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Background: Patients access relevant information concerning their orthopaedic surgery resources through multiple information channels before presenting for clinical treatment. Recently, artificial intelligence (AI)-powered chatbots have become another source of information for patients. The currently developed AI chat technology ChatGPT (OpenAI LP) is an application for such purposes and it has been rapidly gaining popularity, including for patient education. This study sought to evaluate whether ChatGPT can correctly answer frequently asked questions (FAQ) regarding periprosthetic joint infection (PJI). Methods: Twelve FAQs about PJI after hip and knee arthroplasty were identified from the websites of fifteen international clinical expert centres. ChatGPT was confronted with these questions and its responses were analysed for their accuracy using an evidence-based approach by a multidisciplinary team. Responses were categorised in four groups: (1) Excellent response that did not require additional improvement; (2) Satisfactory responses that required a small amount of improvement; (3) Satisfactory responses that required moderate improvement; and (4) Unsatisfactory responses that required a large amount of improvement. Results: From the analysis of the responses given by the chatbot, no reply received an 'unsatisfactory' rating; one did not require any correction; and the majority of the responses required low (7 out of 12) or moderate (4 out of 12) clarification. Although a few responses required minimal clarification, the chatbot responses were generally unbiased and evidence-based, even when asked controversial questions. Conclusions: The AI-chatbot ChatGPT was able to effectively answer the FAQs of patients seeking information around PJI diagnosis and treatment. The given information was also written in a manner that can be assumed to be understandable by patients. The chatbot could be a valuable clinical tool for patient education and understanding around PJI treatment in the future. Further studies should evaluate its use and acceptance by patients with PJI.
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A novel Fe-catalyzed fluorosulfonylation of alkenes with Na2S2O4 and N-fluorobenzenesulfonimide (NFSI) for assembling various lactam-functionalized alkyl sulfonyl fluorides is disclosed. In this reaction, Na2S2O4 acts as both an SO2 source and a reductant. Furthermore, the resulting products can be efficiently transformed into valuable chemicals, including sulfonyl esters and sulfonamides, via the sulfur(VI) fluoride exchange (SuFEx) click reaction. Preliminary mechanistic studies suggest that the transformation proceeds through intramolecular radical cyclization, SO2 insertion, sulfite anion formation, and fluorination.
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Enzymatic hydrolysis contributes to obtaining fermentable sugars using pretreated lignocellulose materials for bioethanol generation. Unfortunately, the pretreatment of lignocellulose causes low substrate enzymatic hydrolysis, which is due to the structure changes of lignin to produce main phenolic by-products and non-productive cellulase adsorption. It is reported that modified lignin enhances the speed of enzymatic hydrolysis through single means to decrease the negative effects of fermentation inhibitors or non-productive cellulase adsorption. However, a suitable modified lignin should be selected to simultaneously reduce the fermentation inhibitors concentration and non-productive cellulase adsorption for saving resources and maximizing the enzymatic hydrolysis productivity. Meanwhile, the adsorption micro-mechanisms of modified lignin with fermentation inhibitors and cellulase remain elusive. In this review, different pretreatment effects toward lignin structure, and their impacts on subsequent enzymatic hydrolysis are analyzed. The main modification methods for lignin are presented. Density functional theory is used to screen suitable modification methods for the simultaneous reduction of fermentation inhibitors and non-productive cellulase adsorption. Lignin-fermentation inhibitors and lignin-cellulase interaction mechanisms are discussed using different advanced analysis techniques. This article addresses the gap in previous reviews concerning the application of modified lignin in the enhancement of bioethanol production. For the first time, based on existing studies, this work posits the hypothesis of applying theoretical simulations to screen efficient modified lignin-based adsorbents, in order to achieve a dual optimization of the detoxification and saccharification processes. We aim to improve the integrated lignocellulose transformation procedure for the effective generation of cleaner bioethanol.
