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Abstract Improvement in outcomes of children with acute myeloid leukemia (AML) is attributed to several refinements in clinical management. We evaluated treatment outcomes of Taiwanese pediatric AML patients in the past 20 years. Overall, 860 de novo AML patients aged 0–18 years and registered in the Childhood Cancer Foundation of R.O.C during January 1996–December 2019 were included. Survival analysis was performed to identify factors that improved treatment outcomes. Regardless of treatment modalities used, patients during 2008–2019 had better 5-year event-free survival (EFS) and overall survival (OS) rates than patients during 1996–2007. For patients received the TPOG-AML-97A treatment, only 5-year OS rates were significantly different between patients diagnosed before and after 2008. Patients with RUNX1–RUNX1T1 had similar relapse-free survival rates, but 5-year OS rates were better during 2008–2019. However, the survival of patients who received hematopoietic stem-cell transplantations (HSCT) did not differ significantly before and after 2008. For patients without relapse, the 5-year OS improved during 2008–2019. Non-relapse mortality decreased annually, and cumulative relapse rates were similar. In conclusion, 5-year EFS and OS rates improved during 2008–2019, though intensities of chemotherapy treatments were similar before and after 2008. Non-relapse mortality decreased gradually. Further treatment strategies including more intensive chemotherapy, novel agents’ use, identification of high-risk patients using genotyping and minimal residual disease, early intervention of HSCT, and antibiotic prophylaxis can be considered for future clinical protocol designs in Taiwan.

As train speeds increase, the aerodynamic effects generated during the passage of high-speed trains in tunnels become more pronounced. This article investigates the influence of line spacing on the aerodynamic forces during the passage of high-speed trains in tunnels at different speeds. The research methodology is based on the three-dimensional transient compressible Reynolds-averaged Navier-Stokes (RANS) equations and the k-ω Shear Stress Transport (SST) turbulence model, using overset grid technology to simulate the train passing process in the tunnel. The results show that the aerodynamic drag, lateral force, and lift experienced by the train increase as the line spacing decreases and as the speed increases. line spacing has the greatest impact on aerodynamic lift, followed by lateral force, with drag having the smallest impact. Compared to line spacing, speed has a much larger effect on aerodynamic forces. The aerodynamic forces experienced by the train during tunnel passage are proportional to the square of the train's speed and have an exponential relationship with the line spacing during train passage., (© 2024. The Author(s).)

Rubus idaeus is a pivotal cultivated species of raspberry known for its attractive color, distinct flavor, and numerous health benefits. It can be used in pharmaceutical, cosmetics, agriculture and food industries not only as fresh but also as a processed product. Nowadays due to climatic changes, genetic diversity of cultivars has decreased dramatically. However, until now, the status of wild R. idaeus resources in China have not been exploited. In this study, we investigated the resources of wild R. idaeus in China to secure its future potential and sustainability. The MaxEnt model was used to predict R. idaeus suitable habitats and spatial distribution patterns for current and future climate scenarios, based on wild domestic geographic distribution data, current and future climate variables, and topographic variables. The results showed that, mean temperature of the coldest quarter (bio11), precipitation of the coldest quarter (bio19), precipitation of the warmest quarter (bio18), and temperature seasonality (bio4) were crucial factors affecting the distribution of R. idaeus. Presently, the suitable habitats were mainly distributed in the north of China including Xinjiang, Inner Mongolia, Gansu, Ningxia, Shaanxi, Shanxi, Hebei, Beijing, Liaoning, Jilin, Heilongjiang. According to our results, in 2050s, the total suitable habitat area of R. idaeus will increase under SSP1-2.6 and then will be decreased with climate change, while in the 2090s, the total suitable habitat area will continue to decrease. From the present to the 2090s, the centroid distribution of R. idaeus in China will shift towards the east and the species will always be present in Inner Mongolia. Our results provide wild resource information and theoretical reference for the protection and rational utilization of R. idaeus., (© 2024. The Author(s).)

Cardiovascular disease (CVD) is the leading cause of death worldwide. To this end, human cardiac organoids (hCOs) have been developed for improved organotypic CVD modeling over conventional in vivo animal models. Utilizing human cells, hCOs hold great promise to bridge key gaps in CVD research pertaining to human-specific conditions. hCOs are multicellular 3D models which resemble heart structure and function. Varying hCOs fabrication techniques leads to functional and phenotypic differences. To investigate heterogeneity across hCO platforms, we performed a transcriptomic analysis utilizing bulk RNA-sequencing from four previously published unique hCO studies. We further compared selected hCOs to 2D and 3D hiPSC-derived cardiomyocytes (hiPSC-CMs), as well as fetal and adult human myocardium bulk RNA-sequencing samples. Upon investigation utilizing Principal Component Analysis, K-means clustering analysis of key genes, and further downstream analyses such as Gene Set Enrichment (GSEA), Gene Set Variation (GSVA), and GO term enrichment, we found that hCO fabrication method influences maturity and cellular heterogeneity across models. Thus, we propose that adjustment of fabrication method will result in an hCO with a defined maturity and transcriptomic profile to facilitate its specified applications, in turn maximizing its modeling potential., (© 2024. The Author(s).)

To investigate the screening and predicting functions of obesity- and lipid-related indices for type 2 diabetes (T2D) in middle-aged and elderly Chinese, as well as the ideal predicted cut-off value. This study's data comes from the 2011 China Health and Retirement Longitudinal Study (CHARLS). A cross-sectional study design was used to investigate the relationship of T2D and 13 obesity- and lipid-related indices, including body mass index (BMI), waist circumference (WC), waist-height ratio (WHtR), visceral adiposity index (VAI), a body shape index (ABSI), body roundness index (BRI), lipid accumulation product (LAP), conicity index (CI), Chinese visceral adiposity index (CVAI), triglyceride- glucose index (TyG index) and its correlation index (TyG-BMI, TyG-WC, TyG-WHtR). The unadjusted and adjusted correlations between 13 indices and T2D were assessed using binary logistic regression analysis. The receiver operating characteristic curve (ROC) was used to determine the usefulness of anthropometric indices for screening for T2D and determining their cut‑off value, sensitivity, specificity, and area under the curve (AUC). The study comprised 9488 people aged 45 years or above in total, of whom 4354 (45.89%) were males and 5134 (54.11%) were females. Among them were 716 male cases of T2D (16.44%) and 870 female cases of T2D (16.95%). A total of 13 obesity- and lipid-related indices were independently associated with T2D risk after adjusted for confounding factors (P < 0.05). According to ROC analysis, the TyG index was the best predictor of T2D among males (AUC = 0.780, 95% CI 0.761, 0.799) and females (AUC = 0.782, 95% CI 0.764, 0.799). The AUC values of the 13 indicators were higher than 0.5, indicating that they have predictive values for T2D in middle-aged and elderly Chinese. The 13 obesity- and lipid-related indices can predict the risk of T2D in middle‑aged and elderly Chinese. Among 13 indicators, the TyG index is the best predictor of T2D in both males and females. TyG-WC, TyG-BMI, TyG-WHtR, LAP, and CVAI all outperformed BMI, WC, and WHtR in predicting T2D., (© 2024. The Author(s).)

