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1.
Environ Res ; : 120058, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39326650

RESUMO

In recent years, the peracetic acid (PAA)-based advanced oxidation process (AOPs) has garnered significant attention in the field of water treatment due to rapid response time and environmentally-friendliness. The activation of PAA systems by diverse carbon-based materials plays a crucial role in addressing emerging environmental contaminants, including various types, structures, and modified forms of carbon materials. However, the structural characteristics and structure-activity relationship of carbon-based materials in the activation of PAA are intricate, while the degradation pathways and dominant active species exhibit diversity. Therefore, it is imperative to elucidate the developmental process of the carbon-based materials/PAA system through resource integration and logical categorization, thereby indicating potential avenues for future research. The present paper comprehensively reviews the structural characteristics and action mechanism of carbon-based materials in PAA system, while also analyzing the development, properties, and activation mechanism of heteroatom-doped carbon-based materials in this system. In conclusion, this study has effectively organized the resources pertaining to prominent research direction of comprehensive remediation of environmental water pollution, thereby elucidating the underlying logic and thought process. Consequently, it establishes robust theoretical foundation for future investigations and applications involving carbon-based materials/PAA system.

2.
Sci Total Environ ; 954: 176206, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39278498

RESUMO

Biogas, a sustainable alternative to fossil fuels, addresses issues of non-renewability and accessibility. Its structural similarity to fossil fuels makes it a potent option for energy systems. With this in mind, this paper discusses a novel trigeneration system that utilizes biogas and Liquefied natural gas cooling to produce methanol, electricity, cold water, hot water, oxygen, and natural gas. The system integrates various components such as a biogas burner, Kalina cycle, organic Rankine cycle, liquefied natural gas liquid gasification cycle, proton exchange membrane electrolyzer, and methanol synthesis unit. Simulation via Aspen HYSYS software includes an analysis of energy, exergy, economic, and environmental aspects. Efficiency assessment in single generation, cogeneration, trigeneration, and chemical trigeneration modes concludes chemical trigeneration as most efficient, with the proton exchange membrane electrolyzer being the most efficient subsystem. Key variables like Kalina cycle evaporator temperature, gas flow rate to the methanol reactor, and organic Rankine cycle working fluid pressure are assessed. Predictions on thermodynamic, environmental, and economic behaviors, along with their fluctuations, are made. Using a thermoeconomic approach, the economic analysis determines an exergy unit cost of 59.79 $/GJ and a total cost rate of 2764 $/h. Overall, this work presents a novel and efficient chemical trigeneration system that utilizes biogas and LNG cooling to produce multiple products.

3.
Int J Ophthalmol ; 17(9): 1696-1706, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39296553

RESUMO

AIM: To investigate whether retinal nerve fiber layer defects (RNFLDs) is a potential risk factor for chronic kidney disease (CKD) in Chinese adults. METHODS: The Kailuan Eye Study was a population-based study that included 14 440 participants. All participants underwent detailed assessments, RNFLDs were diagnosed using color fundus photographs. RESULTS: Overall, 12 507 participants [8533 males (68.23%)] had complete systemic examination data and at least one evaluable fundus photograph. RNFLDs were found in 621 participants [5.0%; 95% confidence interval (CI): 4.6%-5.34%], and 70 cases of multiple RNFLDs were found (11.27%). After adjusting multiple factors, RNFLDs was significantly associated with CKD severity, the ORs of CKD stage 3, stage 4 and stage 5 were 1.698, 4.167, and 9.512, respectively. Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors, the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively. Furthermore, 2294 participants had CKD (18.34%, 95%CI: 17.68%-18.99%). After adjusting for other factors, CKD presence was significantly correlated with the presence of RNFLDs. CONCLUSION: The strongest risk factors for RNFLDs are CKD and hypertension. Conversely, RNFLDs can be an ocular feature in patients with CKD. Fundoscopy can help detect systemic diseases, and assessment for RNFLDs should be considered in CKD patients.

