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OBJECTIVE: This study compared the clinical effects of two different lipid emulsions in premature infants with gestational age < 32 weeks (VPI) or birth weight < 1500 g (VLBWI) to provide an evidence-based medicine basis for optimizing intravenous lipid emulsion. METHODS: This was a prospective multicenter randomized controlled study. A total of 465 VPIs or VLBWIs, admitted to the neonatal intensive care unit of five tertiary hospitals in China from March 1, 2021 to December 31, 2021, were recruited. All subjects were randomly allocated into two groups, namely, medium-chain triglycerides/long-chain triglycerides (MCT/LCT) group (n = 231) and soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) group (n = 234). Clinical features, biochemical indexes, nutrition support therapy, and complications were analyzed and compared between the two groups. RESULTS: No significant differences were found in perinatal data, hospitalization, parenteral and enteral nutrition support between the two groups (P > 0.05). Compared with the MCT/LCT group, the incidence of neonates with a peak value of total bilirubin (TB) > 5 mg/dL (84/231 [36.4% vs. 60/234 [25.6%]), a peak value of direct bilirubin (DB) ≥ 2 mg/dL (26/231 [11.3% vs. 14/234 [6.0%]), a peak value of alkaline phosphatase (ALP) > 900 IU/L (17/231 [7.4% vs. 7/234 [3.0%]), and a peak value of triglycerides (TG) > 3.4 mmol/L (13/231 [5.6% vs. 4/234[1.7%]]) were lower in the SMOF group (P < 0.05). Univariate analysis showed that in the subgroup analysis of < 28 weeks, the incidence of parenteral nutrition-associated cholestasis (PNAC) and metabolic bone disease of prematurity (MBDP) were lower in the SMOF group (P = 0.043 and 0.029, respectively), whereas no significant differences were present in the incidence of PNAC and MBDP between the two groups at > 28 weeks group (P = 0.177 and 0.991, respectively). Multivariate logistic regression analysis revealed that the incidence of PNAC (aRR: 0.38, 95% confidence interval [CI]: 0.20-0.70, P = 0.002) and MBDP (aRR: 0.12, 95% CI: 0.19-0.81, P = 0.029) in the SMOF group were lower than that in the MCT/LCT group. In addition, no significant differences were recorded in the incidence of patent ductus arteriosus, feeding intolerance, necrotizing enterocolitis (Bell's stage ≥ 2), late-onset sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity and extrauterine growth retardation between the two groups (P > 0.05). CONCLUSIONS: The application of mixed oil emulsion in VPI or VLBWI can reduce the risk of plasma TB > 5 mg/dL, DB ≥ 2 mg/dL, ALP > 900 IU/L, and TG > 3.4 mmol/L during hospitalization. SMOF has better lipid tolerance, reduces the incidence of PNAC and MBDP, and exerts more benefits in preterm infants with gestational age < 28 weeks.
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BACKGROUND: The activation of hepatic stellate cells (HSCs) is the key step in the pathogenesis of liver fibrosis, which directly leads to fibrotic pathological changes in the hepatic tissue. Mitochondrial stress exacerbates inflammatory diseases by inducing pathogenic shifts in normal cells. However, the role of mitochondrial stress in HSC activation remains to be elucidated. METHODS: We analyzed the effect of mitochondrial stress on HSC activation. An in vivo hepatic fibrosis model was established by intraperitoneal injection of 40% carbon tetrachloride (CCl4) for 12 weeks. Additionally, using in vitro approach, HSC-T6 cells were treated with 10 ng/mL platelet-derived growth factor-BB (PDGF-BB) for 24 h. RESULTS: Transcriptional activator 4 (ATF4) is highly expressed in fibrotic liver tissue samples and activated HSCs. We found that AAV8-shRNA-Atf4 alleviated liver fibrosis in rats. ATF4 promoted the activation of HSCs, which was induced by mitochondrial stress. The mechanisms involved ATF4 binding to a specific region of the tribble homologue 3 (TRIB3) promoter. Further, TRIB3 promoted HSCs activation mediated by mitochondrial stress. CONCLUSIONS: ATF4 induces mitochondrial stress by upregulating TRIB3, leading to the activation of HSCs. Therefore, the inhibition of ATF4 during mitochondrial stress may be a promising therapeutic target for liver fibrosis.
