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1.
Clin Orthop Surg ; 16(3): 448-454, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38827751

RESUMO

Background: Altering wrist biomechanics, Kienbock's disease leads to progressive carpal collapse that results in early arthritis and degenerative changes. By shifting the loading axis toward the radioscaphoid joint, scaphocapitate arthrodesis (SCA) has been reported as a salvage procedure effective in treating symptomatic patients with advanced Kienbock's disease. In this study, we aimed to evaluate the clinical and radiological outcomes of arthroscopic SCA in symptomatic patients with advanced stages of Kienbock's disease. Methods: Between March 2010 and February 2021, we included 15 patients with symptomatic stage IIIA (n=2) and stage IIIB (n=13) Kienbock's disease who were followed up for a minimum of 24 months after arthroscopic SCA with or without lunate excision. The lunate was excised in 6 patients and retained in 9. Visual analog scale (VAS) pain score, grip strength, range of motion (ROM), active flexion-extension arc, and modified Mayo wrist score (MMWS) were measured preoperatively and at each follow-up examination after surgery. Operation-related complications and radiographic changes were also assessed. Results: There were 13 women and 2 men, with a mean age of 57.6 years (range, 21-74 years) at the time of undergoing arthroscopic SCA. Follow-up ranged from 24 to 116 months, with an average of 56.9 ± 32.3 months. Bony union was achieved in all patients. At preoperative examination, wrist ROM (67%) and grip strength (48%) significantly decreased, compared to the contralateral wrist. At the final follow-up, there were significant improvements in VAS, grip strength, and MMWS, whereas the active wrist ROM showed no significant change. Radioscaphoid angle recovered after surgery, while radiographic carpal collapse and ulnar translation of the carpus occurred. In subgroup analysis according to excision of the lunate, there were no significant differences in VAS, MMWS, grip strength, or total ROM. However, increased ulnar translation and decreased radial deviation were noted in the lunate excision group. Conclusions: Arthroscopic SCA achieved significant improvements in pain and wrist function in patients with advanced Kienbock's disease without any complications. Excision of the lunate when performing arthroscopic SCA seemed to induce progressive carpal ulnar translation, with no apparent clinical benefits over retaining it.


Assuntos
Artrodese , Artroscopia , Osteonecrose , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Artrodese/métodos , Adulto , Artroscopia/métodos , Osteonecrose/cirurgia , Osteonecrose/diagnóstico por imagem , Idoso , Adulto Jovem , Força da Mão , Amplitude de Movimento Articular , Osso Escafoide/cirurgia , Osso Escafoide/diagnóstico por imagem , Medição da Dor , Radiografia , Capitato/cirurgia , Capitato/diagnóstico por imagem , Estudos Retrospectivos , Articulação do Punho/cirurgia , Articulação do Punho/diagnóstico por imagem , Articulação do Punho/fisiopatologia
2.
J Mater Chem B ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860876

RESUMO

Self-assembled DNA nanostructures hold great promise in biosensing, drug delivery and nanomedicine. Nevertheless, challenges like instability and inefficiency in cellular uptake of DNA nanostructures under physiological conditions limit their practical use. To tackle these obstacles, this study proposes a novel approach that integrates the cationic polymer polyethyleneimine (PEI) with DNA self-assembly. The hypothesis is that the positively charged linear PEI can facilitate the self-assembly of DNA nanostructures, safeguard them against harsh conditions and impart them with the cellular penetration characteristic of PEI. As a demonstration, a DNA nanotube (PNT) was successfully synthesized through PEI mediation, and it exhibited significantly enhanced stability and cellular uptake efficiency compared to conventional Mg2+-assembled DNA nanotubes. The internalization mechanism was further found to be both clathrin-mediated and caveolin-mediated endocytosis, influenced by both PEI and DNA. To showcase the applicability of this hybrid nanostructure for biomedical settings, the KRAS siRNA-loaded PNT was efficiently delivered into lung adenocarcinoma cells, leading to excellent anticancer effects in vitro. These findings suggest that the PEI-mediated DNA assembly could become a valuable tool for future biomedical applications.

