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1.
IEEE Trans Cybern ; PP2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39378255

ABSTRACT

This article proposes the two-layer asynchronous control scheme for a class of networked nonlinear jump systems. For the constructed system in a network environment, the data transmission may suffer from many restrictions, such as incomplete acceptable mode information and transition information, nonlinearity of system and inadequate bandwidth resources, etc. Then, the two-layer asynchronous controller is developed to stabilize the plant constructed by Takagi-Sugeno (T-S) fuzzy method and semi-Markov theory (SMT). Herein, the hidden semi-Markov process with time-varying emission probability is introduced to establish the relation between the system modes and the controller modes, in which the interval segmentation method is presented to deal with this time-varying probability. Compared with some published results, this method can make full use of the transition rate information, which may lead to the reduction of conservatism in the proposed asynchronous control design. At the same time, the limited bandwidth problem in the communication channel is addressed by introducing the bilateral quantization strategy, and the new sufficient conditions are derived on the stochastic stability of the nonlinear jump system with/without incomplete transition and sojourn-time information. Finally, the numerical simulation examples about DC motor illustrate the effectiveness and the feasibility of the proposed approach.

2.
Nat Commun ; 15(1): 8737, 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39384741

ABSTRACT

Rosacea is a chronic inflammatory skin disorder, whose underlying cellular and molecular mechanisms remain obscure. Here, we generate a single-cell atlas of facial skin from female rosacea patients and healthy individuals. Among keratinocytes, a subpopulation characterized by IFNγ-mediated barrier function damage is found to be unique to rosacea lesions. Blocking IFNγ signaling alleviates rosacea-like phenotypes and skin barrier damage in mice. The papulopustular rosacea is featured by expansion of pro-inflammatory fibroblasts, Schwann, endothelial and macrophage/dendritic cells. The frequencies of type 1/17 and skin-resident memory T cells are increased, and vascular mural cells are characterized by activation of inflammatory pathways and impaired muscle contraction function in rosacea. Most importantly, fibroblasts are identified as the leading cell type producing pro-inflammatory and vasodilative signals in rosacea. Depletion of fibroblasts or knockdown of PTGDS, a gene specifically upregulated in fibroblasts, blocks rosacea development in mice. Our study provides a comprehensive understanding of the aberrant alterations of skin-resident cell populations and identifies fibroblasts as a key determinant in rosacea development.


Subject(s)
Fibroblasts , Rosacea , Single-Cell Analysis , Skin , Transcriptome , Rosacea/genetics , Rosacea/immunology , Rosacea/pathology , Fibroblasts/metabolism , Animals , Humans , Skin/metabolism , Skin/pathology , Skin/immunology , Mice , Female , Interferon-gamma/metabolism , Keratinocytes/metabolism , Mice, Inbred C57BL , Macrophages/metabolism , Macrophages/immunology , Dendritic Cells/metabolism , Dendritic Cells/immunology , Schwann Cells/metabolism , Schwann Cells/pathology , Adult
3.
Clin Cancer Res ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39226396

ABSTRACT

PURPOSE: Neuroendocrine bladder cancer (NEBC) poses a formidable clinical challenge and attracts keen interests to explore immunotherapy as a viable treatment option. However, a comprehensive immunogenomic landscape has yet to be thoroughly investigated. EXPERIMENTAL DESIGN: Leveraging a long-term cohort of natural NEBC cases, we employed a multimodal approach integrating genomic (n = 19), transcriptomic (n = 3), single-cell RNA sequencing (n = 1), and immunohistochemical analyses (n = 34) to meticulously characterize the immunogenicity and immunotypes of primary NEBC tumors. Clinical, pathological, medical imaging, and treatment information was retrospectively retrieved and analyzed. RESULTS: Our study unveiled that despite a considerable mutational burden, NEBC was typically immunologically inactive, as manifested by 'immune-excluded' or 'immune-desert' microenvironment. Interestingly, a subset of mixed NEBC with concurrent urothelial bladder cancer (UBC) histology displayed an 'immune-infiltrated' phenotype with prognostic relevance. When compared to UBC, NEBC lesions were distinguished by a denser cellular composition and augmented peritumoral extracellular matrix, which might collectively impede lymphatic infiltration. As a result, single-agent immune checkpoint inhibitors demonstrated limited efficacy against NEBC, while pharmacologic immunostimulation with combination chemotherapy conferred a more favorable response. CONCLUSIONS: These new insights derived from genomic profiling and immune phenotyping pave the way for rational immunotherapeutic interventions in NEBC patients, with the potential to ultimately reduce mortality from this otherwise fatal disease.

