Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficient Design for Integrated Photonic Waveguides with Agile Dispersion

Chromatic dispersion engineering of photonic waveguide is of great importance for Photonic Integrated Circuit in broad applications, including on-chip CD compensation, supercontinuum generation, Kerr-comb generation, micro resonator and mode-locked laser. Linear propagation behavior and nonlinear effects of the light wave can be manipulated by engineering CD, in order to manipulate the temporal shape and frequency spectrum. Therefore, agile shapes of dispersion profiles, including typically wideband flat dispersion, are highly desired among various applications. In this study, we demonstrate a novel method for agile dispersion engineering of integrated photonic waveguide. Based on a horizontal double-slot structure, we obtained agile dispersion shapes, including broadband low dispersion, constant dispersion and slope-maintained linear dispersion. The proposed inverse design method is objectively-motivated and automation-supported. Dispersion in the range of 0–1.5 ps/(nm·km) for 861-nm bandwidth has been achieved, which shows superior performance for broadband low dispersion. Numerical simulation of the Kerr frequency comb was carried out utilizing the obtained dispersion shapes and a comb spectrum for 1068-nm bandwidth with a 20-dB power variation was generated. Significant potential for integrated photonic design automation can be expected.
BERT-Kcr: prediction of lysine crotonylation sites by a transfer learning method with pre-trained BERT models

MOTIVATION As one of the most important post-translational modifications (PTMs), protein lysine crotonylation (Kcr) has attracted wide attention, which involves in important physiological activities, such as cell differentiation and metabolism. However, experimental methods are expensive and time-consuming for Kcr identification. Instead, computational methods can predict Kcr sites in silico with high efficiency and low cost. RESULTS In this study, we proposed a novel predictor, BERT-Kcr, for protein Kcr sites prediction, which was developed by using a transfer learning method with pre-trained bidirectional encoder representations from transformers (BERT) models. These models were originally used for natural language processing (NLP) tasks, such as sentence classification. Here, we transferred each amino acid into a word as the input information to the pre-trained BERT model. The features encoded by BERT were extracted and then fed to a BiLSTM network to build our final model. Compared with the models built by other machine learning and deep learning classifiers, BERT-Kcr achieved the best performance with AUROC of 0.983 for 10-fold cross-validation. Further evaluation on the independent test set indicates that BERT-Kcr outperforms the state-of-the-art model Deep-Kcr with an improvement of about 5% for AUROC. The results of our experiment indicate that the direct use of sequence information and advanced pre-trained models of natural language processing could be an effective way for identifying post-translational modification sites of proteins. AVAILABILITY The BERT-Kcr model is publicly available on http://zhulab.org. cn/BERT-Kcr_models/. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Recent developments in systems biology and genetic engineering toward design of vaccines for TB

Abstract Tuberculosis (TB) is one of the most prevalent diseases worldwide. The currently available Bacillus Calmette-Guérin vaccine is not sufficient in protecting against pulmonary TB. Although many vaccines have been evaluated in clinical trials, but none of them yet has proven to be more successful. Thus, new strategies are urgently needed to design more effective TB vaccines. The emergence of new technologies will undoubtedly accelerate the process of vaccine development. This review summarizes the potential and validated applications of emerging technologies, including: systems biology (genomics, proteomics, and transcriptomics), genetic engineering, and other computational tools to discover and develop novel vaccines against TB. It also discussed that the significant implementation of these approaches will play crucial roles in the development of novel vaccines to cure and control TB.
A case series study of an innovative community-based brief psychological model for men in suicidal crisis