The purpose of the study was to determine whether changes in body mass index (BMI) and waist circumference (WC) in middle-aged and elderly Chinese are associated with metabolic syndrome. In this cohort investigation, 3697 middle-aged and elderly people aged 45 or over were recruited from the China Health and Retirement Longitudinal Study (CHARLS). The National Cholesterol Education Program Adult Treatment Panel III (2005) defined metabolic syndrome (MetS). With Cox regression analysis, we calculated hazard ratio (HR) and 95% confidence intervals (CIs) for MetS based on BMI-WC change categories. To assess the prevalence of MetS, the changes in BMI and WC levels were classified into four quartiles based on their relative and absolute changes. In subjects whose BMI and WC decreased (HR = 0.338; 95% CIs 0.264, 0.433) as well as those whose BMI increased and their WC decreased (HR = 0.375; 95% CIs 0.228, 0.499), metabolic syndrome risk was significantly lower compared with those with increases in both BMI and WC. Regarding the absolute changes in BMI, the lowest percentile of BMI was significantly lower in both males (HR = 0.302; 95% CIs 0.204, 0.448) and females (HR = 0.486; 95% CIs 0.354, 0.667) for the risk of metabolic syndrome. Similar results were observed in the absolute changes in WC, with the lowest quantile of WC having a significant impact on MetS risk in males (HR = 0.170; 95% CIs 0.107, 0.270) and females (HR = 0.303; 95% CIs 0.217, 0.424). The risk of metabolic syndrome was significantly associated with changes in BMI and WC in middle-aged and elderly Chinese. A reduced BMI and WC are associated with lower metabolic syndrome risks in middle-aged and elderly people., (© 2024. The Author(s).)

The incidence of acute kidney injury (AKI) due to ischemia-reperfusion (IR) injury is increasing. There is no effective treatment for AKI, and because of this clinical challenge, AKI often progresses to chronic kidney disease, which is closely associated with poor patient outcomes and high mortality rates. Small extracellular vesicles from human umbilical cord mesenchymal stem cells (hUCMSC-sEVs) play increasingly vital roles in protecting tissue function from the effects of various harmful stimuli owing to their specific biological features. In this study, we found that miR-100-5p was enriched in hUCMSC-sEVs, and miR-100-5p targeted FKBP5 and inhibited HK-2 cell apoptosis by activating the AKT pathway. HK-2 cells that were exposed to IR injury were cocultured with hUCMSC-sEVs, leading to an increase in miR-100-5p levels, a decrease in FKBP5 levels, and an increase in AKT phosphorylation at Ser 473 (AKT-473 phosphorylation). Notably, these effects were significantly reversed by transfecting hUCMSCs with an miR-100-5p inhibitor. Moreover, miR-100-5p targeted FKBP5, as confirmed by a dual luciferase reporter assay. In vivo, intravenous infusion of hUCMSC-sEVs into mice suffering from IR injury resulted in significant apoptosis inhibition, functional maintenance and renal histological protection, which in turn decreased FKBP5 expression levels. Overall, this study revealed an effect of hUCMSC-sEVs on inhibiting apoptosis; hUCMSC-sEVs reduced renal IR injury by delivering miR-100-5p to HK-2 cells, targeting FKBP5 and thereby promoting AKT-473 phosphorylation to activate the AKT pathway. This study provides novel insights into the role of hUCMSC-sEVs in the treatment of AKI., (© 2024. The Author(s).)

In this report, we described a new technique of gasless V-NOTES for hysterectomy and salpingectomy on a robotic platform with flexible devices in a porcine model. As a result, the gynecological procedures were successfully completed. The total operative time was 110 min, while the docking time was 10 min. The estimated blood loss was estimated to be 10 mL with no intraoperative complications. It revealed that gasless V-NOTES for hysterectomy and salpingectomy on a robotic platform with flexible devices appeared to be feasible and safe in the porcine model and has the potential for clinical use in human beings., (© 2024. The Author(s).)

There are no models for assessing the factors that determine moderate to poor performance status in patients with cancer after chemotherapy. This study investigated the influencing factors and identified the best model for predicting moderate-poor performance status. A convenience sampling method was used. Demographic and clinical data and evaluation results for fatigue, pain, quality of life and Eastern Cooperative Oncology Group status were collected three days after the end of chemotherapy. Decision tree, random forest and logistic regression models were constructed. Ninety-four subjects in the case group had moderate to poor performance status, and 365 subjects in the control group had no or mild activity disorders. The random forest model was the most accurate model. Physical function, total protein, general quality of life within one week before chemotherapy, hemoglobin, pain symptoms and globulin were the main factors. Total protein and hemoglobin levels reflect nutritional status, and globulin levels are an index of liver function. Therefore, physical function, nutritional status, general quality of life and pain symptoms within one week before chemotherapy and liver function can be used to predict moderate-poor performance status. Nurses should pay more attention to patients with poor physical function, poor nutritional status, lower quality of life and pain symptoms after chemotherapy., (© 2024. The Author(s).)

Global wind power expansion raises concerns about its potential impact on plant biomass production (PBP). Using a high-dimensional fixed effects model, this study reveals significant PBP reduction due to wind farm construction based on 2404 wind farms, 108,361 wind turbines, and 7,904,352 PBP observations during 2000-2022 in China. Within a 1-10 km buffer, the normalized differential vegetation and enhanced vegetation indices decrease from 0.0097 to 0.0045 and 0.0075 to 0.0028, respectively. Similarly, absorbed photosynthetically active radiation and gross primary productivity decline from 0.0094 to 0.0034% and 0.0003-0.0002 g*C/m 2 within a 1-7 km buffer. Adverse effects last over three years, magnified in summer and autumn, and are more pronounced at lower altitudes and in plains. Forest carbon sinks decrease by 12,034 tons within a 0-20 km radius, causing an average economic loss of $1.81 million per wind farm. Our findings underscore the balanced mitigation strategies for renewable energy transition when transiting from fossil fuels., (© 2023. The Author(s).)

The aims of this study on human papilloma virus (HPV) 6/11/16/18 infection among females in Chengdu were to provide more targeted strategies for the prevention and treatment of cervical cancer and genital warts. In this study, the infection status of 20 genotypes was analysed by gene chip technology. The prevalence rates of HPV-6, -11, -16, and -18 infection among 180,276 cases were 0.94%, 0.57%, 3.22%, and 1.28%, respectively. The prevalence of HPV 6/11/16/18 showed a bimodal U-shaped curve with age; the first and second peak occurred among females < 20 and ≥ 60 years old, respectively. As the multiplicity of infections involving HPV6/11/16/18 increases, the infection rate decreases. The ratios of HPV16 single infection showed a yearly increase. The top five genotypes with HPV-16, -18, -6, and -11 in coinfection were HPV52/58/53/51/33, HPV 52/16/53/58/51, HPV52/16/58/51/53 and HPV16/52/58/59/18, respectively, HPV16/18/6/11 were mainly coinfected with HR-HPV. In sum, among the five vaccines available, nonavalent vaccine is more suitable for Chengdu females. For young females prioritizing vaccination is essential in the current context, while HPV screening remains an effective approach for older females. Additionally, in patients with genital warts, it is necessary to assess the presence of high-risk HPV infection and manage it appropriately in patients with genital warts., (© 2023. The Author(s).)

