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1.
World J Clin Oncol ; 15(3): 456-463, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38576599

RESUMO

BACKGROUND: SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting (SWI/SNF) complexes and plays an essential role in oncogenesis. SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis. There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies. Programmed death 1 (PD-1) antibodies, known as immune checkpoint inhibitor antibodies, potentially play a role in treating gastrointestinal tract malignancies. CASE SUMMARY: We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum. For both patients, SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein, while TP53 gene mutations were observed via next-generation sequencing. Both patients were administered chemotherapy in combination with an anti-PD-1 antibody. The two patients exhibited completely different responses to treatment and had different prognoses. Case 1 experienced rapid progression after PD-1 infusion and chemotherapy, case 2 experienced a remarkable response after treatment, and the progression-free survival was more than 6 months. CONCLUSION: This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum. PD-1 combined with chemotherapy showed a certain efficacy in select patients, providing options for treating these highly malignant tumors. Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.

2.
BMC Plant Biol ; 24(1): 256, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594627

RESUMO

BACKGROUND: Climate change has led to severe cold events, adversely impacting global crop production. Eggplant (Solanum melongena L.), a significant economic crop, is highly susceptible to cold damage, affecting both yield and quality. Unraveling the molecular mechanisms governing cold resistance, including the identification of key genes and comprehensive transcriptional regulatory pathways, is crucial for developing new varieties with enhanced tolerance. RESULTS: In this study, we conducted a comparative analysis of leaf physiological indices and transcriptome sequencing results. The orthogonal partial least squares discriminant analysis (OPLS-DA) highlighted peroxidase (POD) activity and soluble protein as crucial physiological indicators for both varieties. RNA-seq data analysis revealed that a total of 7024 and 6209 differentially expressed genes (DEGs) were identified from variety "A" and variety "B", respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of DEGs demonstrated that the significant roles of starch and sucrose metabolism, glutathione metabolism, terpenoid synthesis, and energy metabolism (sucrose and starch metabolism) were the key pathways in eggplant. Weighted gene co-expression network analysis (WGCNA) shown that the enrichment of numerous cold-responsive genes, pathways, and soluble proteins in the MEgrep60 modules. Core hub genes identified in the co-expression network included POD, membrane transporter-related gene MDR1, abscisic acid-related genes, growth factor enrichment gene DELLA, core components of the biological clock PRR7, and five transcription factors. Among these, the core transcription factor MYB demonstrated co-expression with signal transduction, plant hormone, biosynthesis, and metabolism-related genes, suggesting a pivotal role in the cold response network. CONCLUSION: This study integrates physiological indicators and transcriptomics to unveil the molecular mechanisms responsible for the differences in cold tolerance between the eggplant cold-tolerant variety "A" and the cold-sensitive variety "B". These mechanisms include modulation of reactive oxygen species (ROS), elevation in osmotic carbohydrate and free proline content, and the expression of terpenoid synthesis genes. This comprehensive understanding contributes valuable insights into the molecular underpinnings of cold stress tolerance, ultimately aiding in the improvement of crop cold tolerance.


Assuntos
Solanum melongena , Transcriptoma , Solanum melongena/genética , Solanum melongena/metabolismo , Fisiologia Comparada , Perfilação da Expressão Gênica/métodos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Resposta ao Choque Frio/genética , Amido/metabolismo , Sacarose/metabolismo , Terpenos/metabolismo , Regulação da Expressão Gênica de Plantas
3.
J Environ Manage ; 357: 120732, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38560954

