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The hierarchical self-assembly of colloidal particles facilitates the bottom-up manufacturing of metamaterials with synergistically integrated functionalities. Here, we define a modular assembly methodology that enables multinary co-assembly of nanoparticles in one-dimensional confined space. A series of isotropic and anisotropic nanocrystals such as plasmonic, metallic, visible, and near-infrared responsive nanoparticles as well as transition-metal phosphides can be selectively assembled within the single-walled Co(OH)2 nanotubes to achieve various increasingly sophisticated assembly systems, including unary, binary, ternary, and quaternary superstructures. Moreover, the selective assembly of distinct functional nanoparticles produces different integrated functional superstructures. This generalizable methodology provides predictable pathways to complex architectures with structural programming and customization that are otherwise inaccessible.
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In this study, we aim to evaluate the correlation between T score measured by dual X-ray absorptiometry (DXA), volumetric bone mineral density (vBMD) derived from quantitative computed tomography (QCT) and MRI-based vertebral bone quality (VBQ), explore the diagnostic performance of VBQ in osteoporosis and determine the recognition value of VBQ in osteoporotic fracture in a relatively large cohort of elderly patients scheduled to undergo spinal surgery. A total of 260 patients were enrolled in the study. DXA and QCT were used to evaluate osteoporotic status. We calculated the lumbar VBQ score, analyzed the correlation between T score, vBMD and VBQ, and explored whether VBQ was an influential factor of bone quality and fracture by binary logistic regression as well as the diagnostic performance of VBQ in osteoporosis and fracture by ROC curve. VBQ was negatively correlated with vBMD and T score. (r = - 0.487 vs. r = - 0.220). The VBQ score was a risk factor for osteoporosis under the QCT diagnostic criteria (OR = 2.245, 95% CI 1.456-3.460) and osteoporotic fractures (OR = 1.496, 95% CI 1.097-2.040). It exhibited superior discriminant performance for osteoporosis diagnosed by QCT, with a cutoff value of 3.70 and an AUC of 0.7354. Its cutoff value for osteoporotic fractures was 3.72, and its AUC was 0.6717. In a cohort of elderly patients scheduled to undergo spinal surgery, the VBQ score was more strongly associated with vBMD than the T score and could identify patients with osteoporosis and corresponding vertebral compression fracture (VCF).
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Fracturas por Compresión , Osteoporosis , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Humanos , Anciano , Absorciometría de Fotón/métodos , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas por Compresión/diagnóstico por imagen , Fracturas de la Columna Vertebral/diagnóstico por imagen , Densidad Ósea , Osteoporosis/diagnóstico por imagen , Vértebras Lumbares/lesionesRESUMEN
BACKGROUND: Robust evidence on whether diagnostic discordance exists between lumbar osteoporosis detected by quantitative computed tomography (QCT) vs. dual-energy X-ray absorptiometry (DXA) is still lacking. In this study involving a relatively large prospective cohort of older men (aged > 60 years) and postmenopausal women, we assessed lumbar QCT-derived volumetric bone mineral density (vBMD) and DXA-derived area BMD and evaluated their predictive performance for prevalent vertebral fracture (VF). METHODS: A total of 501 patients who underwent spinal surgery from September 2020 to September 2022 were enrolled. The criteria recommended by the American College of Radiology and the World Health Organization were used for lumbar osteoporosis diagnosis. The osteoporosis detection rates between QCT and DXA were compared. QCT-vBMD was plotted against the DXA T score, and the line of best fit was calculated based on linear regression. Multivariate logistic regression was used to analyze the associations between risk factors and VF. Receiver operating characteristic curve analysis was performed, and the corresponding area under the curve (AUC) was calculated. RESULTS: QCT screening showed that 60.7% of patients had osteoporosis, whereas DXA screening showed that 50.7% of patients had osteoporosis. Diagnoses were concordant for 325 (64.9%) patients. In all, 205 patients suffered a VF of at least one anatomic level. Of these, 84.4% (173/205) were diagnosed with osteoporosis by QCT, while only 73.2% (150/205) were diagnosed by DXA. Multivariate logistic regression showed that osteoporosis detected by QCT exhibited a stronger relationship with VF than that detected by DXA (unadjusted OR, 6.81 vs. 5.04; adjusted OR, 3.44 vs. 2.66). For discrimination between patients with and without VF, QCT-vBMD (AUC = 0.802) showed better performance than DXA T score (AUC = 0.76). CONCLUSION: In older patients undergoing spinal surgery, QCT-vBMD is more helpful than DXA in terms of osteoporosis detection rate and prediction of patients with prevalent VFs.