Gastric cancer (GC) has been identified as the third deadly cancer in the world. Accumulating researches suggest a potential role of microorganisms in tumorigenesis. However, the composition of microbiota in GC tissues is not clear and it changes throughout the different stages of GC remain mostly elusive. Our study integrated RNA-Seq data of 727 samples derived from gastric tissues across four datasets and revealed its microbial composition. In order to remove the false positive results, core taxa were defined and characterized. Based on it, we analyzed the influence of biological factors on its composition. The pan-microbiome of gastric tissues was estimated to be over than 1400 genera. Seventeen core genera were identified. Among them, Helicobacter, Lysobacter were significantly enriched in normal tissues, while Pseudomonas was enriched in tumor tissues. Interestingly, Acinetobacter, Pasteurella, Streptomyces, Chlamydia, and Lysobacter, showed a significant increase trend during tumor development and formed strong intra/inter-correlations among them or with other genera. Furthermore, we found that tumor stage played an important role in altering the microbial composition of GC tissues. This study provides support for the in-depth study of tumor microbiome, and the specific microbiome excavated provides a possibility for the subsequent identification of potential biomarkers for GC., (© 2023. The Author(s).)

This study develops forces equilibrium differential equations for the geometric modeling of 1D flexible objects with surface constraints. These second-order equations are an extension of the Cosserat elastic rod theory and include both bending and torsion. Variables were established for the centerline and attitude in the Cartesian coordinate system of the cross section. This paper specifically investigates the case of a 1D flexible object constrained by a cylindrical surface. To solve this problem, a novel hybrid semi-analytical numerical method is proposed. In this process, a Hamiltonian function and an initial integral operator are introduced in a cylindrical coordinate system. The analytical solution, decoupled in polar coordinates, is then derived. The improved finite difference method was then used to obtain three cylindrical coordinates, which ensured numerical stability and efficiency. The results of a geometric shape simulation with differing boundary conditions demonstrate that this proposed method is capable of real-time modeling. As such, this technique could be a promising new tool for use in graphics simulations of elongated structures, such as DNA molecules, drill pipes, and submarine cables., (© 2023. The Author(s).)

Aiming at the traditional ecological footprint model, the improved ecological footprint of the carbon footprint effectively makes up for the singularity of the ecological footprint's consideration of carbon emissions, and plays an important role in promoting high-quality development and ecological sustainability. This paper selects 2015, 2018 and 2020 as important time points for the study, corrects the ecological footprint parameter factors based on net primary productivity (NPP), measures the ecological footprint after the improvement of the carbon footprint, studies the spatial and temporal variation in the ecological footprint at the 100-m grid scale with the support of IPCC greenhouse gas inventory analysis, and analyzes the current ecological conservation status of the Yellow River Delta. Additionally, in the context of a low carbon economy, the decoupling index of carbon emissions and GDP is extended to the evaluation and analysis of high-quality development. The study showed that (1) the ecological footprint of the Yellow River Delta has increased year by year, from 0.721 hm 2 ·person - 1 to 0.758 hm 2 ·person - 1 , an average annual increase of 2.9%; the ecological carrying capacity has decreased from 0.40 hm 2 ·person - 1 to 0.31 hm 2 ·person - 1 , an overall decrease of 28.59%. (2) The overall ecological deficit of the Yellow River Delta grid is lightly overloaded, with most of the ecological surplus occurring in the northern and eastern parts of the study area and a few moderate and heavy overloads in the center of the core area where there is a lot of built-up land and the area is small and easy to gather. (3) Based on the low-carbon economy analysis, 2015, 2017 and 2020 reach absolute decoupling and are in the ideal scenario. However, in the rest of the years, carbon emissions and economic development are still in a large contradiction, and decoupling has fluctuated and varied greatly in the last six years. The effective combination of ecological footprint and low carbon economy analysis provides an important theoretical basis for improving ecological conservation and achieving high-quality development., (© 2023. The Author(s).)

In this study, we explored whether satisfaction with government management, perception of risk, and gratitude influenced public anxiety during the COVID-19 pandemic in China. Using a cross-sectional, anonymous and confidential online survey, a nationwide sample of Chinese adults (N = 876) was targeted between March 25-March 30, 2020, a period in which newly confirmed cases significantly declined in China. The anxiety level was decreased as compared to that assessed during the peak period. Multiple parallel mediation modeling demonstrated that risk perception and gratitude partially mediated the relationship between satisfaction with government management and public anxiety. Increasing satisfaction and gratitude, as well as reducing risk perception contribute to the public's mental health. The results may shed light on the positive factors for psychological well-being during the COVID-19 pandemic and may aid potential strategies for the policy maker, the public, and the clinic to regulate negative emotions or future emerging infectious diseases., (© 2023. The Author(s).)

Straw returning is an effective management measure to improve or maintain soil fertility in agricultural ecosystems. This study investigated the effects of straw returning combined with compound fertilizer on the bacterial community, enzyme activities, and soil nutrients' contents in a rape-rice rotation soil aggregates. To do so, a 5-year field trial (November 2016 to October 2021) was carried out in a paddy soil with three treatments: no straw + no fertilization (CK), compound fertilizer (F), and straw returning + compound fertilizer (SF). Soil aggregates were classified into mega-aggregates (> 2 mm), macro-aggregates (0.25-2 mm), micro-aggregates (0.053-0.25 mm), and silt-clay (< 0.053 mm) using the wet sieve method. High-throughput sequencing was employed to characterize the bacterial community, and Pearson correlation coefficient was used to identify the relationships among bacterial community, organic carbon, nitrogen, phosphorus, and enzyme activities in soil aggregates. Compared with F, the results showed that straw returning increased the content of > 2 mm aggregates by 3.17% and significantly decreased the content of 0.053-0.25 mm aggregates by 20.27%. The contents of organic carbon and total nitrogen in > 0.053 mm straw amended aggregates increased by 15.29 and 18.25%, respectively. Straw returning significantly increased the urease activity of > 0.053 mm aggregates with an average of 43.08%, while it decreased the phosphatase and invertase activities of soil aggregates by 7.71-40.66%. The Shannon indices of the bacterial community in each particle sizes soil aggregates decreased by an average of 1.16% and the Chao indices of the bacterial community in < 2 mm aggregates increased by an average of 3.90% in straw amended soils. Nevertheless, the relative abundances of Chloroflexi and Nitrospirotain in all soil aggregates increased by 6.17-71.77% in straw amended soils. Altogether, our findings suggest that straw returning is an efficient approach to enhance soil structure, carbon and nitrogen contents, and the richness of soil bacterial diversity., (© 2023. The Author(s).)