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Abdominal visceral pain is a predominant symptom in patients with chronic pancreatitis (CP); however, the underlying mechanism of pain in CP remains elusive. We hypothesized that astrocytes in the hypothalamic paraventricular nucleus (PVH) contribute to CP pain pathogenesis. A mouse model of CP was established by repeated intraperitoneal administration of caerulein to induce abdominal visceral pain. Abdominal mechanical stimulation, open field and elevated plus maze tests were performed to assess visceral pain and anxiety-like behavior. Fiber photometry, brain slice Ca2+ imaging, electrophysiology, and immunohistochemistry were used to investigate the underlying mechanisms. Mice with CP displayed long-term abdominal mechanical allodynia and comorbid anxiety, which was accompanied by astrocyte glial fibrillary acidic protein reactivity, elevated Ca2+ signaling, and astroglial glutamate transporter-1 (GLT-1) deficits in the PVH. Specifically, reducing astrocyte Ca2+ signaling in the PVH via chemogenetics significantly rescued GLT-1 deficits and alleviated mechanical allodynia and anxiety in mice with CP. Furthermore, we found that GLT-1 deficits directly contributed to the hyperexcitability of VGLUT2PVH neurons in mice with CP, and that pharmacological activation of GLT-1 alleviated the hyperexcitability of VGLUT2PVH neurons, abdominal visceral pain, and anxiety in these mice. Taken together, our data suggest that dysfunctional astrocyte glutamate uptake in the PVH contributes to visceral pain and anxiety in mice with CP, highlighting GLT-1 as a potential therapeutic target for chronic pain in patients experiencing CP.
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A sensing interface co-constructed from the two-dimensional conductive material (Ag@MXene) and an antifouling cyclic multifunctional peptide (CP) is described. While the large surface area of Ag@MXene loads more CP probes, CP binds to Ag@MXene to form a fouling barrier and ensure the structural rigidity of the targeting sequence. This strategy synergistically enhances the biosensor's sensitivity and resistance to contamination. The SPR results showed that the binding affinity of the CP to the target was 6.23 times higher than that of the antifouling straight-chain multifunctional peptide (SP) to the target. In the 10 mg/mL BSA electrochemical fouling test, the fouling resistance of Ag@MXene + CP (composite sensing interface of CP combined with Ag@MXene) was 30 times higher than that of the bare electrode. The designed electrochemical sensor exhibited good selectivity and wide dynamic response range at PD-L1 concentrations from 0.1 to 50 ng/mL. The lowest detection limit was 24.54 pg/mL (S/N = 3). Antifouling 2D materials with a substantial specific surface area, coupled with non-straight chain antifouling multifunctional peptides, offer a wide scope for investigating the sensitivity and antifouling properties of electrochemical sensors.
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Técnicas Biossensoriais , Técnicas Eletroquímicas , Limite de Detecção , Peptídeos Cíclicos , Prata , Prata/química , Técnicas Eletroquímicas/métodos , Peptídeos Cíclicos/química , Peptídeos Cíclicos/sangue , Técnicas Biossensoriais/métodos , Humanos , Incrustação Biológica/prevenção & controle , EletrodosRESUMO
Programmed cell death-ligand 1 positive (PD-L1+) exosomes play a crucial role in the realm of cancer diagnosis and treatment. Nevertheless, due to the intricate nature of biological specimens, coupled with the heterogeneity, low refractive index (RI), and scant surface coverage density of exosomes, traditional surface plasmon resonance (SPR) sensors still do not meet clinical detection requirements. This study utilizes the exceptional electrical and optical attributes of single-walled carbon nanotubes (SWCNTs) as the substrate for SPR sensing, thereby markedly enhancing sensitivity. Furthermore, sp2 hybridized SWCNTs have the ability to load specific recognition elements. Additionally, through the coordination interaction of Ti with phosphate groups and the ferromagnetism of Fe3O4, efficient exosomes isolation and enrichment in complex samples are achievable with the aid of an external magnetic field. Owing to the high-quality and high-RI of Fe3O4@TiO2, the response signal experiences amplification, thus further improving the performance of the SPR biosensor. The linear range of the SPR biosensor constructed by this method is 1.0 × 103 to 1.0 × 107 particles/mL, with a limit of detection (LOD) of 31.9 particles/mL. In the analysis of clinical serum samples, cancer patients can be differentiated from healthy individuals with an Area Under Curve (AUC) of 0.9835. This study not only establishes a novel platform for exosomes direct detection but also offers new perspectives for the sensitive detection of other biomarkers.