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The carcinogenicity of hexavalent chromium [Cr(VI)] and its compounds has been widely recognized, yet the mechanism of genetic damage is still not fully understood. The ribosomal DNA (rDNA) copy number is recently considered a potential marker of cancer-associated stress. To investigate the roles of rDNA copy number variation (CNV) in DNA damage responses (DDRs) induced by Cr(VI) and the potential mechanism from nucleolar protein HRAS, a cross-sectional study in Cr(â ¥)-exposed workers and an in vitro experiment using HeLa cells were conducted. Our results showed increased levels of rDNA CNV, DDRs, and HRAS expression in Cr(VI)-exposed workers. Generalized linear regression analyses showed that Cr(VI) exposure was significantly positively associated with increased levels of rDNA CNV, DDRs, and HRAS expression in Cr(VI)-exposed workers. Moreover, there were pairwise associations between rDNA CNV, DDRs, and HRAS levels. Mediation analyses found that rDNA CNV significantly mediated the association between Cr(VI) exposure and DDRs. The in vitro experiments further confirmed that Cr(VI) treatment induced increased levels of rDNA CNV, DDRs, and HRAS expression in HeLa cells. Cr(VI)-induced rDNA CNV, ATM activation, and apoptosis damage were then strongly enhanced by HRAS depletion with siRNA in vitro, suggesting the important role of HRAS in CNV and DDRs caused by Cr(VI). The combined results of the human and cell line studies indicated that Cr(VI) exposure might enhance rDNA CNV by regulation of HRAS expression, which leads to Cr(VI)-induced genetic damage.
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Gut barrier disruption is a key event in bridging gut microbiota dysbiosis and high-fat diet (HFD)-associated metabolic disorders. However, the underlying mechanism remains elusive. In the present study, by comparing HFD- and normal diet (ND)-treated mice, we found that the HFD instantly altered the composition of the gut microbiota and subsequently damaged the integrity of the gut barrier. Metagenomic sequencing revealed that the HFD upregulates gut microbial functions related to redox reactions, as confirmed by the increased reactive oxygen species (ROS) levels in fecal microbiota incubation in vitro and in the lumen, which were detected using in vivo fluorescence imaging. This microbial ROS-producing capability induced by HFD can be transferred through fecal microbiota transplantation (FMT) into germ-free (GF) mice, downregulating the gut barrier tight junctions. Similarly, mono-colonizing GF mice with an Enterococcus strain excelled in ROS production, damaged the gut barrier, induced mitochondrial malfunction and apoptosis of the intestinal epithelial cells, and exacerbated fatty liver, compared with other low-ROS-producing Enterococcus strains. Oral administration of recombinant high-stability-superoxide dismutase (SOD) significantly reduced intestinal ROS, protected the gut barrier, and improved fatty liver against the HFD. In conclusion, our study suggests that extracellular ROS derived from gut microbiota play a pivotal role in HFD-induced gut barrier disruption and is a potential therapeutic target for HFD-associated metabolic diseases.
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BACKGROUND: TDP-43 (43-kD transactive response DNA-binding protein) is a DNA-/RNA-binding protein that plays an important role in several nervous system diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Whether it plays an important role in glioma patients is unknown. METHODS: Datasets were downloaded from the Chinese Glioma Genome Atlas (CGGA) website ( http://www.cgga.org.cn/ ). Cox survival analysis was performed to determine the relationship between TARDBP gene expression and the overall survival of glioma patients. GO analyses were performed to determine the biological functions of the TARDBP gene. Finally, we used PRS type, age, grade, IDH mutation status, 1p/19q codeletion status, and expression value of the TARDBP gene to construct a prediction model. With this model, we can predict patients' 1-, 2-, 3-, 5-, and 10-year survival rates. RESULTS: The TARDBP gene plays an important role in glioma patients. The expression of the TARDBP gene has a significant correlation with glioma patient survival. We also constructed an ideal prediction model. CONCLUSION: Our findings suggest that the TARDBP gene and the protein it encodes play important roles in glioma patients. The expression of the TARDBP gene has a significant correlation with the overall survival of glioma patients.
