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Immunological adjuvants are vaccine components that enhance long-lasting adaptive immune responses to weakly immunogenic antigens. Monophosphoryl lipid A (MPLA) is a potent and safe vaccine adjuvant that initiates an early innate immune response by binding to the Toll-like receptor 4 (TLR4). Importantly, the binding and recognition process is highly dependent on the monomeric state of MPLA. However, current vaccine delivery systems often prioritize improving the loading efficiency of MPLA, while neglecting the need to maintain its monomeric form for optimal immune activation. Here, we introduce a Pickering emulsion-guided MPLA monomeric delivery system (PMMS), which embed MPLA into the oil-water interface to achieve the monomeric loading of MPLA. During interactions with antigen-presenting cells, PMMS functions as a chaperone for MPLA, facilitating efficient recognition by TLR4 regardless of the presence of lipopolysaccharide-binding proteins. At the injection site, PMMS efficiently elicited local immune responses, subsequently promoting the migration of antigen-internalized dendritic cells to the lymph nodes. Within the draining lymph nodes, PMMS enhanced antigen presentation and maturation of dendritic cells. In C57BL/6 mice models, PMMS vaccination provoked potent antigen-specific CD8+ T cell-based immune responses. Additionally, PMMS demonstrated strong anti-tumor effects against E.G7-OVA lymphoma. These data indicate that PMMS provides a straightforward and efficient strategy for delivering monomeric MPLA to achieve robust cellular immune responses and effective cancer immunotherapy.
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OBJECTIVE: This study aimed to evaluate the current situation of Chinese mobile apps for hypertension management and explore patients' real requirements for app use, providing a theoretical basis for the future improvement of hypertension apps. METHODS: We reviewed hypertension management apps from mobile app platforms, and summarized their functional characteristics. In addition, we conducted an online survey among 1000 hypertensive patients, collected valid responses, and analyzed the feedback data. RESULTS: Forty hypertension management apps were analyzed, with 72.5% offering no more than six functions, indicating limited coverage of advanced and comprehensive functionalities. Among the 934 valid survey responses, patients emphasized four main functions in apps for hypertension management: long-term dynamic blood pressure monitoring, scientific lifestyle management, strict medication management and systematic health knowledge delivering. CONCLUSION: The existing hypertension management apps mainly serve as "Digital Health" tools with unclear clinical efficacy. The future development of these apps lies in how they transition to "Digital Therapeutics" solutions to better meet patients' needs and provide clear clinical advantages.
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Hipertensión , Aplicaciones Móviles , Humanos , Aplicaciones Móviles/tendencias , Aplicaciones Móviles/estadística & datos numéricos , Hipertensión/terapia , China , Encuestas y Cuestionarios , Telemedicina/tendencias , Masculino , Femenino , Persona de Mediana Edad , Adulto , Manejo de la Enfermedad , Pueblos del Este de AsiaRESUMEN
mRNA delivery systems, such as lipid nanoparticle (LNP), have made remarkable strides in improving mRNA expression, whereas immune system activation operates on a threshold. Maintaining a delicate balance between antigen expression and dendritic cell (DC) activation is vital for effective immune recognition. Here, a water-in-oil-in-water (w/o/w) Pickering emulsion stabilized with calcium phosphate nanoparticles (CaP-PME) is developed for mRNA delivery in cancer vaccination. CaP-PME efficiently transports mRNA into the cytoplasm, induces pro-inflammatory responses and activates DCs by disrupting intracellular calcium/potassium ions balance. Unlike LNP, CaP-PME demonstrates a preference for DCs, enhancing their activation and migration to lymph nodes. It elicits interferon-γ-mediated CD8+ T cell responses and promotes NK cell proliferation and activation, leading to evident NK cells infiltration and ameliorated tumor microenvironment. The prepared w/o/w Pickering emulsion demonstrates superior anti-tumor effects in E.G7 and B16-OVA tumor models, offering promising prospects as an enhanced mRNA delivery vehicle for cancer vaccinations.
