The Global Burden of Disease Attributable to Child and Maternal Malnutrition: 1990-2019.

OBJECTIVE: With this study, we aimed to estimate the disease burden attributable to child and maternal malnutrition (CMM) throughout the world between 1990 and 2019. METHODS: The number, age-standardized rate, population attributable fraction of deaths, disability-adjusted life-years, years of life lost, and years lived with disability associated with CMM were estimated using the Global Burden of Disease Study 2019 by age, sex, year, location, and sociodemographic index at the global level. The slope index of inequality and concentration index were employed to measure socioeconomic-related health inequalities across countries. RESULTS: The number (million) of global deaths, disability-adjusted life-years, and years of life lost related to CMM were 2.9, 294.8, and 250.5 in 2019, showing decreases of 60.8, 57.4, and 60.7% since 1990. However, the number of years lived with CMM-related disability increased from 36.0 in 1990 to 44.3 in 2019. Additionally, the age-standardized rates of these 4 indicators showed varying degrees of decline. The global burden of CMM-related conditions differed with age and sex. The burden was the heaviest in western sub-Saharan Africa, especially in Chad. In terms of diseases, neonatal disorders represented the most significant burden attributed to CMM. Additionally, the CMM burden was more concentrated in regions with low sociodemographic indices, shown by the slope index of inequality and concentration index. CONCLUSIONS: The findings of this study highlight the ongoing global burden of CMM, particularly in terms of years lived with disability. Population-wide actions targeting the effective treatment and relief of CMM may reduce the CMM-related disease burden.

Highly pathogenic PRRSV upregulates IL-13 production through nonstructural protein 9-mediated inhibition of N6-methyladenosine demethylase FTO.

Porcine reproductive and respiratory syndrome virus (PRRSV), a highly infectious virus, causes severe losses in the swine industry by regulating the inflammatory response, inducing tissue damage, suppressing the innate immune response, and promoting persistent infection in hosts. Interleukin-13 (IL-13) is a cytokine that plays a critical role in regulating immune responses and inflammation, particularly in immune-related disorders, certain types of cancer, and numerous bacterial and viral infections; however, the underlying mechanisms of IL-13 regulation during PRRSV infection are not well understood. In this study, we demonstrated that PRRSV infection elevates IL-13 levels in porcine alveolar macrophages. PRRSV enhances m6A-methylated RNA levels while reducing the expression of fat mass and obesity associated protein (FTO, an m6A demethylase), thereby augmenting IL-13 production. PRRSV nonstructural protein 9 (nsp9) was a key factor for this modulation. Furthermore, we found that the residues Asp567, Tyr586, Leu593, and Asp595 were essential for nsp9 to induce IL-13 production via attenuation of FTO expression. These insights delineate PRRSV nsp9's role in FTO-mediated IL-13 release, advancing our understanding of PRRSV's impact on host immune and inflammatory responses.

Global burden of leukemia attributable to occupational exposure to formaldehyde from 1990 to 2019.

The objective of this study was to evaluate the worldwide burden of leukemia owing to occupational exposure to formaldehyde (OEF) from 1990 to 2019. Data on leukemia due to OEF were obtained from the Global Burden of Disease Study (GBD) 2019. By region, age, sex, and disease subtype, the numbers and age-standardized rates (ASRs) associated with deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) were analyzed. Annual average percentage change (AAPC) was used to estimate disease burden trends from 1990 to 2019. To measure the risk of leukemia due to OEF, the population attributable fraction (PAF) was introduced. From 1990 to 2019, the number of deaths, DALYs, YLLs, and YLDs for leukemia caused by OEF increased by 44%, 34%, 33%, and 124%, respectively. Regarding the change in ASRs, the age-standardized YLDs (ASYLDs) rate of leukemia due to OEF, which was 38.03% (AAPC = 1.17 [95% confidence interval [CI] 1.11, 1.23]), indicated an increased trend. But the age-standardized mortality rate (ASMR), age-standardized DALY (ASDALY) rate, and age-standardized YLL (ASYLL) rate showed decline trends, with - 11.90% (AAPC = - 0.41 [95% CI - 0.45, - 0.37]), - 14.19% (AAPC = - 0.5 [95% CI - 0.55, - 0.45]), and - 14.97% (AAPC = - 0.53 [95% CI - 0.58, - 0.48]), respectively. In terms of PAFs, there were increasing trends in PAFs of age-standardized deaths, ASDALYs, ASYLLs, and ASYLDs for leukemia caused by OEF, with 20.15% (95% uncertainty interval [UI] 11.76%, 30.25%), 36.28% (95% UI 21.46%, 53.42%), 51.91% (95% UI 35.05%, 72.07%), and 36.34% (95% UI 21.58%, 53.63%), respectively. Across the socio-demographic index (SDI) regions, the leukemia burden caused by OEF was concentrated in middle and high-middle SDI regions. Besides, OEF poses a more serious risk for acute leukemia among the leukemia subtype. Globally, leukemia caused by OEF remains a public health burden. Policies must be developed to avoid the burden of leukemia caused by OEF.