RESUMO

Pharmaceutical compounds (PhCs) pose a growing concern with potential environmental impacts, commonly introduced into the environment via wastewater treatment plants (WWTPs). The occurrence, removal, and season variations of 60 different classes of PhCs were investigated in the baffled bioreactor (BBR) wastewater treatment process during summer and winter. The concentrations of 60 PhCs were 3400 ± 1600 ng/L in the influent, 2700 ± 930 ng/L in the effluent, and 2400 ± 120 ng/g dw in sludge. Valsartan (Val, 1800 ng/L) was the main contaminant found in the influent, declining to 520 ng/L in the effluent. The grit chamber and BBR tank were substantially conducive to the removal of VAL. Nonetheless, the BBR process showcased variable removal efficiencies across different PhC classes. Sulfadimidine had the highest removal efficiency of 87 ± 17% in the final effluent (water plus solid phase). Contrasting seasonal patterns were observed among PhC classes within BBR process units. The concentrations of many PhCs were higher in summer than in winter, while some macrolide antibiotics exhibited opposing seasonal fluctuations. A thorough mass balance analysis revealed quinolone and sulfonamide antibiotics were primarily eliminated through degradation and transformation in the BBR process. Conversely, 40.2 g/d of macrolide antibiotics was released to the natural aquatic environment via effluent discharge. Gastric acid and anticoagulants, as well as cardiovascular PhCs, primarily experienced removal through sludge adsorption. This study provides valuable insights into the intricate dynamics of PhCs in wastewater treatment, emphasizing the need for tailored strategies to effectively mitigate their release and potential environmental risks.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Águas Residuárias , Esgotos/análise , Eliminação de Resíduos Líquidos , Estações do Ano , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Antibacterianos/análise , Medição de Risco , Macrolídeos/análise , Preparações Farmacêuticas
4.
Artigo em Inglês | MEDLINE | ID: mdl-38642118

RESUMO

Childhood maltreatment has long-term negative effects on individuals' physical and mental well-being, and may increase the risk for suicidal ideation. However, how different patterns of childhood maltreatment affect subsequent suicidal ideation and the underlying mediating mechanisms remain unclear, particularly among Chinese adolescents. This study used latent profile analysis to identify patterns of childhood maltreatment among adolescents and explored how these patterns predicted subsequent suicidal ideation via depression, hope, and expressive suppression. This study used a two-wave, 1-year longitudinal design and included 2156 adolescents (Mage = 13.97 years, SDage = 1.61 years; 49.6% females). We identified three patterns of childhood maltreatment: low maltreatment, high psychological neglect, and high maltreatment. Compared with the low maltreatment group, the high maltreatment group indirectly predicted subsequent suicidal ideation 1 year later via depression through hope and expressive suppression, whereas the direct effect on suicidal ideation was not significant. Compared with the low maltreatment group, the high psychological neglect group had a significant direct effect on subsequent suicidal ideation and indirectly predicted suicidal ideation through depression or hope. Identifying patterns of childhood maltreatment among adolescents will assist mental health workers in developing targeted interventions to effectively alleviate suicidal ideation.

5.
RSC Adv ; 14(16): 11470-11481, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38601703

RESUMO

Sulfur-doped activated carbon has proved to be a promising metal-free catalyst for persulfate (PDS) catalytic activation for the oxidation of aqueous refractory organics. Herein, sulfur-doped porous carbon (ACS) catalysts with different pore structures and doped-S contents were prepared via a template method using d(+)-glucose as the carbon source, sulfur as the sulfur source, and nano-MgO with different particle sizes as templates. Characterization results showed that the particle size of MgO significantly affects the pore structure and doped-S content of ACSs catalysts: a sample synthesized with 20 nm MgO as template (ACS-20) presented the highest content of doped-S and a mesoporous structure, which endowed it with superior adsorption and catalytic performance toward tetracycline (TC) removal. The effect of catalyst dosage, TC concentration, PDS concentration and solution pH on TC removal efficiency were evaluated. The reaction mechanism, investigated by combination of EPR, quenching experiments and LC-MS, indicated that the reactive species included HO·, SO4˙-, and 1O2, but that 1O2 played the dominant role in TC oxidation through a non-radical oxidation pathway. In addition, the reusability and regeneration properties of the ACS-20 catalyst were also studied. This work provides a promising strategy and some theoretical basis for the design and preparation of activated carbon catalysts for advanced oxidation reactions from the viewpoint of pore structure design and S-doping.

