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A high-salt diet (HSD) elicits sustained sterile inflammation and worsens tissue injury. However, how this occurs after stroke, a leading cause of morbidity and mortality, remains unknown. Here, we report that HSD impairs long-term brain recovery after intracerebral hemorrhage, a severe form of stroke, despite salt withdrawal prior to the injury. Mechanistically, HSD induces innate immune priming and training in hematopoietic stem and progenitor cells (HSPCs) by downregulation of NR4a family and mitochondrial oxidative phosphorylation. This training compromises alternative activation of monocyte-derived macrophages (MDMs) without altering the initial inflammatory responses of the stroke brain. Healthy mice transplanted with bone marrow from HSD-fed mice retain signatures of reduced MDM reparative functions, further confirming a persistent form of innate immune memory that originates in the bone marrow. Loss of NR4a1 in macrophages recapitulates HSD-induced negative impacts on stroke outcomes while gain of NR4a1 enables stroke recovery in HSD animals. Together, we provide the first evidence that links HSD-induced innate immune memory to the acquisition of persistent dysregulated inflammatory responses and unveils NR4a1 as a potential therapeutic target.
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Accidente Cerebrovascular , Inmunidad Entrenada , Ratones , Animales , Macrófagos , Inflamación , Cloruro de Sodio Dietético/efectos adversos , Dieta , Inmunidad InnataRESUMEN
The construction of quaternary carbon centers via C-C coupling protocols remains challenging. The coupling of tertiary C(sp3) with secondary or tertiary C(sp3) counterparts has been hindered by pronounced steric clashes and many side reactions. Herein, we have successfully developed a type of bisphosphine ligand iron complex-catalyzed coupling reactions of tertiary alkyl halides with secondary alkyl zinc reagents and efficiently realized the coupling reaction between tertiary C(sp3) and secondary C(sp3) with high selectivity for the initial instance, which provided an efficient method for the construction of quaternary carbon centers with high steric hindrance. The combination of an iron catalyst and directing group of the substrate makes the great challenging transformation possible.
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Diagnostic methods for Helicobacter pylori infection include, but are not limited to, urea breath test, serum antibody test, fecal antigen test, and rapid urease test. However, these methods suffer drawbacks such as low accuracy, high false-positive rate, complex operations, invasiveness, etc. Therefore, there is a need to develop simple, rapid, and noninvasive detection methods for H. pylori diagnosis. In this study, we propose a novel technique for accurately detecting H. pylori infection through machine learning analysis of surface-enhanced Raman scattering (SERS) spectra of gastric fluid samples that were noninvasively collected from human stomachs via the string test. One hundred participants were recruited to collect gastric fluid samples noninvasively. Therefore, 12,000 SERS spectra (n = 120 spectra/participant) were generated for building machine learning models evaluated by standard metrics in model performance assessment. According to the results, the Light Gradient Boosting Machine algorithm exhibited the best prediction capacity and time efficiency (accuracy = 99.54% and time = 2.61 seconds). Moreover, the Light Gradient Boosting Machine model was blindly tested on 2,000 SERS spectra collected from 100 participants with unknown H. pylori infection status, achieving a prediction accuracy of 82.15% compared with qPCR results. This novel technique is simple and rapid in diagnosing H. pylori infection, potentially complementing current H. pylori diagnostic methods.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/diagnóstico , Espectrometría Raman , Estómago , Ureasa/análisis , Sensibilidad y EspecificidadRESUMEN
Extracellular vesicle (EV) molecular phenotyping offers enormous opportunities for cancer diagnostics. However, the majority of the associated studies adopted biomarker-based unimodal analysis to achieve cancer diagnosis, which has high false positives and low precision. Herein, we report a multimodal platform for the high-precision diagnosis of bladder cancer (BCa) through a multispectral 3D DNA machine in combination with a multimodal machine learning (ML) algorithm. The DNA machine was constructed using magnetic microparticles (MNPs) functionalized with aptamers that specifically identify the target of interest, i.e., five protein markers on bladder-cancer-derived urinary EVs (uEVs). The aptamers were hybridized with DNA-stabilized silver nanoclusters (DNA/AgNCs) and a G-quadruplex/hemin complex to form a sensing module. Such a DNA machine ensured multispectral detection of protein markers by fluorescence (FL), inductively coupled plasma mass spectrometry (ICP-MS), and UV-vis absorption (Abs). The obtained data sets then underwent uni- or multimodal ML for BCa diagnosis to compare the analytical performance. In this study, urine samples were obtained from our prospective cohort (n = 45). Our analytical results showed that the 3D DNA machine provided a detection limit of 9.2 × 103 particles mL-1 with a linear range of 4 × 104 to 5 × 107 particles mL-1 for uEVs. Moreover, the multimodal data fusion model exhibited an accuracy of 95.0%, a precision of 93.1%, and a recall rate of 93.2% on average, while those of the three types of unimodal models were no more than 91%. The elevated diagnosis precision by using the present fusion platform offers a perspective approach to diminishing the rate of misdiagnosis and overtreatment of BCa.
