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Objectives: The objective of this study was to investigate the predictive value of erythrocyte distribution width-to-platelet ratio (RPR) combined with procalcitonin (PCT) on 28-day mortality in patients with sepsis. Methods: A total of 193 patients with sepsis admitted to the Affiliated Hospital of Southwest Medical University from January 2013 to January 2018 were selected as the study objects. Univariate and multivariate analyses were used to understand the indicators related to the 28-day prognosis of patients, and the ROC curve was further drawn. The Kaplan-Meier curve was used to evaluate the prognosis of patients. Results: A total of 193 patients were enrolled and divided into the survivor group (=156) and nonsurvivor group (=37) according to the prognosis within 28 days. The median age was 62.5 years, and 64.7% were males. Multivariate analysis showed that PCT and RPR were independent risk factors for 28-day prognosis in sepsis patients. The area under the ROC curve of PCT and RPR were 0.894 and 0.861, respectively, and the cutoff values were 27.04 and 0.12, respectively. Survival curve analysis showed that PCT and RPR were associated with the 28-day prognosis of patients, and the combination of PCT and RPR had a better predictive effect. Conclusions: PCT and RPR are independent predictors of sepsis prognosis. The combined application of PCT and RPR (PCT-RPR) can further improve the predictive performance and provide a reference for the clinical diagnosis, treatment, and prognosis evaluation of sepsis patients.
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ETHNOPHARMACOLOGICAL RELEVANCE: Hyssopus cuspidatus Boriss., a classic Uyghur medicine, is used to treat inflammatory lung diseases such as asthma. But the therapeutic effect and mechanism of the volatile oil of Hyssopus cuspidatus Boriss.(HVO) in asthma therapy remain unclear. AIM OF THE STUDY: We aim to characterize the constituents of HVO, investigate the therapeutic effect in OVA-induced allergic asthmatic mice and further explore the molecular mechanism. MATERIALS AND METHODS: In this study, we applied two-dimensional gas chromatography quadrupole time-of-flight mass spectrometry (GC × GC-QTOF MS) to identify the ingredients of HVO. We established OVA-induced asthmatic model to investigate the therapeutic effect of HVO. To further explore the potential molecular pathways, we used network pharmacology approach to perform GO and KEGG pathways enrichment, and then built an ingredient-target-pathway network to identify key molecular pathways. Finally, LPS-induced RAW 264.7 macrophages and OVA-induced asthmatic model were used to validate the potential signaling pathways. RESULTS: GC × GC-QTOF MS analysis revealed the presence of 123 compounds of HVO. The sesquiterpenes and monoterpenes are the main constituents. The in vivo study indicated that HVO suppressed OVA-induced eosinophilic infiltration in lung tissues, inhibited the elevation of IgE, IL-4, IL-5, and IL-13 levels, downregulated the expressions of phosphorylated PI3K, Akt, JNK and P38, and maintained epithelial barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin. The in vitro study also revealed an inhibition of NO release and downregulation of phosphorylated PI3K, Akt, JNK and P38 levels. CONCLUSION: HVO alleviates airway inflammation in OVA-induced asthmatic mice by inhibiting PI3K/Akt/JNK/P38 signaling pathway and maintaining airway barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin.
