Bruton's tyrosine kinase ablation inhibits B cell responses and antibody production for the prevention of chronic rejection in cardiac transplantation.

Chronic rejection is the primary cause of late allograft failure, however, the current treatments for chronic rejection have not yielded desirable therapeutic effects. B cell activation and donor-specific antibody (DSA) production are the primary factors leading to chronic rejection. Bruton's tyrosine kinase (BTK) plays a key role in the activation and differentiation of B cells and in antibody production. This study investigated the efficacy of blocking BTK signalling in the prevention of chronic rejection. BTK signalling was blocked using the BTK inhibitor ibrutinib and gene knockout. In vitro assays were conducted to examine the consequences and underlying mechanisms of BTK blockade in regards to B cell activation, differentiation, and antibody secretion. Additionally, we established a cardiac transplantation mouse model of chronic rejection to explore the preventive effects and mechanisms of BTK ablation on chronic rejection. Ablating BTK signalling in vitro resulted in the inhibition of B cell activation, differentiation, and antibody production. In vivo experiments provided evidence that ablating BTK signalling alleviated chronic rejection, leading to reduced damage in myocardial tissue, neointimal hyperplasia, interstitial fibrosis, inflammatory cell infiltration, and C4d deposition. Allograft survival was prolonged, and B cell responses and DSA production were inhibited as a result. We confirmed that ablation of BTK signalling inhibited B cell response by blocking downstream PLCγ2 phosphorylation and inhibiting the NF-κB, NFAT, and ERK pathways. Our findings demonstrated that ablation of BTK signalling inhibited B cell activation and differentiation, reduced DSA production, and effectively prevented chronic rejection.

Nickel-Based Metal-Organic Frameworks Promote Diabetic Wound Healing via Scavenging Reactive Oxygen Species and Enhancing Angiogenesis.

Chronic diabetic wounds remain a worldwide challenge for both the clinic and research. Given the vicious circle of oxidative stress and inflammatory response as well as the impaired angiogenesis of the diabetic wound tissues, the wound healing process is disturbed and poorly responds to the current treatments. In this work, a nickel-based metal-organic framework (MOF, Ni-HHTP) with excellent antioxidant activity and proangiogenic function is developed to accelerate the healing process of chronic diabetic wounds. The Ni-HHTP can mimic the enzymatic catalytic activities of antioxidant enzymes to eliminate multi-types of reactive species through electron transfer reactions, which protects cells from oxidative stress-related damage. Moreover, this Ni-based MOF can promote cell migration and angiogenesis by activating transforming growth factor-ß1 (TGF-ß1) in vitro and reprogram macrophages to the anti-inflammatory phenotype. Importantly, Ni-HHTP effectively promotes the healing process of diabetic wounds by suppressing the inflammatory response and enhancing angiogenesis in vivo. This study reports a versatile and promising MOF-based nanozyme for diabetic wound healing, which may be extended in combination with other wound dressings to enhance the management of diabetic or non-healing wounds.

Non-heme Iron Single-Atom Nanozymes as Peroxidase Mimics for Tumor Catalytic Therapy.

Single-atom nanozymes (SAzymes) open new possibilities for the development of artificial enzymes that have catalytic activity comparable to that of natural peroxidase (POD). So far, most efforts have focused on the structural modulation of the Fe-N4 moiety to mimic the metalloprotein heme center. However, non-heme-iron POD with much higher activity, for example, HppE, has not been mimicked successfully due to its structural complexity. Herein, carbon dots (CDs)-supported SAzymes with twisted, nonplanar Fe-O3N2 active sites, highly similar to the non-heme iron center of HppE, was synthesized by exploiting disordered and subnanoscale domains in CDs. The Fe-CDs exhibit an excellent POD activity of 750 units/mg, surpassing the values of conventional SAzymes with planar Fe-N4. We further fabricated an activatable Fe-CDs-based therapeutic agent with near-infrared enhanced POD activity, a photothermal effect, and tumor-targeting ability. Our results represent a big step in the design of high-performance SAzymes and provide guidance for future applications for synergistic tumor therapy.