6.
Int J Mol Sci ; 25(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38612411

RESUMO

Biofilm formation plays a crucial role in the pathogenesis of Candida albicans and is significantly associated with resistance to antifungal agents. Tea seed saponins, a class of non-ionic triterpenes, have been proven to have fungicidal effects on planktonic C. albicans. However, their anti-biofilm activity and mechanism of action against C. albicans remain unclear. In this study, the effects of three Camellia sinensis seed saponin monomers, namely, theasaponin E1 (TE1), theasaponin E2 (TE2), and assamsaponin A (ASA), on the metabolism, biofilm development, and expression of the virulence genes of C. albicans were evaluated. The results of the XTT reduction assay and crystal violet (CV) staining assay demonstrated that tea seed saponin monomers concentration-dependently suppressed the adhesion and biofilm formation of C. albicans and were able to eradicate mature biofilms. The compounds were in the following order in terms of their inhibitory effects: ASA > TE1 > TE2. The mechanisms were associated with reductions in multiple crucial virulence factors, including cell surface hydrophobicity (CSH), adhesion ability, hyphal morphology conversion, and phospholipase activity. It was further demonstrated through qRT-PCR analysis that the anti-biofilm activity of ASA and TE1 against C. albicans was attributed to the inhibition of RAS1 activation, which consequently suppressed the cAMP-PKA and MAPK signaling pathways. Conversely, TE2 appeared to regulate the morphological turnover and hyphal growth of C. albicans via a pathway that was independent of RAS1. These findings suggest that tea seed saponin monomers are promising innovative agents against C. albicans.


Assuntos
Candida albicans , Ácido Oleanólico/análogos & derivados , Saponinas , Saponinas/farmacologia , Biofilmes , Chá
7.
Infect Drug Resist ; 17: 1477-1490, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38634066

RESUMO

Purpose: To analyze the time trends in the notification rates of registered tuberculosis (TB) and bacteriologically confirmed TB in Shandong Province. And analyze the changes in TB treatment outcomes during 2005-2021. Patients and Methods: The information of TB patients registered in the Shandong Information Center for Disease Control and Prevention (CDC) was collected during 2005-2021. We calculated the notification rates of registered TB and bacteriologically confirmed TB. Moreover, we calculated the year-to-year change rate of TB in treatment outcomes before and after COVID-19. The time trends were analyzed using the joinpoint regression method and illustrated as the annual percentage change (APC) of notification rates. Results: A total of 236,898 cases of TB were diagnosed during 2005-2021, of which 51.11% were bacteriologically confirmed cases. Since 2008, the notification rates of registered TB have declined. The notification rates of bacteriologically confirmed TB had been declining during 2005-2016, then remained stable after 2016. In subgroup, the notification rates of both registered TB and bacteriologically confirmed TB were higher among men, rural residents, and people aged ≥ 60 years. Compared with clinically confirmed TB, bacteriologically confirmed TB has shown higher rates of poor outcomes since 2008 and higher case fatality rate since 2005. The rate of poor outcomes remained stable during 2008-2019. However, after the COVID-19 outbreak, the rate of poor outcomes and case fatality rate of TB has risen significantly. Conclusion: After unremitting efforts to fight against TB, the notification rates of registered TB and bacteriologically confirmed TB declined in Shandong Province. The rate of poor outcomes remained stable during 2008-2019, then rise significantly after the COVID-19 outbreak. In the context of the long-term existence of COVID-19, further efforts should be made in TB diagnosis and treatment among high-risk population, especially with regard to males, rural residents and older adults.

8.
Angew Chem Int Ed Engl ; : e202402511, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634323

RESUMO

α-Olefins are valued and abundant building blocks from fossil resources. They are widely used to provide small-molecule or polymeric products. Despite numerous advantages of radical polymerization, it has been well-documented as textbook knowledge that α-olefins and their functionalized derivatives cannot be radically homopolymerized because of the degradative chain transfer side reactions. Herein, we report our studies on the homopolymerization of thiocyanate functionalized α-olefins enabled by 1,4-cyano group migration under radical conditions. By this approach, a library of ABC sequence-controlled polymers with high molecular weights can be prepared. We can also extend this strategy to the homopolymerization of α-substituted styrenic and acylate monomers which are known to be challenging to achieve. Overall, the demonstrated functional group migration radical polymerization could provide new possibilities to synthesize polymers with unprecedented main chain sequences and structures. These polymers are promising candidates for novel polymeric materials.

