PCSK9 induces endothelial cell autophagy by regulating the PI3K/ATK pathway in atherosclerotic coronary heart disease.

OBJECTIVE: Atherosclerosis is a chronic inflammatory disease of the arteries, and its pathogenesis is related to endothelial dysfunction. It has been found that the protein convertase subtilin/kexin9 type (PCSK9) plays an important role in AS, but its specific mechanism is still unclear. METHODS: In this study, we first cultured human umbilical vein endothelial cells (HUVECs) with 50 or 100µg/ml oxidized low-density lipoprotein (ox-LDL) for 24 hours to establish a coronary atherosclerosis cell model. RESULTS: The results showed that ox-LDL induced HUVEC injury and autophagy and upregulated PCSK9 protein expression in HUVECs in a concentration-dependent manner. Silencing PCSK9 expression with siRNA inhibited ox-LDL-induced HUVEC endothelial dysfunction, inhibited the release of inflammatory factors, promoted HUVEC proliferation and inhibited apoptosis. In addition, ox-LDL increased the expression of LC3B-I and LC3B-II and decreased the expression of p62. However, these processes are reversed by sh-PCSK9. In addition, sh-PCSK9 can inhibit PI3K, AKT and mTOR phosphorylation and promote autophagy. CONCLUSION: Taken together, our research shows that silencing PCSK9 inhibits the PI3K/ATK/mTOR pathway to activate ox-LDL-induced autophagy in vascular endothelial cells, alleviating endothelial cell injury and inflammation.

Shallow-marine testate amoebae with internal structures from the Lower Devonian of China.

Testate amoebae, a polyphyletic protist group inhabiting a wide variety of extant ecosystems, have evolved as far back as early Neoproterozoic. However, their fossil record is discontinuous and biased toward empty shells. Here, we report an arcellinid testate amoeba species, Cangwuella ampulliformis gen. nov., sp. nov., from a shallow-marine community in the Early Devonian of Guangxi, southwestern China. With the aid of scanning electron microscopy and X-ray micro-tomography, we find that the shell of our testate amoeba contains some acetabuliform structures. Although such configuration does not match exactly with the known internal structures in extant testate amoebae, our fossils highlight the potential of exploring the ecological relationships between fossil testate amoebae and their associated organisms, and increase our knowledge on the diversity of testate amoebae in Early Devonian environments.

The acceleration on decolorization of azo dyes by magnetic lignin-based materials via enhancing the extracellular electron transfer.

Two novel and eco-friendly redox mediators (RMs), magnetic oxidative vanillin (MOV) and magnetic oxidative syringaldehyde (MOS), both derived from lignin, were prepared to improve the decolorization of the methyl orange (MO) dye. The Decolorization Efficiency (DE) of MO in the batch experiments with MOV and MOS were increased by more than 60% and 22%, respectively, when compared to the control experiment without magnetic RMs. Moreover, the two magnetic RMs could maintain stable DE of MO in sequenced batch reactors (SBRs), and negligible leaching of the oxidized lignin monomers was observed under various environmental conditions. Density Function Theory (DFT) calculations were used to propose three potential biodegradation mechanisms for azo dyes, and the key intermediates were confirmed using high-performance liquid chromatography. This study proposed a feasible strategy for functional utilization of lignin resource, as well as a practical method for effectively treating azo dye-containing wastewater.

Getting Over Past Mistakes: Prospective and Retrospective Regret in Older Adults.

OBJECTIVE: A considerable number of older people who hold powerful positions in governments and corporate are actively engaged in making decisions that have a far-reaching impact on the community. Some of them have to make decisions on behalf of others, and sometimes, the outcomes of their decisions for others are unfavorable. We experience retrospective regret when the obtained outcome turns out to be less attractive than the counterfactual one. We also actively make choices to avoid regretful outcomes if we prospectively anticipate the regret. In the current study, we investigated how older adults experience regret and how they make choices to avoid potential regret, in the context of making decisions for themselves and on behalf of others. METHOD: Sixty younger and 60 older participants performed a gambling task in which two types of regret were independently measured: prospective (planning to avoid regret during decision making) and retrospective (feeling of regret following the comparison of alternative outcomes). RESULTS: Our results showed that compared to younger adults, the older adults were less sensitive to regret-inducing outcomes, whereas they demonstrated comparable ability in using prospective regret to guide decisions, regardless of whether they made decisions for themselves or on behalf of others. DISCUSSION: Our findings indicate that although older adults experience blunted regret, their ability to avoid future regret to guide subsequent choices remains unimpaired. Our research has implications for understanding how older adults cope with regret.

