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The human alkylation B (AlkB) homologs, ALKBH2 and ALKBH3, respond to methylation damage to maintain genomic integrity and cellular viability. Both ALKBH2 and ALKBH3 are direct reversal repair enzymes that remove 1-methyladenine (1meA) and 3-methylcytosine (3meC) lesions commonly generated by alkylating chemotherapeutic agents. Thus, the existence of deficiencies in ALKBH proteins can be exploited in synergy with chemotherapy. In this study, we investigated possible interactions between ALKBH2 and ALKBH3 with other proteins that could alter damage response and discovered an interaction with the mismatch repair (MMR) system. To test whether the lack of active MMR impacts ALKBH2 and/or ALKBH3 response to methylating agents, we generated cells deficient in ALKBH2, ALKBH3, or both in addition to Mlh homolog 1 (MLH1), another MMR protein. We found that MLH1koALKBH3ko cells showed enhanced resistance toward SN1- and SN2-type methylating agents, whereas MLH1koALKBH2ko cells were only resistant to SN1-type methylating agents. Concomitant loss of ALKBH2 and ALKBH3 (ALKBH2ko3ko) rendered cells sensitive to SN1- and SN2-agents, but the additional loss of MLH1 enhanced resistance to both types of damage. We also showed that ALKBH2ko3ko cells have an ATR-dependent arrest at the G2/M checkpoint, increased apoptotic signaling, and replication fork stress in response to methylation. However, these responses were not observed with the loss of functional MLH1 in MLH1koALKBH2ko3ko cells. Finally, in MLH1koALKBH2ko3ko cells, we observed elevated mutant frequency in untreated and temozolomide treated cells. These results suggest that obtaining a more accurate prognosis of chemotherapeutic outcome requires information on the functionality of ALKBH2, ALKBH3, and MLH1.
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In X-ray diffraction measurements, the angular resolution has a detection limit due to the receiving size of the detector. In many cases this detection limit is too large and must be breached to obtain the desired information. A novel method is proposed here by making the detector simultaneously measuring and moving. Using the deconvolution algorithm to remove the convolution effect, the pixel size limitation is finally broken. The algorithm used is not a common one, and suppresses signals at high frequencies, ensuring the reliability of the peak shape after restoration. The feasibility of this method is verified by successfully measuring the crystal truncation rod signal of SrTiO3 single crystal, and the resolution is nearly ten times higher than that of a single pixel. Moreover, this method greatly reduces the noise and improves the signal-to-noise ratio.
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Chronic non-communicable diseases (NCDs) have become diseases that seriously threaten the health and quality of life of the Chinese population, and also become a major public health problem affecting the national economic and social development. With the intensification of China's population aging, the economic burden caused by NCDs will further increase. More and more evidence has shown that NCDs could be prevented, and the prevention and control of NCDs have been considered as a core task of building a healthy China. Therefore, precise personalized nutrition and the prevention of NCDs from the age of zero, which is called the "Double Zero Strategy", would provide a well-consolidated basis for body tissue structure, and prevention of NCDs should also begin at age zero, and then extend to the first 1 000 days of life. The "Double Zero Strategy" preventive intervention can improve the nutritional status, balance diet and nutrition, and increase physical activity among children, adolescents, adults, and the elderly, all of which can reduce the risk of chronic disease, disability, and death. Therefore, launching the "Double Zero Strategy" for full life cycle prevention will help to achieve China's health goals in the new era, and provide more comprehensive measures and plans for implementing the goal of a healthy China.
