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Fish show variation in feeding habits to adapt to complex environments. However, the genetic basis of feeding preference and the corresponding metabolic strategies that differentiate feeding habits remain elusive. Here, by comparing the whole genome of a typical carnivorous fish (Leiocassis longirostris Günther) with that of herbivorous fish, we identify 250 genes through both positive selection and rapid evolution, including taste receptor taste receptor type 1 member 3 (tas1r3) and trypsin We demonstrate that tas1r3 is required for carnivore preference in tas1r3-deficient zebrafish and in a diet-shifted grass carp model. We confirm that trypsin correlates with the metabolic strategies of fish with distinct feeding habits. Furthermore, marked alterations in trypsin activity and metabolic profiles are accompanied by a transition of feeding preference in tas1r3-deficient zebrafish and diet-shifted grass carp. Our results reveal a conserved adaptation between feeding preference and corresponding metabolic strategies in fish, and provide novel insights into the adaptation of feeding habits over the evolution course.
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Sex chromosomes display remarkable diversity and variability among vertebrates. Compared with research on the X/Y and Z/W chromosomes, which have long evolutionary histories in mammals and birds, studies on the sex chromosomes at early evolutionary stages are limited. Here, we precisely assembled the genomes of homozygous XX female and YY male Lanzhou catfish (Silurus lanzhouensis) derived from an artificial gynogenetic family and a self-fertilized family, respectively. Chromosome 24 (Chr24) was identified as the sex chromosome based on resequencing data. Comparative analysis of the X and Y chromosomes showed an approximate 320 kb Y-specific region with a Y-specific duplicate of anti-Mullerian hormone type-II receptor (amhr2y), which is consistent with findings in two other Silurus species but on different chromosomes (Chr24 of S. meridionalis and Chr5 of S. asotus). Deficiency of amhr2y resulted in male-to-female sex reversal, indicating that amhr2y plays a male-determining role in S. lanzhouensis. Phylogenetic analysis and comparative genomics revealed that the common sex-determining gene amhr2y was initially translocated to Chr24 of the Silurus ancestor along with the expansion of transposable elements. Chr24 was maintained as the sex chromosome in S. meridionalis and S. lanzhouensis, whereas a sex-determining region transition triggered sex chromosome turnover from Chr24 to Chr5 in S. asotus. Additionally, gene duplication, translocation, and degeneration were observed in the Y-specific regions of Silurus species. These findings present a clear case for the early evolutionary trajectory of sex chromosomes, including sex-determining gene origin, repeat sequence expansion, gene gathering and degeneration in sex-determining region, and sex chromosome turnover.
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OBJECTIVE: In chronic low back pain (CLBP), the relationship between spinal pathologies and paraspinal muscles fat infiltration remains unclear. This study aims to evaluate the relationship between MRI findings and paraspinal muscles morphology and fat infiltration in CLBP patients by quantitative MRI. METHODS: All the CLBP patients were enrolled from July 2021 to December 2022 in four medical institutions. The cross-sectional area (CSA) and proton density fat fraction (PDFF) of the multifidus (MF) and erector spinae (ES) muscles at the central level of the L4/5 and L5/S1 intervertebral discs were measured. MRI findings included degenerative lumbar spondylolisthesis (DLS), intervertebral disc degeneration (IVDD), facet arthrosis, disc bulge or herniation, and disease duration. The relationship between MRI findings and the paraspinal muscles PDFF and CSA in CLBP patients was analyzed. RESULTS: A total of 493 CLBP patients were included in the study (198 females, 295 males), with an average age of 45.68 ± 12.91 years. Our research indicates that the number of MRI findings are correlated with the paraspinal muscles PDFF at the L4/5 level, but is not significant. Moreover, the grading of IVDD is the primary factor influencing the paraspinal muscles PDFF at the L4-S1 level (BES at L4/5=1.845, P < 0.05); DLS was a significant factor affecting the PDFF of MF at the L4/5 level (B = 4.774, P < 0.05). After including age, gender, and Body Mass Index (BMI) as control variables in the multivariable regression analysis, age has a significant positive impact on the paraspinal muscles PDFF at the L4-S1 level, with the largest AUC for ES PDFF at the L4/5 level (AUC = 0.646, cut-off value = 47.5), while males have lower PDFF compared to females. BMI has a positive impact on the ES PDFF only at the L4/5 level (AUC = 0.559, cut-off value = 24.535). CONCLUSION: The degree of paraspinal muscles fat infiltration in CLBP patients is related to the cumulative or synergistic effects of multiple factors, especially at the L4/L5 level. Although age and BMI are important factors affecting the degree of paraspinal muscles PDFF in CLBP patients, their diagnostic efficacy is moderate.