Analysis of surgical treatment of severe angular kyphosis with keeping the spinal cord length constant in osteotomy area / 中华外科杂志

Objective: To explore the surgical methods and clinical outcomes of severe angular kyphosis with the length of the spinal cord constant in the osteotomy area. Methods: Clinical data from 20 patients with severe angular kyphosis who underwent surgical treatment from January 2017 to December 2020 in the Department of Spinal Surgery,Hangzhou Xiaoshan District Hospital of Traditional Chinese Medicine were retrospectively analyzed. There were 11 males and 9 females, aged (28.5±8.9) years (range:17 to 46 years).There were 15 cases with congenital angular kyphosis,5 cases with tuberculous angular kyphosis.The angle of kyphosis was (107.1±12.9)° (range:93.2° to 131.4°).Frankel classification:2 cases with grade B,4 cases with grade C,3 cases with grade D.The kyphotic vertex is located at the T9 to T12 segments.Pedicle screws were placed in 3 or 4 adjacent segments at the proximal and distal kyphosis apex of the patients using a surgical navigation system.Piezosurgery combined with a grinding drill was used to complete the osteotomy in the apical vertebral region.Titanium mesh or artificial vertebral body was implanted,and the osteotomy surface was closed using this as the fulcrum to complete osteotomy.Spinal X-ray examination was performed before surgery,immediately after surgery and at the last follow-up,and sagittal and coronal Cobb angle,sagittal and coronary balance parameters,anterior vertebral height,posterior vertebral height,and spinal cord length were measured.Pulmonary function,visual analogue scale (VAS),and Oswestry's disability index (ODI) were collected and estimated before and after treatment.The analysis of variance of repeated measurement data was used for each evaluation index before and after treatment,and the t test was used for pairwise comparison. Results: All patients successfully completed surgery,with artificial vertebral body in 11 cases and double titanium mesh in 9 cases.The follow-up time was (28.2±2.3) months (range:26 to 31 months).Sagittal vertical axis improved from (46.9±13.7)mm(range:21.7 to 75.7 mm) before surgery to (10.7±5.5)mm (range:3.6 to 28.1 mm) after surgery,and (11.0±5.7)mm(range:3.6 to 29.3 mm) at the last follow-up,the differences were statistically significant compared to before surgery (all P<0.01).The mean kyphotic Cobb angle was corrected from (107.1±12.9) ° (range:93.2 ° to 131.4°) before surgery to (30.6±8.5) ° (range:20.0 ° to 47.8 °) after surgery (all P<0.01),and (32.1±8.7) ° (range:18.2 ° to 50.8°) at the last follow-up,the differences were statistically significant compared to before surgery(all P<0.01).The anterior vertebral height improved from (14.2±2.9)mm(range:11.04 to 23.6 mm) before surgery to (45.3±7.5)mm(range:29.4 to 56.5 mm) after surgery,and (44.3±6.8)mm(range:29.6 to 56.0 mm) at the last follow-up,the differences were statistically significant compared to before surgery (all P<0.01).The posterior vertebral height was improved from (51.8±5.3)mm (range:43.1 to 61.4 mm)before surgery to (57.6±4.7)mm (range:45.7 to 64.1 mm)after surgery,and (56.3±5.0) mm (range:49.7 to 68.5 mm) at the last follow-up,the differences were statistically significant compared to before surgery (all P<0.01).The spinal cord length of the osteotomy segment was (73.1±12.0)mm (range:56.8 to 98.4 mm) before surgery and (74.8±12.8)mm (range:53.5 to 100.2 mm) after surgery and (75.2±13.7)mm (range:53.9 to 102.4 mm) at the last follow-up,the difference was not statistically significant among them(F=0.144,P=0.866).The ODI and VAS scores improved significantly after surgery and at the last follow-up,and the differences were statistically significant (all P<0.01). Conclusion: The posterior vertebral column resection technique combined with titanium mesh or an artificial vertebral body implant for the treatment of severe angular kyphosis can significantly improve the kyphosis,neurological function,and life quality of patients without affecting the length of the spinal cord.

Exosome-mediated aptamer S58 reduces fibrosis in a rat glaucoma filtration surgery model.

AIM: To confirm whether exosome-mediated delivery of aptamer S58 (Exo-S58) has a better antifibrotic effect than naked S58 in human conjunctival fibroblasts (HConFs) and a rat glaucoma filtration surgery (GFS) model. METHODS: To enhance the effective reaction time of aptamer S58 in vivo, we loaded aptamer S58 into exosomes derived from HEK293T cells by PEI transfection to determine the effect of Exo-S58 in HConFs and a rat GFS model. RESULTS: Exo-S58 can significantly reduce cell proliferation, migration and fibrosis in TGF-ß2-induced HConFs. In an in vivo experiment, Exo-S58 treatment prolonged filtering bleb retention and reduced fibrosis compared with naked S58 treatment in GFS rats. CONCLUSION: The exosomes are safe and valid carriers to deliver aptamers. Furthermore, Exo-S58 exhibited superior antifibrotic effect than naked S58 both in HConFs cells and rat GFS models.