4.
Water Res ; 267: 122417, 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39299138

RESUMO

The higher efficiency of electro-fermentation in synthesizing medium-chain fatty acids (MCFAs) compared to traditional fermentation has been acknowledged. However, the functional mechanisms of electrode-biofilm enhancing MCFAs synthesis remain research gaps. To address this, this study proposed a continuous flow electrode-biofilm reactor for chain elongation (CE). After 225 days of operation, stable electrode-biofilms formed and notably improved caproate yield by more than 38 %. The electrode-biofilm was enriched with more CE microorganisms and electroactive bacteria compared to the suspended sludge microorganisms, including Caproicibacterium, Oscillibacter and Pseudoramibacter. Besides, the upregulated CE pathways were evaluated by metagenomic analysis, and the results indicated that the pathways such as acetyl-CoA and malonyl-[acp] formation, reverse beta-oxidation, and fatty acid biosynthesis pathway were all markedly enhanced in cathodic biofilm, more than anodic biofilm and suspended microorganisms. Moreover, microbial community regulated processes like bacterial chemotaxis, flagellar assembly and quorum sensing, crucial for electrode-biofilm formation. Electron transfer, energy metabolism, and microbial interactions were found to be prominently upregulated in the cathodic biofilm, surpassing levels observed in anodic biofilm and suspended sludge microorganisms, which further enhanced CE efficiency. In addition, the statistical analyses further highlighted key microbial functions and interactions within the cathodic biofilm. Oscillospiraceae_bacterium was identified to be the most active microbe, alongside pivotal roles played by Caproiciproducens_sp._NJN-50, Clostridiales_bacterium, Prevotella_sp. and Pseudoclavibacter_caeni. Eventually, the proposed microbial collaboration mechanisms of cathodic biofilm were ascertained. Overall, this study uncovered the biological effects of the electrode-biofilm on MCFAs electrosynthesis, thereby advancing biochemicals production and filling the knowledge gaps in CE electroactive biofilm reactors.

5.
ACS Nano ; 18(34): 23090-23103, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39143650

RESUMO

Actin- and microtubule (MT)-based transport systems are essential for intracellular transport. During influenza A virus (IAV) infection, MTs provide long tracks for virus trafficking toward the nucleus. However, the role of the actin cytoskeleton in IAV entry and especially the transit process is still ambiguous. Here, by using quantum dot-based single-virus tracking, it was revealed that the actin cytoskeleton was crucial for the virus entry via clathrin-mediated endocytosis (CME). After entry via CME, the virus reached MTs through three different pathways: the virus (1) was driven by myosin VI to move along actin filaments to reach MTs (AF); (2) was propelled by actin tails assembled by an Arp2/3-dependent mechanism to reach MTs (AT); and (3) directly reached MTs without experiencing actin-related movement (NA). Therefore, the NA pathway was the main one and the fastest for the virus to reach MTs. The AT pathway was activated only when plenty of viruses entered the cell. The viruses transported by the AF and AT pathways shared similar moving velocities, durations, and displacements. This study comprehensively visualized the role of the actin cytoskeleton in IAV entry and transport, revealing different pathways for IAV to reach MTs after entry. The results are of great significance for globally understanding IAV infection and the cellular endocytic transport pathway.


Assuntos
Endocitose , Vírus da Influenza A , Microtúbulos , Pontos Quânticos , Pontos Quânticos/química , Microtúbulos/metabolismo , Microtúbulos/virologia , Humanos , Vírus da Influenza A/fisiologia , Internalização do Vírus , Animais , Cães , Células Madin Darby de Rim Canino , Citoesqueleto de Actina/metabolismo
6.
Int J Numer Method Biomed Eng ; : e3842, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39099381

RESUMO

Improper osteotomy during total knee arthroplasty (TKA) can lead to anterior femoral notching, which increases the risk of periprosthetic fractures due to stress concentration. One potential solution is the addition of an intramedullary stem to the femoral component. However, the optimal stem length remains unclear. In this study, we aimed to determine the optimal stem length using finite element models. Finite element models of femurs were developed with unstemmed prostheses and prostheses with stem lengths of 50, 75, and 100 mm. Under squat loading conditions, the von Mises stress at the notch and stress distribution on four transversal sections of the femur were analyzed. Additionally, micromotion of the prosthesis-bone interface was evaluated to assess initial stability. The unstemmed prosthesis exhibited a von Mises stress of 191.8 MPa at the notch, which decreased to 43.1, 8.8, and 23.5 MPa for stem lengths of 50, 75, and 100 mm, respectively. The stress reduction on four selected femoral transversal sections compared with the unstemmed prosthesis was 40.0%, 84.4%, and 67.1% for stem lengths of 50, 75, and 100 mm, respectively. Micromotion analysis showed a maximum of 118.8 µm for the unstemmed prosthesis, which decreased significantly with the application of stems, particularly at the anterior flange. Intramedullary stems effectively reduced stress concentration at the femoral notch. The 50-mm stem length provided the optimal combination of reduced notch stress, minimized stress-shielding effect, and decreased micromotion at the anterior flange.