3.
Microb Cell Fact ; 23(1): 179, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890717

RESUMO

BACKGROUND: Human lysozyme (hLYZ) is a natural antibacterial protein with broad applications in food and pharmaceutical industries. Recombinant production of hLYZ in Komagataella phaffii (K. phaffii) has attracted considerable attention, but there are very limited strategies for its hyper-production in yeast. RESULTS: Here through Atmospheric and Room Temperature Plasma (ARTP)-based mutagenesis and transcriptomic analysis, the expression of two genes MYO1 and IQG1 encoding the cytokinesis core proteins was identified downregulated along with higher hLYZ production. Deletion of either gene caused severe cytokinesis defects, but significantly enhanced hLYZ production. The highest hLYZ yield of 1,052,444 ± 23,667 U/mL bioactivity and 4.12 ± 0.11 g/L total protein concentration were obtained after high-density fed-batch fermentation in the Δmyo1 mutant, representing the best production of hLYZ in yeast. Furthermore, O-linked mannose glycans were characterized on this recombinant hLYZ. CONCLUSIONS: Our work suggests that cytokinesis-based morphology engineering is an effective way to enhance the production of hLYZ in K. phaffii.


Assuntos
Muramidase , Proteínas Recombinantes , Saccharomycetales , Muramidase/metabolismo , Muramidase/genética , Muramidase/biossíntese , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Saccharomycetales/metabolismo , Saccharomycetales/genética , Humanos , Fermentação , Citocinese , Engenharia Metabólica/métodos , Técnicas de Cultura Celular por Lotes
4.
Science ; 384(6701): eadk5382, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38870290

RESUMO

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.


Assuntos
Proteases Dependentes de ATP , Artemisininas , Enzima de Clivagem da Cadeia Lateral do Colesterol , Proteínas Mitocondriais , Síndrome do Ovário Policístico , Animais , Feminino , Humanos , Camundongos , Ratos , Androgênios/metabolismo , Artemisininas/uso terapêutico , Artemisininas/farmacologia , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Modelos Animais de Doenças , Hiperandrogenismo/tratamento farmacológico , Hiperandrogenismo/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Ovário/efeitos dos fármacos , Ovário/metabolismo , Síndrome do Ovário Policístico/tratamento farmacológico , Proteólise , Camundongos Endogâmicos C57BL , Adulto Jovem , Adulto , Ratos Sprague-Dawley , Proteases Dependentes de ATP/genética , Proteases Dependentes de ATP/metabolismo
5.
J Biol Chem ; : 107463, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38876304

RESUMO

Chemotherapeutic agents for treating colorectal cancer primarily induce apoptosis in tumor cells. The ubiquitin-proteasome system (UPS) is critical for apoptosis regulation. Deubiquitinating enzymes (DUBs) remove ubiquitin from substrates to reverse ubiquitination. Although over 100 DUB members have been discovered, the biological functions of only a small proportion of DUBs have been characterized. Here, we aimed to systematically identify the DUBs that contribute to the development of colorectal cancer. Among the DUBs, ubiquitin-specific protease 36 (USP36), is upregulated in colorectal cancer. We showed that the knockdown of USP36 induces intrinsic and extrinsic apoptosis. Through gene silencing and coimmunoprecipitation techniques, we identified survivin and cIAP1 as USP36 targets. Mechanistically, USP36 binds and removes lysine-11 (K11)-linked ubiquitin chains from cIAP1 and lysine-48 (K48)-linked ubiquitin chains from survivin to abolish protein degradation. Overexpression of USP36 disrupts the formation of the XIAP-Smac complex and promotes RIPK1 ubiquitination, validating USP36 as an inhibitor to intrinsic and extrinsic apoptosis through deubiquitinating survivin and cIAP1. Therefore, our results suggest that USP36 is involved in colorectal cancer progression and is a potential therapeutic target.

6.
Adv Sci (Weinh) ; : e2401793, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874469

RESUMO

The rise of antibiotic resistance poses a significant public health crisis, particularly due to limited antimicrobial options for the treatment of infections with Gram-negative pathogens. Here, an antimicrobial peptide (AMP) SR25 is characterized, which effectively kills both Gram-negative and Gram-positive bacteria through a unique dual-targeting mechanism without detectable resistance. Meanwhile, an SR25-functionalized hydrogel is developed for the efficient treatment of infected diabetic wounds. SR25 is obtained through genome mining from an uncultured bovine enteric actinomycete named Nonomuraea Jilinensis sp. nov. Investigations reveal that SR25 has two independent cellular targets, disrupting bacterial membrane integrity and restraining the activity of succinate:quinone oxidoreductase (SQR). In a diabetic mice wound infection model, the SR25-incorporated hydrogel exhibits high efficacy against mixed infections of Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA), accelerating wound healing. Overall, these findings demonstrate the therapeutic potential of SR25 and highlight the value of mining drugs with multiple mechanisms from uncultured animal commensals for combating challenging bacterial pathogens.