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Tecido Adiposo , Dor Crônica , Dor Lombar , Vértebras Lombares , Imageamento por Ressonância Magnética , Músculos Paraespinais , Humanos , Músculos Paraespinais/diagnóstico por imagem , Músculos Paraespinais/patologia , Masculino , Dor Lombar/diagnóstico por imagem , Dor Lombar/etiologia , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Dor Crônica/diagnóstico por imagem , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/patologiaRESUMO
BACKGROUND: The lumbar vertebra and paraspinal muscles play an important role in maintaining the stability of the lumbar spine. Therefore, the aim of this study was to investigate the relationship between paraspinal muscles fat infiltration and vertebral body related changes [vertebral bone quality (VBQ) score and Modic changes (MCs)] in patients with chronic low back pain (CLBP). METHODS: Patients with CLBP were prospectively collected in four hospitals and all patients underwent 3.0T magnetic resonance scanning. Basic clinical information was collected, including age, sex, course of disease (COD), and body mass index (BMI). MCs were divided into 3 types based on their signal intensity on T1 and T2-weighted imaging. VBQ was obtained by midsagittal T1-weighted imaging (T1WI) and calculated using the formula: SIL1-4/SICSF. The Proton density fat fraction (PDFF) values and cross-sectional area (CSA) of paraspinal muscles were measured on the fat fraction map from the iterative decomposition of water and fat with the echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) sequences and in/out phase images at the central level of the L4/5 and L5/S1 discs. RESULTS: This study included 476 patients with CLBP, including 189 males and 287 females. 69% had no Modic changes and 31% had Modic changes. There was no difference in CSA and PDFF for multifidus(MF) and erector spinae (ES) at both levels between Modic type I and type II, all P values>0.05. Spearman correlation analysis showed that VBQ was weakly negatively correlated with paraspinal muscles CSA (all r values < 0.3 and all p values < 0.05), moderately positive correlation with PDFF of MF at L4/5 level (r values = 0.304, p values<0.001) and weakly positively correlated with PDFF of other muscles (all r values<0.3 and all p values<0.001). Multivariate linear regression analysis showed that age (ß = 0.141, p < 0.001), gender (ß = 4.285, p < 0.001) and VBQ (ß = 1.310, p = 0.001) were related to the total PDFF of muscles. For MCs, binary logistic regression showed that the odds ratio values of age, BMI and COD were 1.092, 1.082 and 1.004, respectively (all p values ï¼ 0.05). CONCLUSIONS: PDFF of paraspinal muscles was not associated with Modic classification. In addition to age and gender, PDFF of paraspinal muscles is also affected by VBQ. Age and BMI are considered risk factors for the MCs in CLBP patients.
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Tecido Adiposo , Dor Lombar , Vértebras Lombares , Músculos Paraespinais , Humanos , Feminino , Masculino , Músculos Paraespinais/diagnóstico por imagem , Músculos Paraespinais/patologia , Dor Lombar/diagnóstico por imagem , Estudos Prospectivos , Estudos Transversais , Pessoa de Meia-Idade , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Adulto , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Idoso , Imageamento por Ressonância Magnética , Dor Crônica/diagnóstico por imagemRESUMO
OBJECTIVE: To investigate factors influencing the long-term prognosis of patients with sacral Tarlov syndrome after nerve root cuff reconstruction. METHODS: A total of 42 patients with sacral Tarlov cysts who underwent nerve root cuff reconstruction at the First Medical Center of the Chinese PLA General Hospital between December 2015 and December 2021 were retrospectively reviewed. All cases were confirmed using magnetic resonance imaging and pathology. All patients were followed up for 24 months after surgery. Improvement in self-evaluation of health was defined as a good prognosis, while a decline in self-evaluation of health was defined as a poor prognosis. The demographic characteristics and clinical data were compared between patients with good and poor prognoses. Multivariate logistic regression analysis was performed, taking poor prognosis as the dependent variable and parameters with P < 0.1 in the univariate analysis as independent variables to identify the risk factors. RESULTS: Significant differences were observed in disease duration, lower limb weakness, defecation dysfunction, and defecation dysfunction between patients with good and poor prognoses. Multivariate logistic regression analysis showed that disease duration (Odds ratio: 0.961, 95% confidence interval: 0927-0.995) and defecation dysfunction (Odds ratio: 0.005, 95% confidence interval: 0.0-0.368) were independent risk factors for poor prognosis after nerve cuff reconstruction in patients with sacral Tarlov cysts (all P < 0.05). CONCLUSIONS: Patients with sacral Tarlov cysts undergoing nerve root cuff reconstruction, particularly those with longer preoperative disease duration and dysuria, are at increased risk of poor long-term prognosis.