9.
Small ; : e2400849, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644168

RESUMO

Liquid organic hydrogen carrier is a promising option for the transport and storage of hydrogen as a clean energy source. This study examines the stability and behavior of organic drops immobilized on a substrate during an interfacial hydrogen-evolution reaction (HER) at the drop surface and its surrounding aqueous solution. Hydrogen microbubbles form within the drop and rise to the drop apex. The growth rate of the hydrogen in-drop bubble increases with the concentration of the reactant in the surrounding medium. The drop remains stable till the buoyancy acting on the in-drop bubble is large enough to overcome the capillary force and the external viscous drag. The bubble spontaneously rises and carries a portion drop liquid to the solution surface. These spontaneous rising in-drop bubbles are detected in measurements using a high-precision sensor placed on the upper surface of the aqueous solution, reversing the settling phase from phase separation in the reactive emulsion. The finding from this work provides new insights into the behaviors of drops and bubbles in many interfacial gas evolution reactions in clean technologies.

10.
J Appl Stat ; 51(5): 935-957, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524793

RESUMO

Profile monitoring is one of the most important topics for statistical process control. Traditional self-starting profile monitoring schemes generally use all historical observations to estimate parameters. Because of the rapid increase in the complexity of modern statistical processes, the practitioners often need to deal with massive datasets in process monitoring. However, when observations of each period are of large sample size and the computation is of high complexity, the traditional method is not economical and urgently needs a parameter update strategy. Under the framework of binary profile monitoring, this paper proposes a novel recursive update strategy based on the aggregated estimation equation (AEE) for massive datasets and designs a self-starting control chart accordingly. Numerical simulation verifies that the proposed method performs better in parameter estimation and process monitoring. In addition, we give the asymptotic property of the proposed monitoring statistic and illustrate our method's superiority by a real-data example.

11.
BMC Genomics ; 25(1): 249, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448842

RESUMO

BACKGROUND: Iron plays a crucial role in the growth of Mycobacterium tuberculosis (M. tuberculosis). However, the precise regulatory mechanism governing this system requires further elucidation. Additionally, limited studies have examined the impact of gene mutations related to iron on the transmission of M. tuberculosis globally. This research aims to investigate the correlation between mutations in iron-related genes and the worldwide transmission of M. tuberculosis. RESULTS: A total of 13,532 isolates of M. tuberculosis were included in this study. Among them, 6,104 (45.11%) were identified as genomic clustered isolates, while 8,395 (62.04%) were classified as genomic clade isolates. Our results showed that a total of 12 single nucleotide polymorphisms (SNPs) showed a positive correlation with clustering, such as Rv1469 (ctpD, C758T), Rv3703c (etgB, G1122T), and Rv3743c (ctpJ, G676C). Additionally, seven SNPs, including Rv0104 (T167G, T478G), Rv0211 (pckA, A302C), Rv0283 (eccB3, C423T), Rv1436 (gap, G654T), ctpD C758T, and etgB C578A, demonstrated a positive correlation with transmission clades across different countries. Notably, our findings highlighted the positive association of Rv0104 T167G, pckA A302C, eccB3 C423T, ctpD C758T, and etgB C578A with transmission clades across diverse regions. Furthermore, our analysis identified 78 SNPs that exhibited significant associations with clade size. CONCLUSIONS: Our study reveals the link between iron-related gene SNPs and M. tuberculosis transmission, offering insights into crucial factors influencing the pathogenicity of the disease. This research holds promise for targeted strategies in prevention and treatment, advancing research and interventions in this field.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Mycobacterium tuberculosis/genética , Sequenciamento Completo do Genoma , Ferro , Mutação , Tuberculose/genética
12.
Schizophr Res Cogn ; 36: 100306, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38469136

RESUMO

Deficits in executive control of attention have been reported in schizophrenia patients, but can be ameliorated by treatment of atypical antipsychotics along with the symptoms. However, it remains unclear whether this effect is related to a modulation of hemispheric asymmetry in executive control by the medicine. In this behavioral study, we employed a lateralized version of the attention network test to examine the hemispheric asymmetry of executive control in schizophrenia patients before and after olanzapine treatment, compared to matched healthy controls. Executive control was measured as a conflict effect, indexed as the response time (RT) difference between incongruent versus congruent flanker conditions, and was compared between stimuli presented in the left and the right visual field (i.e., processed by right versus left hemisphere of the brain). Results showed that pre-treatment schizophrenia patients revealed a right hemisphere superiority in conflict effect (i.e., a smaller effect in the right hemisphere than in the left hemisphere), driven by the incongruent condition. Olanzapine treatment reduced this right hemisphere superiority by improving the efficiency of the left hemisphere in the incongruent condition. These results suggested that olanzapine treatment may improve the efficiency of executive control in the left hemisphere in schizophrenia patients.

