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1.
Anal Chim Acta ; 1189: 339208, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34815044

RESUMO

The electrochemical method for highly sensitive determination of arsenic(III) in real water samples with noble-metal-free nanomaterials is still a difficult but significant task. Here, an electrochemical sensor driven by noble-metal-free layered porous Fe3O4/Co3S4 nanosheets was successfully employed for As(III) analysis, which was prepared via a facile two-step method involves a hydrothermal treatment and a subsequent sulfurization process. As expected, the electrochemical detection of As(III) in 0.1 M HAc-NaAc (pH 6.0) by square wave anodic stripping voltammetry (SWASV) with a considerable sensitivity of 4.359 µA/µg·L-1 was obtained, which is better than the commonly used noble metals modified electrodes. Experimental and characterization results elucidate the enhancement of As(III) electrochemical performance could be attributed to its nano-porous structure, the presence of oxygen vacancies and strong synergetic coupling effects between Fe3O4 and Co3S4 species. Besides, the Fe3O4/Co3S4 modified screen printed carbon electrode (Fe3O4/Co3S4-SPCE) shows remarkable stability and repeatability, valuable anti-interference ability and could be used for detection in real water samples. Consequently, the results confirm that as-prepared porous Fe3O4/Co3S4 nanosheets is identified as a promising modifier to detect As(III) in real sample analysis.

2.
J Hazard Mater ; 422: 126860, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34399224

RESUMO

Extradiol dioxygenases (EDOs) catalyze the meta cleavage of catechol into 2-hydroxymuconaldehyde, a critical step in the degradation of aromatic compounds in the environment. In the present work, a novel thermophilic extradiol dioxygenase from Thermomonospora curvata DSM43183 was cloned, expressed, and characterized by phylogenetic and biochemical analyses. This enzyme exhibited excellent thermo-tolerance, displaying optimal activity at 50 °C, remaining >40% activity at 70 °C. Structural modeling and molecular docking demonstrated that both active center and pocket-construction loops locate at the C-terminal domain. Site-specific mutants D285A, H205V, F301V based on a rational design were obtained to widen the entrance of substrates; resulting in significantly improved catalytic performance for all the 3 mutants. Compared to the wild-type, the mutant D285A showed remarkably improved activities with respect to the 3,4-dihydroxyphenylacetic acid, catechol, and 3-chlorocatechol, by 17.7, 6.9, and 3.7-fold, respectively. The results thus verified the effectiveness of modeling guided design; and confirmed that the C-terminal loop structure indeed plays a decisive role in determining catalytic ring-opening efficiency and substrate specificity of the enzyme. This study provided a novel thermostable dioxygenase with a broad substrate promiscuity for detoxifying environmental pollutants and provided a new thinking for further enzyme engineering of EDOs.

3.
Zhongguo Gu Shang ; 34(10): 911-4, 2021 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-34726017

RESUMO

OBJECTIVE: To investigate the effect of femoral offset (FO) on the postoperative functional results of proximal femoral nail antirotation (PFNA) in femoral trochanteric fractures. METHODS: From May 2017 to June 2019, 112 patients receiving PFNA were analyzed, X-ray and CT examination of both hips were performed before operation, and X-ray examination of both hips of pelvis was performed on the first day after operation. Among them, 71 patients showed bilateral FO difference≤ 5 mm on positive X-ray film (group A), and 41 patients showed bilateral FO difference>5 mm (group B). There was no significant difference between two groups in gender, age, operative side, course of disease, Harris score of preoperative hip joint, preoperativeFO(P>0.05). The Harris score of hip joint at 6 and 12 months was compared between two groups. The correlation between FO difference and Harris score was analyzed. RESULTS: Patients in both groups were followed up for 12 months after surgery, and all patients reached the healing criteria. The difference of Harris score of the hip joint at 6 and 12 months after surgery was statistically significant (P<0.05), and the difference of bilateral FO was negatively correlated with the Harris score of the hip joint at 6 and 12 months after surgery (R=-0.213, P<0.05), (R=-0.335, P<0.05). CONCLUSION: In the treatment of trochanteric fractures with PFNA, the greater the difference of FO between the two sides, the worse the postoperative function of the patients. The appropriate FO(the difference of FO between the two sides ≤5 mm) can improve the postoperative function of the patients.


Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Fraturas do Quadril , Pinos Ortopédicos , Fraturas do Quadril/cirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento
4.
Front Plant Sci ; 12: 771058, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804104

RESUMO

Herbivory is one of the important factors that influence spatial heterogeneity of vegetation in grasslands. In this study, we focused on plateau pika (Ochotona curzoniae) to investigate the effects of the presence of small semi-fossorial herbivores and their disturbance intensity on the spatial heterogeneity of vegetation in alpine meadows across three sites in the Qinghai-Tibetan Plateau. A random stratified paired sampling method was used to collect vegetation data, and plant species richness at both fine and coarse scales were used to estimate the spatial heterogeneity of vegetation. This study showed that the presence of plateau pikas led to higher spatial heterogeneity of vegetation in alpine meadows, which increased linearly as the disturbance intensities of plateau pikas increased. The findings of this study demonstrate that small semi-fossorial herbivores have an important impact on the spatial heterogeneity of vegetation, and present a possible approach for estimating the effect of the presence of a small semi-fossorial herbivore and its disturbance intensity on the spatial heterogeneity of vegetation in grasslands.

5.
Materials (Basel) ; 14(21)2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34772228

RESUMO

In order to obtain the desired mechanical properties of products, an innovative method of loading parameter designs for acquiring the desired grain refinement is proposed, and it has been applied in the compression process of Ni80A superalloy. The deformation mechanism maps derived from processing maps based on the Dynamic Materials Model (DMM) theory were constructed, since the critical indicator values corresponding to dynamic recrystallization (DRX) and dynamic recovery (DRV) mechanisms were determined. The processing-parameter domains with DRX mechanisms were separated from the deformation mechanism map, while such domains were chaotic and difficult to apply in innovative parameter loading path design. The speed-loading path derived from strain rate-loading path in a compression process was pursued. The grain refinement domains are discretized into a finite series of sub-domains with clear processing parameters, and the optimal strain rate of each sub-domain is determined by step-by-step finite element simulation. A 3D response surface of the innovative optimal loading path of strain rate was fitted by interpolating methods. Finally, the isothermal compression experiments for Ni80A superalloy were conducted, and the microstructure observations indicated that the desired grain refinement was achieved. This innovative method of parameter loading path design contributes to the microstructure adjustment of the alloys with DRX mechanism.

6.
Materials (Basel) ; 14(20)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34683521

RESUMO

Durability improvement is always important for steel-concrete structures exposed to chloride salt environment. The present research investigated the influence of a novel nano-precursor inhibiting material (NPI), organic carboxylic acid ammonium salt, on the mechanical and transport properties of concrete. The NPI caused a slight reduction in the strength of concrete at later ages. NPI significantly decreased water absorption and slowed down the speed of water absorption of concrete. In addition, the NPI decreased the charge passed and the chloride migration coefficient, and the results of the natural chloride diffusion showed that the NPI decreased the chloride concentration and the chloride diffusion coefficient. The NPI effectively improved the resistance of chloride penetration into testing concrete. The improvement in the impermeability of concrete was ascribed to the incorporation with the NPI, which resulted in increasing the contact angle of cement pastes. The contact angle went up from 17.8° to 85.8° for 0% and 1.2% NPI, respectively, and cement pastes became less hydrophilic. Some small pore throats were unconnected. Besides, the NPI also optimized the pore size distribution of hardened cement paste.

