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Spike length (SL) is one of the most important agronomic traits affecting yield potential and stability in wheat. In this study, a major stable quantitative trait locus (QTL) for SL, i.e., qSl-2B, was detected in multiple environments in a recombinant inbred line (RIL) mapping population, KJ-RILs, derived from a cross between Kenong 9204 (KN9204) and Jing 411 (J411). The qSl-2B QTL was mapped to the 60.06-73.06 Mb region on chromosome 2B and could be identified in multiple mapping populations. An InDel molecular marker in the target region was developed based on a sequence analysis of the two parents. To further clarify the breeding use potential of qSl-2B, we analyzed its genetic effects and breeding selection effect using both the KJ-RIL population and a natural mapping population, which consisted of 316 breeding varieties/advanced lines. The results showed that the qSl-2B alleles from KN9204 showed inconsistent genetic effects on SL in the two mapping populations. Moreover, in the KJ-RILs population, the additive effects analysis of qSl-2B showed that additive effect was higher when both qSl-2D and qSl-5A harbor negative alleles under LN and HN. In China, a moderate selection utilization rate for qSl-2B was found in the Huanghuai winter wheat area and the selective utilization rate for qSl-2B continues to increase. The above findings provided a foundation for the genetic improvement of wheat SL in the future via molecular breeding strategies.
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Locos de Características Quantitativas , Triticum , Mapeamento Cromossômico , Triticum/genética , Ligação Genética , Melhoramento Vegetal , FenótipoRESUMO
Efficient electrocatalysts capable of operating continuously at industrial ampere-level current densities are crucial for large-scale applications of electrocatalytic water decomposition for hydrogen production. However, long-term industrial overall water splitting using a single electrocatalyst remains a major challenge. Here, bimetallic polyphthalocyanine (FeCoPPc)-anchored Ru nanoclusters, an innovative electrocatalyst comprising the hydrogen evolution reaction (HER) active Ru and the oxygen evolution reaction (OER) active FeCoPPc, engineered for efficient overall water splitting are demonstrated. By density functional theory calculations and systematic experiments, the electrocatalytic coenhancement effect resulting from unique charge redistribution, which synergistically boosts the HER activity of Ru and the OER activity of FeCoPPc by optimizing the adsorption energy of intermediates, is unveiled. As a result, even at a large current density of 2.0 A cm-2 , the catalyst exhibits low overpotentials of 220 and 308 mV, respectively, for HER and OER. It exhibits excellent stability, requiring only 1.88 V of cell voltage to achieve a current density of 2.0 A cm-2 in a 6.0 m KOH electrolyte at 70 °C, with a remarkable operational stability of over 100 h. This work provides a new electrocatalytic coenhancement strategy for the design and synthesis of electrocatalyst, paving the way for industrial-scale overall water splitting applications.
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AIMS: The purpose of this study was to find out the relation between visceral adipose index (VAI) levels and stress urinary incontinence (SUI) in adult women. METHODS: From the National Health and Nutrition Examination Survey (NHANES) 2007-2020, females aged 20 or above were identified for this study. Visceral adiposity was determined using the VAI score, and the assessment of urinary incontinence was carried out through a correlation questionnaire. Logistic regression models and restricted cubic spline (RCS) regression were employed to analyze the relationship between VAI levels and SUI. RESULTS: Among the 6522 participants, 2672 (41.0%) were reported SUI. Multivariate logistic regression revealed significantly higher odds of SUI with increasing VAI levels (Q4 vs. Q1), adjusted odds ratio (aOR) = 1.53 (CI: 1.29-1.81, p < 0.001). RCS regression indicated a curvilinear relationship between VAI and SUI (p = 0.003). In threshold analysis, aOR for developing SUI was 1.18 (CI: 1.11-1.26, p < 0.001) for participants with VAI < 4.73, suggesting an 18% increased risk of SUI with each unit increase in VAI. No association between VAI and SUI was observed when VAI was ≥4.73. CONCLUSIONS: Our study has revealed a significant curvilinear relationship between VAI and SUI within a large and representative sample of women. Future research is necessary to evaluate the relationship between the two and explicate the underlying mechanisms of this relationship.