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Aprendizaje Automático , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/orina , Humanos , Biomarcadores de Tumor/orina , Biomarcadores de Tumor/análisis , ADN/química , Plata/química , Aptámeros de Nucleótidos/química , Vesículas Extracelulares/química , Nanopartículas del Metal/químicaRESUMEN
The intricate interaction network necessary for essential physiological functions underscores the interdependence among eukaryotic cells. Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs), specialized junctions between mitochondria and the ER, were recently discovered. These junctions participate in various cellular processes, including calcium level regulation, lipid metabolism, mitochondrial integrity maintenance, autophagy, and inflammatory responses via modulating the structure and molecular composition of various cellular components. Therefore, MAMs contribute to the pathophysiology of numerous ocular disorders, including Diabetic Retinopathy (DR), Age-related Macular Degeneration (AMD) and glaucoma. In addition to providing a concise overview of the architectural and functional aspects of MAMs, this review explores the key pathogenetic pathways involving MAMs in the development of several ocular disorders.
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Diffuse large B-cell lymphoma (DLBCL) is a severe non-Hodgkin's lymphoma. Life expectancy has improved with rituximab, but cause-specific mortality data is lacking. Using the Surveillance, Epidemiology, and End Results (SEER) database to study 27,449 individuals aged 20-74 years diagnosed with primary DLBCL who received chemotherapy between 2000 and 2019, we calculated standardized mortality rate (SMR) and excess absolute risk (EAR) and examined the connection between age, sex, time after diagnosis, and cause of death. Based on 12,205 deaths, 68.7% were due to lymphoma, 20.1% non-cancer causes, and 11.2% other cancers. Non-cancer mortality rates (SMR 1.2; EAR, 21.5) increased with DLBCL compared to the general population. The leading non-cancer death causes were cardiovascular (EAR, 22.6; SMR, 1.6) and infectious (EAR, 9.0; SMR, 2.9) diseases with DLBCL. Risks for non-cancer death and solid neoplasms are highest within the first diagnosis year, then decrease. Among socioeconomic factors, being white, being married, and having a higher income were favorable factors for reducing non-cancer mortality. To improve survival, close surveillance, assessment of risk factors, and early intervention are needed.