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Neoplasias Encefálicas , Proteínas de Ligação a DNA , Glioma , Humanos , Neoplasias Encefálicas/genética , Proteínas de Ligação a DNA/genética , Glioma/genética , Mutação , PrognósticoRESUMO
Memristor-based circuits offer low hardware costs and in-memory computing, but full-memristive circuit integration for different algorithm remains limited. Cellular automata (CA) has been noticed for its well-known parallel, bio-inspired, computational characteristics. Running CA on conventional chips suffers from low parallelism and high hardware costs. Establishing dedicated hardware for CA remains elusive. We propose a recirculated logic operation scheme (RLOS) using memristive hardware and 2D transistors for CA evolution, significantly reducing hardware complexity. RLOS's versatility supports multiple CA algorithms on a single circuit, including elementary CA rules and more complex majority classification and edge detection algorithms. Results demonstrate up to a 79-fold reduction in hardware costs compared to FPGA-based approaches. RLOS-based reservoir computing is proposed for edge computing development, boasting the lowest hardware cost (6 components/per cell) among existing implementations. This work advances efficient, low-cost CA hardware and encourages edge computing hardware exploration.
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A perovskite light-emitting-diode (PeLED) displaying green color is combined with a brown fluorescent coating (FC) layer to form a hybrid FC-PeLED system. The FC-PeLED system can simulate the natural process of bionics of plant colors from green to brown through a low energy (<0.6 mW) input, promoting the development of future low-cost and low-power consumption bionics technology.
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The ectodomain of influenza matrix protein 2 (M2e) is a promising target for the development of universal prophylactic and therapeutic agents against influenza viruses of different subtypes. We constructed three M2e-specific monoclonal antibody variants, M2A1-1 (IgG1), M2A1-2a (IgG2a), M2A1-2b (IgG2b), which have the same Fab region targeting the M2e epitope but different isotypes, and compared their protective efficacy in influenza PR8-infected mice. We found that anti-M2e antibodies provided protection against influenza virus in a subtype-dependent manner, with the IgG2a variant providing significantly better protection with lower virus titers and milder lung injury than IgG1 and IgG2b isotypes. Additionally, we observed that the protective efficacy was dependent on the administration routes, with intranasal administration of antibody providing better protection than intraperitoneal administration. The timing of administration was also critical in determining the protective efficacy; while all the antibody isotypes provided protection when administered before influenza challenge, only IgG2a provided minimal protection when the antibodies were administered after virus challenge. These results provide valuable information for optimizing the therapeutics usage of M2e-based antibodies and furthering the development of M2e-based universal influenza vaccines.
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Vacinas contra Influenza , Influenza Humana , Infecções por Orthomyxoviridae , Orthomyxoviridae , Animais , Camundongos , Humanos , Anticorpos Antivirais , Imunoglobulina G , Proteínas da Matriz Viral/genética , Camundongos Endogâmicos BALB CRESUMO
Backgrounds: The incidence of melanosis coli (MC) has gradually increased annually, attracting significant attention and efforts into this field. A potential risk for MC is the long-term use of anthraquinone laxatives in patients with constipation. Most traditional cathartic drugs are made from herbs containing anthraquinone compounds. This review aims to provide guidance for the application of traditional Chinese herbs containing anthraquinones for physicians and researchers. Materials and methods: We reviewed risk factors and pathogenesis of MC, and natural anthraquinones isolated from TCM herbs. We searched Pubmed and CNKI databases for literature related to MC with keywords such as"traditional Chinese medicine", "Chinese herbs", "anthraquinones", and "melanosis coli". The literature is current to January 2023 when the searches were last completed. After the literature retrieval, the TCM herbs containing anthraquinones (including component identification and anthraquinone content determination) applied in clinical were selected. According to the collected evidence, we provide a list of herbs containing anthraquinones that could cause MC. Results: We identified 20 herbs belonging to 7 families represented by Polygonaceae, Fabaceae, Rhamnaceae, and Rubiaceae, which may play a role in the pathogenesis of MC. Among these, the herbs most commonly used include Dahuang (Rhei Radix et Rhizome), Heshouwu (Radix Polygoni Multiflori), Huzhang (Rhizoma Polygoni Cuspidati), Juemingzi (Semen Cassiae), Luhui (Aloe) and Qiancao (Rubiae Radix et Rhizoma). Conclusion: Due to a lack of awareness of the chemical composition of TCM herbs, many patients with constipation and even some TCM physicians take cathartic herbal remedies containing abundant anthraquinones to relieve defecation disturbances, resulting in long-term dependence on these herbs, which is potentially associated with most cases of MC. When such treatments are prescribed, TCM physicians should avoid long-term use in large doses to reduce their harm on colonic health. Individuals who take healthcare products containing these herbs should also be under the supervision of a doctor.