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Gordura Intra-Abdominal , Inquéritos Nutricionais , Incontinência Urinária por Estresse , Humanos , Feminino , Estudos Transversais , Incontinência Urinária por Estresse/fisiopatologia , Incontinência Urinária por Estresse/epidemiologia , Incontinência Urinária por Estresse/diagnóstico , Pessoa de Meia-Idade , Adulto , Gordura Intra-Abdominal/fisiopatologia , Estados Unidos/epidemiologia , Adiposidade , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/fisiopatologia , Obesidade Abdominal/diagnóstico , Adulto Jovem , Fatores de Risco , IdosoRESUMO
Cotton fabrics with the main constituent of cellulose, which is hydrophilic, bacterial infected, and flammable, are in urgent need of functionalization as a kind of widely applied material. To address these issues, in this work, modified polyelectrolyte complex (MPEC) coatings with polyethylenimine (PEI), polyphosphate (APP), and perfluorodecyltrichlorosilane modified PEI (PFTS-PEI) are prepared to construct multi-functionally gradient MPEC coatings on cotton fabrics. Stability and synergistic effects on hydrophobicity, antibacterial activity, and flame retardancy in this system have been studied. Notably, PFTS-PEI with fluorine and silicone elements are confirmed to provide hydrophobicity and durability for MPEC coatings, which not only has no negative effect on other functions but also makes some improvement in antibacterial activity. This MPEC-treated cotton fabric finally has an antibacterial rate against S. aureus and E. coli of 99.9% and 96.9%, limiting oxygen index of 28.5% and water contact angle of 118°, which can be almost maintained after 20 times washing. The modified PEC will provide an efficient strategy to achieve durable multi-functions on cellulose-based fabrics.
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BACKGROUND: To evaluate the effect of esketamine combined with ropivacaine hydrochloride on the occurrence of postpartum depression (PPD) after labor analgesia under epidural analgesia pump and explore the possible mechanisms. METHODS: A total of 120 women aged 24 to 36 years old who underwent labor analgesia by epidural analgesia pump, with American Society of Anesthesiologists (ASA) physical status II were enrolled. According to the formula of epidural analgesia pump, all participants were randomly divided into two groups: esketamine group (Group E) and control group (Group C). Epidural anaesthesia were operated in all women between L2 and L3 after cervical dilation up to 2 ~ 3 cm. After successful puncture, the epidural catheter was placed 3.5 cm toward the head and 1% lidocaine was injected for 3 ml. The epidural analgesia pump was connected. Esketamine (0.2 mg/kg) combined with 0.75% ropivacaine hydrochloride (20 ml) were diluted by normal saline up to 100 ml in Group E, when only the equal dose of ropivacaine hydrochloride was used in Group C. The visual analogue scale (VAS) before analgesia (T1), 5 (T2), 10 (T3) and 20 (T4) minutes after analgesia were measured. The duration of the first and second stage of labor, the Apgar score of fetus at delivery, postpartum hemorrhage, consumption of esketamine and ropivacaine were recorded. The incidence of PPD was recorded at 1 week and 6 weeks after delivering. The occurrence of side effects such as nausea and vomiting, dizziness, and nightmares were also recorded for 48 h after delivering. The levels of leptin, norepinephrine(NE), and epinephrine(E) in the peripheral venous blood were measured before labor analgesia and at 24 h, 1 week, and 6 weeks after delivering. RESULTS: Compared with Group C, the VAS score at T2, T3 and T4 were significantly lower in Group E (P < 0.01). Compared with Group C, the incidence of PPD was significantly lower at 1 week and 6 weeks after delivering in Group E (P < 0.01). Compared with Group C, the levels of leptin were significantly higher at 24 h and 1 week after delivering in Group E (P < 0.01), while NE and E (P < 0.01) were lower at the same time (P < 0.01). There were no significant difference of the duration of the first and second stage of labor, the Apgar score of fetus at delivery, postpartum hemorrhage, consumption of ropivacaine and the side effects for 48 h after delivering between the two groups. CONCLUSION: Esketamine combined with ropivacaine hydrochloride used in labor analgesia can significantly reduce the incidence of postpartum depression after delivering without increasing related side effects, which may be related to the regulation of leptin, norepinephrine, and epinephrine in the serum. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry on 30/05/2022 (CTRI registration number-ChiCTR2200060387). URL of registry: https://www.chictr.org.cn/bin/home .
