From 60% to 5% in 12 Weeks: A Trastuzumab-Induced Left Ventricular Ejection Fraction Drop.

Trastuzumab is the first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, trastuzumab is associated with cardiotoxicity. It manifests with an asymptomatic reduction of left ventricular ejection fraction (LVEF) and is reversible after discontinuation. Trastuzumab-induced new-onset acute decompensated heart failure is rare (0.5%). We report a case of a 54-year-old woman who received anthracycline (idarubicin, accumulated dose 400 mg/m2 doxorubicin equivalent) for her acute promyelocytic leukocyte 10 years ago, had no relevant comorbidities or other pre-existing cardiovascular diseases, had maintained normal cardiac function, presenting with new-onset dyspnea at rest and bilateral lower extremities swelling 12 weeks after receiving trastuzumab induction chemotherapy for her newly diagnosed early stage HER2-positive breast cancer. Chest X-ray showed severe pulmonary edema. Echocardiography revealed diffuse left ventricular hypokinesis with LVEF 5%. After other possible etiology of cardiomyopathy, including ischemia, infection, substance, or radiation, were excluded by extensive cardiomyopathy workup, a diagnosis of trastuzumab-induced cardiotoxicity was established. Trastuzumab was discontinued, and the patient's symptom was improved with furosemide. Guildline-directed medical therapy was gradually maximized over three months. Repeat transthoracic echocardiography (TTE) at one-year follow-up after the initial diagnosis shows LVEF 33%, and the patient was referred to an advanced heart failure clinic. This case report demonstrated a rare catastrophic cardiac toxicity effect of trastuzumab and its potential association with remote exposure to anthracycline. Studies have investigated the cardiotoxicity in the concurrent use of trastuzumab and anthracycline therapy. However, how trastuzumab affected patients who were exposed to anthracycline for more than eight years had remained unreported. To our knowledge, no previous detailed case report has described the same clinical scenario as in this case. The case also demonstrates the limitation of the commonly used cardio-oncology cardiovascular risk assessment tool and highlights the importance of individualized cardiovascular risk stratification when deciding on chemotherapy plans.

Development and validation of the osteoporosis scale among the system of quality of life instruments for chronic diseases QLICD-OS (V2.0).

BACKGROUND: Quality of life of osteoporosis patients had caused widespread concern, due to high incidence and difficulty to cure. Scale specifics for osteoporosis and suitable for Chinese cultural background lacked. This study aimed to develop an osteoporosis scale in Quality of Life Instruments for Chronic Diseases system, namely QLICD-OS (V2.0). METHODS: Procedural decision-making approach of nominal group, focus group and modular approach were adopted. Our scale was developed based on experience of establishing scales at home and abroad. In this study, Quality of life measurements were performed on 127 osteoporosis patients before and after treatment to evaluate the psychometric properties. Validity was evaluated by qualitative analysis, item-domain correlation analysis, multi-scaling analysis and factor analysis; the SF-36 scale was used as criterion to carry out correlation analysis for criterion-related validity. The reliability was evaluated by the internal consistency coefficients Cronbach's α, test-retest reliability Pearson correlation r. Paired t-tests were performed on data of ​​the scale before and after treatment, with Standardized Response Mean (SRM) being calculated to evaluate the responsiveness. RESULTS: The QLICD-OS, composed of a general module (28 items) and an osteoporosis-specific module (14 items), had good content validity. Correlation analysis and factor analysis confirmed the construct, with the item having a strong correlation (most > 0.40) with its own domains/principle components, and a weak correlation (< 0.40) with other domains/principle components. Correlation coefficient between the similar domains of QLICD-OS and SF-36 showed reasonable criterion-related validity, with all coefficients r being greater than 0.40 exception of physical function of SF-36 and physical domain of QLICD-OS (0.24). Internal consistency reliability of QLICD-OS in all domains was greater than 0.7 except the specific module. The test-retest reliability coefficients (Pearson r) in all domains and overall score are higher than 0.80. Score changes after treatment were statistically significant, with SRM ranging from 0.35 to 0.79, indicating that QLICD-OS could be rated as medium responsiveness. CONCLUSION: As the first osteoporosis-specific quality of life scale developed by the modular approach in China, the QLICD-OS showed good reliability, validity and medium responsiveness, and could be used to measure quality of life in osteoporosis patients.

