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Objective: To assess the efficacy and safety of intracavitary electrocardiography (IC-ECG)-guided peripherally inserted central catheter (PICC) placements in pediatric patients, emphasizing improvements over traditional placement methods. Methods: A literature search was conducted in April 2024 across PubMed, Cochrane Library, and EMBASE. Studies focusing on pediatric patients and reporting the efficacy and safety of IC-ECG-guided PICC placement via the upper extremity were included. This study was registered with the PROSPERO database (CRD42024549037) in accordance with PRISMA guidelines. Results: Eleven studies were included, comprising five randomized controlled trials (RCTs) and six quasi-experimental studies. The pooled analysis showed that IC-ECG had an applicability and feasibility of 97% and 98%, respectively. The first puncture success rate was 91%, and the overall success rate was 98%. Sensitivity and specificity were 97% and 80%, respectively. IC-ECG significantly reduced overall complications compared to traditional methods (RR: 0.31, 95% CI [0.20-0.46], p < 0.00001), particularly in phlebitis (RR: 0.25, 95% CI [0.11-0.57], p = 0.001) and arrhythmias (RR: 0.09, 95% CI [0.01-0.70], p = 0.021). Similar results were observed in neonates. Only one case of catheter-related bloodstream infection (CRBSI) was reported, and no arrhythmia events were noted. Conclusion: IC-ECG-guided PICC placement is a highly effective and safe method for pediatric patients, including neonates, offering significant advantages over traditional techniques. Further high-quality studies are needed to standardize procedural techniques and explore cost-effectiveness.
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Cateterismo Venoso Central , Cateterismo Periférico , Electrocardiografía , Humanos , Niño , Cateterismo Periférico/efectos adversos , Cateterismo Periférico/métodos , Cateterismo Periférico/instrumentación , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/métodos , Cateterismo Venoso Central/instrumentación , Lactante , PreescolarRESUMEN
Cellular communication network factor 2 (CCN2) is a secreted extracellular matrix-associated protein, and its aberrantly increased expression has been implicated in a diversity of diseases involving pathological processes of fibrosis, chronic inflammation, or tissue injury, which has promoted the evaluation of CCN2 as therapeutic targets for multiple disorders. However, human phenotypes associated with CCN2 deficiency have remained enigmatic; variants in CCN2 have not yet been associated with a human phenotype. Here, we collected families diagnosed with spondyloepimetaphyseal dysplasia (SEMD), and screened candidate pathogenic genes for families without known genetic causes using next-generation sequencing. We identified a monoallelic variant in signal peptide of CCN2 (NM_001901.2: c.65 G > C [p.Arg22Pro]) as the cause of SEMD in 14 subjects presenting with different degree of short stature, premature osteoarthritis, and osteoporosis. Affected subjects showed decreased serum CCN2 levels. Cell lines harboring the variant displayed decreased amount of CCN2 proteins in culture medium and an increased intracellular retention, indicating impaired protein secretion. And the variant weakened the stimulation effect of CCN2 on osteogenesis of bone marrow mesenchymal stem cells. Zebrafish ccn2a knockout model and osteoblast lineage-specific Ccn2-deficient mice (Ccn2fl/fl;Prx1Cre) partially recapitulated the phenotypes including low bone mass observed in affected subjects. Pathological mechanism implicated in the skeletal abnormality in Ccn2fl/fl;Prx1Cre mice involved decreased bone formation, increased bone resorption, and abnormal growth plate formation. Collectively, our study indicate that monoallelic variants in CCN2 lead to a human inherited skeletal dysplasia, and highlight the critical role of CCN2 in osteogenesis in human.