Unlocking the NIR-II AIEgen for High Brightness through Intramolecular Electrostatic Locking.

Fluorescent imaging and biosensing in the near-infrared-II (NIR-II) window holds great promise for non-invasive, radiation-free, and rapid-response clinical diagnosis. However, it's still challenging to develop bright NIR-II fluorophores. In this study, we report a new strategy to enhance the brightness of NIR-II aggregation-induced emission (AIE) fluorophores through intramolecular electrostatic locking. By introducing sulfur atoms into the side chains of the thiophene bridge in TSEH molecule, the molecular motion of the conjugated backbone can be locked through intramolecular interactions between the sulfur and nitrogen atoms. This leads to enhanced NIR-II fluorescent emission of TSEH in both solution and aggregation states. Notably, the encapsulated nanoparticles (NPs) of TSEH show enhanced brightness, which is 2.6-fold higher than TEH NPs with alkyl side chains. The in vivo experiments reveal the feasibility of TSEH NPs in vascular and tumor imaging with a high signal-to-background ratio and precise resection for tiny tumors. In addition, polystyrene nanospheres encapsulated with TSEH are utilized for antigen detection in lateral flow assays, showing a signal-to-noise ratio 1.9-fold higher than the TEH counterpart in detecting low-concentration antigens. This work highlights the potential for developing bright NIR-II fluorophores through intramolecular electrostatic locking and their potential applications in clinical diagnosis and biomedical research.

Using red blood cell distribution width to predict death after abdominal aortic aneurysm rupture.

BACKGROUND: An abdominal aortic aneurysm is a life-threatening enlargement in the major vessel at the abdomen level. This study investigated the associations between different levels of red blood cell distribution width and all-cause mortality among patients with abdominal aortic aneurysm rupture. It developed predictive models for all-cause mortality risk. METHODS: This was a retrospective cohort study using 2001 to 2012 MIMIC-III dataset. The study sample included 392 U.S. adults with abdominal aortic aneurysms who were admitted to ICU after the aneurysm rupture. Then we used two single-factor and four multivariable logistic regression models to examine the associations between different levels of red blood cell distribution and all-cause mortality (30 days and 90 days), controlling for demographics, comorbidities, vital signs, and other laboratory measurements. The receiver operator characteristic curves were calculated, and the areas under the curves were recorded. RESULTS: There were 140 (35.7%) patients with an abdominal aortic aneurysm in the red blood cell distribution width range between 11.7 and 13.8%, 117 (29.8%) patients in the range between 13.9 and 14.9%, and 135 (34.5%) patients in the range between 15.0 and 21.6%. Patients with higher red blood cell distribution width level (> 13.8%) tended to have a higher mortality rate (both 30 days and 90 days), congestive heart failure, renal failure, coagulation disorders, lower hemoglobin, hematocrit, MCV, red blood cell count, higher levels of chloride, creatinine, sodium, and BUN (All P < 0.05). Results of multivariate logistic regression models indicated that patients with higher red blood cell distribution width levels (> 13.8%) had the highest statistically significant odd ratios of 30 days and 90 days of all-cause mortality than lower red blood cell distribution width levels. The area under the RDW curve was lower (P = 0.0009) than that of SAPSII scores. CONCLUSIONS: Our study found that patients with abdominal aortic aneurysm rupture with a higher blood cell distribution had the highest risk of all-cause mortality. Using the blood cell distribution width level in patients with abdominal aortic aneurysm rupture to predict mortality should be considered in future clinical practice.

Identification, Screening and Antibacterial Mechanism Analysis of Novel Antimicrobial Peptides from Sturgeon (Acipenser ruthenus) Spermary.

