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1.
ACS Omega ; 9(15): 17681-17690, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38645347

RESUMO

Catalytic aquathermolysis, a crucial aspect of chemical reutilization, converts the heavy components (such as resins and asphaltenes) of residual oil into lighter components. The use of transition-metal-based catalysts accelerates aquathermolysis reactions. It was observed that iron naphthenate exhibited greater efficiency for residual oils compared to manganese naphthenate and zinc naphthenate. Furthermore, the catalytic aquathermolysis of emulsified residual oil with iron naphthenate demonstrated an outstanding catalytic performance. Under the reaction conditions of 340 °C, 3 MPa, and 2 h, there was a remarkable decrease in viscosity and sulfur content of residual oil by 85.0 and 50.01%, respectively. Additionally, the alterations in the components of residual oils before and after aquathermolysis were examined through a four-component analysis and elemental analysis.

2.
J Therm Biol ; 121: 103828, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38604115

RESUMO

Heating, Ventilation, and Air Conditioning (HVAC) systems in high-speed trains (HST) are responsible for consuming approximately 70% of non-operational energy sources, yet they frequently fail to ensure provide adequate thermal comfort for the majority of passengers. Recent advancements in portable wearable sensors have opened up new possibilities for real-time detection of occupant thermal comfort status and timely feedback to the HVAC system. However, since occupant thermal comfort is subjective and cannot be directly measured, it is generally inferred from thermal environment parameters or physiological signals of occupants within the HST compartment. This paper presents a field test conducted to assess the thermal comfort of occupants within HST compartments. Leveraging physiological signals, including skin temperature, galvanic skin reaction, heart rate, and ambient temperature, we propose a Predicted Thermal Comfort (PTC) model for HST cabin occupants and establish an intelligent regulation model for the HVAC system. Nine input factors, comprising physiological signals, individual physiological characteristics, compartment seating, and ambient temperature, were formulated for the PTS model. In order to obtain an efficient and accurate PTC prediction model for HST cabin occupants, we compared the accuracy of different subsets of features trained by Machine Learning (ML) models of Random Forest, Decision Tree, Vector Machine and K-neighbourhood. We divided all the predicted feature values into four subsets, and did hyperparameter optimisation for each ML model. The HST compartment occupant PTC prediction model trained by Random Forest model obtained 90.4% Accuracy (F1 macro = 0.889). Subsequent sensitivity analyses of the best predictive models were then performed using SHapley Additive explanation (SHAP) and data-based sensitivity analysis (DSA) methods. The development of a more accurate and operationally efficient thermal comfort prediction model for HST occupants allows for precise and detailed feedback to the HVAC system. Consequently, the HVAC system can make the most appropriate and effective air supply adjustments, leading to improved satisfaction rates for HST occupant thermal comfort and the avoidance of energy wastage caused by inaccurate and untimely predictive feedback.

3.
Clin Oral Investig ; 28(4): 220, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38492074

RESUMO

OBJECTIVES: This in vitro study aims to compare the fracture resistance of three CAD/CAM materials used in endocrown restoration of interproximal defects in maxillary premolars. MATERIALS AND METHODS: 45 maxillary premolars extracted as part of orthodontic treatment were included. Following standardized root canal treatment, all teeth were prepared into Mesial-Occlusal (MO) cavity types. The samples were then randomly divided into three groups: LD [repaired with lithium disilicate glass ceramics (IPS e.max CAD)], VE [treated with polymer-infiltrated ceramics (Vita Enamic)], and LU [repaired with resin-based nanoceramics (Lava Ultimate)]. Axial static loading was applied using a universal testing machine at 1 mm/min until fracture, and fracture resistance and failure modes were recorded. RESULTS: Regarding Fracture Resistance Values (FRVs), the LD group exhibited significantly higher values than the other two groups, VE (P = 0.028) and LU (P = 0.005), which showed no significant difference (P = 0.778). On the other hand, regarding failure modes, the LD group had a higher prevalence of irreparable fractures compared to the other two groups, VE (P < 0.001) and LU (P < 0.001), which showed no significant difference. CONCLUSIONS: Although lithium disilicate glass ceramics exhibited higher FRVs, they had a lower repair probability. In contrast, polymer-infiltrated ceramics and resin-based nanoceramics contributed to tooth structure preservation. CLINICAL RELEVANCE: For maxillary premolars with interproximal defects following root canal treatment, resin ceramic composites are recommended for restoration to enhance abutment teeth protection.