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Objective: Although surgical resection is one of the most effective way to treat liver cancer, its efficacy and safety in treatment of centrally located hepatocellular carcinoma (HCC) remains elusive. Therefore, it is very important to find a comprehensive treatment mode, such as radical resection combined with neoadjuvant radiotherapy (neoRT). Methods: The centrally located HCC patients who underwent radical resection from July 2015 to April 2021 were enrolled. According to whether the neoRT was implemented or not, these patients were allocated into neoadjuvant radiotherapy combined with liver resection (neoRT+LR) and liver resection alone (LR) group. The research method used propensity-score analysis and Cox proportional-hazards regression models. We generated an E-value to assess the sensitivity to unmeasured confounding. This study is a real-world, retrospective study based on phase II clinical trial. Results: A total of 168 patients were enrolled, including 38 patients treating with neoRT+LR and 130 patients with LR. The 1-, 3-, 5-year disease free survival (DFS) rates were 74%, 55% and 39% in the neoRT+LR group, and 44%, 28%, and 24% in the LR group, respectively. Neoadjuvant radiotherapy was an independent prognostic factor for postoperative recurrence ([HR]0.42, 95% CI [0.25, 0.69]). There was significant association between neoRT+LR and longer disease-free survival (Match, [HR] 0.43, 95% CI [0.24, 0.76]; GenMatch, [HR] 0.32, 95% CI [0.23, 0.43]; Adjusted for propensity score, [HR] 0.41, 95% CI [0.23, 0.73]; Inverse probability weighting, [HR] 0.38, 95% CI [0.22, 0.65], respectively). DFS before and after matching analysis was statistically different in two groups (p-value=0.005, p-value=0.0024, respectively). Neoadjuvant radiotherapy can significantly reduce the postoperative early recurrence (p-value <0.05). E-value analysis suggested robustness to unmeasured confounding. Conclusion: Liver resection combined with neoadjuvant radiotherapy was effective and safe for treatment of centrally located HCC patients, which improved the prognosis of patients and reduced the incidence of early recurrence.
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Cancer-associated fibroblasts (CAFs) are widely involved in the development and progression of tumours. As a direct junction between tumour and normal host tissue, the tumour invasive front can remodel host tissue to generate a microenvironment more suitable for tumour invasion. However, whether CAFs derived from the invasive front (CAFs-F) have a greater ability to promote tumour invasion than CAFs derived from the superficial tumour (CAFs-S) is unclear. In this study, we characterized primary CAFs from different spatial locations of tumours. We demonstrated that CAFs-F had an increased ability to promote oral squamous cell carcinoma (OSCC) proliferation and invasion in vitro and significantly enhanced tumour growth in vivo compared to CAFs-S. Mechanistically, transcriptome profiling analysis revealed that the expression of MFAP5, encoding microfibril associated protein 5, was dramatically increased in CAFs-F compared to CAFs-S, which further confirmed that the MFAP5 protein level was elevated in head and neck squamous cell carcinoma (HNSCC) and that this increase was correlated with poor survival. Genetic ablation of MFAP5 impaired the preinvasive capabilities of CAFs-F. Together, our findings demonstrated that CAFs-F had a greater ability to promote tumour invasion than CAFs-S and that MFAP5 might be involved in this process.
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The efficient intermolecular alkoxylation reactions of various enol acetates and different alcohols are developed in the electrochemical process for the first time. Enol acetates derived from either aromatic, alkyl, or alicyclic ketones, and abundant free alcohols directly used in this synthetic strategy, make this transformation very valuable in synthesis and application in the future.
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Striking antibody evasion by emerging circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants drives the identification of broadly neutralizing antibodies (bNAbs). However, how a bNAb acquires increased neutralization breadth during antibody evolution is still elusive. Here, we identify a clonally related antibody family from a convalescent individual. One of the members, XG005, exhibits potent and broad neutralizing activities against SARS-CoV-2 variants, while the other members show significant reductions in neutralization breadth and potency, especially against the Omicron sublineages. Structural analysis visualizing the XG005-Omicron spike binding interface reveals how crucial somatic mutations endow XG005 with greater neutralization potency and breadth. A single administration of XG005 with extended half-life, reduced antibody-dependent enhancement (ADE) effect, and increased antibody product quality exhibits a high therapeutic efficacy in BA.2- and BA.5-challenged mice. Our results provide a natural example to show the importance of somatic hypermutation during antibody evolution for SARS-CoV-2 neutralization breadth and potency.
