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1.
J Magn Reson Imaging ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733601

RESUMO

BACKGROUND: The use of peritumoral features to determine the survival time of patients with rectal cancer (RC) is still imprecise. PURPOSE: To explore the correlation between intratumoral, peritumoral and combined features, and overall survival (OS). STUDY TYPE: Retrospective. POPULATION: One hundred sixty-six RC patients (53 women, 113 men; average age: 55 ± 12 years) who underwent radical resection after neoadjuvant therapy. FIELD STRENGTH/SEQUENCE: 3 T; T2WI sagittal, T1WI axial, T2WI axial with fat suppression, and high-resolution T2WI axial sequences, enhanced T1WI axial and sagittal sequences with fat suppression. ASSESSMENT: Radiologist A segmented 166 patients, and radiologist B randomly segmented 30 patients. Intratumoral and peritumoral features were extracted, and features with good stability (ICC ≥0.75) were retained through intra-observer analysis. Seven classifiers, including Logistic Regression (LR), Support Vector Machine (SVM), K-Nearest Neighbors (KNN), Random Forest (RF), Extremely randomized trees (ET), eXtreme Gradient Boosting (XGBoost), and LightGBM (LGBM), were applied to select the classifier with the best performance. Next, the Rad-score of best classifier and the clinical features were selected to establish the models, thus, nomogram was built to identify the association with 1-, 3-, and 5-year OS. STATISTICAL TESTS: LASSO, regression analysis, ROC, DeLong method, Kaplan-Meier curve. P < 0.05 indicated a significant difference. RESULTS: Only Node (irregular tumor nodules in the surrounding mesentery) and ExtraMRF (lymph nodes outside the perirectal mesentery) were significantly different in 20 clinical features. Twelve intratumoral, 3 peritumoral, and 14 combined features related to OS were selected. LR, SVM, and RF classier showed the best efficacy in the intratumoral, peritumoral, and combined model, respectively. The combined model (AUC = 0.954 and 0.821) had better survival association than the intratumoral model (AUC = 0.833 and 0.813) and the peritumoral model (AUC = 0.824 and 0.687). DATA CONCLUSION: The proposed peritumoral model with radiomics features may serve as a tool to improve estimated survival time. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 4.

2.
Eur J Med Chem ; 271: 116395, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38626523

RESUMO

The transforming growth factor ß1 (TGFß1)/SMAD signaling pathway regulates many vital physiological processes. The development of potent inhibitors targeting activin receptor-like kinase 5 (ALK5) would provide potential treatment reagents for various diseases. A significant number of ALK5 inhibitors have been discovered, and they are currently undergoing clinical evaluation at various stages. However, the clinical demands were far from being met. In this study, we utilized an alternative conformation-similarity-based virtual screening (CSVS) combined with a fragment-based drug designing (FBDD) strategy to efficiently discover a potent and active hit with a novel chemical scaffold. After structural optimization in the principle of group replacement, compound 57 was identified as the most promising ALK5 inhibitor. Compound 57 demonstrated significant inhibitory effects against the TGF-ß1/SMAD signaling pathway. It could markedly attenuate the production of extracellular matrix (ECM) and deposition of collagen. Also, the lead compound showed adequate pharmacokinetic (PK) properties and good in vivo tolerance. Moreover, treatment with compound 57 in two different xerograph models showed significant inhibitory effects on the growth of pancreatic cancer cells. These results suggested that lead compound 57 refers as a promising ALK5 inhibitor both in vitro and in vivo, which merits further validation.