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Osteoporosis , Fracturas de la Columna Vertebral , Masculino , Humanos , Femenino , Anciano , Absorciometría de Fotón/métodos , Estudios Prospectivos , Osteoporosis/diagnóstico por imagen , Osteoporosis/epidemiología , Densidad Ósea , Tomografía Computarizada por Rayos XRESUMEN
Extracellular vesicles (EVs) are secreted by various tissues and cells under normal physiological or pathological conditions. Exercise-induced EVs may be involved in the adaptation of exercise-induced fatigue. The 1500-m freestyle is the longest pool-based swimming event in the Olympic Games, and there is a paucity of information regarding changes in the miRNA profiles of circulating EVs after a single session of fatiguing swimming. In this study, 13 male freestyle swimmers conducted a fatiguing 1500-m freestyle swimming session at the speed of their best previously recorded swimming performance. Fasting venous blood was collected before and after the swimming session for analysis. 70 miRNAs from the circulating EVs were found to be differentially expressed after the fatiguing 1500-m freestyle swimming session, among which 45 and 25 miRNAs were up-regulated and down-regulated, respectively. As for the target genes of five miRNAs (miR-144-3p, miR-145-3p, miR-509-5p, miR-891b, and miR-890) with the largest expression-fold variation, their functional enrichment analysis demonstrated that the target genes were involved in the regulation of long-term potentiation (LTP), vascular endothelial growth factor (VEGF), glutathione metabolism pathway, dopaminergic synapse, signal transmission, and other biological processes. In summary, these findings reveal that a single session of fatiguing swimming modifies the miRNAs profiles of the circulating EVs, especially miR-144-3p, miR-145-3p, miR-509-5p, miR-891b, and miR-890, which clarifies new mechanisms for the adaptation to a single session of fatiguing exercise from the perspective of EV-miRNAs.
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Vesículas Extracelulares , MicroARNs , Humanos , Natación , Factor A de Crecimiento Endotelial Vascular , MicroARNs/genética , MicroARNs/metabolismo , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , AtletasRESUMEN
PURPOSE: The study evaluated the diagnostic performance of metagenomic next-generation sequencing (mNGS) as a diagnostic test for biopsy samples from patients with suspected spinal infection (SI) and compared the diagnostic performance of mNGS with that of microbial culture. METHODS: All patients diagnosed with clinical suspicion of SI were enrolled, and data were collected through a retrospective chart review of patient records. Biopsy specimens obtained from each patient were tested via mNGS and microbial culture. Samples were enriched for microbial DNA using the universal DNA extraction kit, whole-genome amplified, and sequenced using MGISEQ-200 instrument. After Low-quality reads removed, the remaining sequences for microbial content were analyzed and aligned using SNAP and kraken2 tools. RESULTS: A total of 39 patients (19 men and 20 women) were deemed suitable for enrollment. The detection rate for pathogens of mNGS was 71.8% (28/39), which was significantly higher than that of microbial culture (23.1%, p = 0.016). Mycobacterium tuberculosis complex was the most frequently isolated. Using pathologic test as the standard reference for SI, thirty-one cases were classified as infected, and eight cases were considered aseptic. The sensitivity and specificity values for detecting pathogens with mNGS were 87.1% and 87.5%, while these rates were 25.8% and 87.5% with conventional culture. mNGS was able to detect 88.9% (8/9) of pathogens identified by conventional culture, with a genus-level sensitivity of 100% (8/8) and a species-level sensitivity of 87.5% (7/8). CONCLUSION: The present work suggests that mNGS might be superior to microbial culture for detecting SI pathogens.