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Factor de Crecimiento del Tejido Conjuntivo , Osteocondrodisplasias , Pez Cebra , Humanos , Animales , Osteocondrodisplasias/genética , Osteocondrodisplasias/patología , Osteocondrodisplasias/metabolismo , Pez Cebra/genética , Masculino , Femenino , Factor de Crecimiento del Tejido Conjuntivo/genética , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Ratones , Alelos , Linaje , Osteogénesis/genética , Adolescente , Densidad Ósea/genética , Niño , Ratones NoqueadosRESUMEN
Oily sludge (OS) has long been regarded as a hazardous waste, and improper disposal may lead to serious environmental concerns and human health risks. Despite various methods having been proposed and applied to the treatment of OS, the oil occurrence states and properties in sludge are rarely characterized, which may directly link to the selection and effectiveness of treatment methods. Here, confocal laser scanning microscopy (CLSM), X-ray diffraction (XRD), gas chromatography (GC), and four components (SARA) analysis were utilized to characterize the changes in the oil occurrence states and compositions in OS samples before and after high-speed stirring (HSS) treatment. Our results show a substantial reduction in the oil concentration of OS after HSS treatment (from 32.98% to 1.65%), while SARA analysis reveals a similar oil composition before and after treatment, suggesting the broad applicability of HSS in removing oil and its insignificant selectivity towards various hydrocarbon components. This is further supported by the total petroleum hydrocarbon (TPH) analysis results, which show that the separated oil phase has a hydrocarbon composition similar to that of the original OS sample. The CLSM and fluorescence analysis suggest a homogeneous distribution of oil in the sludge, with relatively light components more concentrated in the pore systems between coarse mineral particles, whereas relatively heavy components tend to coexist with clay minerals. After HSS cleaning, both light and heavy components are removed to varying degrees, but light components are preferentially removed while heavy components tend to be retained in the sludge due to adsorption by clay minerals. This is consistent with TPH analysis, where a significant decrease in n-alkanes with lower carbon numbers (n-C14 to n-C20) was observed in the residual sample. Our findings demonstrate the dynamic response of oil occurrence states and compositions to the OS treatment process and highlight the importance of characterizing these fundamental properties prior to the selection of OS treatment methods.
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Engaging in exercise in an ozone (O3)-polluted environment can lead to lung damage, respiratory inflammation, and deterioration in performance, however, the effects on the heart are undefined. Herein, we report that rats performing moderate-intensity exercise under O3-polluted air evoked pathological myocardial hypertrophy (MH). O3 exposure increased serum levels of MH-promoting factors (angiotensin II [AngII], endothelin-1 [ET-1], and cyclophilin A [CyPA]), and decreased expression of MH-inhibiting factors (adiponectin [ADPN], follistatin-like protein 1 [FSTL1], and apelin). O3 exposure also increased the expression levels of cardiac hypertrophy markers (ANP, BNP, and ß-MHC) in the heart, elicited myocardial hypertrophy and cardiac inflammation. Mechanistically, we identified lncRNA EYA4-au1 overexpression in the above myocardial tissues with pathological hypertrophy. In an AngII-elicited in vitro model, EYA4-au1 was shown to mediate cardiomyocyte hypertrophy. AngII induces nuclear translocation of SP1, leading to high expression of EYA4-au1; And inhibits the expression of ELAVL1, resulting in nuclear retention of EYA4-au1. Nuclear EYA4-au1 recruits Med11 to EYA4 promoter for transcriptional activation, subsequently unleashing the EYA4/p27kip1/CK2α/HDAC2 cascade that signals cardiomyocyte hypertrophy. In summary, O3 exposure is an important factor in pathological MH, mediated by EYA4-au1 that motivates the MH-driving EYA4 pathway. Our findings define the effects of exercise on the heart in an O3-polluted environment and offer a novel mechanistic route for the onset of MH.