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Analgesia Epidural , Analgesia Obstétrica , Depressão Pós-Parto , Hemorragia Pós-Parto , Gravidez , Feminino , Humanos , Adulto Jovem , Adulto , Ropivacaina , Leptina , Hemorragia Pós-Parto/tratamento farmacológico , Depressão Pós-Parto/tratamento farmacológico , Analgésicos/uso terapêutico , Epinefrina , Norepinefrina , Anestésicos Locais/uso terapêuticoRESUMO
Ultrathin 2D porous carbon-based materials offer numerous fascinating electrical, catalytic, and mechanical properties, which hold great promise in various applications. However, it remains a formidable challenge to fabricate these materials with tunable morphology and composition by a simple synthesis strategy. Here, a facile one-step self-flowering method without purification and harsh conditions is reported for large-scale fabrication of high-quality ultrathin (≈1.5 nm) N-doped porous carbon nanosheets (NPC) and their composites. It is demonstrated that the layered tannic/oxamide (TA/oxamide) hybrid is spontaneously blown, exfoliated, bloomed, in situ pore-formed, and aromatized during pyrolysis to form flower-like aggregated NPC. This universal one-step self-flowering system is compatible with various precursors to construct multiscale NPC-based composites (Ru@NPC, ZnO@NPC, MoS2 @NPC, Co@NPC, rGO@NPC, etc.). Notably, the programmable architecture enables NPC-based materials with excellent multifunctional performances, such as microwave absorption and hydrogen evolution. This work provides a facile, universal, scalable, and eco-friendly avenue to fabricate functional ultrathin porous carbon-based materials with programmability.
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Post-translational modifications (PTMs) of proteins contribute to the occurrence and development of tumors. Previous studies have suggested that canonical PTMs such as ubiquitination, glycosylation, and phosphorylation are closely implicated in different aspects of gastrointestinal tumors. Recently, emerging evidence showed that non-canonical PTMs play an essential role in the carcinogenesis, metastasis and treatment of gastrointestinal tumors. Therefore, we summarized recent advances in sumoylation, neddylation, isoprenylation, succinylation and other non-canonical PTMs in gastrointestinal tumors, which comprehensively describe the mechanisms and functions of non-classical PTMs in gastrointestinal tumors. It is anticipated that targeting specific PTMs could benefit the treatment as well as improve the prognosis of gastrointestinal tumors.
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Chondrocytes are the major functional elements of articular cartilage. Force has been demonstrated to influence the structure and function of articular cartilage and chondrocytes. Therefore, it is necessary to evaluate chondrocytes under different force conditions to gain deep insight into chondrocyte function. Six cartilage tissues from the distal tibia (referred to as the AT group) and five cartilage tissues from the trochlear surface of the talus (referred to as the ATa group) were obtained from 6 donors who had experienced fatal accidents. Single-cell RNA sequencing was used on these samples. A total of 149,816 cells were analyzed. Nine chondrocyte subsets were ultimately identified. Pseudotime analyses, enrichment analyses, cell-cell interaction studies, and single-cell regulatory network inference and clustering were performed for each cell type, and the differences between the AT and ATa groups were analyzed. Immunohistochemical staining was used to verify the existence of each chondrocyte subset and its distribution. The results suggested that reactive oxygen species related processes were active in the force-applied region, while tissue repair processes were common in the force-bearing region. Although the number of prehypertrophic chondrocytes was small, these chondrocytes seemed to play an important role in the ankle.