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Afecto , Secuenciación de Nucleótidos de Alto Rendimiento , Masculino , Humanos , Femenino , Estudios Retrospectivos , ADN , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Double eyelid blepharoplasty has gained popularity over decades among Asians. Quantitative assessment of the morphologic changes after double eyelid blepharoplasty remains obscure. A photo-assisted digital method was introduced to measure the outcomes of double eyelid surgery in young Chinese. METHODS: A total of 168 Chinese patients who underwent esthetic upper blepharoplasty were recruited from October 2018 to October 2020. The participants were divided into mini-incision, full-incision, and full-incision double with epicanthoplasty (FIDE) groups. Changes in the eyeball exposure area (EEA), brow eyelid margin distance [brow eyelid distance (BED)], and palpebral crease height after surgery were analyzed using ImageJ software. RESULTS: There was an overall increase in EEA in the 3 groups after upper blepharoplasty surgery. The FIDE group showed the most increase in EEA among these groups. Furthermore, BED was significantly decreased in each group after upper eyelid blepharoplasty; however, the mini-incision double group showed the least BED reduction. The palpebral crease height at 90 days was significantly lower than that at 7 days after surgery. CONCLUSIONS: The photo-assisted anthropometric analysis offers a simple and objective measurement for double eyelid blepharoplasty. The eyes appear larger because of the increase in EEA and decrease in BED after double eyelid blepharoplasty. Distinct results were produced by different surgical techniques. The FIDE group showed the maximum increase in EEA and a decrease in BED. These findings provide important references for preoperative planning and postoperative measurement.
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Blefaroplastia , Humanos , Pueblo Asiatico , Blefaroplastia/métodos , Pueblos del Este de Asia , Párpados/cirugía , Párpados/anatomía & histología , Estudios Retrospectivos , Fotograbar/métodosRESUMEN
Targeted therapies and immunotherapy have brought substantial benefits to patients with melanoma. However, brain metastases remain the biggest threat to the survival and quality of life of melanoma patients. One of the major challenges to an effective therapy is the inability of drugs to penetrate the blood-brain barrier (BBB). Anti-schizophrenic drugs can cross the BBB, and many of them have demonstrated anti-cancer effects. Repurposing existing drugs for new clinical indications is an alluring strategy for anticancer drug discovery. Herein, we applied this strategy and screened a small collection of existing anti-schizophrenic drugs to use as anti-melanoma agents. Among them, trifluoperazine dihydrochloride (TFP) exhibited promising potencies for suppressing the growth and metastasis of melanoma, both in vitro and in vivo. TFP obviously suppressed the viability of melanoma cells within the micromolar range and inhibited the growth of melanoma in the subcutaneous mice models. Notably, intraperitoneal (i.p.) administration of TFP (40 mg/kg/day) obviously inhibited the growth of intra-carotid-injection established melanoma brain metastasis and extended the survival of brain metastasis-bearing mice. Moreover, TFP significantly suppressed lung metastasis and bone metastasis of melanoma in preclinical metastasis models. Mechanistically, TFP caused G0/G1 cell cycle arrest and mitochondrial-dependent intrinsic apoptosis of melanoma cells. In addition, TFP treatment increased the expression of microtubule associated protein 1 light chain 3 beta-II (LC3B-II) and p62 in vitro, suggesting an inhibition of autophagic flux. TFP decreased LysoTracker Red uptake after treatment, indicating impaired acidification of lysosomes. Moreover, the colocalization of LC3 with lysosomal-associated membrane protein 1 (LAMP1), a lysosome marker, was also suppressed after TFP treatment, suggesting that TFP might block the fusion of autophagosomes with lysosomes, which led to autophagosome accumulation. Taken together, our data highlight the potential of repurposing TFP as a new adjuvant drug for treating melanoma patients with brain, lung, and bone metastases.
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Antineoplásicos/uso terapéutico , Antipsicóticos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Trifluoperazina/uso terapéutico , Animales , Autofagia/efectos de los fármacos , Neoplasias Óseas/secundario , Neoplasias Encefálicas/secundario , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Reposicionamiento de Medicamentos , Femenino , Humanos , Neoplasias Pulmonares/secundario , Melanoma/patología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Endogámicos C57BL , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: The nasal ala plays an important role in the aesthetic appearance of the nose. Repairing the nasal alar defect, especially full-thickness alar defect, is one of the difficulties of plastic surgeons. In this article, a new surgical method is introduced about repairing full-thickness alar defect with free auricular composite flaps and local nasal alar rotation and advancement tissue flaps. MATERIALS AND METHODS: We retrospectively reviewed 6 patients with a diagnosis of full-thickness alar defect between 2010 and 2013. All of them accepted this new surgical method. The patients were followed up for 6 to 12 months. The method used local nasal alar rotation and advancement tissue flap to form new nasal rim and made the defect of nasal rim shift to alar groove region. After that, we harvested free auricular composite flap to repair the new defect. RESULT: All patients attained relatively symmetrical nostrils with a natural, smooth, integrated alar rim and inconspicuous scars. All the reconstructed nasal alae were aesthetically satisfactory. Slight atrophy of grafts was observed in all patients. The shape of the donor ear changed a little. Two patients experienced hyperpigmentation change and one patient presented slight hypertrophic scar in the suture site. No other complications were observed. CONCLUSIONS: This simple method not only reconstructed almost normal nasal alar rims and alar grooves but also improved the survival rate of the composite grafts without any free edges. This method also changed the traditional free auricular tissue flap location from the nasal alar rim to the upper alar groove region, which would help achieve more aesthetic appearance. This new method is a creative and useful technique for the repair of full-thickness alar defect.