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PURPOSE: To analyze the immune-related core genes differentially expressed in oral squamous cell carcinoma(OSCC) and construct an immune-related prognostic risk model for OSCC patients. METHODS: Weighted gene co-expression network analysis of RNA sequencing data from OSCC patients in the Cancer Genome Atlas (TCGA) database was conducted to identify immune-related modules and core genes. Core genes associated with immune prognosis were screened using univariate Cox regression analysis and survival analysis to construct an immune-related prognostic risk model for OSCC. The prognostic risk model's predictive ability was evaluated using Kaplan-Meier analysis, receiver operating characteristic curves, and external datasets from GSE41613. The expression of 8 immune prognostic core genes in tumor samples from OSCC patients was detected by real-time quantitative PCR assay(RT-qPCR), and the correlation between risk score and depth of invasion was assessed by calculating risk scores for OSCC patients. Statistical analysis was performed with SPSS 21.0 software package. RESULTS: Prognostic risk model for OSCC was successfully constructed based on 8 immune prognostic core genes(CSF2RA, CLEC4C, COL5A3, CTSG, EDNRA, GPC4, GUCY1A2, ANGPT2). The prognostic risk model demonstrated perfect predictive value validated using Kaplan-Meier analysis, receiver operating characteristic curve, and the GSE41613 dataset. The risk scores of OSCC patients calculated based on this model were positively correlated with the depth of invasion, indicating that the model have the ability to predict the potential risk of OSCC. CONCLUSIONS: An OSCC prognostic risk model is constructed based on the signatures of 8 immune prognostic core genes, which may effectively predict the prognosis of OSCC patients, providing an important reference for immune prevention of OSCC.
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Carcinoma de Células Escamosas , Neoplasias de la Boca , Humanos , Neoplasias de la Boca/genética , Neoplasias de la Boca/inmunología , Neoplasias de la Boca/mortalidad , Pronóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/inmunología , Estimación de Kaplan-Meier , Curva ROCRESUMEN
Ovarian cancer (OC) is the fifth most common cause of death in women worldwide. Chemoresistance is a key reason for treatment failure, causing high mortality. As a member of the tripartite motif-containing (TRIM) protein family, tripartite motif 47 (TRIM47) plays a vital role in the carcinogenesis and drug resistance of various cancers. This study investigated the impact and mechanisms of TRIM47 on cisplatin (DDP) chemosensitivity and apoptosis in OC. OC cell viability was assessed with a cell counting kit-8 assay and OC cell apoptosis was assessed using flow cytometry, caspase-3 and caspase-9 activity, and Bax and Bcl-2 expression assays while gene and protein expression were assessed using qRT-PCR and Western blot assays. The expression of TRIM47 was significantly increased in both DDP-resistant tissues from patients with OC tissues and in cancer cell lines compared with that in normal tissue or parental cell lines. The increased level of TRIM47 correlated with poor prognosis in patients with OC. Functional assays demonstrated that TRIM47 promoted DDP resistance both in vitro and in vivo. The increased viability and reduced apoptosis of OC cells induced by TRIM47 can be rescued by the endoplasmic reticulum (ER) stress-inducer tunicamycin, suggesting that TRIM47 inhibits OC cell apoptosis by suppressing ER stress. Therefore, TRIM47 may be targeted as a therapeutic strategy for DDP resistance in OC.
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Apoptosis , Cisplatino , Resistencia a Antineoplásicos , Estrés del Retículo Endoplásmico , Neoplasias Ováricas , Humanos , Cisplatino/farmacología , Femenino , Apoptosis/efectos de los fármacos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Línea Celular Tumoral , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Animales , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ratones Desnudos , Antineoplásicos/farmacología , Ratones , Proteínas de Motivos Tripartitos/metabolismo , Proteínas de Motivos Tripartitos/genética , Proteínas de Neoplasias , Proteínas NuclearesRESUMEN
The fruits of Alpinia oxyphylla has been used a famous traditional Chinese medicine. A chemical investigation on the fruits of A. oxyphylla resulted in the isolation of one new acetylated flavanol glucuronide (1) and two known compounds (2-3). Compound 1 displayed a weak inhibitory effect on U251 cells with the IC50 value 128.51 µM while the positive control drug temozolomide exhibited the IC50 value 35.37 µM.
