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1.
Cancer Med ; 13(17): e70181, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39279295

ABSTRACT

OBJECTIVES: To assess the efficacy and safety of preoperative neoadjuvant everolimus in renal angiomyolipomas (AML) patients with or without Tuberous Sclerosis Complex (TSC). MATERIALS AND METHODS: This multi-institutional retrospective study enrolled renal AML patients who underwent partial nephrectomy (PN) or total nephrectomy after receiving at least 1 month of pre-operative everolimus. Imaging evaluations were collected before and after treatment, along with demographic, surgical, and follow-up information. The primary outcome was tumor volume reduction of ≥25%, with additional outcomes including recurrence, perioperative outcomes, renal function, and safety. RESULTS: From January 2015 to July 2022, 68 renal AML patients were studied-41 with TSC and 27 without. During everolimus treatment, 61.0% (25/41) of TSC patients and 44.4% (12/27) of non-TSC patients achieved tumor reduction of ≥25%. Additionally, 41.5% (17/41) of TSC patients and 18.5% (5/27) of non-TSC patients achieved a ≥ 50% reduction. Three TSC patients and 1 non-TSC patient discontinued treatment due to side-effects. Most patients (92.7% TSC, 85.2% non-TSC) underwent PN. After everolimus treatment, the necessary total nephrectomy decreased to 41.2% (7/17) from baseline. Postoperatively, 1 grade 3 and 3 grade 2 complications occurred, with no grade 4 or 5 complications. After a median follow-up of 24 months, only 1 TSC patient recurred with a diameter >3 cm. Retrospective nature is the major limitation of this study. CONCLUSION: Everolimus was effective and well-tolerated in neoadjuvant treatment for renal AML, especially in TSC patients. This neoadjuvant combination strategy of everolimus and PN could effectively controls recurrence and preserves renal function.


Subject(s)
Angiomyolipoma , Everolimus , Kidney Neoplasms , Neoadjuvant Therapy , Nephrectomy , Tuberous Sclerosis , Humans , Everolimus/therapeutic use , Everolimus/administration & dosage , Everolimus/adverse effects , Angiomyolipoma/drug therapy , Angiomyolipoma/pathology , Female , Male , Retrospective Studies , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Middle Aged , Neoadjuvant Therapy/methods , Tuberous Sclerosis/complications , Tuberous Sclerosis/drug therapy , Adult , Treatment Outcome , Aged
2.
BMC Cancer ; 24(1): 1095, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39227825

ABSTRACT

PURPOSE: One of the most frequent side effects of radical prostatectomy (RP) is urinary incontinence. The primary cause of urine incontinence is usually thought to be impaired urethral sphincter function; nevertheless, the pathophysiology and recovery process of urine incontinence remains unclear. This study aimed to identify potential risk variables, build a risk prediction tool that considers preoperative urodynamic findings, and direct doctors to take necessary action to reduce the likelihood of developing early urinary incontinence. METHODS: We retrospectively screened patients who underwent radical prostatectomy between January 1, 2020 and December 31, 2023 at the First People 's Hospital of Nantong, China. According to nomogram results, patients who developed incontinence within three months were classified as having early incontinence. The training group's general characteristics were first screened using univariate logistic analysis, and the LASSO method was applied for the best prediction. Multivariate logistic regression analysis was carried out to determine independent risk factors for early postoperative urine incontinence in the training group and to create nomograms that predict the likelihood of developing early urinary incontinence. The model was internally validated by computing the performance of the validation cohort. The nomogram discrimination, correction, and clinical usefulness were assessed using the c-index, receiver operating characteristic curve, correction plot, and clinical decision curve. RESULTS: The study involved 142 patients in all. Multivariate logistic regression analysis following RP found seven independent risk variables for early urinary incontinence. A nomogram was constructed based on these independent risk factors. The training and validation groups' c-indices showed that the model had high accuracy and stability. The calibration curve demonstrates that the corrective effect of the training and verification groups is perfect, and the area under the receiver operating characteristic curve indicates great identification capacity. Using a nomogram, the clinical net benefit was maximised within a probability threshold of 0.01-1, according to decision curve analysis (DCA). CONCLUSION: The nomogram model created in this study can offer a clear, personalised analysis of the risk of early urine incontinence following RP. It is highly discriminatory and accurate, and it can help create efficient preventative measures and identify high-risk populations.