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Cartílago/trasplante , Colgajos Tisulares Libres/cirugía , Enfermedades Nasales/cirugía , Nariz/lesiones , Rinoplastia/métodos , Colgajos Quirúrgicos/cirugía , Adulto , Anastomosis Quirúrgica/métodos , Preescolar , Estética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Infection of open tibial fractures with contamination remains a challenge for orthopedic surgeons. Local use of antibiotic-impregnated polymethylmethacrylate (PMMA) beads and blocks is a widely used procedure to reduce the risk of infection. However, the development of antibiotic-resistant organisms make the management of infection more difficult. Our in vitro study demonstrated that quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan [HACC])-loaded PMMA bone cement exhibits strong antibacterial activity toward antibiotic-resistant bacteria. Therefore, the present study aimed to investigate the in vivo antibacterial activity of quaternized chitosan-loaded PMMA. Twenty-four adult female New Zealand White rabbits were used in this study. The right proximal tibial metaphyseal cavity was prepared, 10(7) CFU of methicillin-resistant Staphylococcus epidermidis was inoculated, and PMMA-only, gentamicin-loaded PMMA (PMMA-G), chitosan-loaded PMMA (PMMA-C), or HACC-loaded PMMA (PMMA-H) bone cement cylinders were inserted. During the follow-up period, the infections were evaluated using X rays on days 21 and 42 and histopathological and microbiological analyses on day 42 after surgery. Radiographic indications of bone infections, including bone lysis, periosteal reactions, cyst formation, and sequestral bone formation, were evident in the PMMA, PMMA-G, and PMMA-C groups but not in the PMMA-H group. The radiographic scores and gross bone pathological and histopathological scores were significantly lower in the PMMA-H group than in the PMMA, PMMA-G, and PMMA-C groups (P < 0.05). Explant cultures also indicated significantly less bacterial growth in the PMMA-H group than in the PMMA, PMMA-G, and PMMA-C groups (P < 0.01). We concluded that PMMA-H bone cement can inhibit the development of bone infections in this animal model inoculated with antibiotic-resistant bacteria, thereby demonstrating its potential application for treatment of local infections in open fractures.
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Cementos para Huesos/química , Cementos para Huesos/uso terapéutico , Quitosano/química , Epidermis/microbiología , Polimetil Metacrilato/química , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus epidermidis/efectos de los fármacos , Staphylococcus epidermidis/patogenicidad , Tibia/microbiología , Animales , Femenino , Resistencia a la Meticilina , ConejosRESUMEN
BACKGROUND AND OBJECTIVE: The deepening of the nasolabial fold (NLF) is a common occurrence during the aging process, necessitating the development of an objective method to evaluate changes in NLFs. The objective of our study was to introduce a method of depth deviation based on three-dimensional (3D) image for evaluating the efficacy of hyaluronic acid (HA) injection in correcting NLFs. METHODS: Between May 2019 and November 2019, we recruited 56 Chinese volunteers with moderate to severe NLFs for this study. The participants received HA injections and were followed up for a period of 12 months. Pre and posttreatment, we collected the Wrinkle Severity Rating Scale (WSRS) scores and 3D images. To assess the efficacy of NLF correction, we used the maximum value of depth deviation (MVD) based on 3D images and the Global Aesthetic Improvement Scale (GAIS) score. Additionally, we compared the relationship between MVD and other clinical parameters. RESULTS: Fifty-four female participants completed the study and were included in the analysis. The HA injection resulted in a significant decrease in NLF severity (p < 0.05). One month after the injection, the average GAIS score was 4.72 ± 0.45, and the average MVD was 2.10 ± 0.56 mm. Both the GAIS score and the average MVD exhibited a decline over time during the follow-up period, with the average MVD showing a significant correlation with the GAIS score at all time points (p < 0.05). CONCLUSIONS: Using 3D technology, we demonstrated that the quantitative data provided by MVD can serve as an objective method for evaluating the correction of NLFs.
