RESUMEN
Proteins are manufactured by ribosomes-macromolecular complexes of protein and RNA molecules that are assembled within major nuclear compartments called nucleoli1,2. Existing models suggest that RNA polymerases I and III (Pol I and Pol III) are the only enzymes that directly mediate the expression of the ribosomal RNA (rRNA) components of ribosomes. Here we show, however, that RNA polymerase II (Pol II) inside human nucleoli operates near genes encoding rRNAs to drive their expression. Pol II, assisted by the neurodegeneration-associated enzyme senataxin, generates a shield comprising triplex nucleic acid structures known as R-loops at intergenic spacers flanking nucleolar rRNA genes. The shield prevents Pol I from producing sense intergenic noncoding RNAs (sincRNAs) that can disrupt nucleolar organization and rRNA expression. These disruptive sincRNAs can be unleashed by Pol II inhibition, senataxin loss, Ewing sarcoma or locus-associated R-loop repression through an experimental system involving the proteins RNaseH1, eGFP and dCas9 (which we refer to as 'red laser'). We reveal a nucleolar Pol-II-dependent mechanism that drives ribosome biogenesis, identify disease-associated disruption of nucleoli by noncoding RNAs, and establish locus-targeted R-loop modulation. Our findings revise theories of labour division between the major RNA polymerases, and identify nucleolar Pol II as a major factor in protein synthesis and nuclear organization, with potential implications for health and disease.
Asunto(s)
Nucléolo Celular/enzimología , Nucléolo Celular/genética , ADN Ribosómico/genética , ARN Polimerasa II/metabolismo , ARN no Traducido/biosíntesis , ARN no Traducido/genética , Ribosomas/metabolismo , Proteína 9 Asociada a CRISPR/genética , Proteína 9 Asociada a CRISPR/metabolismo , Línea Celular Tumoral , Nucléolo Celular/fisiología , ADN Helicasas/metabolismo , ADN Intergénico/genética , Humanos , Enzimas Multifuncionales/metabolismo , Biosíntesis de Proteínas , Estructuras R-Loop , ARN Helicasas/metabolismo , ARN Polimerasa I/antagonistas & inhibidores , ARN Polimerasa I/metabolismo , Ribonucleasa H/metabolismo , Ribosomas/química , Ribosomas/genética , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologíaRESUMEN
All-hydrogel supercapacitors are emerging as promising power sources for next-generation wearable electronics due to their intrinsic mechanical flexibility, eco-friendliness, and enhanced safety. However, the insufficient interfacial adhesion between the electrode and electrolyte and the frozen hydrogel matrices at subzero temperatures largely limit the practical applications of all-hydrogel supercapacitors. Here, an all-hydrogel supercapacitor is reported with robust interfacial contact and anti-freezing property, fabricated by in situ polymerizing hydrogel electrolyte onto hydrogel electrodes. The robust interfacial adhesion is developed by the synergistic effect of a tough hydrogel matrix and topological entanglements. Meanwhile, the incorporation of zinc chloride (ZnCl2) in the hydrogel electrolyte prevents the freezing of water solvents and endows the all-hydrogel supercapacitor with mechanical flexibility and fatigue resistance across a wide temperature range of 20 °C to -60 °C. Such all-hydrogel supercapacitor demonstrates satisfactory low-temperature electrochemical performance, delivering a high energy density of 11 mWh cm-2 and excellent cycling stability with a capacitance retention of 90% over 10000 cycles at -40 °C. Notably, the fabricated all-hydrogel supercapacitor can endure dynamic deformations and operate well under 2000 tension cycles even at -40 °C, without experiencing delamination and electrochemical failure. This work offers a promising strategy for flexible energy storage devices with low-temperature adaptability.