Health-related quality of life in Chinese SLE patients: evidence from 1568 SLE patients and 2610 healthy controls.

OBJECTIVE: To investigate the effects of systemic lupus erythematosus (SLE) on health-related quality of life (HRQOL), the relationship between disease activity and HRQOL, and potential factors affecting HRQOL in Chinese SLE patients. METHODS: This study recruited 1568 patients and 2610 controls to explore the effects of SLE on HRQOL. The association between disease activity and HRQOL, and the influencing factors of HRQOL were determined in 1568 patients. Then, we prospectively followed 1096 patients to explore the association between reduced disease activity and improved HRQOL, and the influencing factors of improved HRQOL. The Short-Form 36 (SF-36) and SLE disease activity index (SLEDAI) were used to evaluate HRQOL and disease activity. RESULTS: Chinese SLE patients had lower HRQOL than controls in all domains (P < 0.001), especially in role-physical (RP) and role-emotional (RE). Compared with SLE patients from outside China, the HRQOL of Chinese patients appeared to be higher in mental component summary (MCS) but lower in RP and RE. SLEDAI was negatively correlated with HRQOL, which was validated using the results of a follow-up study, where SLEDAI reduction was positively associated with HRQOL improvements (P < 0.05). Furthermore, personality, life nervous and experiences of adverse life events may influence HRQOL and HRQOL improvements. CONCLUSION: SLE significantly affected the HRQOL of Chinese patients, especially in RP and RE. Disease activity was negatively correlated with HRQOL. We also found for the first time some factors affecting HRQOL, which can be regarded as the basis for improving the HRQOL of SLE patients.

Temperature variability associated with respiratory disease hospitalisations, hospital stays and hospital expenses the warm temperate sub-humid monsoon climate.

OBJECTIVES: The abrupt change of climate has led to an increasing trend of hospitalised patients in recent years. This study aimed to analyse the temperature variability (TV) associated with respiratory disease (RD) hospitalisations, hospital stays and hospital expenses. STUDY DESIGN: The generalized linear model combined with distributed lag non-linear model was used to investigate the association between TV and RD hospitalisations. METHODS: TV was determined by measuring the standard deviation of maximum and minimum temperatures for the current day and the previous 7 days. RD hospitalisations data were obtained from three major tertiary hospitals in Huaibei City, namely, the Huaibei People's Hospital, the Huaibei Hospital Of Traditional Chinese Medicine and the Huaibei Maternal and Child Health Care Hospital. First, using a time series decomposition model, the seasonality and long-term trend of hospitalisations, hospital stays and hospital expenses for RD were explored in this warm temperate sub-humid monsoon climate. Second, robust models were used to analyse the association between TV and RD hospitalisations, hospital stays and hospital expenses. In addition, this study stratified results by sex, age and season. Third, using the attributable fraction (AF) and attributable number (AN), hospitalisations, hospital stays and hospital expenses for RD attributed to TV were quantified. RESULTS: Overall, 0.013% of hospitalisations were attributed to TV0-1 (i.e. TV at the current day and previous 1 day), corresponding to 220 cases, 1603 days of hospital stays and 1,308,000 RMB of hospital expenses. Females were more susceptible to TV than males, and the risk increased with longer exposure (the highest risk was seen at TV0-7 [i.e. TV at the current day and previous 7 days] exposure). Higher AF and AN were observed at ages 0-5 years and ≥65 years. In addition, it was also found that TV was more strongly linked to RD in the cool season. The hot season was positively associated with hospital stays and hospital expenses at TV0-3 to TV0-7 exposure. CONCLUSIONS: Exposure to TV increased the risk of hospitalisations, longer hospital stays and higher hospital expenses for RD. The findings suggested that more attention should be paid to unstable weather conditions in the future to protect the health of vulnerable populations.