In the development of anti-breast cancer drugs, the quantitative structure-activity relationship model of compounds is usually used to select potential active compounds. However, the existing methods often have problems such as low model prediction performance, lack of overall consideration of the biological activity and related properties of compounds, and difficulty in directly selection candidate drugs. Therefore, this paper constructs a complete set of compound selection framework from three aspects: feature selection, relationship mapping and multi-objective optimization problem solving. In feature selection part, a feature selection method based on unsupervised spectral clustering is proposed. The selected features have more comprehensive information expression ability. In the relationship mapping part, a variety of machine learning algorithms are used for comparative experiments. Finally, the CatBoost algorithm is selected to perform the relationship mapping between each other, and better prediction performance is achieved. In the multi-objective optimization part, based on the analysis of the conflict relationship between the objectives, the AGE-MOEA algorithm is improved and used to solve this problem. Compared with various algorithms, the improved algorithm has better search performance., (© 2022. The Author(s).)

Isosteviol sodium (STVNa) is a beyerane diterpene synthesized via acid hydrolysis of stevioside, which can improve glucose and lipid metabolism in animals with diabetes. However, it remains unknown whether STVNa can exhibit a therapeutic effect on nonalcoholic fatty liver disease (NAFLD) and its underlying mechanism. We hypothesize that autophagic initiation may play a key role in mediating the development of NAFLD. Herein, we assessed the effects of STVNa on NAFLD and its underlying mechanisms. The results demonstrated that STVNa treatment effectively ameliorated NAFLD in rats fed high-fat diet (HFD). Moreover, STVNa decreased the expression of inflammation-related genes and maintained a balance of pro-inflammatory cytokines in NAFLD rats. STVNa also reduced lipid accumulation in free fatty acid (FFA)-exposed LO2 cells. In addition, STVNa attenuated hepatic oxidative stress and fibrosis in NAFLD rats. Furthermore, STVNa enhanced autophagy and activated Sirtuin 1/adenosine monophosphate-activated protein kinase (Sirt1/AMPK) pathway both in vivo and in vitro, thus attenuating intracellular lipid accumulation. In summary, STVNa could improve lipid metabolism in NAFLD by initiating autophagy via Sirt1/AMPK pathway. Therefore, STVNa may be an alternative therapeutic agent for treatment of NAFLD., (© 2022. The Author(s).)

Protein functional effector sncRNAs (pfeRNAs) are approximately 30-60 nucleotides (nt), of which the extraction method from plasma has not yet been reported. Silver staining in a high-resolution polyacrylamide gel suggested that the majority of plasma sncRNAs extracted by some broadly used commercial kits were sncRNAs from 100 nt upwards. Additionally, TRIzol's protocol is for long RNA but not sncRNA recovery. Here, we report a TRIzol-based frozen precipitation method (TFP method), which shows rigor and reproducibility in high yield and quality for plasma sncRNAs approximately 30-60 nt. In contrast to the yields by the commercial kit, plasma sncRNAs extracted by the TFP method enriched more sncRNAs. We used four different pfeRNAs of 34 nt, 45 nt, 53 nt, and 58 nt to represent typical sizes of sncRNAs from 30 to 60 nt and compared their levels in the recovered sncRNAs by the TFP method and by the commercial kit. The TFP method showed lower cycle threshold (CT) values by 2.01-9.17 cycles in 38 plasma samples from 38 patients, including Caucasian, Asian, African American, Latin, Mexican, and those who were a mix of more than one race. In addition, pfeRNAs extracted by two organic-based extraction methods and four commercial kits were undetermined in 22 of 38 samples. Thus, the quick and unbiased TFP method enriches plasma sncRNA ranging from 30 to 60 nt., (© 2022. The Author(s).)

Steel-concrete (SC) composite widely used in military defensive project is due to its impressive mechanical properties, long-lived service, and low cost. However, the growing use of hypervelocity kinetic weapons in the present war puts forward higher requirements for the anti-explosion and penetration performance of military protection engineering. Here, inspired by the special 'brick-and-mortar' (BM) structural feature of natural nacre, we successfully construct a nacre-inspired steel-concrete (NISC) engineering composite with 2510 kg/m 3 , possessing nacre-like lamellar architecture via a bottom-up assembling technique. The NISC engineering composite exhibits nacreous BM structural similarity, high compressive strength of 68.5 MPa, compress modulus of 42.0 GPa, Mohs hardness of 5.5, Young's modulus of 41.5 GPa, and shear modulus of 18.4 GPa, higher than pure concrete. More interestingly, the hypervelocity impact tests reveal the penetration capability of our NISC target material is obviously stronger than that of pure concrete, enhanced up to about 46.8% at the striking velocity of 1 km/s and approximately 30.9% at the striking velocity of 2 km/s, respectively, by examining the damages of targets, the trajectories, penetration depths, and residual projectiles. This mechanically integrated enhancement can be attributed to the nacre-like BM structural architecture derived from assembling the special steel-bar array frame-reinforced concrete platelets. This study highlights a key role of nacre-like structure design in promoting the enhanced hypervelocity impact resistance of steel-concrete composites., (© 2021. The Author(s).)

Descurainia sophia L. is a notorious weed in winter wheat field and has serious resistance to tribenuron-methyl. Xinjiang is a main wheat production region in China with no information on D. sophia resistance to tribenuron-methyl. Here, resistance levels of D. sophia populations to tribenuron-methyl from Xinjiang and Henan were investigated. In addition, homozygous mutation subpopulations of high resistant D. sophia populations from Xinjiang and Henan were generated and then cross-resistance and fitness cost were determined. Results showed that 5 out of 31 populations from Xinjiang developed resistance to tribenuron-methyl, including two high resistant populations (X30 and X31). While 10 out of 11 populations from Henan showed resistance to tribenuron-methyl, including three high resistant populations (H5, H6 and H7). X30 and X31 shared the same mutation type of Pro197Thr in ALS1, while the mutation type of ALS1 in H5, H6 and H7 were Pro197Ser, Pro197His and Pro197Ala, respectively. The homozygous mutation subpopulations (SX30, SX31, SH5, SH6, SH7) showed cross-resistance to flucarbazone-sodium, bensulfuron methyl and flumetsulam. Under monoculture condition, relative growth rates of SX30, SX31 were higher than susceptible population (SX13), while that in SH5, SH6, SH7 were almost same with SX13. When mix planted with SX13, SX30 and SX31 displayed weaker competitiveness than SX13, while SH5, SH6, SH7 showed stronger competitiveness than SX13. The results suggested that D. sophia from Xinjiang had low resistance frequency to tribenuron-methyl and the high resistant populations had fitness costs., (© 2021. The Author(s).)