RESUMEN
BACKGROUND: Sessile serrated lesions (SSLs) are obscured lesions predominantly in the right-sided colon and associated with interval colorectal cancer; however, their prevalence and risk factors among younger individuals remain unclear. METHODS: This retrospective study enrolled individuals who underwent index colonoscopy. The primary outcome was the SSL prevalence in the younger (<50 years) and older (≥50 years) age groups, while the secondary outcomes included clinically significant serrated polyps (CSSPs). Multivariable logistic regression was employed to identify predictors. RESULTS: Of the 9854 eligible individuals, 4712 (47.8%) were categorized into the younger age group. Individuals in the younger age group exhibited lower prevalences of adenomas (22.6% vs. 46.2%; P<0.001) and right-sided adenomas (11.2% vs. 27.2%; P<0.001) compared with their older counterparts. However, both groups exhibited a similar prevalence of SSLs (7.2% vs. 6.5%; P=0.16) and CSSPs (10.3% vs. 10.3%;P=0.96). Multivariable analysis revealed that age 40-49 years (odds ratio [OR] 1.81, 95%CI 1.01-3.23), longer withdrawal time (OR 1.17, 95%CI 1.14-1.20, per minute increment), and endoscopist performance (OR 3.35, 95%CI 2.44-4.58) were independent predictors of SSL detection in the younger age group. No significant correlation was observed between adenoma and SSL detection rates among endoscopists. CONCLUSION: SSLs are not uncommon among younger individuals. Moreover, diligent effort and expertise are of paramount importance in SSL detection. Future studies should explore the clinical significance of SSLs in individuals of younger age.
Asunto(s)
Adenoma , Pólipos del Colon , Colonoscopía , Neoplasias Colorrectales , Humanos , Persona de Mediana Edad , Femenino , Masculino , Estudios Retrospectivos , Prevalencia , Colonoscopía/estadística & datos numéricos , Adulto , Pólipos del Colon/epidemiología , Pólipos del Colon/patología , Pólipos del Colon/diagnóstico , Adenoma/epidemiología , Adenoma/patología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Factores de Edad , Factores de Riesgo , AncianoRESUMEN
Thermosensitive nanoparticles can be activated by externally applying heat, either through laser irradiation or magnetic fields, to trigger the release of drug payloads. This controlled release mechanism ensures that drugs are specifically released at the tumor site, maximizing their effectiveness while minimizing systemic toxicity and adverse effects. However, its efficacy is limited by the low concentration of drugs at action sites, which is caused by no specific target to tumor sties. Herein, hyaluronic acid (HA), a gooey, slippery substance with CD44-targeting ability, was conjugated with a thermosensitive polymer poly(acrylamide-co-acrylonitrile) to produce tumor-targeting and thermosensitive polymeric nanocarrier (HA-P) with an upper critical solution temperature (UCST) at 45 °C, which further coloaded chemo-drug doxorubicin (DOX) and photosensitizer Indocyanine green (ICG) to prepare thermosensitive nanoreactors HA-P/DOX&ICG. With photosensitizer ICG acting as the "temperature control element", HA-P/DOX&ICG nanoparticles can respond to temperature changes when receiving near-infrared irradiation and realize subsequent structure depolymerization for burst drug release when the ambient temperature was above 45 °C, achieving programmable and on-demand drug release for effective antitumor therapy. Tumor inhibition rate increased from 61.8 to 95.9% after laser irradiation. Furthermore, the prepared HA-P/DOX&ICG nanoparticles possess imaging properties, with ICG acting as a probe, enabling real-time monitoring of drug distribution and therapeutic response, facilitating precise treatment evaluation. These results provide enlightenment for the design of active tumor targeting and NIR-triggered programmable and on-demand drug release of thermosensitive nanoreactors for tumor therapy.
Asunto(s)
Hipertermia Inducida , Nanopartículas , Neoplasias , Humanos , Fármacos Fotosensibilizantes/uso terapéutico , Hipertermia Inducida/métodos , Fototerapia/métodos , Doxorrubicina/química , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Verde de Indocianina/farmacología , Verde de Indocianina/química , Nanotecnología , Liberación de Fármacos , Línea Celular TumoralRESUMEN
We experimentally study two-body Coulomb explosions of CO2, O2, and CH3Cl molecules in intense femtosecond laser pulses. We observe an obvious variation in the ionic angular distribution of the fragments with respect to the kinetic energy releases (KERs). Using a classical model based on ab initio potential energy curves, we find that the dependence of the ionic angular distribution on the KER is relevant to the fact that the accurate potential energy deviates significantly from the value determined by applying the Coulomb interaction approximation at a relatively small internuclear distance of the molecule. We show that the KER-dependent ionic angular distribution provides an effective way to determine the critical internuclear distance at which the Coulomb interaction approximation holds or breaks down without relying on the knowledge of the accurate potential energy curves.