Abstract Objectives To conduct a 1-year evaluation of James’ Place, a suicidal crisis centre delivering a clinical intervention in a community setting. Design A case series study, following men entering the service during the first year of operation. Participants Men experiencing a suicidal crisis referred to the service (N = 265), with N = 176 going on to engage in therapy. Intervention The James’ Place Model is a therapeutic intervention offered to men who are in a suicidal crisis. Trained therapists provide a range of therapeutic approaches and interventions, focusing on decreasing suicidal distress and supporting men to develop resilience and coping strategies. Main outcome measures CORE-34 Clinical Outcome Measure (CORE-OM). Results For all subscales of the CORE-OM there was a significant reduction in mean scores between assessment and discharge (p < 0.001), with all outcomes demonstrating a large effect size. All reductions illustrated a clinically significant change or a reliable change. Conclusions Our results support the use of the James’ Place Model for men in suicidal distress to aid in potentially preventing suicides in this high-risk group of the population. Highlights Evaluates a brief psychological clinical intervention delivered in the community. Model effectively reduces suicide risk and findings can inform future services. Accessed men receiving an innovative intervention at the time of suicidal crisis.
NLRP3 inflammasome is involved in ambient PM2.5-related metabolic disorders in diabetic model mice but not in wild-type mice

Abstract Aims To explore the role of nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome in ambient fine particulate matter (PM2.5)-related metabolic disorders. Methods In this study, the C57BL/6 and db/db mice were exposed to concentrated PM2.5 or filtered air (FA) using Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) for 12 weeks. Indices of lipid metabolism, glucose metabolism, insulin sensitivity, and protein expression of NLRP3 inflammasome in visceral adipose tissue (VAT) were measured, respectively. Results The results showed that PM2.5 exposure increased circulatory insulin, triglycerides (TG), and total cholesterol (TC), and decreased high-density lipoprotein (HDL) in both C57BL/6 and db/db mice. The levels of NLRP3-related circulatory inflammatory cytokines including both interleukin (IL)-18 and IL-1β in serum were increased in the PM2.5-exposed mice and accompanied by the elevation in fasting blood glucose and insulin. The results also showed that exposure to PM2.5 promoted the activation of NLRP3, pro-caspase-1, caspase-1, and apoptosis-associated speck-like protein containing CARD (ASC), simultaneously accompanied by the increase of IL-18 and IL-1β expression in VAT, but the statistically significant difference only found in the db/db mice, not in C57BL/6 mice. Conclusion The activation of NLRP3 inflammasome might be not the main mechanism of PM2.5-related metabolic disorders in wide type mice but it partly mediated the exacerbation of metabolic disorders in diabetic model mice.
Cellular and Molecular Engineering of Glycan Sialylation in Heterologous Systems

Glycans have been shown to play a key role in many biological processes, such as signal transduction, immunogenicity, and disease progression. Among the various glycosylation modifications found on cell surfaces and in biomolecules, sialylation is especially important, because sialic acids are typically found at the terminus of glycans and have unique negatively charged moieties associated with cellular and molecular interactions. Sialic acids are also crucial for glycosylated biopharmaceutics, where they promote stability and activity. In this regard, heterogenous sialylation may produce variability in efficacy and limit therapeutic applications. Homogenous sialylation may be achieved through cellular and molecular engineering, both of which have gained traction in recent years. In this paper, we describe the engineering of intracellular glycosylation pathways through targeted disruption and the introduction of carbohydrate active enzyme genes. The focus of this review is on sialic acid-related genes and efforts to achieve homogenous, humanlike sialylation in model hosts. We also discuss the molecular engineering of sialyltransferases and their application in chemoenzymatic sialylation and sialic acid visualization on cell surfaces. The integration of these complementary engineering strategies will be useful for glycoscience to explore the biological significance of sialic acids on cell surfaces as well as the future development of advanced biopharmaceuticals.
Colchicine — From rheumatology to the new kid on the block: Coronary syndromes and COVID-19

