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Mengdi Xie,1,* Kang Yuan,2,* Xinyi Zhu,2,* Jingjing Chen,3 Xiaohao Zhang,4 Yi Xie,2 Min Wu,1 Zhaojun Wang,2 Rui Liu,2 Xinfeng Liu1,2,5 1Department of Neurology, Jinling Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Neurology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China; 3Department of Neurology, Changhai Hospital, Navy Medical University, Shanghai, People’s Republic of China; 4Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 5Stroke Center & Department of Neurology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinfeng Liu, Department of Neurology, Jinling Hospital, Nanjing Medical University, No. 305 East Zhongshan Road, Nanjing, Jiangsu Province, 210000, People’s Republic of China, Tel +86 2584801861, Fax +86 2584805169, Email xfliu2@vip.163.com Rui Liu, Department of Neurology, Affiliated Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210000, Jiangsu Province, People’s Republic of China, Tel +86 2584801861, Fax +86 2584805169, Email liurui8616@163.comBackground: Systemic immune inflammation has been investigated as a prognostic marker of different diseases. This study is designed to assess the association of systemic immune-inflammation index (SII) with long-term mortality of stroke-associated pneumonia (SAP) patients.Methods: Patients aged ≥ 18 years with SAP were selected from the Nanjing Stroke Registry Program in China. We retrospectively evaluated systemic immune-inflammation response with SII and pneumonia severity with the pneumonia severity index and the confusion, uremia, elevated respiratory rate, hypotension, and aged 65 years or older score. To explore the correlation between SII and mortality in SAP patients, multivariable Cox regressions and competing risk regressions were conducted. Mediation analysis was also performed to assess the role of pneumonia severity.Results: Among 611 patients in the SAP population, death occurred in 164 patients (26.8%) during the median follow-up of 3.0 (1.2– 4.6) years. In multivariate analysis, higher SII scores could predict increased mortality in patients with SAP (adjusted hazard ratio 2.061; 95% confidence interval, 1.256– 3.383; P = 0.004), and the association was mediated by pneumonia severity. Moreover, adding SII to traditional models improved their predictive ability for mortality.Conclusion: Our study displayed that SII was characterized in SAP patients with different prognoses. Elevated SII scores increased the risk of mortality. Further research is required for the clinical practice of the index among SAP patients.Keywords: systemic immune-inflammation index, stroke-associated pneumonia, mortality, China

We sought to assess cognitive benefits of a community-based multidomain intervention for improving cognition among older adults at risk of cognitive decline (COMBAT).A two-armed cluster-randomized controlled trial.Community-dwelling older adults aged 60 years or older and were at risk of cognitive decline (n = 209).In this 9-month intervention study, 10 community hospitals in Beijing, China, were randomized (1:1) to receive either a multidomain intervention of meditation, cognitive training, exercise, and nutrition counseling or usual care. The intervention was delivered with weekly 1-hour group training sessions and weekly home homework.Primary outcome was change in cognition as measured by a composite Z score of seven cognitive tests. Secondary outcomes included subjective cognitive abilities, positive and negative affective experiences, physical activity, and dietary habits. Assessments were administered at baseline, end of the intervention, and 1 year after completing the intervention (1-year follow-up).Immediately after the intervention, the intervention group showed significant enhancement in cognitive performance (p = 0.026). The between-group difference in the Z score of change of cognition was 0.20 (95% CI: 0.053, 0.35), with a Hedges' g of 0.40 (95% CI: 0.29, 0.50). However, this cognitive benefit was not significant at 1-year follow-up.This multidomain intervention was effective to improve cognition for at-risk individuals. Long-term effects on cognitive function and individual differences in response to the intervention deserve further investigation.

Although previous studies have applied artificial intelligence techniques to improve the accuracy and efficiency of ship selection in port state control (PSC) inspections, the new inspection regime (NIR) is still in effect and widely adopted by PSC authorities in the Tokyo Memorandum of Understanding to select ships for inspection. It considers seven features, and each candidate value of a certain feature is assigned a fixed weighting point. The sum of the weighting points of these seven features determines the risk level of a ship. The assumption behind the NIR is that ships with values attached with higher weighting points should have more deficiencies. However, this paper finds that Simpson's paradox may exist for this assumption; that is, the average number of deficiencies of ships with values attached with higher weighting points is lower than that of ships with values attached with lower weighting points. Therefore, this paper examines the plausibility of the NIR's weighted-sum method and further explores which feature flips the effect. Finally, we arrive at the conclusion that the features selected by NIR are coupled with each other, so we should not use a simple weighted-sum method to determine the risk level of a candidate ship. Based on the results, we further provide suggestions for PSC authorities with respect to the improvement of the ship selection scheme of NIR.