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Doenças não Transmissíveis , Adulto , Criança , Adolescente , Humanos , Idoso , Recém-Nascido , Prevalência , Doenças não Transmissíveis/epidemiologia , Doenças não Transmissíveis/prevenção & controle , Qualidade de Vida , Saúde Pública , DietaRESUMO
Objective: To evaluate the efficacy and safety of glaucoma drainage implants(XEN-45 Gel Stent) for glaucoma treatment. Methods: A prospective study was conducted to continuously collect the clinical data of patients who were diagnosed with glaucoma and underwent XEN-45 Gel Stent implantation in the Ophthalmology Department of Peking University People's Hospital from January 2022 to August 2023. The visual acuity, intraocular pressure, number of glaucoma medications, and success rate of the patients were analyzed before and after surgery at 1 day, 1 week, 1 month, 3 months, 6 months, 12 months, and 18 months. The differences in intraocular pressure and number of glaucoma medications among primary open-angle glaucoma, primary angle closure glaucoma, secondary glaucoma, and different implantation methods of XEN-45 Gel Stent among patients with primary open-angle glaucoma were compared. The intraoperative and postoperative complications were observed, and the risk factors for needling and surgical complete success were analyzed. Results: A total of 48 eyes from 48 patients were included in this study, comprising 27 males and 21 females, with a mean age of (54.4±18.0) years and the disease duration was 36.0(7.3, 81.0) months.There were 28 cases of primary open-angle glaucoma, 4 cases of primary angle closure glaucoma, and 16 cases of secondary glaucoma.The follow-up period was 8.0 (3.0, 12.0) months. At 12 months after surgery, the intraocular pressure decreased from 20.5 (17.0, 26.0) mmHg to (13.5±3.3) mmHg (P<0.05), and the number of glaucoma medications decreased from 3.0 (3.0, 4.0) to 0.0 (0.0, 0.0) (P<0.05). The complete success rate and qualified success rate were 73.9% (17/23) and 91.3% (21/23), respectively. The most common postoperative complications were shallow anterior chamber in 6 cases (12.5%), hypotony in 3 cases (6.3%), and blocked stent in 3 cases (6.3%). The most common postoperative treatment was needling in 27 cases (56.3%). There was no significant difference in intraocular pressure among different types of glaucoma. In the comparison of postoperative effects of different surgical implantation methods for primary open-angle glaucoma, there were no statistically significant differences in intraocular pressure and the number of glaucoma medications at other follow-up time points except 1 month after surgery (P<0.05). Univariate logistic regression analysis did not find any risk factors associated with needling and surgical complete success. Conclusions: XEN-45 Gel Stent implantation is an effective and safe surgical option for different types of glaucoma patients in China, which can significantly reduce intraocular pressure and the use of glaucoma medications and has a high success rate. However, some patients may need needling or other treatments after surgery.
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Implantes para Drenagem de Glaucoma , Glaucoma de Ângulo Aberto , Glaucoma , Pressão Intraocular , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Glaucoma/cirurgia , Glaucoma de Ângulo Aberto/cirurgia , Resultado do Tratamento , Idoso , Glaucoma de Ângulo Fechado/cirurgiaRESUMO
To better understand reproductive physiology of humpback whales Megaptera novaeangliae that reside in Hawai'i and Alaska, enzyme immunoassays were validated for both progesterone and testosterone in free-ranging and stranded animals (n = 185 biopsies). Concentrations were analyzed between different depths of large segments of blubber taken from skin to muscle layers of stranded female (n = 2, 1 pregnant, 1 non-pregnant) and male (n = 1) whales. Additionally, progesterone metabolites were identified between pregnant (n = 1) and non-pregnant (n = 3) females using high pressure liquid chromatography (HPLC). Progesterone concentrations were compared between juvenile (i.e., sexually immature), lactating, and pregnant females, and male whales, and pregnancy rates of sexually mature females were calculated. Based on replicate samples from ship struck animals collected at 7 depth locations, blubber containing the highest concentration of progesterone was located 1 cm below the skin for females, and the highest concentration of testosterone was in the skin layer of one male whale. HPLC of blubber samples of pregnant and non-pregnant females contain different immunoreactive progesterone metabolites, with the non-pregnant female eluate comprised of a more polar, and possibly conjugated, form of progesterone than the pregnant female. In females, concentrations of progesterone were highest in the blubber of pregnant (n = 28, 28.6 ± 6.9 ng/g), followed by lactating (n = 16, 0.9 ± 0.1 ng/g), and female juvenile (n = 5, 1.0 ± 0.2 ng/g) whales. Progesterone concentrations in male (n = 24, 0.6 ng/g ± 0.1 ng/g) tissues were the lowest all groups, and not different from lactating or juvenile females. Estimated summer season pregnancy rate among sexually mature females from the Hawai'i stock of humpback whales was 0.562 (95 % confidence interval 0.528-0.605). For lactating females, the year-round pregnancy rate was 0.243 (0.09-0.59), and varies depending on the threshold of progesterone assumed for pregnancy in the range between 3.1 and 28.5 ng/g. Our results demonstrate the synergistic value added when combining immunoreactive assays, HPLC, and long-term sighting histories to further knowledge of humpback whale reproductive physiology.