Understanding the Impact of Communicating Uncertainty About COVID-19 in the News: Randomized Between-Subjects Factorial Experiment.

BACKGROUND: Whether and how the uncertainty about a public health crisis should be communicated to the general public have been important and yet unanswered questions arising over the past few years. As the most threatening contemporary public health crisis, the COVID-19 pandemic has renewed interest in these unresolved issues by both academic scholars and public health practitioners. OBJECTIVE: The aim of this study was to investigate the impact of communicating uncertainty about COVID-19-related threats and solutions on individuals' risk perceptions and misinformation vulnerability, as well as the sequential impact of these effects on health information processing and preventative behavioral intentions. METHODS: A 2×2 (threat uncertainty [presence vs absence]×solution uncertainty [presence vs absence]) full-fractional between-subjects online experiment was conducted with 371 Chinese adults. Focusing on the discussion of whether the asymptomatic cases detected during the COVID-19 pandemic would further lead to an uncontrolled pandemic, news articles were manipulated in terms of whether the infectiousness of asymptomatic cases and the means to control the transmission are presented in terms of their certainty or uncertainty. Participants were randomly assigned to one of the four experimental conditions, being instructed to read one news article. After reading the news article assigned, participants were asked to respond to a series of questions to assess their cognitive and behavioral responses. RESULTS: Individuals were more susceptible to believing false COVID-19-related information when a certain threat and uncertain solution were framed in the news article. Moreover, individuals' perceptions of crisis severity increased when exposed to news information containing uncertain solutions. Both misinformation vulnerability and perceived severity were positively associated with information processing. Information seeking was positively associated with protective behavioral intention, whereas information avoidance was negatively associated with protective behavioral intention. CONCLUSIONS: Our findings imply that uncertainty, depending on its aspect, can be effectively communicated to the public during an emerging public health crisis. These results have theoretical and practical implications for health communicators and journalists. Given its limited influence on individuals' cognitive and behavioral responses, uncertainty related to a health threat should be disseminated to meet the public's expectation of information transparency. However, caution is advised when communicating uncertainty related to potential solutions, as this factor exhibited a mixed impact on individual responses during a crisis.

Effective cryopreservation of human brain tissue and neural organoids.

Human brain tissue models and organoids are vital for studying and modeling human neurological disease. However, the high cost of long-term cultured organoids inhibits their wide-ranging application. It is therefore urgent to develop methods for the cryopreservation of brain tissue and organoids. Here, we establish a method using methylcellulose, ethylene glycol, DMSO, and Y27632 (termed MEDY) for the cryopreservation of cortical organoids without disrupting the neural cytoarchitecture or functional activity. MEDY can be applied to multiple brain-region-specific organoids, including the dorsal/ventral forebrain, spinal cord, optic vesicle brain, and epilepsy patient-derived brain organoids. Additionally, MEDY enables the cryopreservation of human brain tissue samples, and pathological features are retained after thawing. Transcriptomic analysis shows that MEDY can protect synaptic function and inhibit the endoplasmic reticulum-mediated apoptosis pathway. MEDY will enable the large-scale and reliable storage of diverse neural organoids and living brain tissue and will facilitate wide-ranging research, medical applications, and drug screening.

Comparative Analysis of the Expression Patterns of TM9SF Family Members in Mice.

Transmembrane 9 superfamily proteins (TM9SFs) define a highly conserved protein family, each member of which is characterized by a variable extracellular domain and presumably nine transmembrane domains. Although previous studies have delineated the potential cytological roles of TM9SFs like autophagy and secretory pathway, their functions during development are largely unknown. To establish the basis for dissecting the functions of TM9SFs in vivo, we employed the open-source database, structure prediction, immunofluorescence and western blot to describe the gene and protein expression patterns of TM9SFs in human and mouse. While TM9SFs are ubiquitously and homogeneously expressed in all tissues in human with RNA sequencing and proteomics analysis, we found that all mice Tm9sf proteins are preferentially expressed in lung except Tm9sf1 which is enriched in brain although they all distributed in various tissues we examined. In addition, we further explored their expression patterns in the mice central nervous system (CNS) and its extension tissue retina. Interestingly, we could show that Tm9sf1is developmentally up-regulated in brain. In addition, we also detected all Tm9sf proteins are located in neurons and microglia instead of astrocytes. Importantly, Tm9sf3 is localized in the nuclei which is distinct from the other members that are dominantly targeted to the plasma membrane/cytoplasm as expected. Finally, we also found that Tm9sf family members are broadly expressed in the layers of INL, OPL, and GCL of retina and likely targeted to the plasma membrane of retinal cells. Thus, our data provided a comprehensive overview of TM9SFs expression patterns, illustrating their ubiquitous roles in different organs, implying the possible roles of Tm9sf2/3/4 in lung functions and Tm9sf1 in neurodevelopment, and highlighting a unique cell biological functions of TM9SF3 in neuronal and microglia.