Assuntos
Desenho de Fármacos , Inibidores de Proteínas Quinases , Pirazóis , Pirimidinas , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptor do Fator de Crescimento Transformador beta Tipo I/antagonistas & inibidores , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Humanos , Pirazóis/farmacologia , Pirazóis/química , Pirazóis/síntese química , Pirimidinas/farmacologia , Pirimidinas/química , Pirimidinas/síntese química , Relação Estrutura-Atividade , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Animais , Estrutura Molecular , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Camundongos , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Receptores de Fatores de Crescimento Transformadores beta/metabolismo
3.
Physiol Mol Biol Plants ; 30(3): 369-382, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38633272

RESUMO

The Cellulose Synthase gene (CS) superfamily and COBRA-like (COBL) gene family are essential for synthesizing cellulose and hemicellulose, which play a crucial role in cell wall biosynthesis and the hardening of plant tissues. Our study identified 126 ZbCS and 31 ZbCOBL genes from the Zanthoxylum bungeanum (Zb) genome. Phylogenetic analysis and conservative domain analysis unfolded that ZbCS and ZbCOBL genes were divided into seven and two subfamilies, respectively. Gene duplication data suggested that more than 75% of these genes had tandem and fragment duplications. Codon usage patterns analysis indicated that the ZbCS and ZbCOBL genes prefer ending with A/T base, with weak codon preference. Furthermore, seven key ZbCS and five key ZbCOBL genes were identified based on the content of cellulose and hemicellulose and the expression characteristics of ZbCS and ZbCOBL genes in various stages of stipule thorns. Altogether, these results improve the understanding of CS and COBL genes and provide valuable reference data for cultivating Zb with soft thorns. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01432-x.

4.
Front Oncol ; 14: 1358422, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577343

RESUMO

Prostate cancer is a major contributor to male cancer-related mortality globally. It has a particular affinity for the skeletal system with metastasis to bones seriously impacting prognosis. The identification of prostate cancer biomarkers can significantly enhance diagnosis and patient monitoring. Research has found that cancer and metastases exhibit abnormal expression of numerous non-coding RNA. Some of these RNA facilitate prostate cancer bone metastasis by activating downstream signaling pathways, while others inhibit this process. Elucidating the functional processes of non-coding RNA in prostate cancer bone metastasis will likely lead to innovative treatment strategies for this malignant condition. In this review, the mechanistic role of the various RNA in prostate cancer is examined. Our goal is to provide a new avenue of approach to the diagnosis and treatment of bone metastasis in this cancer.

5.
Sci Rep ; 14(1): 9649, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671074

RESUMO

The precision of workpiece machining is critically influenced by the geometric errors in the kinematics of grind robots, which directly affect their absolute positioning accuracy. To tackle this challenge, this paper introduces a logistic-tent chaotic mapping Levenberg Marquardt algorithm designed to accurately identify and compensate for this geometric error. the approach begins with the construction of a forward kinematic model and an error model specific to the robot. Then the algorithm is adopted to identify and compensate for the geometric error. The method establishes a mapping interval around the initial candidate solutions derived from iterative applications of the Levenberg Marquardt algorithm. Within this interval, the logistic-tent chaotic mapping method generates a diverse set of candidate solutions. These candidates are evaluated based on their fitness values, with the optimal solution selected for subsequent iterations. Empirical compensation experiments have validated the proposed method's precision and effectiveness, demonstrating a 6% increase in compensation accuracy and a 47.68% improvement in efficiency compared to existing state-of-the-art approaches. This process not only minimizes the truncation error inherent in the Levenberg Marquardt algorithm but also significantly enhances solution efficiency. Moreover, simulation experiments on grind processes further validate the method's ability to significantly improve the quality of workpiece machining.

6.
Adv Mater ; : e2404834, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678302

RESUMO

Alkaline zinc-based flow batteries (AZFBs) have emerged as a promising electrochemical energy storage technology owing to Zn abundance, high safety, and low cost. However, zinc dendrite growth and the formation of dead zinc greatly impede the development of AZFBs. Herein, a dual-function electrolyte additive strategy is proposed to regulate zinc nucleation and mitigate the hydroxide corrosion of zinc depositions for stable AZFBs. This strategy, as exemplified by urea, introduces an electrolyte additive to coordinate with Zn2+/Zn with proper strength, slowing zinc deposition kinetics to induce uniform nucleation and protecting the deposited zinc surface from attack by hydroxide ions through preferable adsorption. The zincate complexes with urea are identified to be Zn(OH)2(urea)(H2O)2 and Zn2(OH)4(H2O)4(urea), which exhibit slow zinc deposition kinetics, allowing instantaneous nucleation. Calculation results reveal an additional energy barrier of 1.29 eV for the subsequent adsorption of an OH- group when a urea molecule absorbs on the zinc cluster, significantly mitigating the formation of dead zinc. Consequently, prolonged cell cycling of the prototype alkaline zinc-iron flow battery demonstrates stable operation for over 130 h and an average coulombic efficiency of 98.5%. It is anticipated that this electrolyte additive strategy will pave the way for developing highly stable AZFBs.