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Asma , Aceites Volátiles , Ovalbúmina , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Animales , Femenino , Ratones , Antiasmáticos/farmacología , Asma/tratamiento farmacológico , Asma/inducido químicamente , Modelos Animales de Enfermedad , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones Endogámicos BALB C , Aceites Volátiles/farmacología , Aceites Volátiles/química , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pyroglyphidae/inmunología , Células RAW 264.7 , Transducción de Señal/efectos de los fármacosRESUMEN
The role of melatonin (MT), an essential phytohormone controlling the physiological and biochemical reactions of plants to biotic and abiotic stress, in alleviating pesticide phytotoxicity remains unclear. This study explores the effects of MT (0 and 200 mg/L) and six doses of fluroxypyr-meptyl (FLUME) (0-0.14 mg/L) on the physiological response of rice (Oryza sativa). FLUME exposure inhibited the growth of rice seedlings, with MT treatment ameliorating this effect. To determine the biochemical processes and catalytic events involved in FLUME breakdown in rice, six rice root and shoot libraries exposed to either FLUME or FLUME-MT were generated and then subjected to RNA-Seq-LC-Q-TOF-HRMS/MS analyses. The results showed that 1510 root genes and 139 shoot genes exhibited higher upregulation in plants treated with an ecologically realistic FLUME concentration and MT than in those treated with FLUME alone. Gene enrichment analysis revealed numerous FLUME-degradative enzymes operating in xenobiotic tolerance to environmental stress and molecular metabolism. Regarding the FLUME degradation process, certain differentially expressed genes were responsible for producing important enzymes, such as cytochrome P450, glycosyltransferases, and acetyltransferases. Four metabolites and ten conjugates in the pathways involving hydrolysis, malonylation, reduction, glycosylation, or acetylation were characterized using LC-Q-TOF-HRMS/MS to support FLUME-degradative metabolism. Overall, external application of MT can increase rice tolerance to FLUME-induced oxidative stress by reducing phytotoxicity and FLUME accumulation. This study provides insights into MT's role in facilitating FLUME degradation, with potential implications for engineering genotypes supporting FLUME degradation in paddy crops.
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Melatonina , Oryza , Oryza/efectos de los fármacos , Oryza/metabolismo , Oryza/genética , Oryza/crecimiento & desarrollo , Melatonina/farmacología , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Brotes de la Planta/efectos de los fármacos , Brotes de la Planta/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacosAsunto(s)
Neoplasias Testiculares , Humanos , Masculino , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patología , Diagnóstico Diferencial , Tuberculosis de los Genitales Masculinos/diagnóstico , Tuberculosis de los Genitales Masculinos/tratamiento farmacológico , Enfermedades Testiculares/diagnóstico , Testículo/diagnóstico por imagen , Testículo/patología , Tuberculosis/diagnóstico , AdultoRESUMEN
OBJECTIVES: To investigate the impact of combined treatment of colorectal cancer (CRC) with electroacupuncture (EA) and capeOX (combined administration of fluorouracil, oxaliplatin and capecitabine) on the tumor volume, weight, spleen coefficient, apoptosis and ferroptosis of tumor tissue, and liver and kidney functions in nude mice with CRC, so as to explore its mechanisms underlying inhibiting CRC and alleviating toxic reactions of capeOX. METHODS: Female Balb/c nude mice were randomly assigned to 3 groupsï¼model, capeOX, and EA+capeOX, with 8 nude mice in each group. The CRC model was established by subcutaneous injection of colon cancer cells at the right inguinal region. Nude mice of the capeOX group received intraperitoneal injection of oxaliplatin for 1 day and gavage of capecitabine from day 2 to day 7. EA (1 mA, 2 Hz/100 Hz) was applied to bilateral "Zusanli" (ST36) for 20 min, once daily for 7 days. During the interven-tion, the tumor volume and weight were measured every day, and at the end of intervention, the weight of the tumor tissue and spleen were measured, with tumor volume difference and spleen coefficient calculated. The proportion of apoptotic cells was measured by flow cytometry, and the contents of serum malondialdehyde (MDA), alanine aninotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were detected using ELISA. The expression level of glutathione peroxidase 4 (GPX4, a key regulator for ferroptosis) protein of the tumor tissue was determined using Western blot. RESULTS: Compared to the model group, both the capeOX group and EA+capeOX group showed a decrease in the tumor volume (on day 3 and 4 in the capeOX group, and from day 2 to 7 in the EA+capeOX group) and body weight (P<0.05, on day 3 to 7 in the EA+capeOX group and on day 2 to 7 in the capeOX group), being evidently lower in the tumor volume on day 7 in the EA+capeOX than in the capeOX group (P<0.05), and evidently higher in the body weight on day 6 and 7 in the EA+capeOX group than in the capeOX group (P<0.05). In comparison with the model group, the tumor volume difference, tumor weight and spleen coefficient in both capeOX and EA+capeOX groups were significantly decreased (P<0.05), and MDA content in EA+capeOX group was significantly decreased (P<0.05), while the contents of ALT, BUN and Cr in the capeOX group, the proportion of apoptotic cells in both capeOX and EA+capeOX groups, and the GPX4 expression level in the EA+capeOX group were all significantly increased (P<0.05). The tumor volume difference, tumor weight, and contents of MDA, ALT, AST, BUN and Cr in the EA+capeOX group were markedly lower than in the capeOX group (P<0.05), while the spleen coefficient, proportion of apoptotic cells and GPX4 expression level in the EA+capeOX group were markedly higher than those in the capeOX group (P<0.05). CONCLUSIONS: EA of ST36 can enhance the effect of capeOX in inhibiting colorectal cancer growth in nude mice with CRC, which may be related with its functions in promoting tumor cell apoptosis, inhibiting ferroptosis, and modulating immune tolerance. In addition, EA can lower the side effects of capeOX in hematopoietic and immune, liver, and kidney functions.