Subject(s)
Nomograms , Prostatectomy , Prostatic Neoplasms , Urinary Incontinence , Humans , Prostatectomy/adverse effects , Urinary Incontinence/etiology , Urinary Incontinence/diagnosis , Male , Middle Aged , Retrospective Studies , Prostatic Neoplasms/surgery , Aged , Risk Factors , Postoperative Complications/etiology , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , ROC Curve , China/epidemiology
3.
Arch Esp Urol ; 77(7): 772-778, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39238302

ABSTRACT

OBJECTIVE: Renal calculi are solid crystals that form in the kidneys and cause severe pain and discomfort. This study aims to investigate risk factors for postoperative recurrence of renal calculi in elderly patients and provide background knowledge on the prevalence and management of renal calculi in this demographic. METHODS: The clinical data of 123 elderly patients with renal calculi were included from 1 June 2021 to 1 June 2023 for their 6-month follow-up study. The patients were divided into recurrence group and non-recurrence group according to whether they had recurrence after surgery. The general sociological characteristics and disease-related characteristics of the two groups were counted. Logistic regression equation was used to calculate differences, and the influencing factors of postoperative recurrence in elderly patients with kidney stones were obtained. A receiver operating characteristic (ROC) curve was drawn to analyse the value of the factors in predicting postoperative recurrence in patients with kidney stones. RESULTS: A total of 123 elderly patients with renal calculi were enrolled. The patients were divided according to the presence or absence of stone recurrence into the recurrence group (25 cases, 20.33%) and the non-recurrence group (98 cases, 79.67%). Postoperative water intake, excessive intake of animal protein, exercise and postoperative complications significantly differed between the recurrence group and the non-recurrence group (p < 0.001). Logistic regression analysis showed that the above-mentioned indicators were the influencing factors of postoperative recurrence. The area under the curve (AUC) values of postoperative water intake (AUC = 0.767), animal protein intake (AUC = 0.752), exercise (AUC = 0.707) and postoperative complications (AUC = 0.727) were statistically significant, and they were identified as the most important factors with high sensitivity and specificity and were of high value in predicting postoperative recurrence of renal calculi. CONCLUSIONS: Elderly patients with kidney stones are prone to recurrence after surgery. Influencing factors should be given attention, and corresponding measures should be formulated for intervention as soon as possible.


Subject(s)
Kidney Calculi , Recurrence , Humans , Kidney Calculi/surgery , Male , Female , Aged , Risk Factors , Case-Control Studies , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Risk Assessment , Aged, 80 and over
4.
Nucleic Acids Res ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39265120

ABSTRACT

Perturb-Seq combines CRISPR (clustered regularly interspaced short palindromic repeats)-based genetic screens with single-cell RNA sequencing readouts for high-content phenotypic screens. Despite the rapid accumulation of Perturb-Seq datasets, there remains a lack of a user-friendly platform for their efficient reuse. Here, we developed PerturbDB (http://research.gzsys.org.cn/perturbdb), a platform to help users unveil gene functions using Perturb-Seq datasets. PerturbDB hosts 66 Perturb-Seq datasets, which encompass 4 518 521 single-cell transcriptomes derived from the knockdown of 10 194 genes across 19 different cell lines. All datasets were uniformly processed using the Mixscape algorithm. Genes were clustered by their perturbed transcriptomic phenotypes derived from Perturb-Seq data, resulting in 421 gene clusters, 157 of which were stable across different cellular contexts. Through integrating chemically perturbed transcriptomes with Perturb-Seq data, we identified 552 potential inhibitors targeting 1409 genes, including an mammalian target of rapamycin (mTOR) signaling inhibitor, retinol, which was experimentally verified. Moreover, we developed a 'Cancer' module to facilitate the understanding of the regulatory role of genes in cancer using Perturb-Seq data. An interactive web interface has also been developed, enabling users to visualize, analyze and download all the comprehensive datasets available in PerturbDB. PerturbDB will greatly drive gene functional studies and enhance our understanding of the regulatory roles of genes in diseases such as cancer.