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Técnicas Cosméticas , Rellenos Dérmicos , Envejecimiento de la Piel , Humanos , Femenino , Surco Nasolabial , Imagenología Tridimensional , Estudios Prospectivos , Ácido Hialurónico , Resultado del TratamientoRESUMEN
Solid polymer electrolytes (SPEs) have shown great promise in the development of lithium-metal batteries (LMBs), but SPEs' interfacial instability and limited ionic conductivity still prevent their widespread applications. Herein, high-concentration hybrid dual-salt "polymer-in-salt" electrolytes (HDPEs) through formulation optimization were facilely prepared to simultaneously boost ionic conductivity, improve interfacial compatibility, and ensure a wide-temperature-range operation with high safety. An optimized electrolyte (HDPE-0.6) shows negligible corrosion to the aluminum current collector after manipulating the salt ratio of lithium bis(trifluoromethane)sulfonimide and lithium bis(oxalato)borate. In addition, HDPE-0.6 has excellent ionic conductivity (i.e., â¼0.536, â¼0.898, and â¼1.28 mS cm-1 at 0, 30, and 60 °C), approaching 1 mS cm-1 at room temperature. Furthermore, HDPE-0.6 exhibits a high lithium transference number of 0.6 and a high electrochemical oxidation stability potential of > 4.8 V vs. Li/Li+. Additionally, due to the formulation of high-concentration thermally stable lithium salts and the employment of flame-retardant trimethyl phosphate as the solvent, HDPE-0.6 has no safety issues. The resultant LiFePO4|HDPE-0.6|Li cell exhibits high discharge capacity, good rate capability, and excellent cycle stability at extended temperatures of 0, 30, and 60 °C. By coupling theoretical calculations and in-depth X-ray photoelectron spectroscopy, we attribute the excellent cycle stability to the formation of a stable interphase. Moreover, our formulation strategy is suitable for the Na3V2(PO4)3//Na battery when replacing the lithium salts with sodium salts (i.e., sodium bis(trifluoromethane)sulfonimide and sodium bis(oxalato)borate) to yield HDPE-0.6-Na, as demonstrated by excellent cycle stability (e.g., 98.6 % of capacity retention after 300 cycles). Our work demonstrates that the as-developed quasi-solid HDPEs are suitable for LMBs and sodium-metal batteries, and HDPEs can function normally in a wide temperature range.
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BACKGROUND: Skin cutaneous melanoma (SKCM) is one of the fastest developing malignancies with strong aggressive ability and no proper curative treatments. Numerous studies illustrated the importance of N6-methyladenosine (m6A) RNA modification to tumorigenesis. The aim of this study was to identify novel prognostic signature by using m6A-related lncRNAs, thus to improve the survival for SKCM patients and guide SKCM therapy. METHODS: We downloaded the Presentational Matrix data from The Cancer Genome Atlas (TCGA) and analyzed all the expressed lncRNAs among 468 SKCM samples. Pearson correlation analysis was performed to assess the correlations between lncRNAs and 29 m6A-related genes. Least absolute shrinkage and selection operator (LASSO), univariate and multivariate Cox regression analysis were performed to construct m6A-related lncRNAs prognostic signature (m6A-LPS). The accuracy and prognostic value of this signature were validated by using receiver operating characteristic (ROC) curves, Kaplan-Meier (K-M) survival analysis, univariate COX or multivariate COX analyses. After calculating risk scores, patients were divided into low- and high-risk subgroups by the median value of risk scores. RESULTS: A total of 2973 lncRNAs were found expressed among SKCM tissues. Prognostic analysis showed that 98 lncRNAs had a significant effect on the survival of SKCM patients. The m6A-LPS was validated using K-M and ROC analysis and the predictive accuracy of the risk score was also high according to the AUC of the ROC curve in training and testing sets. A nomogram based on tumor stage, gender and risk score that had a strong ability to forecast the 1-, 2-, 3-, 5-year OS of SKCM patients confirmed by calibrations. Enrichment analysis indicated that malignancy-associated biological processes and pathways were more common in the high-risk subgroup. CONCLUSION: Collectively, m6A-related lncRNAs exert as potential biomarkers for prognostic stratification of SKCM patients and may assist clinicians achieving individualized treatment for SKCM.