4.
Cell Signal ; 124: 111381, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39243918

ABSTRACT

Pancreatic cancer (PC) is highly malignancy with poor survival. Ferroptosis offers a novel therapeutic target for cancer treatment and glutathione peroxidase 4 (GPX4) shields tumor cells from ferroptosis damage. Although Sterol regulatory element-binding protein 1 (SREBP1) has been implicated in the development of pancreatic cancer, its underlying mechanisms remain unclear. This research aims to explore the role of SREBP1 in ferroptosis by using its inhibitor Fatostatin. In this study, Fatostatin was found to inhibit the proliferation and clonogenicity of pancreatic cancer cell lines. This was accompanied by a reduction in intracellular lipid synthesis, increased iron accumulation, elevated levels of reactive oxygen species (ROS), and accumulation of malondialdehyde (MDA). The JASPAR database shows that there is a binding site of the SREBP1 on the promoter region of GPX4. What's more, it was verified that SREBP1 can transcriptionally regulate GPX4 by CHIP. In vivo experiments further revealed that Fatostatin could suppress the growth of subcutaneous tumors in nude mice. In conclusion, our study suggests that Fatostatin may inhibit pancreatic cancer cell proliferation by inducing ferroptosis through the SREBP1/GPX4 pathway. These findings shed light on the therapeutic potential of Fatostatin and lay the groundwork for future investigations into its mechanism of action in pancreatic cancer.

5.
Vaccines (Basel) ; 12(9)2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39340023

ABSTRACT

Madin-Darby canine kidney (MDCK) cells are commonly used to produce cell-based influenza vaccines. However, the role of the low-serum medium on the proliferation of MDCK cells and the propagation of the influenza virus has not been well studied. In the present study, we used 5 of 15 culture methods with different concentrations of a mixed medium and neonatal bovine serum (NBS) to determine the best culture medium. We found that a VP:M199 ratio of 1:2 (3% NBS) was suitable for culturing MDCK cells. Furthermore, the stable growth of MDCK cells and the production of the influenza virus were evaluated over long-term passaging. We found no significant difference in terms of cell growth and virus production between high and low passages of MDCK cells under low-serum culture conditions, regardless of influenza virus infection. Lastly, we performed a comparison of the transcriptomics and proteomics of MDCK cells cultured in VP:M199 = 1:2 (3% NBS) with those cultured in VP:M199 = 1:2 (5% NBS) before and after influenza virus infection. The transcriptome analysis showed that differentially expressed genes were predominantly enriched in the metabolic pathway and MAPK signaling pathway, indicating an activated state. This suggests that decreasing the concentration of serum in the medium from 5% to 3% may increase the metabolic activity of cells. Proteomics analysis showed that only a small number of differentially expressed proteins could not be enriched for analysis, indicating minimal difference in the protein levels of MDCK cells when the serum concentration in the medium was decreased from 5% to 3%. Altogether, our findings suggest that the screening and application of a low-serum medium provide a background for the development and optimization of cell-based influenza vaccines.