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Malignant tumors are predominant in the esophagus, in which benign tumors are rare, and esophageal schwannoma is extremely rare. Here, we present a case of a 68-year-old woman with an unexpected chest computed tomography of inhomogeneous, well-defined, progressive delayed enhancement mass, and a paraesophageal lymph node. Mediastinal magnetic resonance imaging revealed an external growth mass in the lower esophagus, with an inhomogeneous signal, multiple internal cysts, and limited diffusion on diffuse-weighted imaging. Upper gastrointestinal radiography revealed a filling defect in the lower segment of the esophagus with no damage to the mucosal surface. Surgical resection and further pathological histology and immunohistochemical examination confirmed the diagnosis of esophageal schwannoma.
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Canopy height serves as an important dynamic indicator of crop growth in the decision-making process of field management. Compared with other commonly used canopy height measurement techniques, ultrasonic sensors are inexpensive and can be exposed in fields for long periods of time to obtain easy-to-process data. However, the acoustic wave characteristics and crop canopy structure affect the measurement accuracy. To improve the ultrasonic sensor measurement accuracy, a four-year (2018-2021) field experiment was conducted on maize and wheat, and a measurement platform was developed. A series of single-factor experiments were conducted to investigate the significant factors affecting measurements, including the observation angle (0-60°), observation height (0.5-2.5 m), observation period (8:00-18:00), platform moving speed with respect to the crop (0-2.0 m min-1), planting density (0.2-1 time of standard planting density), and growth stage (maize from three-leaf to harvest period and wheat from regreening to maturity period). The results indicated that both the observation angle and planting density significantly affected the results of ultrasonic measurements (p-value< 0.05), whereas the effects of other factors on measurement accuracy were negligible (p-value > 0.05). Moreover, a double-input factor calibration model was constructed to assess canopy height under different years by utilizing the normalized difference vegetation index and ultrasonic measurements. The model was developed by employing the least-squares method, and ultrasonic measurement accuracy was significantly improved when integrating the measured value of canopy heights and the normalized difference vegetation index (NDVI). The maize measurement accuracy had a root mean squared error (RMSE) ranging from 81.4 mm to 93.6 mm, while the wheat measurement accuracy had an RMSE from 37.1 mm to 47.2 mm. The research results effectively combine stable and low-cost commercial sensors with ground-based agricultural machinery platforms, enabling efficient and non-destructive acquisition of crop height information.
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The demands for novel and efficient therapies have gradually increased with the rising concerns of osteoporosis (OP). The most popular method in promoting bone regeneration during osteoporotic conditions consists of loading bioactive materials with different drugs to treat osteoporotic bones by either promoting the process of osteogenesis, or by inhibiting the activity of osteoclasts. By analyzing single cell sequencing results, we found that divalent metal transporter 1 (DMT1) played a role in OP. Based on our previous results, we found that melatonin (MT) suppressed expression of DMT1 induced by high glucose during OP, so we determined the efficacy of MT for the treatment of OP. However, the clinical effects of MT on OP were unsatisfactory. To enhance its biological efficacy, we combined MT with porous gelatin chitosan (chitosan) and the conductive material, PLA-b-AP-b-PLA (PAP), then determined how MT incorporation in chitosan@PAP nanoparticles affected the ability to promote MC3T3-E1 osteogenesis and mineralization, both in vitro and in vivo. The results confirmed the effect of MT on DMT1. We then prepared and characterized composites prepared as nanofibers, and determined the efficacy of MT combined with chitosan-PAP modified hydrogels as a slow-release system in a femur model of osteoporosis mice, with associated properties suitable for bone tissue engineering. The results indicated that MT-loaded chitosan@PAP nanospheres showed favorable osteogenic functions, both in vivo and in vitro, providing a practical solution for bone regeneration for OP patients.