7.
Front Cell Dev Biol ; 9: 722960, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646824

RESUMO

One contributor to the high mortality of osteosarcoma is its reduced sensitivity to chemotherapy, but the mechanism involved is unclear. Improving the sensitivity of osteosarcoma to chemotherapy is urgently needed to improve patient survival. We found that chemotherapy triggered apoptosis of human osteosarcoma cells in vitro and in vivo; this was accompanied by increased Sestrin2 expression. Importantly, autophagy was also enhanced with increased Sestrin2 expression. Based on this observation, we explored the potential role of Sestrin2 in autophagy of osteosarcoma. We found that Sestrin2 inhibited osteosarcoma cell apoptosis by promoting autophagy via inhibition of endoplasmic reticulum stress, and this process is closely related to the PERK-eIF2α-CHOP pathway. In addition, our study showed that low Sestrin2 expression can effectively reduce autophagy of human osteosarcoma cells after chemotherapy, increase p-mTOR expression, decrease Bcl-2 expression, promote osteosarcoma cell apoptosis, and slow down tumour progression in NU/NU mice. Sestrin2 activates autophagy by inhibiting mTOR via the PERK-eIF2α-CHOP pathway and inhibits apoptosis via Bcl-2. Therefore, our results explain one underlying mechanism of increasing the sensitivity of osteosarcoma to chemotherapy and suggest that Sestrin2 is a promising gene target.

8.
Bioorg Chem ; 117: 105407, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34653945

RESUMO

A series of quinazolinyl-containing benzamide derivatives were designed, synthesized and evaluated for their in vitro histone deacetylase 1 (HDAC1) inhibitory activities. Compounds 11a surpassed the known class I selective HDAC inhibitor MS-275 in both HDAC1 enzymatic inhibitory activity and cellular anti-proliferative activity against a selected set of cancer cell types (Hut78, K562, Hep3B and HCT116 cells) with no observed effects on human normal cells. In particular, compound 11a inhibited HDAC1 over the other tested HDACs isoforms (HDAC2, HDAC6 and HDAC8) with acceptable safety profiles. Moreover, compound 11a displayed favorable oral pharmacokinetic properties and showed significant antitumor activity in the A549 tumor xenograft model in vivo.

9.
Commun Biol ; 4(1): 1223, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34697396

RESUMO

Aging or injury in Drosophila intestine promotes intestinal stem cell (ISC) proliferation and enteroblast (EB) differentiation. However, the manner the local physiology couples with dynamic EB differentiation assessed by traditional lineage tracing method is still vague. Therefore, we developed a 3D-printed platform "FlyVAB" for intravital imaging strategy that enables the visualization of the Drosophila posterior midgut at a single cell level across the ventral abdomen cuticle. Using ISCs in young and healthy midgut and enteroendocrine cells in age-associated hyperplastic midgut as reference coordinates, we traced ISC-EB-enterocyte lineages with Notch signaling reporter for multiple days. Our results reveal a "differentiation-poised" EB status correlated with slow ISC divisions and a "differentiation-activated" EB status correlated with ISC hyperplasia and rapid EB to enterocyte differentiation. Our FlyVAB imaging strategy opens the door to long-time intravital imaging of intestinal epithelium.

10.
Gene ; : 146022, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34673209

RESUMO

BACKGROUND: Genome-wide association studies have demonstrated that genetic variants are closely related to tumorigenesis and progression of cancer. However, the correlation between genetic variants in splicing factor genes and bladder cancer susceptibility remains unclear. METHOD: A case-control study with 580 cases of bladder cancer and 1,101 controls was conducted to explore the association of single-nucleotide polymorphisms (SNPs) in splicing factors with bladder cancer susceptibility by logistic regression models, and multiple testing errors were justified by the false discovery rate (FDR) method. Next, we used the Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) datasets to further analyze the differential expression of candidate genes. RESULTS: We found that rs978416 G>A in RBFOX3 contributed to a reduced risk of bladder cancer [adjusted odds ratio (OR) = 0.72, 95% confidence internal (CI) = 0.62-0.84, P = 3.54 × 10-5], especially in individuals who never smoked (P = 7.83 × 10-5). Stratified analysis showed that the protective effect of rs978416 was more significant in the subgroup of low grade and non-muscle invasive bladder cancer. Furthermore, the RBFOX3 mRNA expression was decreased in bladder tumor tissues. However, the relatively high expression of RBFOX3 was related to a higher bladder cancer stage. CONCLUSIONS: Our findings indicated that SNP rs978416 G>A in RBFOX3 may be related to bladder cancer predisposition in Chinese population and might serve as a novel biomarker for bladder cancer risk.