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Antígeno B7-H1 , Exossomos , Nanotubos de Carbono , Ressonância de Plasmônio de Superfície , Titânio , Humanos , Antígeno B7-H1/sangue , Antígeno B7-H1/análise , Antígeno B7-H1/isolamento & purificação , Técnicas Biossensoriais/métodos , Exossomos/química , Limite de Detecção , Nanotubos de Carbono/química , Neoplasias/sangue , Ressonância de Plasmônio de Superfície/métodos , Titânio/químicaRESUMO
To facilitate studies of engagement of protein targets by small molecules in living cells, we synthesized fluorinated derivatives of the fluorophore 7-hydroxycoumarin-3-carboxylic acid (7OHCCA). Compared to the related difluorinated coumarin Pacific Blue (PB), amide derivatives of 6-fluoro-7-hydroxycoumarin-3-carboxylic acid (6FC) exhibited substantially brighter fluorescence. When linked to the anticancer drug paclitaxel (Taxol) via gamma-aminobutyric acid (GABA), the acidity of the phenol of these coumarins profoundly affected cellular efflux and binding to microtubules in living cells. In contrast to the known fluorescent taxoid PB-GABA-Taxol, the less acidic 6FC-GABA-Taxol was more cell-permeable due to a lower susceptibility to active efflux. In living cells, this facilitated the imaging of microtubules by confocal microscopy and enabled quantification of binding to microtubules by flow cytometry without added efflux inhibitors. The photophysical, chemical, and biological properties of 6FC derivatives make these compounds particularly attractive for the construction of fluorescent molecular probes suitable for quantitative analysis of intracellular small molecule-protein interactions.
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Transformation optics (TO) provides a powerful tool to manipulate electromagnetic waves, enabling the design of invisibility cloaks, which can render objects invisible. Despite many years of research, however, invisibility cloaks experimentally realized thus far can only operate at a single frequency. The narrow bandwidth significantly restricts the practical applications of invisibility cloaks and other TO devices. Here, a general design strategy is proposed to realize a multiband anisotropic metamaterial characterized by two principal permittivity components, i.e., one infinite and the other spatially gradient. Through a proper transformation and combination of such metamaterials, an omnidirectional invisibility cloak is experimentally implemented, which is impedance-matched to free space at multiple frequencies. Both far-field numerical simulations and near-field experimental mappings confirm that this cloak can successfully suppress scattering from multiple large-scale objects simultaneously at 5 and 10 GHz. The design strategy and corresponding practical realization bring multiband transformation optical devices one step closer to reality.
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Spinal Cord Injury (SCI) is a debilitating disease associated with a significant economic burden owing to its high level of disability; however, current treatment options have only limited efficacy. Past research has shown that iron-dependent programmed cell death, also known as ferroptosis, plays a critical role in the pathogenesis of SCI. The sigma-1 receptor (Sig-1R) is widely distributed in the central nervous system, and has been implicated in the pathophysiology of several neurological and psychiatric disorders. Several in vivo and ex vivo studies have shown that Sig-1R activation exerts unique neuroprotective effects. However, the underlying mechanisms remain unclear. To date, no study has yet demonstrated the association between Sig-1R activation and ferroptosis in patients with SCI. However, the present study found that Sig-1R activation effectively promoted the recovery of motor function in mice after spinal cord injury, attenuated neuronal apoptosis, reduced the production of pro-inflammatory cytokines and iron accumulation, and inhibited ferroptosis in spinal cord tissues following SCI in mice. Ferroptosis and IRE1α were significantly upregulated after spinal cord injury, while sigma-1 receptor agonists were able to facilitate this result through the elimination of inositol-requiring enzyme-1 alpha (IRE1α)-mediated neuronal ferroptosis. Therefore, sigma-1 receptor activation could attenuate ferroptosis after SCI by reducing IRE1α and improving functional recovery after SCI, potentially representing a new therapeutic strategy for treating SCI.