Fish is an important source of antimicrobial peptides. This study aimed to identify and screen antibacterial peptides with excellent antibacterial activity derived from sturgeon spermary peptides (SSPs) and to analyze their antibacterial activity and mechanism. Liquid chromatography-mass spectrometry/mass spectrometry methods were used to analyze and identify peptide sequences, computational prediction tool and molecular docking methods were used for virtual screening of antimicrobial peptides, and finally, candidate peptides were synthesized by solid-phase synthesis method. The results demonstrate that SSPs have excellent inhibitory activity against Escherichia coli with an inhibitory rate of 76.46%. Most parts of the SSPs were derived from the sturgeon (Acipenser ruthenus) histones, and the coverage of histone H2B was the highest (45%). Two novel peptides (NDEELNKLM and RSSKRRQ) were obtained by in silico prediction tools and molecular docking, which may interact with the DNA gyrase and dihydrofolate reductase of E. coli by forming salt bridges and hydrogen bonds. Compared to the individual peptides, the antibacterial effect was significantly improved by mixing the two peptides in equal proportions. Two novel peptides change the permeability of the E. coli cell membranes and may exert antimicrobial activity by inhibiting the metabolic process of the nucleic acids.

Metabolomics and Proteomics Responses of Largemouth Bass (Micropterus salmoides) Muscle under Organic Selenium Temporary Rearing.

Organic selenium has been widely studied as a nutritional supplement for animal feed. However, there are few studies on the effect of organic selenium on flesh quality. In this study, the effects of organic selenium (yeast selenium (YS), Se 0.002 mg/L) on the metabolism and protein expression in Micropterus salmoides muscle under temporary fasting condition (6 weeks) were investigated. The muscle structure was observed through a microscope, and regulatory pathways were analyzed using proteomics and metabolomics methods. Electron microscopy showed that YS made the muscle fibers of M. salmoides more closely aligned. Differential analysis identified 523 lipid molecules and 268 proteins. The numbers of upregulated and downregulated proteins were 178 and 90, respectively, including metabolism (46.15%), cytoskeleton (11.24%) and immune oxidative stress (9.47%), etc. Integrated analyses revealed that YS enhanced muscle glycolysis, the tricarboxylic acid cycle and oxidative phosphorylation metabolism. In the YS group, the content of eicosapentaenoic acid was increased, and that of docosahexaenoic acid was decreased. YS slowed down protein degradation by downregulating ubiquitin and ubiquitin ligase expression. These results suggest that organic selenium can improve M. salmoides muscle quality through the aforementioned pathways, which provides potential insights into the improvement of the quality of aquatic products, especially fish.

Increased circulating sclerostin levels in rheumatoid arthritis patients: an updated meta-analysis.

BACKGROUND: Sclerostin, a regulator of bone metabolism and vascular calcification involved in regulating the Wnt/ß-catenin signaling pathway, has been shown to be involved in the pathogenesis of rheumatoid arthritis (RA). However, current results regarding the circulating sclerostin level of RA patients are debatable. This study aimed to evaluate the circulating level of sclerostin in RA patients and briefly summarize its role. METHOD: PubMed, EMBASE, and the Cochrane Library databases were systematically searched till May 27, 2021, for eligible articles. Useful data from all qualified papers were systematically extracted and analyzed using Stata 12.0 software (Stata Corp LP, College Station, TX, USA). RESULTS: Overall, 13 qualifying studies including 1030 cases and 561 normal controls were analyzed in this updated meta-analysis. Forest plot of this meta-analysis showed that RA patients had higher circulating sclerostin levels (P < 0.001, standardized mean difference [SMD] = 0.916, 95% CI: 0.235-1.597) compared to normal controls. Subgroup analyses implied that age, region, and assay method were associated with sclerostin level in RA patients. CONCLUSION: RA patients have higher circulating sclerostin levels, and these was influenced by age, region, and assay method.

A Joint Extraction Model for Entity Relationships Based on Span and Cascaded Dual Decoding.