Global disease burden attributed to high sugar-sweetened beverages in 204 countries and territories from 1990 to 2019.

High sugar-sweetened beverages (SSBs) are a controllable risk factor for chronic non-communicable diseases (NCDs), but their effect on the global disease burden is uncertain. The study aims to assess the global burden of high SSBs from 1990 to 2019. Global Burden of Disease (GBD) 2019 provides data on deaths, disability-adjusted life years (DALYs), years of life with disabilities (YLDs) and years of life lost (YLLs) ascribe to high SSBs by ages, genders, regions and countries. For the past 30 years, overall exposure to high SSBs decreased for males and increased for females. The number of deaths from chronic NCDs ascribed to high SSBs increased from 149,988 (110,278-182,947) to 242,218 (172,045-302,250), DALYs increased from 3,698,578 (2,693,476-4,559,740) to 6,307,562 (4,300,765-8,079,556), especially the males. Age-standardized YLDs rate (ASYLDs) increased from 11.58 to 17.03. The number of ischemic heart disease (IHD) and diabetes mellitus (DM) deaths and DALYs ascribed to high SSBs has been increasing. Age-standardized death rate (ASDR) for DM risen from 0.56 to 0.62, age-standardized DALYs rate (ASDALYs) risen from 21.41 to 28.21. The burden of disease ascribed to high SSBs was in the elderly significantly higher than in the young and middle-aged, mainly concentrated in Central Asia and Oceania. The disease burden was highest in regions with moderate sociodemographic index (SDI). More extraordinary efforts should be made to raise awareness among the general public about interventions aimed at limiting the use of high SSBs, to reduce disease burden ascribed to high SSBs.

Nucleocapsid protein residues 35, 36, and 113 are critical sites in up-regulating the Interleukin-8 production via C/EBPα pathway by highly pathogenic porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly infectious and pathogenic agent that causes considerable economic damage in the swine industry. It regulates the inflammatory response, triggers inflammation-induced tissue damage, suppresses the innate immune response, and leads to persistent infection. Interleukin-8 (IL-8), a pro-inflammatory chemokine, plays a crucial role in inflammatory response during numerous bacteria and virus infections. However, the underlying mechanisms of IL-8 regulation during PRRSV infection are not well understood. In this study, we demonstrate that PRRSV-infected PAMs and Marc-145 cells release higher levels of IL-8. We screened the nucleocapsid protein, non-structural protein (nsp) 9, and nsp11 of PRRSV to enhance IL-8 promoter activity via the C/EBPα pathway. Furthermore, we identified that the amino acids Q35A, S36A, R113A, and I115A of the nucleocapsid protein play a crucial role in the induction of IL-8. Through reverse genetics, we generated two mutant viruses (rQ35-2A and rR113A), which showed lower induction of IL-8 in PAMs during infection. This finding uncovers a previously unrecognized role of the PRRSV nucleocapsid protein in modulating IL-8 production and provides insight into an additional mechanism by which PRRSV modulates immune responses and inflammation.

The global burden and trends of four major types of heart disease, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

OBJECTIVES: The global burden of heart disease is severe and increasing in the coming years. This study aims to analyze the global burden of heart disease. STUDY DESIGN: Rheumatic heart disease (RHD), ischemic heart disease (IHD), hypertensive heart disease (HHD), and non-rheumatic valvular heart disease (NRVHD) were selected and analyzed from the Global Burden of Disease Study 2019. METHODS: The prevalence, deaths, disability-adjusted life years and their corresponding age-standardized rates were obtained from the Global Burden of Disease Study 2019. In addition, estimated annual percentage change was calculated to better assess epidemiological trends. In addition, we performed an age-period-cohort analysis using the Nordpred package in R program to predict death trends over the next 20 years. RESULTS: Globally, the prevalence of four heart diseases (RHD, IHD, HHD, and NRVHD) increased by 70.5%, 103.5%, 137.9%, and 110.0% compared with 1990, respectively. The deaths cases of RHD decreased by 15.6%, whereas IHD, HHD, and NRVHD increased by 60.4%, 76.6%, and 110.6%. Compared with absolute values, their corresponding age-standardized rates only showed a slight increase trend or even decreased in some areas with high sociodemographic index. In the next 20 years, the absolute values of deaths will continue to increase, whereas their age-standardized rates of deaths will flatten out. CONCLUSIONS: Globally, the absolute values of heart disease have increased over the past 30 years and will continue to increase over the next 20 years. Targeted prevention and control strategies and measures need to be developed and improved to reduce this burden.