7.
Adv Clin Exp Med ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38439609

RESUMO

Alzheimer's disease (AD) affects millions of people worldwide. The most commonly used drugs are acetylcholinesterase inhibitors, i.e., donepezil, galantamine and rivastigmine, which increase levels of acetylcholine. However, the exact efficacy and safety of acetylcholinesterase inhibitors in the treatment of AD is still unclear. The main objective of the current study was to determine the exact safety and efficacy profile of acetylcholinesterase inhibitors in the treatment of AD by conducting a systematic review and meta-analysis of clinical trials according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a web-based literature search of PubMed and clinical trial websites using relevant keywords. Data were extracted from eligible records and pooled as mean difference (MD) or risk ratio (RR) values with their 95% confidence interval (95% CI) using Review Manager software (v. 5.3 for Windows). Heterogeneity was calculated using χ2 and I2 tests. The standard mean difference (SMD) was -0.33 [-0.52, -0.13] for donepezil, -0.48 [-0.58, -0.38] for galantamine and -0.65 [-1.06, -0.23] for rivastigmine, indicating a significant effect of these drugs on cognitive outcomes. Here we show the significant effects of all available acetylcholinesterase inhibitors on cognitive function in patients with AD. However, further studies are needed to draw valid conclusions about the effects of acetylcholinesterase inhibitors on functional outcomes and adverse events.

8.
Alzheimers Dement (Amst) ; 16(1): e12569, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545543

RESUMO

The relationship between sex-specific blood biomarkers and memory changes in middle-aged adults remains unclear. We aimed to investigate this relationship using the data from the Framingham Heart Study (FHS). We conducted association analysis, partial correlation analysis, and causal dose-response curves using blood biomarkers and other data from 793 middle-aged participants (≤ 60 years) from the FHS Offspring Cohort. The results revealed associations of adiponectin and fasting blood glucose with midlife memory change, along with a U-shaped relationship of high-density lipoprotein cholesterol with memory change. No significant associations were found for the other blood biomarkers (e.g., amyloid beta protein 42) with memory change. To our knowledge, this is the first sex-specific network analysis of blood biomarkers related to midlife memory change in a prospective cohort study. Our findings highlight the importance of targeting cardiometabolic risks and the need to validate midlife-specific biomarkers that can accelerate the development of primary preventive strategies.

9.
Carbohydr Polym ; 332: 121889, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38431406

RESUMO

Metabolic alterations within mitochondria, encompassing processes such as autophagy and energy metabolism, play a pivotal role in facilitating the swift proliferation, invasion, and metastasis of cancer cells. Despite this, there is a scarcity of currently available medications with proven anticancer efficacy through the modulation of mitochondrial dysfunction in a clinical setting. Here, we introduce the structural characteristics of RN0D, a galactoglucan isolated and purified from Panax notoginseng flowers, mainly composed of ß-1,4-galactan and ß-1,3/1,6-glucan. RN0D demonstrates the capacity to induce mitochondrial impairment in cancer cells, leading to the accumulation of reactive oxygen species, initiation of mitophagy, and reduction in both mitochondrial number and size. This sequence of events ultimately results in the inhibition of mitochondrial and glycolytic bioenergetics, culminating in the demise of cancer cells due to adenosine triphosphate (ATP) deprivation. Notably, the observed bioactivity is attributed to RN0D's direct targeting of Galectin-3, as affirmed by surface plasmon resonance studies. Furthermore, RN0D is identified as an activator of the PTEN-induced kinase 1 (PINK1)/Parkin pathway, ultimately instigating cytotoxic mitophagy in tumor cells. This comprehensive study substantiates the rationale for advancing RN0D as a potentially efficacious anticancer therapeutic.