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OBJECTIVE: To evaluate effects of bone marrow sparing (BMS) radiotherapy on decreasing the incidence of acute hematologic toxicity (HT) for locoregionally advanced cervical cancer (LACC) patients treated by pelvic irradiation. MATERIALS AND METHODS: LACC patients were recruited prospectively from May 2021 to May 2022 at a single center and were evenly randomized into the BMS group and the control group. All patients received pelvic irradiation with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy and BM V40 < 25% in the BMS group was additionally prescribed. Acute HT was assessed weekly. Binary logistic regression model and receiver operating characteristic (ROC) curve were used for predictive value analysis. The trial was registered with Chinese clinical trial registry (ChiCTR2200066485). RESULTS: A total of 242 patients were included in the analysis. Baseline demographic, disease and treatment characteristics were balanced between the two groups. In the intention-to-treat population, BMS was associated with a lower incidence of grade ≥ 2 and grade ≥ 3 acute HT, leukopenia and neutropenia s(72.70% v 90.90%, P < 0.001*; 16.50% vs. 65.30%, P < 0.001*; 66.10% vs. 85.10%, P = 0.001*; 13.20% vs. 54.50%, P < 0.001*; 37.20% vs. 66.10%, P < 0.001*; 10.70% vs. 43.80%, P < 0.001*). BMS also resulted in decreased dose delivered to the organs at risk (OARs) including rectum, bladder and left and right femoral head. Univariate and multivariate analyses showed that BM V40 was an independent risk factor for grade ≥ 3 acute HT (odds ratio [OR] = 2.734, 95% confidence interval [CI] = 1.959-3.815, P < 0.001*). Cutoff value was 25.036% and area under the curve (AUC) was 0.786. The nomogram was constructed, which was rigorously evaluated and internally cross-validated, showing good predictive performance. CONCLUSIONS: Receiving BMS pelvic irradiation could reduce the incidence of acute HT in LACC patients, and BM V40 < 25% may be a significant factor in reducing the risks of acute HT.
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Leucopenia , Lesões por Radiação , Radioterapia de Intensidade Modulada , Neoplasias do Colo do Útero , Feminino , Humanos , Medula Óssea/efeitos da radiação , Neoplasias do Colo do Útero/radioterapia , Estudos Prospectivos , Radioterapia de Intensidade Modulada/métodos , Dosagem Radioterapêutica , Cisplatino , Leucopenia/etiologia , Quimiorradioterapia/efeitos adversos , Lesões por Radiação/etiologiaRESUMO
Objective: Mercury (Hg) contamination in the environment around mercury mines is often accompanied by heavy metal contamination. Methods: Here, we determined concentrations of chromium (Cr), zinc (Zn), strontium (Sr), barium (Ba), and lead (Pb) in duck eggs from a Hg mining area in Southwest China to assess the contamination and health risk. Results: Duck eggs obtained from the mining area exhibit higher concentrations of Cr, Zn, Sr, Ba, and Pb compared to those from the background area, with egg yolks containing higher metal levels than egg whites. Specifically, the mean Cr, Zn, Sr, Ba, and Pb concentrations of duck eggs from the Hg mining area are 0.38, 63.06, 4.86, 10.08, and 0.05 µg/g, respectively, while those from the background area are only 0.21, 24.65, 1.43, 1.05, and 0.01 µg/g. Based on the single-factor contamination index and health risk assessment, heavy metal contamination in duck eggs poses an ecological risk and health risk. Conclusion: This study provides important insight into heavy metal contamination in duck eggs from Hg mining areas.