Performance of Thermal-Oxidative Aging on the Structure and Properties of Ethylene Propylene Diene Monomer (EPDM) Vulcanizates.

A thermal-oxidative aging test at 120 °C was conducted on ethylene propylene diene monomer (EPDM) vulcanizates of the semi-efficient vulcanization system. The effect of thermal-oxidative aging on EPDM vulcanizates was systematically studied by curing kinetics, aging coefficient, crosslinking density, macroscopic physical properties, contact angle, Fourier Transform Infrared Spectrometer (FTIR), Thermogravimetric analysis (TGA) and thermal decomposition kinetics. The results show that the content of hydroxyl and carbonyl groups as well as the carbonyl index increased with increasing aging time, indicating that EPDM vulcanizates were gradually oxidized and degraded. As a result, the EPDM vulcanized rubber chains were crosslinked with limited conformational transformation and weakened flexibility. The thermogravimetric analysis demonstrates that the thermal degradation of EPDM vulcanizates had competitive reactions of crosslinking and degradation, and the thermal decomposition curve can be divided into three stages; meanwhile, the thermal stability of EPDM vulcanizates gradually decreased with increasing aging time. The introduction of antioxidants in the system can promote the crosslinking speed and reduce the crosslinking density of EPDM vulcanizates while inhibiting the surface thermal and oxygen aging reaction. This was attributed to the fact that the antioxidant can reduce the thermal degradation reaction level, but it is not conducive to the formation of a perfect crosslinking network structure and reduces the activation energy of thermal degradation of the main chain.

Catalytic Decarboxylative Radical Sulfinylation.

Sulfoxides are ubiquitous in both naturally and synthetically bioactive molecules. We report herein a redox-neutral and mild approach for radical sulfinylation of redox-active esters via dual photoredox and copper catalysis, furnishing a series of functionalized sulfoxides. The reaction could accommodate a range of tertiary, secondary, and primary carboxylic acids, as well as exhibit wide functional group compatibility. The chemistry features a high degree of practicality, is scalable, and allows late-stage modification of bioactive pharmaceuticals.

Porcine Reproductive and Respiratory Syndrome Virus Modulates the Switch of Macrophage Polarization from M1 to M2 by Upregulating MoDC-Released sCD83.

Porcine reproductive and respiratory syndrome virus (PRRSV), the most economically important infectious disease of pigs, elicits poor innate and adaptive immune responses. Soluble CD83 (sCD83), a secretion from various immune cell populations, especially MoDCs, is involved in negatively regulating the immune response. We speculate sCD83 may be a critical factor in the process of PRRSV-coordinated macrophage polarization. In this study, we found that PAMs co-cultured with PRRSV-infected MoDCs inhibited the M1 macrophage while enhancing the M2 macrophage. This was accompanied by a decrease in the pro-inflammatory cytokine TNF-α and iNOS and an increase in the anti-inflammatory cytokine IL-10 and Arg1. Meanwhile, sCD83 incubation causes the same specific effects lead to a switch in macrophage from M1 to M2. Neutralization of sCD83 removes the inhibitory effects of PRRSV on PAMs. Using reverse genetics, we generated recombinant PRRSVs with mutations in N protein, nsp1α, and nsp10 (knockout sCD83-concerned key amino acid site). Four mutant viruses lost the suppression of M1 macrophage markers, in contrast to the restriction of the upregulation of M2 macrophage markers. These findings suggest that PRRSV modulates the switch of macrophage polarization from M1 to M2 by upregulating the MoDC-induced secretion of CD83, providing new insights into the mechanism by which PRRSV regulates host immunity.

The global burden of disease attributable to metabolic risks in 204 countries and territories from 1990 to 2019.

AIM: Our study aimed to survey the burden of disease attributed to metabolic risks (MRs) and secondary MR from 1990 to 2019. METHODS: Using methodological framework of the Global Burden of Disease Study 2019, we reported the global number, age-standardized rate and population attributable fraction of deaths and disability adjusted life years related to MRs and secondary MR. Furthermore, we analyzed the global burden caused by MRs and secondary MR in detail by gender, age, region, country, disease and Socio-demographic Index level. RESULTS: The number (million) of deaths and DALYs caused by MRs was 18.6 and 462.8 in 2019, with an increase of 43.6 % and 75.0 % since 1990. However, the ASR of deaths and DALYs attributed to MRs had a decrease of 23.3 % and 17.0 % since 1990. The burden caused by MRs and secondary MR raised with age, and the burden was the heaviest in low - and middle-income countries, especially in Middle East & North Africa. For diseases, the heaviest burden attributed to MRs was observed in ischemic heart disease, followed by stroke. CONCLUSION: The burden of disease attributed to MRs has continued to rise in the past 30 years, particularly for men and low-middle SDI regions. Therefore, the government should take corresponding actions to reduce the impact of MRs on population health.