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Ferroptose , Camundongos Endogâmicos C57BL , Neurônios , Proteínas Serina-Treonina Quinases , Receptores sigma , Receptor Sigma-1 , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/metabolismo , Animais , Receptores sigma/metabolismo , Receptores sigma/agonistas , Ferroptose/fisiologia , Ferroptose/efeitos dos fármacos , Camundongos , Proteínas Serina-Treonina Quinases/metabolismo , Neurônios/metabolismo , Endorribonucleases/metabolismo , Masculino , Recuperação de Função Fisiológica/fisiologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Apoptose/fisiologia , Apoptose/efeitos dos fármacos , Medula Espinal/metabolismoRESUMO
Solid-state batteries are commonly acknowledged as the forthcoming evolution in energy storage technologies. Recent development progress for these rechargeable batteries has notably accelerated their trajectory toward achieving commercial feasibility. In particular, all-solid-state lithium-sulfur batteries (ASSLSBs) that rely on lithium-sulfur reversible redox processes exhibit immense potential as an energy storage system, surpassing conventional lithium-ion batteries. This can be attributed predominantly to their exceptional energy density, extended operational lifespan, and heightened safety attributes. Despite these advantages, the adoption of ASSLSBs in the commercial sector has been sluggish. To expedite research and development in this particular area, this article provides a thorough review of the current state of ASSLSBs. We delve into an in-depth analysis of the rationale behind transitioning to ASSLSBs, explore the fundamental scientific principles involved, and provide a comprehensive evaluation of the main challenges faced by ASSLSBs. We suggest that future research in this field should prioritize plummeting the presence of inactive substances, adopting electrodes with optimum performance, minimizing interfacial resistance, and designing a scalable fabrication approach to facilitate the commercialization of ASSLSBs.
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OBJECTIVES: This study aimed to investigate tumor heterogeneity of colorectal liver metastases (CRLM) and stratify the patients into different risk groups of prognoses following liver resection by applying an unsupervised radiomics machine-learning approach to preoperative CT images. METHODS: This retrospective study retrieved clinical information and CT images of 197 patients with CRLM from The Cancer Imaging Archive (TCIA) database. Radiomics features were extracted from a segmented liver lesion identified at the portal venous phase. Those features which showed high stability, non-redundancy, and indicative information were selected. An unsupervised consensus clustering analysis on these features was adopted to identify subgroups of CRLM patients. Overall survival (OS), disease-free survival (DFS), and liver-specific DFS were compared between the identified subgroups. Cox regression analysis was applied to evaluate prognostic risk factors. RESULTS: A total of 851 radiomics features were extracted, and 56 robust features were finally selected for unsupervised clustering analysis which identified two distinct subgroups (96 and 101 patients respectively). There were significant differences in the OS, DFS, and liver-specific DFS between the subgroups (all log-rank p < 0.05). The subgroup with worse outcome using the proposed radiomics model was consistently associated with shorter OS, DFS, and liver-specific DFS, with hazard ratios of 1.78 (95 %CI: 1.12-2.83), 1.72 (95 %CI: 1.16-2.54), and 1.59 (95 %CI: 1.10-2.31), respectively. The general performance of this radiomics model outperformed the traditional Clinical Risk Score and Tumor Burden Score in the prognosis prediction after surgery for CRLM. CONCLUSION: Radiomics features derived from preoperative CT images can reveal the heterogeneity of CRLM and stratify the patients with CRLM into subgroups with significantly different clinical outcomes.