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Background: Data on which frailty scales are most suitable for estimating risk in Chinese community populations remain limited. Herein we examined and compared four commonly used frailty scales in predicting adverse outcomes in a large population-based cohort of Chinese older adults. Methods: A total of 5402 subjects (mean age 66.3 ± 9.6 years, 46.6% male) from the WHO Study on global AGEing and adult health (SAGE) in Shanghai were studied. Frailty was measured using a 35-item frailty index (FI), the frailty phenotype (FP), FRAIL, and Tilburg Frailty Indicator (TFI). Multivariate logistic regression models were performed to evaluate the independent association between frailty and outcomes including 4-year disability, hospitalization, and 4- and 7-year all-cause mortality. The accuracy for predicting these outcomes was determined by evaluating the area under the curve (AUC). The prevalence of frailty, sensitivity, and specificity were calculated using our proposed cut-off points and other different values. Results: Prevalence of frailty ranged from 4.2% (FRAIL) to 16.9% (FI). FI, FRAIL and TFI were comparably associated with 4-year hospitalization, and 4- and 7-year mortality (adjusted odds ratios [aORs] 1.44-1.69, 1.91-2.22 and 1.85-2.88, respectively). FRAIL conferred the greatest risk of 4-year disability, followed by FI and TFI (aOR 5.55, 3.50, and 1.91, respectively). FP only independently predicted 4- and 7-year mortality (aOR 1.57 and 2.21, respectively). AUC comparisons showed that FI, followed by TFI and FRAIL, exhibited acceptable predictive accuracy for 4-year disability, 4- and 7-year mortality (AUCs 0.76-0.78, 0.71-0.71, 0.65-0.72, respectively), whereas all scales poorly predicted 4-year hospitalization (AUCs 0.53-0.57). For each scale, while specificity estimates (85.3-97.3%) were high and similar across all outcomes, their sensitivity estimates (6.3-56.8%) were not sufficient yet. Prevalence of frailty, sensitivity, and specificity varied considerably when different cut-off points were used. Conclusion: Frailty defined using any of the four scales was associated with an increased risk of adverse outcomes. Although FI, FRAIL and TFI exhibited fair-to-moderate predictive accuracy and high specificity estimates, their sensitivity estimates were not sufficient yet. Overall, FI performed best in estimating risk, while TFI and FRAIL were additionally useful, the latter perhaps being more applicable to Chinese community-dwelling older adults.
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Fragilidade , Humanos , Idoso , Masculino , Feminino , Fragilidade/epidemiologia , Idoso Fragilizado , Vida Independente , Avaliação Geriátrica , China/epidemiologiaRESUMO
BACKGROUND: The purpose of the study was to compare the efficacy of two novel obesity indices, lipid accumulation product (LAP) and visceral adiposity index (VAI), with traditional obesity indices in predicting early-onset type 2 diabetes (T2DM). METHODS: In this cross-sectional study, a total of 744 participants, including 605 patients newly diagnosed with T2DM and 139 non-diabetic control subjects, were enrolled from a tertiary care hospital in Tianjin, China. Participants with T2DM were divided into two groups based on their age at diagnosis, namely early-onset T2DM (age less than 40 years, n = 154) and late-onset T2DM (age 40 years or older, n = 451). The predictive power of each obesity index was evaluated using receiver operating characteristic (ROC) curve analysis. Furthermore, binary logistic regression analysis was conducted to examine the independent relationship between LAP and VAI with early-onset T2DM risk. The relationship between novel obesity indices and the age of T2DM onset was also evaluated through correlation and multiple linear regression analysis. RESULTS: In males, LAP had the highest predictive power for early-onset T2DM with an area under the ROC curve (AUC) of 0.742 (95% CI 0.684-0.799, P < 0.001). In females, VAI had the highest AUC for early-onset T2DM with a value of 0.748 (95% CI 0.657-0.839, P < 0.001), which was superior to traditional indices. Patients in the 4th quartile of LAP and VAI had 2.257 (95% CI 1.116-4.563, P = 0.023) and 4.705 (95% CI 2.132-10.384, P < 0.001) times higher risk of T2DM before age 40, compared to those in the 1st quartile, respectively. A tenfold increase in LAP was associated with a decrease in T2DM onset age of 12.862 years in males (ß = -12.862, P < 0.001) and 6.507 years in females (ß = -6.507, P = 0.013). A similar decrease in T2DM onset age was observed for each tenfold increase in VAI in both male (ß = -15.222, P < 0.001) and female (ß = -12.511, P < 0.001) participants. CONCLUSIONS: In young Chinese individuals, LAP and VAI are recommended over traditional obesity indices for improved prediction of early-onset T2DM risk.