Research on DUAL-ADGAN Model for Anomaly Detection Method in Time-Series Data.

In recent years, anomaly detection techniques in time-series data have been widely used in manufacturing, cybersecurity, and other fields. Meanwhile, various anomaly detection models based on generative adversarial networks (GAN) are gradually used in time-series anomaly detection tasks. However, there are problems of unstable generator training, missed detection of anomalous data, and inconsistency between the discriminator's discriminant and the anomaly detection target in GAN networks. Aiming at the above problems, the paper proposes a DUAL-ADGAN (Dual Anomaly Detection Generative Adversarial Networks) model for the detection of anomalous data in time series. First, the Wasserstein distance satisfying the Lipschitz constraint is used as the loss function of the data reconstruction module, which improves the stability of the traditional GAN network training. Second, by adding a data prediction module to the DUAL-ADGAN model, the distinction between abnormal and normal samples is increased, and the rate of missing abnormal data in the model is reduced. Third, by introducing the Fence-GAN loss function, the discriminator is aligned with the anomaly detection target, which effectively reduces the anomaly data false detection rate of the DUAL-ADGAN model. Finally, anomaly scores derived from the DUAL-ADGAN model are compared with dynamic thresholds to detect anomalies. The experimental results show that the average F1 of the DUAL-ADGAN model is 0.881, which is better than the other nine baseline models. The conclusions demonstrate that the DUAL-ADGAN model proposed in the paper is more stable in training while effectively solving the problems of anomaly miss detection and discriminator inconsistency with the anomaly detection target in the anomaly detection task.

Research on mobile traffic data augmentation methods based on SA-ACGAN-GN.

With the rapid development and application of the mobile Internet, it is necessary to analyze and classify mobile traffic to meet the needs of users. Due to the difficulty in collecting some application data, the mobile traffic data presents a long-tailed distribution, resulting in a decrease in classification accuracy. In addition, the original GAN is difficult to train, and it is prone to "mode collapse". Therefore, this paper introduces the self-attention mechanism and gradient normalization into the auxiliary classifier generative adversarial network to form SA-ACGAN-GN model to solve the long-tailed distribution and training stability problems of mobile traffic data. This method firstly converts the traffic into images; secondly, to improve the quality of the generated images, the self-attention mechanism is introduced into the ACGAN model to obtain the global geometric features of the images; finally, the gradient normalization strategy is added to SA-ACGAN to further improve the data augmentation effect and improve the training stability. It can be seen from the cross-validation experimental data that, on the basis of using the same classifier, the SA-ACGAN-GN algorithm proposed in this paper, compared with other comparison algorithms, has the best precision reaching 93.8%; after adding gradient normalization, during the training process of the model, the classification loss decreases rapidly and the loss curve fluctuates less, indicating that the method proposed in this paper can not only effectively improve the long-tail problem of the dataset, but also enhance the stability of the model training.

Network Anomaly Traffic Detection Algorithm Based on RIC-SC-DeCN.

In the research of network abnormal traffic detection, in view of the characteristics of high dimensionality and redundancy in traffic data and the loss of original information caused by the pooling operation in the convolutional neural network, which leads to the problem of unsatisfactory detection effect, this paper proposes a network abnormal traffic detection algorithm based on RIC-SC-DeCN to improve the above problems. Firstly, a recursive information correlation (RIC) feature selection mechanism is proposed, which reduces data redundancy through the maximum information correlation feature selection algorithm and recursive feature elimination method. Secondly, a skip-connected deconvolutional neural network model (SC-DeCN) is proposed to reduce the information loss by reconstructing the input signal. Finally, the RIC mechanism and the SC-DeCN model are merged to form a network abnormal traffic detection algorithm based on RIC-SC-DeCN. The experimental results on the CIC-IDS-2017 dataset show that the RIC feature selection mechanism proposed in this paper has the highest accuracy when using MSCNN as the detection model compared to the other three, which can reach 96.22%. Compared with the other five models, the SC-DeCN model has the highest detection accuracy, while the model training time is moderate and can reach 96.55%. Compared with the SC-DeCN model, the RIC-SC-DeCN model reduces the overall training time by 45.50%, while the accuracy rate is increased to 97.68%. It shows that the algorithm proposed in this paper has a good detection effect in the detection of network abnormal traffic.