5.
Int J Biol Macromol ; 277(Pt 4): 134562, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39116982

ABSTRACT

Antifreeze proteins (AFPs) can inhibit ice crystal growth. The ice-binding mechanism of AFPs remains unclear, yet the hydration shells of AFPs are thought to play an important role in modulating the binding of AFPs and ice. Here, we performed all-atom molecular dynamics simulations of an AFP from Choristoneura fumiferana (CfAFP) at four different temperatures, with a focus on analysis at 240 and 300 K, to investigate the dynamic and thermodynamic characteristics of hydration shells around ice-binding surfaces (IBS) and non-ice-binding surfaces (NIBS). Our results revealed that the dynamics of CfAFP hydration shells were highly heterogeneous, with its IBS favoring a less dense and more tetrahedral solvation shell, and NIBS hydration shells having opposite features to those of the IBS. The IBS of nine typical hyperactive AFPs were found to be in pure low-entropy hydration shell region, indicating that low-entropy hydration shell region of IBS and the tetrahedral arrangements of water molecules around them mediate the ice-binding mechanism of AFPs. It is because the entropy increase of the low-entropy hydration shell around IBS, while the higher entropy water molecules at NIBS most likely prevent ice crystal growth. These findings provide new mechanistic insights into the ice-binding of AFPs.


Subject(s)
Antifreeze Proteins , Insect Proteins , Moths , Antifreeze Proteins/chemistry , Antifreeze Proteins/metabolism , Moths/chemistry , Moths/metabolism , Insect Proteins/chemistry , Insect Proteins/metabolism , Ice , Entropy , Animals , Adsorption , Computer Simulation
6.
Nat Commun ; 15(1): 6973, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39143058

ABSTRACT

Mechanochemistry studies the effect of mechanical force on chemical bonds, bringing opportunities for synthesizing alloys, ceramics, organics, polymers, and biomaterials. A vital issue of applying macro-scale mechanical force to manipulate crystal structures is finding ways to precisely adjust the force directions to break micro-scale target chemical bonds. Inspired by a common technique of driving a wedge into the wood to make wood chopping much easier, a wedging strategy of splitting three-dimensional structured crystalline frameworks and then converting them to nanosheets was proposed, where specific molecules were wedged into crystalline frameworks to drive the directional transmission of mechanical force to break chemical bonds. As a result, various crystalline framework nanosheets including metal-organic framework nanosheets, covalent organic framework nanosheets, and coordination polymer nanosheets were fabricated. This wedging crystal strategy exhibits advantages of operability, flexibility and designability, and furthermore, it is expected to expand mechanochemistry applications in material preparation.

7.
Huan Jing Ke Xue ; 45(7): 3919-3929, 2024 Jul 08.
Article in Chinese | MEDLINE | ID: mdl-39022940

ABSTRACT

Organophosphates (OPEs) are widely used as flame retardants and additives and thus are commonly detected in the environment. In order to explore their environmental behavior, the concentrations of 13 OPEs in the surface water and sediment of Dongting Lake were analyzed using UPLC-MS/MS. The results showed that 11 OPEs were detected, with detection frequencies of 5.26%-100% and 58.3%-100%, and the concentrations of OPEs were 2.06-2 028 ng·L-1 and 19.6-2 232 ng·g-1 in water and sediment, respectively. Overall, contamination concentrations were ranked in descending order as follows: inflowing rivers, lake area, and outlet, whereas the spatial distribution of concentrations in sediment was inversely proportional to hydrodynamics. The concentration of OPEs in Dongting Lake was at a high level compared with that of domestic and foreign lakes. Among the detected 11 OPEs, tri-iso-butyl phosphate (TnBP) and (TiBP) were dominant in water, accounting for 52.3% and 22.4% of ∑OPEs, respectively. TPhP was the dominant OPEs in sediment, accounting for 31.2% of ∑OPEs. The correlation and principal component analysis indicated that OPEs pollution in Dongting Lake was mainly affected by industrial production emissions, fishery aquaculture, and atmospheric deposition. The assessment results of the risk entropy showed that most of the detected OPEs in water had relatively low ecological risks, whereas the ecological risk of 2-ethylhexyl diphenyl phosphate (EHDPP) at some sampling points requires further attention.