13.
Medicine (Baltimore) ; 103(12): e37617, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38518003

RESUMO

Multidrug-resistant tuberculosis (MDR-TB) has imposed a significant economic and health burden worldwide, notably in China. Using whole genome sequence, we sought to understand the mutation and transmission of MDR-TB in Shandong. A retrospective study of patients diagnosed with pulmonary tuberculosis in Shandong from 2009 to 2018 was conducted. To explore transmission patterns, we performed whole genome sequencing on MDR-TB isolates, identified genomic clusters, and assessed the drug resistance of TB isolates. Our study analyzed 167 isolates of MDR-TB, finding that 100 were clustered. The predominant lineage among MDR-TB isolates was lineage 2, specifically with a notable 88.6% belonging to lineage 2.2.1. Lineage 4 constituted a smaller proportion, accounting for 4.2% of the isolates. We discovered that Shandong has a significant clustering percentage for MDR-TB, with Jining having the highest percentage among all Shandong cities. The clustering percentages of MDR-TB, pre-extensively drug-resistant tuberculosis, and extensively drug-resistant tuberculosis were 59.9%, 66.0%, and 71.4%, respectively, and the clustering percentages increased with the expansion of the anti-TB spectrum. Isolates from genomic clusters 1 and 3 belonged to lineage 2.2.1 and showed signs of cross-regional transmission. The distribution of rrs A1401G and katG S315T mutations in lineage 2.2.1 and 2.2.2 strains differed significantly (P < .05). MDR-TB isolates with rpoB I480V, embA-12C > T, and rrs A1401G mutations showed a higher likelihood of clustering (P < .05). Our findings indicate a significant problem of local transmission of MDR-TB in Shandong, China. Beijing lineage isolates and some drug-resistant mutations account for the MDR-TB transmission in Shandong.


Assuntos
Tuberculose Extensivamente Resistente a Medicamentos , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla/genética , Estudos Retrospectivos , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Mutação , China/epidemiologia , Testes de Sensibilidade Microbiana , Genótipo
14.
Front Plant Sci ; 15: 1304121, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38486852

RESUMO

Chionanthus retusus (C. retusus) has a high economic and medicinal value, but in recent years it has been included in the list of China's major protected plants and China's Red List of Biodiversity due to the serious destruction of its wild germplasm resources. Based on 131 sample points of C. retusus, this study simulated potential habitats and spatial changes of C. retusus in the 21st century using the Maxent model combined with the geographic information system ArcGIS, predicted prioritized protected areas by the Marxan model, and assessed current conservation status through GAP analysis. The results showed that (1) when the regularization multiplier was 1.5 and the feature combinations were linear, quadratic, and fragmented, the area under the curve of the subjects in the training and test sets were both above 0.9, the true skill statistic value was 0.80, and the maximum Kappa value was 0.62, meaning that the model had high accuracy; (2) Temperature seasonality, annual precipitation, min temperature for coldest month, and precipitation of wettest month had relatively strong influences on species' ranges. (3) The moderately and optimally suitable habitats of C. retusus were primly located in the areas of southwestern Shanxi, central Hebei, western Henan, Shandong, Shaanxi, Anhui and Hubei; (4) Under different future climate scenarios, the area of each class of suitable habitat will increase for varied amounts compared to the current period, with a general trend of expansion to the south; (5) The C. retusus priority protected areas were mainly located in most of Shandong, southern Liaoning, southwestern Shanxi, western Henan, and central Hebei, and its conservation vacancy area was relatively large compared to its protected area. These results will provide scientific strategies for implementing long-term conservation of C. retusus in China and similar regions under warming conditions in the 21st century.