Assuntos
Cerâmica , Coroas , Dente Pré-Molar , Teste de Materiais , Cerâmica/química , Porcelana Dentária/química , Resinas Compostas/química , Polímeros , Desenho Assistido por Computador , Análise do Estresse Dentário , Falha de Restauração Dentária
4.
Child Adolesc Psychiatry Ment Health ; 18(1): 39, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521915

RESUMO

BACKGROUND: Adolescent mental health problems are becoming increasingly prevalent, and there are correlations between weight-related concerns and adolescent mental health. The aim of this study is to explore the association between three weight-related factors (actual weight, weight perception, and weight teasing) and mental health problems (depressive symptoms, anxiety symptoms, and loneliness) in Chinese adolescents. METHODS: 10,070 adolescents between the ages of 11-18 from schools in Shanghai, China were selected using a stratified random cluster sampling method. Self-reported questionnaires were collected to investigate weight-related factors and mental health problems. Logistic regression analysis was used to examine the relationship. RESULTS: The prevalence of depressive symptoms, loneliness, mild anxiety symptoms, and moderate to severe anxiety symptoms among adolescents were 18.0%, 53.8%, 26.5%, and 12.3%, respectively, with a higher prevalence found in females. After adjusting for weight perception and weight teasing, actual weight had no harmful impact on adolescents' mental health. Adolescents' perception of being overweight increased the risk of depressive symptoms, loneliness, mild anxiety symptoms, and moderate to severe anxiety symptoms, while the perception of being underweight had a similar but more profound impact (depressive symptoms OR = 1.590, 95% CI: 1.342-1.883; loneliness OR = 1.537, 95% CI: 1.353-1.746; mild anxiety symptoms OR = 1.368, 95% CI: 1.178-1.589; moderate to severe anxiety symptoms OR = 1.780, 95% CI: 1.449-2.186). Experiencing weight teasing more than once a year had a greater effect on adolescents' mental health, especially among adolescents with overweight/obesity (depressive symptoms OR = 2.970, 95% CI: 2.325-3.793; loneliness OR = 3.839, 95% CI: 3.119-4.727; mild anxiety symptoms OR = 2.822, 95% CI: 2.236-3.562; moderate to severe anxiety symptoms OR = 5.212, 95% CI: 3.846-7.065). CONCLUSIONS: The prevalence of mental health problems among adolescents was high, especially loneliness. Weight perception and weight teasing, but not the actual weight, independently influenced adolescent mental health.

5.
ACS Omega ; 9(10): 12037-12045, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38496941

RESUMO

The nitration reaction of aromatic compounds is one of the extensively studied chemical reactions that result in the manufacturing of various industrial products applied in pharmaceuticals, dyes, perfumes, and explosives. A series of modified sulfated zirconia (SZ) catalysts SO42-/ZrO2-MxOy (M=Ce, Co, Mn, Zn, and M/SZ) doped with different metal elements by a coprecipitation method were investigated in the toluene nitration reaction. Various characterization techniques (X-ray diffraction, Brunauer-Emmett-Teller, thermogravimetric analysis, X-ray photoelectron spectroscopy, and temperature-programmed desorption of ammonia) indicated that doping metal elements in SZ led to excellent catalytic properties, increasing the specific surface area of the catalyst and facilitating the formation of a stable tetragonal zirconia phase. Doping zinc and cobalt in SZ enhanced the acidity of the catalyst and formed stronger acidic sites, promoting the generation of nitronium ions and providing more active sites for the toluene nitration reaction. Additionally, it reduced the loss of sulfate ions in the catalytic system that helped in improving the stability of the catalyst. Under the same conditions, the catalytic activity of toluene nitration reaction demonstrated the following order: Zn/SZ > Ce/SZ > Co/SZ > Mn/SZ > SZ, with the zinc-doped SZ catalyst exhibiting the best catalytic performance, achieving a toluene conversion rate of 78.58% and a para/ortho nitrotoluene ratio of 0.67.