8.
Article in English | MEDLINE | ID: mdl-39004908

ABSTRACT

BACKGROUND: Prostate cancer is an adverse tumor that occurs in the male reproductive system. The symptoms of patients in the early stage are not obvious and are generally difficult to detect. AIM: The aim of this study was to determine the regulation of lncRNA GABPB1-AS1 (GABPB1-AS1) on prostate cancer progression and explore the diagnostic potential of GABPB1-AS1. METHODS: The contents of serum GABPB1-AS1 and miR-330-3p were examined by RT-qPCR assay. The functions of silencing GABPB1-AS1 and miR-330-3p inhibitor in prostate cancer cells were determined using transfection assay, CCK-8 assay and Transwell assay. The target of GABPB1-AS1 was predicted and verified at the molecular level by bioinformatics and luciferase reporter gene assay. The function of GABPB1-AS1 in prostate cancer diagnosis was evaluated via ROC method. RESULTS: GABPB1-AS1 was upregulated in prostate cancer serum, which was associated with patients' Gleason score and TNM stage. Mechanistically, GABPB1-AS1 directly targeted miR-330-3p, and there was a negative correlation between them. Reduced levels of GABPB1-AS1 in cells after knockdown of GABPB1-AS1 resulted in decreased prostate cancer cell growth and activity, and these inhibitory effects were repaired by miR-330-3p inhibitor. CONCLUSION: The present study confirmed that GABPB1-AS1 was overexpressed in prostate cancer, and its sponge miR-330-3p may be an effective target for timely diagnosis of prostate cancer.

9.
Neural Netw ; 178: 106491, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38972131

ABSTRACT

In this paper, we propose a novel two-layer fuzzy neural network model (TLFNN) for solving the inequality-constrained ℓ1-minimization problem. The stability and global convergence of the proposed TLFNN model are detailedly analyzed using the Lyapunov theory. Compared with the existing three-layer neural network model (TLNN) recently designed by Yang et al., the proposed TLFNN model possesses less storage, stronger robustness, faster convergence rate and higher convergence accuracy. These advantages are illustrated by some numerical experiments, where it is shown that the TLFNN model can achieve a convergence accuracy of 10-13 within 5s while the TLNN model can only acquire 10-6 in 105s when some random coefficient matrices are applied. Since the linear equality-constrained conditions can be equivalently transformed into double inequality-constrained ones, some simulation experiments for sparse signal reconstruction show that the proposed TLFNN model also has less convergence time and stronger robustness than the existing state-of-the-art neural network models for the equality-constrained ℓ1-minimization problem.


Subject(s)
Fuzzy Logic , Neural Networks, Computer , Algorithms , Computer Simulation , Humans
10.
Food Chem ; 459: 140345, 2024 Nov 30.
Article in English | MEDLINE | ID: mdl-38986204

ABSTRACT

Considering the high abundance of bound polyphenols (BP) in whole grain dietary fiber (DF), this study utilized multi-omics approach to evaluate the impact of BP of defatted rice bran insoluble DF (RIDF) in modulating obesity. Mice on high-fat diet were gavage-administered RIDF, BP-removed or formulated RIDF. The results indicated that DF significantly reduced serum total cholesterol, triglycerides, high-density and low-density lipoprotein cholesterol levels. Moreover, hepatic lipid accumulation and damage induced by high-fat diet were significantly ameliorated with DF intervention. The presence of BP increased the abundance of beneficial bacteria g_Akkermansia and g_Butyricicocus, as well as the expression of butyric acid/propionic acid. Furthermore, the expression of hepatic lipids and lipid-like molecules was significantly decreased under the combined intervention of BP and DF, and this was accompanied by alterations in genes related to lipid, sterol, and cholesterol metabolic biological processes. These findings suggest that BP contribute to the anti-obesity effects of DF.


Subject(s)
Anti-Obesity Agents , Diet, High-Fat , Dietary Fiber , Obesity , Oryza , Polyphenols , Animals , Humans , Male , Mice , Anti-Obesity Agents/administration & dosage , Anti-Obesity Agents/chemistry , Anti-Obesity Agents/pharmacology , Bacteria/genetics , Bacteria/metabolism , Bacteria/classification , Bacteria/isolation & purification , Bacteria/drug effects , Cholesterol/metabolism , Diet, High-Fat/adverse effects , Dietary Fiber/metabolism , Dietary Fiber/analysis , Dietary Fiber/pharmacology , Gastrointestinal Microbiome/drug effects , Lipid Metabolism/drug effects , Liver/metabolism , Liver/drug effects , Mice, Inbred C57BL , Multiomics , Obesity/metabolism , Obesity/drug therapy , Obesity/diet therapy , Obesity/genetics , Oryza/chemistry , Oryza/metabolism , Polyphenols/pharmacology , Polyphenols/chemistry , Polyphenols/administration & dosage , Polyphenols/metabolism , Triglycerides/metabolism
11.
Food Res Int ; 189: 114535, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38876588