RESUMEN
AIM: Clinical diagnosis and surgical treatment of chondrosarcoma (CS) are continuously improving. The purpose of our study is to evaluate the effectiveness of microwave ablation (MWA) assisted degradation therapy in the surgical treatment of intramedullary chondrosarcoma of the extremities, to provide a new reference and research basis for the surgical treatment of CS. METHODS: We recruited 36 patients with intramedullary CS who underwent MWA assisted extended curettage. Preoperative patient demographics and clinical data were recorded. Surgery was independently assisted by a medical team. Patients were followed up strictly and evaluated for oncological prognosis, radiological results, limb joint function, pain, and complications. RESULTS: We included 15 men and 21 women (mean age: 43.5 ± 10.1). The average length of the lesion was 8.1 ± 2.5 cm. Based on preoperative radiographic, clinical manifestations, and pathological results of puncture biopsy, 28 patients were preliminarily diagnosed with CS-grade I and eight patients with CS-grade II. No recurrence or metastasis occurred in the postoperative follow-up. The average Musculoskeletal Tumor Society score was 28.8 ± 1.0, significantly better than presurgery. Secondary shoulder periarthritis and abduction dysfunction occurred in early postoperative stage CS of the proximal humerus in some, but returned to normal after rehabilitation exercise. Secondary bursitis occurred at the knee joint in some due to the internal fixation device used in treatment; however, secondary osteoarthritis and avascular necrosis of the femoral head were not observed. Overall, oncological and functional prognoses were satisfactory. CONCLUSIONS: The application of MWA assisted degradation therapy in intramedullary CS can achieve satisfactory oncology and functional prognosis, providing a new option for the limited treatment of CS.
Asunto(s)
Neoplasias Óseas , Condrosarcoma , Microondas , Humanos , Masculino , Femenino , Condrosarcoma/cirugía , Condrosarcoma/patología , Adulto , Neoplasias Óseas/cirugía , Neoplasias Óseas/patología , Microondas/uso terapéutico , Persona de Mediana Edad , Estudios de Seguimiento , Pronóstico , Extremidades/cirugía , Extremidades/patología , Legrado/métodos , Técnicas de Ablación/métodosRESUMEN
OBJECTIVE: Report three cases of simultaneous triple semicircular canal occlusion (TSCO) and cochlear implantation (CI) as the treatment of intractable Meniere's disease (MD). CASE REPORTS: Patients with MD can present occasionally with intractable vertigo and profound sensorineural hearing loss (SNHL). TSCO and CI have been proposed to control vertigo and restore profound deafness in patients with MD separately. However, a few studies have reported simultaneous TSCO and CI in the same surgical procedure for the treatment of MD. In the present study, we described three patients with MD showing incapacitating vertigo and severe SNHL who underwent simultaneous TSCO and CI after examinations of auditory system, vestibular system, and imaging. Their symptoms were significantly alleviated during the follow-up period. CONCLUSION: The combined TSCO and CI remains a viable treatment option which is effective for the control of vertigo as well as the restoring of hearing in patients with MD.
Asunto(s)
Implantación Coclear , Pérdida Auditiva Sensorineural , Enfermedad de Meniere , Humanos , Enfermedad de Meniere/complicaciones , Enfermedad de Meniere/cirugía , Vértigo/etiología , Vértigo/cirugía , Canales Semicirculares/cirugía , Audición , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Sensorineural/cirugíaRESUMEN
Mandatory waste classification has been widely considered as an effective solution for reducing the production and treatment amount of municipal solid waste. However, there is limited evidence regarding whether and how waste classification can affect the composition of residual waste (RW) and its environmental economic impacts. Here, an accounting method recommended by the Intergovernmental Panel on Climate Change, field surveys and cost-benefit analysis was utilized to investigate the changes in RW composition, environmental impacts and economic benefits under the waste classification policies implementation in Xiamen, China. This study found that: (1) The implementation of waste classification policies led to a significant increase in recyclable content from 17% to 51% and a decrease in organic content from 56% to 32%. (2) Waste classification effectively reduces greenhouse gas emissions from landfilling and incineration by an additional 0.34 tCO2-eq t-1 RW. (3) The introduction of mechanical recycling achieves a saving of 0.47 tCO2-eq t-1 RW at 40% recycling efficiency, a 4.5-fold increase compared to business as usual (BAU). (4) The operational benefits (900 yuan t-1 RW) from the recyclables sorting system offset the total expenses of investment, operation and waste disposal. The study successfully demonstrated that RW source-classified management can optimize the structure of waste composition, reduce environmental emissions and offer detailed guidance for the development of solid waste management systems in other cities in China.