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Mercúrio , Metais Pesados , Animais , Mercúrio/análise , Patos , Chumbo , Metais Pesados/análise , Zinco/análise , MineraçãoRESUMO
BACKGROUND: Recently, there has been a concerted effort within medical schools to depart from conventional lecture-based learning approaches to alternative teaching methods such as team-based learning (TBL) and problem-based learning (PBL), with the aim of enhancing both student engagement and instructional efficacy. Despite this shift, a comprehensive review that directly compares the impacts of PBL and TBL methods in medical education is lacking. This study seeks to address this gap by conducting a meta-analysis that compares the effects of TBL and PBL in the context of medical education. METHODS: Studies from Embase, PubMed, Web of Science, China National Knowledge Infrastructure, and Chinese Wanfang Database were searched, from inception to July 11, 2023. A meta-analysis was performed using Stata 14.0, and a total of 10 studies (including 752 participants) were included. The standardized mean difference (SMD) was used to estimate pooled effects. Heterogeneity was detected using the I2 statistic and further explored using meta-regression analysis. RESULTS: Compared with PBL, TBL significantly increased the number of theoretical tests (SMD = 0.37, 95% CI: 0.02-0.73). Additionally, TBL greatly improved teamwork skills compared with PBL. However, there were no significant differences between the TBL and PBL groups concerning practical skill scores, learning interest, or understanding skills. CONCLUSION: TBL in the theoretical aspects of medical education appears to be more effective than PBL in improving theoretical test scores and teamwork skills, providing evidence for the implementation of TBL in medical education.
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Educação Médica , Aprendizagem Baseada em Problemas , Humanos , Educação Médica/métodos , Processos Grupais , Estudantes de Medicina , Avaliação EducacionalRESUMO
Disc degeneration often leads to a highly prevalent symptom known as low back pain. Healthy nucleus pulposus tissue exhibited a hypoxic environment devoid of blood vessels, while degenerated nucleus pulposus experienced hypoxic deterioration and the formation of new blood vessels. In this study, the expression of important genes like HIF-2α was found to vary between normal and degenerated nucleus pulposus cells when compared to the hypoxic surroundings. The aim of this study was to examine how HIF-2α is controlled in nucleus pulposus cells under hypoxic conditions and its role in angiogenic mechanisms. To assess the impact of gradual inhibition of HIF-2α on disc degeneration, we utilized PHBV-based synthetic materials loaded with inhibitors of HIF-2α. Specifically, we employed LPS and PT2399 loaded PHBV-PEG20k (PP20) to intervene with human nucleus pulposus cells. Additionally, we treated APD rat models with PT2399 loaded PP20 to evaluate its effects. The expression levels of target markers in nucleus pulposus cells were detected using PCR, WB, and immunofluorescence. Additionally, the effect of drugs on disc degeneration was identified through HE staining. The findings indicated that HIF-2α, CAIX, PPP1R15A, VEGFA, and EGLN3 could potentially serve as new indicators of disc degeneration. Additionally, HIF-2α might contribute to the progression of disc degeneration through involvement in angiogenesis and the regulation of hypoxia. Furthermore, the utilization of PT2399 loaded PHBV-PEG20k (PP20) could potentially offer a fresh alternative for treating disc degeneration.
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Mercury (Hg) is a globally distributed toxic metal and could pose serious harm to birds, which may ultimately threaten human health through poultry consumption. However, the avian Hg metabolism remains unclear. Poultry, like chickens, are more accessible human dietary sources than wild birds and are ideal proxies to study Hg metabolism in birds. In this study, the avian Hg metabolism is carefully investigated with hens fed by Hg-spiked (both inorganic mercury IHg and methylmercury MeHg) foods. Our results demonstrate that feces and eggs are the main removal pathways of Hg from hens, rather than feathers. Eggs show particularly rapid responses towards Hg exposures, thus could be more sensitive to environmental Hg pollution than feathers, feces or internal organs (and tissues). Egg yolk (with THg peak of 55.92 ng/g on Day 6) and egg white (THg peak of 1195.03 ng/g on Day 4) react as an effective bioindicator for IHg and MeHg exposure, respectively. In 90-day-single-dose exposure, IHg is almost completely excreted, while approximately 11% of MeHg remains in internal organs. Our study provides new insight into the metabolism and lifetime of IHg and MeHg in birds, advancing the understanding of the dynamics for human exposure to Hg through poultry products.