11.
Front Genet ; 12: 720874, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527023

RESUMO

Background: In epidemiological studies, it has been proven that the occurrence of type 2 diabetes mellitus (T2DM) is related to an increased risk of infectious diseases. However, it is still unclear whether the relationship is casual. Methods: We employed a two-sample Mendelian randomization (MR) to clarify the causal effect of T2DM on high-frequency infectious diseases: sepsis, skin and soft tissue infections (SSTIs), urinary tract infections (UTIs), pneumonia, and genito-urinary infection (GUI) in pregnancy. And then, we analyzed the genome-wide association study (GWAS) meta-analysis of European-descent individuals and conducted T2DM-related single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) that were associated with genome-wide significance (p < 5 × 10-8). MR estimates were obtained using the inverse variance-weighted (IVW), the MR-Egger regression, the simple mode (SM), weighted median, and weighted mode. Results: The UK Biobank (UKB) cohort (n > 500,000) provided data for GWASs on infectious diseases. MR analysis showed little evidence of a causal relationship of T2DM with five mentioned infections' (sepsis, SSTI, UTI, pneumonia, and GUI in pregnancy) susceptibility [odds ratio (OR) = 0.99999, p = 0.916; OR = 0.99986, p = 0.233; OR = 0.99973, p = 0.224; OR = 0.99997, p = 0.686; OR, 1.00002, p = 0.766]. Sensitivity analysis showed similar results, indicating the robustness of causality. There were no heterogeneity and pleiotropic bias. Conclusion: T2DM would not be causally associated with high-frequency infectious diseases (including sepsis, SSTI, UTI, pneumonia, and GUI in pregnancy).

12.
EPMA J ; : 1-31, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34539937

RESUMO

First two decades of the twenty-first century are characterised by epidemics of non-communicable diseases such as many hundreds of millions of patients diagnosed with cardiovascular diseases and the type 2 diabetes mellitus, breast, lung, liver and prostate malignancies, neurological, sleep, mood and eye disorders, amongst others. Consequent socio-economic burden is tremendous. Unprecedented decrease in age of maladaptive individuals has been reported. The absolute majority of expanding non-communicable disorders carry a chronic character, over a couple of years progressing from reversible suboptimal health conditions to irreversible severe pathologies and cascading collateral complications. The time-frame between onset of SHS and clinical manifestation of associated disorders is the operational area for an application of reliable risk assessment tools and predictive diagnostics followed by the cost-effective targeted prevention and treatments tailored to the person. This article demonstrates advanced strategies in bio/medical sciences and healthcare focused on suboptimal health conditions in the frame-work of Predictive, Preventive and Personalised Medicine (3PM/PPPM). Potential benefits in healthcare systems and for society at large include but are not restricted to an improved life-quality of major populations and socio-economical groups, advanced professionalism of healthcare-givers and sustainable healthcare economy. Amongst others, following medical areas are proposed to strongly benefit from PPPM strategies applied to the identification and treatment of suboptimal health conditions:Stress overload associated pathologiesMale and female healthPlanned pregnanciesPeriodontal healthEye disordersInflammatory disorders, wound healing and pain management with associated complicationsMetabolic disorders and suboptimal body weightCardiovascular pathologiesCancersStroke, particularly of unknown aetiology and in young individualsSleep medicineSports medicineImproved individual outcomes under pandemic conditions such as COVID-19.

13.
Chem Commun (Camb) ; 57(74): 9394-9397, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528982

RESUMO

An efficient kinetic resolution of N-aryl ß-amino alcohols has been developed via asymmetric para-aminations of anilines with azodicarboxylates enabled by chiral phosphoric acid catalysis. Broad substrate scope and high kinetic resolution performances were afforded with this method. Control experiments supported the critical roles of the NH and OH group in these reactions.