7.
Acad Radiol ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39043516

RESUMO

RATIONALE AND OBJECTIVES: To investigate the diagnostic performance of water-specific T1 mapping for staging liver fibrosis in a non-alcoholic fatty liver disease (NAFLD) rabbit model, in comparison to Modified Look-Locker Inversion recovery (MOLLI) T1 mapping. MATERIALS AND METHODS: 60 rabbits were randomly divided into the control group (12 rabbits) and NAFLD model groups (eight rabbits per subgroup) corresponding to different durations of high-fat high cholesterol diet feeding. All rabbits underwent MRI examination including MOLLI T1 mapping and 3D multi-echo variable flip angle (VFAME- GRE) sequences were acquired before and 20 min after the administration of Gd- EOB-DTPA. Histological assessments were performed to evaluate steatosis, inflammation, ballooning, and fibrosis. Statistical analysis included the intraclass correlation coefficient, analysis of variance, spearman correlation, multiple linear regression, and receiver operating characteristic curve. RESULTS: A moderate correlation was observed between conventional native T1 and MRI-PDFF (r = -0.513, P < 0.001), as well as between conventional native T1 and liver steatosis grades (r = -0.319, P = 0.016). However, no significant correlation was found between the native wT1 and PDFF (r = 0.137, P = 0.314), or between the native wT1 and steatosis grades (r = 0.106, P = 0.435). In the multiple regression analysis, liver fibrosis, and hepatocellular ballooning were identified as independent factors influencing native wT1 in this study (R2 =0.545, P < 0.05), while steatosis was independently associated with conventional native T1 (R2 =0.321, P < 0.05). The AUC values for native T1, native wT1, HBP T1, and HBP wT1 were 0.549(0.410-0.682), 0.811(0.684-0.903), 0.775(0.644-0.876), and 0.752(0.619-0.858) for F1 or higher, 0.581(0.441-0.711), 0.828(0.704-0.916), 0.832(0.708-0.919), and 0.854(0.734-0.934) for F2 or higher, respectively. CONCLUSION: The native wT1 may provide a more reliable assessment of early liver fibrosis in the context of NAFLD compared to conventional native T1.

8.
Nano Lett ; 24(28): 8752-8762, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38953881

RESUMO

Acute methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is a common and serious lung infection with high morbidity and mortality rates. Due to the increasing antibiotic resistance, toxicity, and pathogenicity of MRSA, there is an urgent need to explore effective antibacterial strategies. In this study, we developed a dry powder inhalable formulation which is composed of porous microspheres prepared from poly(lactic-co-glycolic acid) (PLGA), internally loaded with indocyanine green (ICG)-modified, heat-resistant phages that we screened for their high efficacy against MRSA. This formulation can deliver therapeutic doses of ICG-modified active phages to the deep lung tissue infection sites, avoiding rapid clearance by alveolar macrophages. Combined with the synergistic treatment of phage therapy and photothermal therapy, the formulation demonstrates potent bactericidal effects in acute MRSA pneumonia. With its long-term stability at room temperature and inhalable characteristics, this formulation has the potential to be a promising drug for the clinical treatment of MRSA pneumonia.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Animais , Camundongos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Microesferas , Terapia Fototérmica , Pneumonia Estafilocócica/terapia , Terapia por Fagos/métodos , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Verde de Indocianina/uso terapêutico , Verde de Indocianina/administração & dosagem , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Administração por Inalação , Humanos , Bacteriófagos/química
9.
J Hazard Mater ; 477: 135291, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39047571

