. Logistic regression was performed to determine the association of large SSIs with morphologic features of LSAs and plaques. The Spearman correlation between the morphologic characteristics of LSAs and plaque features in asymptomatic PAD was analyzed. Of the 121 patients recruited with symptomatic PAD, 102 had coexisting asymptomatic contralateral PAD. The mean length of LSAs (odds ratio, 0.84 [95% CI, 0.73-0.95]; P=0.007), mean tortuosity of LSAs (odds ratio, 1.13 [95% CI, 1.05-1.22]; P=0.002), dilated LSAs (odds ratio, 22.59 [95% CI, 2.46-207.74]; P=0.006), and normalized wall index (odds ratio, 1.08 [95% CI, 1.01-1.15]; P=0.022) were significantly associated with large SSIs. Moreover, the normalized wall index was negatively correlated with the mean length of LSAs (r=-0.348, P<0.001), and the remodeling index was negatively correlated with the mean tortuosity of LSAs (r=-0.348, P<0.001) in asymptomatic PAD. CONCLUSIONS: Our findings suggest that mean length of LSAs, mean tortuosity of LSAs, dilated LSAs, and normalized wall index are associated with large SSIs. Moreover, plaque features in asymptomatic PAD are correlated with morphologic features of LSAs.


Plaque, Atherosclerotic , Humans , Male , Female , Aged , Middle Aged , Prospective Studies , Cerebral Infarction/diagnostic imaging , Cerebral Infarction/pathology , Magnetic Resonance Angiography , Basal Ganglia Cerebrovascular Disease/diagnostic imaging , Basal Ganglia Cerebrovascular Disease/pathology , Asymptomatic Diseases , Cerebral Angiography/methods
19.
Eur J Med Chem ; 272: 116466, 2024 May 01.
Article En | MEDLINE | ID: mdl-38704938

P-glycoprotein (Pgp) modulators are promising agents for overcoming multidrug resistance (MDR) in cancer chemotherapy. In this study, via structural optimization of our lead compound S54 (nonsubstrate allosteric inhibitor of Pgp), 29 novel pyxinol amide derivatives bearing an aliphatic heterocycle were designed, synthesized, and screened for MDR reversal activity in KBV cells. Unlike S54, these active derivatives were shown to transport substrates of Pgp. The most potent derivative 4c exhibited promising MDR reversal activity (IC50 of paclitaxel = 8.80 ± 0.56 nM, reversal fold = 211.8), which was slightly better than that of third-generation Pgp modulator tariquidar (IC50 of paclitaxel = 9.02 ± 0.35 nM, reversal fold = 206.6). Moreover, the cytotoxicity of this derivative was 8-fold lower than that of tariquidar in human normal HK-2 cells. Furthermore, 4c blocked the efflux function of Pgp and displayed high selectivity for Pgp but had no effect on its expression and distribution. Molecular docking revealed that 4c bound preferentially to the drug-binding domain of Pgp. Overall, 4c is a promising lead compound for developing Pgp modulators.

20.
Gerontology ; 2024 May 02.
Article En | MEDLINE | ID: mdl-38697041

INTRODUCTION: Motoric cognitive risk syndrome (MCR) is a newly proposed pre-dementia syndrome characterized by subjective cognitive complaints (SCC) and slow gait (SG). Increasing evidence links MCR to several adverse health outcomes, but the specific relationship between MCR and the risk of frailty, Alzheimer's disease (AD) and vascular dementia (VaD) remains unclear. Additionally, literature lacks analysis of MCR's components and associated health outcomes, complicating risk identification. This systematic review and meta-analysis aim to provide a comprehensive overview of MCR's predictive value for adverse health outcomes. METHODS: Relevant cross-sectional, cohort, and longitudinal studies examining the association between MCR and adverse health outcomes were extracted from seven electronic databases. The Newcastle Ottawa Scale (NOS) and modified NOS were used to assess the risk of bias in studies included in the analysis. Relative ratios (RRs) and 95% confidence intervals (CIs) were pooled for outcomes associated with MCR. RESULTS: Twenty-eight longitudinal or cohort studies and four cross-sectional studies with 1,224,569 participants were included in the final analysis. The risk of bias in all included studies was rated as low or moderate. Pooled analysis of RR indicated that MCR had a greater probability of increased the risk of dementia (adjusted RR=2.02; 95%CI=1.94-2.11), cognitive impairment (adjusted RR=1.72; 95%CI=1.49-1.99), falls (adjusted RR=1.32; 95%CI=1.17-1.50), mortality (adjusted RR=1.66; 95%CI=1.32-2.10); MCR had more prominent predictive efficacy for AD (adjusted RR=2.23; 95%CI=1.81-2.76) compared to VaD (adjusted RR=3.78; 95%CI=0.49-28.95), while excluding analyses from the study that utilized the Timed-up-and-go test and one-leg-standing to evaluate gait speed. One study examined the association between MCR and disability (HR=1.69; 95%CI=1.08-2.02) and frailty (OR=5.53; 95%CI=1.46-20.89). SG was a stronger predictor of the risk for dementia and falls than SCC (adjusted RR=1.22; 95%CI=1.11-1.34 vs. adjusted RR=1.19; 95%CI= 1.03-1.38). CONCLUSION: MCR increases the risk of developing any discussed adverse health outcomes and the predictive value for AD is superior to VaD. Additionally, SG is a stronger predictor of dementia and falls than SCC. Therefore, MCR should be routinely assessed among adults to prevent poor prognosis, and provide evidence to support future targeted interventions.

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