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Mercúrio , Compostos de Metilmercúrio , Humanos , Animais , Feminino , Compostos de Metilmercúrio/toxicidade , Biomarcadores Ambientais , Galinhas/metabolismo , Mercúrio/análise , Monitoramento Ambiental , OvosRESUMO
Postherpetic neuralgia (PHN) seriously affects the quality of life of the elderly population. This study aimed to evaluate the efficacy of ozonated autohemotherapy (O3-AHT) combined with pulsed radiofrequency (PRF) in the treatment of thoracic PHN in older adults. The medical records of patients with thoracic PHN aged 65 years and older from June 2018 until March 2021 in Shengli Oilfield Central Hospital were reviewed. They were assigned into two groups: PRF alone (PRF group, n = 107) and PRF combined with O3-AHT (PRF + O3-AHT group, n = 109). Visual Analogue Scale for pain was evaluated at pre-treatment, 1 day, 1, 3 and 6 months after treatment. Quality of life and sleep quality were assessed using Short-Form 36 Health Survey and Athens Insomnia Scale at pre-treatment and 6 months post-treatment, respectively. The median age of patients in the PRF and PRF + O3-AHT groups were 69 (67-73) years and 68 (67-72) years, respectively. The former included 62 females and the latter included 51 females. Compared with pre-treatment, the Visual Analogue Scale scores of two groups declined at post-treatment. Patients in the PRF + O3-AHT group showed obviously lower Visual Analogue Scale scores compared with those in the PRF group at 1, 3, and 6 months after treatment and they had earlier withdrawal time for drugs. However, dizziness, tachycardia, sleepiness, and nausea were presented after combination therapy. These symptoms resolved spontaneously after a period of rest. Additionally, O3-AHT combined with PRF was associated with a significant decrease in the Athens Insomnia Scale score and with a significant improvement in every dimension of the Short-Form 36 Health Survey. To conclude, O3-AHT combined with PRF is an effective way to relieve thoracic PHN in older patients.
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Neuralgia Pós-Herpética , Tratamento por Radiofrequência Pulsada , Distúrbios do Início e da Manutenção do Sono , Feminino , Humanos , Idoso , Neuralgia Pós-Herpética/terapia , Estudos Retrospectivos , Tratamento por Radiofrequência Pulsada/métodos , Qualidade de VidaRESUMO
Ferric stearate (FeSt3) is very efficient in accelerating polyethylene (PE) degradation, but there is a lack of exploration of its role in accelerating the early stages of polyethylene photo-oxidative degradation. This study aimed to investigate the effect of FeSt3 on the photo-oxidative degradation of PE films, especially in the early stages of photo-oxidative degradation. The results show that FeSt3 not only promotes the oxidative degradation of PE but also contributes significantly to the early behavior of photo-oxidative degradation. Moreover, the results of the density functional theory (DFT) calculations proved that the C-H in the FeSt3 ligand was more easily dissociated compared with the PE matrix. The generated H radicals participate in the coupling reaction of the primary alkyl macro radicals leading to the molecular weight reduction, thus significantly increasing the initial rate of molecular weight reduction of PE. Meanwhile, the transfer reaction of the dissociation-generated C-centered radicals induced the PE matrix to produce more secondary alkyl macroradicals, which shortened the time to enter the oxidative degradation stage. This finding reveals the mechanism by which FeSt3 promotes the degradation of PE at the early stage of photo-oxidative degradation. It provides guiding significance for the in-depth study of the early degradation behavior in photo-oxidative degradation on polyolefin/FeSt3 films.
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Rheumatoid arthritis (RA) is a multifaceted, chronic, progressive autoimmune disease. This study aims to explore the potential benefits of an enhanced drug delivery system utilizing optimized Gelatin Methacryloyl (GelMA) vectors in RA management. We evaluated the levels of miR-1124-3p and AGO1 in RA tissues and cell lines using qPCR, WB, and immunofluorescence. The effects of osthole on inflammatory response and joint morphology were determined by qPCR, H&E staining, and micro-CT. The data showed that miR-1224-3p was downregulated in RA tissues and HUM-iCell-s010RA cells, while the overexpression of miR-1224-3p in HUM-iCell-s010RA cells reduced the expression of IL-6 and IL-1ß. Luciferase assay demonstrated that AGO1 was a direct target gene of miR-1224-3p. Additionally, osthole treatment increased miR-1224-3p levels and decreased AGO1 expression. The release data showed that osthole loaded on GelMA was released at a slower rate than free osthole. Further studies in a mouse model of CIA confirmed that osthole-loaded GelMA was more effective in attenuating osteopenia in RA as well as alleviating autoimmune arthritis. These findings suggest that osthole can regulate the miR-1224-3p/AGO1 axis in RASFs cells and has the potential to be developed as a clinical anti-RA drug. GelMA could provide a new approach to long-term RA treatment.