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BACKGROUND: The achievement of optimal vaccine efficacy is contingent upon the collaborative interactions between T and B cells in adaptive immunity. Although multiple immunization strategies have been proposed, there is a notable scarcity of comprehensive investigations pertaining to enhance immune effects through immune strategy adjustments for individual vaccine. METHODS: The hierarchically structured aluminum hydroxide microgel-stabilized Pickering emulsion (ASPE) was prepared by ultrasonic method. This study explored the influence of the immune strategy of ASPE to immune responses, including antigen exposure pattern, adjuvants and antigen dosage, and administration interval. RESULTS: The findings revealed that external antigen adsorption facilitated increased exposure of antigen epitopes, leading to elevated IgG titers and secretion of cytokines such as interferon-gamma (IFN-γ) or interleukin-4 (IL-4). Additionally, even a low dose (1 µg/dose) of antigens of ASPE boosted sufficient neutralizing antibody levels and memory T cells compared to high-dose antigens, which consistent with the adjuvant dosage effect. Furthermore, maintaining a 4-week immunization interval yielded optimal levels of antigen-specific IgG titers in both short-term and long-term scenarios, as compared to intervals of 2, 3, and 5 weeks. A consistent trend was observed in the proliferation of memory B cells, reaching a superior level at the 4-week interval, which could enhance protection against viral re-infection. CONCLUSION: Tailoring immunization strategies for specific vaccines has emerged as powerful driver in maximizing vaccine efficacy and eliciting robust immune responses, thereby presenting cutting-edge approaches to enhanced vaccination.
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Cerebral infarction (CI) is a common cerebrovascular disease worldwide, and the burden caused by the sequelae of CI has increased significantly. However, current treatment guidelines lack standardized recommendations for pharmacotherapy of sequelae of CI. This retrospective study collected and analyzed 1.98 million prescriptions concerning sequelae of CI from patients admitted to Zhiyun Health Internet Hospital in 2022. The mean age of patients was 66.2 ± 11.4 years, and 52.40% were male. 79.73% had one or more comorbidities. For treatment, the prescriptions of 1-, 2- and ≥ 3-drug accounted for 64.55%, 23.77% and 11.68% respectively. Chinese patent medicine (CPM) prescriptions, western medicine (WM) prescriptions, and CPM and WM combined (CPM + WM) prescriptions accounted for 53.81%, 27.33%, and 18.86% respectively. In CPM prescriptions, the most frequently prescribed medications were Salvia miltiorrhiza (34.81%), Ginkgo biloba (24.96%), Panax notoginseng (20.67%), Gastrodia (7.15%) and Ligusticum Wallichii (4.90%). For WM prescriptions, the most commonly prescribed agents were anti-hypertensive (32.82%), anti-thrombotic (16.06%), vasodilator (15.70%), anti-dementia (10.88%), and lipid-lowering (9.58%) drugs. Among CPM + WM prescriptions, 72.61% had CPM/WM = 1, 21.20% had CPM/WM < 1, and 6.19% had CPM/WM > 1. This research utilized real-world data extracted from internet hospitals in China to present valuable evidence of online prescription patterns among patients experiencing sequelae of CI.
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Infarto Cerebral , Humanos , Masculino , Femenino , Infarto Cerebral/tratamiento farmacológico , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Medicamentos Herbarios Chinos/uso terapéutico , China/epidemiología , Prescripciones de Medicamentos/estadística & datos numéricos , Medicina Tradicional China/métodos , InternetRESUMEN
(1) Background: The research group has developed a new small molecule, 6-Isopropyldithio-2'-deoxyguanosine analogs-YLS004, which has been shown to be the most sensitive in acute T-lymphoblastic leukemia cells. Moreover, it was found that the structure of Nelarabine, a drug used to treat acute T-lymphoblastic leukemia, is highly similar to that of YLS004. Consequently, the structure of YLS004 was altered to produce a new small molecule inhibitor for this study, named YLS010. (2) Results: YLS010 has exhibited potent anti-tumor effects by inducing cell apoptosis and ferroptosis. A dose gradient was designed for in vivo experiments based on tentative estimates of the toxicity dose using acute toxicity in mice and long-term toxicity in rats. The study found that YLS010 at a dose of 8 mg/kg prolonged the survival of late-stage acute T-lymphoblastic leukemia mice in the mouse model study. (3) Conclusions: YLS010 has demonstrated specific killing effects against acute T-lymphoblastic leukemia both in vivo and in vitro. Preclinical studies of YLS010 offer a new opportunity for the treatment of patients with acute T-lymphoblastic leukemia in clinical settings.