7.
Chemosphere ; 362: 142589, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866334

RESUMO

The enrichment of phosphorus (P) and nitrogen (N) in aquatic systems can cause eutrophication. Moreover, P rocks may become exhausted in the next 100 years. A slow-release fertilizer called struvite (MgNH4PO4.6H2O) can reduce surface runoff. However, the high cost of raw material or chemicals is a bottleneck in their economical production. Therefore, incinerated sewage sludge ash, food wastewater, and bittern were combined as the sources of P, N, and Mg, respectively. Sawdust biochar was used to enhance the adsorptive recovery of nutrients. First, recovery kinetics was studied by comparing bittern-impregnated biochar (BtB) with the Mg-impregnated biochar (MgB). Subsequently, the synergistic physical and chemical interactions were observed for P and N recovery. Almost complete PO43-P recoveries were achieved within 10 min for both biochars. However, NH4+-N recovery was stable after 2 h, with 26% recovery by MgB and 20% recovery by BtB. Biochars activated with steam (steam-activated biochar) and KOH (KOH-activated biochar) gave superior activities to those of unactivated biochars and activated carbon (AC) nutrient recovery and struvite purity. Moreover, the activated biochars showed a lower risk of surface runoff, similar to that of AC. Therefore, activated biochars can be used as an alternative to AC for economical struvite production from a combination of wastewater sources.

8.
Heliyon ; 10(11): e31542, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38882386

RESUMO

Considering the granularity of embedded data in the design of reversible data hiding scheme has important research significance for the permission control and management of multi-granularity information. To broaden the application possibilities of encrypted data in cloud environments, the researchers propose a fine-grained reversible data hiding method leveraging the cipher-text redundancy of ElGamal encryption. Initially, prior to the encryption process, pixels are organized into a full binary tree based on fine-grained access permissions. Subsequently, a chaotic sequence generator is employed to assign distinct embedding keys to each layer of the full binary tree according to the access permissions. Following this, an XOR operation is conducted between the embedding key and the corresponding secret information in each layer to derive the target features of the cipher-text, facilitating subsequent fine-grained data hiding. Throughout the ElGamal encryption process, iterative manipulation of the random variable ensures alignment between the cipher-text output and the target feature, enabling the embedding of secret information across different layers. This approach facilitates the fine-grained blind extraction of secret information from an encrypted state, thereby expanding the potential applications of cipher-text by extracting information without revealing the original data. Furthermore, the scheme enhances information security through distributed storage and conceals the presence of information hiding by leveraging the separability of lossless decryption and information extraction. Simulation results demonstrate that secret information of three granularities can be embedded and extracted without interference within a three-layer full binary structure, with a maximum embedding capacity of up to 1.75 bpp.

10.
Nature ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866053

RESUMO

Nucleotide-binding leucine-rich repeat (NLR) proteins have a pivotal role in plant immunity by recognizing pathogen effectors1,2. Maintaining a balanced immune response is crucial, as excessive NLR expression can lead to unintended autoimmunity3,4. Unlike most NLRs, plant NLR required for cell death 2 (NRC2) belongs to a small NLR group characterized by constitutively high expression without self-activation5. The mechanisms underlying NRC2 autoinhibition and activation are not yet understood. Here we show that Solanum lycopersicum (tomato) NRC2 (SlNRC2) forms dimers and tetramers, and higher-order oligomers at elevated concentrations. Cryo-electron microscopy (cryo-EM) reveals an inactive conformation of SlNRC2 within these oligomers. Dimerization and oligomerization not only stabilize the inactive state but also sequester SlNRC2 from assembling into an active form. Mutations at the dimeric or inter-dimeric interfaces enhance pathogen-induced cell death and immunity in Nicotiana (N.) benthamiana. The cryo-EM structures unexpectedly reveal inositol hexakisphosphate (IP6) or pentakisphosphate (IP5) bound to the inner surface of SlNRC2's C-terminal LRR domain as confirmed by mass spectrometry. Mutations at the IP-binding site impair inositol phosphate binding of SlNRC2 and pathogen-induced SlNRC2-mediated cell death in N. benthamiana. Together, our study unveils a novel negative regulatory mechanism of NLR activation and suggests inositol phosphates as cofactors of NRCs.