ABSTRACT

The impact of different forms of dietary fiber (total, insoluble or soluble) derived from the same source on health remains incompletely understood. In this study, the effects of total, insoluble, and soluble dietary fiber extracted from highland barley (HDF, HIDF, and HSDF) on combating obesity were evaluated and compared. A high-fat diet (HFD) was used to induce obesity in a murine model, followed by gavage administration of HDF, HIDF, or HSDF, and a comprehensive multi-omics approach was utilized to assess and compare the effects of these dietary fibers on obesity-related parameters. The results showed that all three dietary fibers significantly reduced body weight, modified blood lipid profiles, and ameliorated tissue damage in HFD-fed mice. Additionally, 16S rRNA sequencing analysis of mice feces showed that three types of dietary fiber exerted varying degrees of impact on the composition and abundance of gut microbiota while simultaneously promoting the biosynthesis of short-chain fatty acids. Specifically, HDF supplementation remarkably enhanced the abundance of Coprococcus, while HIDF and HSDF supplementation elevated the levels of Akkermansia and Allobaculum, respectively. Transcriptomic and proteomic results suggested the PPAR signaling pathway as a central regulatory mechanism influenced by these fibers. HDF and HIDF were particularly effective in modulating biological processes related to triglyceride and fatty acid metabolism, identifying Abcc3 and Dapk1 as potential targets. Conversely, HSDF primarily affected processes related to membrane lipids, ceramides, and phospholipids metabolism, with Pck1 identified as a potential target. Collectively, HDF, HIDF, and HSDF demonstrated distinct mechanisms in exerting exceptional anti-obesity properties. These insights may inform the development of personalized dietary interventions for obesity.


Subject(s)
Anti-Obesity Agents , Diet, High-Fat , Dietary Fiber , Gastrointestinal Microbiome , Hordeum , Mice, Inbred C57BL , Obesity , Hordeum/chemistry , Dietary Fiber/pharmacology , Animals , Mice , Male , Anti-Obesity Agents/pharmacology , Gastrointestinal Microbiome/drug effects , Proteomics , Disease Models, Animal , Multiomics
12.
J Agric Food Chem ; 72(25): 14315-14325, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38847877

ABSTRACT

This study aimed to investigate the mitigation effect of epigallocatechin gallate (EGCG) on aging induced by 3-monochloropropane-1,2-diol (3-MCPD) in Caenorhabditis elegans, evaluate health indicators during the process, and reveal the underlying mechanism through transcriptomics and identification of mutants. The results showed that EGCG alleviated the declined fertility, shortened lifespan, reduced body size, weakened movement, increased reactive oxygen species and lipofuscin, and damaged antioxidative stress response and excessive heat shock proteins caused by 3-MCPD. Transcriptomics study indicated that treatment with 3-MCPD and EGCG altered gene expression, and gene mutants confirmed the involvement of insulin/IGF-1 signaling pathway in mediating the process that EGCG alleviated the aging toxicity induced by 3-MCPD. The study showed that EGCG alleviated the aging toxicity induced by 3-MCPD.


Subject(s)
Aging , Caenorhabditis elegans Proteins , Caenorhabditis elegans , Catechin , Heat-Shock Proteins , Reproduction , alpha-Chlorohydrin , Animals , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Catechin/analogs & derivatives , Catechin/pharmacology , Reproduction/drug effects , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , Aging/drug effects , alpha-Chlorohydrin/toxicity , Signal Transduction/drug effects , Reactive Oxygen Species/metabolism , Oxidative Stress/drug effects , Longevity/drug effects
13.
ACS Appl Mater Interfaces ; 16(27): 35024-35032, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38935758