Dynamic Structure of Yeast Septin by Fast Fluctuation-Enhanced Structured Illumination Microscopy.

When Saccharomyces cerevisiae divides, a structure composed of different septin proteins arranged according to a certain rule is formed at the cell division site. The structure undergoes multiple remodeling stages during the cell cycle, thus guiding the yeast cells to complete the entire division process. Although the higher-order structure of septins can be determined using electron microscopy, the septin's dynamic processes are poorly understood because of limitations in living cell super-resolution imaging technology. Herein, we describe a high lateral resolution and temporal resolution technique, known as fast fluctuation-enhanced structured illumination microscopy (fFE-SIM), which more than doubles the SIM resolution at a frame rate of 38 Hz in living cells. This allows a highly dynamic and sparse septin structure to be observed in Saccharomyces cerevisiae.

An Image Preprocessing Model of Coal and Gangue in High Dust and Low Light Conditions Based on the Joint Enhancement Algorithm.

The lighting facilities are affected due to conditions of coal mine in high dust pollution, which bring problems of dim, shadow, or reflection to coal and gangue images, and make it difficult to identify coal and gangue from background. To solve these problems, a preprocessing model for low-quality images of coal and gangue is proposed based on a joint enhancement algorithm in this paper. Firstly, the characteristics of coal and gangue images are analyzed in detail, and the improvement ways are put forward. Secondly, the image preprocessing flow of coal and gangue is established based on local features. Finally, a joint image enhancement algorithm is proposed based on bilateral filtering. In experimental, K-means clustering segmentation is used to compare the segmentation results of different preprocessing methods with information entropy and structural similarity. Through the simulation experiments for six scenes, the results show that the proposed preprocessing model can effectively reduce noise, improve overall brightness and contrast, and enhance image details. At the same time, it has a better segmentation effect. All of these can provide a better basis for target recognition.

An update on the emerging approaches for histone deacetylase (HDAC) inhibitor drug discovery and future perspectives.

INTRODUCTION: HDACs catalyze the removal of acetyl groups from the ε-N-acetylated lysine residues of various protein substrates including both histone and nonhistone proteins. Different HDACs have distinct biological functions and are recruited to specific regions of the genome. HDAC inhibitors have attracted much attention in recent decades; indeed, there have been more than thirty HDAC inhibitors investigated in clinic trials with five approvals being achieved. AREAS COVERED: This review covers the emerging approaches for HDAC inhibitor drug discovery from the past five years and includes discussion of structure-based rational design, isoform selectivity, and dual mechanism/multi-targeting. Chemical structures in addition to the in vitro and in vivo inhibiting activity of these compounds have also been discussed. EXPERT OPINION: The exact role and biological functions of HDACs is still under investigation with a variety of HDAC inhibitors having been designed and evaluated. HDAC inhibitors have shown promise in treating cancer, AD, metabolic disease, viral infection, and multiple sclerosis, but there is still a lot of room for clinical improvement. In the future, more efforts should be put into (i) HDAC isoform identification (ii) the optimization of selectivity, activity, and pharmacokinetics; and (iii) unconventional approaches for discovering different effective scaffolds and pharmacophores.

ß-Relaxation and Crystallization Behaviors in a Pulse-Current-Thermoplastic-Formed La-Based Bulk Metallic Glass.

We use the pulse current thermoplastic forming technique based on joule heating to rejuvenate the atomic structure of a La62Al14Ag2.34Ni10.83Co10.83 bulk metallic glass (BMG). The pulse-formed sample exhibits more pronounced ß-relaxation than the as-cast one due to the increased free volume. Instead, the sub-Tg annealing clearly weakens the ß-relaxation and also makes it more isolated from the α-relaxation, showing contributions from free volume and preferred structure. However, both treatments exhibit little influence on the following α-relaxation and high temperature crystallization kinetics. Our results open an effective way to rejuvenate the structure of BMGs and provide an in-depth understanding of the relationship between structural relaxations and crystallization kinetics of BMGs.