11.
Cell Biosci ; 14(1): 83, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909262

RESUMO

Clinical outcome after traumatic brain injury (TBI) is closely associated conditions of other organs, especially lungs as well as degree of brain injury. Even if there is no direct lung damage, severe brain injury can enhance sympathetic tones on blood vessels and vascular resistance, resulting in neurogenic pulmonary edema. Conversely, lung damage can worsen brain damage by dysregulating immunity. These findings suggest the importance of brain-lung axis interactions in TBI. However, little research has been conducted on the topic. An advanced disease model using stem cell technology may be an alternative for investigating the brain and lungs simultaneously but separately, as they can be potential candidates for improving the clinical outcomes of TBI.In this review, we describe the importance of brain-lung axis interactions in TBI by focusing on the concepts and reproducibility of brain and lung organoids in vitro. We also summarize recent research using pluripotent stem cell-derived brain organoids and their preclinical applications in various brain disease conditions and explore how they mimic the brain-lung axis. Reviewing the current status and discussing the limitations and potential perspectives in organoid research may offer a better understanding of pathophysiological interactions between the brain and lung after TBI.

12.
Viruses ; 16(5)2024 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-38793564

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen that causes severe abortions in sows and high piglet mortality, resulting in huge economic losses to the pig industry worldwide. The emerging and novel PRRSV isolates are clinically and biologically important, as there are likely recombination and pathogenic differences among PRRSV genomes. Furthermore, the NADC34-like strain has become a major epidemic strain in some parts of China, but the characterization and pathogenicity of the latest strain in Inner Mongolia have not been reported in detail. In this study, an NADC34-like strain (CHNMGKL1-2304) from Tongliao City, Inner Mongolia was successfully isolated and characterized, and confirmed the pathogenicity in pigs. The phylogenetic tree showed that this strain belonged to sublineage 1.5 and had high homology with the strain JS2021NADC34. There is no recombination between CHNMGKL1-2304 and any other domestic strains. Animal experiments show that the CHNMGKL1-2304 strain is moderately virulent to piglets, which show persistent fever, weight loss and high morbidity but no mortality. The presence of PRRSV nucleic acids was detected in both blood, tissues, nasal and fecal swabs. In addition, obvious pathological changes and positive signals were observed in lung, lymph node, liver and spleen tissues when subjected to hematoxylin-eosin (HE) staining and immunohistochemistry (IHC). This report can provide a basis for epidemiological investigations and subsequent studies of PRRSV.


Assuntos
Genoma Viral , Filogenia , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Animais , Suínos , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Vírus da Síndrome Respiratória e Reprodutiva Suína/patogenicidade , Vírus da Síndrome Respiratória e Reprodutiva Suína/isolamento & purificação , Vírus da Síndrome Respiratória e Reprodutiva Suína/classificação , China , Síndrome Respiratória e Reprodutiva Suína/virologia , Síndrome Respiratória e Reprodutiva Suína/patologia , Virulência , Evolução Molecular
13.
mBio ; 15(6): e0064024, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38727246