New insights into the South China Lower Devonian flora based on fossils from Hezhang, Guizhou Province.

The Early Devonian flora of South China is composed of many endemic members and has been studied mainly based on Yunnan materials. We in this study report a new Lower Devonian plant locality, recognize four sub-regions of the Early Devonian flora from South China and furthermore demonstrate these plants' distribution pattern and probable dispersal route. The new finds of plant fossils are from the Lower Devonian of Hezhang County, Guizhou Province, and include Zosterophyllopsida Demersatheca and Euphyllophytopsida Pauthecophyton. Demersatheca contigua, consisting of cylindrical strobili with four longitudinal rows of sporangia decussately arranged, shows great similarities to the plant from Yunnan and Guangxi localities. Pauthecophyton hezhangensis sp. nov. has distinct fertile units with grouped sporangia and each unit with two or three fusiform sporangia. The new locality belongs to the Guizhou sub-region and shares some taxa with the eastern Yunnan and Cathaysia sub-regional floras within South China, in which the shared plant members are distributed around the epicontinental sea. We suggest that the Guizhou sub-region might act as a bridge during plant dispersal from eastern Yunnan to Cathaysia Oldland in the Early Devonian. This article is part of the theme issue 'The impact of Chinese palaeontology on evolutionary research'.

[Transformation Characteristics of Dissolved Organic Matter During UV/Chlorine Treatment of Municipal Secondary Effluent].

As an emerging advanced oxidation technology, UV/chlorine treatment is capable of effectively oxidizing various organic pollutants. Till now, the transformation of dissolved effluent organic matter (dEfOM) in real wastewater during UV/chlorine treatment remains unclear. In this study, ultraviolet and fluorescence spectroscopy were combined with Fourier transform ion cyclotron resonance mass spectrometry to probe the transformation of dEfOM in two municipal secondary effluents during UV/chlorine treatment. Meanwhile, the newly formed chlorinated byproducts (Cl-BPs) are particularly concerned. Generally, aromatic compounds and fluorescent components could be readily removed after UV/chlorine treatment, and most of the dEfOM underwent transformation rather than mineralization. Protein-like components, which accounted for the largest proportion of fluorescent components, were subject to a preferential reaction. UV/chlorine treatment could result in the degradation of CHOS compounds and the formation of CHO compounds. During this process, unsaturated and reduced compounds of large molecules were preferentially removed, whereas saturated and oxidized compounds with low molecular weight were produced. Moreover, the concentrations of trihalomethanes and haloacetic acids increased substantially after UV/chlorine treatment. In total, 255 and 133 Cl-BPs were detected in the respective effluents after UV/chlorine treatment. In addition, 12 and 43 possible precursor-Cl-BPs pairs were identified, respectively, based on electrophilic substitution and addition reactions by means of mass difference analysis. This study is expected to provide fundamental information for practical application of the UV/chlorine treatment process.

The influence of tolfenpyrad on fitness, development, and reproduction in parents and offspring of Coccinella septempunctata.

Coccinella septempunctata (ladybird) is one of the foremost natural predators that feed on aphids. Thus, C. septempunctata serves as an effective biological control agent in integrated pest management (IPM) programs. To supplement the activity of biological control agents, IPM programs often incorporate chemical pesticides to bolster crop protection. To evaluate the effects of a potent insecticide, tolfenpyrad, on C. septempunctata, we tested the sublethal effects of tolfenpyrad on all developmental stages of the life cycle of C. septempunctata and its effects on the next generation. For sublethal testing of the parent generation, the LR50 of tolfenpyrad for C. septempunctata was determined to range from 1.04 to 8.43 g a.i. /hm2 within a set exposure period, while the hazard quotient (HQ) values were above our threshold value of 2 during the entire observation period. These data indicated a potential toxicity risk from tolfenpyrad exposure. The no observed effect application rates (NOERs) of tolfenpyrad on parents (F0) were determined for survival (0.485 g a.i. /hm2), developmental time of pupation (0.242 g a.i. /hm2), and fecundity (0.485 g a.i. /hm2). Application of sublethal doses to unexposed progeny (F1) of exposed parents, prolonged the L1 (1st instar of larvae) and L2 (2nd instar of larvae) stage, while the total longevity, intrinsic rate of increase (r), finite rate of increase (γ), net reproductive rate (R0), and mean generation time (T) were significantly reduced. These results demonstrated the negative influence of sublethal concentrations of tolfenpyrad on C. septempunctata and its persistent effects on subsequent generations.

Inhibition of the INa/K and the activation of peak INa contribute to the arrhythmogenic effects of aconitine and mesaconitine in guinea pigs.