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The market demand for essential oil containing citral is increasing. Our research group identified a rare chemotype of Camphora officinarum whose leaves are high in citral content by examining over 1000 wild trees across the entire native distribution area of C. officinarum in China. Because C. officinarum is suitable for large-scale cultivation, it is therefore seen as a promising source of natural citral. However, the molecular mechanism of citral biosynthesis in C. officinarum is poorly understood. In this study, transcriptomic analyses of C. officinarum with different citral contents revealed a strong positive correlation between the expression of a putative geraniol synthase gene (CoGES) and citral content. The CoGES cDNA was cloned, and the CoGES protein shared high similarity with other monoterpene synthases. Enzymatic assays of CoGES with geranyl diphosphate (GPP) as substrate yielded geraniol as the single product, which is the precursor of citral. Further transient expression of CoGES in Nicotiana benthamiana resulted in a higher relative content of geranial and the appearance of a new substance, neral. These findings indicate that CoGES is a geraniol synthase-encoding gene, and the encoded protein can catalyze the transformation of GPP into geraniol, which is further converted into geranial and neral through an unknown mechanism in vivo. These findings expand our understanding of citral biosynthesis in Lauraceae plants. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01463-4.
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Ovarian cancer is a common gynecological malignancy, and its treatment remains challenging. Although ovarian cancer may respond to immunotherapy because of endogenous immunity at the molecular or T cell level, immunotherapy has so far not had the desired effect. The functional status of preexisting T cells is an indispensable determinant of powerful antitumor immunity and immunotherapy. T cell exhaustion and senescence are two crucial states of T cell dysfunction, which share some overlapping phenotypic and functional features, but each status possesses unique molecular and developmental signatures. It has been widely accepted that exhaustion and senescence of T cells are important strategies for cancer cells to evade immunosurveillance and maintain the immunosuppressive microenvironment. Herein, this review summarizes the phenotypic and functional features of exhaust and senescent T cells, and describes the key drivers of the two T cell dysfunctional states in the tumor microenvironment and their functional roles in ovarian cancer. Furthermore, we present a summary of the molecular machinery and signaling pathways governing T cell exhaustion and senescence. Possible strategies that can prevent and/or reverse T cell dysfunction are also explored. An in-depth understanding of exhausted and senescent T cells will provide novel strategies to enhance immunotherapy of ovarian cancer through redirecting tumor-specific T cells away from a dysfunctional developmental trajectory.
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Senescencia Celular , Inmunoterapia , Neoplasias Ováricas , Linfocitos T , Microambiente Tumoral , Humanos , Femenino , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/terapia , Neoplasias Ováricas/patología , Inmunoterapia/métodos , Senescencia Celular/inmunología , Microambiente Tumoral/inmunología , Linfocitos T/inmunología , Animales , Agotamiento de Células TRESUMEN
Aims/Background Although electromyography has been extensively used in the diagnosis of neurological diseases, there is no comprehensive understanding of the electromyography manifestations of spinal dural arteriovenous fistula. Given the widespread use of electromyography in the diagnosis of neurological conditions, it is worthwhile to holistically analyse the electromyography findings of spinal dural arteriovenous fistula to differentiate it from neurological diseases that share similar clinical manifestations. The aim of this study is to evaluate whether electromyography can distinguish spinal dural arteriovenous fistula from longitudinally extensive transverse myelitis. Methods We holistically reviewed files of all patients who were diagnosed with spinal dural arteriovenous fistula or longitudinally extensive transverse myelitis at The First Medical Centre of PLA General Hospital from 1 January 2010 to 31 December 2020. We compared the symptomology, epidemiology, and imaging results of patients with spinal dural arteriovenous fistula and longitudinally extensive transverse myelitis, placing emphasis on their electromyography manifestations. Student's t test was used to analyse normally distributed data, while Chi-square test was used to compare classification statistics. Results Lesions of spinal dural arteriovenous fistula shown on images tend to appear at lower lumbar and sacral segments, whereas lesions of the cervical and upper thoracic segments are more characteristic of longitudinally extensive transverse myelitis. Spinal dural arteriovenous fistula patients and longitudinally extensive transverse myelitis patients overlap in terms of clinical manifestations. After comparison, the two groups of patients had different demographics (age, sex), onset mode, predisposing factors before onset, and electromyographic features. The electromyographic features of patients with spinal dural arteriovenous fistula were associated with neurogenic damage (p < 0.001). Conclusions In patients with spinal dural arteriovenous fistula, electromyography can help clinicians to identify early disease, avoid patient treatment delay, and eliminate unnecessary treatment.