6.
J Agric Food Chem ; 72(38): 20831-20841, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39284582

ABSTRACT

This research adopted the Fischer indole synthesis method to continue constructing a novel drug-like chemical entity based on the guidance of isocryptolepine and obtained four series of derivatives: Y, Da, Db, and Dc. The antimicrobial activity of these derivatives against plant pathogens was further evaluated. The results showed that Dc-2 had the best antifungal effect against Botrytis cinerea, and its EC50 value was up to 1.29 µg/mL. In addition, an in vivo activity test showed that the protective effect of Dc-2 on apples was 82.2% at 200 µg/mL, which was better than that of Pyrimethanil (45.4%). Meanwhile, it was found by scanning electron microscopy and transmission electron microscopy that the compound Dc-2 affected the morphology of mycelia. The compound Dc-2 was found to damage the cell membrane by PI and ROS staining. Through experiments such as leakage of cell contents, it was found that the compound Dc-2 changed the permeability of the cell membrane and caused the leakage of substances in the cell. According to the above studies, compound Dc-2 can be used as a candidate lead compound for further structural optimization and development.


Subject(s)
Botrytis , Drug Design , Fungicides, Industrial , Plant Diseases , Botrytis/drug effects , Botrytis/growth & development , Plant Diseases/microbiology , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/chemistry , Structure-Activity Relationship , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Microbial Sensitivity Tests , Malus/chemistry , Malus/microbiology , Bacteria/drug effects , Molecular Structure
7.
Heliyon ; 10(18): e37549, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39309929

ABSTRACT

Since time immortal, people have used the well-known Chinese Chaenomeles fruit Xuan-Mugua for both traditional medicine and nourishment. With an aim to explore the digestive and antioxidant properties of the phenolics, Xuan-Mugua peel and pulp were extracted, digested and analyzed in vitro. Our results indicated that the total phenolics content (TPC), total flavonoids content (TFC) and the antioxidant activity of the peel were 3.24-8.89 times higher than that of pulp. The contents and activity of the peel and pulp consistently dropped in the sequence of oral, gastric, and small intestine digestions, from 22.78 % to 52.16 %. With a level of 1.590 ± 0.060 and 0.395 ± 0.015 mg g-1 dried weight in the peel and pulp, respectively, chlorogenic acid was the primary phenolic ingredient in Xuan-Mugua, with a promising recovery (81.39-82.23 %) during the digestion. According to these results, Xuan-Mugua exhibited an appreciable level of phenolic content and antioxidant activity during digestion, making it a suitable ingredient for use in functional foods.

8.
IEEE Trans Cybern ; PP2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39288055

ABSTRACT

The robust LQ optimal regulator problem for discrete-time uncertain singular Markov jump systems (SMJSs) is solved by introducing a new quadratic cost function established by the penalty function method, which combines the penalty function and the weighting matrices. First, the indefinite robust optimal regulator problem for uncertain SMJSs is transformed into the robust optimal regulator problem with positive definite weighting matrices for uncertain Markov jump systems (MJSs). The transformed robust LQ problem is settled by the robust least-squares method, and the condition of the existence and analytic form of the robust optimal regulator are proposed. On the infinite horizon, the optimal state feedback is obtained, which can guarantee the regularity, causality, and stochastic stability of the corresponding optimal closed-loop system and eliminate the uncertain parameters of the closed-loop system. A numerical example and a practical example of DC motor are used to verify the validity of the conclusions.

9.
Pharmacol Res ; : 107404, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39306020

ABSTRACT

Increased astrocytic lactoferrin (Lf) expression was observed in the brains of elderly individuals and Alzheimer's disease (AD) patients. Our previous study revealed that astrocytic Lf overexpression improved cognitive capacity by facilitating Lf secretion to neurons to inhibit ß-amyloid protein (Aß) production in APP/PS1 mice. Here, we further discovered that astrocytic Lf overexpression inhibited neuronal loss by decreasing iron accumulation and increasing glutathione peroxidase 4 (GPX4) expression in neurons within APP/PS1 mice. Furthermore, human Lf (hLf) treatment inhibited ammonium ferric citrate (FAC)-induced ferroptosis by chelating intracellular iron. Additionally, machine learning analysis uncovered a correlation between Lf and GPX4. hLf treatment boosted low-density lipoprotein receptor-related protein 1 (LRP1) internalization and facilitated its interaction with heat shock cognate 70 (HSC70), thereby inhibiting HSC70 binds to GPX4, and eventually attenuating GPX4 degradation and FAC-induced ferroptosis. Overall, astrocytic Lf overexpression inhibited neuronal ferroptosis through two pathways: reducing intracellular iron accumulation and promoting GPX4 expression via inhibiting chaperone-mediated autophagy (CMA)-mediated GPX4 degradation. Hence, upregulating astrocytic Lf expression is a promising strategy for combating AD.