RESUMO

Interleukin-18 binding protein (IL-18BP), a natural regulator molecule of the pro-inflammatory cytokine interleukin-18 (IL-18), plays an important role in regulating the expression of the cellular immunity factor interferon-γ (IFN-γ). In a previous RNA-seq analysis of porcine alveolar macrophages (PAM) infected with the TIM and TJ strains of porcine reproductive and respiratory syndrome virus (PRRSV), we unexpectedly found that the mRNA expression of porcine interleukin 18-binding protein (pIL-18BP) in PAM cells infected with the TJM strain was significantly higher than that infected with the TJ strain. Studies have shown that human interleukin-18 binding protein (hIL-18bp) plays an important role in regulating cellular immunity in the course of the disease. However, there is a research gap on pIL-18BP. At the same time, PRRSV infection in pigs triggers weak cellular immune response problems. To explore the expression and the role of pIL-18BP in the cellular immune response induced by PRRSV, we strived to acquire the pIL-18BP gene from PAM or peripheral blood mononuclear cell (PBMC) with RT-PCR and sequencing. Furthermore, pIL-18BP and pIL-18 were both expressed prokaryotically and eukaryotically. The colocalization and interaction based on recombinant pIL-18BP and pIL-18 on cells were confirmed in vitro. Finally, the expression of pIL-18BP, pIL-18, and pIFN-γ was explored in pigs with different PRRSV infection states to interpret the biological function of pIL-18BP in vivo. The results showed there were five shear mutants of pIL-18BP. The mutant with the longest coding region was selected for subsequent functional validation. First, it was demonstrated that TJM-induced pIL-18BP mRNA expression was higher than that of TJ. A direct interaction between pIL-18BP and pIL-18 was confirmed through fluorescence colocalization, bimolecular fluorescent complimentary (BIFC), and co-immunoprecipitation (CO-IP). pIL-18BP also can regulate pIFN-γ mRNA expression. Finally, the expression of pIL-18BP, pIL-18, and pIFN-γ was explored in different PRRSV infection states. Surprisingly, both mRNA and protein expression of pIL-18 were suppressed. These findings fill the gap in understanding the roles played by pIL-18BP in PRRSV infection and provide a foundation for further research.IMPORTANCEPRRSV-infected pigs elicit a weak cellular immune response and the mechanisms of cellular immune regulation induced by PRRSV have not yet been fully elucidated. In this study, we investigated the role of pIL-18BP in PRRSV-induced immune response referring to the regulation of human IL-18BP to human interferon-gamma (hIFN-γ). This is expected to be used as a method to enhance the cellular immune response induced by the PRRSV vaccine. Here, we mined five transcripts of the pIL-18BP gene and demonstrated that it interacts with pIL-18 and regulates pIFN-γ mRNA expression. Surprisingly, we also found that both mRNA and protein expression of pIL-18 were suppressed under different PRRSV strains of infection status. These results have led to a renewed understanding of the roles of pIL-18BP and pIL-18 in cellular immunity induced by PRRSV infection, which has important implications for the prevention and control of PRRS.


Assuntos
Vírus da Síndrome Respiratória e Reprodutiva Suína , RNA Mensageiro , Animais , Suínos , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Síndrome Respiratória e Reprodutiva Suína/virologia , Síndrome Respiratória e Reprodutiva Suína/imunologia , Síndrome Respiratória e Reprodutiva Suína/genética , Síndrome Respiratória e Reprodutiva Suína/metabolismo , Macrófagos Alveolares/virologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Interações Hospedeiro-Patógeno/genética , Interferon gama/genética , Interferon gama/metabolismo , Interferon gama/imunologia , Transcrição Gênica
14.
Angiology ; : 33197241253313, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775330

RESUMO

The present study aimed to develop a model to predict functional disability at 3 months in patients with acute ischemic stroke (AIS) (n = 5,406). The primary outcome was functional disability (modified Rankin Scale [mRS] >2) at 3 months. A prediction model including blood biomarkers was developed based on a multivariable logistic regression model, which was internally validated by the 100-time bootstrap method. A nomogram and a web-based calculator were developed for usage in clinical practice. At 3 months, 11% (638/5,406) of the patients had functional disability. Seven independent predictors of functional disability at 3 months were incorporated into the FAITHS2 model (fasting plasma glucose, age, interleukin-6, stroke history, National Institute of Health Stroke Scale [NIHSS] at admission, sex, and systolic blood pressure). The Area Under Curves (AUCs) were 0.814 (95% confidence interval [CI] 0.796-0.832) and 0.808 (95% CI 0.806-0.810), and the Brier scores were 0.088 ± 0.214 and 0.089 ± 0.003 for the derivation cohort and internal validation, respectively, showing optimal performance of the model. The FAITHS2 model has excellent potential to be a dependable application for individualized clinical decision making.