RESUMEN
OBJECTIVES: Proximal femur tumor resection often leads to hip joint instability and functional loss. Various methods have been clinically applied to repair hip joint soft tissue function, but deficiencies remain. This study aims to evaluate the advantages and disadvantages of the ligament advanced reinforcement system (LARS) tumor tube in assisting soft tissue function reconstruction in patients undergoing tumor type artificial hip replacement surgery. METHODS: This study included 85 patients (41 males, 44 females) with proximal femoral tumors treated at the Xiangya Bone Tumor Treatment Center from January 2012 to January 2022, aged 10 to 79 (38.5±18.2) years. Among them, 13 cases had benign aggressive tumors, 45 had primary malignant bone tumors, and 27 had bone metastases. Clinical data, imaging data, and intraoperative photos were collected. Patients were followed up and postoperative functional evaluations were conducted using the Musculoskeletal Tumor Society (MSTS) scoring system and Harris hip joint scoring system to assess limb function and hip joint function. RESULTS: Preoperative pathological fractures were present in 37 cases (43.5%), with a lesion length of (9.4±2.9) cm. Among non-metastatic tumor patients, 7 experienced postoperative recurrence, including 6 cases of osteosarcoma and 1 case of fibrosarcoma. Pulmonary metastases occurred in 9 osteosarcoma patients. Five patients required reoperation due to postoperative complications, including 3 cases of deep vein thrombosis, 1 case of giant cell granuloma, and 1 case of prosthesis infection. Postoperatively, 5 patients exhibited Trendelenburg gait, and 6 had leg length discrepancies. The postoperative MSTS score was 26.7±1.4, and the Harris score was 89.6±5.3. CONCLUSIONS: The LARS tumor tube can effectively assist in reconstructing the soft tissue function of the hip joint and greatly reduce postoperative complications, making it an effective technical improvement in joint function reconstruction in tumor type artificial hip replacement surgery.
Asunto(s)
Artroplastia de Reemplazo de Cadera , Neoplasias Femorales , Articulación de la Cadera , Humanos , Masculino , Femenino , Artroplastia de Reemplazo de Cadera/métodos , Adulto , Persona de Mediana Edad , Adolescente , Niño , Articulación de la Cadera/cirugía , Anciano , Neoplasias Femorales/cirugía , Adulto Joven , Osteosarcoma/cirugía , Procedimientos de Cirugía Plástica/métodos , Neoplasias Óseas/cirugía , Neoplasias Óseas/secundario , Inestabilidad de la Articulación/cirugía , Inestabilidad de la Articulación/etiología , Fémur/cirugía , Prótesis de CaderaRESUMEN
Obesity is a major global health problem that significantly increases the risk of many other diseases. Herein, a facile method of suppressing lipogenesis and obesity using L-arginine-functionalized carbon dots (L-Arg@CDots) is reported. The prepared CDots with a negative surface charge form stronger bonds than D-arginine and lysine with L-Arg in water. The L-Arg@CDots in the aqueous solution offer a high photoluminescence quantum yield of 23.6% in the red wavelength region. The proposed L-Arg functionalization strategy not only protects the red emission of the CDots from quenching by water molecules but also enhances the intracellular uptake of L-Arg to reduce lipogenesis. Injection of L-Arg@CDots can reduce the body weight increase in ob/ob mice by suppressing their food intake and shrinking the white adipose tissue cells, thereby significantly inhibiting obesity.