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Tornozelo , Cartilagem Articular , Cartilagem Articular/metabolismo , Condrócitos , Espécies Reativas de Oxigênio/metabolismo , Análise de Sequência de RNARESUMO
Wheat starch (WS) is a common adhesive material used in mounting of calligraphy and paintings. Potassium alum (PA) has indeed been used for many centuries to modify the physicochemical properties of starch. Thermal analysis revealed that the presence of PA led to an increase in the gelatinization temperature and enthalpy of the starch gels. The leached amylose and the swelling power of the starch gels exhibited a maximum at the ratio of 100:6.0 (WS:PA, w/w). The rheological properties of starch gels were consistent with changes in the swelling power of starch granules. SEM observations confirmed that the gel structure became more regular, and the holes grew larger with the addition of PA below the ratio of 100:6.0 (WS:PA, w/w). The short-range molecular order in the starch gels was enhanced by the addition of PA, confirmed by FT-IR analysis. Mechanical experiments demonstrated that the binding strength of the starch gels increased with higher PA concentrations and decreased significantly after the aging process. TGA results revealed that PA promoted the acid degradation of starch molecules. This study provides a detailed guide for the preparation of starch-based adhesive and its applications in paper conservation.
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Droplet impact is a ubiquitous phenomenon in nature, daily life, and industrial processes. It is thus crucial to tune the impact outcomes for various applications. As a special outcome of droplet impact, the bouncing of droplets keeps the form of the droplets after the impact and minimizes the energy loss during the impact, being beneficial in many applications. A unified understanding of droplet bouncing is in high demand for effective development of new techniques to serve applications. This review shows the fundamentals, regulations, and applications of millimeter-sized droplet bouncing on solid surfaces and same/miscible liquids (liquid pool and another droplet). Regulation methods and current applications are summarized, and potential directions are proposed.
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With the presence of an external magnetic field, a ferrofluid droplet exhibits a rich variety of interesting phenomena notably different from nonmagnetic droplets. Here, a ferrofluid droplet impacting on a liquid-repellent surface is systematically investigated using high-speed imaging. The pre- and post-impact, including the droplet stretching, maximum spreading diameter, and final impact modes, are shown to depend on the impact velocity and the magnitude of the external magnetic field. A scaling relation involving the Weber and magnetic Bond numbers is fitted to predict the maximum spreading diameter based on the magnetic field-induced effective surface tension. The impact outcome is also investigated and classified into three patterns depending on the occurrence of the rim interface instability and the fission phenomenon. Two types of fission (i.e., evenly and unevenly distributed sizes of the daughter droplets) are first identified, and the corresponding mechanism is revealed. Last, according to Rayleigh-Taylor instability, a semiempirical formula is proposed to estimate the number of the daughter droplets in the regime of evenly distributed size, which agrees well with the experimental data. The present study can provide more insight into large-scale droplet generation with monodispersive sizes.
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To compare the different actions of the two representative transition metal cations of Co2+ and Ni2+ in layered double hydroxides (LDHs), CoAl-LDH and NiAl-LDH intercalated with CO32- were synthesized, and the chemical structures, microstructures, and surface areas thereof were successfully characterized. Then, the two LDHs were utilized as flame retardants and smoke suppressants for silicone foam (SiF). The densities, flame retardancy, smoke suppression, thermal stabilities, and compressive strengths of the two SiF/LDHs nanocomposites were investigated. The introduction of LDHs slightly decreased the density of SiF due to the catalytic actions of Co and Ni during the foaming process of SiF. With respect to the flame retardancy, the addition of only 1 phr of either CoAl-LDH or NiAl-LDH could effectively improve the limiting oxygen index of SiF from 28.7 to 29.6%. Based on the results of vertical flame testing and a cone calorimeter test, the flame retardancy and fire safety of the SiF were effectively enhanced by the incorporation of LDHs. In addition, owing to the good catalytic action and large specific surface area (NiAl-LDH: 174.57 m2 g-1; CoAl-LDH: 51.47 m2 g-1), NiAl-LDH revealed higher efficiencies of flame retardancy and smoke suppression than those of CoAl-LDH. According to the results of energy-dispersive X-ray spectroscopy, Co and Ni participated in the formation of protective char layers, which inhibited the release of SiO2 into the gas phase. Finally, the influences on the thermal decomposition and compressive strength for SiF resulting from the addition of LDHs are discussed.