15.
Biomed Environ Sci ; 37(4): 406-417, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38727163

RESUMO

Objective: This study aimed to efficiently reduce the release of radon from water bodies to protect the environment. Methods: Based on the sizes of the experimental setup and modular float, computational fluid dynamics (CFD) was used to assess the impact of the area coverage rate, immersion depth, diffusion coefficient, and radon transfer velocity at the gas-liquid interface on radon migration and exhalation of radon-containing water. Based on the numerical simulation results, an estimation model for the radon retardation rate was constructed. The effectiveness of the CFD simulation was evaluated by comparing the experimental and simulated variation values of the radon retardation rate with the coverage area rates. Results: The effect of radon transfer velocity on radon retardation in water bodies was minor and insignificant according to the appropriate value; therefore, an estimation model of the radon retardation rate of the coverage of a radon-containing water body was constructed using the synergistic impacts of three factors: area coverage rate, immersion depth, and diffusion coefficient. The deviation between the experimental and simulated results was < 4.3%. Conclusion: Based on the numerical simulation conditions, an estimation model of the radon retardation rate of covering floats in water bodies under the synergistic effect of multiple factors was obtained, which provides a reference for designing covering floats for radon retardation in radon-containing water.


Assuntos
Hidrodinâmica , Radônio , Radônio/análise , Simulação por Computador , Poluentes Radioativos da Água/análise
16.
Front Immunol ; 15: 1310239, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711515

RESUMO

Background: For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after systemic treatment progression based on immune checkpoint inhibitors (ICIs). The aim of this study was to assess the patterns of disease progression in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for surgical intervention, following the use of immune checkpoint inhibitors. Methods: This is a retrospective study that involved patients with inoperable China liver stage (CNLC) IIIa and/or IIIb. The patients were treated at eight centers across China between January 2017 and October 2022. All patients received at least two cycles of first-line treatment containing immune checkpoint inhibitors. The patterns of disease progression were assessed using RECIST criteria 1.1. Different progression modes have been identified based on the characteristics of imaging progress. The study's main outcome measures were post-progression survival (PPS) and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method to compare the difference among the four groups. Subgroup analysis was conducted to compare the efficacy of different immunotherapy combinations. Variations in the efficacy of immunotherapy have also been noted across patient groups exhibiting alpha-fetoprotein (AFP) levels equal to or exceeding 400ng/mL, in contrast to those with AFP levels below 400ng/mL. Results: The study has identified four distinct patterns of progress, namely p-IIb, p-IIIa, p-IIIb, and p-IIIc. Diverse patterns of progress demonstrate notable variations in both PPS and OS. The group p-IIb had the longest PPS of 12.7m (95% 9.3-16.1) and OS 19.6m (95% 15.6-23.5), the remaining groups exhibited p-IIIb at PPS 10.5 months (95%CI: 7.9-13.1) and OS 19.2 months (95%CI 15.1-23.3). Similarly, p-IIIc at PPS 5.7 months (95%CI: 4.2-7.2) and OS 11.0 months (95%CI 9.0-12.9), while p-IIIa at PPS 3.4 months (95%CI: 2.7-4.1) and OS 8.2 months (95%CI 6.8-9.5) were also seen. Additional stratified analysis was conducted and showed there were no differences of immunotherapy alone or in combination in OS (HR= 0.92, 95%CI: 0.59-1.43, P=0.68) and PPS (HR= 0.88, 95%CI: 0.57-1.36, P=0.54); there was no significant difference in PPS (HR=0.79, 95% CI: 0.55-1.12, P=0.15) and OS (HR=0.86, 95% CI: 0.61-1.24, P=0.39) for patients with AFP levels at or over 400ng/mL. However, it was observed that patients with AFP levels above 400ng/mL experienced a shorter median progression of PPS (8.0 months vs. 5.0 months) after undergoing immunotherapy. Conclusion: In this investigation of advanced hepatocellular carcinoma among Chinese patients treated with immune checkpoint inhibitors, we identified four distinct progression patterns (p-IIb, p-IIIa, p-IIIb and p-IIIc) that showed significant differences in PPS and OS. These findings demonstrate the heterogeneity of disease progression and prognosis after immunotherapy failure. Further validation in large cohorts is necessary to develop prognostic models that integrate distinct progression patterns to guide subsequent treatment decisions. Additionally, post-immunotherapy progression in patients with AFP levels ≥400ng/mL indicates a shortened median PPS. These findings provide valuable insights for future personalized treatment decisions.