Assuntos
Amino Álcoois/química , Compostos de Anilina/síntese química , Aminação , Compostos de Anilina/química , Cinética , Estrutura Molecular , Estereoisomerismo
14.
Chin J Traumatol ; 24(6): 320-327, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34429227

RESUMO

Post-traumatic osteomyelitis (PTO) is a worldwide problem in the field of orthopaedic trauma. So far, there is no ideal treatment or consensus-based gold standard for its management. This paper reviews the representative literature focusing on PTO, mainly from the following four aspects: (1) the pathophysiological mechanism of PTO and the interaction mechanism between bacteria and the body, including fracture stress, different components of internal fixation devices, immune response, occurrence and development mechanisms of inflammation in PTO, as well as the occurrence and development mechanisms of PTO in skeletal system; (2) clinical classification, mainly the etiological classification, histological classification, anatomical classification and the newly proposed new classifications (a brief analysis of their scope and limitations); (3) imaging diagnosis, including non-invasive examination and invasive examination (this paper discusses their advantages and disadvantages respectively, and briefly compares the sensitivity and effectiveness of the current examinations); and (4) strategies, including antibiotic administration, surgical choices and other treatment programs. Based on the above-mentioned four aspects, we try to put forward some noteworthy sections, in order to make the existing opinions more specific.


Assuntos
Fraturas Ósseas , Osteomielite , Antibacterianos/uso terapêutico , Fraturas Ósseas/complicações , Fraturas Ósseas/diagnóstico por imagem , Humanos , Osteomielite/diagnóstico por imagem , Osteomielite/terapia
15.
Zhongguo Gu Shang ; 34(8): 755-8, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34423620

RESUMO

OBJECTIVE: To explore the influencing factors of perioperative blood transfusion in the treatment of elderly femoral intertrochanteric fractures with proximal femoral nail antirotation(PFNA). METHODS: The clinical data of 109 elderly patients with intertrochanteric fractures who received PFNA treatment from July 2018 to January 2020 were retrospectively analyzed. Both pelvic hip X-rays and CT plain scans were performed before surgery. All patients were diagnosed by X-ray and CT plain scan of pelvis and hip before operation. Through the statistical analysis of the basic data of patients before and during operation, the risk factors of perioperative blood transfusion were explored. RESULTS: Logistic regression analysis showed that age (P=0.013), fracture type (P<0.01), diabetes history (P=0.031) and preoperative hemoglobin (P<0.01) were independent risk factors for perioperative blood transfusion in the treatment of intertrochanteric fractures in elderly patients with 109 patients. Spearman correlation analysis showed that there was a positive correlation between blood transfusion and age of patients (P= 0.017), fracture type (P<0.01), diabetes history (P=0.023), and negatively correlated with preoperative hemoglobin (P<0.01). However, gender (P=0.297), history of hypertension (P=0.318) and operation time(P=0.325) had no significant relationship with perioperative blood transfusion. CONCLUSION: Age, fracture type, diabetes history, and preoperative hemoglobin are independent risk factors for perioperative blood transfusion in the treatment of elderly intertrochanteric fractures with PFNA. The older the patient, the history of diabetes, the more unstable the fracture, and the lower preoperative hemoglobin, the more likely it is to require a blood transfusion, which may provide a reference for clinical perioperative blood transfusion decisions.


Assuntos
Fixação Intramedular de Fraturas , Fraturas do Quadril , Idoso , Transfusão de Sangue , Pinos Ortopédicos , Fixação Intramedular de Fraturas/efeitos adversos , Fraturas do Quadril/cirurgia , Humanos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
16.
Bone Joint J ; 103-B(8): 1421-1427, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34334045