6.
Immunity ; 57(3): 528-540.e6, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38417442

RESUMO

RNA splicing is involved in cancer initiation and progression, but how it influences host antitumor immunity in the metabolically abnormal tumor microenvironment (TME) remains unclear. Here, we demonstrate that lactate modulates Foxp3-dependent RNA splicing to maintain the phenotypic and functional status of tumor-infiltrating regulatory T (Treg) cells via CTLA-4. RNA splicing in Treg cells was correlated with the Treg cell signatures in the TME. Ubiquitin-specific peptidase 39 (USP39), a component of the RNA splicing machinery, maintained RNA-splicing-mediated CTLA-4 expression to control Treg cell function. Mechanistically, lactate promoted USP39-mediated RNA splicing to facilitate CTLA-4 expression in a Foxp3-dependent manner. Moreover, the efficiency of CTLA-4 RNA splicing was increased in tumor-infiltrating Treg cells from patients with colorectal cancer. These findings highlight the immunological relevance of RNA splicing in Treg cells and provide important insights into the environmental mechanism governing CTLA-4 expression in Treg cells.


Assuntos
Neoplasias , Linfócitos T Reguladores , Humanos , Antígeno CTLA-4 , Fatores de Transcrição Forkhead/genética , Ácido Láctico/metabolismo , Linfócitos do Interstício Tumoral , Neoplasias/genética , Neoplasias/metabolismo , Microambiente Tumoral , Proteases Específicas de Ubiquitina/metabolismo
8.
BMC Psychiatry ; 24(1): 90, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38297253

RESUMO

BACKGROUND: A lack of confidence in perinatal bereavement care (PBC) and the psychological trauma experienced by nurses and midwives during bereavement care leads to their strong need for sufficient organisational support. The current study intended to test a hypothesised model of the specific impact paths among organisational support, confidence in PBC, secondary traumatic stress, and emotional exhaustion among nurses and midwives. METHODS: A descriptive, cross-sectional survey was conducted in sixteen maternity hospitals in Zhejiang Province, China, from August to October 2021. The sample (n = 779) consisted of obstetric nurses and midwives. A path analysis was used to test the relationships among study variables and assess model fit. RESULTS: Organisational support directly and positively predicted confidence in PBC and demonstrated a direct, negative, and significant association with secondary traumatic stress and emotional exhaustion. Confidence in PBC had a positive direct effect on secondary traumatic stress and a positive indirect effect on emotional exhaustion via secondary traumatic stress. Secondary traumatic stress exhibited a significant, direct effect on emotional exhaustion. CONCLUSIONS: This study shows that nurses' and midwives' confidence in PBC and mental health were leadingly influenced by organisational support in perinatal bereavement practice. It is worth noting that higher confidence in PBC may lead to more serious psychological trauma symptoms in nurses and midwives. Secondary traumatic stress plays an essential role in contributing to emotional exhaustion. The findings suggest that support from organisations and self-care interventions were required to improve confidence in PBC and reduce negative psychological outcomes among those providing PBC. The development of objective measures for assessing competence in PBC and organizational support are essential.


Assuntos
Luto , Esgotamento Profissional , Fadiga por Compaixão , Cuidados Paliativos na Terminalidade da Vida , Tocologia , Humanos , Feminino , Gravidez , 60672 , Estudos Transversais , China , Inquéritos e Questionários
9.
BMC Nurs ; 23(1): 80, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38291385