Assuntos
Neoplasias , Panax notoginseng , Polissacarídeos Bacterianos , Humanos , Mitofagia , Galactanos , Glucanos , Morte Celular , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Quinases/metabolismo
10.
Materials (Basel) ; 17(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38473624

RESUMO

As a thermal interface material, diamond/GaInSn composites have wide-ranging application prospects in the thermal management of chips. However, studies on systematic reliability that can guide the practical application of diamond/GaInSn in the high-temperature, high-temperature impact, or high-humidity service environments that are faced by chips remain lacking. In this study, the performance evolution of diamond/GaInSn was studied under high-temperature storage (150 °C), high- and low-temperature cycling (-50 °C to 125 °C), and high temperature and high humidity (85 °C and 85% humidity). The experimental results reveal the failure mechanism of semi-solid composites during high temperature oxidation. It is revealed that core oxidation is the key to the degradation of liquid metal composites' properties under high-temperature storage and high- and low-temperature cycling conditions. Under the conditions of high temperature and high humidity, the failure of Ga-based liquid metal and its composite materials is significant. Therefore, the material should avoid high-temperature and high-humidity environments.

11.
Int J Biol Macromol ; 264(Pt 2): 130705, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458300

RESUMO

The mitochondria are known to exert significant influence on various aspects of cancer cell physiology. The suppression of mitochondrial function represents a novel avenue for the advancement of anti-cancer pharmaceuticals. The heat shock protein HSP90 functions as a versatile regulator of mitochondrial metabolism in cancer cells, rendering as a promising target for anticancer interventions. In this work, a novel acid polysaccharide named as XQZ3 was extracted from Chlorella pyrenoidosa and purified by DEAE-cellulose and gel-filtration chromatography. The structural characteristic of XQZ3 was evaluated by monosaccharides composition, methylation analysis, TEM, FT-IR, and 2D-NMR. It was found that XQZ3 with a molecular weight of 29.13 kDa was a complex branched polysaccharide with a backbone mainly composed of galactose and mannose. It exhibited good antitumor activity in vitro and in vivo by patient-derived 3D organoid models and patient-derived xenografts models. The mechanistic investigations revealed that XQZ3 specifically interacted with HSP90, impeding the activation of the HSP90/AKT/mTOR signaling cascade. This, in turn, led to the induction of mitochondrial dysfunction, autophagy, and apoptosis, ultimately resulting in the demise of cancer cells due to nutrient deprivation. This study offers a comprehensive theoretical foundation for the advancement of XQZ3, a novel polysaccharide inhibitor targeting HSP90, with potential as an effective therapeutic agent against cancer.


Assuntos
Chlorella , Neoplasias , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Chlorella/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Transdução de Sinais , Proteínas de Choque Térmico HSP90/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Apoptose , Metabolismo Energético , Mitocôndrias/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo
12.
Ecotoxicol Environ Saf ; 274: 116191, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38460408

RESUMO

The reproduction toxicity of pubertal exposure to Microcystin-LR (MC-LR) and the underlying mechanism needs to be further investigated. In the current study, pubertal male ICR mice were intraperitoneally injected with 2 µg/kg MC-LR for four weeks. Pubertal exposure to MC-LR decreased epididymal sperm concentration and blocked spermatogonia proliferation. In-vitro studies found MC-LR inhibited cell proliferation of GC-1 cells and arrested cell cycle in G2/M phase. Mechanistically, MC-LR exposure evoked excessive reactive oxygen species (ROS) and induced DNA double-strand break in GC-1 cells. Besides, MC-LR inhibited DNA repair by reducing PolyADP-ribosylation (PARylation) activity of PARP1. Further study found MC-LR caused proteasomal degradation of SIRT6, a monoADP-ribosylation enzyme which is essential for PARP1 PARylation activity, due to destruction of SIRT6-USP10 interaction. Additionally, MG132 pretreatment alleviated MC-LR-induced SIRT6 degradation and promoted DNA repair, leading to the restoration of cell proliferation inhibition. Correspondingly, N-Acetylcysteine (NAC) pre-treatment mitigated the disturbed SIRT6-USP10 interaction and SIRT6 degradation, causing recovered DNA repair and subsequently restoration of cell proliferation inhibition in MC-LR treated GC-1 cells. Together, pubertal exposure to MC-LR induced spermatogonia cell cycle arrest and sperm count reduction by oxidative DNA damage and simultaneous SIRT6-mediated DNA repair failing. This study reports the effect of pubertal exposure to MC-LR on spermatogenesis and complex mechanism how MC-LR induces spermatogonia cell proliferation inhibition.