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Retardadores de Chama , Fumaça , Cátions , Hidróxidos/química , Oxigênio , Dióxido de Silício , SiliconesRESUMO
A substantial proportion of prostatic adenocarcinoma (PRAD) patients experience biochemical failure (BCF) after radical prostatectomy (RP). The immune microenvironment plays a vital role in carcinogenesis and the development of PRAD. This study aimed to identify a novel immune-related gene (IRG)-based signature for risk stratification and prognosis of BCF in PRAD. Weighted gene coexpression network analysis was carried out to identify a BCF-related module in a discovery cohort of patients who underwent RP at the Massachusetts General Hospital. The median follow-up time was 70.32 months. Random forest and multivariate stepwise Cox regression analyses were used to identify an IRG-based signature from the specific module. Risk plot analyses, Kaplan-Meier curves, receiver operating characteristic curves, univariate and multivariate Cox regression analyses, stratified analysis, and Harrell's concordance index were used to assess the prognostic value and predictive accuracy of the IRG-based signature in the internal discovery cohort; The Cancer Genome Atlas database was used as a validation cohort. Tumor immune estimation resource database analysis and CIBERSORT algorithm were used to assess the immunophenotype of PRAD. A novel IRG-based signature was identified from the specific module. Five IRGs (BUB1B, NDN, NID1, COL4A6, and FLRT2) were verified as components of the risk signature. The IRG-based signature showed good prognostic value and predictive accuracy in both the discovery and validation cohorts. Infiltrations of various immune cells were significantly different between low-risk and high-risk groups in PRAD. We identified a novel IRG-based signature that could function as an index for assessing tumor immune status and risk stratification in PRAD.
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Adenocarcinoma/genética , Redes Reguladoras de Genes , Antígenos HLA/genética , Neoplasias da Próstata/genética , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Proteínas de Ciclo Celular/genética , Estudos de Coortes , Colágeno Tipo IV/genética , Seguimentos , Perfilação da Expressão Gênica , Marcadores Genéticos , Humanos , Imunidade Celular , Imunofenotipagem , Estimativa de Kaplan-Meier , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Proteínas Serina-Treonina Quinases/genética , Curva ROC , Análise de Regressão , Medição de Risco , Falha de Tratamento , Microambiente Tumoral/imunologia , Proteínas Supressoras de Tumor/genéticaRESUMO
Human poly(ADP-ribose) polymerases (PARPs) are a class of nuclear enzymes involved in the pathogenesis of diverse gynecologic tumors. The PARP1 and PARP2 are the two most documented members in PARP family, which have been approved as the druggable targets of ovarian and cervical cancers. Selective targeting of the two enzymes with small-molecule inhibitors is a great challenge due to the high conservation in catalytic domain and active site. Here, we investigate the systematic selectivity profile of sophisticated PARP inhibitors between the two enzymes. Computational methods are used to model/optimize the complex structures of inhibitor ligands with PARP1/2 catalytic domains and then to estimate the theoretical Fenzymatic assays exhibit a good consistence with theoretical selectivity over six tested inhibitor samples (rc2 = 0.857). It is revealed that the inhibitor selectivity is conferred from the exquisite difference in the residue composition and structural architecture of both the local activity sites and the whole catalytic domains of the two enzymes. In particular, the TMZ50 and ME0328 show strong selectivity between PARP1 and PARP2, but only the former has a potent activity on the two enzymes, whereas the latter can only inhibit the enzymes moderately. These compounds can be considered as potential lead molecular entities to develop new specific PARP-selective inhibitor drugs for personalized therapy combating gynecologic cancers.
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Antineoplásicos/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Poli(ADP-Ribose) Polimerases/química , Medicina de Precisão , Bibliotecas de Moléculas Pequenas/farmacologia , Domínio Catalítico , Feminino , Humanos , Modelos Moleculares , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/patologiaRESUMO
As a non-noble-metal catalyst, CuO has great potential in the catalytic combustion of CO and CH4. In this work, the influence of loading active copper components onto perovskites and essential operating parameters in flame aerosol synthesis has been experimentally and theoretically investigated to optimize the catalytic efficiency for the complete oxidation of lean CO and CH4. Herein, the CuO-SrTiO3 nanocatalysts are one-step-synthesized by flame spray pyrolysis with varied copper loadings and precursor feeding rates. The sample under the precursor flow rate of 3 mL/min and the CuO loading of 15 mol % demonstrates optimal catalytic performance. It is primarily attributed to the excellent low-temperature reducibility and improved activity of copper species originated by CuO quantum dots and metal-support interaction. Besides, SrTiO3 perovskite as a support can effectively inhibit the sintering of CuO quantum dots at high temperatures, which is responsible for the excellent sintering and water deactivation resistances.