The entity-relationship joint extraction model plays a significant role in entity relationship extraction. The existing entity-relationship joint extraction model cannot effectively identify entity-relationship triples in overlapping relationships. This paper proposes a new joint entity-relationship extraction model based on the span and a cascaded dual decoding. The model includes a Bidirectional Encoder Representations from Transformers (BERT) encoding layer, a relational decoding layer, and an entity decoding layer. The model first converts the text input into the BERT pretrained language model into word vectors. Then, it divides the word vectors based on the span to form a span sequence and decodes the relationship between the span sequence to obtain the relationship type in the span sequence. Finally, the entity decoding layer fuses the span sequences and the relationship type obtained by relation decoding and uses a bi-directional long short-term memory (Bi-LSTM) neural network to obtain the head entity and tail entity in the span sequence. Using the combination of span division and cascaded double decoding, the overlapping relations existing in the text can be effectively identified. Experiments show that compared with other baseline models, the F1 value of the model is effectively improved on the NYT dataset and WebNLG dataset.

Second near-infrared fluorescent dye for lateral flow immunoassays rapid detection of influenza A/B virus.

Sensitive and rapid diagnostic point of care testing (POCT) system is of great significance to prevent and control human virus infection. Here reported an immunochromatographic strip technology. The second near-infrared (NIR-II) fluorescent dye encapsulated into polystyrene (PS) nanoparticles, was integrated into a lateral flow assay platform to achieve excellent detection of influenza A/B. This surface-functionalized and mono-dispersed PS nanoparticles has been conjugated with influenza nucleoprotein monoclonal antibody as targets for influenza antigen-detection. This assay achieved the detection limit of 0.015 ng/mL for influenza A nucleoprotein and 4.3*10-5 HAU/mL (102.08 TCID50/mL) influenza A virus (influenza B: 0.037 ng/mL, 9.7*10-7 HAU/mL (100.43 TCID50/mL)). Compared with an Au-based lateral flow test strip, the strip's sensitivity is about 16-fold higher than it. Strip detection properties remain stable for 6 months under 4 °C to 30 °C storage. The assay's intra assay variation is 5.14% and the inter assay variation is 7.74%. Other potential endogenous and exogenous interfering substances (whole blood, nasal mucin, saliva, antipyretics, antihistamines and neuraminidase inhibitors) showed negative results, which verified the excellent specificity of this method. This assay was successfully applied to the POCT quantitative detection of influenza A/B virus, the sensitivity to influenza A and B viruses was 70% and 87.5% respectively, and the specificity was 100%. Therefore, these microspheres can be used as an effective material for rapid POCT detection in clinical specimens.

Multiplexed evaluation of immunity against SARS-CoV-2 variants using surface enhanced fluorescence from a nanostructured plasmonic chip.

Generated by the immune system post-infection or through vaccination, the effectiveness of antibodies against emerging SARS-CoV-2 variants is crucial for protecting individuals from the COVID-19 pandemic. Herein, a platform for the multiplexed evaluation of SARS-CoV-2 neutralizing antibodies against various variants was designed on the basis of near-infrared (NIR) surface enhanced fluorescence by nano-plasmonic gold chip (pGOLD). Antibody level across variants (Wild-type, Alpha, Beta, Delta, Omicron) was confirmed by the sera from recovered-individuals who were unvaccinated and had infected with Wild-type, Delta, Omicron variants. However, the neutralizing activity against Omicron variant was markedly decreased for individuals infected by Wild-type (~ 5.6-fold) and Delta variant (~ 19.1-fold). To the opposite, neutralizing antibody from individuals recovered from Omicron variant infection showed weak binding strength against non-Omicron variants. Antibody evolution over time was studied with individuals 196-530 days post Wild-type infection. Decreasing IgG antibody titer accompanied by increasing IgG binding avidity with elongated post-infection period were observed for the sera from Wild-type recovered-individuals with different post-infection times, suggesting that after the primary infection, a great number of antibodies were generated and then gradually decreased, while the antibody matured over time. By comparing the IgG level of individuals vaccinated for 27-51 days with individual post-infection, we found that ca. 1 month after two doses of vaccination, the antibody level was comparable to that of 500 days post-infection, and vaccination could enhance IgG avidity more efficiently. This work demonstrated a platform for the multiplexed, high-throughput and rapid screening of acquired immunity against SARS-CoV-2 variants, providing a new approach for the analysis of vaccine effectiveness, immunity against emerging variants, and related serological study.