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Puntos de Acupuntura , Apoptosis , Neoplasias Colorrectales , Electroacupuntura , Ferroptosis , Ratones Endogámicos BALB C , Ratones Desnudos , Animales , Ratones , Ferroptosis/efectos de los fármacos , Humanos , Apoptosis/efectos de los fármacos , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Femenino , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genéticaRESUMEN
Due to rapid technological advancements, remote patient monitoring (RPM) technology has gained traction in recent years. While the effects of specific RPM interventions are known, few published reviews examine RPM in the context of care transitions from an inpatient hospital setting to a home environment. In this systematic review, we addressed this gap by examining the impacts of RPM interventions on patient safety, adherence, clinical and quality of life outcomes and cost-related outcomes during care transition from inpatient care to a home setting. We searched five academic databases (PubMed, CINAHL, PsycINFO, Embase and SCOPUS), screened 2606 articles, and included 29 studies from 16 countries. These studies examined seven types of RPM interventions (communication tools, computer-based systems, smartphone applications, web portals, augmented clinical devices with monitoring capabilities, wearables and standard clinical tools for intermittent monitoring). RPM interventions demonstrated positive outcomes in patient safety and adherence. RPM interventions also improved patients' mobility and functional statuses, but the impact on other clinical and quality-of-life measures, such as physical and mental health symptoms, remains inconclusive. In terms of cost-related outcomes, there was a clear downward trend in the risks of hospital admission/readmission, length of stay, number of outpatient visits and non-hospitalisation costs. Future research should explore whether incorporating intervention components with a strong human element alongside the deployment of technology enhances the effectiveness of RPM. The review highlights the need for more economic evaluations and implementation studies that shed light on the facilitators and barriers to adopting RPM interventions in different care settings.
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Although data on the blockchain cannot be tampered with, malicious access by insiders can also lead to data leakage. Access records of block are an important basis for tracing the source of data breaches; however, access records themselves may be tampered with. Therefore, it is important to study how to protect the block access records. So far, the protection of block access records has not received much attention. To make block access records a protected data resource as well, this paper proposes a storage mechanism of data access record on consortium chain based on master-slave blocks. In this mechanism, the master block is used to store data resources, and the slave block of the master block is used to store access records of the master block. This method ensures that the slave block has the security characteristics of the single chain block, making the access record traceable and immutable. The storage mechanism's viability is confirmed by real-world experimentation. The proposed mechanism outperforms the single chain in terms of data query performance, according to the testing results on public data sets.
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BACKGROUND: Chronic stress-induced neuroinflammation plays a pivotal role in the development and exacerbation of mental disorders, such as anxiety and depression. Dimethyl Fumarate (DMF), an effective therapeutic agent approved for the treatment of multiple sclerosis, has been widely reported to display anti-inflammatory and anti-oxidative effects. However, the impact of DMF on chronic stress-induced anxiety disorders and the exact underlying mechanisms remain largely unknown. METHODS: We established a mouse model of chronic social defeat stress (CSDS). DMF was administered orally 1 h before daily stress session for 10 days in CSDS + DMF group. qRT-PCR and western blotting were used to analyze mRNA and protein expression of NLRP3, Caspase-1 and IL-1ß. Immunofluorescence staining was carried out to detect the expression of Iba 1 and c-fos positive cells as well as morphological change of Iba 1+ microglia. Whole-cell patch-clamp recording was applied to evaluate synaptic transmission and intrinsic excitability of neurons. RESULTS: DMF treatment significantly alleviated CSDS-induced anxiety-like behaviors in mice. Mechanistically, DMF treatment prevented CSDS-induced neuroinflammation by inhibiting the activation of microglia and NLRP3/Caspase-1/IL-1ß signaling pathway in basolateral amygdala (BLA), a brain region important for emotional processing. Furthermore, DMF treatment effectively reversed the CSDS-caused disruption of excitatory and inhibitory synaptic transmission balance, as well as the increased intrinsic excitability of BLA neurons. CONCLUSIONS: Our findings provide new evidence that DMF may exert anxiolytic effect by preventing CSDS-induced activation of NLRP3/Caspase-1/IL-1ß signaling pathway and alleviating hyperactivity of BLA neurons.