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Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Humanos , Causas de Muerte , Programa de VERF , Linfoma de Células B Grandes Difuso/patología , Linfoma no Hodgkin/epidemiología , Rituximab/uso terapéuticoRESUMEN
Diffuse large B-cell lymphoma (DLBCL), accounts for 30-40% of newly diagnosed lymphomas, has an overall cure rate of approximately 60%. Despite previous reports suggesting a negative prognostic association between CCND3 mutations and Burkitt lymphoma, their prognostic implications in DLBCL remain controversial. To investigate this, we evaluated CCND3 mutation status in 2059 DLBCL patient samples from four database (integrated cohort) and additional 167 DLBCL patient samples in our center (JSPH cohort). The mutation was identified in 5.5% (113/2059) of the cases in the integrated cohort, with 86% (97/113) found in exon 5. Furthermore, P284, R271, I290 and Q276 are described as CCND3 mutation hotspots. CCND3 mutation was associated with decreased overall survival (OS) in the integrated cohort (P = 0.0407). Further subgroup analysis revealed that patients diagnosed as EZB subtype DLBCL by LymphGen algorithm with CCND3 mutations had poorer OS than patients diagnosed as EZB subtype without CCND3 mutations (P = 0.0140). Using the next-generation sequencing (NGS) in the JSPH cohort, it was found that both cell cycle and DNA replication pathways were highly upregulated in patients with CCND3 mutations. Our results suggest that CCND3 mutations can serve as a novel prognostic factor in DLBCL pathogenesis. Consequently, the development of personalized therapeutic strategies for DLBCL patients with CCND3 mutations might enhance their prognosis.
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Xylitol, as an important food additive and fine chemical, has a wide range of applications, including food, medicine, chemical, and feed. This review paper focuses on the research progress of xylitol biosynthesis, from overcoming the limitations of traditional chemical hydrogenation and xylose bioconversion, to the full biosynthesis of xylitol production using green and non-polluting glucose as substrate. In the review, the molecular strategies of wild strains to increase xylitol yield, as well as the optimization strategies and metabolic reconfiguration during xylitol biosynthesis are discussed. Subsequently, on the basis of existing studies, the paper further discusses the current status of research and future perspectives of xylitol production using glucose as a single substrate. The evolution of raw materials from xylose-based five-carbon sugars to glucose is not only cost-saving, but also safe and environmentally friendly, which brings new opportunities for the green industrial chain of xylitol.
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Electrocatalytic carbon dioxide/carbon monoxide reduction reaction (CO(2)RR) has emerged as a prospective and appealing strategy to realize carbon neutrality for manufacturing sustainable chemical products. Developing highly active electrocatalysts and stable devices has been demonstrated as effective approach to enhance the conversion efficiency of CO(2)RR. In order to rationally design electrocatalysts and devices, a comprehensive understanding of the intrinsic structure evolution within catalysts and micro-environment change around electrode interface, particularly under operation conditions, is indispensable. Synchrotron radiation has been recognized as a versatile characterization platform, garnering widespread attention owing to its high brightness, elevated flux, excellent directivity, strong polarization and exceptional stability. This review systematically introduces the applications of synchrotron radiation technologies classified by radiation sources with varying wavelengths in CO(2)RR. By virtue of in situ/operando synchrotron radiationanalytical techniques, we also summarize relevant dynamic evolution processes from electronic structure, atomic configuration, molecular adsorption, crystal lattice and devices, spanning scales from the angstrom to the micrometer. The merits and limitations of diverse synchrotron characterization techniques are summarized, and their applicable scenarios in CO(2)RR are further presented. On the basis of the state-of-the-art fourth-generation synchrotron facilities, a perspective for further deeper understanding of the CO(2)RR process using synchrotron radiation analytical techniques is proposed.
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In the context of oxygen evolution reaction (OER), the construction of high-valent transition metal sites to trigger the lattice oxygen oxidation mechanism is considered crucial for overcoming the performance limitations of traditional adsorbate evolution mechanism. However, the dynamic evolution of lattice oxygen during the reaction poses significant challenges for the stability of high-valent metal sites, particularly in high-current-density water-splitting systems. Here, we have successfully constructed Co-O-Fe catalytic active motifs in cobalt-iron Prussian blue analogs (CoFe-PBA) through oxygen plasma bombardment, effectively activating lattice oxygen reactivity while sustaining robust stability. Our spectroscopic and theoretical studies reveal that the Co-O-Fe bridged motifs enable a unique double-exchange interaction between Co and Fe atoms, promoting the formation of high-valent Co species as OER active centers while maintaining Fe in a low-valent state, preventing its dissolution. The resultant catalyst (CoFe-PBA-30) requires an overpotential of only 276 mV to achieve 1000 mA cm-2. Furthermore, the assembled alkaline exchange membrane electrolyzer using CoFe-PBA-30 as anode material achieves a high current density of 1 A cm-2 at 1.76 V and continuously operates for 250 hours with negligible degradation. This work provides significant insights for activating lattice oxygen redox without compromising structure stability in practical water electrolyzers.