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BACKGROUND: Although DHFR gene amplification has long been known as a major mechanism for methotrexate (MTX) resistance in cancer, the early changes and detailed development of the resistance are not yet fully understood. METHODS: We performed genomic, transcriptional and proteomic analyses of human colon cancer cells with sequentially increasing levels of MTX-resistance. RESULTS: The genomic amplification evolved in three phases (pre-amplification, homogenously staining region (HSR) and extrachromosomal DNA (ecDNA)). We confirm that genomic amplification and increased expression of DHFR, with formation of HSRs and especially ecDNAs, is the major driver of resistance. However, DHFR did not play a detectable role in the early phase. In the late phase (ecDNA), increase in FAM151B protein level may also have an important role by decreasing sensitivity to MTX. In addition, although MSH3 and ZFYVE16 may be subject to different posttranscriptional regulations and therefore protein expressions are decreased in ecDNA stages compared to HSR stages, they still play important roles in MTX resistance. CONCLUSION: The study provides a detailed evolutionary trajectory of MTX-resistance and identifies new targets, especially ecDNAs, which could help to prevent drug resistance. It also presents a proof-of-principal approach which could be applied to other cancer drug resistance studies.
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Resistencia a Antineoplásicos , Amplificación de Genes , Metotrexato , Tetrahidrofolato Deshidrogenasa , Humanos , Metotrexato/farmacología , Resistencia a Antineoplásicos/genética , Tetrahidrofolato Deshidrogenasa/genética , Tetrahidrofolato Deshidrogenasa/metabolismo , Línea Celular Tumoral , Neoplasias del Colon/genética , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Antimetabolitos Antineoplásicos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Genómica/métodosRESUMEN
BACKGROUND: Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 2 (APOBEC2) is associated with nucleotide alterations in the transcripts of tumor-related genes which are contributed to carcinogenesis. Expression and prognosis value of APOBEC2 in stomach adenocarcinoma (STAD) remains unclear. METHODS: The APOBEC2 gene alteration frequency of STAD and APOBEC2 gene expression in STAD and normal tissues were investigated in cBioportal and GEPIA, respectively. We detected expression of APOBEC2, infiltration of CD66b+ tumor-associated neutrophils and CD163+ tumor-associated macrophages in tissue microarrays by immunohistochemistry. APOBEC2 gene expression was explored by western blot and qRT-PCR. Relationships between APOBEC2 and CD66b, CD163, and other clinicopathological characteristics were investigated. Associations among APOBEC2 expression status and patient survival outcome were further analyzed. RESULTS: APOBEC2 gene alteration frequency was 5%, and APOBEC2 gene was downexpressed in STAD compared to normal tissues (P < 0.05). APOBEC2 expression status were associated with the infiltration of CD66b+ TANs, differentiation grade, TNM stage, histological type and gender (all P < 0.05) in STAD. Little or no APOBEC2 expression was detected in STAD and adjacent normal tissues by western blot. We failed to show that APOBEC2 was an independent risk factor for OS (Hazard Ratio 0.816, 95%CI 0.574-1.161, P = 0.259) or DFS (Hazard Ratio 0.821, 95%CI 0.578-1.166, P = 0.270) in STAD by multivariate Cox regression analysis, but APOBEC2 negative subgroup has a worse OS and DFS among patients with adjuvant chemotherapy. CONCLUSIONS: APOBEC2 correlates with CD66b, differentiation grade, TNM stages, histological classification, and gender in STAD. APOBEC2 is not an independent prognostic factor for STAD, our results suggest that patients with positive APOBEC2 can benefit from postoperative chemotherapy, and combination of APOBEC2 and CD66b is helpful to further stratify patients into different groups with distinct prognoses.