Asunto(s)
Carbono , Puntos Cuánticos , Ratones , Animales , Carbono/química , Obesidad , Arginina , Puntos Cuánticos/químicaRESUMEN
BACKGROUND: Metabolic derangements and systemic inflammation are related to the progression of colorectal cancer (CRC) and the prognoses of these patients. The survival of stage II and III CRC patients existed considerable heterogeneity highlighting the urgent need for new prediction models. This study aimed to develop and validate prognostic nomograms based on preoperative serum liver enzyme as well as evaluate the clinical utility. METHODS: A total of 4014 stage II/III primary CRC patients pathologically diagnosed from January 2007 to December 2013 were included in this study. These patients were randomly divided into a training set (n = 2409) and a testing set (n = 1605). Univariate and multivariate Cox analyses were used to select the independent factors for predicting overall survival (OS) and disease-free survival (DFS) of stage II/III CRC patients. Next, nomograms were constructed and validated to predict the OS and DFS of individual CRC patients. The clinical utility of nomograms, tumor-node-metastasis (TNM), and the American Joint Committee on Cancer (AJCC) system was evaluated using time-dependent ROC and decision curve analyses. RESULTS: Among seven preoperative serum liver enzyme markers, aspartate aminotransferase-to-alanine aminotransferase ratio (De Ritis ratio) was identified as an independent factor for predicting both OS and DFS of stage II/III CRC patients. The nomograms incorporated De Ritis ratio and significant clinicopathological features achieved good accuracy in terms of OS and DFS prediction, with C-index of 0.715 and 0.692, respectively. The calibration curve showed good agreement between prediction by nomogram and actual observation. The results of time-dependent ROC and decision curve analyses suggested that the nomograms had improved discrimination and greater clinical benefits compared with TNM and AJCC staging. CONCLUSIONS: De Ritis ratio was an independent predictor in predicting both the OS and DFS of patients with stage II/III CRC. Nomograms based on De Ritis ratio and clinicopathological features showed better clinical utility, which is expected to help clinicians develop appropriate individual treatment strategies for patients with stage II /III CRC.
Asunto(s)
Neoplasias Colorrectales , Nomogramas , Humanos , Pronóstico , Estadificación de Neoplasias , Supervivencia sin Enfermedad , Neoplasias Colorrectales/patologíaRESUMEN
PURPOSE: Abnormalities in autonomic function are associated with an overactive bladder (OAB). Heart rate variability is generally used as the sole assessment of autonomic activity; however, we utilized neuECG, a novel method of recording skin electrical signals, to assess autonomic nervous function in healthy controls and patients with OAB before and after treatment. METHODS: The prospective sample included 52 participants: 23 patients newly diagnosed with OAB and 29 controls. Autonomic function was assessed in all participants in the morning using neuECG, which analyzed the average skin sympathetic nerve activity (aSKNA) and electrocardiogram simultaneously. All patients with OAB were administered antimuscarinics; urodynamic parameters were assessed before treatments; autonomic and bladder functions using validated questionnaires for OAB symptoms were evaluated before and after OAB treatment. RESULTS: Patients with OAB had significantly higher baseline aSKNA (p = 0.003), lower standard deviation of the normal-to-normal beat intervals, lower root mean square of the successive differences, lower high-frequency, and higher low-frequency than did controls. Baseline aSKNA had the highest value in predicting OAB (AUROC = 0.783, p < 0.001). The aSKNA was negatively correlated with first desire and normal desire in urodynamic studies (both p = 0.025) and was significantly decreased after treatment at rest, stress, and recovery phases, as compared to those before treatment (p = 0.046, 0.017, and 0.017, respectively). CONCLUSION: Sympathetic activity increased significantly in patients with OAB compared to that in healthy controls, and decreased significantly post-treatment. Higher aSKNA is associated with decreased bladder volume at which voiding is desired. SKNA may be a potential biomarker for diagnosing OAB.
Asunto(s)
Vejiga Urinaria Hiperactiva , Humanos , Estudios Prospectivos , Micción/fisiología , Antagonistas Muscarínicos/uso terapéutico , Biomarcadores , UrodinámicaRESUMEN
OBJECTIVES: Lower-extremity peripheral arterial disease (PAD) results in limb ischemia and is strongly associated with sarcopenia. This study aimed to retrospectively evaluate the association between the quantity of muscle mass in the lower extremities and the severity of vascular stenosis in PAD patients. METHODS: Between January 2018 and August 2021, 128 patients with PAD and 53 individuals without PAD, diagnosed by computed tomography, were enrolled. The severity of stenosis of lower-extremity arteries was measured using a grading system. The muscle and fat mass areas were calculated in the abdomen at the L3 or L4 level, mid-thigh, and lower leg. Multivariable logistic regression was conducted to clarify the risk associated with low muscle mass. The difference in muscle mass between PAD and non-PAD patients was evaluated by using propensity score matching. RESULTS: A strong positive correlation between the abdomen muscle area and leg muscle area was observed. The muscle area and muscle index of the leg were lower in PAD patients. These changes occurred earlier than in the abdomen muscle area. The group with more severe artery stenosis had more muscle wasting in the lower extremities. Greater age, female, lower BMI, and PAD were associated with low muscle mass. After propensity score matching, the leg muscle area was still lower in PAD patients. CONCLUSIONS: There is a direct association between PAD and regional muscle wasting. This occurs earlier regionally in the lower extremities than in central muscles. Early diagnosis of PAD might prevent progressive muscle loss, improving disease outcome and quality of life. KEY POINTS: ⢠Peripheral arterial disease is strongly associated with sarcopenia. ⢠Muscle wasting in the lower extremities is earlier and more prominent than that in the abdomen. ⢠More severe arterial stenoses are associated with higher muscle wasting in the lower extremities.