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The "Guidelines for parenteral nutrition in preterm infants: the American Society for parenteral and enteral nutrition" were developed by the American Society for Parenteral and Enteral Nutrition and published in the Journal of Parenteral and Enteral Nutrition in September 2023. The guidelines provide recommendations on 12 key clinical questions regarding parenteral nutrition (PN) for preterm infants. In comparison to similar guidelines, this set offers more detailed perspectives on PN for preterm infants. It presents evidence-based recommendations for the commencement time, nutrient dosage, and composition of PN, considering primary outcomes such as growth and development, as well as secondary outcomes like sepsis, retinopathy of prematurity, parenteral nutrition-related liver disease, and jaundice. This article aims to interpret the guidelines to provide a reference for colleagues in the field.
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Nutrición Enteral , Recien Nacido Prematuro , Nutrición Parenteral , Guías de Práctica Clínica como Asunto , Humanos , Nutrición Parenteral/normas , Nutrición Parenteral/métodos , Recién Nacido , Nutrición Enteral/normas , Nutrición Enteral/métodos , Sociedades MédicasRESUMEN
BACKGROUND: Long terminal repeat (LTR)-retrotransposons (LTR-RTs) are ubiquitous and make up the majority of nearly all sequenced plant genomes, whereas their pivotal roles in genome evolution, gene expression regulation as well as their epigenetic regulation are still not well understood, especially in a large number of closely related species. RESULTS: Here, we analyzed the abundance and dynamic evolution of LTR-RTs in 54 species from an economically and agronomically important family, Fabaceae, and also selected two representative species for further analysis in expression of associated genes, transcriptional activity and DNA methylation patterns of LTR-RTs. Annotation results revealed highly varied proportions of LTR-RTs in these genomes (5.1%~68.4%) and their correlation with genome size was highly positive, and they were significantly contributed to the variance in genome size through species-specific unique amplifications. Almost all of the intact LTR-RTs were inserted into the genomes 4 Mya (million years ago), and more than 50% of them were inserted in the last 0.5 million years, suggesting that recent amplifications of LTR-RTs were an important force driving genome evolution. In addition, expression levels of genes with intronic, promoter, and downstream LTR-RT insertions of Glycine max and Vigna radiata, two agronomically important crops in Fabaceae, showed that the LTR-RTs located in promoter or downstream regions suppressed associated gene expression. However, the LTR-RTs within introns promoted gene expression or had no contribution to gene expression. Additionally, shorter and younger LTR-RTs maintained higher mobility and transpositional potential. Compared with the transcriptionally silent LTR-RTs, the active elements showed significantly lower DNA methylation levels in all three contexts. The distributions of transcriptionally active and silent LTR-RT methylation varied across different lineages due to the position of LTR-RTs located or potentially epigenetic regulation. CONCLUSION: Lineage-specific amplification patterns were observed and higher methylation level may repress the activity of LTR-RTs, further influence evolution in Fabaceae species. This study offers valuable clues into the evolution, function, transcriptional activity and epigenetic regulation of LTR-RTs in Fabaceae genomes.
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Fabaceae , Retroelementos , Retroelementos/genética , Epigénesis Genética , Fabaceae/genética , Evolución Molecular , Genoma de Planta , Secuencias Repetidas Terminales/genética , FilogeniaRESUMEN
The progress of effective and durable electrocatalysts for oxygen evolution reaction (OER) is urgent, which is essential to promote the overall efficiency of green hydrogen production. To improve the performance of spinel cobalt-based oxides, which serve as promising water oxidation electrocatalysts in alkaline electrolytes, most researches have been concentrated on cations modification. Here, an anionic regulation mechanism is employed to adopt sulfur(S) anion substitution to supplant NiCo2 O4 by NiCo2 S4 , which contributed to an impressive OER performance in alkali. It is revealed that the substitution of S constructs a sub-stable spinel structure that facilitates its reconstruction into active amorphous oxysulfide under OER conditions. More importantly, as the active phase in the actual reaction process, the hetero-anionic amorphous oxysulfide has an appropriately tuned electronic structure and efficient OER electrocatalytic activity. This work demonstrates a promising approach for achieving anion conditioning-based tunable structure reconstruction for robust and easy preparation spinel oxide OER electrocatalysts.