Vaporization of perfluorocarbon attenuates sea-water-drowning-induced acute lung injury by deactivating the NLRP3 inflammasomes in canines.

Seawater-drowning-induced acute lung injury (SD-ALI) is a life-threatening disorder characterized by increased alveolar-capillary permeability, an excessive inflammatory response, and refractory hypoxemia. Perfluorocarbons (PFCs) are biocompatible compounds that are chemically and biologically inert and lack toxicity as oxygen carriers, which could reduce lung injury in vitro and in vivo. The aim of our study was to explore whether the vaporization of PFCs could reduce the severity of SD-ALI in canines and investigate the underlying mechanisms. Eighteen beagle dogs were randomly divided into three groups: the seawater drowning (SW), perfluorocarbon (PFC), and control groups. The dogs in the SW group were intratracheally administered seawater to establish the animal model. The dogs in the PFC group were treated with vaporized PFCs. Probe-based confocal laser endomicroscopy (pCLE) was performed at 3 h. The blood gas, volume air index (VAI), pathological changes, and wet-to-dry (W/D) lung tissue ratios were assessed. The expression of heme oxygenase-1 (HO-1), nuclear respiratory factor-1 (NRF1), and NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasomes was determined by means of quantitative real-time polymerase chain reaction (qRT-PCR) and immunological histological chemistry. The SW group showed higher lung injury scores and W/D ratios, and lower VAI compared to the control group, and treatment with PFCs could reverse the change of lung injury score, W/D ratio and VAI. PFCs deactivated NLRP3 inflammasomes and reduced the release of caspase-1, interleukin-1ß (IL-1ß), and interleukin-18 (IL-18) by enhancing the expression of HO-1 and NRF1. Our results suggest that the vaporization of PFCs could attenuate SD-ALI by deactivating NLRP3 inflammasomes via the HO-1/NRF1 pathway.

Safety and effectiveness of the sutureless integrated stented graft prosthesis in an animal model.

Background: Prolonged circulatory arrest time is an independent risk factor for postoperative adverse events of type A aortic dissection (TAAD) surgery. Further reduction of the circulatory arrest time is essential to improve surgical outcomes. This study aimed to evaluate the safety and effectiveness of the novel Sutureless Integrated Stented (SIS) graft prosthesis in an animal experiment. Materials and methods: Straight type of the SIS graft prosthesis was implanted into the descending aorta of 10 adult male sheep, and the use of the device was scored on a scale of 1-10. Aortic digital subtraction angiography (DSA) was performed at 4, 14, and 26 weeks to investigate the prostheses. After 26 weeks, the animals were sacrificed for histological analysis. Results: The immediate success rate of the surgery was 100 %, and the overall mean score of the use of the device was 9.65 ± 0.99. Three animals died from non-device-related causes during follow-up. Aortic DSA showed filling defects in 5 animals. Histological analysis revealed that all prostheses were intact. Except for 2 early deaths, the other 8 prostheses were endothelialized with mild inflammation, foreign body reactions, and intimal fibrosis. The mean cross-sectional area of the sutureless region was reduced by 26.4 % (range, 1.3-39.1 %). Conclusions: The safety and effectiveness of the novel SIS graft prosthesis were acceptable, and the delivery system exhibited a promising performance. Using the SIS graft prosthesis in TAAD surgery was expected to simplify the procedures and shorten the circulatory arrest time. Further large-scale clinical trials are required to verify these findings.

Optimal channel dynamic selection for Constructing lightweight Data EEG-based emotion recognition.