ABSTRACT

Inorganic metal sulfides have received extensive investigation as anode materials in lithium-ion batteries (LIBs). However, applications of crystalline organic hybrid metal sulfides as anode materials in LIBs are quite rare. In addition, combining the nanoparticles of crystalline organic hybrid metal sulfides with conductive materials is expected to enhance the electrochemical lithium storage performance. Nevertheless, due to the difficulty of harvesting the nanoparticles of crystalline organic hybrid metal sulfides, this approach has never been tried to date. Herein, nanoparticles of a crystalline organic hybrid cadmium antimony sulfide (1,4-DABH2)Cd2Sb2S6 (DCAS) were prepared by a top-down method, including the procedures of solvothermal synthesis, ball milling, and ultrasonic pulverization. Thereafter, the nanoparticles of DCAS with sizes of ∼500 nm were intercalated into graphene oxide nanosheets through a freeze-drying treatment and a DCAS@GO composite was obtained. Compared with the reported Sb2S3- and CdS-based composites, the DCAS@GO composite exhibited superior electrochemical Li+ ion storage performance, including a high capacity of 1075.6 mAh g-1 at 100 mA g-1 and exceptional rate tolerances (646.8 mAh g-1 at 5000 mA g-1). In addition, DCAS@GO can provide a high capacity of 705.6 mAh g-1 after 500 cycles at 1000 mA g-1. Our research offers a viable approach for preparing the nanoparticles of crystalline organic hybrid metal sulfides and proves that intercalating organic hybrid metal sulfide nanoparticles into GO nanosheets can efficiently boost the electrochemical Li+ ion storage performance.

14.
Aging (Albany NY) ; 16(11): 9386-9409, 2024 05 30.
Article in English | MEDLINE | ID: mdl-38819232

ABSTRACT

OBJECTIVE: To investigate whether telomerase-associated lncRNA expression affects the prognosis and anti-tumor immunity of patients with renal clear cell carcinoma (ccRCC). METHODS: A series of analyses were performed to establish a prognostic risk model and validate its accuracy. Immune-related analyses were performed to assess further the association between immune status, tumor microenvironment, and prognostic risk models. RESULTS: Eight telomerase-associated lncRNAs associated with prognosis were identified and applied to establish a prognostic risk model. Overall survival was higher in the low-risk group. CONCLUSION: The established prognostic risk model has a good predictive ability for the prognosis of ccRCC patients and provides a new possible therapeutic target for ccRCC.


Subject(s)
Carcinoma, Renal Cell , Immunotherapy , Kidney Neoplasms , RNA, Long Noncoding , Telomerase , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/therapy , Carcinoma, Renal Cell/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/immunology , Kidney Neoplasms/mortality , Kidney Neoplasms/therapy , Telomerase/genetics , Telomerase/metabolism , Prognosis , Immunotherapy/methods , Gene Expression Regulation, Neoplastic , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Signal Transduction/genetics , Male , Female , Gene Regulatory Networks
15.
ACS Chem Biol ; 19(6): 1237-1242, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38723147

ABSTRACT

As an important functional monosaccharide, glucosamine (GlcN) is widely used in fields such as medicine, food nutrition, and health care. Here, we report a distinct GlcN biosynthesis method that utilizes engineered Bacillus subtilis glucosamine-6-phosphate synthase (BsGlmS) to convert D-fructose to directly generate GlcN. The best variant obtained by using a combinatorial active-site saturation test/iterative saturation mutagenesis (CAST/ISM) strategy was a quadruple mutant S596D/V597G/S347H/G299Q (BsGlmS-BK19), which has a catalytic activity 1736-fold that of the wild type toward D-fructose. Upon using mutant BK19 as a whole-cell catalyst, D-fructose was converted into GlcN with 65.32% conversion in 6 h, whereas the wild type only attained a conversion rate of 0.31% under the same conditions. Molecular docking and molecular dynamics simulations were implemented to provide insights into the mechanism underlying the enhanced activity of BK19. Importantly, the BsGlmS-BK19 variant specifically catalyzes D-fructose without the need for phosphorylated substrates, representing a significant advancement in GlcN biosynthesis.


Subject(s)
Bacillus subtilis , Glucosamine , Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) , Protein Engineering , Glucosamine/biosynthesis , Glucosamine/metabolism , Glucosamine/chemistry , Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/metabolism , Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/genetics , Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/chemistry , Bacillus subtilis/enzymology , Bacillus subtilis/metabolism , Bacillus subtilis/genetics , Molecular Docking Simulation , Fructose/metabolism , Fructose/chemistry , Fructose/biosynthesis , Molecular Dynamics Simulation , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/chemistry , Catalytic Domain
16.
Food Funct ; 15(11): 5942-5954, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38738974