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Desaminasas APOBEC , Adenocarcinoma , Neoplasias Gástricas , Humanos , Adenocarcinoma/patología , Desaminasas APOBEC/metabolismo , Proteínas Musculares , Neutrófilos/patología , Nucleótidos/metabolismo , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias Gástricas/metabolismoRESUMEN
Although past experimental and theoretical research has made substantial progress in understanding evaporation behaviors in various suspensions, the fundamental mechanism for polymer sessile droplets is still lacking. One critical effect is the molecular weight on the evaporation behaviors. Here, systematic experiments are carried out to investigate the evaporation behavior of polymer droplets under the effects of polymer concentration, evaporation rate, and especially molecular weight. We obtain polymer films with various morphologies with molecular weights ranging from 2 orders of magnitude to 4 orders of magnitude and polymer concentration across 4 orders of magnitude. We further develop a theoretical model based on the Onsager principle to explain the evaporation mechanism from a dynamic perspective. Analysis indicates that increasing molecular weight or polymer concentration enhances the contact angle hysteresis and slows down the evaporation, resulting in the transition from multiring to coffee ring and eventually to uniform films. The findings offer a guideline for achieving the desired deposition patterns via droplet processing techniques.
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BACKGROUND: It has been demonstrated that circularRNA (circRNAs) plays a critical role in various cancers. While the potential molecular mechanism of circRNAs in the progression of colorectal cancer (CRC) remains uncertain. METHODS: Differentially expressed circRNAs were identified by RNA sequencing. RT-qPCR detected the expression of circ_0009092, miR-665, and NLK in CRC tissues and cells. Functions of circ_0009092 on tumor cell proliferation, migration, and invasion were investigated by a series of in vitro assays. The underlying mechanism of circ_0009092 was explored by bioinformatics analysis, RNA immunoprecipitation (RIP) and luciferase assays. A co-culture assay in vitro was performed to detect the affection of circ_0009092 on macrophage recruitment in the tumor microenvironment (TME). A xenograft mouse model was used to explore the effect of circ_0009092 on tumor growth. RESULTS: Circ_0009092 was downregulated in CRCand predicted a good prognosis. Overexpression of circ_0009092 reduced tumor cell EMT, proliferation, migration, and invasion in vitro and in vivo. Mechanistically, circ_0009092 elevated the NLK expression via sponging miR-665 and suppressed the Wnt/ß-catenin signaling pathway. EIF4EA3 induced circ_0009092 expression in CRC cells. In addition, NLK regulates phosphorylation and O-GlcNAcylation of STAT3 by binding to STAT3, thereby inhibiting CCL2 expression, in which it inhibits macrophage recruitment in the tumor microenvironment (TME). CONCLUSION: EIF4A3 suppressed circ_0009092 biogenesis, whichinhibits CRC progression by sponging miR-665 to downregulate NLK. Circ_0009092/miR-665/NLK suppressed tumor EMT, proliferation, migration, and invasion by acting on the Wnt/ß-catenin signaling pathway. NLK directly interacted with STAT3 and decreased the CCL2 expression, inhibiting the recruitment of tumor-associated macrophages (TAMs) in the TME. Our study provided novel insights into the roles of circ_0009092 as a novel promising prognostic and therapeutic target in CRC.