Aconitine (ACO), a main active ingredient of Aconitum, is well-known for its cardiotoxicity. However, the mechanisms of toxic action of ACO remain unclear. In the current study, we investigated the cardiac effects of ACO and mesaconitine (MACO), a structurally related analog of ACO identified in Aconitum with undocumented cardiotoxicity in guinea pigs. We showed that intravenous administration of ACO or MACO (25 µg/kg) to guinea pigs caused various types of arrhythmias in electrocardiogram (ECG) recording, including ventricular premature beats (VPB), atrioventricular blockade (AVB), ventricular tachycardia (VT), and ventricular fibrillation (VF). MACO displayed more potent arrhythmogenic effect than ACO. We conducted whole-cell patch-clamp recording in isolated guinea pig ventricular myocytes, and observed that treatment with ACO (0.3, 3 µM) or MACO (0.1, 0.3 µM) depolarized the resting membrane potential (RMP) and reduced the action potential amplitude (APA) and durations (APDs) in a concentration-dependent manner. The ACO- and MACO-induced AP remodeling was largely abolished by an INa blocker tetrodotoxin (2 µM) and partly abolished by a specific Na+/K+ pump (NKP) blocker ouabain (0.1 µM). Furthermore, we observed that treatment with ACO or MACO attenuated NKP current (INa/K) and increased peak INa by accelerating the sodium channel activation with the EC50 of 8.36 ± 1.89 and 1.33 ± 0.16 µM, respectively. Incubation of ventricular myocytes with ACO or MACO concentration-dependently increased intracellular Na+ and Ca2+ concentrations. In conclusion, the current study demonstrates strong arrhythmogenic effects of ACO and MACO resulted from increasing the peak INa via accelerating sodium channel activation and inhibiting the INa/K. These results may help to improve our understanding of cardiotoxic mechanisms of ACO and MACO, and identify potential novel therapeutic targets for Aconitum poisoning.

Sparse Extended Redundancy Analysis: Variable Selection via the Exclusive LASSO.

Extended Redundancy Analysis is a statistical tool for exploring the directional relationships of multiple sets of exogenous variables on a set of endogenous variables. This approach posits that the endogenous and exogenous variables are related via latent components, each of which is extracted from a set of exogenous variables, that account for the maximum variation of the endogenous variables. However, it is often difficult to distinguish between the true variables that form the latent components and the false variables that do not, especially when the association between the true variables and the exogenous set is weak. To overcome this limitation, we propose a Sparse Extended Redundancy Analysis via the Exclusive LASSO that performs variable selection while maintaining model specification. We validate the performance of the proposed approach in a simulation study. Finally, the empirical utility of this approach is demonstrated through two examples-one on a study of youth academic achievement and the other on a text analysis of newspaper data.

Biomechanical effects of different bone cement diffusion patterns after vertebroplasty:finite element analysis / 中国骨伤

OBJECTIVE@#To investigate the biomechanical effects of different bone cement diffusion patterns in the treatment of osteoporotic vertebral compression fractures.@*METHODS@#One volunteer with L1 osteoporotic vertebral compression fracture was selected, male, aged 68 years old, heighed 172 cm, weighted 60 kg, and healthy before. CT scans were used from T@*RESULTS@#After the establishing the finite element model of osteoporotic vertebral compression fracture in the thoracolumbar segment, it was found that the deformation of three different bone cement distribution models above was not significantly different. In L@*CONCLUSION@#The bone cement contact with both upper and lower endplates can effectively absorb and transfer the stress level brought by the load, reduce the stress level of cancellous bone, and reduce the possibility of refracture of the operative vertebral body.

Trust in Robots: Challenges and Opportunities.

PURPOSE OF REVIEW: To assess the state-of-the-art in research on trust in robots and to examine if recent methodological advances can aid in the development of trustworthy robots. RECENT FINDINGS: While traditional work in trustworthy robotics has focused on studying the antecedents and consequences of trust in robots, recent work has gravitated towards the development of strategies for robots to actively gain, calibrate, and maintain the human user's trust. Among these works, there is emphasis on endowing robotic agents with reasoning capabilities (e.g., via probabilistic modeling). SUMMARY: The state-of-the-art in trust research provides roboticists with a large trove of tools to develop trustworthy robots. However, challenges remain when it comes to trust in real-world human-robot interaction (HRI) settings: there exist outstanding issues in trust measurement, guarantees on robot behavior (e.g., with respect to user privacy), and handling rich multidimensional data. We examine how recent advances in psychometrics, trustworthy systems, robot-ethics, and deep learning can provide resolution to each of these issues. In conclusion, we are of the opinion that these methodological advances could pave the way for the creation of truly autonomous, trustworthy social robots.