RESUMO

BACKGROUND: The appropriate nurse staffing reflects the situation of nursing management of human resources. Nurse managers have a pivotal role in determining a competent and sufficient number of nurses. It is important to understand the factors influencing nurse staffing to promote appropriate staffing levels. The study aimed to explore the factors affecting nurse staffing from the perspective of nursing managers. METHODS: Purposive sampling was adopted to recruit 14 nurse managers from secondary and tertiary hospitals located in the central region of China, and semi-structured interviews via telephone were conducted from April to May 2022. Interview transcripts were analyzed and collated using thematic analysis. RESULTS: This research identified four themes and ten subthemes influencing nurse staffing. Extracted themes include: government level (inadequacy of mandatory policies, budgetary constraints), hospital level (hospital characteristics, the control of nurse labor costs, inadequate support on nursing), patient level (patient characteristics, increasing care needs), and nurse level (nurse shortage, skill-mix, individual high-level needs). CONCLUSION: The findings indicate that it is crucial for decision-makers or policymakers to legislate for safe nurse staffing and establish effective supervision and funding incentives. Tailored interventions are also needed to improve the organizational context, address the nurse workforce and balance the structure of nurse staff.

10.
Clin Oral Investig ; 28(1): 120, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280059

RESUMO

OBJECTIVES: In this study, we investigated the dispersion patterns of aerosols and droplets in dental clinics and developed a suction device to evaluate its effectiveness in reducing aerosols during dental procedures. MATERIALS AND METHODS: Firstly, the continuous images of oral aerosols and droplets were photographed with a high-speed camera, and the trajectories of these particles were recognized and processed by Image J to determine key parameters affecting particle dispersion: diffusion velocity, distance, and angle. Secondly, based on the parameter data, the flow field of aerosol particles around the oral cavity was simulated using computational fluid dynamics (CFD), and the flow field under adsorption conditions was simulated to demonstrate the aerodynamic characteristics and capture efficiencies of the single-channel and three-channel adsorption ports at different pressures. Finally, according to the simulated data, a three-channel suction device was developed, and the capture efficiency of the device was tested by the fluorescein tracer method. RESULTS: The dispersion experimental data showed that aerosol particles' maximum diffusion velocity, distance, and angle were 6.2 m/s, 0.55 m, and 130°, respectively. The simulated aerosol flow-field distribution was consistent with the aerosol dispersion patterns. The adsorption simulation results showed that the outlet flow rate of single-channel adsorption was 184.5 L/s at - 350 Pa, and the aerosol capture efficiency could reach 79.4%. At - 350 Pa and - 150 Pa, the outlet flow rate of three-channel adsorption was 228.9 L/s, and the capture efficiency was 99.23%. The adsorption experimental data showed that the capture efficiency of three-channel suction device was 97.71%. CONCLUSIONS: A three-channel suction device was designed by simulations and experiments, which can capture most aerosols in the dental clinic and prevent them from spreading. CLINICAL RELEVANCE: Using three-channel suction devices during oral treatment effectively reduces the spread of oral aerosols, which is essential to prevent the spread of epidemics and ensure the health and safety of patients and dental staff.


Assuntos
Aerossóis , Humanos , Simulação por Computador
11.
Int Dent J ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38238210

RESUMO

INTRODUCTION: During dental treatment procedures ultrasonic scalers generate droplets containing microorganisms such as bacteria and viruses. Hence, it is necessary to study the dynamic properties of generated droplets in order to investigate the risks associated with the spread of infection. The aim of this study was to visualise the flow state of droplets and to evaluate the impact of droplets generated during the use of an ultrasonic scaler during an oral surgical procedure. METHODS: We studied the spatial flow of liquid droplets through a combination of imaging and numeric simulation of a simulated dental treatment processes. First, we photographed the real time images of the ultrasonic scaler and evaluated the images using image-processing software Image J to visualise the flow of liquid droplets. Finally we simulated the flow process of liquid droplets by using the initial velocity of droplet splashing and the angle of the obtained information using computerised fluid dynamics technology. RESULTS: Under different working conditions, the droplet particle splashing velocity, maximum height, and spray angle varied, but the particle trajectory was generally parabolic. The maximum droplet velocity varied between 3.56 and 8.56 m/s, and the splashing height was between 40 and 110 mm. CONCLUSIONS: During risk assessment of an ultrasonic scaler usage, difficulties arise due to the insufficient research on droplet velocity and distribution. This study aims to address this gap by visualising the flow trajectories of droplets generated by ultrasonic scalers. The obtained data will assist in developing more effective interventions based on spatial and temporal distribution of droplets. This provides a new approach for droplet particle research and offers new strategies for public health prevention and control.