Lonicerae Japonicae Flos (LJF) is an important traditional Chinese medicine for the treatment of various ailments and plays a vital role in improving global human health. However, as unable to escape from adversity, the quality of sessile organisms is dramatically affected by salt stress. To systematically explore the quality formation of LJF in morphology, physiology, and bioactive constituents' response to multiple levels of salt stress, UFLC-QTRAP-MS/MS and multivariate statistical analysis were performed. Lonicera japonica Thunb. was planted in pots and placed in the field, then harvested after 35 days under salt stress. Indexes of growth, photosynthetic pigments, osmolytes, lipid peroxidation, and antioxidant enzymes were identified to evaluate the salt tolerance in LJF under different salt stresses (0, 100, 200, and 300 mM NaCl). Then, the total accumulation and dynamic variation of 47 bioactive constituents were quantitated. Finally, Partial least squares discrimination analysis and gray relational analysis were performed to systematically cluster, distinguish, and evaluate the samples, respectively. The results showed that 100 mM NaCl induced growth, photosynthetic, antioxidant activities, osmolytes, lipid peroxidation, and multiple bioactive constituents in LJF, which possessed the best quality. Additionally, a positive correlation was found between the accumulation of phenolic acids with antioxidant enzyme activity under salt stress, further confirming that phenolic acids could reduce oxidative damage. This study provides insight into the quality formation and valuable information to improve the LJF medicinal value under salt stress.

Telomere dysfunction causes chromosomal instability which is associated with many cancers and age-related diseases. The non-coding telomeric repeat-containing RNA (TERRA) forms a structural and regulatory component of the telomere that is implicated in telomere maintenance and chromosomal end protection. The basic N-terminal Gly/Arg-rich (GAR) domain of telomeric repeat-binding factor 2 (TRF2) can bind TERRA but the structural basis and significance of this interaction remains poorly understood. Here, we show that TRF2 GAR recognizes G-quadruplex features of TERRA. We show that small molecules that disrupt the TERRA-TRF2 GAR complex, such as N-methyl mesoporphyrin IX (NMM) or genetic deletion of TRF2 GAR domain, result in the loss of TERRA, and the induction of γH2AX-associated telomeric DNA damage associated with decreased telomere length, and increased telomere aberrations, including telomere fragility. Taken together, our data indicates that the G-quadruplex structure of TERRA is an important recognition element for TRF2 GAR domain and this interaction between TRF2 GAR and TERRA is essential to maintain telomere stability.

Wind speed and variability are the most critical climatic factors affecting sand/dust storms, which have not been sufficiently studied in the middle reaches of the Yarlung Tsangpo River (MYR). In this study, wind speed variability was investigated using the moving average over shifting horizon method (MASH), combined with the modified Mann-Kendall test and Sen's slope based on data from the Tsetang, Lhasa, and Nyêmo meteorological stations during 1960-2015. The results indicated that annual wind speeds for the MYR wide valley regions declined significantly at decadal rates of - 0.216 m/s and underwent three stages from 1960 to 2015: an increasing trend from 1960 to 1975 (0.44 m/s per decade), a weakening until 2006 (- 0.46 m/s per decade), and a remarkable subsequent recovery (1.05 m/s per decade). Different variability trends were observed for the three stations: wind speed decreased significantly during all months at the Tsetang and Nyêmo stations, particularly in the spring, while for Lhasa, a non-significant wind speed increase was detected in summer, and the highest decline occurred in winter. The MASH method resulted in the effective visualization of different patterns, making seasonal process analysis and trend detection easier. In addition, the possible main causes for wind speed change were also discussed. The wind speed change in the study region was strongly associated with the large-scale atmospheric patterns, and the surface pressure gradient variability between the mid and low latitudes may have been a primary driving force. Positive/negative phases of the Pacific Decadal Oscillation (PDO) corresponded well with wind speed decreases/increases and were regarded as an indicator of wind speed variations. The effects of human activities associated with surface roughness change in the MYR were minor compared with the climatic changes.

The El Niño-Southern Oscillation (ENSO) is the principal climatic system in the modern Pacific Ocean, and it potentially influences the global climate. The South China Sea (SCS), in the western tropical Pacific, is significantly affected by ENSO activity. We have conducted a high-resolution oxygen isotope study of the shells of one modern and four fossil Tridacna from the Xisha Islands in the SCS. The results for the modern sample reveal that the shells of Tridacna are a good proxy of ENSO variability. We used the results of the oxygen isotope composition of four fossil Tridacna to produce high-resolution records of ENSO activity during four time slices in the Holocene. The results indicate that ENSO variability in the early Holocene was comparable to that of today, and that a minimum in the frequency and intensity of ENSO activity occurred in the mid Holocene. These findings are consistent with paleoclimatic results from corals, mollusks and sedimentary records. However, the observed extremely low frequency and moderate ENSO intensity at 4.7 ka indicate an anomalous pattern of ENSO changes within this interval of climatic transition. In addition, seasonal temperature variations during the Holocene were different from those of today and extreme seasonality may also occur during warmer periods.

Recent studies have shown that transforming microglia phenotype from pro-inflammation of M1 phenotype to anti-inflammation and tissue-repairing M2 phenotype may be an effective therapeutic strategy for preventing ischemic stroke brain injury. Isosteviol Sodium (STV-Na) has shown promise as a neuroprotective agent in cerebral ischemia model, although its effect on microglial polarization and chronic recovery after stroke is not clear. Here, we demonstrated that STV-Na treatment significantly reduced cerebral ischemic damage at both acute and chronic time points. STV-Na has a profound regulatory effect on microglia response after stroke. It can promote M2 polarization and inhibit microglia-mediated inflammation (M1) response following stroke in vivo and in vitro. Furthermore, we also found that Growth Arrest-Specific 5 (GAS5) altered OGD/R-induced microglial activation by increasing Notch1 expression via miR-146a-5p, the mRNA level of GAS5 and the protein level of Notch1 in vivo and in vitro, were discovered that both downgraded with STV-Na. Taken together, the present study demonstrated that STV-Na exerted neuroprotective effects by modulating microglia/macrophage polarization in ischemic stroke via the GAS5/miR-146a-5p sponge. These findings provide new evidence that targeting STV-Na could be a treatment for the prevention of stroke-related brain damage.

The lymphatic system contains intraluminal leaflet valves that function to bias lymph flow back towards the heart. These valves are present in the collecting lymphatic vessels, which generally have lymphatic muscle cells and can spontaneously pump fluid. Recent studies have shown that the valves are open at rest, can allow some backflow, and are a source of nitric oxide (NO). To investigate how these valves function as a mechanical valve and source of vasoactive species to optimize throughput, we developed a mathematical model that explicitly includes Ca 2+ -modulated contractions, NO production and valve structures. The 2D lattice Boltzmann model includes an initial lymphatic vessel and a collecting lymphangion embedded in a porous tissue. The lymphangion segment has mechanically-active vessel walls and is flanked by deformable valves. Vessel wall motion is passively affected by fluid pressure, while active contractions are driven by intracellular Ca 2+ fluxes. The model reproduces NO and Ca 2+ dynamics, valve motion and fluid drainage from tissue. We find that valve structural properties have dramatic effects on performance, and that valves with a stiffer base and flexible tips produce more stable cycling. In agreement with experimental observations, the valves are a major source of NO. Once initiated, the contractions are spontaneous and self-sustained, and the system exhibits interesting non-linear dynamics. For example, increased fluid pressure in the tissue or decreased lymph pressure at the outlet of the system produces high shear stress and high levels of NO, which inhibits contractions. On the other hand, a high outlet pressure opposes the flow, increasing the luminal pressure and the radius of the vessel, which results in strong contractions in response to mechanical stretch of the wall. We also find that the location of contraction initiation is affected by the extent of backflow through the valves.