Colchicine is an effective anti-inflammatory agent used to treat gout, coronary artery disease, viral pericarditis, and familial Mediterranean fever. It has been found to act by preventing the polymerization of the protein called tubulin, thus inhibiting inflammasome activation, proinflammatory chemokines, and cellular adhesion molecules. Accumulating evidence suggests that some patients with coronavirus disease 2019 (COVID-19) suffer from “cytokine storm” syndrome. The ideal anti-inflammatory in this setting would be one that is readily available, cheap, orally administered, with a good safety profile, well-tolerated, and that prevents or modulates inflammasome activation. The researchers selected colchicine for their study. This paper is a review of the literature describing the effects of colchicine, which is a drug that is being increasingly used, especially when standard therapy fails. Colchicine was shown to reduce inflammatory lung injury and respiratory failure by interfering with leukocyte activation and recruitment. In this publication, we try to systematically review the current data on new therapeutic options for colchicine. The article focuses on new data from clinical trials in COVID-19, rheumatic, cardiovascular, and other treatment such as familial Mediterranean fever, chronic urticaria, and PFAPA syndrome (periodic fever, aphthous, stomatitis, pharyngitis, and cervical adenitis). We also summarize new reports on the side effects, drug interactions, and safety of colchicine.
White Chocolate with Resistant Starch: Impact on Physical Properties, Dietary Fiber Content and Sensory Characteristics

Resistant starch (RS) is a part of insoluble dietary fiber, and it could be recognized as a functional food ingredient in some types of confectionery products that lack dietary fiber. Unlike dark and milk chocolate, white chocolate does not contain fat-free cocoa solids rich in dietary fiber. In the present study, 5%, 10%, and 15% of white chocolate were substituted with RS in order to improve the nutritional value of enriched white chocolate. The influence of RS on rheological, textural, and thermal properties of the chocolate fat phase was firstly investigated, and then further influence on physical properties, dietary fiber content, and sensory characteristics of enriched white chocolates were investigated. The obtained results showed that enriched chocolates had increased content of total dietary fiber and reduced total fats and protein content in accordance with the added amount of RS. At the same time, RS increased viscosity and reduced the hardness and volume mean diameter in enriched chocolates in accordance with the added amount. RS improved the nutritional composition of white chocolate by increasing the content of dietary fiber. At the same time, RS did not impair the color and sensory characteristics of enriched white chocolates.
Bioequivalence and Food Effect Assessment of 2 Rivaroxaban Formulations in Healthy Chinese Volunteers: An Open, Randomized, Single‐Dose, and 4‐Period Crossover Study

Rivaroxaban is a direct factor Xa inhibitor used for the management of thromboembolic disorders. The aim of this study was to evaluate the safety, pharmacokinetic profile, and bioequivalence of a generic and a branded rivaroxaban formulation (Xarelto) under fasted and fed conditions in healthy Chinese volunteers. An open‐label, randomized, single‐dose, 4‐period complete, and replicate crossover study in healthy Chinese volunteers was performed. A single oral dose of 20 mg of 2 rivaroxaban formulations was administered to 72 healthy volunteers, with 36 in the fasted group and 36 consuming a high‐fat diet. The evaluated pharmacokinetic parameters, including maximum rivaroxaban concentration, the area under the concentration‐time curve (AUC) from time 0 to the last measurable concentration, and AUC from time 0 to infinity, were assessed for BE. The plasma concentrations of rivaroxaban were measured by a validated liquid chromatography–tandem mass spectrometry method. The geometric mean ratios with 90% confidence intervals of the maximum rivaroxaban concentration, AUC from time 0 to the last measurable concentration, and AUC from time 0 to infinity were all within the range of 80% to 125% under fasted and fed conditions. The within‐subject variability of the test and reference products was compared, and the upper limit of the 90% confidence intervals for the test‐to‐reference ratio of the within‐subject variability was <2.5, which indicated that the rivaroxaban test and the rivaroxaban reference formulation were bioequivalent. No serious adverse events were reported during either fasted or fed conditions of the study.
Cost-effectiveness of tapentadol immediate release versus oxycodone immediate release for acute post-operative pain after major hip surgeries