12.
Exp Brain Res ; 242(2): 477-490, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38184806

RESUMO

Several volatile anesthetics have presented neuroprotective functions in ischemic injury. This study investigates the effect of desflurane (Des) on neurons following oxygen-glucose deprivation (OGD) challenge and explores the underpinning mechanism. Mouse neurons HT22 were subjected to OGD, which significantly reduced cell viability, increased lactate dehydrogenase release, and promoted cell apoptosis. In addition, the OGD condition increased oxidative stress in HT22 cells, as manifested by increased ROS and MDA contents, decreased SOD activity and GSH/GSSG ratio, and reduced nuclear protein level of Nrf2. Notably, the oxidative stress and neuronal apoptosis were substantially blocked by Des treatment. Bioinformatics suggested potassium voltage-gated channel subfamily A member 1 (Kcna1) as a target of Des. Indeed, the Kcna1 expression in HT22 cells was decreased by OGD but restored by Des treatment. Artificial knockdown of Kcna1 negated the neuroprotective effects of Des. By upregulating Kcna1, Des activated the Kv1.1 channel, therefore enhancing K+ currents and inducing neuronal repolarization. Pharmacological inhibition of the Kv1.1 channel reversed the protective effects of Des against OGD-induced injury. Collectively, this study demonstrates that Des improves electrical activity of neurons and alleviates OGD-induced neuronal injury by activating the Kcna1-dependent Kv1.1 channel.


Assuntos
Oxigênio , Traumatismo por Reperfusão , Camundongos , Animais , Glucose/metabolismo , Desflurano/farmacologia , Transdução de Sinais , Estresse Oxidativo , Neurônios/metabolismo , Apoptose , Canal de Potássio Kv1.1/metabolismo
13.
Neuroendocrinology ; 114(2): 192-206, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37827134

RESUMO

INTRODUCTION: Neuroendocrine neoplasms (NENs) harbored significantly suppressive tumor immune microenvironments (TIMEs). However, the immunological effects of neuroendocrine differentiation (NED) on non-NENs, such as gastric cancer (GC), were unknown. METHODS: Between pure gastric cancer (PGC) and GC-NED, TIME features were scored based on expression data and validated on serial whole-tissue sections of surgical samples, with tertiary lymphoid structures (TLSs) and the extra-TLS zone evaluated independently using multi-marker immunohistochemical staining. Risk analyses of TIME features on tumor behaviors were performed in GC-NED. The universal immunological effects of NED were explored preliminarily in adenocarcinomas arising in other organs. RESULTS: Based on over 11,500 annotated TLSs and 2,700 extra-TLS zones, compared with PGC, GC-NED harbored a distinctively more suppressive TIME characterized by increased but immature TLSs, with higher naïve B-cell and follicular regulatory T-cell densities and downregulated TLS maturation-related cell ratios inside TLSs; increased naïve B-cell and regulatory T-cell densities; and a high proportion of exhausted T cells in the extra-TLS zone. The upregulated tumor PD-L1 expression and its close correlations with TLS formation and maturation were remarkable exclusively in GC-NED. TIME features, especially those regarding TLSs, were significantly correlated with tumor growth and invasion. The desynchrony between TLS formation and maturation and increased naïve or regulatory immune cell infiltration was observed in adenocarcinomas of the colorectum, pancreas, lung, and prostate. CONCLUSION: NED highlighted a distinct GC entity with more suppressive TIME features correlated with tumor behaviors, indicating a cohort that would benefit more from immunotherapies.