15.
J Gastrointest Oncol ; 15(1): 397-414, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38482221

RESUMO

Background: Hepatocellular carcinoma (HCC) is a malignancy with a bleak prognosis. Although emerging research increasingly supports the involvement of chromatin regulators (CRs) in cancer development, CRs in HCC patients have not received proportionate attention. This study aimed to investigate the role and prognostic significance of CRs in HCC patients, providing new insights for clinical diagnosis and treatment strategies. Methods: We analyzed 424 samples in The Cancer Genome Atlas-Liver hepatocellular carcinoma (TCGA-LIHC) data to identify key CR genes associated with HCC prognosis by differential expression and univariate Cox regression analyses. LASSO-multivariate Cox regression method was used for construction of a prognostic signature and development of a CR-related prognosis model. The prognosis capacity of the model was evaluated via Kaplan-Meier method. Relationship between the model and tumor microenvironment (TME) was evaluated. Additionally, clinical variables and the model were incorporated to create a nomogram. The role of the prognostic gene MRG-binding protein (MRGBP) in HCC was elucidated by immunohistochemistry and semiquantitative analysis. Results: A risk score model, comprising B-lymphoma Mo-MLV insertion region 1 (BMI1), chromobox 2 (CBX2), and MRGBP, was constructed. The area under the curve (AUC) of the CR-based signature is 0.698 (P<0.05), exhibiting robust predictive power. Functional and pathway analyses illuminated the biological relevance of these genes. Immune microenvironment analysis suggested potential implications for immunotherapy. Drug sensitivity analysis identified agents for targeted treatment. Clinical samples show that MRGBP is highly expressed in HCC tissues. Conclusions: This CR-based signature shows promise as a valuable prognostic tool for HCC patients. It demonstrates predictive capabilities, independence from other clinical factors, and potential clinical applicability. In addition, we need more experiments to validate our findings. These findings offer insights into HCC prognosis and treatment, with implications for personalized medicine and improved patient outcomes.

16.
J Gastrointest Oncol ; 15(1): 468-477, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38482229

RESUMO

Background: Given the pivotal role of neuroinflammation in chronic pain and that the paraventricular nucleus of the hypothalamus (PVN) is a crucial brain region involved in visceral pain regulation, we sought to investigate whether the targeted modulation of microglia and astrocytes in the PVN could ameliorate pancreatic cancer-induced visceral pain (PCVP) in mice. Methods: Using a mouse model of PCVP, achieved by tumor cell injection at the head of the pancreas, we measure the number of glial cells, and at the same time we employed minocycline to inhibit microglia and chemogenetic methods to suppress astrocytes in order to investigate the respective roles of microglia and astrocytes within the PVN in PCVP. Results: Mice exhibited visceral pain at 12, 15 and 18 days post-tumor cell injection. We observed a significant increase in the population of both microglia and astrocytes. Inhibition of microglial activity through minocycline microinjection into the PVN resulted in alleviation of visceral pain within 30 and 60 min. Similarly, chemogenetic inhibition of astrocyte function at 14 and 21 days post-injection also led to relief from visceral pain. Conclusions: This study found that PVN microglia and astrocytes were involved in regulating PCVP. Our results suggest that targeting glia may be a potential approach for alleviating visceral pain in patients with pancreatic cancer.

17.
J Gastrointest Oncol ; 15(1): 458-467, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38482250

RESUMO

Background: For patients with pancreatic cancer, visceral pain is a debilitating symptom that significantly compromises their quality of life. Unfortunately, the lack of effective treatment options can be attributed to our limited understanding of the neural circuitry underlying this phenomenon. The primary objective of this study is to elucidate the fundamental mechanisms governing visceral pain induced by pancreatic cancer in murine models. Methods: A mouse model of pancreatic cancer visceral pain was established in C57BL/6N mice through the intrapancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were employed to evaluate visceral pain, whereas the in vitro electrophysiological patch-clamp technique was utilized to record the electrophysiological activity of GABAergic neurons. Specific neuron ablation and chemogenetics methods were employed to investigate the involvement of GABAergic neurons in pancreatic cancer-induced visceral pain. Results: In vitro electrophysiological results showed that the firing frequency of GABAergic neurons in the paraventricular nucleus of the hypothalamus (PVN) was decreased. Specific destruction of GABAergic neurons in the PVN exacerbated visceral pain induced by pancreatic cancer. Chemogenetics activation of GABAergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer. Conclusions: GABAergic neurons located in PVN play a crucial role in precipitating visceral pain induced by pancreatic cancer in mice, thereby offering novel insights for identifying effective targets to treat pancreatic cancer-related visceral pain.