At present, most methods to improve the accuracy of emotion recognition based on electroencephalogram (EEG) are achieved by means of increasing the number of channels and feature types. This is to use the big data to train the classification model but it also increases the code complexity and consumes a large amount of computer time. We propose a method of Ant Colony Optimization with Convolutional Neural Networks and Long Short-Term Memory (ACO-CNN-LSTM) which can attain the dynamic optimal channels for lightweight data. First, transform the time-domain EEG signal to the frequency domain by Fast Fourier Transform (FFT), and the Differential Entropy (DE) of the three frequency bands (α, ß and γ) are extracted as the feature data; Then, based on the DE feature dataset, ACO is employed to plan the path where the electrodes are located in the brain map. The classification accuracy of CNN-LSTM is used as the objective function for path determination, and the electrodes on the optimal path are used as the optimal channels; Next, the initial learning rate and batchsize parameters are exactly matched the data characteristics, which can obtain the best initial learning rate and batchsize; Finally, the SJTU Emotion EEG Dataset (SEED) dataset is used for emotion recognition based on the ACO-CNN-LSTM. From the experimental results, it can be seen that: the average accuracy of three-classification (positive, neutral, negative) can achieve 96.59 %, which is based on the lightweight data by means of ACO-CNN-LSTM proposed in the paper. Meanwhile, the computer time consumed is reduced. The computational efficiency is increased by 15.85 % compared with the traditional CNN-LSTM method. The accuracy can achieve more than 90 % when the data volume is reduced to 50 %. In summary, the proposed method of ACO-CNN-LSTM in the paper can get higher efficiency and accuracy.

CARMIL1 regulates liver cancer cell proliferation by activating the ERK/mTOR pathway through the TRIM27/p53 axis.

Capping protein regulatory factor and myosin 1 linker 1 is termed CARMIL1. CARMIL1 is involved in several physiological processes; it forms an actin filament network and plasma membrane-bound cellular projection tissues and positively regulates the cellular components and tissues. CARMIL1 exhibits important biological functions in cancer; nonetheless, these functions have not been completely explored. We aimed to investigate the novel functions of CARMIL1 in liver cancer, particularly in cell proliferation. The cell counting kit-8, 5-ethynyl-2'-deoxyuridine, Component A experiments, and subcutaneous tumor formation model suggest that CARMIL1 is central to the proliferation of liver cancer cells both in vivo and in vitro. We extracted CARMIL1 samples from The Cancer Genome Atlas Program and analyzed its enrichment. CARMIL1 regulated the pathway activity by affecting the expression of star molecular proteins of the extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR). Moreover, it influenced the proliferation ability of liver cancer cells. Western blotting suggested that CARMIL1 downregulation could affect ERK and mTOR phosphorylation. Results of the co-immunoprecipitation demonstrated that CARMIL1 binds to tripartite motif (TRIM)27, which in turn binds to p53. Subsequently, CARMIL1 can regulate p53 stability and promote its degradation through TRIM27. Additionally, CARMIL1 inhibition enhanced the sensitivity of liver cancer cells to sorafenib. Tumor growth was significantly inhibited in the group treated with sorafenib and CARMIL1, compared with the group treated with CARMIL1 alone. Sorafenib is a first-line targeted chemotherapeutic drug for hepatocellular carcinoma treatment. It increases the long-term survival of hepatocellular carcinoma by 44%. In this study, downregulated CARMIL1 combined with sorafenib significantly reduced the tumor volume and weight of the mouse subcutaneous tumor model, indicating the potential possibility of combining CARMIL1 with sorafenib in hepatocellular carcinoma treatment. In summary, CARMIL1 promotes liver cancer cell proliferation by regulating the TRIM27/p53 axis and activating the ERK/mTOR pathway.

Association Between Sleep Quality and Cognitive Symptoms in Patients with Major Depressive Disorder.

Cognitive symptoms and sleep disturbance (SD) are common non-mood-related symptoms of major depressive disorder (MDD). In clinical practice, both cognitive symptoms and SD are related to MDD progression. However, there are only a few studies investigating the connection between cognitive symptoms and SD in patients with MDD, and only preliminary evidence suggests a significant association between cognitive symptoms and SD in patients with mood disorders. This study investigates the relationship between cognitive symptoms and sleep quality in patients with major depressive disorder. Patients (n = 20) with MDD were enrolled; their mean Hamilton Depression Scale-17 score was 21.95 (±2.76). Gold standard polysomnography (PSG) was used to assess sleep quality, and the validated THINC-integrated tool (the cognitive screening tool) was used to evaluate cognitive function in MDD patients. Overall, the results showed significant correlations between the cognitive screening tool's total score and sleep latency, wake-after-sleep onset, and sleep efficiency. These findings indicate that cognitive symptoms are associated with poor sleep quality among patients with MDD.