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Malformaciones Vasculares del Sistema Nervioso Central , Electromiografía , Mielitis Transversa , Humanos , Electromiografía/métodos , Masculino , Femenino , Mielitis Transversa/diagnóstico , Malformaciones Vasculares del Sistema Nervioso Central/complicaciones , Malformaciones Vasculares del Sistema Nervioso Central/fisiopatología , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Anciano , Diagnóstico Diferencial , Enfermedades de la Médula Espinal/diagnóstico , Enfermedades de la Médula Espinal/fisiopatología , Imagen por Resonancia Magnética/métodosRESUMEN
Introduction: The effects of vitamin B12 metabolism on musculoskeletal health and the exact mechanism have not been fully determined. Our study aimed to assess the association of vitamin B12 and its biomarkers with musculoskeletal health in middle-aged and older adults. Methods: The data from the National Health and Nutrition Examination Survey 2001-2002 were used to investigate the effects of serum vitamin B12 and its biomarkers (homocysteine and methylmalonic acid) on skeletal muscle health. Bone mineral density (BMD), lean mass, gait speed and knee extensor strength were used as indicators for musculoskeletal health. Results: Serum vitamin B12 level was positively correlated with the total and appendicular lean mass (ß = 584.83, P = 0.044; ß = 291.65, P = 0.043) in older adults over 65 years of age. In the full population, plasma homocysteine was associated with total lean mass, appendicular lean mass, gait speed, and knee extensor strength (all P < 0.05). Among older adults over 65 years of age, homocysteine level was significantly negatively correlated with gait speed and knee extensor strength (ß = -12.75, P = 0.019; ß = -0.06, P <0.001). Plasma methylmalonic acid was negatively associated with total BMD and femur BMD in the full population (ß = -0.01, P = 0.018; ß = -0.01, P = 0.004). In older adults, methylmalonic acid significantly affected total BMD, femur BMD and knee extensor strength (ß = -0.01, P = 0.048; ß = -0.01, P = 0.025; ß = -7.53, P = 0.015). Conclusions: Vitamin B12 and its biomarkers are closely related to BMD, body composition, muscle strength and physical function in middle-aged and older adults. Vitamin B12 may be an important indicator of musculoskeletal health in the elderly.
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Biomarcadores , Densidad Ósea , Homocisteína , Ácido Metilmalónico , Fuerza Muscular , Vitamina B 12 , Humanos , Vitamina B 12/sangre , Anciano , Femenino , Masculino , Biomarcadores/sangre , Persona de Mediana Edad , Densidad Ósea/fisiología , Homocisteína/sangre , Ácido Metilmalónico/sangre , Fuerza Muscular/fisiología , Músculo Esquelético/metabolismo , Encuestas Nutricionales , Composición Corporal , Estudios Transversales , Anciano de 80 o más AñosRESUMEN
Citrus reticulata cv. Chachiensis (CRC) is an important medicinal plant, its dried mature peels named "Guangchenpi", has been used as a traditional Chinese medicine to treat cough, indigestion, and lung diseases for several hundred years. However, the biosynthesis of the crucial natural products polymethoxylated flavonoids (PMFs) in CRC remains unclear. Here, we report a chromosome-scale genome assembly of CRC with the size of 314.96 Mb and a contig N50 of 16.22 Mb. Using multi-omics resources, we discover a putative caffeic acid O-methyltransferase (CcOMT1) that can transfer a methyl group to the 3-hydroxyl of natsudaidain to form 3,5,6,7,8,3',4'-heptamethoxyflavone (HPMF). Based on transient overexpression and virus-induced gene silencing experiments, we propose that CcOMT1 is a candidate enzyme in HPMF biosynthesis. In addition, a potential gene regulatory network associated with PMF biosynthesis is identified. This study provides insights into PMF biosynthesis and may assist future research on mining genes for the biosynthesis of plant-based medicines.