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Adenina/análogos & derivados , Melanoma , ARN Largo no Codificante , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico , Melanoma/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , ARN Largo no Codificante/genética , Lipopolisacáridos , PronósticoRESUMEN
OBJECTIVE: This study aimed to investigate the impact of lifelong exercise, including both moderate-intensity continuous training and high-intensity interval training, on blood lipid levels and mental behaviour in naturally ageing mice to identify effective exercise strategies for ageing-related health issues. METHODS: Six-week-old male BALB/c mice were randomly assigned to one of four groups: young control (YC), natural ageing control (OC), lifelong moderate-intensity continuous exercise (EM), and lifelong high-intensity interval exercise (EH) groups. The EM group was trained at a speed corresponding to 70 % of the maximum running speed, while the EH group was trained at a running speed alternating between 50 % of the maximum running speed, 70 % of the maximum running speed, and 90 % of the maximum running speed. All exercise sessions were conducted three times per week, with each session lasting 50 min. Behavioural tests and blood sample collection were conducted at 72 weeks of age. RESULTS: Ageing in mice led to changes in muscle and fat mass. Both the EM and EH groups showed greater muscle mass and lower fat mass than did the OC group. Ageing was associated with elevated anxiety (fewer open arm entries, time spent in the central region) and depression (lower sucrose preference) indicators. However, these changes were reversed in both exercise groups, with no differences between the two exercise groups. Blood lipid levels, including total cholesterol (TC), total triglycerides (TGs), low-density lipoprotein (LDL), and free fatty acid (FFA) levels, were greater in the OC group than in the YC group. Additionally, the OC group exhibited lower high-density lipoprotein (HDL) levels. However, both the EM and EH groups exhibited improved lipid profiles compared to those of the YC group. CONCLUSION: Lifelong exercise, whether moderate-intensity continuous or high-intensity interval training, can preserve body health during ageing, prevent anxiety and depression, and maintain stable blood lipid levels. Both exercise types are equally effective, suggesting that exercise intensity may not be the critical factor underlying these beneficial adaptations.
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Envejecimiento , Entrenamiento de Intervalos de Alta Intensidad , Lípidos , Ratones Endogámicos BALB C , Condicionamiento Físico Animal , Animales , Masculino , Condicionamiento Físico Animal/fisiología , Entrenamiento de Intervalos de Alta Intensidad/métodos , Envejecimiento/fisiología , Lípidos/sangre , Ratones , Depresión/sangre , Ansiedad/sangre , Conducta Animal , Salud Mental , Triglicéridos/sangre , Músculo Esquelético/metabolismoRESUMEN
BACKGROUND: The incidence of melanoma brain metastasis (MBM) is high and significantly compromises patient survival and quality of life. Effective treatment of MBM is made difficult by the blood-brain barrier (BBB), since it restricts the entry of drugs into the brain. Certain anti-psychotic drugs able to cross the BBB have demonstrated efficacy in suppressing brain metastasis in preclinical studies. However, the activity of zuclopenthixol against MBM is not yet clear. METHODS: Cell viability assays were employed to investigate the potential of zuclopenthixol in the treatment of MBM. Subsequently, the mechanism of action was investigated by RNA-sequencing (RNAseq), flow cytometry-based cell cycle and apoptosis assays, protein expression analysis, and autophagy flux detection. Additionally, the efficacy of zuclopenthixol against tumor growth was investigated in vivo, including MBM models. RESULTS: Zuclopenthixol inhibited the proliferation of various melanoma cell lines at minimal doses by causing cell cycle arrest in the G0/G1 phase and mitochondrial-mediated intrinsic apoptosis. Zuclopenthixol also induced cytoprotective autophagy, and inhibition of autophagy enhanced the anti-melanoma effects of zuclopenthixol. Furthermore, zuclopenthixol inhibited the growth of human melanoma tumors in nude mice, as well as the growth of intracranial metastases in a mouse model of MBM. CONCLUSIONS: These results demonstrate that zuclopenthixol has significant potential as an effective therapeutic agent for MBM.