Assuntos
Toxinas Marinhas , Microcistinas , Sirtuínas , Espermatogônias , Animais , Masculino , Camundongos , Apoptose , Proliferação de Células , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Reparo do DNA , Toxinas Marinhas/metabolismo , Toxinas Marinhas/toxicidade , Camundongos Endogâmicos ICR , Microcistinas/metabolismo , Microcistinas/toxicidade , Sêmen , Sirtuínas/efeitos dos fármacos , Sirtuínas/metabolismo , Espermatogônias/efeitos dos fármacos , Espermatogônias/metabolismo
13.
World J Clin Cases ; 12(3): 587-595, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38322461

RESUMO

BACKGROUND: Paramyotonia congenita (PMC) stands as a rare sodium channelopaty of skeletal muscle, initially identified by Eulenburg. The identification of PMC often relies on electromyography (EMG), a diagnostic technique. The child's needle EMG unveiled trains of myotonic discharges with notably giant amplitudes, alongside irregular wave trains of myotonic discharges. This distinctive observation had not surfaced in earlier studies. CASE SUMMARY: We report the case of a 3-year-old female child with PMC, who exhibited laryngeal stridor, muffled speech, myotonia from birth. Cold, exposure to cool water, crying, and physical activity exacerbated the myotonia, which was relieved in warmth, yet never normalized. Percussion myotonia was observable in bilateral biceps. Myotonia symptoms remained unchanged after potassium-rich food consumption like bananas. Hyperkalemic periodic paralysis was excluded. Cranial magnetic resonance imaging yielded normal results. Blood potassium remained within normal range, while creatine kinase showed slight elevation. Exome-wide genetic testing pinpointed a heterozygous mutation on chromosome SCN4A: c.3917G>A (p.G1306E). After a six-month mexiletine regimen, symptoms alleviated. CONCLUSION: In this case revealed the two types of myotonic discharges, and had not been documented in other studies. We underscore two distinctive features: Giant-amplitude potentials and irregular waves.

14.
Biomed Pharmacother ; 173: 116278, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401513

RESUMO

Riboflavin (RF) as a photosensitizer has been used in corneal surgery and the inactivation of blood products. However, the effect of RF on immune cells after ultraviolet (UV) light stimulation has not been investigated. This study pioneered a novel application method of RF. Firstly, UV-stimulated RF was co-cultured with human peripheral blood mononuclear cells in vitro, and the apoptosis rate of lymphocyte subsets, cell proliferation inhibition rate and concentrations of IL-1ß, IL-6, IL-10, TNF-α were assessed. UV-stimulated RF was then administered intravenously to mice via the tail vein for a consecutive period of 5 days. The levels of immunoglobulin (IgG, IgM, IgA), complement (C3, C4) and cytokines (IFN-γ, IL-4, IL17, TGF-ß) were detected by ELISA. Flow cytometry was employed to analyze the populations of CD3+T, CD4+T, CD8+T and CD4+T/CD8+T cells in spleen lymphocytes of mice. The data showed that UV-stimulated RF can effectively induce apoptosis in lymphocytes, and different lymphocyte subtypes exhibited varying degrees of treatment tolerance. Additionally, the proliferative capacity of lymphocytes was suppressed, while their cytokine secretion capability was augmented. The animal experiments demonstrated that UV-stimulated RF led to a significant reduction observed in serum immunoglobulin and complement levels, accompanied by an elevation in IFN-γ, IL-17 and TGF-ß levels, as well as a decline in IL-4 level. In summary, the results of both in vitro and in vivo experiments have demonstrated that UV-stimulated RF, exhibits the ability to partially inhibit immune function. This novel approach utilizing RF may offer innovative perspectives for diseases requiring immunosuppressive treatment.