To evaluate the effect of glandular differentiation (GD) on tumor recurrence and progression of pT1 bladder urothelial carcinoma (UC). We performed a retrospective analysis of 82 bladder urothelial carcinoma with glandular differentiation (UCGD) patients which was pathologically diagnosed as pT1, 166 patients of pT1 UC of bladder without histologic variants served as controls. Patients of UCGD were more likely to have higher recurrence (P = 0.002) rate and higher progression rate (P < 0.001). Moreover, UCGD and a poor 5 -year overall survival (OS) (P = 0.02) while there was no difference in cancer-specific survival (CSS) (P = 0.062) between two groups. According to univariate analysis, largest tumor size (HR 1.502, CI 1.158-1.861, P = 0.029), UCGD (HR 1.787, CI 1.298-2.552, P = 0.001), lymphovascular invasion (LVI) (HR 1.226, CI 1.013-1.945, P = 0.039). UCGD (HR 1.367, CI 1.115-1.853, P = 0.038) and LVI (HR 1.416, CI 1.120-2.254, P = 0.013) were prognostic factors associated with disease recurrence and progression, respectively. Additionally, Additionally, UCGD significantly influence disease recurrence (HR 1.871, CI 1.338-2.589, P < 0.001) and progression (HR 1.462, CI 1.138-2.393, p = 0.007). Similarly, LVI significantly influence disease recurrence (HR 1.356, CI 1.053-2.174, P = 0.042) and progression (HR 1.348, CI 1.052-1.944, p = 0.022) in multivariate analysis. UCGD is significantly associated with higher recurrence and progression rate in patients with newly diagnosed pT1. Recurrent cases should be performed radical cystectomy (RC) earlier.

Metallographic, electrolytic method and RTO(room temperature organic) technique were applied in the present study to more accurately determine non-metallic inclusion in a ultra-low carbon interstitial free(IF) steel and further to confirm their origination in a Compact Strip Production Process (CSP Process) continuous casting (CC) slab. Results show that inclusions detected by metallographic method usually appear relative smaller size and are mainly Al 2 O 3 based or TiN based in composition, whereas those extracted by electrolytic method usually have larger size and are much more calcium-silicate based in composition. In addition, inner structures of extracted inclusions were detected by applying of RTO technique. The large size calcium-silicate based inclusions are confirmed high possibilities originating from mold flux and/or tundish flux entrapment, which are less affected by the liquid steel composition; while the smaller ones are generally endogenous inclusion precipitating during the refining or solidification process that strongly depending on the liquid steel composition and temperature.

Qinghai-Tibetan Plateau is the most sensitive region to global warming on Earth. Qinghai Lake, the largest lake on the plateau, has experienced evident area variation during the past several decades. To quantify the area changes of Qinghai Lake, a satellite-based survey based on Landsat images from the 1980s to 2010s has been performed. In addition, meteorological data from all the seven available stations on Qinghai-Tibetan Plateau has been analyzed. Area of Qinghai Lake shrank ~2% during 1987-2005, and then increased ~3% from 2005-2016. Meanwhile, the average annual temperature increased 0.319 °C/10 y in the past 50 years, where the value is 0.415 °C/10 y from 2005-2016. The structural equation modeling (SEM) shows that precipitation is the primary factor influencing the area of Qinghai Lake. Moreover, temperature might be tightly correlated with precipitation, snow line, and evaporation, thereby indirectly causes alternations of the lake area. This study elucidated the significant area variation of water body on the Qinghai-Tibetan Plateau under global warming since 1980s.

We developed a novel technique of bi-enzyme single-step hydrolysis, using recombinant chitosanase (McChoA) and exo-β-D-glucosaminidase (AorCsxA) constructed previously in our lab, to degrade chitosan. The hydrolysis product was shown by HPLC, FTIR, and chemical analyses to be a mixture (termed "GC") composed primarily of glucosamine (80.00%) and chitooligosaccharides (9.80%). We performed experiments with a mouse osteoarthritis (OA) model to evaluate the anti-inflammatory effects of GC against OA. The three "GC groups" (which underwent knee joint damage followed by oral administration of GC at concentrations 40, 80, and 160 mg/kg·bw·d for 15 days) showed significantly downregulated serum expression of pre-inflammatory cytokines (IL-1β, IL-6, TNF-α), and significant, dose-dependent enhancement of anti-inflammatory cytokine IL-2, in comparison with Model group. Levels of C-reactive protein, which typically rise in response to inflammatory processes, were significantly lower in the GC groups than in Model group. Thymus index and levels of immunoglobulins (IgG, IgA, IgM) were higher in the GC groups. Knee joint swelling was relieved and typical OA symptoms were partially ameliorated in the GC-treated groups. Our findings indicate that GC has strong anti-inflammatory effects and potential as a therapeutic agent against OA and other inflammatory diseases.

Serine protease inhibitors (SPIs) regulate protease-mediated activities by inactivating their cognate proteinases, and are involved in multiple physiological processes. SPIs have been extensively studied in vertebrates and invertebrates; however, little SPI information is available in parasitoids. Herein, we identified 57 SPI genes in total through the genome of a parasitoid wasp, Pteromalus puparum. Gene structure analyses revealed that these SPIs contain 7 SPI domains. Depending on their mode of action, these SPIs can be categorized into serpins, canonical inhibitors and alpha-2-macroglobulins (A2Ms). For serpins and canonical inhibitors, we predicted their putative inhibitory activities to trypsin/chymotrypsin/elastase-like enzymes based on the amino acids in cleaved reactive sites. Sequence alignment and phylogenetic tree indicated that some serpins similar to known functional inhibitory serpins may participate in immune responses. Transcriptome analysis also showed some canonical SPI genes displayed distinct expression patterns in the venom gland and this was confirmed by quantitative real-time PCR (qPCR) analysis, suggesting their specific physiological functions as venom proteins in suppressing host immune responses. The study provides valuable information to clarify the functions of SPIs in digestion, development, reproduction and innate immunity.

Pyruvate kinase M2 (PKM2), a key protein in glucose and lipid metabolism, has been reported to be related to carcinogenesis in various malignancies. However, its roles in hepatocellular carcinoma with cirrhotic liver (CL) and hepatocellular carcinoma with non-cirrhoticliver (NCL) haves not been investigated. In our study western bloting, qRT-PCR and immunohistochemistry were performed to evaluate the clinical significance of PKM2 protein expression in CL and NCL. The results revealed that PKM2 protein expression was significantly higher in HCC tissues than in their adjacent non-tumour tissues. The high expression rates of PKM2 were more frequently noted in CL (45. 6%) than in NCL (31. 9%) tissues. High PKM2 expression in CL and NCL tissues was significantly associated with vascular invasion (P = 0.002 and P = 0.004, respectively) and intrahepatic metastasis (P < 0.001 and P = 0.019, respectively). Importantly, Kaplan-Meier survival analysis showed that the disease-specific survival (DSS) and recurrence-free survival (RFS) were lower in CL with high PKM2 expression than in NCL with high PKM2 expression (P = 0.003 and P = 0.003, respectively). Overall, high PKM2 expression was more frequently found in CL than in NCL, and PKM2 overexpression was associated with poor survival rates in patients with CL and NCL.