Assuntos
Adenocarcinoma , Tumores Neuroendócrinos , Neoplasias Gástricas , Masculino , Humanos , Neoplasias Gástricas/metabolismo , Prognóstico , Microambiente Tumoral
15.
Cell Rep ; 42(12): 113518, 2023 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-38041812

RESUMO

The dysfunction and clonal constriction of tumor-infiltrating CD8+ T cells are accompanied by alterations in cellular metabolism; however, how the cell-intrinsic metabolic pathway specifies intratumoral CD8+ T cell features remains elusive. Here, we show that cell-autonomous generation of nicotinamide adenine dinucleotide (NAD+) via the kynurenine pathway (KP) contributes to the maintenance of intratumoral CD8+ T cell metabolic and functional fitness. De novo NAD+ synthesis is involved in CD8+ T cell metabolism and antitumor function. KP-derived NAD+ promotes PTEN deacetylation, thereby facilitating PTEN degradation and preventing PTEN-dependent metabolic defects. Importantly, impaired cell-autonomous NAD+ synthesis limits CD8+ T cell responses in human colorectal cancer samples. Our results reveal that KP-derived NAD+ regulates the CD8+ T cell metabolic and functional state by restricting PTEN activity and suggest that modulation of de novo NAD+ synthesis could restore CD8+ T cell metabolic fitness and antitumor function.


Assuntos
Linfócitos T CD8-Positivos , NAD , Humanos , NAD/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Cinurenina/metabolismo , Redes e Vias Metabólicas
16.
Pak J Med Sci ; 39(6): 1751-1756, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37936744

RESUMO

Objective: To investigate patient-reported outcomes of taste alterations and quality of life (QoL) in patients with nasopharyngeal carcinoma (NPC). Methods: In this single-center retrospective study medical records of 191 patients with NPC undergoing chemoradiotherapy (CRT) in the Department of Radiotherapy, Jiangsu Cancer Hospital, the Affiliated Cancer Hospital of Nanjing Medical University from January 2021 to December 2021 were reviewed. A total of 120 patients met eligibility criteria and were included. The taste alterations and QoL at multiple time points during radiotherapy (RT) were compared. Results: There were significant differences in the intensity of taste, discomfort, phantogeusia and parageusia or overall taste alterations at multiple time points during CRT (p-Value<0.001). These four parameters were significantly higher two or four weeks after CRT, or at the end of CRT compared to before CRT (p-Value <0.001). The intensity of taste, discomfort, phantogeusia and parageusia or overall taste alterations were all significantly higher four weeks after CRT compared to two weeks after CRT (p-Value <0.001), and at the end of CRT compared to four weeks after CRT (p-Value <0.001). The chemotherapy-induced taste alteration scale (CiTAS) scores were highest at the end of CRT (p-Value <0.001). There were significant differences in QoL at multiple time points during CRT (p-Value <0.001), and each parameter differed significantly at various time points (p <0.05). The QoL of all areas at the end of CRT were significantly higher than those before CRT, or two or four weeks after CRT (p-Value <0.001). Conclusions: In patients with NPC undergoing CRT, taste alterations increasingly worsen as treatment progresses, with poor QoL outcomes.