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Neoplasias Colorrectales , MicroARNs , Humanos , Animales , Ratones , ARN Circular/genética , ARN Circular/metabolismo , Macrófagos Asociados a Tumores/metabolismo , Microambiente Tumoral/genética , Línea Celular Tumoral , Neoplasias Colorrectales/patología , MicroARNs/genética , MicroARNs/metabolismo , Vía de Señalización Wnt , Proliferación Celular/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Factor 4A Eucariótico de Iniciación/metabolismo , ARN Helicasas DEAD-box/metabolismoRESUMEN
Extrachromosomal DNAs (ecDNAs), also known as double minutes (DMs), can induce a fast increase in gene copy numbers and promote the development of cancer, including drug resistance. MutS homolog 3 (MSH3), a key protein in mismatch repair, has been indicated to participate in the regulation of DNA doublestrand break (DSB) repair, which has been reported to be associated with the formation of ecDNAs. However, it remains unclear whether MSH3 can influence drug resistance via ecDNAs in cancer. In the present study, high MSH3 expression was observed in methotrexate (MTX)resistant HT29 cells [DM and homogeneously staining region (HSR)containing cells] compared with parental HT29 cells. Additionally, decreased amounts of ecDNAs, HSRs and amplified genes locating on ecDNAs and HSRs were detected following depletion of MSH3 and this could be reversed by overexpressing MSH3 in DMcontaining cells. No corresponding changes were found in HSRcontaining cells. The present study further verified the involvement of MSH3regulated DNA DSB repair pathways in the formation of ecDNAs by detecting the expression of core proteins and pathway activity. Furthermore, expulsion of ecDNAs/HSRs was detected and increased frequencies of micronuclei/nuclear buds with dihydrofolate reductase (DHFR) signals were observed in MSH3depleted DMcontaining cells. Finally, changes in MSH3 expression could affect DHFR amplificationderived DHFR expression and cell sensitivity to MTX, suggesting that MSH3 may influence cancer drug resistance by altering the amount of ecDNAs. In conclusion, the present study revealed a novel mechanism involving MSH3 in the regulation of ecDNAs by DSB repair, which will have clinical value in the treatment of ecDNAbased drug resistance in cancer.
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Neoplasias Colorrectales , Metotrexato , Humanos , Metotrexato/farmacología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Reparación del ADN , Aberraciones Cromosómicas , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , ADN , Proteína 3 Homóloga de MutS/genética , Proteína 3 Homóloga de MutS/metabolismoRESUMEN
Widening the photoresponse range while enhancing the electrical properties of semiconductors could reduce the complexity and cost of photodetectors or increase the power conversion efficiency of solar cells. Surface doping through charge transfer with organic species is one of the most effective and widely used approaches to achieve this aim. It usually features easier preparation over other doping methods but is still limited by the low physicochemical stability and high cost of the used organic species or low improvement of electrical properties. This work shows unprecedented surface doping of semiconductors with highly stable, easily obtained, and strong electron-accepting viologen components, realizing the significant improvement of both the photoresponse range and conductivity. Coating the chalcogenide semiconductor KGaS2 with dimethyl viologen dichloride (MV) yields a charge-transfer complex (CTC) on the surface, which broadens the photoresponse range by nearly 300 nm and improves the conductivity by 5 orders of magnitude. The latter value surpasses all records obtained by surface doping through charge transfer with organic species.
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Peritoneal metastasis (PM) is a frequent manifestation of advanced abdominal malignancies. Accurately assessing the extent of PM before surgery is essential for patients to receive optimal treatment. Therefore, we propose to construct a deep learning (DL) model based on enhanced computed tomography (CT) images to stage PM preoperatively in patients. All 168 patients with PM underwent contrast-enhanced abdominal CT before either open surgery or laparoscopic exploration, and peritoneal cancer index (PCI) was used to evaluate patients during the surgical procedure. DL features were extracted from portal venous-phase abdominal CT scans and subjected to feature selection using the Spearman correlation coefficient and LASSO. The performance of models for preoperative staging was assessed in the validation cohort and compared against models based on clinical and radiomics (Rad) signature. The DenseNet121-SVM model demonstrated strong patient discrimination in both the training and validation cohorts, achieving AUC was 0.996 in training and 0.951 validation cohort, which were both higher than those of the Clinic model and Rad model. Decision curve analysis (DCA) showed that patients could potentially benefit more from treatment using the DL-SVM model, and calibration curves demonstrated good agreement with actual outcomes. The DL model based on portal venous-phase abdominal CT accurately predicts the extent of PM in patients before surgery, which can help maximize the benefits of treatment and optimize the patient's treatment plan.