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Pirólise , Pontos Quânticos , Compostos de Cálcio , Catálise , Cobre , Óxidos , TitânioRESUMO
OBJECTIVE: To identify the key genes associated with the pathogenesis of PCa using the bioinformatics approach for a deeper insight into the molecular mechanisms underlying the development and progression of PCa. METHODS: The microarray datasets GSE70770, GSE32571 and GSE46602 were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEG) in the normal prostate tissue and PCa were identified with the GEO2R tool, followed by functional enrichment analysis. A protein-protein interaction (PPI) network of DEGs was constructed by STRING and visualized with the Cytoscape software. RESULTS: A total of 235 DEGs were identified, including 61 up-regulated and 174 down-regulated genes, which were mainly enriched in focal adhesion kinase (FAK), ECM-receptor interaction, and other signaling pathways. From the PPI network were screened out 12 highly connected hub genes, including MYH11, TPM1, TPM2, SMTN, MYL9, VCL, ACTG1, CNN1, CALD1, ACTC1, MYLK and SORBS1, which were shown by hierarchical cluster analysis to be capable of distinguishing prostate cancer from non-cancer tissue. CONCLUSIONS: A total of 235 DEGs and 12 hub genes were identified in this study, which may contribute to a further understanding of the molecular mechanisms of the development and progression of PCa, and provide new candidate targets for the diagnosis and treatment of the malignancy.
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Biologia Computacional , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/genéticaRESUMO
OBJECTIVE: To compare the safety and effectiveness of using a conventional nephrostomy sheath (NS) vs using a new NS with suction and evacuation functions in minimally invasive percutaneous nephrolithotomy (MPCNL) for the treatment of staghorn stones. PATIENTS AND METHODS: A prospective and randomised study of 60 patients with staghorn stones randomly assigned into two groups of 30 patients. One group underwent MPCNL using conventional NS, whereas the other group underwent MPCNL with suction-evacuation NS (SENS). Patient demographics, stone characteristics, intraoperative data, perioperative data, and surgical results were collected and analysed. RESULTS: The patient demographics and stone characteristics were similar amongst the two groups. The SENS group had a significantly lower peak and a significantly lower average renal pelvic pressure (RPP) throughout the procedure. The SENS group was more efficient for stone removal and had a much shorter stone treatment time, a lesser use of the stone extractor, and ultimately a higher stone-free rate (SFR). The effects of a lower RPP and shorter stone treatment time translated into less severe postoperative complications as measured per modified Clavien grade. CONCLUSION: Using SENS in MPCNL for the treatment of staghorn stones has the advantages of lower RPP, increased effectiveness in stone retrieval, decreased surgery related complications, and an improved SFR.
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Nefrostomia Percutânea , Cálculos Coraliformes/cirurgia , Adulto , Desenho de Equipamento , Feminino , Humanos , Pelve Renal/cirurgia , Masculino , Pessoa de Meia-Idade , Nefrostomia Percutânea/efeitos adversos , Nefrostomia Percutânea/instrumentação , Nefrostomia Percutânea/métodos , Complicações Pós-Operatórias , Estudos Prospectivos , Sucção/instrumentaçãoRESUMO
Osteoporosis, osteopenia, and pathological bone fractures are frequent complications of iron-overload conditions such as hereditary hemochromatosis, thalassemia, and sickle cell disease. Moreover, animal models of iron overload have revealed increased bone resorption and decreased bone formation. Although systemic iron overload affects multiple organs and tissues, leading to significant changes on bone modeling and remodeling, the cell autonomous effects of excessive iron on bone cells remain unknown. Here, to elucidate the role of cellular iron homeostasis in osteoclasts, we generated two mouse strains in which solute carrier family 40 member 1 (Slc40a1), a gene encoding ferroportin (FPN), the sole iron exporter in mammalian cells, was specifically deleted in myeloid osteoclast precursors or mature cells. The FPN deletion mildly increased iron levels in both precursor and mature osteoclasts, and its loss in precursors, but not in mature cells, increased osteoclastogenesis and decreased bone mass in vivo Of note, these phenotypes were more pronounced in female than in male mice. In vitro studies revealed that the elevated intracellular iron promoted macrophage proliferation and amplified expression of nuclear factor of activated T cells 1 (Nfatc1) and PPARG coactivator 1ß (Pgc-1ß), two transcription factors critical for osteoclast differentiation. However, the iron excess did not affect osteoclast survival. While increased iron stimulated global mitochondrial metabolism in osteoclast precursors, it had little influence on mitochondrial mass and reactive oxygen species production. These results indicate that FPN-regulated intracellular iron levels are critical for mitochondrial metabolism, osteoclastogenesis, and skeletal homeostasis in mice.