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Three new cyano-bridged FeII-MoIII complexes assembled from the [MoIII(CN)7]4- unit, FeII ions, and three pentadentate N3O2 ligands, namely {[Fe2H3(dapab)2][Mo(CN)6]}n·2H2O·3.5MeCN (1), [Fe(H2dapb)(H2O)][Fe(Hdapb)(H2O)][Mo(CN)6]·4H2O·3MeCN (2), and [Fe(H2dapba)(H2O)]2[Mo(CN)7]·6H2O (3) (H2dapab = 2,6-diacetylpyridine bis(2-aminobenzoylhydrazone), H2dapb = 2,6-diacetylpyridine bis(benzoylhydrazone), H2dapba = 2,6-diacetylpyridine bis(4-aminobenzoylhydrazone)), have been synthesized and characterized. Single-crystal structure analyses suggest that complex 1 contains a one-dimensional (1D) chain structure where two FeII ions are bridged by the in situ generated [MoIII(CN)6]3- unit through two trans-cyanide groups into trinuclear Fe2IIMoIII clusters that are further linked by the amino of the ligand into an infinite chain. Complexes 2 and 3 are cyano-bridged Fe2IIMoIII trinuclear clusters with two FeII ions connected by the [MoIII(CN)6]3- and [MoIII(CN)7]4- units, respectively. Direct current magnetic studies confirmed the ferromagnetic interactions between the cyano-bridged FeII and MoIII centers and significant easy-axis magnetic anisotropy for all three complexes. Furthermore, complexes 1-3 exhibit slow magnetic relaxation under a zero dc field, with relaxation barriers of 42.3, 21.6, and 14.4 K, respectively, making them the first examples of cyano-bridged FeII-MoIII single-molecule magnets.
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BACKGROUND: Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. METHODS: We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. RESULTS: Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. CONCLUSIONS: We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment.
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Linitis Plástica , Neoplasias Gástricas , Humanos , Linitis Plástica/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Transcriptoma , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Mutación , Proteínas Tirosina Fosfatasas no Receptoras/genética , Proteínas Portadoras/genéticaRESUMEN
OBJECTIVES: The aim of this study was to investigate the computed tomography (CT) features of recurrent acute pancreatitis (RAP) in the early phase and late phase. METHODS: Recurrent acute pancreatitis data were obtained over the past 5 years. Recurrent acute pancreatitis patients were divided into 2 groups according to the time from RAP onset to performing CT examination: the early phase (first week) and late phase (after the first week) based on the 2012 revised Atlanta classification (RAC). Evaluation and comparison of patients' demographic data, RAC, CT findings, CT severity index (CTSI) score, and extrapancreatic inflammation on CT (EPIC) score were conducted in the 2 groups. RESULTS: Hypertriglyceridemia was the most common cause of RAP in 679 of 686 patients (positive CT rate: 98.98%). Among 679 CT-positive patients, interstitial edematous pancreatitis and necrotizing pancreatitis accounted for 61.71% (419/679) and 38.29% (260/679), respectively. The CTSI and EPIC scores were higher in the late phase than in the early phase (both P 's < 0.05). The proportion of moderately severe and severe RAP patients based on RAC was higher in the late phase than in the early phase ( P < 0.05). Early-stage EPIC score was more accurate than CTSI and Acute Physiology and Chronic Health Evaluation (APACHE) II scores in predicting clinically severe RAP (EPIC vs CTSI; EPIC vs APACHE II, both P 's < 0.05). CONCLUSIONS: Recurrent acute pancreatitis is more severe in the late phase than in the early phase. The EPIC score is more indicative of clinically severe RAP than CTSI and APACHE II scores in the early phase of RAP.