Asunto(s)
Enfermedad Arterial Periférica , Sarcopenia , Humanos , Femenino , Sarcopenia/complicaciones , Sarcopenia/diagnóstico por imagen , Sarcopenia/patología , Estudios Retrospectivos , Calidad de Vida , Constricción Patológica/patología , Extremidad Inferior/diagnóstico por imagen , Extremidad Inferior/irrigación sanguínea , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/diagnóstico por imagen , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Tomografía Computarizada por Rayos XRESUMEN
The development of metal-organic framework (MOF) adsorbents with a potential molecule sieving effect for CO2 capture and separation from flue gas is of critical importance for reducing the CO2 emissions to the atmosphere yet challenging. Herein, a cagelike MOF with a suitable cage window size falling between CO2 and N2 and the cavity has been constructed to evaluate its CO2/N2 separation performance. It is noteworthy that the introduction of coordinated dimethylamine (DMA) and N,N'-dimethylformamide (DMF) molecules not only significantly reduces the cage window size but also enhances the framework-CO2 interaction via C-H···O hydrogen bonds, as proven by molecular modeling, thus leading to an improved CO2 separation performance. Moreover, transient breakthrough experiments corroborate the efficient CO2/N2 separation, revealing that the introduction of DMA and DMF molecules plays a vital role in the separation of a CO2/N2 gas mixture.
RESUMEN
N6-methyladenosine (m6A) is the most abundant and well-studied internal modification of messenger RNAs (mRNAs). Although m6A mRNA modification has been frequently observed in osteosarcoma, the roles and underlying mechanisms of m6A modification are not yet fully elucidated. In this study, an m6A regulator, METTL3, showed to be dramatically up-regulated within osteosarcoma tissues and cells than non-cancerous healthy samples and human normal osteoblasts, respectively. In vitro, knockdown of METTL3 suppressed the viability of osteosarcomas, and their abilities to migrate and invade; in vivo, knockdown of METTL3 repressed tumor growth within xenotransplant tumor model. METTL3 upregulates COPS5 expression may be through promoting COPS5 methylation to stabilize COPS5 mRNA. The expression level of COPS5 also showed to be up-regulated within osteosarcoma tissue samples and cells. COPS5 knockdown caused no changes in METTL3 effects on METTL3 expression but partially eliminated METTL3 effects on COPS5 expression. METTL3 overexpression promoted, whereas COPS5 knockdown inhibited the malignant behaviors of osteosarcoma cells; COPS5 knockdown partially eliminated the effects of METTL3 overexpression on osteosarcoma cells. Conclusively, METTL3 and COPS5 serve as oncogenic regulators in osteosarcoma. METTL3 upregulates COPS5 expression in osteosarcoma in an m6A-related manner.