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Reabsorção Óssea/genética , Proteínas de Transporte de Cátions/genética , Deleção de Genes , Ferro/metabolismo , Células Mieloides/patologia , Osteoclastos/patologia , Animais , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Proteínas de Transporte de Cátions/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides/citologia , Células Mieloides/metabolismo , Osteoclastos/citologia , Osteoclastos/metabolismo , OsteogêneseRESUMO
Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors in the urinary system. Surgical intervention is the preferred treatment for ccRCC, but targeted biological therapy is required for postoperative recurrent or metastatic ccRCC. Autophagy is an intracellular degradation system for misfolded/aggregated proteins and dysfunctional organelles. Defective autophagy is associated with many diseases. Mul1 is a mitochondrion-associated E3 ubiquitin ligase and involved in the regulation of divergent pathophysiological processes such as mitochondrial dynamics, and thus affects the development of various diseases including cancers. Whether Mul1 regulates ccRCC development and what is the mechanism remain unclear. Histochemical staining and immunoblotting were used to analyze the levels of Mul1 protein in human renal tissues. Statistical analysis of information associated with tissue microarray and The Cancer Genome Atlas (TCGA) database was conducted to show the relationship between Mul1 expression and clinical features and survival of ccRCC patients. Impact of Mul1 on rates of cell growth and migration and autophagy flux were tested in cultured cancer cells. Herein we show that Mul1 promoted autophagy flux to facilitate the degradation of P62-associated protein aggresomes and adipose differentiation-related protein (ADFP)-associated lipid droplets and suppressed the growth and migration of ccRCC cells. Levels of Mul1 protein and mRNA were significantly reduced so that autophagy flux was likely blocked in ccRCC tissues, which is potentially correlated with enhancement of malignancy of ccRCC and impairment of patient survival. Therefore, Mul1 may promote autophagy to suppress the development of ccRCC.
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Autofagia , Carcinoma de Células Renais/enzimologia , Neoplasias Renais/enzimologia , Mitocôndrias/enzimologia , Ubiquitina-Proteína Ligases/metabolismo , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Rim/enzimologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Proteólise , Proteínas de Ligação a RNA/metabolismo , Ubiquitina-Proteína Ligases/análiseRESUMO
Morella rubra, red bayberry, is an economically important fruit tree in south China. Here, we assembled the first high-quality genome for both a female and a male individual of red bayberry. The genome size was 313-Mb, and 90% sequences were assembled into eight pseudo chromosome molecules, with 32 493 predicted genes. By whole-genome comparison between the female and male and association analysis with sequences of bulked and individual DNA samples from female and male, a 59-Kb region determining female was identified and located on distal end of pseudochromosome 8, which contains abundant transposable element and seven putative genes, four of them are related to sex floral development. This 59-Kb female-specific region was likely to be derived from duplication and rearrangement of paralogous genes and retained non-recombinant in the female-specific region. Sex-specific molecular markers developed from candidate genes co-segregated with sex in a genetically diverse female and male germplasm. We propose sex determination follow the ZW model of female heterogamety. The genome sequence of red bayberry provides a valuable resource for plant sex chromosome evolution and also provides important insights for molecular biology, genetics and modern breeding in Myricaceae family.