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Citrus , Flavonoides , Metiltransferasas , Citrus/genética , Citrus/metabolismo , Flavonoides/biosíntesis , Flavonoides/metabolismo , Metiltransferasas/metabolismo , Metiltransferasas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Redes Reguladoras de Genes , MultiómicaRESUMEN
Homologous recombination (HR) plays a key role in maintaining genomic stability, and the efficiency of the HR system is closely associated with tumor response to chemotherapy. Our previous work reported that CK2 kinase phosphorylates HIV Tat-specific factor 1 (HTATSF1) Ser748 to facilitate HTATSF1 interaction with TOPBP1, which in turn, promotes RAD51 recruitment and HR repair. However, the clinical implication of the CK2-HTATSF1-TOPBP1 pathway in tumorigenesis and chemotherapeutic response remains to be elucidated. Here, we report that the CK2-HTATSF1-TOPBP1 axis is generally hyperactivated in multiple malignancies and renders breast tumors less responsive to chemotherapy. In contrast, deletion mutations of each gene in this axis, which also occur in breast and lung tumor samples, predict higher HR deficiency scores, and tumor cells bearing a loss-of-function mutation of HTATSF1 are vulnerable to poly(ADP-ribose) polymerase inhibitors or platinum drugs. Taken together, our study suggests that the integrity of the CK2-HTATSF1-TOPBP1 axis is closely linked to tumorigenesis and serves as an indicator of tumor HR status and modulates chemotherapy response.
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Proteínas Portadoras , Quinasa de la Caseína II , Proteínas de Unión al ADN , Transducción de Señal , Humanos , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Transducción de Señal/efectos de los fármacos , Quinasa de la Caseína II/metabolismo , Quinasa de la Caseína II/genética , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Animales , Femenino , Ratones , Línea Celular Tumoral , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/patologíaRESUMEN
Ovarian cancer is a common tumor among women. It is often asymptomatic in the early stages, with most cases already at stage III to IVE at the time of diagnosis. Direct spread and lymphatic metastasis are the primary modes of metastasis, whereas hematogenous spread is rare. An initial diagnosis of ovarian cancer that has metastasized to the stomach is also uncommon. Therefore, clear treatment methods and prognostic data for such metastasis are lacking. In our hospital, we encountered a patient with an initial imaging diagnosis of a gastric tumor and a history of an ovarian tumor with endoscopic abdominal metastasis. Based on the characteristics of the case, the two tumors were considered to be the same. After chemotherapy, a partial response was observed in the stomach and pelvic lesions, suggesting the effectiveness of the treatment. Through three treatments of recurrence, gastroscopy confirmed the stomach to be a metastatic site. Therefore, determining the primary source of advanced tumors is crucial in guiding treatment decisions. Clinicians must approach this comprehensively, relying on thorough evaluation and personal experience.
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Cistadenocarcinoma Seroso , Neoplasias Ováricas , Neoplasias Gástricas , Femenino , Humanos , Carcinoma Epitelial de Ovario , Neoplasias Ováricas/patología , Pronóstico , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Estómago/diagnóstico por imagen , Estómago/patologíaRESUMEN
Home health care companies provide health care services to patients in their homes. Due to increasing demand, the provision of home health care services requires effective management of operational costs while satisfying both patients and caregivers. In practice, uncertain service times might lead to considerable delays that adversely affect service quality. To this end, this paper proposes a new bi-objective optimization problem to model the routing and scheduling problems under uncertainty in home health care, considering the qualification and workload of caregivers. A mixed-integer linear programming formulation is developed. Motivated by the challenge of computational time, we propose the Adaptive Large Neighborhood Search embedded in an Enhanced Multi-Directional Local Search framework (ALNS-EMDLS). A stochastic ALNS-EMDLS is introduced to handle uncertain service times for patients. Three kinds of metrics for evaluating the Pareto fronts highlight the efficiency of our proposed method. The sensitivity analysis validates the robustness of the proposed model and method. Finally, we apply the method to a real-life case and provide managerial recommendations.