This minireview discloses the underlying challenges of perovskite indoor photovoltaics and summarizes the advanced strategies for indoor efficiency improvement.

This study aims to analyze advantages and disadvantages of different leadership style. Look into various leadership philosophies and relevant real-life examples online. The author has gathered thorough knowledge on examples of leadership style. This analysis is built on examples of several leadership styles. Different leadership styles have different impacts on enterprises, and the advantages and disadvantages of different leadership styles will also have various of impacts on enterprises. Can also affects employees. Enterprises have appropriate leadership styles at that stage in each stage of development. Enterprises with different development prospects need to have different leadership styles. Only by finding the most suitable leadership style can they develop better. All our preliminary result throw light on the nature of different leadership styles.

To investigate whether loneliness and social isolation could independently predict subsequent risk of cognitive impairment in Chinese oldest old, and to examine possible gender differences.The sample included 2,732 older adults aged 80 years and above with intact cognitive function from the Chinese Longitudinal Healthy Longevity Survey 2002-2018 waves, with an average follow-up of 4.24 years. Loneliness was measured by a single-item question about how often the participant felt lonely. Social isolation was defined by marital status, frequent visits by family members, and social activity engagement. Cognitive impairment was defined based on Mini-Mental State Examination scores.Cox regression showed that social isolation independently predicted a higher risk of developing cognitive impairment at follow-up (HR = 1.14, 95% CI [1.03, 1.27],To prevent cognitive impairment and promote healthy longevity, socially isolated adults in their oldest old age should receive more attention, and men who often feel lonely should be offered with more emotional support.

Creative industries have been mushrooming in the past few decades and gradually emerged as one of the most potent industries in China. In the book Creative Industries and Digital Transformation in China, various scholars approached it from diverse perspectives, including reviving the traditional culture, cyberspace in Shanghai, gaming culture, and the fashion eco-system. It reveals the gradually emerging creative industries from historical, modern, and cultural points of view. In general, it is a comprehensive book that incorporates the essential points from the growing process of the contemporary creative industry and embedded the digital transformation process based on the root of Chinese culture. However, there are weaknesses that exist in this book; it majorly lies in the lack of understanding of the political situation and lack of sufficient empirical examples of other major industries to investigate the general understanding of creative industries in China.

Background2021 World Health Organization (WHO) Central Nervous System (CNS) tumor classification increasingly emphasizes the important role of molecular markers in glioma diagnoses. Preoperatively non-invasive “integrated diagnosis” will bring great benefits to the treatment and prognosis of these patients with special tumor locations that cannot receive craniotomy or needle biopsy. Magnetic resonance imaging (MRI) radiomics and liquid biopsy (LB) have great potential for non-invasive diagnosis of molecular markers and grading since they are both easy to perform. This study aims to build a novel multi-task deep learning (DL) radiomic model to achieve preoperative non-invasive “integrated diagnosis” of glioma based on the 2021 WHO-CNS classification and explore whether the DL model with LB parameters can improve the performance of glioma diagnosis.MethodsThis is a double-center, ambispective, diagnostical observational study. One public database named the 2019 Brain Tumor Segmentation challenge dataset (BraTS) and two original datasets, including the Second Affiliated Hospital of Nanchang University, and Renmin Hospital of Wuhan University, will be used to develop the multi-task DL radiomic model. As one of the LB techniques, circulating tumor cell (CTC) parameters will be additionally applied in the DL radiomic model for assisting the “integrated diagnosis” of glioma. The segmentation model will be evaluated with the Dice index, and the performance of the DL model for WHO grading and all molecular subtype will be evaluated with the indicators of accuracy, precision, and recall.DiscussionSimply relying on radiomics features to find the correlation with the molecular subtypes of gliomas can no longer meet the need for “precisely integrated prediction.” CTC features are a promising biomarker that may provide new directions in the exploration of “precision integrated prediction” based on the radiomics, and this is the first original study that combination of radiomics and LB technology for glioma diagnosis. We firmly believe that this innovative work will surely lay a good foundation for the “precisely integrated prediction” of glioma and point out further directions for future research.Clinical trail registrationThis study was registered on ClinicalTrails.gov on 09/10/2022 with Identifier NCT05536024.