Short-term association of NO2 with hospital visits for chronic kidney disease and effect modification by temperature in Hefei, China: A time series study.

BACKGROUND: A large body of evidence has linked air pollution and temperature with chronic kidney disease (CKD) prevalence and hospitalizations. However, most studies have focused on the influence of heat stress on CKD prevalence, and the potential effect modification of temperature on the association between air pollution and CKD has not been well-investigated. In this study, we examined the associations of the whole temperature spectrum and air pollution with CKD-related hospital visits and explored whether temperature modifies the short-term association of air pollution with CKD-related hospital visits. METHODS AND FINDINGS: We collected 40 276 CKD-related hospital visits from the first Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital in Hefei, China, during 2015-2019. A two-stage time-series design was conducted to investigate the associations of air pollution and daily mean temperature with CKD-related hospital visits. First, we estimated the associations between air pollution and CKD-related hospital visits as well as temperature and CKD-related hospital visits. Second, we analyzed the associations of air pollution with CKD hospital visits at different temperatures. We found that NO2 exposure and low temperature were associated with an increased risk of CKD-related hospital visits. Low temperature enhanced the association between NO2 exposure and CKD-related hospital visits, with an increase of 4.30% (95% CI: 2.47-5.92%) per 10 µg/m3 increment in NO2 at low temperature. Effect modification of the association between NO2 and the risk of CKD-related hospital visits was stronger at low temperature across the whole population. CONCLUSIONS: Our findings indicate that low temperature-related chronic kidney damage should be of immediate public health concern. Impact of NO2 exposure on the risk of CKD-related hospital visits may increase under the low temperature, which suggests the need for NO2 exposure mitigation strategies in the context of climate change and an enhanced understanding of the mechanisms underlying the temperature variance of air pollution effect to help reduce the magnitude of the CKD burden on the healthcare systems.

The Quality and Bacterial Community Changes in Freshwater Crawfish Stored at 4 °C in Vacuum Packaging.

Crawfish can be easily spoiled due to their rich nutrition and high water content, which is difficult to preserve. In this study, the dominant spoilage organisms in crawfish which were stored at 4 °C in vacuum packaging were identified by high-throughput sequencing technology; after sequencing the full-length 16S rRNA gene, the changes in the bacterial community structure, diversity and quality (texture, flavor, etc.) were analyzed. Our results reflected that the specific spoilage organisms (SSOs) of crawfish were Aeromonas sobria, Shewanella putrefaciens, Trichococcus pasteurii and Enterococcus aquimarinus, since their abundances significantly increased after being stored for 12 days at 4 °C under vacuum conditions. At the same time, the abundance and diversity of the microbial community decreased with storage time, which was related to the rapid growth of the dominant spoilage organisms and the inhibition of other kinds of microorganisms at the end of the spoilage stage. Function prediction results showed that the gene which contributed to metabolism influenced the spoilage process. Moreover, the decline in texture of crawfish was negatively correlated to the richness of SSOs; this may be because SSOs can produce alkaline proteases to degrade the myofibrillar protein. On the contrary, the unpleasant flavor of crawfish, resulting from volatile flavor compounds such as S-containing compounds and APEOs, etc., is negatively correlated to the richness of SSOs, due to the metabolism of SSOs by secondary metabolites such as terpenoids, polyketides and lips, which can lead to decarboxylation, deamination and enzymatic oxidation. These results are very important to achieve the purpose of targeted inhibition of crawfish spoilage at 4 °C in vacuum packaging.

Comparing the effect of benzoic acid and cinnamic acid hydroxyl derivatives on polyphenol oxidase: activity, action mechanism, and molecular docking.