RESUMO

AIMS: We have previously reported cryoablation-assisted joint-sparing surgery for osteosarcoma with epiphyseal involvement. However, it is not clear whether this is a comparable alternative to conventional joint arthroplasty in terms of oncological and functional outcomes. METHODS: A total of 22 patients who had localized osteosarcoma with epiphyseal involvement around the knee and underwent limb salvage surgery were allocated to joint preservation (JP) group and joint arthroplasty (JA) group. Subjects were followed with radiographs, Musculoskeletal Tumor Society (MSTS) score, and clinical evaluations at one, three, and five years postoperatively. RESULTS: Patients in both groups (ten in JP and 12 in JA) did not differ in local recurrence (p ≥ 0.999) and occurrence of metastases (p ≥ 0.999). Overall survival was similar in both groups (p = 0.858). Patients in the JP group had less range of motion (ROM) of the knee (p < 0.001) and lower MSTS scores (p = 0.010) compared with those of the JA group only at one year postoperatively. There was no difference between groups either at three years for ROM (p = 0.185) and MSTS score (p = 0.678) or at five years for ROM (p = 0.687) and MSTS score (p = 0.536), postoperatively. Patients in the JA group tended to have more complications (p = 0.074). Survival of primary reconstruction in the JP group was better than that of the JA group (p = 0.030). CONCLUSION: Cryoablation-aided joint-sparing surgery offers native joint preservation with comparable functional recovery and more durable reconstruction without jeopardizing oncological outcomes compared with conventional limb salvage surgery. Cite this article: Bone Joint J 2021;103-B(8):1421-1427.


Assuntos
Artroplastia do Joelho , Neoplasias Ósseas/cirurgia , Criocirurgia , Neoplasias Femorais/cirurgia , Articulação do Joelho/cirurgia , Osteossarcoma/cirurgia , Adolescente , Criança , Epífises/cirurgia , Feminino , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento
17.
ASAIO J ; 67(10): 1170-1175, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34374501

RESUMO

To analyze the risk factors for intracranial hemorrhage (ICH) in congenital heart disease (CHD) patients supported with venoarterial extracorporeal membrane oxygenation (VA-ECMO). We performed a retrospective analysis of VA ECMO patients after open heart surgery in Shanghai Children's Medical Center from February 2017 to December 2018, with a total of 50 patients: 14 patients in the ICH group and 36 patients in the control group. Clinical data were analyzed and compared between groups to search for risk factors for ICH. The overall incidence of ICH was 28% (14/50). The in-hospital mortality rate of the ICH group was 57.1% (8/14) vs. 58.3% (21/36) in the control group. The proportion of neonates in the ICH group was 64.3% (9/14) vs. 25% in the control group (9/36) (p = 0.009), and the ICH incidence in extracorporeal cardiopulmonary resuscitation (ECPR) patients was 64.3% (9/14) vs. 13.9% (5/36) (p = 0.000). The percentage of selective cerebral perfusion in the ICH group was 64.3% (9/14) vs. 16.7% (6/36) (p = 0.001) in the control group, and the maximum procalcitonin (PCT) was 43.70 ± 30.48 ng/ml in the ICH group versus 26.92 ± 23.28 ng/ml (p = 0.050) in the control group. Multivariate analysis showed that neonates (odds ratio [OR] = 6.47 [1.09-38.46]), ECPR use (OR = 7.48 [1.26-44.41]), and maximum PCT values (OR = 1.04 [1.001-1.070]) were independent risk factors for ICH. The probability of ICH remains high in children supported with VA-ECMO after cardiac surgery. Neonatal patients, ECPR use, and PCT peak values are independent risk factors for ICH.