Chloride intracellular channels (CLIC) are non-classical ion channels lacking a signal sequence for membrane targeting. In eukaryotes, they are implicated in cell volume regulation, acidification, and cell cycle. CLICs resemble the omega class of Glutathione S-transferases (GST), yet differ from them in their ability to form ion channels. They are ubiquitously found in eukaryotes but no prokaryotic homolog has been characterized. We found that indanyloxyacetic acid-94 (IAA-94), a blocker of CLICs, delays the growth of Escherichia coli. In silico analysis showed that the E. coli stringent starvation protein A (SspA) shares sequence and structural homology with CLICs. Similar to CLICs, SspA lacks a signal sequence but contains an omega GST fold. Electrophysiological analysis revealed that SspA auto-inserts into lipid bilayers and forms IAA-94-sensitive ion channels. Substituting the ubiquitously conserved residue leucine 29 to alanine in the pore-forming region increased its single-channel conductance. SspA is essential for cell survival during acid-induced stress, and we found that acidic pH increases the open probability of SspA. Further, IAA-94 delayed the growth of wild-type but not sspA null mutant E. coli. Our results for the first time show that CLIC-like proteins exist in bacteria in the form of SspA, forming functional ion channels.

Myeloid differentiation protein 1 (MD1) has been implicated in numerous pathophysiological processes, including immune regulation, obesity, insulin resistance, and inflammation. However, the role of MD1 in cardiac remodelling remains incompletely understood. We used MD1-knockout (KO) mice and their wild-type littermates to determine the functional significance of MD1 in the regulation of aortic banding (AB)-induced left ventricular (LV) structural and electrical remodelling and its underlying mechanisms. After 4 weeks of AB, MD1-KO hearts showed substantial aggravation of LV hypertrophy, fibrosis, LV dilation and dysfunction, and electrical remodelling, which resulted in overt heart failure and increased electrophysiological instability. Moreover, MD1-KO-AB cardiomyocytes showed increased diastolic sarcoplasmic reticulum (SR) Ca 2+ leak, reduced Ca 2+ transient amplitude and SR Ca 2+ content, decreased SR Ca 2+ -ATPase2 expression, and increased phospholamban and Na + /Ca 2+ -exchanger 1 protein expression. Mechanistically, the adverse effects of MD1 deletion on LV remodelling were related to hyperactivated CaMKII signalling and increased impairment of intracellular Ca 2+ homeostasis, whereas the increased electrophysiological instability was partly attributed to exaggerated prolongation of cardiac repolarisation, decreased action potential duration alternans threshold, and increased diastolic SR Ca 2+ leak. Therefore, our study on MD1 could provide new therapeutic strategies for preventing/treating heart failure.

Myeloid differentiation 1 (MD-1), a secreted protein interacting with radioprotective 105 (RP105), plays an important role in Toll-like receptor 4 (TLR4) signalling pathway. Previous studies showed that MD-1 may be restricted in the immune system. In this study, we demonstrated for the first time that MD-1 was highly expressed in both human and animal hearts. We also discovered that cardiac-specific overexpression of MD-1 significantly attenuated pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction, whereas loss of MD-1 had the opposite effects. Similar results were observed for in vitro angiotensin II-induced neonatal rat cardiomyocyte hypertrophy. The antihypertrophic effects of MD-1 under hypertrophic stimuli were associated with the blockage of MEK-ERK 1/2 and NF-κB signalling. Blocking MEK-ERK 1/2 signalling with a pharmacological inhibitor (U0126) greatly attenuated the detrimental effects observed in MD-1 knockout cardiomyocytes exposed to angiotensin II stimuli. Similar results were observed by blocking NF-κB signalling with a pharmacological inhibitor (BAY11-7082). Our data indicate that MD-1 inhibits cardiac hypertrophy and suppresses cardiac dysfunction during the remodelling process, which is dependent on its modulation of the MEK-ERK 1/2 and NF-κB signalling pathways. Thus, MD-1 might be a novel target for the treatment of pathological cardiac hypertrophy., Competing Interests: The authors declare no competing financial interests.

A technical challenge in the registration of dynamic contrast-enhanced magnetic resonance (DCE-MR) imaging in the liver is intensity variations caused by contrast agents. Such variations lead to the failure of the traditional intensity-based registration method. To address this problem, a manifold-based registration framework for liver DCE-MR time series is proposed. We assume that liver DCE-MR time series are located on a low-dimensional manifold and determine intrinsic similarities between frames. Based on the obtained manifold, the large deformation of two dissimilar images can be decomposed into a series of small deformations between adjacent images on the manifold through gradual deformation of each frame to the template image along the geodesic path. Furthermore, manifold construction is important in automating the selection of the template image, which is an approximation of the geodesic mean. Robust principal component analysis is performed to separate motion components from intensity changes induced by contrast agents; the components caused by motion are used to guide registration in eliminating the effect of contrast enhancement. Visual inspection and quantitative assessment are further performed on clinical dataset registration. Experiments show that the proposed method effectively reduces movements while preserving the topology of contrast-enhancing structures and provides improved registration performance.

Previous experimental study measuring the binding affinities of biotin to the wild type streptavidin (WT) and three mutants (S45A, D128A and S45A/D128A double mutant) has shown that the loss of binding affinity from the double mutation is larger than the direct sum of those from two single mutations. The origin of this cooperativity has been investigated in this work through molecular dynamics simulations and the end-state free energy method using the polarized protein-specific charge. The results show that this cooperativity comes from both the enthalpy and entropy contributions. The former contribution mainly comes from the alternations of solvation free energy. Decomposition analysis shows that the mutated residues nearly have no contributions to the cooperativity. Instead, N49 and S88, which are located at the entry of the binding pocket and interact with the carboxyl group of biotin, make the dominant contribution among all the residues in the first binding shell around biotin.

Interleukin 15 (IL-15) expression induces the secretion of inflammatory cytokines, inhibits the apoptosis of activated T cells and prolongs the survival of CD8(+) memory T cells. Here we identified an IL-15 isoform lacking exon-6, IL-15ΔE6, generated by alternative splicing events of activated immune cells, including macrophages and B cells. In vitro study showed that IL-15ΔE6 could antagonize IL-15-mediated T cell proliferation. The receptor binding assay revealed that IL-15ΔE6 could bind to IL-15Rα and interfere with the binding between IL-15 and IL-15Rα. Over-expression of IL-15ΔE6 in the murine EAE model ameliorated the EAE symptoms of the mice. The clinical scores were significantly lower in the mice expressing IL-15ΔE6 than the control mice and the mice expressing IL-15. The inflammation and demyelination of the EAE mice expressing IL-15ΔE6 were less severe than the control group. Furthermore, flow cytometry analysis demonstrated that IL-15ΔE6 expression reduced the percentages of inflammatory T cells in the spleen and spinal cord, and inhibited the infiltration of macrophages to the CNS. Our results demonstrated that IL-15ΔE6 could be induced during immune activation and function as a negative feedback mechanism to dampen IL-15-mediated inflammatory events.