Assuntos
Interleucina-4 , Leucócitos Mononucleares , Humanos , Camundongos , Animais , Interleucina-4/farmacologia , Camundongos Endogâmicos BALB C , Citocinas/farmacologia , Riboflavina/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Imunoglobulinas/farmacologia , Linfócitos T CD4-Positivos
15.
Neurotoxicology ; 101: 82-92, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38346645

RESUMO

Recent evidence showed that general anesthesia produces long-term neurotoxicity and cognitive dysfunction. However, it remains unclear whether maternal non-obstetric surgery under ketamine anesthesia during second trimester causes cognitive impairment in offspring. The present study assigned pregnant rats into three groups: 1) normal control group receiving no anesthesia and no surgery, 2) ketamine group receiving ketamine anesthesia for 2 h on the 14th day of gestation but no surgery, and 3) surgery group receiving abdominal surgery under ketamine anesthesia on the 14th day of gestation. On postnatal day 1, the offspring rats in Ketamine group and surgery group were assigned to receive intra-peritoneal injection of Senegenin (15 mg/kg), once per day for consecutive 14 days. The offspring's spatial perception, anxiety-like behavior, and learning and memory were evaluated. Then the offspring's hippocampal tissues were collected. The offspring of the surgery group were impaired in the spatial perception in the cliff avoidance test and the spatial learning and memory in the Morris water maze test. Accordingly, the activity of histone deacetylases increased, the protein levels of NEDD9, BDNF, p-TrkB, Syn and PSD-95 decreased, and the density of dendritic spines reduced in the hippocampus of the offspring of the surgery group, and such effects were not seen in the offspring of the ketamine group, neither in the offspring of control group. Senegenin alleviated the learning and memory impairment, and increased the protein levels of NEDD9, BDNF, p-TrkB, Syn and PSD-95 and the density of dendritic spines in the offspring of the surgery group. ketamine anesthesia plus surgery during second trimester impairs hippocampus-dependent learning and memory, and the deficits could be rescued by treatment with Senegenin.


Assuntos
Anestesia , Ketamina , Gravidez , Feminino , Ratos , Animais , Ketamina/toxicidade , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Aprendizagem Espacial , Hipocampo , Dendritos , Aprendizagem em Labirinto
16.
J Transl Med ; 22(1): 206, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38414027

RESUMO

BACKGROUND: The global cellular landscape of the tumor microenvironment (TME) combining primary and metastatic liver tumors has not been comprehensively characterized. METHODS: Based on the scRNA-seq and spatial transcriptomic data of non-tumor liver tissues (NTs), primary liver tumors (PTs) and metastatic liver tumors (MTs), we performed the tissue preference, trajectory reconstruction, transcription factor activity inference, cell-cell interaction and cellular deconvolution analyses to construct a comprehensive cellular landscape of liver tumors. RESULTS: Our analyses depicted the heterogeneous cellular ecosystems in NTs, PTs and MTs. The activated memory B cells and effector T cells were shown to gradually shift to inhibitory B cells, regulatory or exhausted T cells in liver tumors, especially in MTs. Among them, we characterized a unique group of TCF7+ CD8+ memory T cells specifically enriched in MTs that could differentiate into exhausted T cells likely driven by the p38 MAPK signaling. With regard to myeloid cells, the liver-resident macrophages and inflammatory monocyte/macrophages were markedly replaced by tumor-associated macrophages (TAMs), with TREM2+ and UBE2C+ TAMs enriched in PTs, while SPP1+ and WDR45B+ TAMs in MTs. We further showed that the newly identified WDR45B+ TAMs exhibit an M2-like polarization and are associated with adverse prognosis in patients with liver metastases. Additionally, we addressed that endothelial cells display higher immune tolerance and angiogenesis capacity, and provided evidence for the source of the mesenchymal transformation of fibroblasts in tumors. Finally, the malignant hepatocytes and fibroblasts were prioritized as the pivotal cell populations in shaping the microenvironments of PTs and MTs, respectively. Notably, validation analyses by using spatial or bulk transcriptomic data in clinical cohorts concordantly emphasized the clinical significance of these findings. CONCLUSIONS: This study defines the ontological and functional heterogeneities in cellular ecosystems of primary and metastatic liver tumors, providing a foundation for future investigation of the underlying cellular mechanisms.