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Neoplasias Colorretais , Neoplasias Hepáticas , Tomografia Computadorizada por Raios X , Aprendizado de Máquina não Supervisionado , Humanos , Masculino , Feminino , Neoplasias Colorretais/patologia , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Prognóstico , Estudos Retrospectivos , Idoso , Adulto , Taxa de Sobrevida , Idoso de 80 Anos ou mais , Aprendizado de Máquina , RadiômicaRESUMO
BACKGROUND: Delayed graft function (DGF) is an important complication after kidney transplantation surgery. The present study aimed to develop and validate a nomogram for preoperative prediction of DGF on the basis of clinical and histological risk factors. METHODS: The prediction model was constructed in a development cohort comprising 492 kidney transplant recipients from May 2018 to December 2019. Data regarding donor and recipient characteristics, pre-transplantation biopsy results, and machine perfusion parameters were collected, and univariate analysis was performed. The least absolute shrinkage and selection operator regression model was used for variable selection. The prediction model was developed by multivariate logistic regression analysis and presented as a nomogram. An external validation cohort comprising 105 transplantation cases from January 2020 to April 2020 was included in the analysis. RESULTS: 266 donors were included in the development cohort, 458 kidneys (93.1%) were preserved by hypothermic machine perfusion (HMP), 96 (19.51%) of 492 recipients developed DGF. Twenty-eight variables measured before transplantation surgery were included in the LASSO regression model. The nomogram consisted of 12 variables from donor characteristics, pre-transplantation biopsy results and machine perfusion parameters. Internal and external validation showed good discrimination and calibration of the nomogram, with Area Under Curve (AUC) 0.83 (95%CI, 0.78-0.88) and 0.87 (95%CI, 0.80-0.94). Decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSION: A DGF predicting nomogram was developed that incorporated donor characteristics, pre-transplantation biopsy results, and machine perfusion parameters. This nomogram can be conveniently used for preoperative individualized prediction of DGF in kidney transplant recipients.
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Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Função Retardada do Enxerto , Nomogramas , Sobrevivência de Enxerto , Rim , Doadores de Tecidos , Biópsia/efeitos adversos , Fatores de RiscoRESUMO
In the original publication [...].
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We aimed to evaluate the role of the spinal lymphatic system in spinal cord injury and whether it has an impact on recovery after spinal cord injury. Flow cytometry was used to evaluate the changes in the number of microvesicles after spinal cord injury. Evans blue extravasation was used to evaluate the function of the lymphatic system. Evans blue extravasation and immunofluorescence were used to evaluate the permeability of blood spinal cord barrier. The spinal cord edema was evaluated by dry and wet weight.Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was used to evaluate apoptosis after spinal cord injury. Nuclear factor-kappa B pathway was detected by Western blot. Behavioral tests were used to evaluate limb function. Microvesicles released after spinal cord injury can enter the thoracic duct and then enter the blood through the lymph around the spine. After ligation of the thoracic duct, it can aggravate the neuropathological manifestations and limb function after spinal cord injury. The potential mechanism may involve nuclear factor-kappa B pathway.
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Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Medula Espinal , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/metabolismo , Animais , Recuperação de Função Fisiológica/fisiologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Medula Espinal/fisiopatologia , NF-kappa B/metabolismo , Masculino , Apoptose/fisiologia , Ratos Sprague-Dawley , Modelos Animais de Doenças , Sistema Linfático/fisiopatologia , Sistema Linfático/patologia , Edema/patologia , Ducto Torácico/fisiopatologia , Feminino , Micropartículas Derivadas de Células/metabolismoRESUMO
Recent studies have suggested that dogs were domesticated during the Last Glacial Maximum (LGM) in Siberia, which contrasts with previous proposed domestication centers (e.g. Europe, the Middle East, and East Asia). Ancient DNA provides a powerful resource for the study of mammalian evolution and has been widely used to understand the genetic history of domestic animals. To understand the maternal genetic history of East Asian dogs, we have made a complete mitogenome dataset of 120 East Asian canids from 38 archaeological sites, including 102 newly sequenced from 12.9 to 1â ka BP (1,000â years before present). The majority (112/119, 94.12%) belonged to haplogroup A, and half of these (55/112, 49.11%) belonged to sub-haplogroup A1b. Most existing mitochondrial haplogroups were present in ancient East Asian dogs. However, mitochondrial lineages in ancient northern dogs (northeastern Eurasia and northern East Asia) were deeper and older than those in southern East Asian dogs. Results suggests that East Asian dogs originated from northeastern Eurasian populations after the LGM, dispersing in two possible directions after domestication. Western Eurasian (Europe and the Middle East) dog maternal ancestries genetically influenced East Asian dogs from approximately 4â ka BP, dramatically increasing after 3â ka BP, and afterwards largely replaced most primary maternal lineages in northern East Asia. Additionally, at least three major mitogenome sub-haplogroups of haplogroup A (A1a, A1b, and A3) reveal at least two major dispersal waves onto the Qinghai-Tibet Plateau in ancient times, indicating eastern (A1b and A3) and western (A1a) Eurasian origins.