High-efficiency and economical uranium extraction from seawater with easily prepared supramolecular complexes.

Developing effective adsorbents for uranium extraction from natural seawater is strategically significant for the sustainable fuel supply of nuclear energy. Herein, stable and low-cost supramolecular complexes (PA-bPEI complexes) were facilely constructed through the assembly of phytic acid and hyperbranched polyethyleneimine based on the multiple modes of electrostatic interaction and hydrogen bonding. The PA-bPEI complexes exhibited not only high uptake (841.7 mg g-1) and selectivity (uranium/vanadium selectivity = 84.1) toward uranium but also good antibacterial ability against biofouling. Mechanism analysis revealed that phosphate chelating groups and amine assistant groups coordinated the uranyl ions together with a high affinity. To be more suitable for practical applications, powdery PA-bPEI complexes were compounded with sodium alginate to fabricate various macroscopic adsorbents with engineered forms, which achieved an extraction capacity of 9.0 mg g-1 in natural seawater after 50 days of testing. Impressively, the estimated economic cost of the macroscopic adsorbent for uranium extraction from seawater ($96.5 âˆ¼ 138.1 kg-1 uranium) was lower than that of all currently available uranium adsorbents. Due to their good uranium extraction performance and low economic cost, supramolecular complex-based adsorbents show great potential for industrial uranium extraction from seawater.

Selected humanization of yeast U1 snRNP leads to global suppression of pre-mRNA splicing and mitochondrial dysfunction in the budding yeast.

The recognition of 5' splice site (5' ss) is one of the earliest steps of pre-mRNA splicing. To better understand the mechanism and regulation of 5' ss recognition, we selectively humanized components of the yeast U1 snRNP to reveal the function of these components in 5' ss recognition and splicing. We targeted U1C and Luc7, two proteins that interact with and stabilize the yeast U1 (yU1) snRNA and the 5' ss RNA duplex. We replaced the Zinc-Finger (ZnF) domain of yU1C with its human counterpart, which resulted in a cold-sensitive growth phenotype and moderate splicing defects. We next added an auxin-inducible degron to yLuc7 protein (to mimic the lack of Luc7Ls in human U1 snRNP) and found that Luc7-depleted yU1 snRNP resulted in the concomitant loss of PRP40 and Snu71 (two other essential yeast U1 snRNP proteins), and further biochemical analyses suggest a model of how these three proteins interact with each other in the U1 snRNP. The loss of these proteins resulted in a significant growth retardation accompanied by a global suppression of pre-mRNA splicing. The splicing suppression led to mitochondrial dysfunction as revealed by a release of Fe2+ into the growth medium and an induction of mitochondrial reactive oxygen species. Together, these observations indicate that the human U1C ZnF can substitute that of yeast, Luc7 is essential for the incorporation of the Luc7-Prp40-Snu71 trimer into yeast U1 snRNP, and splicing plays a major role in the regulation of mitochondrial function in yeast.

An abundant bacterial phylum with nitrite-oxidizing potential in oligotrophic marine sediments.

Nitrite-oxidizing bacteria (NOB) are important nitrifiers whose activity regulates the availability of nitrite and dictates the magnitude of nitrogen loss in ecosystems. In oxic marine sediments, ammonia-oxidizing archaea (AOA) and NOB together catalyze the oxidation of ammonium to nitrate, but the abundance ratios of AOA to canonical NOB in some cores are significantly higher than the theoretical ratio range predicted from physiological traits of AOA and NOB characterized under realistic ocean conditions, indicating that some NOBs are yet to be discovered. Here we report a bacterial phylum Candidatus Nitrosediminicolota, members of which are more abundant than canonical NOBs and are widespread across global oligotrophic sediments. Ca. Nitrosediminicolota members have the functional potential to oxidize nitrite, in addition to other accessory functions such as urea hydrolysis and thiosulfate reduction. While one recovered species (Ca. Nitrosediminicola aerophilus) is generally confined within the oxic zone, another (Ca. Nitrosediminicola anaerotolerans) additionally appears in anoxic sediments. Counting Ca. Nitrosediminicolota as a nitrite-oxidizer helps to resolve the apparent abundance imbalance between AOA and NOB in oxic marine sediments, and thus its activity may exert controls on the nitrite budget.