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Apoptosis , Neoplasias Encefálicas , Puntos de Control del Ciclo Celular , Proliferación Celular , Melanoma , Apoptosis/efectos de los fármacos , Animales , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/patología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Melanoma/metabolismo , Proliferación Celular/efectos de los fármacos , Ratones , Antipsicóticos/farmacología , Autofagia/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Desnudos , Supervivencia Celular/efectos de los fármacosRESUMEN
Measuring causal brain network is a significant topic for exploring complex brain functions. While various data-driven algorithms have been proposed, they still have some drawbacks such as ignoring time non-separability, cumbersome parameter settings, and poor robustness. To solve these deficiencies, we developed a novel framework: "time-shift permutation cross-mapping, TPCM," integrating steps of (1) delayed improved phase-space reconstruction (DIPSR), (2) rank transformation of embedding vectors' distances, (3) cross-mapping with a fitting estimation, and (4) causality quantification using multi-delays. Based on synthetic models and comparison with baseline methods, numerical validation results demonstrate that TPCM significantly improves the robustness for data length with or without noise interference, and achieves the best quantification accuracy in detecting time delay and coupling strength, with the highest determination coefficient ( R2 = 0. 96 ) of fitting verse coupling parameters. The developed TPCM was finally applied to ictal electrocorticogram (ECoG) analysis of patients with drug-resistant epilepsy (DRE). A total of 17 patients with DRE were included into the retrospective study. For 8 patients undergoing successful surgeries, the causal coupling strength (0.58 ± 0.20) within epileptogenic zone network is significantly higher than those suffering failed surgeries (0.38 ± 0.16) with P < 0. 001 through Mann-Whitney-U-test. Therefore, the epileptic brain network measured by TPCM is a credible biomarker for predicting surgical outcomes. These findings additionally confirm TPCM's superior performance and promising potential to advance precision medicine for neurological disorders.
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Lower extremity nodular melanoma (NM) is a common malignant tumor with a poor prognosis. We aims to identify the prognostic factors and develop a nomogram model to predict overall survival (OS) in patients with lower extremity NM. A total of 746 patients with lower extremity NM were selected and randomly divided into a training set (522 cases) and a validation set (224 cases) from the Surveillance, Epidemiology, and End Results(SEER) database. The training set underwent univariate and multivariate Cox regression analyses to identify independent prognostic factors associated with patient outcomes, and to develop a nomogram model. The effectiveness of the nomogram was subsequently validated using the validation set. Multivariable Cox regression analysis of the training set indicated that age, ulceration, radiotherapy, chemotherapy, primary site of first malignant tumor, and Breslow thickness were independent variables associated with OS. In the training set, the area under the curve (AUC) of the nomogram for predicting 3-year and 5-year OS was 0.796 and 0.811, respectively. In the validation set, the AUC for predicting 3-year and 5-year OS was 0.694 and 0.702, respectively. The Harrell's C-index for the training set and validation set were 0.754 (95% CI: 0.721-0.787) and 0.670 (95% CI: 0.607-0.733), respectively. Calibration curves for both training and validation sets showed good agreement. In this study, we develop and validate a nomogram to predict OS in patients with lower extremity NM. The nomogram demonstrated reasonable reliability and clinical applicability. Nomograms are important tools assessing prognosis and aiding clinical decision-making.