18.
J Lipid Res ; 62: 100095, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34214600

RESUMO

The pleiotropic actions of adiponectin in improving cell survival and metabolism have motivated the development of small-molecule therapeutic agents for treating diabetes and lipotoxicity. AdipoRon is a synthetic agonist of the adiponectin receptors, yet is limited by its poor solubility and bioavailability. In this work, we expand on the protective effects of AdipoRon in pancreatic ß-cells and examine how structural modifications could affect the activity, pharmacokinetics, and bioavailability of this small molecule. We describe a series of AdipoRon analogs containing amphiphilic ethylene glycol (PEG) chains. Among these, AdipoRonPEG5 induced pleiotropic effects in mice under insulinopenic and high-fat diet (HFD) conditions. While both AdipoRon and AdipoRonPEG5 substantially attenuate palmitate-induced lipotoxicity in INS-1 cells, only AdipoRonPEG5 treatment is accompanied by a significant reduction in cytotoxic ceramides. In vivo, AdipoRonPEG5 can substantially reduce pancreatic, hepatic, and serum ceramide species, with a concomitant increase in the corresponding sphingoid bases and improves insulin sensitivity of mice under HFD feeding conditions. Furthermore, hyperglycemia in streptozotocin (STZ)-induced insulinopenic adiponectin-null mice is also attenuated upon AdipoRonPEG5 treatment. Our results suggest that AdipoRonPEG5 is more effective in reducing ceramides and dihydroceramides in the liver of HFD-fed mice than AdipoRon, consistent with its potent activity in activating ceramidase in vitro in INS-1 cells. Additionally, these results indicate that the beneficial effects of AdipoRonPEG5 can be partially attributed to improved pharmacokinetics as compared with AdipoRon, thus suggesting that further derivatization may improve affinity and tissue-specific targeting.

19.
J Hepatocell Carcinoma ; 8: 773-782, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277508

RESUMO

Objective: To construct a predictive model of short-term response and overall survival for transcatheter arterial chemoembolization (TACE) treatment in hepatocellular carcinoma (HCC) patients based on non-contrast computed tomography (NC-CT) radiomics and clinical features. Methods: Ninety-four HCC patients who underwent CT scanning 1 week before the first TACE treatment were retrospectively recruited and divided randomly into a training group (n = 47) and a validation group (n = 47). NC-CT radiomics data were extracted using MaZda software, and the compound model was calculated from radiomics and clinical features by logistic regression. The performance of the different models was compared by examining the area under the receiver operating characteristic curve (AUC). The prediction of prognosis was evaluated using survival analysis. Results: Thirty NC-CT radiomic features were extracted and analyzed. The compound model was formed using four NC-CT run-length matrix (RLM) features and general image features, which included the maximum diameter (cm) of the tumor and the number of tumors (n). The AUCs of the model for TACE response were 0.840 and 0.815, whereas the AUCs of the six-and-twelve grade were 0.754 and 0.750 in the training and validation groups, respectively. HCC patients were divided into two groups using the cutoff value of the model: a group in which the TACE-response led to good survival and a group in which TACE-nonresponse caused poor prognosis. Conclusion: Radiomic features from NC-CT predicted TACE-response. The compound model generated by NC-CT radiomics and clinical features is effective and directly predicts TACE-response and overall survival. The model may be used repeatedly and is easy to operate.

20.
Mater Sci Eng C Mater Biol Appl ; 127: 112250, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225889

RESUMO

Customized spinal implants fabricated by additive manufacturing have been increasingly used clinically to restore the physiological functions. However, the mechanisms and methods about the design for the spinal implants are not clear, especially for the reconstruction of multi-segment vertebral. This study aims to develop a novel multi-objective optimization methodology based on various normal spinal activities, to design the artificial vertebral implant (AVI) with lightweight, high-strength and high-stability. The biomechanical performance for two types of AVI was analyzed and compared under different loading conditions by finite element method. These implants were manufactured via selective laser melting technology and evaluated via compressive testing. Results showed the maximum Mises stress of the optimized implant under various load cases were about 41.5% of that of the trussed implant, and below fatigue strength of 3D printed titanium materials. The optimized implant was about 2 times to trussed implant in term of the maximum compression load and compression stiffness to per unit mass, which indicated the optimized implant can meet the safety requirement. Finally, the optimized implant has been used in clinical practice and good short-term clinical outcomes were achieved. Therefore, the novel developed method provides a favorable guarantee for the design of 3D printed multi-segment artificial vertebral implants.


Assuntos
Próteses e Implantes , Titânio , Fenômenos Biomecânicos , Análise de Elementos Finitos , Lasers , Impressão Tridimensional , Estresse Mecânico
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