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Ansiedad , Dimetilfumarato , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Neuronas , Estrés Psicológico , Animales , Dimetilfumarato/farmacología , Dimetilfumarato/uso terapéutico , Masculino , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/inmunología , Ratones , Ansiedad/tratamiento farmacológico , Neuronas/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/metabolismo , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/inmunología , Modelos Animales de Enfermedad , Interleucina-1beta/metabolismo , Microglía/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Caspasa 1/metabolismo , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Transducción de Señal/efectos de los fármacos , Derrota SocialRESUMEN
OBJECTIVES: Psychological resilience is a crucial component of mental health and well-being for health care workers. It is positively linked to compassion satisfaction and inversely associated with burnout. The current literature on health care worker resilience has mainly focused on primary care and tertiary hospitals, but there is a lack of studies in post-acute and transitional care settings. Our study aims to address this knowledge gap and evaluate the factors associated with psychological resilience among health care professionals working in community hospitals. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Physicians, nurses, rehabilitation therapists (consisting of physiotherapists, occupational therapists, and speech therapists), pharmacists, dietitians, and social workers in 2 community hospitals in Singapore. METHODS: Eligible health care workers were invited to fill in anonymous, self-reported questionnaires consisting of sociodemographic, lifestyle, and work-related factors together with the Connor-Davidson Resilience Scale (CD-RISC-10). Univariate analysis and multiple linear regression were conducted to study the relationship between each factor and resilience scores. RESULTS: A total of 574 responses were received, giving a response rate of 81.1%. The mean CD-RISC-10 score reported was 28.4. Multiple linear regression revealed that male gender (B = 1.49, P = .003), Chinese (B = -3.18, P < .001), active smokers (B = -3.82, P = .01), having perceived work crisis support (B = 2.95, P < .001), work purpose (B = 1.84, P = .002), job satisfaction (B = 1.01, P = .04), and work control (B = 2.53, P < .001) were significantly associated with psychological resilience scores among these health care workers. CONCLUSION AND IMPLICATIONS: Our study highlights the importance of certain individual and organizational factors that are associated with psychological resilience. These findings provide valuable insight into developing tailored interventions to foster resilience, such as strengthening work purpose and providing effective work crisis support, thus reducing burnout among health care workers in the post-acute care setting.
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Hospitales Comunitarios , Resiliencia Psicológica , Humanos , Estudios Transversales , Singapur , Masculino , Femenino , Adulto , Persona de Mediana Edad , Agotamiento Profesional/psicología , Encuestas y Cuestionarios , Personal de Salud/psicología , Atención Subaguda , Satisfacción en el TrabajoRESUMEN
Due to the highly stable structure of keratin, the extraction and dissolution steps of animal medicines rich in keratin are complex, which seriously restricts the detection efficiency and flux. Therefore, this study simplified the pre-treatment steps of horn samples and optimized the detection methods of characteristic peptides to improve the efficiency of identifying the specificity of horn-derived animal medicines. For detection of the characteristic peptides in horn-derived animal medicines treated with/without iodoace-tamide(IAA), the ion pair conditions of the characteristic peptides were optimized, and the retention time, intensity and other data of the specific peptides were compared between the samples treated with/without IAA. Two pre-treatment methods, direct enzymatic hydrolysis and total protein extraction followed by enzymatic hydrolysis, were used to prepare horn-derived animal medicine samples. The effects of different methods on the detection of specific peptides in the samples of Saiga antelope horn, water buffalo horn, goat horn, and yak horn were compared regarding the retention time of specific peptides and ion intensity. The results indicated that after direct enzymatic hydrolysis, the specific peptides in the samples without IAA treatment can be detected. Compared with the characteristic peptides in the samples treated with IAA, their retention time shifted back and the mass spectrometry response slightly decreased. The specific peptides of the samples without IAA treatment had good specificity and did not affect the specificity identification of horn-derived animal medicines. Overall, the process of direct enzymatic hydrolysis can be used to treat horn samples, omitting the steps of protein extraction and dithiothreitol and IAA treatment, significantly improving the pre-treatment efficiency without affecting the specificity identification of horn-derived animal medicines. This study provides ideas for quality research and standard improvement of horn-derived animal medicines.