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Jubarte , Feminino , Masculino , Animais , Gravidez , Progesterona , Taxa de Gravidez , Lactação , TestosteronaRESUMO
Conventional tumor culture models include two-dimensional tumor cell cultures and xenograft models. The former has disadvantages including lack of tumor heterogeneity and poor clinical relevance, while the latter are limited by the slow growth, low engraftment successful rate, and high cost. In recent years, in vitro three-dimensional (3D) tumor models have emerged as the tool to better recapitulate the spatial structure and the in vivo environment of tumors. In addition, they preserve the pathological and genetic features of tumor cells and reflect the complex intracellular and extracellular interactions of tumors, which have become a powerful tool for investigating the tumor mechanism, drug screening, and personalized cancer treatment. 3D tumor model technologies such as spheroids, organoids, and microfluidic devices are maturing. Application of new technologies such as co-culture, 3D bioprinting, and air-liquid interface has further improved the clinical relevance of the models. Some models recapitulate the tumor microenvironment, and some can even reconstitute endogenous immune components and microvasculature. In recent years, some scholars have combined xenograft models with organoid technology to develop matched in vivo/in vitro model biobanks, giving full play to the advantages of the two technologies, and providing an ideal research platform for individualized precision therapy for specific molecular targets in certain subtypes of tumors. So far, the above technologies have been widely applied in the field of colorectal cancer research. Our research team is currently studying upon the application of patient-derived tumor cell-like clusters, a self-assembly 3D tumor model, in guiding the selection of postoperative chemotherapy regimens for colorectal cancer. A high modeling success rate and satisfactory results in the drug screening experiments have been achieved. There is no doubt that with the advancement of related technologies, 3D tumor models will play an increasingly important role in the research and clinical practice of colorectal cancer.
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Neoplasias Colorretais , Organoides , Humanos , Organoides/patologia , Técnicas de Cultura de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Microambiente TumoralRESUMO
Objective: To investigate the value of plasma cells for diagnosing lymph node diseases. Methods: Common lymphadenopathy (except plasma cell neoplasms) diagnosed from September 2012 to August 2022 were selected from the pathological records of Changhai Hospital, Shanghai, China. Morphological and immunohistochemical features were analyzed to examine the infiltration pattern, clonality, and IgG and IgG4 expression of plasma cells in these lymphadenopathies, and to summarize the differential diagnoses of plasma cell infiltration in common lymphadenopathies. Results: A total of 236 cases of lymphadenopathies with various degrees of plasma cell infiltration were included in the study. There were 58 cases of Castleman's disease, 55 cases of IgG4-related lymphadenopathy, 14 cases of syphilitic lymphadenitis, 2 cases of rheumatoid lymphadenitis, 18 cases of Rosai-Dorfman disease, 23 cases of Kimura's disease, 13 cases of dermal lymphadenitis and 53 cases of angioimmunoblastic T-cell lymphoma (AITL). The main features of these lymphadenopathies were lymph node enlargement with various degrees of plasm cell infiltration. A panel of immunohistochemical antibodies were used to examine the distribution of plasma cells and the expression of IgG and IgG4. The presence of lymph node architecture could help determine benign and malignant lesions. The preliminary classification of these lymphadenopathies was based on the infiltration features of plasma cells. The evaluation of IgG and IgG4 as a routine means could exclude the lymph nodes involvement of IgG4-related dieases (IgG4-RD), and whether it was accompanied by autoimmune diseases or multiple-organ diseases, which were of critical evidence for the differential diagnosis. For common lesions of lymphadenopathies, such as Castleman's disease, Kimura's disease, Rosai-Dorfman's disease and dermal lymphadenitis, the expression ratio of IgG4/IgG (>40%) as detected using immunhistochemistry and serum IgG4 levels should be considered as a standard for the possibility of IgG4-RD. The differential diagnosis of multicentric Castleman's diseases and IgG4-RD should be also considered. Conclusions: Infiltration of plasma cells and IgG4-positive plasma cells may be detected in some types of lymphadenopathies and lymphomas in clinicopathological daily practice, but not all of them are related to IgG4-RD. It should be emphasized that the characteristics of plasma cell infiltration and the ratio of IgG4/IgG (>40%) should be considered for further differential diagnosis and avoiding misclassification of lymphadenopathies.