10.
Int J Mol Sci ; 25(15)2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39126096

ABSTRACT

With-no-lysine kinase (WNK) is a unique serine/threonine kinase family member. WNK differs from other protein kinases by not having a standard lysine in subdomain II of the universally preserved kinase catalytic region. Conversely, the amino acid lysine located in subdomain I plays a crucial role in its phosphorylation. The WNK family has been reported to regulate Arabidopsis flowering, circadian rhythm, and abiotic stress. Eighteen members of the WNK gene family were discovered in apples in this research, and they were primarily grouped into five categories on the phylogenetic tree. Conserved domains and motifs also confirmed their identity as members of the WNK family. Promoter cis-acting element analysis indicated their potential role in responses to both abiotic stress and phytohormones. Furthermore, qRT-PCR analysis showed that the expression of MdWNK family genes was stimulated to different extents by Colletotrichum siamense, NaCl, mannitol, ABA, JA, and SA, with Colletotrichum siamense being the most prominent stimulant. MdWNK family genes were expressed across all apple tissues, with young fruits showing the greatest expression and roots showing the least expression. The research offered detailed insights into the MdWNK gene family, serving as a crucial basis for investigating the biological roles of MdWNK genes.


Subject(s)
Colletotrichum , Gene Expression Regulation, Plant , Malus , Multigene Family , Phylogeny , Plant Proteins , Protein Serine-Threonine Kinases , Stress, Physiological , Malus/genetics , Malus/microbiology , Stress, Physiological/genetics , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Diseases/microbiology , Plant Diseases/genetics , Plant Growth Regulators/metabolism , Promoter Regions, Genetic , Genome, Plant
11.
Oral Oncol ; 158: 107001, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39216209

ABSTRACT

OBJECTIVES: To identify the failure patterns and prognostic factors of nonmetastatic nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. METHODS: Data on 847 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2012 and 2016 were retrospectively reviewed. Survival outcome, failure patterns and prognosis factors were analyzed. RESULTS: The 5-year local relapse-free survival, nodal relapse-free survival, distant metastasis-free survival, disease-free survival, and overall survival rates were 94.3%, 95.3%, 84.8%, 76.5% and 85.7%, respectively. The major local recurrence sites were the nasopharynx (91.5%, 43/47) and skull base (68.1%, 32/47); 39 patients had in-field failures, four had marginal failures, and four had out-field failures. Level IIb (62.2%, 23/37) was the most frequent regional recurrence site, followed by IIa (35.1%, 13/37) and retropharyngeal region (32.4%, 12/37); 35 cases had in-field failure alone, one had out-field failure alone, and one had both in- and out-field failure. TNM stage was the most significant factor for prognosis prediction. 402 (47.5%) patients had acute adverse events of grade 3 or 4; leukopenia (31.5%) and mucositis (26.7%) was the most common hematological and non-hematological event, respectively. Late complications were slight or moderate damages; xerostomia (647/847, 76.4%) and hearing impairment (422/847, 49.8%) remained the most troublesome. CONCLUSION: NPC patients treated with IMRT obtained satisfactory survival outcomes. The key failure pattern was distant metastasis. The main pattern of local-regional failure was in-field failure. Screening high risk patients with distant metastases and optimizing radiotherapy targets should be studied.