Asunto(s)
Neoplasias Óseas , Osteosarcoma , Neoplasias Óseas/genética , Complejo del Señalosoma COP9/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Metilación , Metiltransferasas/metabolismo , Osteosarcoma/genética , Osteosarcoma/metabolismo , Péptido Hidrolasas/metabolismo , ARN Mensajero/genéticaRESUMEN
BACKGROUND: Despite being a common malignant tumor, the molecular mechanism underlying the initiation and progression of triple-negative breast cancers (TNBCs) remain unclear. Tumor-associated macrophages (TAMs) are often polarized into a pro-tumor phenotype and are associated with a poor prognosis of TNBCs. Exosomes, important mediators of cell-cell communication, can be actively secreted by donor cells to reprogram recipient cells. The functions and molecular mechanisms of tumor cell-derived exosomes in TNBCs progression and TAMs reprogramming urgently need to be further explored. RESULTS: We demonstrated that tumor cell-derived exosomes enriched with miR-184-3p were taken up by macrophages to inhibit JNK signaling pathway by targeting EGR1, thereby inducing M2 polarization of macrophages and synergistically promoting tumor progression. Nanoparticles loaded with oncogene c-Myc inhibitor JQ1 could suppress the polarization process by reducing Rac1-related exosome uptake by macrophage. More importantly, it was found for the first time that tumor-suppressive miR-184-3p was actively sorted into exosomes by binding to RNA-binding protein heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), thus facilitating tumor cell proliferation and metastasis by relieving the inhibitory effect of miR-184-3p on Mastermind-like 1 (MAML1). Overexpressing miR-184-3p in tumor cells and simultaneously knocking down hnRNPA2B1 to block its secretion through exosomes could effectively inhibit tumor growth and metastasis. CONCLUSIONS: Our study revealed that hnRNPA2B1-mediated exosomal transfer of tumor-suppressive miR-184-3p from breast cancer cells to macrophages was an important mediator of TNBCs progression, providing new insights into TNBCs pathogenesis and therapeutic strategies.
Asunto(s)
MicroARNs , Neoplasias , MicroARNs/genética , MicroARNs/metabolismo , Línea Celular Tumoral , Microambiente Tumoral , Proliferación CelularRESUMEN
BACKGROUND: Allograft reconstruction following the resection of malignant bone tumors is associated with high rates of complications and failures. This study aimed to evaluate the efficacy and current problems of allograft reconstruction techniques to optimize treatment strategies at our center. MATERIALS AND METHODS: Thirty-eight cases (16 men and 22 women), who were diagnosed with malignant bone tumors and had undergone allograft reconstruction, were recruited. Allograft was fixed by intramedullary nail, single steel plate, double plate, and intramedullary nail combined plate in 2, 4, 17, and 15 cases, respectively. Allograft union, local recurrence, and complications were assessed with clinical and radiological tests. Tumor grade was assessed using the Enneking staging of malignant bone tumors. Functional prognosis was evaluated by the Musculoskeletal Tumor Society (MSTS) scoring system. RESULTS: Intercalary and osteoarticular reconstructions were performed in 32 and 6 cases, respectively. Six patients underwent reoperation related to allograft complications, four patients had local recurrence, and three patients with allograft fracture underwent allograft removal. A total of eight host-donor junctions showed nonunion, including seven cases (18.4%) in diaphysis and one case (3.1%) in metaphysis (p < 0.01). Host rejection and secondary osteoarthritis occurred in nine and two cases, respectively. No deep infection and internal fixation device fracture occurred. The overall allograft survival rate was 81.6%. Postoperative MSTS score of patients with allograft survival was 26.8 ± 2.9, indicating a significant improvement as compared to their preoperative function. CONCLUSIONS: Allograft represents an excellent choice for intercalary bone defects after malignant bone tumor resection. Robust internal fixation protection across the whole length of the allograft is an important prerequisite for the survival of the allograft, while multidimensional osteotomy, intramedullary cement reinforcement, and pedicled muscle flap transfer can effectively improve the survival rate and healing rate of the allograft.