Construction and application value of CT-based radiomics model for predicting recurrence of early-stage hepatocellular carcinoma after resection / 中华消化外科杂志

Objective:To construct a computed tomography (CT)-based radiomics model for predicting tumor recurrence of early-stage hepatocellular carcinoma (HCC) after resection, and explore its application value.Methods:The retrospective cohort study was conducted. The clinicopathological data of 243 patients with early-stage HCC who underwent hepatectomy in 2 medical centers between January 2009 and December 2016 were collected, including 165 in the First Affiliated Hospital of Nanjing Medical University and 78 in the Wuxi People′s Hospital. There were 182 males and 61 females, aged from 30 to 86 years, with a median age of 57 years. According to the random numbers showed in the computer, 243 patients were randomly assigned into training dataset consisting of 162 patients and test dataset consisting of 81 patients, with a ratio of 2∶1. Using radiomics technique, a total of 3 384 radiomics features were extracted from the tumor and its periphery at arterial-phase and portal-phase images of CT scan. In the training dataset, a radiomics signature was constructed and predicted its performance after dimension reduction of stable features by using aggregated feature selection algorithms [feature ranking via maximal relevance and minimal redundancy (MRMR) combined with random survival forest (RSF) + LASSO-COX regression analysis]. Risk factors for tumor recurrence were selected using the univariate COX regression analysis, and two radiomics models including radiomics 1 (preoperative) and radiomics 2 (postoperative) were constructed and predicted their performance using backward stepwise multivariate COX regression analysis. The two models were validated in the training and test dataset. Observation indicators: (1) follow-up; (2) construction of HCC recurrence-related radiomics signature for early-stage HCC after resection; (3) prediction performance of HCC recurrence-related radiomics signature for early-stage HCC after resection; (4) construction of HCC recurrence-related radiomics prediction model for early-stage HCC after resection; (5) validation of HCC recurrence-related radiomics prediction model for early-stage HCC after resection; (6) comparison of the prediction performance of radiomics model with that of other clinical statistical models and current HCC staging systems; (7) stratification analysis of postoperative recurrence risk based on radiomics models for early-stage HCC after resection. Patients were followed up using outpatient examination or telephone interview once every 3 months within the first 2 years and once every 6 months after 2 years. The follow-up included collection of medical history, laboratory examination, and abdominal ultrasound examination. Contrast-enhanced CT or magnetic resonance imaging (MRI) examination was performed once every 6 months, and they were performed in advance on patients who had suspected recurrence based on laboratory examination or abdominal ultrasound for further diagnosis. Follow-up was up to January 2019. The endpoint was time to recurrence, which was from the date of surgery to the date of first detected disease recurrence or metastasis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were described as M (range), and comparison between groups was analyzed by the Mann-Whitney U test. Count data were described as absolute numbesr or percentages, and comparison between groups was analyzed using the chi-square test. The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method, and the survival analysis was performed using the Log-rank test. Serum alpha-fetoprotein level was analyzed after the natural logarithm transformation. X-tile software was used to select the optimal cut-point for continuous markers. Results:(1) Follow-up: all the 243 HCC patients received follow-up. Patients in the training dataset were followed up for 4.2-109.2 months, with a median follow-up time of 51.6 months. Patients in the test dataset were followed up for 12.7-107.6 months, with a median follow-up time of 73.2 months. The 2-, 5-year disease-free survival rates were 77.8% and 53.1% of the training dataset respectively, versus 86.4% and 61.7% of the test dataset. There was no significant difference in terms of disease-free survival between two datasets ( χ2=1.773, P>0.05). (2) Construction of HCC recurrence-related radiomics signature for early-stage HCC after resection: of the 3 384 radiomics features, 2 426 radiomics features with high stability were selected for analysis. There were 37 radiomics features identified after combining the top 20 radiomics features ranked by MRMR and RSF algorithms. LASSO-COX regression algorithm further reduced their dimensionality to retain 7 radiomics features and construct a radiomics signature. The indicators including region, scanning phase, and weighting coefficient of above mentioned seven features were Feature 1 (peritumoral, arterial phase, 0.041), Feature 2 (peritumoral, arterial phase, -0.103), Feature 3 (peritumoral, arterial phase, -0.259), Feature 4 (intratumoral, arterial phase, 0.211), Feature 5 (peritumoral, portal venous phase, -0.170), Feature 6 (intratumoral, portal venous phase, 0.130), and Feature 7 (intratumoral, portal venous phase, 0.090), respectively. Radiomics signature score=0.041×Feature 1-0.103×Feature 2-0.259×Feature 3+ 0.211×Feature 4-0.170×Feature 5+ 0.130×Feature 6+ 0.090×Feature 7. (3) Prediction performance of HCC recurrence-related radiomics signature for early-stage HCC after resection: the radiomics signature showed favorable prediction performance in both training and test datasets, with respective C-index of 0.648 [95% confidence interval ( CI): 0.583-0.713] and 