RESUMO

Metal-based catalytic materials exhibit exceptional properties in degrading emerging pollutants within Fenton-like systems. However, the potential risk of metal leaching has become pressing environmental concern. This study addressed scientific issues pertaining to the leaching behavior and control strategies for metal-based catalytic materials. Innovative cobalt-aluminum hydrotalcite (CoAl-LDH) triggered peroxymonosulfate (PMS) activation system was constructed and achieved near-complete removal of Ciprofloxacin (CIP) across diverse water quality environments. Notably, it was found that the tunable ion exchange and Al3+ stabilization of CoAl-LDH occurred due to the particularity of neutral water quality, resulting in significantly lower Co2+ leaching levels (0.321 mg/L) compared to acidic conditions (5.103 mg/L). In light of this, machine learning technology was then employed for the first time to simulate the dynamic trend of Co2+ leaching and elucidated the critical regulatory roles and mechanisms of Al3+, aqueous matrix, and reaction rate. Furthermore, degradation systems based on different water quality and metal leaching levels regulated the generation levels of SO4.- and O2∙-, and the unique advantages of free radical attack paths were clarified through CIP degradation products and ecotoxicity analysis. These findings introduced novel insights and approaches for engineering application and pollution control in metal-based Fenton-like water treatment.

10.
Chem Commun (Camb) ; 60(66): 8670-8683, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39046327

RESUMO

Sulfoxides have emerged as pivotal constituents in modern carbohydrate chemistry. As anomeric leaving groups, sulfinyl moieties may occupy positions directly at the anomeric position or at a more remote site. This feature article is focused on the evolution and notable advancements of glycosyl sulfoxide donors in glycosylation reactions. Its objective is to elucidate the obstacles and prospects within this evolving research domain, with the aim of enhancing comprehension and progress in the field of carbohydrate chemistry.

11.
Org Lett ; 26(28): 6053-6058, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38985301

RESUMO

We have developed a highly effective glycosylation method that involves the activation of 2-(2-propylsulfinyl)benzyl 1,2-orthoester glycosides using triflic anhydride (Tf2O). Our research indicates that half of the glycosyl donor is activated through Tf2O via an interrupted Pummerer reaction mechanism, while the remaining portion is activated by triflic acid (TfOH) generated in situ. As a result, as little as 0.5 equiv of Tf2O is adequate for activating the orthoester glycoside donors. This glycosylation procedure offers several benefits, such as high efficiency, wide applicability, and the utilization of a recyclable leaving group.

12.
Water Res ; 259: 121851, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38851110

RESUMO

Overuse of antibiotics has led to their existence in nitrogen-containing water. The impacts of antibiotics on bio-denitrification and the metabolic response of denitrifiers to antibiotics are unclear. We systematically analyzed the effect of ciprofloxacin (CIP) on bio-denitrification and found that 5 mg/L CIP greatly inhibited denitrification with a model denitrifier (Paracoccus denitrificans). Nitrate reduction decreased by 32.89 % and nitrous oxide emission increased by 75.53 %. The balance analysis of carbon and nitrogen metabolism during denitrification showed that CIP exposure blocked electron transfer and reduced the flow of substrate metabolism used for denitrification. Proteomics results showed that CIP exposure induced denitrifiers to use the pentose phosphate pathway more for substrate metabolism. This caused a substrate preference to generate NADPH to prevent cellular damage rather than NADH for denitrification. Notably, despite denitrifiers having antioxidant defenses, they could not completely prevent oxidative damage caused by CIP exposure. The effect of CIP exposure on denitrifiers after removal of extracellular polymeric substances (EPS) demonstrated that EPS around denitrifiers formed a barrier against CIP. Fluorescence and infrared spectroscopy revealed that the binding effect of proteins in EPS to CIP prevented damage. This study shows that denitrifiers resist antibiotic stress through different intracellular and extracellular defense strategies.