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Hiperplasia do Linfonodo Gigante , Doença Relacionada a Imunoglobulina G4 , Linfadenite , Linfadenopatia , Humanos , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/patologia , Plasmócitos/metabolismo , Plasmócitos/patologia , China , Linfadenopatia/patologia , Inflamação/diagnóstico , Inflamação/patologia , Linfonodos/patologia , Diagnóstico Diferencial , Linfadenite/diagnóstico , Linfadenite/patologia , Imunoglobulina G/metabolismoRESUMO
Objective: To investigate the relationship between obstructive sleep apnea (OSA), apnea hypopnea index (AHI) and vascular injury in hypertensive patients. Methods: This cross-sectional study enrolled patients admitted to the Hypertension Department of TEDA International Cardiovascular Hospital from April 2020 to April 2023, who finished portable sleep monitoring. Sleep monitoring indicators, flow-mediated vasodilation (FMD), carotid artery ultrasound, carotid intima-media thickness, cervical and femoral pulse wave conduction velocity (cfPWV), brachial and ankle pulse wave conduction velocity (baPWV) were analyzed. OSA was classified into mild (5 times/h≤AHI<15 times/h), moderate (15≤AHI<30 times/h), and severe (AHI≥30 times/h) based on AHI levels. FMD<6.0% was defined as vascular endothelial injury, and cfPWV>10 m/s and/or baPWV>18 m/s was defined as arterial stiffness. Multivariate logistic regression analysis was used to explore the correlation between AHI, OSA severity and vascular injury, and subgroup analysis was performed in young (age≤45 years) and middle-to-old patients (age>45 years). Sensitivity analysis was performed by excluding patients with diabetes, cerebrovascular disease and coronary heart disease. The correlation between AHI and vascular injury index was analyzed by restricted cubic spline. Results: A total of 555 adult hypertensive patients were included, the mean age was (39.7±9.2) years, 422 were males (76.0%), and the prevalence of OSA was 66.7% (370/555). Multivariate logistic regression analysis showed that moderate OSA (OR=2.83, P=0.019) and severe OSA (OR=3.40, P=0.016) were positively correlated with vascular endothelial injury after adjusting for age, sex, body mass index and mean arterial pressure. Subgroup analysis showed that log AHI (OR=1.99, P=0.035), moderate OSA (OR=4.83, P=0.010) and severe OSA (OR=4.64, P=0.015) were associated with vascular endothelial injury in young hypertensive patients. The results of sensitivity analysis were similar to the above results. The results of restricted cubic spline analysis showed that AHI was correlated with FMD (P=0.022), and the slope of the curve was the largest when AHI was between 0 and 10 times/h. There was no correlation between log AHI and OSA severity and carotid intima-media thickening and arterial stiffness (all P<0.05). Conclusions: OSA is associated with vascular endothelial injury in hypertensive patients, especially in young patients.
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Hipertensão , Apneia Obstrutiva do Sono , Rigidez Vascular , Lesões do Sistema Vascular , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Espessura Intima-Media Carotídea , Estudos Transversais , Hipertensão/complicações , Apneia Obstrutiva do Sono/complicações , Artérias CarótidasRESUMO
14 workers in the 1, 8-diaminonaphthalene workshop of a chemical company in Nantong City had symptoms or signs of varying degrees of pruritus and pigmentation of the face, neck and waist. Pathological examination of skin biopsies showed hyperkeratosis, the basal cells were liquefied and denatured. Seven workers were eventually diagnosed with occupational melanosis. To explore the causes of occupational melanosis caused by exposure to 1, 8-dinitronaphthalene and 1, 8-diaminonaphthalene, and to provide reference for the prevention and treatment of occupational melanosis in the future, this paper reported 14 cases of melanosis in the skin of workers in chemical industry.