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Genoma Mitocondrial , Animais , Cães , Animais Domésticos/genética , Ásia Oriental , DNA Mitocondrial/genética , Variação Genética , Haplótipos , Mamíferos/genética , FilogeniaRESUMO
OBJECTIVE: The mechanism behind SDAVF is still unclear. We discovered that the vessel wall of the SDAVF-DV occasionally showed enhancement in MRI, and this study assessed the relationship between the enhancement of the draining vein's wall and its histology. METHODS: For histopathologic analysis, 16 draining vein samples from 16 patients with SDAVF were included, 3 normal arteries and 3 normal veins were chosen as comparison. We assessed the imaging and microscopic characteristics of the draining veins in SDAVF patients. The former included the presence of significant enhancement of the wall of the draining vein in MRI, and the latter included the adherence, aggregation, infiltration of pro-inflammatory factors and inflammatory cells. Immuno-histochemical staining was performed using IL-1ß, IL-8, TGF-ß as well as MPO and MMP-9, and positive results were counted. Multiple logistic regression analysis was used to determine whether the infiltration of inflammatory cells was connected to vessel wall enhancement in the SDAVF-DV. RESULTS: Infiltration of inflammatory cells was significantly higher in SDAVF-DV compared to normal vessels, 7 out of 16 patients significantly had enhancement of the vessel wall of SDAVF-DV, and logistic regression analysis showed that samples with more infiltration of inflammatory cells were more likely to show enhancement of the SDAVF-DV walls. CONCLUSION: There was considerable inflammatory cells infiltration in SDAVF-DV, and this may explain why their vessel wall had such a significant enhancement in MRI.
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Malformações Vasculares do Sistema Nervoso Central , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Veias/patologia , Veias/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Medula Espinal/irrigação sanguíneaRESUMO
AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease. Chemotherapy based on gemcitabine (GEM) remains the first-line drug for patients with advanced PDAC. However, GEM resistance impairs its therapeutic effectiveness. Therefore, identifying effective therapeutic targets are urgently needed to overcome GEM resistance. METHODS: The clinical significance of Tripartite Motif Containing 29 (TRIM29) was identified by exploring GEO datasets and TCGA database and its potential biological functions were predicted by GSEA analysis. The regulatory axis was established by bioinformatics analysis and validated by mechanical experiments. Then, in vitro and in vivo assays were performed to validate the roles of TRIM29 in PDAC GEM resistance. RESULTS: High TRIM29 expression was associated with poor prognosis of PDAC and functional experiments demonstrated that TRIM29 promoted GEM resistance in PDAC GEM-resistant (GR) cells. Furthermore, we revealed that circRPS29 promoted TRIM29 expression via competitive interaction with miR-770-5p and then activated MEK/ERK signaling pathway. Additionally, both in vitro and in vivo functional experiments demonstrated that circRPS29/miR-770-5p/TRIM29 axis promoted PDAC GEM resistance via activating MEK/ERK signaling pathway. CONCLUSION: Our results identify the significance of the signaling axis, circRPS29/miR-770-5p/TRIM29-MEK/ERK, in PDAC GEM resistance, which will provide novel therapeutic targets for PDAC treatment.