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Pancreatitis Aguda Necrotizante , Humanos , Enfermedad Aguda , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Estudios Retrospectivos , Valor Predictivo de las PruebasRESUMEN
CONTEXT: A patient classification-based payment system called diagnosis-intervention packet (DIP) was piloted in a large city in southeast China in 2018. OBJECTIVE: This study evaluates the impact of DIP payment reform on total costs, out-of-pocket (OOP) payments, length of stay (LOS), and quality of care in hospitalised patients of different age. METHODS: An interrupted time series model was employed to examine the monthly trend changes of outcome variables before and after the DIP reform in adult patients, who were stratified into a younger (18-64 years) and an older group (≥ 65 years), further stratified into young-old (65-79 years) and oldest-old (≥ 80 years) groups. RESULTS: The adjusted monthly trend of costs per case significantly increased in the older adults (0.5%, P = 0.002) and oldest-old group (0.6%, P = 0.015). The adjusted monthly trend of average LOS decreased in the younger and young-old groups (monthly slope change: -0.058 days, P = 0.035; -0.025 days, P = 0.024, respectively), and increased in the oldest-old group (monthly slope change: 0.107 days, P = 0.030) significantly. The changes of adjusted monthly trends of in-hospital mortality rate were not significant in all age groups. CONCLUSION: Implementation of the DIP payment reform associated with increase in total costs per case in the older and oldest-old groups, and reduction in LOS in the younger and young-old groups without deteriorating quality of care.
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Gastos en Salud , Pacientes Internos , Anciano , Anciano de 80 o más Años , Humanos , China , Análisis de Series de Tiempo Interrumpido , Tiempo de InternaciónRESUMEN
Co-loading doxorubicin (DOX) and Schizandrin A (SchA) long-circulating liposome (SchA-DOX-Lip) have been confirmed to have good antitumor activity in vitro. However, in vivo pharmacodynamics, targeting, safety, and mechanism of action of SchA-DOX-Lip still need to be further verified. We investigated the tumor inhibition effect, targeting, safety evaluation, and regulation of tumor apoptosis-related proteins of the SchA-DOX-Lip. MTT assay was used to investigate the inhibitory effect of SchA-DOX-Lip on CBRH7919 cells. The drug uptake of CBRH7919 cells was observed by inverted fluorescence microscope. The tumor-bearing nude mice models of CBRH7919 were established, and the anti-tumor effect of SchA-DOX-Lip in vivo was evaluated by tumor biological observation, H&E staining, and TUNEL staining. The distribution and targeting of SchA-DOX-Lip in nude mice models were investigated by small animal imaging and tissue distribution experiment of CBRH7919. The biosafety of SchA-DOX-Lip was evaluated by blood routine parameters, biochemical indexes, and H&E staining. The expression of tumor-associated apoptotic proteins (Bcl-2, Bax, and Caspase-3) was detected by immunohistochemistry anvd western blotting. The results showed that SchA-DOX-Lip had cytotoxicity to CBRH7919 cells which effectively inhibited the proliferation of CBRH7919 cells, improved the uptake of drugs by CBRH7919 cells and the targeting effect of drugs on tumor site. H&E staining and biochemical detection results showed that SchA-DOX-Lip had high biosafety and did not cause serious damage to normal tissues. Western-blotting and TUNEL staining results showed that SchA-DOX-Lip could improve the regulatory effect of drugs on tumor apoptosis proteins. It was demonstrated that SchA-DOX-Lip had high safety and strong tumor inhibition effects, providing a new method for the clinical treatment of hepatocellular carcinoma (HCC).