0.669 (95% CI: 0.587-0.750). (4) Construction of HCC recurrence-related radiomics prediction model for early-stage HCC after resection: results of univariate analysis showed that ln(serum alpha-fetoprotein), liver cirrhosis, tumor margin status, arterial peritumoral enhancement, intratumoral necrosis, radiomics signature, satellite nodules, and microvascular invasion were related factors for tumor recurrence after resection of early-stage HCC ( hazard ratio=1.202, 1.776, 1.889, 2.957, 1.713, 4.237, 4.364, 4.258, 95% CI: 1.083-1.333, 1.068-2.953, 1.181-3.024, 1.462-5.981, 1.076-2.728, 2.593-6.923, 2.468-7.717, 2.427-7.468, P<0.05 ). Results of multivariate analysis showed that the radiomics model 1 (preoperative) consisted of ln(serum alpha-fetoprotein), tumor margin status, and radiomics signature ( hazard ratio=1.145, 1.838, 3.525, 95% CI: 1.029-1.273, 1.143-2.955, 2.172-5.720, P<0.05); the radiomics model 2 (postoperative) consisted of ln(serum alpha-fetoprotein), radiomics signature, microvascular invasion, and satellite nodules ( hazard ratio=1.123, 2.386, 3.456, 3.481, 95% CI: 1.005-1.254, 1.501-3.795, 1.863-6.410, 1.891-6.408, P<0.05). Risk prediction formulas: radiomics model 1 = 0.135×ln(serum alpha-fetoprotein)+ 0.608×tumor margin status (0: smooth; 1: non-smooth)+ 1.260×radiomics signature; radiomics model 2 = 0.116×ln(serum alpha-fetoprotein)+ 0.870×radiomics signature + 1.240×microvascular invasion (0: absent; 1: present)+ 1.247×satellite nodules (0: absent; 1: present). (5) Validation of HCC recurrence-related radiomics prediction model for early-stage HCC after resection: in both training and test datasets, radiomics model 1 provided good prediction performance, with respective C-index of 0.716 (95% CI: 0.662-0.770) and 0.724 (95% CI: 0.642-0.806), while radiomics model 2 provided better prediction performance, with respective C-index of 0.765 (95% CI: 0.712-0.818) and 0.741 (95% CI: 0.662-0.820). Calibration curves demonstrated good agreement between model-predicted probabilities and observed outcomes. (6) Comparison of the prediction performance of radiomics model with that of other clinical statistical models and current HCC staging systems: in the training dataset, the prediction performance of radiomics model 1 for tumor recurrence after resection of early-stage HCC was significantly different from that of ERASL model (preoperative), Barcelona clinic liver cancer (BCLC) staging, Hong Kong liver cancer (HKLC) staging, and cancer of the liver Italian program (CLIP) classification (C-index=0.562, 0.484, 0.520, 0.622, 95% CI: 0.490-0.634, 0.311-0.658, 0.301-0.740, 0.509-0.736, P<0.05); the prediction performance of radiomics model 2 for tumor recurrence after resection of early-stage HCC was significantly different from that of ERASL model (postoperative), Korean model, and the eighth edition TNM staging (C-index=0.601, 0.523, 0.513, 95% CI: 0.524-0.677, 0.449-0.596, 0.273-0.753, P<0.05). In the test dataset, the prediction performance of radiomics model 1 for tumor recurrence after resection of early-stage HCC was significantly different from that of ERASL model (preoperative), BCLC staging, HKLC staging, CLIP classification (C-index=0.540, 0.473, 0.504, 0.545, 95% CI: 0.442-0.638, 0.252-0.693, 0.252-0.757, 0.361-0.730, P<0.05); the prediction performance of radiomics model 2 for tumor recurrence after resection of early-stage HCC was significantly different from that of ERASL model (postoperative), Korean model, and the eighth edition TNM staging (C-index=0.562, 0.513, 0.521, 95% CI: 0.451-0.672, 0.399-0.626, 0.251-0.791, P<0.05). (7) Stratification analysis of postoperative recurrence risk based on radiomics models for tumor recurrence after resection of early-stage HCC: according to the analysis of X-tile, the score of radiomics model 1 < 1.4 (corresponding to total points < 62.0 in nomogram) was classified into low-risk group while the score of radiomics model 1 ≥ 1.4 (corresponding to total points ≥ 62.0 in nomogram) was classified into high-risk group. The score of radiomics model 2 < 1.7 (corresponding to total points < 88.0 in nomogram) was classified into low-risk group while the score of radiomics model 2 ≥ 1.7 (corresponding to total points ≥ 88.0 in nomogram) was classified into high-risk group. In the training dataset, the 2- and 5-year recurrence rates were 14.1%, 35.3% for low-risk patients and 63.0%, 100.0% for high-risk patients, which were predicted by radiomics model 1. There were significant differences between the two groups ( χ2= 70.381, P<0.05). The 2- and 5-year recurrence rates were 12.9%, 38.2% for low-risk patients and 81.8%, 100.0% for high-risk patients, which were predicted by radiomics model 2. There were significant differences between the two groups ( χ2= 98.613, P<0.05). In the test dataset, the 2- and 5-year recurrence rates were 5.6%, 29.3% for low-risk patients and 70.0%, 100.0% for high-risk patients, which were predicted by radiomics model 1. There were significant differences between the two groups ( χ2= 64.453, P<0.05). Ther 2- and 5-year recurrence rates were 5.7%, 28.1% for low-risk patients and 63.6%, 100.0% for high-risk patients, which were predicted by radiomics model 2. There were significant differences between the two groups ( χ2= 58.032, P<0.05). Conclusions:The 7-feature-based radiomics signature is built by selection of CT radiomics features in this study, and then HCC recurrence-related radiomics prediction model for early-stage HCC after resection is constructed. The proposed radiomics models can complement the existing clinical-radiological-pathological prognostic sources, accurately and individually predict tumor recurrence risk preoperatively and postoperatively, which facilitate clinical decision-support for patients with early-stage HCC.