Abstract Objective To evaluate the cost-effectiveness of tapentadol immediate-release (IR) versus oxycodone IR for post-operative pain after a major hip surgery. Methods This study has been conducted using an Australian societal perspective, focusing on adult patients after a major hip surgery. A cost-effectiveness analysis was conducted using a decision-analytic model. The model incorporated drug and other resource costs, the probability of opioid-related adverse events, and quality-adjusted life months (QALM) in each treatment arm. A willingness to pay (WTP) threshold of AU$2500 was used per QALM gained. A probabilistic sensitivity analysis was conducted to examine the uncertainty of the assumptions. The primary outcome was the incremental cost-effectiveness ratio (ICER) of tapentadol IR versus oxycodone IR, expressed as Australian dollars (AU$) per QALM gained. Results Tapentadol IR dominated oxycodone IR, with a cost savings of AU$201 and an increase in QALM by 0.014. The ICER was −13,946 AU$/QALM (negative value attributed to numerator). In the probabilistic sensitivity analysis, 84.2% of the simulations were in favour of tapentadol IR at the WTP threshold. Conclusions Tapentadol IR may be more cost-effective than oxycodone IR for the treatment of acute postoperative pain after major hip surgeries.
An Incremental Class-Learning Approach with Acoustic Novelty Detection for Acoustic Event Recognition

Acoustic scene analysis (ASA) relies on the dynamic sensing and understanding of stationary and non-stationary sounds from various events, background noises and human actions with objects. However, the spatio-temporal nature of the sound signals may not be stationary, and novel events may exist that eventually deteriorate the performance of the analysis. In this study, a self-learning-based ASA for acoustic event recognition (AER) is presented to detect and incrementally learn novel acoustic events by tackling catastrophic forgetting. The proposed ASA framework comprises six elements: (1) raw acoustic signal pre-processing, (2) low-level and deep audio feature extraction, (3) acoustic novelty detection (AND), (4) acoustic signal augmentations, (5) incremental class-learning (ICL) (of the audio features of the novel events) and (6) AER. The self-learning on different types of audio features extracted from the acoustic signals of various events occurs without human supervision. For the extraction of deep audio representations, in addition to visual geometry group (VGG) and residual neural network (ResNet), time-delay neural network (TDNN) and TDNN based long short-term memory (TDNN–LSTM) networks are pre-trained using a large-scale audio dataset, Google AudioSet. The performances of ICL with AND using Mel-spectrograms, and deep features with TDNNs, VGG, and ResNet from the Mel-spectrograms are validated on benchmark audio datasets such as ESC-10, ESC-50, UrbanSound8K (US8K), and an audio dataset collected by the authors in a real domestic environment.
Crazing Effect on the Bio-Based Conducting Polymer Film

The biodegradability problem of polymer waste is one of the fatal pollutFions to the environment. Enzymes play an essential role in increasing the biodegradability of polymers. In a previous study, antistatic polymer film based on poly(lactic acid) (PLA) as a matrix and polyaniline (PAni) as a conductive filler, was prepared. To solve the problem of polymer wastes pollution, a crazing technique was applied to the prepared polymer film (PLA/PAni) to enhance the action of enzymes in the biodegradation of polymer. This research studied the biodegradation test based on crazed and non-crazed PLA/PAni films by enzymes. The presence of crazes in PLA/PAni film was evaluated using an optical microscope and scanning electron microscopy (SEM). The optical microscope displayed the crazed in the lamellae form, while the SEM image revealed microcracks in the fibrils form. Meanwhile, the tensile strength of the crazed PLA/PAni film was recorded as 19.25 MPa, which is almost comparable to the original PLA/PAni film with a tensile strength of 20.02 MPa. However, the Young modulus decreased progressively from 1113 MPa for PLA/PAni to 651 MPa for crazed PLA/PAni film, while the tensile strain increased 150% after crazing. The significant decrement in the Young modulus and increment in the tensile strain was due to the craze propagation. The entanglement was reduced and the chain mobility along the polymer chain increased, thus leading to lower resistance to deformation of the polymer chain and becoming more flexible. The presence of crazes in PLA/PAni film showed a substantial change in weight loss with increasing the time of degradation. The weight loss of crazed PLA/PAni film increased to 42%, higher than that of non-crazed PLA/PAni film with only 31%. The nucleation of crazes increases the fragmentation and depolymerization of PLA/PAni film that induced microbial attack and led to higher weight loss. In conclusion, the presence of crazes in PLA/PAni film significantly improved enzymes’ action, speeding up the polymer film’s biodegradability.
A Dynamically Correlated Network Model for the Collective Dynamics in Glass-Forming Molecular Liquids and Polymers