Assuntos
Células Endoteliais , Neoplasias Hepáticas , Humanos , Ecossistema , Neoplasias Hepáticas/genética , Perfilação da Expressão Gênica , Microambiente Tumoral
17.
J Coll Physicians Surg Pak ; 34(2): 146-150, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38342862

RESUMO

OBJECTIVE: To identify the predictive factors of intestinal ischaemia in adhesive small bowel obstruction (ASBO) and develop an intestinal ischaemia risk score. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China, from January 2017 to February 2022. METHODOLOGY: ASBO was determined by findings at laparotomy. The assessment of small bowel's viability was conducted through surgical inspection and subsequent histological examination of the surgical specimen. Univariate and multivariate analyses were conducted to ascertain the risk factors associated with intestinal ischaemia. RESULTS: In total, 79 patients were included. Factors entered into multivariate analysis associated with intestinal ischaemia were; rebound tenderness (odds ratio (OR): 7.8, 95% confidence interval (CI):1.7-35.3; p=0.008), procalcitonin (PCT) >0.5 ng/mL (OR: 11.7, 95% CI: 2.3-58.1; p=0.003), and reduced bowel wall enhancement on computerised tomography (CT) scan (OR: 12.2, 95% CI:2.4-61.5; p=0.003). Among patients with 0, 1, 2, and 3 factors, the rate of intestinal ischaemia increased from 0% to 49%, 72%, and 100%, respectively. According to the number of risk factors, the area under the receiver operating characteristic curve for the determination of intestinal ischaemia was 0.848 (95% CI: 0.764-0.932). CONCLUSION: Rebound tenderness, PCT levels >0.5 ng/mL, and reduced bowel wall enhancement are risk factors of intestinal ischemic injury that require surgery within the context of ASBO. These factors need to be closely monitored that could assist clinicians in avoiding unnecessary laparotomies and selecting patients eligible for surgery. KEY WORDS: Intestinal obstruction, Ischaemia, Adhesions.


Assuntos
Obstrução Intestinal , Isquemia Mesentérica , Aderências Teciduais , Lesões do Sistema Vascular , Humanos , Dor Abdominal/etiologia , Obstrução Intestinal/complicações , Obstrução Intestinal/patologia , Obstrução Intestinal/cirurgia , Laparotomia , Isquemia Mesentérica/etiologia , Isquemia Mesentérica/cirurgia , Pró-Calcitonina , Estudos Retrospectivos , Aderências Teciduais/complicações , Aderências Teciduais/cirurgia , Lesões do Sistema Vascular/etiologia , Lesões do Sistema Vascular/cirurgia
18.
Ecol Evol ; 14(2): e11052, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38414570

RESUMO

Exploring how interactions between species evenness and dominant species identity affect litter decomposition processes is vital to understanding the relationship between biodiversity and ecosystem functioning in the context of global changes. We carried out a 127-day litter decomposition experiment under controlled conditions, with interactions of four species evenness types (high, medium, low and single species) and three dominant species identity (Leymus chinensis, Serratula centauroides, Artemisia capillaris). After collecting the remaining litter, we estimated how evenness and dominant species identity affected litter mass loss rate, carbon (C) loss rate, nitrogen (N) loss rate and remaining litter C/N directly or indirectly, and assessed relative mixture effects (RMEs) on litter mass loss. The main results are shown as follows. (1) By generalized linear models, litter mass loss rate was significantly affected by evenness after 69-day decomposition; N loss rate was affected by dominant species identity after 69-day decomposition, with treatment dominated by Serratula centauroides being at least 9.26% higher than that dominated by any of other species; and remaining litter C/N was affected by the interactions between evenness and dominant species identity after 30-, 69- and 127-day decomposition. (2) Twenty-three out of 27 RMEs were additive, and dominant species identity showed a significant effect on RMEs after 127-day decomposition. (3) By confirmatory path analyses, litter mass loss rate was affected by dominant species identity directly after 127-day decomposition, and by both species evenness and dominant species identity indirectly which was mediated by initial litter functional dispersion (FDis) after 30- and 69-day decomposition; remaining litter C/N was affected by evenness indirectly which was mediated by initial litter FDis after 127-day decomposition. These findings highlight the importance of evenness and dominant species identity on litter decomposition. The study provides insights into communities during retrogressive successions in semi-arid grasslands in the context of global changes.