Assuntos
Carcinoma Hepatocelular , Progressão da Doença , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , China , Idoso , Adulto , Estadiamento de Neoplasias , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/análise , Resultado do Tratamento , População do Leste Asiático
17.
Discov Oncol ; 15(1): 147, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717631

RESUMO

BACKGROUND: Supraglottic squamous cell carcinoma (SGSCC) is characterized by low differentiation, rapid growth, and inconspicuous initial manifestations. Early detection and prompt treatment can significantly improve survival rates. The main focus of treatment is to maintain optimal laryngeal function. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we conducted univariate and multivariate Cox regression analyses to identify independent prognostic factors for T1-T2 SGSCC. We also enrolled 109 patients with T1-T2 SGSCC from the First Affiliated Hospital of Xinjiang Medical University as an external validation set. In addition, we developed a nomogram to predict the prognosis of T1-T2 SGSCC, assessed the predictive accuracy and discriminatory ability of the nomogram using the area under the curve (AUC), C-index, receiver operating characteristic (ROC) curve and calibration curve, and confirmed the clinical validity of the nomogram using decision curve analysis (DCA). RESULTS: Our investigation identified nine prognostic indicators for T1-T2 SGSCC: age (≥ 65 years), marital status, American Joint Committee on Cancer (AJCC) stage (II-IV), grade (III-IV), M stage (M1), radiotherapy, chemotherapy, sex (female), and surgery. These variables were used to create accurate nomograms that predict overall and specific survival rates at 1, 3, and 5 years. The nomograms demonstrated superior prognostic value and accuracy compared to AJCC staging. Laryngectomy with partial laryngectomy is the preferred treatment option for T1-T2 SGSCC cases, providing superior overall survival (OS) and cancer-specific survival (CSS). Radiotherapy also improves OS and CSS. Our results were based on a comprehensive analysis of various indicators, including the C-index, ROC curve, calibration curve, and DCA curve. CONCLUSION: Nomograms provide significant advantages in treatment decision making and diagnosis. Laryngectomy with partial laryngectomy is the most appropriate method for T1-T2 SGSCC cases. However, radiotherapy can also be used. Thus, patients with T1-T2 SGSCC should be evaluated to determine if combination therapy is the optimal treatment approach. Nevertheless, further research is needed to understand the role of chemotherapy. Overall, this study identified nine key predictors of future outcomes, aiding healthcare professionals in assessing risks and making treatment decisions for T1-T2 SGSCC patients.

18.
J Am Chem Soc ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728652

RESUMO

Porous organic polymers (POPs) with inherent porosity, tunable pore environment, and semiconductive property are ideally suitable for application in various advanced semiconductor-related devices. However, owing to the lack of processability, POPs are usually prepared in powder forms, which limits their application in advanced devices. Herein, we demonstrate an example of information storage application of POPs with film form prepared by an electrochemical method. The growth process of the electropolymerized films in accordance with the Volmer-Weber model was proposed by observation of atomic force microscopy. Given the mechanism of the electron transfer system, we verified and mainly emphasized the importance of porosity and interfacial properties of porous polymer films for memristor. As expected, the as-fabricated memristors exhibit good performance on low turn-on voltage (0.65 ± 0.10 V), reliable data storage, and high on/off current ratio (104). This work offers inspiration for applying POPs in the form of electropolymerized films in various advanced semiconductor-related devices.

19.
NPJ Precis Oncol ; 8(1): 111, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773241

RESUMO

Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform.

20.
Antioxidants (Basel) ; 13(5)2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38790700

RESUMO

Facial nerve injury can cause significant functional impairment, impacting both the peripheral and central nervous systems. The present study evaluated changes in facial motor function, numbers of cholinergic neurons and microglia, and nNOS levels in the facial nucleus of the central nervous system (CNS) following peripheral facial nerve injury. Facial nerve function, as determined by eyeblink and whisker-movement reflexes, was evaluated at baseline and 1, 2, 3, 4, 8, and 12 weeks after inducing facial nerve injury through compression or axotomy. The expression of choline acetyltransferase (ChAT), ionized calcium-binding adaptor molecule 1 (Iba-1), and neuronal nitric oxide synthase (nNOS) in the facial nucleus of the CNS was analyzed 2, 4, and 12 weeks after peripheral facial nerve injury. Compression-induced facial nerve injury was found to lead to temporary facial motor impairment, whereas axotomy resulted in persistent impairment. Moreover, both compression and axotomy reduced ChAT expression and increased Iba-1 and nNOS expression in the facial nucleus, indicating upregulation of an inflammatory response and neurodegeneration. These results indicate that, compared with compression-induced injury, axotomy-induced facial nerve injury results in greater facial motor dysfunction and more persistent microglial and nitric oxide activation in the facial nucleus of the CNS.

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