BACKGROUND: Polyphenol oxidase (PPO) is considered to have a key role in the food industry because it initiates enzymatic browning in the processing and storage of fruit and vegetables. Increasing numbers of benzoic and cinnamic acid derivatives have been found to be efficient inhibitors of polyphenol oxidase, but a comparison study on activity and action mechanism is lacking. In this study, 18 benzoic acid and cinnamic acid hydroxy derivatives were selected and investigated. RESULTS: Three substrates, four activators and 11 inhibitors were identified from benzoic and cinnamic acid derivatives. 2,4-Dihydroxycinnamic acid and benzoic acid showed the strongest inhibitory effect on PPO, with IC50 of 0.092 and1.425 mmol L-1 , respectively. Benzoic acid reversibly inhibited PPO in a competitive manner, while 2,4-dihydroxycinnamic acid showed a mixed-type inhibition. Both of them showed that static-type fluorescence quenching and electrostatic interaction were the main driving force in the bonding process. Compared with benzoic acid, 2,4-dihydroxycinnamic acid more easily formed hydrogen bonds in the active site of PPO, making the interaction more stable. CONCLUSION: Comparative analysis showed that the inhibition effect of cinnamic acid hydroxyl derivatives on PPO was stronger than that of benzoic acid derivatives. Benzoic acid and 2,4-dihydroxycinnamic acid were the strongest inhibitors. PPO inhibitors identified from benzoic and cinnamic acid derivatives are expected to be promising inhibitors for controlling fruit and vegetable browning. © 2021 Society of Chemical Industry.

Purification and characterization of Se-enriched Grifola frondosa glycoprotein, and evaluating its amelioration effect on As3+ -induced immune toxicity.

BACKGROUND: Selenium (Se)-enriched glycoproteins have been a research highlight for the role of both Se and glycoproteins in immunoregulation. Arsenic (As) is a toxicant that is potentially toxic to the immune function and consequently to human health. Several reports suggested that Se could reduce the toxicity of heavy metals. Moreover, more and more nutrients in food had been applied to relieve As-induced toxicity. Hence glycoproteins were isolated and purified from Se-enriched Grifola frondosa, and their preliminary characteristics as well as amelioration effect and mechanism on As3+ -induced immune toxicity were evaluated. RESULTS: Four factions, namely Se-GPr11 (electrophoresis analysis exhibited one band: 14.32 kDa), Se-GPr22 (two bands: 20.57 and 31.12 kDa), Se-GPr33 (three bands: 15.08, 20.57 and 32.78 kDa) and Se-GPr44 (three bands: 16.73, 32.78 and 42.46 kDa), were obtained from Se-enriched G. frondosa via DEAE-52 and Sephacryl S-400 column. In addition, Se-GPr11 and Se-GPr44 are ideal proteins that contain high amounts of almost all essential amino acids. Thereafter, the RAW264.7 macrophage model was adopted to estimate the effect of Se-GPr11 and Se-GPr44 on As3+ -induced immune toxicity. The results showed that the pre-intervention method was the best consequent and the potential mechanisms were, first, by improving the oxidative stress state (enhancing the activity of superoxide dismutase and glutathione peroxidase, decreasing the levels of reactive oxygen species and malondialdehyde); secondly, through nuclear factor-κB and mitogen-activated protein kinase-mediated upregulation cytokines (interleukin-2 and interferon-γ) secretion induced by As3+ . CONCLUSION: The results suggested Se-enriched G. frondosa may be a feasible supplement to improve health level of the As3+ pollution population. © 2021 Society of Chemical Industry.

Nested Named Entity Recognition Based on Dual Stream Feature Complementation.

Named entity recognition is a basic task in natural language processing, and there is a large number of nested structures in named entities. Nested named entities become the basis for solving many tasks in NLP. A nested named entity recognition model based on dual-flow features complementary is proposed for obtaining efficient feature information after text coding. Firstly, sentences are embedded at both the word level and the character level of the words, then sentence context information is obtained separately via the neural network Bi-LSTM; Afterward, two vectors perform low-level feature complementary to reinforce low-level semantic information; Sentence-local information is captured with the multi-head attention mechanism, then the feature vector is sent to the high-level feature complementary module to obtain deep semantic information; Finally, the entity word recognition module and the fine-grained division module are entered to obtain the internal entity. The experimental results show that the model has a great improvement in feature extraction compared to the classical model.

Compact Magneto-Fluorescent Colloids by Hierarchical Assembly of Dual-Components in Radial Channels for Sensitive Point-of-Care Immunoassay.