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Cuernos , Queratinas , Péptidos , Animales , Cuernos/química , Péptidos/química , Queratinas/química , Bovinos , Cabras , Búfalos , Cromatografía Líquida de Alta PresiónRESUMEN
Bleeding and thrombosis are known as common complications of polycythemia for a long time. However, the role of coagulation system in erythropoiesis is unclear. Here, we discover that an anticoagulant protein tissue factor pathway inhibitor (TFPI) plays an essential role in erythropoiesis via the control of heme biosynthesis in central macrophages. TFPI levels are elevated in erythroblasts of human erythroblastic islands with JAK2V617F mutation and hypoxia condition. Erythroid lineage-specific knockout TFPI results in impaired erythropoiesis through decreasing ferrochelatase expression and heme biosynthesis in central macrophages. Mechanistically, the TFPI interacts with thrombomodulin to promote the downstream ERK1/2-GATA1 signaling pathway to induce heme biosynthesis in central macrophages. Furthermore, TFPI blockade impairs human erythropoiesis in vitro, and normalizes the erythroid compartment in mice with polycythemia. These results show that erythroblast-derived TFPI plays an important role in the regulation of erythropoiesis and reveal an interplay between erythroblasts and central macrophages.
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Eritroblastos , Eritropoyesis , Factor de Transcripción GATA1 , Hemo , Lipoproteínas , Macrófagos , Policitemia , Policitemia/metabolismo , Policitemia/genética , Policitemia/patología , Eritroblastos/metabolismo , Hemo/metabolismo , Humanos , Animales , Lipoproteínas/metabolismo , Macrófagos/metabolismo , Ratones , Factor de Transcripción GATA1/metabolismo , Factor de Transcripción GATA1/genética , Janus Quinasa 2/metabolismo , Janus Quinasa 2/genética , Trombomodulina/metabolismo , Trombomodulina/genética , Ratones Noqueados , Ferroquelatasa/metabolismo , Ferroquelatasa/genética , Masculino , Sistema de Señalización de MAP Quinasas , Ratones Endogámicos C57BL , FemeninoAsunto(s)
Absceso , Vértebras Cervicales , Tuberculosis de la Columna Vertebral , Humanos , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/microbiología , Tuberculosis de la Columna Vertebral/diagnóstico por imagen , Tuberculosis de la Columna Vertebral/diagnóstico , Tuberculosis de la Columna Vertebral/complicaciones , Absceso/microbiología , Masculino , Antituberculosos/uso terapéuticoRESUMEN
Vascular restenosis following angioplasty continues to pose a significant challenge. The heterocyclic trioxirane compound [1, 3, 5-tris((oxiran-2-yl)methyl)-1, 3, 5-triazinane-2, 4, 6-trione (TGIC)], known for its anticancer activity, was utilized as the parent ring to conjugate with a non-steroidal anti-inflammatory drug, resulting in the creation of the spliced conjugated compound BY1. We found that BY1 induced ferroptosis in VSMCs as well as in neointima hyperplasia. Furthermore, ferroptosis inducers amplified BY1-induced cell death, while inhibitors mitigated it, indicating the contribution of ferroptosis to BY1-induced cell death. Additionally, we established that ferritin heavy chain1 (FTH1) played a pivotal role in BY1-induced ferroptosis, as evidenced by the fact that FTH1 overexpression abrogated BY1-induced ferroptosis, while FTH1 knockdown exacerbated it. Further study found that BY1 induced ferroptosis by enhancing the NCOA4-FTH1 interaction and increasing the amount of intracellular ferrous. We compared the effectiveness of various administration routes for BY1, including BY1-coated balloons, hydrogel-based BY1 delivery, and nanoparticles targeting OPN loaded with BY1 (TOP@MPDA@BY1) for targeting proliferated VSMCs, for prevention and treatment of the restenosis. Our results indicated that TOP@MPDA@BY1 was the most effective among the three administration routes, positioning BY1 as a highly promising candidate for the development of drug-eluting stents or treatments for restenosis.