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miR-144/451 and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulate two antioxidative systems that have been identified to maintain redox homeostasis in erythroid cells by removing excess reactive oxygen species (ROS). Whether these two genes coordinate to affect ROS scavenging and the anemic phenotype, or which gene is more important for recovery from acute anemia, has not been explored. To address these questions, we crossed miR-144/451 knockout (KO) and Nrf2 KO mice and examined the phenotype change in the animals as well as the ROS levels in erythroid cells either at baseline or under stress condition. Several discoveries were made in this study. First, Nrf2/miR-144/451 double-KO mice unexpectedly exhibit similar anemic phenotypes as miR-144/451 single-KO mice during stable erythropoiesis, although compound mutations of miR-144/451 and Nrf2 lead to higher ROS levels in erythrocytes than single gene mutations. Second, Nrf2/miR-144/451 double-mutant mice exhibit more dramatic reticulocytosis than miR-144/451 or Nrf2 single-KO mice during days 3 to 7 after inducing acute hemolytic anemia using phenylhydrazine (PHZ), indicating a synergistic effect of miR-144/451 and Nrf2 on PHZ-induced stress erythropoiesis. However, the coordination does not persist during the whole recovery stage of PHZ-induced anemia; instead, Nrf2/miR-144/451 double-KO mice follow a recovery pattern similar to miR-144/451 single-KO mice during the remaining period of erythropoiesis. Third, the complete recovery from PHZ-induced acute anemia in miR-144/451 KO mice takes longer than in Nrf2 KO mice. Our findings demonstrate that complicated crosstalk between miR-144/451 and Nrf2 does exist and the crosstalk of these two antioxidant systems is development-stage-dependent. Our findings also demonstrate that miRNA deficiency could result in a more profound defect of erythropoiesis than dysfunctional transcription factors.
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Anemia Hemolítica , Fator 2 Relacionado a NF-E2 , Animais , Camundongos , Fator 2 Relacionado a NF-E2/genética , Espécies Reativas de Oxigênio , Anemia Hemolítica/genética , Anemia Hemolítica/induzido quimicamente , Hemólise , Eritrócitos , Antioxidantes/farmacologia , Camundongos KnockoutRESUMO
BACKGROUND: It is proposed that the development of parenteral nutrition-associated cholestasis (PNAC) was significantly associated with preterm birth, low birth weight, infection, etc.; however, the etiology and pathogenesis of PNAC are not fully understood. Most of the studies examining PNAC-associated risk factors were single-center studies with relatively small sample sizes. OBJECTIVE: To analyze the risk factors associated with PNAC in preterm infants in China. METHODS: This is a retrospective multicenter observational study. Clinical data on the effect of multiple oil-fat emulsions (soybean oil-medium chain triglycerides-olive oil-fish oil, SMOF) in preterm infants were collected from a prospective multicenter randomized controlled study. A secondary analysis was performed in which preterm infants were divided into the PNAC group and the non-PNAC group based on the PNAC status. RESULTS: A total of 465 cases very preterm infants or very low birth weight infants were included in the study in which 81 cases were assigned to the PNAC group and 384 cases were assigned to the non-PNAC group. The PNAC group had a lower mean gestational age, lower mean birth weight, longer duration of invasive and non-invasive mechanical ventilation, a longer duration oxygen support, and longer hospital stay (P < 0.001 for all). The PNAC group had higher respiratory distress syndrome, hemodynamically significant patent ductus arteriosus, necrotizing enterocolitis (NEC) with stage II or higher, surgically treated NEC, late-onset sepsis, metabolic bone disease, and extrauterine growth retardation (EUGR) compared to the non-PNAC group (P < 0.05 for all). In contrast with the non-PNAC group, the PNAC group received a higher maximum dose of amino acids and fat emulsion, more medium/long-chain fatty emulsion, less SMOF, had a longer duration of parenteral nutrition, lower rates of breastfeeding, higher incidence of feeding intolerance (FI), more accumulated days to achieve total enteral nutrition, less accumulated days of total calories up to standard 110 kcal/kg/day and slower velocity of weight growth (P < 0.05 for all). Logistic regression analysis indicated that the maximum dose of amino acids (OR, 5.352; 95% CI, 2.355 to 12.161), EUGR (OR, 2.396; 95% CI, 1.255 to 4.572), FI (OR, 2.581; 95% CI, 1.395 to 4.775), surgically treated NEC (OR, 11.300; 95% CI, 2.127 ~ 60.035), and longer total hospital stay (OR, 1.030; 95% CI, 1.014 to 1.046) were independent risk factors for the development of PNAC. SMOF (OR, 0.358; 95% CI, 0.193 to 0.663) and breastfeeding (OR, 0.297; 95% CI, 0.157 to 0.559) were protective factors for PNAC. CONCLUSIONS: PNAC can be reduced by optimizing the management of enteral and parenteral nutrition and reducing gastrointestinal comorbidities in preterm infants.