Asunto(s)
Neoplasias Óseas , Procedimientos de Cirugía Plástica , Masculino , Humanos , Femenino , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias Óseas/patología , Aloinjertos/patología , Trasplante Óseo/métodosRESUMEN
BACKGROUND: Shoulder soft tissue function reconstruction during tumor-type hemishoulder replacement is an important step to restore shoulder function. This study evaluates the functional prognosis and postoperative complications of ligament advanced reinforcement system (LARS)-assisted soft tissue functional reconstruction in tumor-type hemi-shoulder replacement. MATERIALS AND METHODS: Twenty-two patients with an average age of 37.5 ± 17.8 years diagnosed with benign invasive tumors, primary malignant bone tumors, or bone metastases were enrolled in this study. The patient's medical records (history and surgical details), histological sections, imaging files, oncological prognosis, functional prognosis, and postoperative complications were collected. The upper limb function and shoulder joint function were evaluated using the Musculoskeletal Tumor Society (MSTS) system and American Shoulder and Elbow Surgeons (ASES) scoring criteria, respectively. RESULTS: Twenty-two patients comprising 12 males and 10 females were enrolled. Overall, 9 patients had preoperative pathological fractures. The mean lesion length was 8.6 ± 3.0 cm. The local recurrence was observed in 3 cases, including 2 cases of osteosarcoma and 1 case of MGCT. A further 4 cases had pulmonary metastasis, including 2 cases with local tumor recurrence. The average postoperative MSTS score was 25.8 ± 1.7, and the score of postoperative ASES was 85.7 ± 6.0, both of which showed satisfactory functional recovery. Two cases experienced postoperative complications requiring surgical intervention, including one periprosthetic fracture and one giant cell granuloma. Prosthesis dislocation occurred in 1 case. None of the cases of periprosthetic infection or postoperative complications resulted in implant failure. CONCLUSIONS: LARS-assisted soft tissue function reconstruction in benign and malignant proximal humerus tumors after a tumor-type hemi-shoulder replacement is an effective technical improvement, which can effectively repair the integrity of the joint capsule to restore joint stability, provide a medium for soft tissue attachment to rebuild the muscular dynamic system, and eliminate residual dead space around the prosthesis, effectively improving limb function and reduce postoperative infection complications.
Asunto(s)
Artroplastía de Reemplazo de Hombro , Neoplasias Óseas , Osteosarcoma , Articulación del Hombro , Masculino , Femenino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Articulación del Hombro/cirugía , Osteosarcoma/cirugía , Osteosarcoma/patología , Neoplasias Óseas/patología , Complicaciones Posoperatorias/cirugía , Ligamentos/patologíaRESUMEN
The potential benefits to surgical outcomes of intraoperative and/or same-day computed tomography (CT) during isolated orbital fracture reconstruction are debatable, and previous research on this topic is limited by small sample size. This retrospective IBM MarketScan Commercial and Medicare Supplemental research database study examined patients undergoing isolated orbital reconstruction from January 1, 2012 to December 31, 2018, to assess whether same-day CT affected postoperative outcomes. The average age of the 5,023 participants was 37 (standard deviation [SD]: 16) years and 63% were males. The data revealed that 16.2% (815 of 5,023) patients underwent a same-day CT. Those who underwent a same-day CT scan exhibited reduced odds of postoperative enophthalmos (adjusted odds ratio [aOR]: 0.269; 95% confidence interval [CI]: 0.167-0.433) and diplopia (aOR: 0.670; 95% CI: 0.495-906). Interestingly, these patients also displayed a higher rate of revision surgeries (aOR: 2.721; 95% CI: 1.893-3.912). In summary, while same-day CT scans diminish certain postoperative complications of orbital fracture repair, they are also associated with an increased likelihood of subsequent surgical revision.
RESUMEN
A glucose biosensor was layer-by-layer assembled on a modified glassy carbon electrode (GCE) from a nanocomposite of NAD(P)+-dependent glucose dehydrogenase, aminated polyethylene glycol (mPEG), carboxylic acid-functionalized multi-wall carbon nanotubes (fMWCNTs), and ionic liquid (IL) composite functional polymers. The electrochemical electrode was denoted as NF/IL/GDH/mPEG-fMWCNTs/GCE. The composite polymer membranes were characterized by cyclic voltammetry, ultraviolet-visible spectrophotometry, electrochemical impedance spectroscopy, scanning electron microscopy, and transmission electron microscopy. The cyclic voltammogram of the modified electrode had a pair of well-defined quasi-reversible redox peaks with a formal potential of -61 mV (vs. Ag/AgCl) at a scan rate of 0.05 V s-1. The heterogeneous electron transfer constant (ks) of GDH on the composite functional polymer-modified GCE was 6.5 s-1. The biosensor could sensitively recognize and detect glucose linearly from 0.8 to 100 µM with a detection limit down to 0.46 µM (S/N = 3) and a sensitivity of 29.1 nA µM-1. The apparent Michaelis-Menten constant (Kmapp) of the modified electrode was 0.21 mM. The constructed electrochemical sensor was compared with the high-performance liquid chromatography method for the determination of glucose in commercially available glucose injections. The results demonstrated that the sensor was highly accurate and could be used for the rapid and quantitative determination of glucose concentration.