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Carcinoma Ductal Pancreático , Resistencia a Medicamentos Antineoplásicos , Gencitabina , Sistema de Sinalização das MAP Quinases , Neoplasias Pancreáticas , Fatores de Transcrição , Animais , Humanos , Camundongos , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Prognóstico , RNA Circular/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal semi-dominant disease, characterized by markedly elevated levels of low-density lipoprotein cholesterol (LDL-c) from conception and accelerated atherosclerotic cardiovascular disease, often resulting in early death. The aim of this study was to evaluate the prevalence of clinically defined FH in Chinese Han patients with acute coronary syndrome (ACS) and compare the long-term prognosis of ACS patients with and without FH receiving lipid-lowering therapy containing statins after a coronary event. METHODS: All ACS patients were screened at the Second Affiliated Hospital of Xi'an Jiaotong University between Jan 2019 and Sep 2020, and 531 participants were enrolled. All were examined for FH under the Dutch Lipid Clinical Network (DLCN) criteria, and those patients were divided into definite/probable FH, possible FH and unlikely FH. The severity of coronary artery disease was evaluated by the Gensini scoring system. Plasma levels of total cholesterol (TC), triacylglycerol (TG), HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), very low-density lipoproteins-cholesterol (VLDL-c), apolipoprotein A1 (apoA1), apolipoprotein B (apoB) and lipoprotein (a) (Lp(a)) were determined centrally at baseline and the last follow-up visit in the fasting state. The non-high-density lipoprotein cholesterol (non-HDL-c) concentration, the TC/HDL-c and apoB/apoA1 ratios were calculated. After FH patients received lipid-lowering treatment containing statin, the target LDL-c levels recommended by the guidelines (LDL-c < 1.8 mmol/L or < 1.4 mmol/L and a reduction > 50% from baseline) were evaluated, and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) during the 12-month follow-up was recorded. RESULTS: The prevalence of clinically definite or probable FH was 4.3%, and the prevalence of possible FH was 10.6%. Compared with the unlikely FH patients with ACS, the FH patients had higher levels of TC, LDL-c, apoB, Lp(a), non-HDL-c, TC/HDL-c and apoB/apoA1 ratio, more severe coronary artery diseases and greater prevalence of left main and triple or multiple vessel lesions. After lipid-lowering therapy containing statins, a minority of FH patients reached the target LDL-c levels defined by the guidelines (χ2 = 33.527, P < 0.001). During the 12-month follow-up, a total of 72 patients experienced MACCE. The survival curve in patients in the FH group was significantly lower than that in the unlikely FH group (HR = 1.530, log-rank test: P < 0.05). Furthermore, the survival curve in patients with high LDL-c (≥ 1.8 mmol/L) was significantly lower than that in patients with low LDL-c (< 1.8 mmol/L) at the 12-month follow-up visit (HR = 1.394, log-rank test: P < 0.05). No significant difference was observed between patients with LDL-c levels ≥ 1.4 mmol/L and with < 1.4 mmol/L at the 12-month follow-up visit by using Kaplan-Meier survival analysis (HR = 1.282, log-rank test: P > 0.05). CONCLUSIONS: FH was an independent risk factor for MACCE in adult patients after a coronary event during long-term follow-up. However, there was inadequate high-intensity statins prescriptions for high-risk patients in this current study. It is important for FH patients to optimize lipid-lowering treatment strategies to reach the target LDL-c level to improve the long-term prognosis of clinical outcomes.
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Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipoproteinemia Tipo II , Adulto , Humanos , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Apolipoproteínas B , China/epidemiologia , HDL-Colesterol , LDL-Colesterol , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/epidemiologia , Prevalência , Prognóstico , Estudos RetrospectivosRESUMO
Tetrabromobisphenol A (TBBPA) that widely exists in soil and poses a potential threat to ecological environment urgently needs economically efficient remediation techniques. This study utilized both homogeneous Fe2⺠solution and heterogeneous iron-based nanomaterials (chemically synthesized nano zero-valence iron (nZVI) and green-synthesized iron nanoparticles (G-Fe NPs)) to activate persulfate (PS) and assess their efficacy in degrading TBBPA in soil. The results demonstrate the superior performance of heterogeneous catalytic systems (WG-Fe NPs/PS (82.07%) and WnZVI/PS (78.32%)) over homogeneous catalytic system (WFe2+/PS (71.69%)), In addition, G-Fe NPs and nZVI effectively controlled the slow release of Fe2+. The optimization analysis using response surface methodology (RSM) reveal the remarkable significance of the experimental model based on the box-behnken design. RSM show that G-Fe NPs/PS exhibited optimal process parameters and predicted the maximum soil TBBPA degradation efficiency reaching 98.77%. The results of density functional theory calculations suggest that C-Br are the primary targets for electrophilic substitution reactions. Based on the f0 value and â³G, the degradation pathway of TBBPA is inferred to involve a sequential debromination process, followed by the cleavage of intermediate carbon-carbon bonds and subsequent oxidation reactions. Hence, G-Fe NPs/PS not only facilitate waste resource utilization but also hold significant application potential.