19.
Eur J Radiol Open ; 12: 100550, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38314183

RESUMO

Objectives: To determine whether contrast-enhanced CT radiomics features can preoperatively predict lymphovascular invasion (LVI) and perineural invasion (PNI) in gastric cancer (GC). Methods: A total of 148 patients were included in the LVI group, and 143 patients were included in the PNI group. Three predictive models were constructed, including clinical, radiomics, and combined models. A nomogram was developed with clinical risk factors to predict LVI and PNI status. The predictive performance of the three models was mainly evaluated using the mean area under the curve (AUC). The performance of three predictive models was assessed concerning calibration and clinical usefulness. Results: In the LVI group, the predictive power of the combined model (AUC=0.871, 0.822) outperformed the clinical model (AUC=0.792, 0.728) and the radiomics model (AUC=0.792, 0.728) in both the training and testing cohorts. In the PNI group, the combined model (AUC=0.834, 0.828) also had better predictive power than the clinical model (AUC=0.764, 0.632) and the radiomics model (AUC=0.764, 0.632) in both the training and testing cohorts. The combined models also showed good calibration and clinical usefulness for LVI and PNI prediction. Conclusion: CECT-based radiomics analysis might serve as a non-invasive method to predict LVI and PNI status in GC.

20.
Exp Ther Med ; 27(3): 110, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38361517

RESUMO

Diabetic kidney disease (DKD) is a severe microvascular complication of diabetes, one key feature of which includes renal fibrosis. As apelin is an adipokine closely related to diabetes, the present study aimed to evaluate apelin-13 expression levels and the relationship between apelin-13 and disease indicators in patients with diabetic kidney disease (DKD). The present case-control study enrolled 70 patients with diabetes, including 31 with diabetic kidney disease (DKD group), 39 without DKD (non-DKD group) and 30 healthy controls. The levels of serum apelin-13 and TGF-ß1, the key driver of renal fibrosis, were determined by ELISA. Additionally, age, mean disease duration, weight, blood pressure, fasting blood glucose, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein, cholesterol, urea nitrogen, blood creatinine and 24-hour urinary total protein (24-h UTP) were recorded. The results demonstrated that apelin-13 and TGF-ß1 expression levels, age, blood pressure, fasting blood glucose, cholesterol and blood urea nitrogen levels were significantly higher in patients with diabetes compared with the healthy controls (P<0.05). Moreover, apelin-13 and TGF-ß1 expression levels, mean disease duration, systolic pressure, blood creatinine, blood urea nitrogen and 24-h UTP were significantly higher in the DKD group compared with the non-DKD group (P<0.05). The estimated glomerular filtration rate (eGFR) was significantly reduced in the DKD group compared with the non-DKD group (P<0.05). Correlation analysis demonstrated a negative correlation between apelin-13 and eGFR expression and a positive correlation between apelin-13 expression and 24-h UTP in both the DKD and non-DKD groups (P<0.05). A negative correlation was also demonstrated between apelin-13 and TGF-ß1 expression levels in the DKD group and non-DKD groups (both P<0.05). In conclusion, apelin-13 and TGF-ß1 expression levels were significantly higher in the DKD group compared with those in the non-DKD group. Additionally, apelin-13 expression was negatively correlated with TGF-ß1 expression in the DKD and non-DKD groups. Therefore, apelin-13 could potentially be used in the future as an indicator of renal fibrosis or destruction in patients with DKD. The present trial was retrospectively registered in the Chinese Clinical Trial Registry (trial registration no. ChiCTR2200060945) on 14.06.2022.

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