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Colestase , Nascimento Prematuro , Feminino , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Emulsões/química , Peso ao Nascer , Estudos Prospectivos , Nascimento Prematuro/etiologia , Colestase/etiologia , Colestase/epidemiologia , Nutrição Parenteral/efeitos adversos , Recém-Nascido de muito Baixo Peso , Aminoácidos , Fatores de RiscoRESUMO
Orthodontic treatment is a common dental treatment. A complete treatment often takes several years and is costly. In order to increase the degree of satisfaction and reduce the gap between the expectations of the patient and the limitations of orthodontics, orthodontists and patients should have sufficient communication. A simulation system can provide a good channel for communication between orthodontists and patients. This paper proposes a 3D dentist-patient communication system for the simulation of orthodontics in advance. The system collects the clinical paradigms of orthodontic cases, which must contain photos from before, during, and after maxillofacial treatment. This research simulates treatment processes by tuning a 3D virtual model of the oral and maxillofacial areas, including the face, mouth, and teeth, to demonstrate the processes of clinical paradigms. These 3D models could be edited and synthesized to generate new 3D models for simulation with the 3DS Max tool. In addition, the proposed system provides a function for the orthodontist to manually operate the 3D virtual model, such as tooth arrangement, morphing of the gums with movement of the teeth, the placement (attachment) of arch-wires and brackets, and changes of facial appearance. The orthodontist can demonstrate the treatment processes, show movements of the teeth, and answer possible questions from the patient about the treatment processes by using the 3D model. To show the effectiveness of the proposed system, a questionnaire about the system was also used to demonstrate its acceptance, usability, and validity. Qualitative interviews with dentists and questionnaires for patients about the system are both performed. The results showed that the proposed system is an effective vehicle for communication between patients and orthodontists.
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BACKGROUND: Hepatocellular carcinoma (HCC) is a highly vascularized tumor with a poor prognosis. Novel vascular-related therapeutic targets and prognostic markers remain urgently needed. AIMS: To investigate the role and mechanism of CLCA1 in hepatocellular carcinoma. METHODS: Immunofluorescence, Co-immunoprecipitation and rescue experiment were used to determine the specific mechanisms of CLCA1. Chemosensitivity assay was used to measure the impact of CLCA1 on Sorafenib. RESULTS: CLCA1 was dramatically downregulated in hepatocellular carcinoma cell lines and tissues. Ectopic expression of CLCA1 induced cell apoptosis and G0/G1 phase arrest while suppressed cell growth, inhibited migration and invasion, reversal of epithelial mesenchymal transition in vitro and reduced xenograft tumor growth in vivo. Mechanistically, CLCA1 could co-localize and interact with TGFB1, thereby suppressing HCC angiogenesis through the TGFB1/SMAD/VEGF signaling cascade in vitro and in vivo. Moreover, CLCA1 also enhanced the sensitivity of HCC cells to the first-line targeted therapy, Sorafenib. CONCLUSION: CLCA1 sensitizes HCC cells to Sorafenib and suppresses hepatocellular carcinoma angiogenesis through downregulating TGFB1 signaling cascade. This newly identified CLCA1 signaling pathway may help guide the anti-angiogenesis therapies for hepatocellular carcinoma. We also support the possibility of CLCA1 being a prognostic biomarker for hepatocellular carcinoma.