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Melanose , Humanos , Melanose/diagnóstico , Melanose/patologia , Pigmentação , Pele/patologiaRESUMO
Diamond-reinforced metal matrix composites (DMMC) prepared by cold spray are emerging materials simultaneously featuring outstanding thermal conductivity and wear resistance. In our paper, their mechanical and fatigue properties relevant to perspective engineering applications were investigated using miniature bending specimens. Two different diamond mass concentrations (20 and 50%) embedded in two metal matrices (Al-lighter than diamond, Cu-heavier than diamond) were compared with the respective cold-sprayed pure metals, as well as bulk Al and Cu references. The pure Al, Cu coatings showed properties typical for cold spray deposits, i.e., decreased elastic moduli (50 GPa for Al, 80 GPa for Cu), limited ductility (< 1 × 10-3) and low fracture toughness (3.8 MPa·m0.5 for Al, 5.6 MPa·m0.5 for Cu) when compared to the bulks. Significantly improved properties (strain at fracture, ultimate strength, fatigue crack growth resistance, fracture toughness) were then observed for the produced DMMC. The improvement can be explained by a combination of two factors: changes in the properties of the metallic matrix triggered by the reinforcement particles peening effect and stress redistribution due to the particles presence.
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Cold Spray (CS) is a deposition process, part of the thermal spray family. In this method, powder particles are accelerated at supersonic speed within a nozzle; impacts against a substrate material triggers a complex process, ultimately leading to consolidation and bonding. CS, in its modern form, has been around for approximately 30 years and has undergone through exciting and unprecedented developmental steps. In this article, we have summarized the key inventions and sub-inventions which pioneered the innovation aspect to the process that is known today, and the key breakthroughs related to the processing of materials CS is currently mastering. CS has not followed a liner path since its invention, but an evolution more similar to a hype cycle: high initial growth of expectations, followed by a decrease in interest and a renewed thrust pushed by a number of demonstrated industrial applications. The process interest is expected to continue (gently) to grow, alongside with further development of equipment and feedstock materials specific for CS processing. A number of current applications have been identified the areas that the process is likely to be the most disruptive in the medium-long term future have been laid down.
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Background: The optimal management of intra-articular calcaneal fractures is still controversial. Open reduction and internal fixation are always associated with serious complications. Aim: Various alternative methods have been used with variable effects. This retrospective study aimed to analyze the clinical efficacy and safety of a new "below-the-ankle" Ilizarov frame in patients with calcaneal fractures caused by high-energy trauma. Patients and Methods: We retrospectively explored ten patients with calcaneal fractures, of which four, five, and one were Sanders type II, III, and IV, respectively. All fractures were caused by high-energy trauma and were followed up for an average period of 21 months (range: 9-29 months). Clinical outcomes were primarily assessed by radiological criteria, functional scores of the foot and ankle, rate of complications, and ankle range of movement. Results: The Ilizarov frame was removed after an average period of 12 weeks (range: 11-15 weeks). Only two patients developed pin-tract infections, and none developed osteomyelitis, deep infections, neurovascular injury, malunion, and ankle arthrodesis. Based on the radiological assessment of the reduction of the subtalar joint and fracture fragments, all patients had excellent restored joint structure, with eight and two patients having good-to-excellent and fair ankle scores, respectively. The ranges of plantarflexion and dorsiflexion were 25°-43° and 8°-22°, respectively. Conclusion: The Ilizarov frame could be safe and effective for calcaneal fractures caused by high-energy trauma. This treatment protocol provides an effective approach to treat severe calcaneal fractures caused by high-energy events; however, long-term outcomes are still unknown.