ABSTRACT

Our laboratory previously extracted bound polyphenols (BPP) in insoluble dietary fiber from navel orange peel (NOP-IDF), and the aim of this study was to investigate the anti-inflammatory activity and potential molecular mechanisms of BPP by establishing an LPS-induced intestinal-like Caco-2/RAW264.7 co-culture inflammation model. The results demonstrated that BPP reduced the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), as well as the production of pro-inflammatory cytokines, nitric oxide (NO), and reactive oxidative species (ROS) during the inflammatory damage process. Furthermore, BPP alleviated the lipopolysaccharides (LPS)-induced intestinal barrier damage by attenuating the decrease in trans-epithelial electrical resistance (TEER), diamine oxidase (DAO) activity, and intestinal alkaline phosphatase (IAP) activity, as well as the downregulation of ZO-1, Occludin, and Claudin-1 protein expression levels. RNA-seq results on RAW264.7 cells in the co-culture model showed that the NF-κB and JAK-STAT pathways belonged to the most significantly affected signaling pathways in the KEGG analysis, and western blot confirmed that they are essential for the role of BPP in intestinal inflammation. Additionally, overexpression of the granulocyte-macrophage colony-stimulating factor (CSF2) gene triggered abnormal activation of the NF-κB and JAK-STAT pathways and high-level expression of inflammatory factors, while BPP effectively improved this phenomenon. The above results suggested that BPP could inhibit intestinal inflammatory injury and protect intestinal barrier integrity through CSF2-mediated NF-κB and JAK-STAT pathways.


Subject(s)
Citrus sinensis , Coculture Techniques , Dietary Fiber , Lipopolysaccharides , Polyphenols , Signal Transduction , Animals , Humans , Mice , Caco-2 Cells , Citrus sinensis/chemistry , Dietary Fiber/pharmacology , Fruit/chemistry , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Inflammation/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Intestines/drug effects , Janus Kinases/metabolism , Lipopolysaccharides/adverse effects , NF-kappa B/metabolism , NF-kappa B/genetics , Polyphenols/pharmacology , RAW 264.7 Cells , Signal Transduction/drug effects , STAT Transcription Factors/metabolism
17.
BMC Cancer ; 24(1): 549, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693523

ABSTRACT

BACKGROUND: Accurate assessment of axillary status after neoadjuvant therapy for breast cancer patients with axillary lymph node metastasis is important for the selection of appropriate subsequent axillary treatment decisions. Our objectives were to accurately predict whether the breast cancer patients with axillary lymph node metastases could achieve axillary pathological complete response (pCR). METHODS: We collected imaging data to extract longitudinal CT image features before and after neoadjuvant chemotherapy (NAC), analyzed the correlation between radiomics and clinicopathological features, and developed models to predict whether patients with axillary lymph node metastasis can achieve axillary pCR after NAC. The clinical utility of the models was determined via decision curve analysis (DCA). Subgroup analyses were also performed. Then, a nomogram was developed based on the model with the best predictive efficiency and clinical utility and was validated using the calibration plots. RESULTS: A total of 549 breast cancer patients with metastasized axillary lymph nodes were enrolled in this study. 42 independent radiomics features were selected from LASSO regression to construct a logistic regression model with clinicopathological features (LR radiomics-clinical combined model). The AUC of the LR radiomics-clinical combined model prediction performance was 0.861 in the training set and 0.891 in the testing set. For the HR + /HER2 - , HER2 + , and Triple negative subtype, the LR radiomics-clinical combined model yields the best prediction AUCs of 0.756, 0.812, and 0.928 in training sets, and AUCs of 0.757, 0.777 and 0.838 in testing sets, respectively. CONCLUSIONS: The combination of radiomics features and clinicopathological characteristics can effectively predict axillary pCR status in NAC breast cancer patients.


Subject(s)
Axilla , Breast Neoplasms , Lymph Nodes , Lymphatic Metastasis , Neoadjuvant Therapy , Nomograms , Tomography, X-Ray Computed , Humans , Female , Breast Neoplasms/pathology , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/drug therapy , Lymphatic Metastasis/diagnostic imaging , Middle Aged , Lymph Nodes/pathology , Lymph Nodes/diagnostic imaging , Tomography, X-Ray Computed/methods , Neoadjuvant Therapy/methods , Adult , Aged , Retrospective Studies , Radiomics
18.
Org Lett ; 26(21): 4526-4531, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38761124

ABSTRACT

We report a novel organic photoredox catalysis to achieve unprecedented γ-(hetero)aryl/alkenyl-δ-silyl aliphatic amines via silyl-mediated distal (hetero)aryl/alkenyl migration of aromatic/alkenyl amines bearing unactivated alkenes with hydrosilanes. This protocol features mild and metal-free reaction conditions, high atom economy, excellent selectivity, and functional group compatibility. Mechanistic studies suggest that silylation and (hetero)aryl/alkenylation involve photoredox hydrogen atom transfer catalysis and subsequent 1,4-migration of a remote (hetero)aryl/alkenyl group from nitrogen to carbon.