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Aprendizaje Profundo , Neoplasias Peritoneales , Humanos , Neoplasias Peritoneales/diagnóstico por imagen , Neoplasias Peritoneales/cirugía , Peritoneo/diagnóstico por imagen , Peritoneo/cirugía , Tomografía Computarizada por Rayos X , Estudios RetrospectivosRESUMEN
Lanthanide ions are widely used as dopants for halide perovskites for their broad energy level coverage from the visible to near-infrared (NIR) range. In this work, Cs2NaScCl6:Er3+ was synthesized by an improved solid-state reaction method, which showed effective NIR emission under ultraviolet excitation. Through calculations based on density functional theory and Bader charge analysis, it is shown that [ErCl6]3- octahedra show a strong localization effect in the Cs2NaScCl6:Er3+ lattice, which is conducive to the charge transfer process of Cl-Er3+, and charge transfer sensitization is responsible for the efficient visible to NIR luminescence of Er3+, where the NIR emission around λem = 1540 nm originated from the Er3+:4I13/2 â 4I15/2 transition with an ultrahigh photoluminescence quantum yield that reached â¼28.3%. Notably, Cs2NaScCl6:Er3+ also exhibited bright upconversion luminescence of green light (at 540 nm) under excitation by a variety of NIR laser diodes (808, 980, and 1550 nm) via self-sensitization processes.
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The neuroprotective role of 5-hydroxymethyl-2-furfural (5-HMF) has been demonstrated in a variety of neurological diseases. The aim of this study is to investigate the effect of 5-HMF on multiple sclerosis (MS). IFN-γ-stimulated murine microglia (BV2 cells) are considered a cell model of MS. With 5-HMF treatment, microglial M1/2 polarization and cytokine levels are detected. The interaction of 5-HMF with migration inhibitory factor (MIF) is predicted using online databases. The experimental autoimmune encephalomyelitis (EAE) mouse model is established, followed by a 5-HMF injection. The results show that 5-HMF facilitates IFN-γ-stimulated microglial M2 polarization and attenuates the inflammatory response. According to the network pharmacology and molecular docking results, 5-HMF has a binding site for MIF. Further results show that blocking MIF activity or silencing CD74 enhances microglial M2 polarization, reduces inflammatory activity, and prevents ERK1/2 phosphorylation. 5-HMF inhibits the MIF-CD74 interaction by binding to MIF, thereby inhibiting microglial M1 polarization and enhancing the anti-inflammatory response. 5-HMF ameliorates EAE, inflammation, and demyelination in vivo. In conclusion, our research indicates that 5-HMF promotes microglial M2 polarization by inhibiting the MIF-CD74 interaction, thereby attenuating inflammation and demyelination in EAE mice.
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Encefalomielitis Autoinmune Experimental , Factores Inhibidores de la Migración de Macrófagos , Animales , Ratones , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Ratones Endogámicos C57BL , Microglía/metabolismo , Simulación del Acoplamiento MolecularRESUMEN
The COVID-19 pandemic is a huge public health crisis in the 21st century. In addition to the acute symptoms, a considerable proportion of patients worldwide have suffered from post-COVID-19 syndrome, commonly known as Long COVID. The impact of Long COVID on individual and public health burden cannot be ignored. According to recent researches, Long COVID has been affecting multiple organ systems throughout the body, with respiratory, mental, nervous and digestive symptoms often seen in Chinese population. Clinical studies have proved that symptoms were alleviated by a variety of treatments, such as physical therapy, rehabilitation training, psychological support, behavioral cognitive therapy, stem cell therapy, etc. Based on the current clinical evidence, it is recommended to strengthen the scientific research on Long COVID and actively carry out early monitoring and intervention in the future, so as to effectively prevent the long-term disease burden and economic pressure.