Because of the rapid economic growth in China, many regions are subjected to severe particulate matter pollution. Thus, improving the methods of determining the spatiotemporal distribution and uncertainty of air pollution can provide considerable benefits when developing risk assessments and environmental policies. The uncertainty assessment methods currently in use include the sequential indicator simulation (SIS) and indicator kriging techniques. However, these methods cannot be employed to assess multi-temporal data. In this work, a spatiotemporal sequential indicator simulation (STSIS) based on a non-separable spatiotemporal semivariogram model was used to assimilate multi-temporal data in the mapping and uncertainty assessment of PM2.5 distributions in a contaminated atmosphere. PM2.5 concentrations recorded throughout 2014 in Shandong Province, China were used as the experimental dataset. Based on the number of STSIS procedures, we assessed various types of mapping uncertainties, including single-location uncertainties over one day and multiple days and multi-location uncertainties over one day and multiple days. A comparison of the STSIS technique with the SIS technique indicate that a better performance was obtained with the STSIS method.

Deficits in inhibitory control have been linked to aggression and violent behaviour. This study aimed to observe whether violent adolescents show different brain activation patterns during response inhibition and to ascertain the roles these brain regions play. A self-report method and modified overt aggression scale (MOAS) were used to evaluate violent behaviour. Functional magnetic resonance imaging was performed in 22 violent adolescents and 17 matched healthy subjects aged 12 to 18 years. While scanning, a go/no-go task was performed. Between-group comparisons revealed that activation in the bilateral middle and superior temporal gyrus, hippocampus, and right orbitofrontal area (BA11) regions were significantly reduced in the violent group compared with the control group. Meanwhile, the violent group had more widespread activation in the prefrontal cortex than that observed in the control group. Activation of the prefrontal cortex in the violent group was widespread but lacking in focus, failing to produce intensive activation in some functionally related regions during response inhibition.

Myelodysplastic syndromes (MDS) are clonal disorders of haematopoiesis characterised by dysplastic changes of major myeloid cell lines. However, the mechanisms underlying these dysplastic changes are poorly understood. Here, we used a genetically modified mouse model and human patient data to examine the physiological roles of H2AX in haematopoiesis and how the loss of H2AX contributes to dyserythropoiesis in MDS. H2AX knockout mice showed cell-autonomous anaemia and erythroid dysplasia, mimicking dyserythropoiesis in MDS. Also, dyserythropoiesis was increased in MDS patients with the deletion of chromosome 11q23, where H2AX is located. Although loss of H2AX did not affect the early stage of terminal erythropoiesis, enucleation was decreased. H2AX deficiency also led to the loss of quiescence of hematopoietic stem and progenitor cells, which dramatically compromised their bone marrow engraftment. These results reveal important roles of H2AX in late-stage terminal erythropoiesis and hematopoietic stem cell function.

The Fenna-Matthews-Olson (FMO) light-harvesting complex is now one of the primary model systems for the study of excitation energy transfer (EET). However, the mechanism of the EET in this system is still controversial. In this work, molecular dynamics simulations and the electrostatic-embedding quantum-mechanics/molecular-mechanics single-point calculations have been employed to predict the energy transfer pathways utilizing the polarized protein-specific charge (PPC), which provides a more realistic description of Coulomb interaction potential in the protein than conventional mean-field charge scheme. The recently discovered eighth pigment has also been included in this study. Comparing with the conventional mean-field charges, more stable structures of FMO complex were found under PPC scheme during molecular dynamic simulation. Based on the electronic structure calculations, an exciton model was constructed to consider the couplings during excitation. The results show that pigments 3 and 4 dominate the lowest exciton levels whereas the highest exciton level are mainly constituted of pigments 1 and 6. This observation agrees well with the assumption based on the spatial distribution of the pigments. Moreover, the obtained spectral density in this study gives a reliable description of the diverse local environment embedding each pigment.

The synergy effect in nature could enable fantastic improvement of functional properties and associated effects. The detection performance of surface-enhanced Raman scattering (SERS) can be highly strengthened under the cooperation with other factors. Here, greatly-enhanced SERS detection is realized based on rolled-up tubular nano-resonators decorated with silver nanoparticles. The synergy effect between whispering-gallery-mode (WGM) and surface plasmon leads to an extra enhancement at the order of 10(5) compared to non-resonant flat SERS substrates, which can be well tuned by altering the diameter of micron- and nanotubes and the excitation laser wavelengths. Such synchronous and coherent coupling between plasmonics and photonics could lead to new principle and design for various sub-wavelength optical devices, e.g. plasmonic waveguides and hyperbolic metamaterials.

A new modification to the AMBER force field that incorporates the coupled two-dimensional main chain torsion energy has been evaluated for the balanced representation of secondary structures. In this modified AMBER force field (AMBER03(2D)), the main chain torsion energy is represented by 2-dimensional Fourier expansions with parameters fitted to the potential energy surface generated by high-level quantum mechanical calculations of small peptides in solution. Molecular dynamics simulations are performed to study the folding of two model peptides adopting either α-helix or β-hairpin structures. Both peptides are successfully folded into their native structures using an AMBER03(2D) force field with the implementation of a polarization scheme (AMBER03(2D)p). For comparison, simulations using a standard AMBER03 force field with and without polarization, as well as AMBER03(2D) without polarization, fail to fold both peptides successfully. The correction to secondary structure propensity in the AMBER03 force field and the polarization effect are critical to folding Trpzip2; without these factors, a helical structure is obtained. This study strongly suggests that this new force field is capable of providing a more balanced preference for helical and extended conformations. The electrostatic polarization effect is shown to be indispensable to the growth of secondary structures.

Lipid metabolism is important for cellular energy homeostasis. Excessive cellular lipid accumulation is associated with various human diseases such as obesity, cardiovascular disease or even cancer. It has been recognized that miR-181a is an important modulator in regulating T lymphocyte differentiation, vascular development and cerebellar neurodegeneration. Here we reports a novel function of miR-181a in the regulation of lipid metabolism. MiR-181a is able to target isocitrate dehydrogenase 1 (IDH1), a metabolic enzyme in TCA cycle. Via targeting IDH1, miR-181a decreases expression of genes involved in lipid synthesis and increases expression of genes involved in β-oxidation, thereafter inhibiting lipid accumulation. MiR-181a transgenic mice show a lower body weight as compared with their wild-type littermates, and moreover, miR-181a transgenic mice exhibit less lipid accumulation. Collectively, these findings uncover a novel miR-181a-IDH1 axis that has an important role in regulating lipid metabolism, and implicate miR-181a as a potential therapeutic target for lipid metabolism disorders.