Subject(s)
Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Radiotherapy, Intensity-Modulated , Humans , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods , Male , Female , Middle Aged , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/pathology , Adult , Aged , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/pathology , Young Adult , Retrospective Studies , Adolescent , Prognosis , Neoplasm Recurrence, Local/radiotherapy , Aged, 80 and over
12.
Bioorg Med Chem ; 112: 117880, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39216382

ABSTRACT

Berberine is a quaternary ammonium isoquinoline alkaloid derived from traditional Chinese medicines Coptis chinensis and Phellodendron chinense. It has many pharmacological activities such as hypoglycemic, hypolipidemic, anti-tumor, antimicrobial and anti-inflammatory. Through structural modifications at various sites of berberine, the introduction of different groups can change berberine's physical and chemical properties, thereby improving the biological activity and clinical efficacy, and expanding the scope of application. This paper reviews the research progress and structure-activity relationships of berberine in recent years, aiming to provide valuable insights for the exploration of novel berberine derivatives.


Subject(s)
Berberine , Berberine/chemistry , Berberine/pharmacology , Berberine/analogs & derivatives , Structure-Activity Relationship , Humans , Molecular Structure , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemical synthesis , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis
13.
IEEE Trans Cybern ; PP2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39093678

ABSTRACT

This article intends to study the asynchronous control problem for 2-D Markov jump systems (MJSs) with nonideal transition probabilities (TPs) under the Roesser model. Two practical considerations motivate the current work. First, considering that the system mode cannot always be observed accurately, a hidden Markov model (HMM) is adopted to describe the relationship between the mismatched modes. Second, considering that the TPs information related to the Markov process and the observation process is difficult to obtain, the nonideal TPs (unknown or uncertain) are simultaneously considered on the two processes. Under the considerations, several new sufficient conditions are developed for concerned closed-loop 2-D MJSs with nonideal TPs, by which the asymptotic mean square stability is ensured with an H∞ performance index. A nonconservative separation strategy is utilized to decouple the system mode TPs and the observation TPs to facilitate the analysis of nonideal TPs. An unified LMI-based condition is finally developed for the concerned closed-loop 2-D MJSs with/without nonideal TPs, showing more satisfactory conservatism than that in the literature. In the end, we present two examples to validate the superiority of the proposed design method.

14.
World J Gastrointest Surg ; 16(7): 2329-2336, 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39087117

ABSTRACT

BACKGROUND: Programmed cell death 1 (PD-1) inhibitors are immune checkpoint inhibitors (ICI) that have demonstrated significant efficacy in treating various advanced malignant tumors. While most patients tolerate treatment well, several adverse drug reactions, such as fatigue, myelosuppression, and ICI-associated colitis, have been reported. CASE SUMMARY: This case involved a 57-year-old male patient with ulcerative colitis complicated by hepatocarcinoma who underwent treatment with tirelizumab (a PD-1 inhibitor) for six months. The treatment led to repeated life-threatening lower gastrointestinal hemorrhage. The patient received infliximab, vedolizumab, and other salvage procedures but ultimately required subtotal colectomy due to uncontrollable massive lower gastrointestinal bleeding. Currently, postoperative gastrointestinal bleeding has stopped, the patient's stool has turned yellow, and his full blood cell count has returned to normal. CONCLUSION: This case highlights the necessity of early identification, timely and adequate treatment of ICI-related colitis, and rapid escalation to achieve the goal of improving prognosis.

15.
Heliyon ; 10(15): e34949, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39157351

ABSTRACT

Breast cancer ranks as the most prevalent cancer globally, surpassing lung cancer, with recurrence/metastasis to be its main account for the cancer-related mortality. MicroRNAs (miRNAs) participate critically in various physiological and pathological processes through posttranscriptional regulation of downstream genes. Our preliminary findings identified miR-338-5p, potentially linked to metastasis in breast cancer, a previously unexplored area. Analysis of the GSE38867 dataset revealed the decreased miR-338-5p expression in metastatic breast cancer compared to normal tissues. Cellular function experiments and a xenograft tumor model demonstrated the inhibitory function of miR-338-5p on the progression of breast cancer in vitro and in vivo. Furthermore, it downregulated the expression of mesenchymal biomarkers and NOTCH1 significantly. With the predicting targets of miR-338-5p and transcription factors of the NOTCH1 gene, coupled with dual luciferase reporter assays, it is identified ETS1 as the interactor between miR-338-5p and NOTCH1. In breast cancer tissues, as well as in our xenograft tumor model, expression of ETS1 and NOTCH1 was positively correlated using immunohistochemical staining. This study reports, for the first time, on the miR-338-5p/ETS1/NOTCH1 axis and its pivotal role in breast cancer proliferation and metastasis. These findings propose a novel therapeutic strategy for breast cancer patients and lays a foundation for its clinical detection and treatment evaluation.