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Servicios de Atención de Salud a Domicilio , Medicina , Humanos , Incertidumbre , Factores de Tiempo , Eficiencia OrganizacionalRESUMEN
The impaired differentiation ability of resident cells and disordered immune microenvironment in periodontitis pose a huge challenge for bone regeneration. Herein, we construct a piezoelectric hydrogel to rescue the impaired osteogenic capability and rebuild the regenerative immune microenvironment through bioenergetic activation. Under local mechanical stress, the piezoelectric hydrogel generated piezopotential that initiates osteogenic differentiation of inflammatory periodontal ligament stem cells (PDLSCs) via modulating energy metabolism and promoting adenosine triphosphate (ATP) synthesis. Moreover, it also reshapes an anti-inflammatory and pro-regenerative niche through switching M1 macrophages to the M2 phenotype. The synergy of tilapia gelatin and piezoelectric stimulation enhances in situ regeneration in periodontal inflammatory defects of rats. These findings pave a new pathway for treating periodontitis and other immune-related bone defects through piezoelectric stimulation-enabled energy metabolism modulation and immunomodulation.
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Generalist microbes have adapted to a multitude of environmental stresses through their integrated stress response system. Individual stress responses have been quantified by E. coli metabolism and expression (ME) models under thermal, oxidative and acid stress, respectively. However, the systematic quantification of cross-stress & cross-talk among these stress responses remains lacking. Here, we present StressME: the unified stress response model of E. coli combining thermal (FoldME), oxidative (OxidizeME) and acid (AcidifyME) stress responses. StressME is the most up to date ME model for E. coli and it reproduces all published single-stress ME models. Additionally, it includes refined rate constants to improve prediction accuracy for wild-type and stress-evolved strains. StressME revealed certain optimal proteome allocation strategies associated with cross-stress and cross-talk responses. These stress-optimal proteomes were shaped by trade-offs between protective vs. metabolic enzymes; cytoplasmic vs. periplasmic chaperones; and expression of stress-specific proteins. As StressME is tuned to compute metabolic and gene expression responses under mild acid, oxidative, and thermal stresses, it is useful for engineering and health applications. The modular design of our open-source package also facilitates model expansion (e.g., to new stress mechanisms) by the computational biology community.
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Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Estrés Fisiológico/genética , Oxidación-Reducción , Proteínas de Choque Térmico/metabolismo , Ácidos/metabolismo , Expresión GénicaRESUMEN
Appropriate DNA end synapsis, regulated by core components of the synaptic complex including KU70-KU80, LIG4, XRCC4, and XLF, is central to non-homologous end joining (NHEJ) repair of chromatinized DNA double-strand breaks (DSBs). However, it remains enigmatic whether chromatin modifications can influence the formation of NHEJ synaptic complex at DNA ends, and if so, how this is achieved. Here, we report that the mitotic deacetylase complex (MiDAC) serves as a key regulator of DNA end synapsis during NHEJ repair in mammalian cells. Mechanistically, MiDAC removes combinatorial acetyl marks on histone H2A (H2AK5acK9ac) around DSB-proximal chromatin, suppressing hyperaccumulation of bromodomain-containing protein BRD4 that would otherwise undergo liquid-liquid phase separation with KU80 and prevent the proper installation of LIG4-XRCC4-XLF onto DSB ends. This study provides mechanistic insight into the control of NHEJ synaptic complex assembly by a specific chromatin signature and highlights the critical role of H2A hypoacetylation in restraining unscheduled compartmentalization of DNA repair machinery.