Assuntos
Antibacterianos , Ciprofloxacina , Desnitrificação , Ciprofloxacina/farmacologia , Antibacterianos/farmacologia , Paracoccus denitrificans/metabolismo
13.
Cancer Med ; 13(12): e7328, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38924332

RESUMO

BACKGROUND: Sarcopenia is highly prevalent among patients with colorectal cancer (CRC). Computed tomography (CT)-based assessment of low skeletal muscle index (SMI) is widely used for diagnosing sarcopenia. However, there are conflicting findings on the association between low SMI and overall survival (OS) in CRC patients. The objective of this study was to investigate whether CT-determined low SMI can serve as a valuable prognostic factor in CRC. METHODS: We collected data from patients with CRC who underwent radical surgery at our institution between June 2020 and November 2021. The SMI at the third lumbar vertebra was calculated using CT scans, and the cutoff values for defining low SMI were determined using receiver operating characteristic curves. Univariate and multivariate analyses were performed to assess the associations between clinical characteristics and postoperative major complications. RESULTS: A total of 464 patients were included in the study, 229 patients (46.7%) were classified as having low SMI. Patients with low SMI were older and had a lower body mass index (BMI), a higher neutrophil to lymphocyte ratio (NLR), and higher nutritional risk screening 2002 (NRS2002) scores compared to those with normal SMI. Furthermore, patients with sarcopenia had a higher rate of major complications (10.9% vs. 1.3%; p < 0.001) and longer length of stay (9.09 ± 4.86 days vs. 8.25 ± 3.12 days; p = 0.03). Low SMI and coronary heart disease were identified as independent risk factors for postoperative major complications. Moreover, CRC patients with low SMI had significantly worse OS. Furthermore, the combination of low SMI with older age or TNM stage II + III resulted in the worst OS in each subgroup analysis. CONCLUSIONS: CT-determined low SMI is associated with poor prognosis in patients with CRC, especially when combined with older age or advanced TNM stage.


Assuntos
Neoplasias Colorretais , Músculo Esquelético , Sarcopenia , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/complicações , Neoplasias Colorretais/diagnóstico por imagem , Sarcopenia/diagnóstico por imagem , Idoso , Tomografia Computadorizada por Raios X/métodos , Prognóstico , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Índice de Massa Corporal , Curva ROC
14.
Bioresour Technol ; 406: 130959, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38876286

RESUMO

Despite the increased research efforts aimed at understanding iron-based conductive materials (CMs) for facilitating chain elongation (CE) to produce medium chain fatty acids (MCFAs), the impact of these materials on microbial community functions and the adaptation mechanisms to their biotoxicity remain unclear. This study found that the supply of zero-valent iron (ZVI) and magnetite enhanced the MCFAs carbon-flow distribution by 26 % and 52 %, respectively. Metagenomic analysis revealed the upregulation of fatty acid metabolism, pyruvate metabolism and ABC transporters with ZVI and magnetite. The predominant functional microorganisms were Massilibacterium and Tidjanibacter with ZVI, and were Petrimonas and Candidatus_Microthrix with magnetite. Furthermore, it was demonstrated that CE microorganisms respond and adapt to the biotoxicity of iron-based CMs by adjusting Two-component system and Quorum sensing for the first time. In summary, this study provided a new deep-insight on the feedback mechanisms of CE microorganisms on iron-based CMs.


Assuntos
Ferro , Ferro/farmacologia , Ferro/metabolismo , Adaptação Fisiológica/efeitos dos fármacos , Ácidos Graxos/metabolismo , Bactérias/metabolismo , Bactérias/efeitos dos fármacos , Óxido Ferroso-Férrico/química , Percepção de Quorum/efeitos dos fármacos
15.
Bioresour Technol ; 406: 130958, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38876284

RESUMO

To address the environmental hazards posed by high-yield soybean dreg (SD), a high-value strategy is firstly proposed by synthesizing caproate through chain elongation (CE). Optimized conditions for lactate-rich broth as intermediate, utilizing 50 % inoculum ratio, 40 g/L substrate concentration, and pH 5, resulting in 2.05 g/L caproate from direct fermentation. Leveraging lactate-rich broth supplemented with ethanol, caproate was optimized to 2.76 g/L under a refined electron donor to acceptor of 2:1. Furthermore, incorporating 20 g/L biochar elevated caproate production to 3.05 g/L and significantly shortened the lag phase. Mechanistic insights revealed that biochar's surface-existed quinone and hydroquinone groups exhibit potent redox characteristics, thereby facilitating electron transfer. Moreover, biochar up-regulated the abundance of key genes involved in CE process (especially fatty acids biosynthesis pathway), also enriching Lysinibacillus and Pseudomonas as an unrecognized cooperation to CE. This study paves a way for sustainable development of SD by upgrading to caproate.