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Ferroptosis , Músculo Liso Vascular , Nanopartículas , Ferroptosis/efectos de los fármacos , Animales , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citología , Humanos , Nanopartículas/química , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Oxidorreductasas/metabolismo , FerritinasRESUMEN
Anorectal malformation (ARM) is a prevalent early pregnancy digestive tract anomaly. The intricate anatomy of the embryonic cloaca region makes it challenging for traditional high-throughput sequencing methods to capture location-specific information. Spatial transcriptomics was used to sequence libraries of frozen sections from embryonic rats at gestational days (GD) 14 to 16, covering both normal and ARM cases. Bioinformatics analyses and predictions were performed using methods such as WGCNA, GSEA, and PROGENy. Immunofluorescence staining was used to verify gene expression levels. Gene expression data was obtained with anatomical annotations of clusters, focusing on the cloaca region's location-specific traits. WGCNA revealed gene modules linked to normal and ARM cloacal anatomy development, with cooperation between modules on GD14 and GD15. Differential gene expression profiles and functional enrichment were presented. Notably, protein levels of Pcsk9, Hmgb2, and Sod1 were found to be downregulated in the GD15 ARM hindgut. The PROGENy algorithm predicted the activity and interplay of common signaling pathways in embryonic sections, highlighting their synergistic and complementary effects. A competing endogenous RNA (ceRNA) regulatory network was constructed from whole transcriptome data. Spatial transcriptomics provided location-specific cloaca region gene expression. Diverse bioinformatics analyses deepened our understanding of ARM's molecular interactions, guiding future research and providing insights into gene regulation in ARM development.
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Malformaciones Anorrectales , Redes Reguladoras de Genes , Transducción de Señal , Transcriptoma , Animales , Malformaciones Anorrectales/genética , Malformaciones Anorrectales/metabolismo , Malformaciones Anorrectales/embriología , Transducción de Señal/genética , Transcriptoma/genética , Ratas , Femenino , Regulación del Desarrollo de la Expresión Génica , Embarazo , Embrión de Mamíferos/metabolismo , Perfilación de la Expresión Génica/métodos , Biología Computacional/métodos , Ratas Sprague-Dawley , Cloaca/embriología , Cloaca/metabolismoRESUMEN
Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disease due to loss-of-function mutations in the DYSTROPHIN gene. DMD-related skeletal muscle wasting is typified by an aberrant immune response involving upregulation of TGFß family of cytokines. We previously demonstrated that bone morphogenetic protein 4 (BMP4) is increased in DMD and BMP4 stimulation induces a 20-fold upregulation of Smad8 transcription. However, the role of BMP4 in severely affected DMD skeletal muscle is unknown. We hypothesized that transcriptomic signatures in severely affected human DMD skeletal muscle are driven by BMP4 signaling. Transcriptomes from skeletal muscle biopsies of late-stage DMD vs. non-DMD controls and C2C12 muscle cells with or without BMP4 stimulation were generated by RNA-Seq and analyzed for single transcript differential expression as well as by Ingenuity Pathway Analysis and weighted gene co-expression network analyses. A total of 2,328 and 5,291 transcripts in the human muscle and C2C12 muscle cells, respectively, were differentially expressed. We identified an overlapping molecular signature of 1,027 genes dysregulated in DMD muscle that were induced in BMP4-stimulated C2C12 muscle cells. Highly upregulated DMD transcripts that overlapped with BMP4-stimulated C2C12 muscle cells included ADAMTS3, HCAR2, SERPING1, SMAD8 , and UNC13C. The DMD transcriptome was characterized by dysregulation of pathways involving immune function, extracellular matrix remodeling, and metabolic/mitochondrial function. In summary, we define a late-stage DMD skeletal muscle transcriptome that substantially overlaps with the BMP4-induced molecular signature in C2C12 muscle cells. This supports BMP4 as a disease-driving regulator of transcriptomic changes in late-stage DMD skeletal muscle and expands our understanding of the evolution of dystrophic signaling pathways and their associated gene networks that could be explored for therapeutic development.