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Traumatismos do Tornozelo , Calcâneo , Fraturas Ósseas , Articulação Talocalcânea , Tornozelo , Calcâneo/lesões , Calcâneo/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Humanos , Estudos Retrospectivos , Articulação Talocalcânea/cirurgia , Resultado do TratamentoRESUMO
Mesoscopic conductance fluctuations are a ubiquitous signature of phase-coherent transport in small conductors, exhibiting universal character independent of system details. In this Letter, however, we demonstrate a pronounced breakdown of this universality, due to the interplay of local and remote phenomena in transport. Our experiments are performed in a graphene-based interaction-detection geometry, in which an artificial magnetic texture is induced in the graphene layer by covering a portion of it with a micromagnet. When probing conduction at some distance from this region, the strong influence of remote factors is manifested through the appearance of giant conductance fluctuations, with amplitude much larger than e^{2}/h. This violation of one of the fundamental tenets of mesoscopic physics dramatically demonstrates how local considerations can be overwhelmed by remote signatures in phase-coherent conductors.
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Herein, 3D honeycomb hierarchical porous network scaffold carbon is synthesized by a unique PVP-SiO2-boiling method with the boiling bubbles as soft template and SiO2nanospheres as hard template. Then MnO2nanosheets intimately grow on the carbon matrix and are further decomposed to Mn3O4nanocrystalline with size of 7-9 nm. The obtained Mn3O4nanocrystalline@3D honeycomb hierarchical porous network scaffold carbon has abundant mesopores and large specific surface area (92 m2g-1). When used as a cathode material for zinc-ion batteries, the synthesized composites exhibit high reversible capacity (546.2 mAh g-1at 0.5 A g-1), remarkable cycling stability (discharge capacity of 97.8 mAh g-1at 3 A g-1after 600 cycles) and superior rate capability (15.7 mAh g-1at 10 A g-1). The kinetics analyses indicate zinc storage mechanism includes diffusion process and capacitive process of Zn2+and H+ions, and the capacitive storage is dominant. The outstanding zinc storage performance benefits from the structural advantages. The unique carbon matrix improves electronic conductivity of Mn3O4, facilitates penetration of electrolyte, and well supports Mn3O4nanocrystalline. The small size and large specific surface area of Mn3O4nanocrystalline induce significant capacitive storage effect.
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AIM: To evaluate the radiation dose and diagnostic image quality of low-dose computed tomography (CT) of the paranasal sinus in children, with acquisition at an ultra-low tube voltage (70 kVp) combined with the Flash technique. MATERIALS AND METHODS: Eighty paediatric patients underwent CT of the paranasal sinus and were divided into two groups according to different protocols (group A: 80 kVp protocol with conventional spiral mode [n=40] and group B: 70 kVp protocol with Flash scan mode [n=40]). For each examination, the CT dose index (CTDIvol), dose-length product (DLP), and effective dose (ED) were estimated. The image noise, signal-to-noise ratio (SNR), and overall subjective diagnostic image quality were also evaluated. RESULTS: For radiation dose, the CTDIvol (mGy), DLP (mGy·cm), and ED (mSv) values of the 70 kVp protocol were significantly lower than those of the 80 kVp protocol (CTDIvol: 1.57±0.009 versus 0.39±0.004 mGy, p<0.001; DLP: 19.88±2.01 versus 6.31±0.52 mGy·cm, p<0.001; ED: 0.079±0.016 versus 0.024±0.005 mSv, p<0.001). Compared with those of the 80-kVp protocol, the image noise increased by 40.7% (p=0.113), the SNRsoft-tissue decreased by 48.9%, and the SNRbone increased by 10.1% with the 70-kVp protocol (p=0.176 and 0.227, respectively). There was no significant difference in the overall subjective image quality grades between these two groups (p=0.15). CONCLUSION: When imaging the paranasal sinus in children, an ultra-low tube voltage (70 kVp) combined with the Flash CT technique can reduce the radiation dose significantly while maintaining diagnostic image quality with clinically acceptable image noise.