19.
Int J Biol Macromol ; 270(Pt 1): 132066, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705323

ABSTRACT

A comprehensive multiscale analysis was conducted to explore the effects of different ratios of these materials on its properties. The results show that KC played a crucial role in controlling solution viscosity and gel and sol temperatures. The dissolution time at high water temperatures primarily decreased with an increase in SA content. Higher KC and CS content increased tensile strength (TS) and elongation at break (ε), while also exhibiting better thermal stability. Water vapor transmission (WVT) and permeability (PV) initially decreased, then increased with the increase of SA and CS contents. Finally, an SA:KC:CS ratio of 1:3:2 showed optimal comprehensive properties, with a dissolution time of about 60.0 ± 3.8 s, TS of 23.80 ± 0.29 MPa, ε of 18.61 ± 0.34 %, WVT of 21.74 ± 0.62 g/m2·24h, and PV of 5.39 ± 0.17 meq/kg. Meanwhile, the SA:KC:CS edible food packaging only introduced minimal effects on food after dissolution, and the total bacterial count met regulatory standards.


Subject(s)
Edible Films , Food Packaging , Permeability , Water , Food Packaging/methods , Water/chemistry , Polysaccharides/chemistry , Solubility , Hot Temperature , Viscosity , Tensile Strength , Steam , Mechanical Phenomena , Fast Foods/analysis
20.
Sci Total Environ ; 927: 172338, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38608897

ABSTRACT

Algal blooms in lakes have been a challenging environmental issue globally under the dual influence of human activity and climate change. Considerable progress has been made in the study of phytoplankton dynamics in lakes; The long-term in situ evolution of dominant bloom-forming cyanobacteria in meso-eutrophic plateau lakes, however, lacks systematic research. Here, the monthly parameters from 12 sampling sites during the period of 1997-2022 were utilized to investigate the underlying mechanisms driving the superiority of bloom-forming cyanobacteria in Erhai, a representative meso-eutrophic plateau lake. The findings indicate that global warming will intensify the risk of cynaobacteria blooms, prolong Microcystis blooms in autumn to winter or even into the following year, and increase the superiority of filamentous Planktothrix and Cylindrospermum in summer and autumn. High RUETN (1.52 Biomass/TN, 0.95-3.04 times higher than other species) under N limitation (TN < 0.5 mg/L, TN/TP < 22.6) in the meso-eutrophic Lake Erhai facilitates the superiority of Dolichospermum. High RUETP (43.8 Biomass/TP, 2.1-10.2 times higher than others) in TP of 0.03-0.05 mg/L promotes the superiority of Planktothrix and Cylindrospermum. We provided a novel insight into the formation of Planktothrix and Cylindrospermum superiority in meso-eutrophic plateau lake with low TP (0.005-0.07 mg/L), which is mainly influenced by warming, high RUETP and their vertical migration characteristics. Therefore, we posit that although the obvious improvement of lake water quality is not directly proportional to the control efficacy of cyanobacterial blooms, the evolutionary shift in cyanobacteria population structure from Microcystis, which thrives under high nitrogen and phosphorus conditions, to filamentous cyanobacteria adapted to low nitrogen and phosphorus levels may serve as a significant indicator of water quality amelioration. Therefore, we suggest that the risk of filamentous cyanobacteria blooms in the meso-eutrophic plateau lake should be given attention, particularly in light of improving water quality and global warming, to ensure drinking water safety.


Subject(s)
Cyanobacteria , Eutrophication , Lakes , Temperature , Lakes/microbiology , Lakes/chemistry , China , Environmental Monitoring , Nitrogen/analysis , Phytoplankton , Climate Change , Seasons , Phosphorus/analysis , Nutrients/analysis , Global Warming
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