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An optimized metastructure (MS) switchable between ultra-wideband (UWB) angle-insensitive absorption, and transmissive linear-to-circular (LTC) polarization conversion (PC), is proposed, which is a theoretical study. The structural parameters of this MS are optimized by the thermal exchange optimization algorithm. By modulating the chemical potential (µc) of the graphene-based hyperbolic metamaterial embedded in the MS, the MS can achieve UWB absorption in the absorption state and LTC PC in the transmission state. At normal incidence, in the absorption state, the MS exhibits absorptivity exceeding 0.9 within 7-15.45 THz, with a relative bandwidth (RBW) of 75.28%. By elevating µc, an UWB LTC PC is realized, with a RBW of 118.8%, achieving transmittance above 0.9 and the axial ratio below 3 dB. When prioritizing the angular stability, in the absorption state, the MS secures the angular stability of 75° for TE waves and 65° for TM ones. In the transmission state, the angular stability of PC reaches 60°, with RBW = 100.7%. Moreover, by manipulating µc, the tunability of UWB absorption is realized. The optimized MS provides a reference for designing multifunctional intelligent terahertz modulators, with promising application potential in domains like electromagnetic shielding, communication systems, and THz modulation.
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[This corrects the article DOI: 10.3892/ol.2017.7635.].
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The integration of electrokinetic and bioremediation (EK-BIO) represents an innovative approach for addressing trichloroethylene (TCE) contamination in low-permeability soil. However, there remains a knowledge gap in the impact of the inoculation approach on TCE dechlorination and the microbial response with the presence of co-existing substances. In this study, four 1-dimensional columns were constructed with different inoculation treatments. Monitoring the operation conditions revealed that a stabilization period (â¼40 days) was required to reduce voltage fluctuation. The group with inoculation into the soil middle (Group B) exhibited the highest TCE dechlorination efficiency, achieving a TCE removal rate of 84%, which was 1.1-3.2 fold higher compared to the others. Among degraded products in Group B, 39% was ethylene. The physicochemical properties of the post-soil at different regions illustrated that dechlorination coincided with the Fe(III) and SO42- reduction, meaning that the EK-BIO system promoted the formation of a reducing environment. Microbial community analysis demonstrated that Dehalococcoides was only detected in the treatment of injection at soil middle or near the cathode, with abundance enriched by 2.1%-7.2%. The principal components analysis indicated that the inoculation approach significantly affected the evolution of functional bacteria. Quantitative polymerase chain reaction (qPCR) analysis demonstrated that Group B exhibited at least 2.8 and 4.2-fold higher copies of functional genes (tceA, vcrA) than those of other groups. In conclusion, this study contributes to the development of effective strategies for enhancing TCE biodechlorination in the EK-BIO system, which is particularly beneficial for the remediation of low-permeability soils.
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Biodegradación Ambiental , Microbiología del Suelo , Contaminantes del Suelo , Tricloroetileno , Tricloroetileno/metabolismo , Contaminantes del Suelo/metabolismo , Permeabilidad , Suelo/químicaRESUMEN
OBJECTIVE: Glucose-6-phosphate isomerase (GPI) deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants. This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics, often posing challenges for precise diagnoses using conventional methods. To this end, this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family. METHODS: The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis. Novel compound heterozygous variants of the GPI gene, c.174C>A (p.Asn58Lys) and c.1538G>T (p.Trp513Leu), were identified using whole-exome and Sanger sequencing. The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure. RESULTS: By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study, we found that most variants were located in exons 3, 4, 12, and 18, with a few localized in exons 8, 9, and 14. This study identified novel compound heterozygous variants associated with GPI deficiency. These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids. CONCLUSION: Early family-based sequencing analyses, especially for patients with congenital anemia, can help increase diagnostic accuracy for GPI deficiency, improve child healthcare, and enable genetic counseling.