16.
Cancer Lett ; 598: 217130, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39089666

ABSTRACT

PURPOSE: Cholesterol metabolism reprograming has been acknowledged as a novel feature of cancers. Pancreatic ductal adenocarcinoma (PDAC) is a cancer with a high demand of cholesterol for rapid growth. The underlying mechanism of how cholesterol metabolism homestasis are disturbed in PDAC is explored. EXPERIMENTAL DESIGN: The relevance between PDAC and cholesterol was confirmed in TCGA database. The expression and clinical association were discovered in TCGA and GEO datasets. Knockdown and overexpression of AGFG1 was adopted to perform function studies. RNA sequencing, cholesterol detection, transmission electron microscope, co-immunoprecipitation, and immunofluorescence et al. were utilized to reveal the underlying mechanism. RESULTS: AGFG1 was identified as one gene positively correlated with cholesterol metabolism in PDAC as revealed by bioinformatics analysis. AGFG1 expression was then found associated with poor prognosis in PDAC. AGFG1 knockdown led to decreased proliferation of tumor cells both in vitro and in vivo. By RNA sequencing, we found AGFG1 upregulated expression leads to enhanced intracellular cholesterol biosynthesis. AGFG1 knockdown suppressed cholesterol biosynthesis and an accumulation of cholesterol in the ER. Mechanistically, we confirmed that AGFG1 interacted with CAV1 to relocate cholesterol for the proceeding of cholesterol biosynthesis, therefore causing disorders in intracellular cholesterol metabolism. CONCLUSIONS: Our study demonstrates the tumor-promoting role of AGFG1 by disturbing cholesterol metabolism homestasis in PDAC. Our study has present a new perspective on cancer therapeutic approach based on cholerstrol metabolism in PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal , Cell Proliferation , Cholesterol , Homeostasis , Pancreatic Neoplasms , Humans , Cholesterol/metabolism , Cholesterol/biosynthesis , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/genetics , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/genetics , Animals , Cell Line, Tumor , Mice , Gene Expression Regulation, Neoplastic , Disease Progression , Prognosis , Caveolin 1/genetics , Caveolin 1/metabolism , Mice, Nude , Male
17.
IEEE Trans Cybern ; 54(10): 6269-6280, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39159029

ABSTRACT

The event-based H∞ control problem is investigated for a class of nonhomogeneous Markov jump systems (MJSs) with partially unknown transition probabilities (TPs). The MJS is characterized by a piecewise nonhomogeneous Markovian chain, where the switching of the system TP matrix is governed by a higher-level chain. A hidden Markov model (HMM) is employed to observe the system mode, which cannot always be correctly detected in practice. Under this framework, the partially unknown TPs existing in both higher-level TPs (HTPs) and conditional TPs (CTPs) are taken into account for practical consideration. Additionally, an observed-mode-dependent event-triggered mechanism (ETM) is employed to design an asynchronous controller, which is expected to alleviate the burden of the communication network. Evidently, the considered scenario is fairly general and covers some special cases. With the above consideration, sufficient conditions are established to guarantee stochastic stability of the resulting closed-loop system with a prescribed H∞ performance. Finally, two examples are presented to demonstrate the effectiveness and applicability of the proposed method.