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Cromatina , Proteínas Nucleares , Animales , Cromatina/genética , Proteínas Nucleares/metabolismo , Factores de Transcripción/metabolismo , ADN/genética , Reparación del ADN por Unión de Extremidades , Histonas/genética , Histonas/metabolismo , Emparejamiento Cromosómico , Autoantígeno Ku/genética , Autoantígeno Ku/metabolismo , Mamíferos/metabolismoRESUMEN
Mulberry (Morus alba L.), a kind of common fruits widely cultivated worldwide, has been proven various biological activities. However, its potential role in the progression of knee osteoarthritis (KOA) remains unclear. This study aims to investigate the potential protective effects of crude polysaccharide extracted from mulberry fruit, referred to as a complex blend of polysaccharides and other unidentified extracted impurities, on KOA progression. The KOA rats were established by injection of 1 mg sodium monoiodoacetate into knee, and administrated with crude mulberry polysaccharide (Mup) by gastric gavage for 4 weeks. Furthermore, intestinal bacteria clearance assay (IBCA) and fecal microbiota transplantation were conducted for the evaluation of the effect of gut microbiota (GM) on KOA. Our findings demonstrated that Mup, particularly at a dosage of 200 mg/kg, effectively improved abnormal gait patterns, reduced the level of inflammation, mitigated subchondral bone loss, restored compromised joint surfaces, alleviated cartilage destruction, and positively modulated the dysregulated profile of GM in KOA rats. Moreover, IBCA compromised the protective effects of Mup, while transplantation of fecal bacteria from Mup-treated rats facilitated KOA recovery. Collectively, our study suggested that Mup had the potential to ameliorate the progression of KOA, potentially through its modulation of GM profile.
Asunto(s)
Microbioma Gastrointestinal , Morus , Osteoartritis de la Rodilla , Ratas , Animales , Osteoartritis de la Rodilla/tratamiento farmacológico , Frutas , Polisacáridos/farmacología , Polisacáridos/uso terapéuticoRESUMEN
BACKGROUND: Cinnamomum camphora (L.) Presl (C. camphora) is an evergreen broad-leaved tree cultivated in subtropical China. The use of C. camphora as clonal cuttings for coppice management has become popular recently. However, little is known about the relationship between soil core microbiota and ecosystem multi-functionality under tree planting. Particularly, the effects of soil core microbiota on maintaining ecosystem multi-functionality under C. camphora coppice planting remained unclear. MATERIALS AND METHODS: In this study, we collected soil samples from three points (i.e., the abandoned land, the root zone, and the transition zone) in the C. camphora coppice planting to investigate whether core microbiota influences ecosystem multi-functions. RESULTS: The result showed a significant difference in soil core microbiota community between the abandoned land (AL), root zone (RZ), and transition zone (TZ), and soil ecosystem multi-functionality of core microbiota in RZ had increased significantly (by 230.8%) compared to the AL. Soil core microbiota played a more significant influence on ecosystem multi-functionality than the non-core microbiota. Moreover, the co-occurrence network demonstrated that the soil ecosystem network consisted of five major ecological clusters. Soil core microbiota within cluster 1 were significantly higher than in cluster 4, and there is also a higher Copiotrophs/Oligotrophs ratio in cluster 1. Our results corroborated that soil core microbiota is crucial for maintaining ecosystem multi-functionality. Especially, the core taxa within the clusters of networks under tree planting, with the same ecological preferences, had a significant contribution to ecosystem multi-functionality. CONCLUSION: Overall, our results provide further insight into the linkage between core taxa and ecosystem multi-functionality. This enables us to predict how ecosystem functions respond to the environmental changes in areas under the C. camphora coppice planting. Thus, conserving the soil microbiota, especially the core taxa, is essential to maintaining the multiple ecosystem functions under the C. camphora coppice planting.