Adaptive Cruise Control Based on Safe Deep Reinforcement Learning.

Adaptive cruise control (ACC) enables efficient, safe, and intelligent vehicle control by autonomously adjusting speed and ensuring a safe following distance from the vehicle in front. This paper proposes a novel adaptive cruise system, namely the Safety-First Reinforcement Learning Adaptive Cruise Control (SFRL-ACC). This system aims to leverage the model-free nature and high real-time inference efficiency of Deep Reinforcement Learning (DRL) to overcome the challenges of modeling difficulties and lower computational efficiency faced by current optimization control-based ACC methods while simultaneously maintaining safety advantages and optimizing ride comfort. Firstly, we transform the ACC problem into a safe DRL formulation Constrained Markov Decision Process (CMDP) by carefully designing state, action, reward, and cost functions. Subsequently, we propose the Projected Constrained Policy Optimization (PCPO)-based ACC Algorithm SFRL-ACC, which is specifically tailored to solve the CMDP problem. PCPO incorporates safety constraints that further restrict the trust region formed by the Kullback-Leibler (KL) divergence, facilitating DRL policy updates that maximize performance while keeping safety costs within their limit bounds. Finally, we train an SFRL-ACC policy and compare its computation time, traffic efficiency, ride comfort, and safety with state-of-the-art MPC-based ACC control methods. The experimental results prove the superiority of the proposed method in the aforementioned performance aspects.

Artificial Intelligence-Assisted Optimization of Antipigmentation Tyrosinase Inhibitors: De Novo Molecular Generation Based on a Low Activity Lead Compound.

Artificial intelligence (AI) de novo molecular generation is a highly promising strategy in the drug discovery, with deep reinforcement learning (RL) models emerging as powerful tools. This study introduces a fragment-by-fragment growth RL forward molecular generation and optimization strategy based on a low activity lead compound. This process integrates fragment growth-based reaction templates, while target docking and drug-likeness prediction were simultaneously performed. This comprehensive approach considers molecular similarity, internal diversity, synthesizability, and effectiveness, thereby enhancing the quality and efficiency of molecular generation. Finally, a series of tyrosinase inhibitors were generated and synthesized. Most compounds exhibited more improved activity than lead, with an optimal candidate compound surpassing the effects of kojic acid and demonstrating significant antipigmentation activity in a zebrafish model. Furthermore, metabolic stability studies indicated susceptibility to hepatic metabolism. The proposed AI structural optimization strategies will play a promising role in accelerating the drug discovery and improving traditional efficiency.

Thermal Stability and Crystallization Processes of Pd78Au4Si18 Thin Films Visualized via In Situ TEM.

Amorphous alloys or metallic glasses (MGs) thin films have attracted extensive attention in various fields due to their unique functional properties. Here, we use in situ heating transmission electron microscopy (TEM) to investigate the thermal stability and crystallization behavior of Pd-Au-Si thin films prepared by a pulsed laser deposition (PLD) method. Upon heating treatment inside a TEM, we trace the structural changes in the Pd-Au-Si thin films through directly recording high-resolution images and diffraction patterns at different temperatures. TEM observations reveal that the Pd-Au-Si thin films started to nucleate with small crystalline embryos uniformly distributed in the glassy matrix upon approaching the glass transition temperature Tg=625K, and subsequently, the growth of crystalline nuclei into sub-10 nm Pd-Si nanocrystals commenced. Upon further increasing the temperature to 673K, the thin films transformed to micro-sized patches of stacking-faulty lamellae that further crystallized into Pd9Si2 and Pd3Si intermetallic compounds. Interestingly, with prolonged thermal heating at elevated temperatures, the Pd9Si2 transformed to Pd3Si. Simultaneously, the solute Au atoms initially dissolved in glassy alloys and eventually precipitated out of the Pd9Si2 and Pd3Si intermetallics, forming nearly spherical Au nanocrystals. Our TEM results reveal the unique thermal stability and crystallization processes of the PLD-prepared Pd-Au-Si thin films as well as demonstrate a possibility of producing a large quantity of pure nanocrystals out of amorphous solids for various applications.

Goal-Guided Graph Attention Network with Interactive State Refinement for Multi-Agent Trajectory Prediction.