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Artrite Reumatoide , Doenças Autoimunes , MicroRNAs , Animais , Camundongos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Hidrogéis , MicroRNAs/genéticaRESUMO
Introduction: Postoperative comprehensive treatment has become increasingly important in recent years. This study was to repair tissue defects resulting from the removal of diseased tissue and to eliminate or inhibit the recurrence and metastasis of residual tumors under the condition of reducing the systemic side effects of chemotherapeutic drugs. To address these challenges, multifunctional scaffolds based local drug delivery systems will be a promising solution. Methods: An optimal drug-loaded scaffold material PHBV-mPEG5k (PP5) was prepared, which is biocompatible, hydrophilic and biodegradable. Furthermore, this material showed to promote bone healing, and could be conveniently prepared into porous scaffold by freeze-drying the solution. By means of introducing melatonin (MT) into the porous surfaces, the MT loaded PP5 scaffold with desirable sustained release ability was successfully prepared. The effectiveness of the MT loaded PP5 scaffold in promoting bone repair and anti-tumor properties was evaluated through both in vivo and in vitro experiments. Results and Discussion: The MT loaded PP5 scaffold is able to achieve the desired outcome of bone tissue repair and anti-bone tumor properties. Furthermore, our study demonstrates that the PP5 scaffold was able to enhance the anti-tumor effect of melatonin by improving cellular autophagy, which provided a therapeutic strategy for the comprehensive postoperative treatment of osteosarcoma.
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Soil microorganisms play important roles in promoting soil ecosystem restoration, but much of the current research has been limited to changes in microbial community structure in general, and little is known regarding the soil physicochemical property and microbial community structure. In this study, four organic fertilizers were first prepared based on tea oil camellia shell (TOCS). Our findings indicate that the application of BOFvo increased both total pore volume and BET surface area of the rhizosphere soils, as well there was a remarkable enhancement in total organic matter (TOM), total nitrogen (TN), available nitrogen (AN), total phosphorus (TP), total potassium (TK), and available potassium (AK) contents of the rhizosphere soils. Meanwhile, in comparison to the CK and CF groups, the utilization of BOFvo led to a substantial increase in both average yield and fruiting rate per plant at maturity, as well resulted in a significant increase in TN and TP contents of tea oil camellia leaves. Furthermore, our findings suggest that the application of TOCS-based organic fertilizers significantly enhances the microbial diversity in the rhizosphere soils with Proteobacteria and Ascomycota being the dominant bacterial and fungal phyla, respectively, and Rhodanobacter and Fusarium being the dominant bacterial and fungal genus, respectively. Redundancy analysis (RDA) indicates that the physicochemical characteristics of TOCS-based organic fertilizers had a significant impact on the composition and distribution of microbial communities in the rhizosphere soils. This study will facilitate the promotion and application of TOCS-based organic fertilizers, thereby establishing a foundation for the reuse of tea oil camellia waste resources.
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Exploiting novel strategies for simultaneously harvesting ubiquitous, renewable, and easily accessible solar energy based on the photothermal effect, and efficiently storing the acquired thermal energy plays a vital role in revolutionizing the current fossil fuel-dominating energy structure. Developing black phosphorene-based phase-change composites with optimized photothermal conversion efficiencyand high latent heat is the most promising way to achieve efficient solar energy harvesting and rapid thermal energy storage. However, exfoliating high-quality black phosphorene nanosheets remains challenging, Furthermore, an efficient strategy that can construct the aligned black phosphorene frameworks to maximize thermal conductivity enhancement is still lacking. Herein, high-quality black phosphorene nanosheets are prepared by an optimized exfoliating strategy. Meanwhile, by regulating the temperature gradient during freeze-casting, the framework consisting of shipshape aligned black phosphorene at long-range is successfully fabricated, improving the thermal conductivity of the poly(ethylene glycol) matrix up to 1.81 W m-1 K-1 at 20 vol% black phosphorene loading. The framework also endows the composite with excellent phase-change material encapsulation capacity and high latent heat of 103.91 J g-1 . It is envisioned that the work advances the paradigm of contrasting frameworks with nanosheets toward controllable structure thermal enhancement of the composites.
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BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION: Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.