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Ratones , Liposomas/farmacología , Ratones Desnudos , Neoplasias Hepáticas/tratamiento farmacológico , Carcinoma Hepatocelular/tratamiento farmacológico , Doxorrubicina/farmacología , Apoptosis , Línea Celular TumoralRESUMEN
To investigate the clinical application effects of artificial dermis scaffold and autologous split-thickness skin composite grafts combined with vacuum-assisted closure (V.A.C) in refractory wounds. A retrospective analysis was performed on 70 patients with refractory wounds admitted to the First Affiliated Hospital of Soochow University from June 2019 to December 2021 (44 males and 25 females, with an average age of 49.3 ± 21.4 years). There were 26 patients with chronic ulcers; 3 patients with cancerous wounds; 16 patients with hot crush injuries; and 25 patients with traumatic wounds, including 21 cases of hands, 33 cases of feet, 6 cases of upper limbs, and 10 cases of lower limbs. The patients were divided into an artificial dermis scaffold group (35 patients, including 21 males and 14 females, aged 49.5 ± 21.3 years) and a skin graft group (35 patients, including 23 males and 11 females, aged 49.1 ± 21.5 years). In the artificial dermis scaffold group, after debridement, the artificial dermis scaffold was transplanted for approximately 2 weeks until the wound surface was well vascularized, after which the autologous split-thick skin graft was transplanted. Negative pressure wound therapy was performed throughout the treatment. In the skin grafting group, after debridement, the autologous split-thickness skin graft (aSTSG) was transplanted, and negative pressure wound therapy was performed continuously. The wound healing rate; skin graft survival rate; postoperative wound infection; exudative fluid volume; subcutaneous haematoma; hospitalisation time; hospitalisation cost; Vancouver Scar Scale (VSS) score, used to evaluate the scar of the recipient area at 6 months after the operation; and the sensory disorder grading method, used to evaluate the sensory recovery of the recipient area, were compared between the two groups. All 70 refractory wounds healed. In the artificial dermis scaffold group, the skin graft survival rate was 90% (86%-95%), the hospitalisation time was 38 (29-45) days, the hospitalisation cost was 148 102 (118242-192327) yuan, and the VSS score was 1.9 ± 1.3. There were significant differences in skin graft survival rate (70% [60%-80%]), length of hospital stay (21 [14-28] days), hospitalisation cost (76 201 [39228-135 919] yuan) and VSS score [6.1 ± 3.6] between the skin graft group and the artificial dermis scaffold group (P < .05). The skin graft survival rate, scar hyperplasia and sensory recovery of the recipient area in the artificial dermis scaffold group were better than those in the skin graft group, but the hospitalisation time was relatively longer, and the hospitalisation cost was relatively higher. Wound healing rate, postoperative wound infection, exudate volume, and subcutaneous haematoma of patients in the two groups were similar, and there were no significant differences (P > .05). The artificial dermis scaffold and composite transplantation of autologous aSTSG with V.A.C can promote painless wound healing and improve the skin survival rate, skin colour and lustre, and flexible smooth texture and is conducive to less scar hyperplasia and postoperative functional exercise and recovery. This method provides a reasonable and effective scheme for the treatment of clinical refractory wounds.
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Quemaduras , Terapia de Presión Negativa para Heridas , Piel Artificial , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Trasplante de Piel/métodos , Cicatriz/cirugía , Terapia de Presión Negativa para Heridas/métodos , Estudios Retrospectivos , Hiperplasia , Infección de la Herida Quirúrgica/cirugía , Dermis , Quemaduras/cirugíaRESUMEN
Herein we report the first method for highly enantioselective Brønsted acid catalyzed Heyns rearrangements. These reactions, catalyzed by a chiral spiro phosphoric acid, afforded synthetically valuable chiral α-aryl-α-aminoketones which cannot be obtained by means of previously reported Heyns rearrangement methods. This method features low catalyst loadings, high yields and high enantioselectivities, making these reactions highly practical. We used the method to efficiently synthesize various chiral amines, including some biologically active molecules. We experimentally proved that these acid-catalyzed Heyns rearrangements proceeded via a proton-transfer process involving an enol intermediate and the stereocontrol was realized during the proton-transfer step.