The accurate prediction of the future trajectories of traffic participants is crucial for enhancing the safety and decision-making capabilities of autonomous vehicles. Modeling social interactions among agents and revealing the inherent relationships is crucial for accurate trajectory prediction. In this context, we propose a goal-guided and interaction-aware state refinement graph attention network (SRGAT) for multi-agent trajectory prediction. This model effectively integrates high-precision map data and dynamic traffic states and captures long-term temporal dependencies through the Transformer network. Based on these dependencies, it generates multiple potential goals and Points of Interest (POIs). Through its dual-branch, multimodal prediction approach, the model not only proposes various plausible future trajectories associated with these POIs, but also rigorously assesses the confidence levels of each trajectory. This goal-oriented strategy enables SRGAT to accurately predict the future movement trajectories of other vehicles in complex traffic scenarios. Tested on the Argoverse and nuScenes datasets, SRGAT surpasses existing algorithms in key performance metrics by adeptly integrating past trajectories and current context. This goal-guided approach not only enhances long-term prediction accuracy, but also ensures its reliability, demonstrating a significant advancement in trajectory forecasting.

Dissecting the shared genetic landscape of anxiety, depression, and schizophrenia.

BACKGROUND: Numerous studies highlight the genetic underpinnings of mental disorders comorbidity, particularly in anxiety, depression, and schizophrenia. However, their shared genetic loci are not well understood. Our study employs Mendelian randomization (MR) and colocalization analyses, alongside multi-omics data, to uncover potential genetic targets for these conditions, thereby informing therapeutic and drug development strategies. METHODS: We utilized the Consortium for Linkage Disequilibrium Score Regression (LDSC) and Mendelian Randomization (MR) analysis to investigate genetic correlations among anxiety, depression, and schizophrenia. Utilizing GTEx V8 eQTL and deCODE Genetics pQTL data, we performed a three-step summary-data-based Mendelian randomization (SMR) and protein-protein interaction analysis. This helped assess causal and comorbid loci for these disorders and determine if identified loci share coincidental variations with psychiatric diseases. Additionally, phenome-wide association studies, drug prediction, and molecular docking validated potential drug targets. RESULTS: We found genetic correlations between anxiety, depression, and schizophrenia, and under a meta-analysis of MR from multiple databases, the causal relationships among these disorders are supported. Based on this, three-step SMR and colocalization analyses identified ITIH3 and CCS as being related to the risk of developing depression, while CTSS and DNPH1 are related to the onset of schizophrenia. BTN3A1, PSMB4, and TIMP4 were identified as comorbidity loci for both disorders. Molecules that could not be determined through colocalization analysis were also presented. Drug prediction and molecular docking showed that some drugs and proteins have good binding affinity and available structural data. CONCLUSIONS: Our study indicates genetic correlations and shared risk loci between anxiety, depression, and schizophrenia. These findings offer insights into the underlying mechanisms of their comorbidities and aid in drug development.

A highly efficient blocking ELISA based on p72 monoclonal antibody for the detection of African swine fever virus antibodies and identification of its linear B cell epitope.

Due to the absence of effective vaccine and treatment, African swine fever virus (ASFV) control is entirely dependent on accurate and early diagnosis, along with culling of infected pigs. The B646L/p72 is the major capsid protein of ASFV and is an important target for developing a diagnostic assays and vaccines. Herein, we generated a monoclonal antibody (mAb) (designated as 2F11) against the trimeric p72 protein, and a blocking ELISA (bELISA) was established for the detection of both genotype I and II ASFV antibodies. To evaluate the performance of the diagnostic test, a total of 506 porcine serum samples were tested. The average value of percent of inhibition (PI) of 133 negative pig serum was 8.4 % with standard deviation (SD) 6.5 %. Accordingly, the cut-off value of the newly established method was set at 28 % (mean + 3SD). Similarly, a receiver operating characteristic (ROC) was applied to determine the cut off value and the p72-bELISA exhibited a sensitivity of 100 % and a specificity of 99.33 % when the detection threshold was set at 28 %. The bELISA was also able to specifically recognize anti-ASFV sera without cross-reacting with other positive serums for other major swine pathogens. Moreover, by designing a series of overlapped p72 truncated proteins, the linear B cell epitope recognized by 2F11 mAb was defined to be 283NSHNIQ288. Amino acid sequence comparison revealed that the amino acid sequence 283NSHNIQ288 is highly conserved between different ASFV isolates. Our findings indicate that the newly established mAb based blocking ELISA may have a great potential in improving the detection of ASFV antibodies and provides solid foundation for further studies.