18.
Nature ; 633(8031): 923-931, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39143213

ABSTRACT

Most kidney cancers are metabolically dysfunctional1-4, but how this dysfunction affects cancer progression in humans is unknown. We infused 13C-labelled nutrients in over 80 patients with kidney cancer during surgical tumour resection. Labelling from [U-13C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all tumour metabolic reprogramming. Compared with the adjacent kidney, clear cell renal cell carcinomas (ccRCCs) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in ex vivo organotypic cultures, indicating that suppressed labelling is tissue intrinsic. [1,2-13C]acetate and [U-13C]glutamine infusions in patients, coupled with measurements of respiration in isolated human kidney and tumour mitochondria, reveal lower electron transport chain activity in ccRCCs that contributes to decreased oxidative and enhanced reductive TCA cycle labelling. However, ccRCC metastases unexpectedly have enhanced TCA cycle labelling compared with that of primary ccRCCs, indicating a divergent metabolic program during metastasis in patients. In mice, stimulating respiration or NADH recycling in kidney cancer cells is sufficient to promote metastasis, whereas inhibiting electron transport chain complex I decreases metastasis. These findings in humans and mice indicate that metabolic properties and liabilities evolve during kidney cancer progression, and that mitochondrial function is limiting for metastasis but not growth at the original site.


Subject(s)
Electron Transport Complex I , Kidney Neoplasms , Mitochondria , Neoplasm Metastasis , Animals , Female , Humans , Male , Mice , Acetates/metabolism , Carbon Isotopes/metabolism , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Cell Respiration , Citric Acid Cycle , Disease Progression , Electron Transport , Electron Transport Complex I/metabolism , Glucose/metabolism , Glutamine/metabolism , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Mitochondria/metabolism , NAD/metabolism , Oxidation-Reduction
19.
World J Gastroenterol ; 30(23): 2959-2963, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38946873

ABSTRACT

In this editorial, we comment on the article entitled "Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?" by Agatsuma et al. Colorectal cancer (CRC) is emerging as an important health issue as its incidence continues to rise globally, adversely affecting the quality of life. Although the public has become more aware of CRC prevention, most patients lack screening awareness. Some poor lifestyle practices can lead to CRC and symptoms can appear in the early stages of CRC. However, due to the lack of awareness of the disease, most of the CRC patients are diagnosed already at an advanced stage and have a poor prognosis.


Subject(s)
Colorectal Neoplasms , Early Detection of Cancer , Humans , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/prevention & control , Colorectal Neoplasms/epidemiology , Early Detection of Cancer/methods , Quality of Life , Neoplasm Staging , Mass Screening/methods , Mass Screening/standards , Prognosis , Colonoscopy , Incidence , Health Knowledge, Attitudes, Practice , Life Style
20.
Wideochir Inne Tech Maloinwazyjne ; 19(1): 52-59, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38974767

ABSTRACT

Introduction: While cryoablation (CA) and microwave ablation (MWA) have both been implemented as approaches to the treatment of adrenal metastasis (AM), the outcomes associated with these two therapeutic strategies remain unclear. Aim: To compare the safety and efficacy of CA and MWA as treatments for AM in patients with non-small-cell lung cancer (NSCLC). Material and methods: Consecutive patients with AM secondary to NSCLC from January 2015 to December 2020 underwent CA or MWA. Treatment-related outcomes and complications were retrospectively compared between these groups. Results: In total, 68 NSCLC patients with isolated AM were enrolled in this study, of whom 35 and 33 underwent treatment with CA and MWA, respectively. Primary complete ablation rates in the CA and MWA groups were 91.4% (32/35) and 93.9% (31/33) respectively (p = 1.000), while a 100% secondary complete ablation rate was observed for both groups. Hypertensive crisis incidence affected 11.4% (4/35) and 9.1% (3/33) of patients in the CA and MWA groups (p = 1.000), respectively, while 8 (22.9%) and 8 (24.2%) patients in these corresponding groups experienced local progression after ablation that was detected during the follow-up period (p = 0.893). Patients in the CA and MWA groups exhibited a median progression-free survival of 18 and 22 months, respectively (p = 0.411), while the corresponding median overall survival of patients in these groups was 25 and 29 months (p = 0.786). Conclusions: CT-guided CA and MWA appear to exhibit similar safety and efficacy profiles when employed to treat isolated AM in NSCLC patients.

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