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Extremidad Inferior , Melanoma , Nomogramas , Programa de VERF , Neoplasias Cutáneas , Humanos , Melanoma/mortalidad , Melanoma/diagnóstico , Melanoma/patología , Melanoma/terapia , Melanoma/epidemiología , Masculino , Femenino , Programa de VERF/estadística & datos numéricos , Persona de Mediana Edad , Pronóstico , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , Anciano , Adulto , Anciano de 80 o más AñosRESUMEN
OBJECTIVE: Patients with drug-resistant epilepsy (DRE) are commonly treated using neurosurgery, while its success rate is limited with approximately 50%. Predicting surgical outcomes is currently a prominent topic. The DRE is recognized as a network disorder involving a seizure triggering mechanism within epileptogenic zone (EZ); however, a systematic exploration of the EZ causal network remains lacking. METHODS: This paper will advance DRE study by: (1) developing a novel causal coupling algorithm, "full convergent cross mapping (FCCM)" to improve the quantization performance; (2) characterizing the DRE's multi-frequency epileptogenic network by FCCM calculation of ictal iEEG; (3) predicting surgical outcomes using network features and machine learning. Numerical validations demonstrate the FCCM's superior quantization in terms of nonlinearity, accuracy, and stability. A multicenter cohort containing 22 DRE patients with 81 seizures is included. RESULT: Based on the Mann-Whitney-U-test, coupling strength of the epileptogenic network in successful surgeries is significantly higher than that of the failed group, with the most significant difference observed in α -iEEG network (p = 1.52e - 07 ) Other clinical covariates are also considered and all th α -iEEG networks demonstrate consistent differences comparing successful and failed groups, with p = 0.014 and 9.23e - 06 for lesional and non-lesional DRE, p = 2.32e - 05, 0.0074 and 0.0030 for three clinical centers CHFU, JHU and NIH. Using FCCM features and 10-fold cross validation, the SVM achieves the highest accuracy of 87.65% in predicting surgical outcomes. CONCLUSION: The epileptogenic causal network is a reliable biomarker for estimating DRE's surgical outcomes. SIGNIFICANCE: The proposed approach is promising to facilitate DRE precision medicine.
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[This corrects the article DOI: 10.3389/fphys.2023.1190095.].
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A noncovalent organocatalytic concerted addition of phenol to glycal is developed for the stereoselective and regioselective construction of biologically important phenolic 2-deoxyglycosides, featuring wide substrate tolerance. The method relies on an anion-bridged dual hydrogen bond interaction which is experimentally proved by Nuclear Magnetic Resonance (NMR), Ultraviolet and visible (UV-vis), and fluorescence analysis. Experimental evidence including kinetic analysis, Kinetic Isotope Effect (KIE) studies, linear free energy relationship, Hammett plot, and density functional theory (DFT) calculations is provided for a concerted mechanism where a high-energy oxocarbenium ion is not formed. In addition, the potential utility of this method is further demonstrated by the synthesis of biologically active glycosylated flavones. The benchmarking studies demonstrate significant advances in this newly developed method compared to previous approaches.
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BACKGROUND CONTEXT: Establishing good screw-bone structural stability is conducive to reducing the risk of postoperative screw loosening. Screw insertion torque is an objective index for evaluating screw-bone structural stability. Therefore, accurate prediction of screw insertion torque can improve the preoperative evaluation of patients, optimize the surgical plan, and improve the surgical effect. At present, the correlation between different bone assessment methods and screw insertion torque is unclear. PURPOSE: The aim of this study was to evaluate the correlation between different bone assessment methods and screw insertion torque and to optimize the predictive performance of screw insertion torque through mathematical modeling combined with different radiology methods. DESIGN: Prospective cross-sectional study. PATIENT SAMPLES: 77 patients with preoperatively available DXA, CT and MRI data who underwent spinal fixation surgeries between October 2022 and September 2023 and 357 sets of screw data were included in this analysis. OUTCOME MEASURES: Spinal, vertebrae-specific and screw trajectory's BMD were measured preoperatively by different imaging modalities. Intraoperative screw insertion torque was measured using an electronic torque wrench. METHODS: Pearson linear correlation, scatter plots and univariate linear regression were used to evaluate the correlation between different bone evaluation methods and screw insertion torque. Different bone evaluation methods were fitted into the prediction model of screw torque and the related equations were obtained. RESULTS: Screw insertion torque had the strongest positive correlation with the volumetric bone mineral density (vBMD) of the screw trajectory (Pedicle screw insertion torque (PSIT): R = 0.618, p<.001; Terminal screw insertion torque (TSIT): R = 0.735, p<.001). A weak negative correlation was found between the screw insertion torque and level specific vertebral bone quality (VBQ) (PSIT: R = -0.178, p=.001; TSIT: R = -0.147, p=.006). We also found that the PSIT was strongly correlated with the TSIT (R = 0.812, p<.001). CONCLUSIONS: Compared to other bone quality assessment methods, screw trajectory vBMD may be better predict the magnitude of screw insertion torque. In addition, we further optimized preoperative assessments by constructing a mathematical model to better predict screw insertion torque. In conclusion, clinicians should select appropriate preoperative bone quality assessment methods, identify potential low-torque patients, optimize surgical plans, and ultimately improve screw insertion accuracy and reduce postoperative screw loosening rate.