Assuntos
Carvão Vegetal , Glycine max , Ácido Láctico , Glycine max/metabolismo , Carvão Vegetal/química , Ácido Láctico/metabolismo , Fermentação
16.
Bioresour Technol ; 406: 131041, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38925404

RESUMO

To effectively treat actual ammonia-rich Chinese medicine residue (CMR) resource utilization wastewater, we optimized an anaerobic-microaerobic two-stage expanded granular sludge bed (EGSB) and moving bed sequencing batch reactor (MBSBR) combined process. By controlling dissolved oxygen (DO) levels, impressive removal efficiencies were achieved. Microaeration, contrasting with anaerobic conditions, bolstered dehydrogenase activity, enhanced electron transfer, and enriched the functional microorganism community. The increased relative abundance of Synergistetes and Proteobacteria facilitated hydrolytic acidification and fostered nitrogen and phosphorus removal. Furthermore, we examined the impact of DO concentration in MBSBR on pollutant removal and microbial metabolic activity, pinpointing 2.5 mg/L as the optimal DO concentration for superior removal performance and energy conservation.


Assuntos
Amônia , Reatores Biológicos , Oxigênio , Águas Residuárias , Águas Residuárias/química , Oxigênio/metabolismo , Purificação da Água/métodos , Biodegradação Ambiental , Esgotos , Poluentes Químicos da Água , Eliminação de Resíduos Líquidos/métodos , Fósforo , Medicamentos de Ervas Chinesas/farmacologia , Nitrogênio
17.
Front Immunol ; 15: 1376276, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745658

RESUMO

Background: Hepatic Inflammatory Pseudotumor (IPT) is an infrequent condition often masquerading as a malignant tumor, resulting in misdiagnosis and unnecessary surgical resection. The emerging concept of IgG4-related diseases (IgG4-RD) has gained widespread recognition, encompassing entities like IgG4-related hepatic IPT. Clinically and radiologically, corticosteroids and immunosuppressive therapies have proven effective in managing this condition. Case Presentation: A 3-year-old Chinese boy presented to the clinic with an 11-month history of anemia, fever of unknown origin, and a tender hepatic mass. Blood examinations revealed chronic anemia (Hb: 6.4 g/L, MCV: 68.6 fl, MCH: 19.5 pg, reticulocytes: 1.7%) accompanied by an inflammatory reaction and an elevated serum IgG4 level (1542.2 mg/L). Abdominal contrast-enhanced computed tomography unveiled a 7.6 cm low-density mass in the right lateral lobe, while magnetic resonance imaging demonstrated slight hypointensity on T1-weighted images and slight hyperintensity on T2-weighted images, prompting suspicion of hepatic malignancy. A subsequent liver biopsy revealed a mass characterized by fibrous stroma and dense lymphoplasmacytic infiltration. Immunohistochemical analysis confirmed the presence of IgG4-positive plasma cells, leading to the diagnosis of IgG4-related hepatic IPT. Swift resolution occurred upon initiation of corticosteroid and mycophenolate mofetil therapies. Conclusion: This study underscores the diagnostic approach to hepatic IPT, utilizing histopathology, immunostaining, imaging, serology, organ involvement, and therapeutic response. Early histological examination plays a pivotal role in clinical guidance, averting misdiagnosis as a liver tumor and unnecessary surgical interventions.


Assuntos
Granuloma de Células Plasmáticas , Doença Relacionada a Imunoglobulina G4 , Imunoglobulina G , Humanos , Masculino , Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/imunologia , Granuloma de Células Plasmáticas/tratamento farmacológico , Pré-Escolar , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Doença Relacionada a Imunoglobulina G4/diagnóstico , Hepatopatias/diagnóstico , Hepatopatias/imunologia , Diagnóstico Diferencial , Fígado/patologia , Fígado/diagnóstico por imagem , Fígado/imunologia , Tomografia Computadorizada por Raios X , Biópsia , Imunossupressores/uso terapêutico
18.
Adv Sci (Weinh) ; 11(28): e2400790, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38741381