17.
Artigo em Inglês | MEDLINE | ID: mdl-37980653

RESUMO

AIM: To investigate the mechanism by which NF-κB p65 activates miR-150 to suppress TRPC6 expression and promote renal ischemia-reperfusion injury. METHODS: To assess the transcription of miR-150, NF-B p65, and TRPC6 in HK-2 cells treated with hypoxia reperfusion and rat kidney tissue damaged by ischemia-reperfusion (I/R), qPCR was implemented. The protein production of NF-κB p65 and TRPC6 was assessed by Western blot (WB) analysis. The histological score of rat kidney tissue was assessed using H&E (hematoxylin and eosin) staining. To assess the rate of apoptosis of renal tissue cells following I/R injury, we used the TACS TdT In Situ Apoptosis Detection Kit. To find out the impairment of renal function, blood levels of creatinine (Cr) and blood urea nitrogen (BUN) were tested in rats. Concentrations of inflammatory cytokines, including IL-1ß, IL-10, and TNF-α, were detected in HK-2 cells and rat renal tissue cells utilizing ELISA kits. FITC and CCK-8 were employed to analyze the death rate and cellular proliferation of HK-2 cells. To analyse the mechanism of engagement between NF-κB p65 and the miR-150 promoter, coupled with the detrimental impact of miR-150 on TRPC6, we adopted the dual-luciferase reporter assay. To confirm the activating effect of NF-κB p65 on miR-150,we implemented the ChIP assay. RESULTS: NF-κB p65 expression was significantly upregulated in rat renal tissue following IRI. Applying the dual-luciferase reporter assay, we demonstrated that the specific attachment of NF-B p65 with the miR-150 promoter location is viable, resulting in the promotion of the activity of the promoter. When miR-150 was overexpressed, we observed a notable reduction in cell proliferation. And it notably increased the rate of cellular apoptosis rate and amounts of the proinflammatory cytokines IL-1ß, IL-10, and TNF-α. Employing the dual-luciferase reporter assay, we demonstrated that miR-150 transfection diminished the function of luciferase in the TRPC6-WT group, whereas luciferase activity in the TRPC6-MUT group remained unchanged, indicating that miR-150 is a targeted inhibitor of TRPC6. In the rat renal I/R model, when miR-150 was inhibited or TRPC6 was overexpressed in the rat kidney I/R model, the histological score of rat kidney tissue significantly decreased, so did the quantities of proinflammatory cytokines IL-1ß, IL-10, TNF-α, creatinine (Cr) and blood urea nitrogen (BUN) contents and the rate of cell apoptosis in kidney tissue. CONCLUSION: Activation of miR-150 by NF-κB p65 results in downregulation of TRPC6 expression and promotion of IRI in the kidney.

18.
Cell Metab ; 35(12): 2107-2118.e6, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37863051

RESUMO

Fructose consumption is associated with tumor growth and metastasis in mice, yet its impact on antitumor immune responses remains unclear. Here, we show that dietary fructose modulates adipocyte metabolism to enhance antitumor CD8+ T cell immune responses and control tumor growth. Transcriptional profiling of tumor-infiltrating CD8+ T cells reveals that dietary fructose mediates attenuated transition of CD8+ T cells to terminal exhaustion, leading to a superior antitumor efficacy. High-fructose feeding initiates adipocyte-derived leptin production in an mTORC1-dependent manner, thereby triggering leptin-boosted antitumor CD8+ T cell responses. Importantly, high plasma leptin levels are correlated with elevated plasma fructose concentrations and improved antitumor CD8+ T cell responses in patients with lung cancer. Our study characterizes a critical role for dietary fructose in shaping adipocyte metabolism to prime antitumor CD8+ T cell responses and highlights that the fructose-leptin axis may be harnessed for cancer immunotherapy.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Humanos , Camundongos , Animais , Leptina/metabolismo , Neoplasias/metabolismo , Imunoterapia , Ativação Linfocitária
19.
J Clin Invest ; 133(23)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37788092

RESUMO

The functional integrity of Tregs is interwoven with cellular metabolism; however, the mechanisms governing Treg metabolic programs remain elusive. Here, we identified that the deubiquitinase USP47 inhibited c-Myc translation mediated by the RNA N6-methyladenosine (m6A) reader YTHDF1 to maintain Treg metabolic and functional homeostasis. USP47 positively correlated with the tumor-infiltrating Treg signature in samples from patients with colorectal cancer and gastric cancer. USP47 ablation compromised Treg homeostasis and function in vivo, resulting in the development of inflammatory disorders, and boosted antitumor immune responses. USP47 deficiency in Tregs triggered the accumulation of the c-Myc protein and in turn exacerbated hyperglycolysis. Mechanistically, USP47 prevented YTHDF1 ubiquitination to attenuate the association of YTHDF1 with translation initiation machinery, thereby decreasing m6A-based c-Myc translation efficiency. Our findings reveal that USP47 directs m6A-dependent metabolic programs to orchestrate Treg homeostasis and suggest novel approaches for selective immune modulation in cancer and autoimmune diseases by targeting of USP47.


Assuntos
Doenças Autoimunes , Neoplasias , Humanos , Homeostase , Linfócitos T Reguladores , Ubiquitinação
20.
Crit Care Med ; 51(10): e207-e208, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37707387
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