18.
J Am Chem Soc ; 146(10): 7076-7087, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38428949

RESUMO

The present polyolefin hydrogenolysis recycling cases acknowledge that zerovalent Ru exhibits high catalytic activity. A pivotal rationale behind this assertion lies in the propensity of the majority of Ru species to undergo reduction to zerovalent Ru within the hydrogenolysis milieu. Nonetheless, the suitability of zerovalent Ru as an optimal structural configuration for accommodating multiple elementary reactions remains ambiguous. Here, we have constructed stable Ru0-Ruδ+ complex species, even under reaction conditions, through surface ligand engineering of commercially available Ru/C catalysts. Our findings unequivocally demonstrate that surface-ligated Ru species can be stabilized in the form of a Ruδ+ state, which, in turn, engenders a perturbation of the σ bond electron distribution within the polyolefin carbon chain, ultimately boosting the rate-determining step of C-C scission. The optimized catalysts reach a solid conversion rate of 609 g·gRu-1·h-1 for polyethylene. This achievement represents a 4.18-fold enhancement relative to the pristine Ru/C catalyst while concurrently preserving a remarkable 94% selectivity toward valued liquid alkanes. Of utmost significance, this surface ligand engineering can be extended to the gentle mixing of catalysts in ligand solution at room temperature, thus rendering it amenable for swift integration into industrial processes involving polyolefin degradation.

19.
J Agric Food Chem ; 72(11): 5690-5698, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38447177

RESUMO

There is currently a lack of effective olfaction-based techniques to control diamondback moth (DBM) larvae. Identifying behaviorally active odorants for DBM larvae and exploring their recognition mechanisms can provide insights into olfaction-based larval control strategies. Through the two-choice assay, (E,E)-2,6-farnesol (farnesol) was identified as a compound exhibiting significant attractant activity toward DBM larvae, achieving an attraction index of 0.48 ± 0.13. PxylGOBP1 and PxylGOBP2, highly expressed in the antennae of DBM larvae, both showed high affinity toward farnesol. RNAi technology was used to knock down PxylGOBP1 and PxylGOBP2, revealing that the attraction of DBM larvae to farnesol nearly vanished following the knockdown of PxylGOBP2, indicating its critical role in recognizing farnesol. Further investigation into the PxylGOBP2-farnesol interaction revealed the importance of residues like Thr9, Trp37, and Phe118 in PxylGOBP2's binding to farnesol. This research is significant for unveiling the olfactory mechanisms of DBM larvae and developing larval behavior regulation techniques.


Assuntos
Farneseno Álcool , Mariposas , Animais , Larva/genética , Farneseno Álcool/farmacologia , Farneseno Álcool/metabolismo , Odorantes , Mariposas/metabolismo , Olfato
20.
Mol Med Rep ; 29(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38456482

RESUMO

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, concerrning the Transwell cell migration and invasion assay data shown in Fig. 6A and B for the 786­O cell line on p. 7206, the pcDNA3.1­EGOT 'Migration' and 'Invasion' (a­1 and b­1) data panels appeared to contain overlapping sections of data, such that they were potentially derived from the same original source, where these panels were intended to show the results from differently performed experiments. The authors have re­examined their original data, and realize that the 'Invasion' (b­1) panel in Fig. 6B was inadvertently chosen incorrectly. The revised version of Fig. 6, now featuring the correct data for the 'Invasion' experiment (B1 in the replacement figure) in Fig. 6B, is shown on the next page. Note that this error did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused.[Molecular Medicine Reports 16: 7072­7079, 2017; DOI: 10.3892/mmr.2017.7470].

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