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Seios Paranasais/diagnóstico por imagem , Doses de Radiação , Tomografia Computadorizada por Raios X/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , Interpretação de Imagem Radiográfica Assistida por Computador , Razão Sinal-RuídoRESUMO
Xenoestrogens and phytoestrogens are referred to as "foreign estrogens" that are produced outside of the human body and have been shown to exert estrogen-like activity. Xenoestrogens are synthetic industrial chemicals, whereas phytoestrogens are chemicals present in the plant. Considering that these environmental estrogen mimics potentially promote hormone-related cancers, an understanding of how they interact with estrogenic pathways in human cells is crucial to resolve their possible impacts in cancer. Here, we conducted an extensive literature evaluation on the origins of these chemicals, emerging research techniques, updated molecular mechanisms, and ongoing clinical studies of estrogen mimics in human cancers. In this review, we describe new applications of patient-derived xenograft (PDX) models and single-cell RNA sequencing (scRNA-seq) techniques in shaping the current knowledge. At the molecular and cellular levels, we provide comprehensive and up-to-date insights into the mechanism of xenoestrogens and phytoestrogens in modulating the hallmarks of cancer. At the systemic level, we bring the emerging concept of window of susceptibility (WOS) into focus. WOS is the critical timing during the female lifespan that includes the prenatal, pubertal, pregnancy, and menopausal transition periods, during which the mammary glands are more sensitive to environmental exposures. Lastly, we reviewed 18 clinical trials on the application of phytoestrogens in the prevention or treatment of different cancers, conducted from 2002 to the present, and provide evidence-based perspectives on the clinical applications of phytoestrogens in cancers. Further research with carefully thought-through concepts and advanced methods on environmental estrogens will help to improve understanding for the identification of environmental influences, as well as provide novel mechanisms to guide the development of prevention and therapeutic approaches for human cancers.
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Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Fitoestrógenos/uso terapêutico , Análise de Célula Única/métodos , Animais , Biomarcadores Tumorais/genética , Ensaios Clínicos como Assunto , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Neoplasias/genética , Fitoestrógenos/farmacologia , Análise de Sequência de RNA , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The cingulate cortex contributes to complex, adaptive behaviors, but the exact nature of its contributions remains unresolved. Proposals from previous studies, including evaluating past actions or selecting future ones, have been difficult to distinguish in part because of an incomplete understanding of the task-relevant variables that are encoded by individual cingulate neurons. In this study, we recorded from individual neurons in parts of both the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) in 2 male rhesus monkeys performing a saccadic reward task. The task required them to use adaptive, feedback-driven strategies to infer the spatial location of a rewarded saccade target in the presence of different forms of uncertainty. We found that task-relevant, spatially selective feedback signals were encoded by the activity of individual neurons in both brain regions, with stronger selectivity for spatial choice and reward-target signals in PCC and stronger selectivity for feedback in ACC. Moreover, neurons in both regions were sensitive to sequential effects of feedback that partly reflected sequential behavioral patterns. However, neither brain region exhibited systematic modulations by the blockwise conditions that governed the reliability of the trial-by-trial feedback and drove adaptive behavioral patterns. There was also little evidence that single-neuron responses in either brain region directly predicted the extent to which feedback and contextual information were used to inform choices on the subsequent trial. Thus, certain cingulate neurons encode diverse, evaluative signals needed for adaptive, feedback-driven decision-making, but those signals may be integrated elsewhere in the brain to guide actions.SIGNIFICANCE STATEMENT Effective decision-making in dynamic environments requires adapting to changes in feedback and context. The anterior and posterior cingulate cortex have been implicated in adaptive decision-making, but the exact nature of their respective roles remains unresolved. Here we compare patterns of task-driven activity of subsets of individual neurons from parts of the two brain regions in monkeys performing a saccadic task with dynamically changing reward locations. We find evidence for regional specializations in neural representations of choice and feedback, including task-relevant modulations of activity that could be used for performance monitoring. However, we find little evidence that these neural representations are used directly to adjust choice behavior, which thus likely requires integration of these signals elsewhere in the brain.