Protective Effects of Scutellarin on Testicular Vessels of Rat with Type II Diabetes Mellitus-Induced Testicular Damages / 中山大学学报(医学科学版)

@#【Objective】To evaluate the protective effect of Scutellarin（SCU）on type II diabetes-induced disorder of testes and show the mechanism of Scutellarin′s action.【Method】We divided 24 Wistar rats equally into 3 groups：control group，diabetes group and diabetes + SCU group. We used streptozotocin and high-fat diet to establish type Ⅱ diabetic rat model on Wistar rat. Haematoxylin and eosin staining were used to evaluate the testicular morphologic changes. Immunohistochemical staining was used to measure the expression level of vascular endothelial growth factor（VEGF）in testes. Oxidative stress in testes and epididymis was tested by fluorescence spectrophotometer and enzyme linked immunosorbent assay（ELISA）. The blood flow rate in testicular vessels was measured by Doppler. 【Results】 Our results showed that hyperglycemia induced morphologic impairments in testes of rats, higher concentrations of Malondialdehyde（MDA） and ROS in testes and epididymis, lower testicular blood flow rate, while administration of Scutellarin could significantly inhibit these damages（DCF：12.93 vs. 7.63 mg/min ；MDA：2.37 vs. 1.48 mg/min ；testicular blood flow rate：110.0 vs. 210.2 mm/s；P < 0.05）.【Conclusion】Our data suggest that SCU has the potential to reverse male reproductive disorder in diabetes by reducing the concentrations of ROS and improving. microcirculatory disturbances.

Dynamic molecular changes during the first week of human life follow a robust developmental trajectory.

Systems biology can unravel complex biology but has not been extensively applied to human newborns, a group highly vulnerable to a wide range of diseases. We optimized methods to extract transcriptomic, proteomic, metabolomic, cytokine/chemokine, and single cell immune phenotyping data from <1 ml of blood, a volume readily obtained from newborns. Indexing to baseline and applying innovative integrative computational methods reveals dramatic changes along a remarkably stable developmental trajectory over the first week of life. This is most evident in changes of interferon and complement pathways, as well as neutrophil-associated signaling. Validated across two independent cohorts of newborns from West Africa and Australasia, a robust and common trajectory emerges, suggesting a purposeful rather than random developmental path. Systems biology and innovative data integration can provide fresh insights into the molecular ontogeny of the first week of life, a dynamic developmental phase that is key for health and disease.

Effect of Long-time Slow-frozen Storage on Epigenetic Changes of Histone in Cleavage-stage Embryos / 中山大学学报(医学科学版)

@#【Objective】To investigate the impact of long- term storage time on epigenetic modification of histone in human cleavage stage embryos.【Methods】According to the length of storage time，donated embryos after slow-freezing were divided into 3 groups ：6-year group ，9-year group ，and 12-year group ，while the control group consisted of donated fresh embryos. Immunocytochemistry was performed to compare the expression levels of HDAC1， H3K9ac， H3K4me3 ，and H3K9me3 among 4 groups. Transcription levels of HDAC1 ，SUV39H1 ，SETDB1 ，and KDM5A were analyzed through Single-Cell qRT-PCR.【Results】The relative abundances of HDAC1 and SUV39H1 mRNA showed no significant differences among 4 groups（P > 0.05）. SETDB1 exhibited a climbing pattern as storage time increased，but no significant difference was observed（P > 0.05）. There were no differences in H3K9 trimethylation and H3K9 methylation among 4 groups. However ，the expression level of KDM5A increased with the increasing storage time（P < 0.05）.【Conclusions】 Storage time did not affect the expression of deacetylase HDAC1，methylase SUV39H1 and SETDB1. H3K9ac/me3 and H3K4me3 also exhibited no significant difference as the storage time increases. However ，the increasing storage length might induce the elevating expression of demethylase KDM5A，which may be associated with inhibition of embryonic transcription.