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Background: Nicotinamide N-methyltransferase (NNMT) and Dickkopf-1 (DKK1) play an important role in the development of breast cancer, and the purpose of this study was designed to examine the clinical and prognostic significance of NNMT and DKK1 in breast cancer. Methods: The GEPIA2 database was used to evaluate the expression and survival of NNMT mRNA and DKK1 mRNA of breast cancer. Then an immunohistochemical study was carried out on 374 cases of breast tissue to identify the protein expression and significance of NNMT and DKK1. Next, the prognostic significance of DKK1 in breast cancer was explored by COX and Kaplan-Meier models. Results: Protein NNMT expression was correlated with lymph node metastasis and histological grade (P < .05) while protein DKK1 expression was related to tumor size, pT stage, histological grade, and Ki-67 (P < .05). Protein DKK1 was related to disease-specific survival (DSS), and low DKK1 expression indicated a poor prognosis of breast cancer patients (P < .05). Combined expression of protein NNMT and protein DKK1 predicted different prognosis of DSS (P < .05). Conclusions: Nicotinamide N-methyltransferase and DKK1 were linked to breast cancer malignancy and invasion. Breast cancer patients with low DKK1 expression had a worse prognosis. Oncotypes of NNMT and DKK1 expression predicted patient outcomes.
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Liquid-liquid phase separation at complex interfaces is a common phenomenon in biological systems and is also a fundamental basis to create synthetic materials in multicomponent mixtures. Understanding the liquid-liquid phase separation in well-defined macromolecular systems is anticipated to shed light on similar behaviors in cross-disciplinary areas. Here we study a series of immiscible polymers and reveal a generic phase diagram of liquid-liquid phase separation at double emulsion interfaces, which depicts the equilibrium structures by interfacial tension and polymer fraction. We further reveal that the interfacial tensions in various systems fall on a linear relationship with spreading coefficients. Based on this theoretical guideline, the liquid-liquid phase separation can be modulated by a low fraction of amphiphilic block copolymers, leading the double emulsion droplets configurable between compartments and anisotropic shapes. The solidified anisotropic microcapsules could provide unique orientation-sensitive optical properties and thermomechanical responses. The theoretical analysis and experimental protocol in this study yield a generalizable strategy to prepare multiphase double emulsions with controlled structures and desired properties.
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OBJECTIVE: To explore the rapid evaluation of the early pathogen of severe Chlamydophila psittaci pneumonia by bedside diagnostic bronchoscopy, so as to start effective anti-infection treatment before the results of macrogenome next generation sequencing (mNGS) test. METHODS: The clinical data of three patients with severe Chlamydophila psittaci pneumonia who were successfully treated in the First Affiliated Hospital of Xinjiang Medical University, the First People's Hospital of Aksu District, and the First Division Hospital of Xinjiang Production and Construction Corps from October 2020 to June 2021 were retrospectively analyzed, including the rapid assessment of early pathogens by bedside diagnostic bronchoscopy and the use of antibiotics to start anti-infection treatment. These patients were successfully treated. RESULTS: The three patients were male, aged 63, 45 and 58 years old, respectively. Before the onset of the penumonia, they had a clear medical history of bird exposure. The clinical manifestations mainly included fever, dry cough, shortness of breath and dyspnea. One case had abdominal pain and lethargy. The results of laboratory examination indicated that the peripheral blood white blood cell count (WBC) of two patients were high [(10.2-11.9)×109/L], the percentage of neutrophils increased (85.2%-94.6%) and the percentage of lymphocytes decreased (3.2%-7.7%) in all 3 patients after admission to hospital and entering into intensive care unit (ICU). The procalcitonin (PCT) of 3 patients increased after admission, and still increased when entering ICU (0.3-4.8 ng/L), so did C-reactive protein (CRP, 58.0-162.0 mg/L) and erythrocyte sedimentation rate (ESR, 36.0-90.0 mm/1 h). After admission, serum alanine transaminase (ALT) increased in 2 cases (136.7 U/L, 220.5 U/L), so did aspartate transaminase (AST) in 2 cases (249.6 U/L, 164.2 U/L). ALT (162.2-267.9 U/L) and AST (189.8-223.2 U/L) increased in 3 patients when they entered ICU. The level of serum creatinine (SCr) of 3 patients were normal after admission and entering ICU. The chest computed tomography (CT) findings of 3 patients were acute interstitial pneumonia, bronchopneumonia and lung consolidation, of which 2 cases were accompanied by a small amount of pleural effusion, and 1 case was accompanied by more regular small air sacs. Multiple lung lobes were involved, but mainly one lung lobe. The oxygenation index (PaO2/FiO2) of the 3 patients admitting to ICU were 100.0, 57.5 and 105.4 mmHg (1 mmHg ≈ 0.133 kPa), respectively, which met with the diagnostic criteria of moderate and severe acute respiratory distress syndrome (ARDS). All three patients received endotracheal intubation and mechanical ventilation. Under the bedside bronchoscope, the bronchial mucosa of 3 patients were obviously congested and edematous, without purulent secretion, and there was 1 case with mucosal hemorrhage. Three patients underwent bedside diagnostic bronchoscopy, and the evaluation result of the pathogen was that it might be atypical pathogen infection, so they were given moxifloxacin, cisromet and doxycycline intravenously, respectively, and combined with carbapenem antibiotics intravenously. After 3 days, the detection results of mNGS in bronchoalveolar lavage fluid (BALF) showed that only Chlamydia psittaci was infected. At this time, the condition was significantly improved, and PaO2/FiO2 was significantly increased. Therefore, the antibiotic treatment scheme remained unchanged, and mNGS only served to verify the initial diagnosis. Two patients were extubated on the 7th and 12th day of admission to the ICU, respectively, while one patient was extubated on the 16th day of admission to the ICU due to nosocomial infection. All 3 patients were transferred to the respiratory ward after the condition was stable. CONCLUSIONS: The bedside diagnostic bronchoscopy based on clinical characteristics is conducive to not only the rapid assessment of the early pathogens of severe Chlamydia psittaci pneumonia, but also effective anti-infection treatment before the returning of mNGS test results, which can make up for the lag and uncertainty of the mNGS test results.
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Chlamydophila psittaci , Neumonía , Animales , Humanos , Masculino , Persona de Mediana Edad , Antibacterianos , Aspartato Aminotransferasas , Broncoscopía , Hospitalización , Estudios RetrospectivosRESUMEN
Farnesoid X receptor (FXR) is a nuclear receptor known to play protective roles in anti-hepatocarcinogenesis and regulation of the basal metabolism of glucose, lipids, and bile acids. FXR expression is low or absent in HBV-associated hepatocarcinogenesis. Full-length HBx and HBx C-terminal truncation are frequently found in clinical HCC samples and play distinct roles in hepatocarcinogenesis by interacting with FXR or FXR signaling. However, the impact of C-terminal truncated HBx on the progression of hepatocarcinogenesis in the absence of FXR is unclear. In this study, we found that one known FXR binding protein, a C-terminal truncated X protein (HBx C40) enhanced obviously and promoted tumor cell proliferation and migration by altering cell cycle distribution and inducing apoptosis in the absence of FXR. HBx C40 enhanced the growth of FXR-deficient tumors in vivo. In addition, RNA-sequencing analysis showed that HBx C40 overexpression could affect energy metabolism. Overexpressed HSPB8 aggravated the metabolic reprogramming induced by down-regulating glucose metabolism-associated hexokinase 2 genes in HBx C40-induced hepatocarcinogenesis. Overall, our study suggests that C-terminal truncated HBx C40 synergizes with FXR deficiency by altering cell cycle distribution as well as disturbing glucose metabolism to promote HCC development.