Exploring signal amplification strategies to enhance the sensitivity of lateral flow immunoassay (LFIA) is of great significance for point-of-care (POC) testing of low-concentrated targets in the field of in vitro diagnostics. Here, a highly-sensitive LFIA platform using compact and hierarchical magneto-fluorescent assemblies as both target-enrichment substrates and optical sensing labels is demonstrated. The large-pored dendritic templates are utilized for high-density incorporation of both superparamagnetic iron oxide nanoparticles (IOs) and quantum dots (QDs) within the vertical channels. The hierarchical structure is built via affinity-driven assembly of IOs and QDs from organic phase with silica surface and mercapto-organosilica intermediate layer, respectively. The sequential assembly with central-radial channels enables 3D loading of dual components and separately controlling of discrete functionalities. After the alkyl-organosilica encapsulation and silica sealing, the composite spheres exhibit high stabilities and compatibility with LFIA for procalcitonin (PCT) detection. With the assistance of liquid-phase antigen-capturing, magnetic enrichment, and fluorescence-signal amplification, a limit of detection of 0.031 ng mL-1 for PCT is achieved with a linear range from 0.012 to 10 ng mL-1 . The current LFIA is robust and validated for PCT detection in real serum, which holds great diagnostic significance for precise guidance of antibiotic therapy with POC manner.

Association of MALAT-1 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus.

Background: Abnormal expression and function of long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) gene single-nucleotide polymorphisms (SNPs) with susceptibility and clinical characteristics of SLE patients. Methods: A case-control study including 489 SLE patients and 492 healthy controls was conducted. Four MALAT-1 SNPs (rs4102217, rs591291, rs11227209, and rs619586) were genotyped in all subjects, their correlation with SLE susceptibility and clinical characteristics were also analyzed. Results: Results showed that the rs4102217 locus was associated with the risk of SLE. In recessive models, the GG+CG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.036, OR = 0.348, 95% CI: 0.124-0.975). In additive models, the GG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.040, OR = 0.355, 95% CI: 0.127-0.996). However, no association was found between MALAT-1 gene polymorphism and clinical manifestations of SLE (all p > 0.05). Conclusion: In summary, MALAT-1 rs4102217 is associated with susceptibility to SLE, suggesting that MALAT-1 may play a role in SLE.

Polymorphic microstructure of MDI/BD-block polyurethane as determined by temperature-sensitive conformation variation.

MDI/BD-block thermoplastic polyurethanes (TPUs) crystallized at different isothermal temperatures and different cooling rates were investigated using multiple techniques. The MDI/BD blocks crystallized in form II when the isothermal temperature was equal to or higher than 150 °C, and in form I at lower isothermal temperatures. Form II had a higher crystal elastic modulus of 6.75 GPa than form I of 1.31 GPa. Form I exhibited contracted conformation, while form II exhibited an extended conformation when viewed from the length of the c-axis in the crystalline state. Based on an analysis of the second derivative in FTIR spectroscopy and simple modeling, the conformation differences were considered to stem from the urethane group's internal bond rotation concerning the phenyl ring and the opening bond angle of phenyl-CH2-phenyl. The generation of form II above 150 °C may be due to the activation of urethane and the flexible methylene elevated by the high temperature. Overall, it was seen that the crystallization of MDI/BD blocks involved a physicochemical change.

Training data generation and validation for a neural network-based equalizer.

The neural network (NN) has been widely used as a promising technique in fiber optical communication owing to its powerful learning capabilities. The NN-based equalizer is qualified to mitigate mixed linear and nonlinear impairments, providing better performance than conventional algorithms. Many demonstrations employ a traditional pseudo-random bit sequence (PRBS) as the training and test data. However, it has been revealed that the NN can learn the generation rules of the PRBS during training, degrading the equalization performance. In this work, to address this problem, we propose a combination strategy to construct a strong random sequence that will not be learned by the NN or other advanced algorithms. The simulation and experimental results based on data over an additive white Gaussian noise channel and a real intensity modulation and direct detection system validate the effectiveness of the proposed scheme.