Established a Preimplantation Genetic Testing-derived and Xeno-free Human Embryonic Stem Cell Line / 中山大学学报(医学科学版)

@#【Objective】 A human embryonic stem cell line derived from Preimplantation genetic testing （PGT） embryos was established in a xeno- free stem cell culture system to provide disease models for medical research. 【Methods】The xeno-free culture system using xeno-free human foreskin fibroblast feeder layers（XF-HFF）mixed with commercially available chemically-defined medium（CDM）was assessed. In the culture system，a new hESC cell line was established using discarded embryos derived from PGT in patients with chromosomal balance translocation.【Results】The new availabled stem cell line was successfully cultured in the xeno-free culture system for a long time（> 45 passages）. The karyotype analysis revealed that the new line kept the same karyotype over 45 passages. Moreover，the expression of pluripotent markers was detected by fluorescent immunostaining including SSEA- 3，SSEA- 4，SSEA- 1，TRA- 1- 60， and TRA-1-81. RT-PCR analysis showed that the stem cell markers were present in hESC grown on XF-HFF-CDM. In addition，the teratoma formation analysis demonstrated that the cells cultured in XF-HFF/CDM maintained their pluripotency in vivo.【Conclusions】Our study may provide the possibility to establish embryonic stem cells with certain pathogenic genes，which could be applied for clinical research and treatment.

Choosing for you: Diminished self-other discrepancies in financial decisions under risk in the elderly.

Many older adults hold powerful positions in governments and corporate boards throughout the world. Accordingly, older adults often have to make important financial decisions on behalf of others under risk. Although it is common to observe younger adults taking more risks when making financial decisions for others, it is unclear if older adults exhibit the same self-other discrepancies. Here, we conducted 2 studies (88 and 124 participants, respectively) to examine self-other discrepancies in financial decision making under risk in older adults. We focused on 3 aspects of financial decision making: loss aversion (a tendency to weight potential losses more strongly than potential gains), risk-aversion asymmetry (a tendency to be risk-averse for potential gains and risk-seeking for potential losses), and risk preferences separately in gain and loss domains. Using computational modeling and behavioral economics tasks, we found weaker self-other discrepancies in older adults (compared with younger adults) across all 3 aspects. We also replicated the age differences in self-other discrepancies in loss aversion across 2 largely nonoverlapping cohorts. Thus, it appears that when making financial decisions on behalf of others, older adults, relative to younger adults, have a stronger disposition to regard others' financial outcomes as important as their own. (PsycINFO Database Record

Reduction of Tat-interacting Protein 30 Expression Could be a Prognostic Marker in Bladder Urothelial Cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tat-interacting protein 30 (TIP30) has been reported to be a tumor suppressor, with reduced or absent expression in various tumors. However, its role in bladder urothelial cancer (BUC) has not been investigated. Therefore, herein, we investigated the expression of TIP30 protein in BUC and normal bladder mucosa and the clinical significance of TIP30 expression in the prognosis of BUC.</p><p><b>METHODS</b>We reviewed data from 79 cases of BUC and 15 adjacent tissue samples from 79 patients treated at our institution between 2004 and 2007. TIP30 expression was examined by immunohistochemistry. The relationship between TIP30 expression and tumor stage, histological grade, and survival was analyzed. Differences between groups were evaluated using the t-test or matched-pairs test, and differences in the survival rates were analyzed with the log-rank test.</p><p><b>RESULTS</b>TIP30 protein expression was significantly reduced in BUC tissue (t = -6.91, P < 0.05) compared with normal tissue samples, and in invasive bladder cancer (t = 10.89, P < 0.05) compared with superficial bladder cancer. TIP30 protein expression differed significantly among different differentiated groups classified either according to the World Health Organization (2004, F = 17.48, P < 0.01) or World Health Organization (1973, F = 10.68, P < 0.01). TIP30 protein expression was significantly reduced in high-grade papillary urothelial carcinoma compared with papillary urothelial neoplasm of low malignant potential (P < 0.05) and low-grade papillary urothelial carcinoma (P < 0.05). Meanwhile, TIP30 protein expression was significantly reduced in Grade III BUC, compared with Grade I (P < 0.05) and Grade II (P < 0.05). Patients with low TIP30 expression showed a higher incidence of disease progression than those with high TIP30 expression (t = 2.63, P < 0.05). Kaplan-Meier survival analysis showed a strong positive relationship between TIP30 expression and overall survival (OS) (χ2 = 17.29, P < 0.05).</p><p><b>CONCLUSIONS</b>TIP30 expression was associated with clinical tumor stage in BUC, suggesting that it might play an important role in disease progression. Furthermore, TIP30 might predict postoperative OS. Thus, its evaluation might be useful for predicting prognosis.</p>