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Tomada de Decisões/fisiologia , Giro do Cíngulo/fisiologia , Neurônios/fisiologia , Autoimagem , Adaptação Psicológica/fisiologia , Animais , Comportamento de Escolha/fisiologia , Condicionamento Operante , Eletroencefalografia , Retroalimentação Psicológica , Giro do Cíngulo/citologia , Macaca mulatta , Masculino , Recompensa , Movimentos SacádicosRESUMO
Pomegranate-like C@TiO2 mesoporous honeycomb spheres have been synthesized through two simple steps: formation of TiO2 mesoporous honeycomb spheres and the coating of polypyrrole followed by carbonization. TiO2 mesoporous honeycomb spheres are of large specific surface area of 153 m2 g-1 and contain abundant mesopores, which leads to high electrochemical activity and good kinetic performance of TiO2. A layer of amorphous carbon shell with the thickness of 30-40 nm tightly encapsulates a TiO2 mesoporous honeycomb sphere, forming a novel pomegranate-like small sphere, which significantly improves electronic conductivity and structural stability of TiO2. Benefiting from the unique pomegranate-like structure, C@TiO2 mesoporous honeycomb spheres exhibit high specific capacity, stable long-term cycling performance and good rate capability as an anode material for lithium ion batteries (LIBs). After 500 cycles at 1 C, the discharge capacity still reaches 184 mAh g-1. The electrochemical performance is superior to pure TiO2 mesoporous honeycomb spheres and most of the reported high-performance TiO2-based composites. This work provides a new high-performance TiO2-carbon-based composite material for LIBs as well as a new valuable research strategy.
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To overcome the inferior rate capability and cycling performance of TiO2 nanomaterials as an anode material of lithium-ion batteries, we encapsulate TiO2 nanoparticles (P25) in carbon spheres through a facile pyrrole polymerization and carbonization. Material characterization demonstrates TiO2 nanoparticles are uniformly embedded in microporous amorphous carbon spheres, forming a watermelon-like structure. P25@C exhibits excellent high rate capability with average discharge capacity of 496, 416, 297, 240, 180, 99, 49 and 25 mAh g-1 at current rate of 0.5C, 1C, 5C, 10C, 20C, 50C, 100C and 200C, which shows superior long-term cycling performance with discharge capacity of 106.9 mAh g-1 at 20C after 5000 cycles. The capacity loss rate is only 0.008% per cycle. The outstanding lithium storage performance is ascribed to the watermelon-like composite structure, which remarkably improves electronic conductivity and structure stability of TiO2 nanoparticles. More importantly, the agglomeration of TiO2 nanoparticles is eliminated, and the entire surface of every TiO2 nanoparticle participates in the electrochemical reaction, which brings about an intense capacitive Li storage effect and leads to the high specific capacity and excellent rate capability of P25@C. This is confirmed through qualitative and quantitative analysis of the contributions from surface capacitive storage and bulk intercalation storage to the total capacity of the composite.
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Objective: To explore the connection between severe perioperative complications and preoperative basic diseases of surgical patients with non-small cell lung cancer (NSCLC). Methods: We retrospectively analyzed the data of surgical patients with NSCLC from January 1, 2016 to December 31, 2018 in Cancer Hospital, Chinese Academy of Medical Sciences (CAMS). The single factor analysis and logistic multivariate regression analysis were conducted to explicate the correlation of the risk factors especially preoperative basic diseases with severe perioperative complications. Results: A total of 12, 650 cases meeting our inclusion and exclusion criteria were included, of whom 5, 409 (42.76%) cases had various preoperative basic diseases and 140 (1.11%)cases occurred severe perioperative complications. Pulmonary and intrathoracic complications and circulatory system complications dominantly accounted for the severe perioperative complications, with incidence of 0.64% and 0.25%, respectively. The gender, age, tumor differentiation, surgical method, surgical approach, and preoperative basic diseases were significantly associated with the occurrence of severe perioperative complications in surgical patients with NSCLC according to the single factor analysis outcomes (P<0.05). Patients with pulmonary disease (P=0.02), heart disease (P=0.03) and diabetes (P=0.02) were more likely to occur severe complications according to the multivariate analysis outcomes. Conclusions: The forms of severe perioperative complications of surgical patients with NSCLC are various. Patients with pulmonary disease, heart disease and diabetes are likely to occur severe complications, besides patients with male sex, elder age, poorly differentiated tumor, and undergoing open thoracotomy. We should take more effective measures to avoid severe complications when deal with these patients.