RESUMO

Heterotopic ossification (HO), the pathological formation of bone within soft tissues such as tendon and muscle, is a notable complication resulting from severe injury. While soft tissue injury is necessary for HO development, the specific molecular pathology responsible for trauma-induced HO remains a mystery. The previous study detected abnormal autophagy function in the early stages of tendon HO. Nevertheless, it remains to be determined whether autophagy governs the process of HO generation. Here, trauma-induced tendon HO model is used to investigate the relationship between autophagy and tendon calcification. In the early stages of tenotomy, it is observed that autophagic flux is significantly impaired and that blocking autophagic flux promoted the development of more rampant calcification. Moreover, Gt(ROSA)26sor transgenic mouse model experiments disclosed lysosomal acid dysfunction as chief reason behind impaired autophagic flux. Stimulating V-ATPase activity reinstated both lysosomal acid functioning and autophagic flux, thereby reversing tendon HO. This present study demonstrates that autophagy-lysosomal dysfunction triggers HO in the stages of tendon injury, with potential therapeutic targeting implications for HO.


Assuntos
Autofagia , Modelos Animais de Doenças , Lisossomos , Camundongos Transgênicos , Ossificação Heterotópica , Tendões , Ossificação Heterotópica/metabolismo , Ossificação Heterotópica/genética , Ossificação Heterotópica/patologia , Animais , Autofagia/fisiologia , Camundongos , Lisossomos/metabolismo , Tendões/metabolismo , Tendões/patologia , Tendões/fisiopatologia , Tenotomia/métodos , Masculino , Traumatismos dos Tendões/fisiopatologia , Traumatismos dos Tendões/metabolismo , Traumatismos dos Tendões/patologia , Camundongos Endogâmicos C57BL
19.
Cell Death Dis ; 15(4): 300, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684648

RESUMO

The treatment of hepatocellular carcinoma (HCC) is particularly challenging due to the inherent tumoral heterogeneity and easy resistance towards chemotherapy and immunotherapy. Arsenic trioxide (ATO) has emerged as a cytotoxic agent effective for treating solid tumors, including advanced HCC. However, its effectiveness in HCC treatment remains limited, and the underlying mechanisms are still uncertain. Therefore, this study aimed to characterize the effects and mechanisms of ATO in HCC. By evaluating the susceptibilities of human and murine HCC cell lines to ATO treatment, we discovered that HCC cells exhibited a range of sensitivity to ATO treatment, highlighting their inherent heterogeneity. A gene signature comprising 265 genes was identified to distinguish ATO-sensitive from ATO-insensitive cells. According to this signature, HCC patients have also been classified and exhibited differential features of ATO response. Our results showed that ATO treatment induced reactive oxygen species (ROS) accumulation and the activation of multiple cell death modalities, including necroptosis and ferroptosis, in ATO-sensitive HCC cells. Meanwhile, elevated tumoral immunogenicity was also observed in ATO-sensitive HCC cells. Similar effects were not observed in ATO-insensitive cells. We reported that ATO treatment induced mitochondrial injury and mtDNA release into the cytoplasm in ATO-sensitive HCC tumors. This subsequently activated the cGAS-STING-IFN axis, facilitating CD8+ T cell infiltration and activation. However, we found that the IFN pathway also induced tumoral PD-L1 expression, potentially antagonizing ATO-mediated immune attack. Additional anti-PD1 therapy promoted the anti-tumor response of ATO in ATO-sensitive HCC tumors. In summary, our data indicate that heterogeneous ATO responses exist in HCC tumors, and ATO treatment significantly induces immunogenic cell death (ICD) and activates the tumor-derived mtDNA-STING-IFN axis. These findings may offer a new perspective on the clinical treatment of HCC and warrant further study.


Assuntos
Trióxido de Arsênio , Carcinoma Hepatocelular , Morte Celular Imunogênica , Neoplasias Hepáticas , Proteínas de Membrana , Nucleotidiltransferases , Trióxido de Arsênio/farmacologia , Trióxido de Arsênio/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Humanos , Animais , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos , Morte Celular Imunogênica/efeitos dos fármacos , Linhagem Celular Tumoral , Interferons/metabolismo , Transdução de Sinais/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BL
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