The non-Arrhenius behavior of segmental dynamics in glass-forming liquids is one of the most profound mysteries in soft matter physics. In this article, we propose a dynamically correlated network (DCN) model to understand the growing behavior of dynamically correlated regions during cooling, which leads to the viscous slowdown of supercooled liquids. The fundamental concept of the model is that the cooperative region of collective motions has a network structure that consists of string-like parts, and networks of various sizes interpenetrate each other. Each segment undergoes dynamical coupling with its neighboring segments via a finite binding energy. Monte Carlo simulations showed that the fractal dimension of the DCNs generated at different temperatures increased and their size distribution became broader with decreasing temperature. The segmental relaxation time was evaluated based on a power law with four different exponents for the activation energy of rearrangement with respect to the DCN size. The results of the present DCN model are consistent with the experimental results for various materials of molecular and polymeric liquids.
Regulation of Hepatitis B Virus Virion Release and Envelopment Timing by Nucleocapsid and Envelope Interactions

Hepatitis B virus (HBV) is a major human pathogen causing serious liver diseases, including cancer. Interactions between the HBV capsid and the large (L) envelope protein are required for formation of infectious viral particles and also negatively regulate formation of an HBV DNA episome in the host cell nucleus, which serves as the sole transcriptional template capable of supporting all viral gene expression to sustain HBV replication and, therefore, is the molecular basis of HBV persistence. ABSTRACT Interactions between the N-terminal (assembly) domain (NTD), the linker region of the hepatitis B virus (HBV) capsid protein, and the large (L) envelope protein are required for virion formation, which occurs via budding of cytoplasmic mature nucleocapsids (NCs) containing the relaxed circular (RC) DNA genome into an intracellular membrane compartment containing viral envelope proteins. L-capsid interactions also negatively regulate covalently closed circular (CCC) DNA formation, which occurs after RC DNA release from mature NCs and nuclear import. We have now found that L could increase RC DNA in cytoplasmic mature NCs that are destabilized due to mutations in the NTD or the linker, even in those that apparently fail to support secretion of complete virions extracellularly. Other mutations in the capsid linker could block the effects of L on both cytoplasmic NC DNA and nuclear CCC DNA. Furthermore, the maturity of RC DNA in cytoplasmic NCs that was enhanced by L or found in secreted virions was modulated by the capsid linker sequence. The level and maturity of the cytoplasmic RC DNA were further influenced by the efficiency of extracellular virion secretion dependent on viral genotype-specific envelope proteins. These results suggest that interactions between the capsid and envelope proteins regulate one or more steps during virion secretion beyond initial capsid envelopment and highlight the critical role of the capsid linker in regulating capsid-envelope interaction, including the timing of envelopment during NC maturation. IMPORTANCE Hepatitis B virus (HBV) is a major human pathogen causing serious liver diseases, including cancer. Interactions between the HBV capsid and the large (L) envelope protein are required for formation of infectious viral particles and also negatively regulate formation of an HBV DNA episome in the host cell nucleus, which serves as the sole transcriptional template capable of supporting all viral gene expression to sustain HBV replication and, therefore, is the molecular basis of HBV persistence. Here, we report evidence indicating that L-capsid interactions modulate the timing of formation of infectious HBV particles during replication and facilitate extracellular release following their formation. Furthermore, a short linker sequence in the capsid protein plays a critical role in these processes as well as controls the amplification of the nuclear episome. These findings inform fundamental mechanisms of HBV replication as well as antiviral development targeting the HBV capsid and DNA episome.