Embryo selection is a key point of in vitro fertilization (IVF). The most commonly used method for embryo selection is morphological assessment. However, it is sometimes inaccurate. Follicular fluid (FF) contains a complex mixture of proteins that are essential for follicle development and oocyte maturation. Analyzing human FF proteomic profiles and identifying predictive biomarkers might be helpful for evaluating embryo quality. A total of 22 human FF samples were collected from 19 infertile women who underwent IVF/intracytoplasmic sperm injection (ICSI) treatment between October 2021 and November 2021. FFs were grouped into two categories on the basis of the day 3 embryo quality, grade Ⅰ or Ⅱ in the hqFF group and grade Ⅲ in the nhqFF group. FF was analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The key differentially expressed proteins (DEPs) were validated by parallel reaction monitoring (PRM). Differentially expressed proteins were further analyzed using DAVID software. A total of 558 proteins were identified, of which 50 proteins were differentially expressed inthe hqFF vs. nhqFF group, including 32 upregulated proteins (>1.20-fold, P

Background: Fine particulate matter (particulate matter 2.5, PM2.5) is considered one of the harmful factors to neuronal functions. Apoptosis is one of the mechanisms of neuronal injury induced by PM2.5. Methylcobalamine (MeCbl) has been shown to have anti-apoptotic and neuroprotective effects. Objective: The current work tried to explore the neuroprotective effects and mechanisms that MeCbl protects mice against cognitive impairment and neuronal apoptosis induced by chronic real-time PM2.5 exposure. Methods: Twenty-four 6-week-old male C57BL/6 mice were exposed to ambient PM2.5 and fed with MeCbl for 6 months. Morris water maze was used to evaluate the changes of spatial learning and memory ability in mice. PC12 cells and primary hippocampal neurons were applied as the in vitro model. Cell viability, cellular reactive oxygen species (ROS) and the expressions of apoptosis-related proteins were examined. And cells were stained with JC-1 and mitochondrial membrane potential was evaluated. Results: In C57BL/6 mice, MeCbl supplementation alleviated cognitive impairment and apoptosis-related protein expression induced by PM2.5 exposure. In in vitro cell model, MeCbl supplementation could effectively rescue the downregulation of cell viability induced by PM2.5, and inhibited the increased levels of ROS, cellular apoptosis, and the expressions of apoptosis related proteins related to PM2.5 treatment, which may be associated with modulation of mitochondrial function. Conclusion: MeCbl treatment alleviated cognitive impairment and neuronal apoptosis induced by PM2.5 both in vivo and in vitro. The mechanism for the neuroprotective effects of MeCbl may at least be partially dependent on the regulation of mitochondrial apoptosis.

Objective Older adults with subjective memory complaints (SMC) have a higher risk of dementia and commonly demonstrate symptoms of depression and anxiety. The study aimed to examine the effect of a memory training program for individuals with SMC, and whether additional group counseling aimed at alleviating depression and anxiety would boost memory training gains. Design A three-armed, double-blind, randomized controlled trial. Setting and Participants Community-dwelling older adults with SMC, age ≥60. Methods Participants (n = 124) were randomly assigned to memory training (MT), group counseling (GC), or GC + MT intervention. The GT + MT group received 3 sessions of group counseling followed by a 4-week memory training, while the MT group attended reading and memory training, and the GC group received group counseling and health lectures. Cognitive function and symptoms of depression and anxiety were assessed at baseline, mid-, and post-intervention. Results After group counseling, the GC + MT and GC groups showed reduced symptoms of anxiety compared to the MT group. Memory training enhanced associative learning in both MT and GC + MT groups compare with the GC group, but the GC + MT group demonstrated a larger memory improvement (Cohen's d = 0.57) than the MT group (Cohen's d = 0.44). Conclusion and Implications Group counseling decreased symptoms of anxiety, memory training increased associative learning, and the combination of two intervention induced larger memory gain than memory training alone. The results suggest that it may need to integrate treatment for anxiety into memory training for older adults with SMC to achieve better intervention effect. Trial Registration ChiCTR-IOR-15006165 in the Chinese Clinical Trial Registry.

Background and Objectives Individuals with subjective cognitive decline (SCD) who perform normally on objective cognitive tests may have an increased risk of pathological cognitive decline and progression to Alzheimer’s disease (AD) and related dementia (ADRD). Working memory is widely regarded as an early sign of pathological cognitive decline. We tested the hypothesis that older adults with SCD already exhibit aberrant neurocognitive processing underlying working memory. Research Design and Methods Electroencephalography (EEG) was recorded during a delayed match-to-sample (DMS) task and an eyes-closed resting condition in cognitively healthy community-dwelling older adults who were assigned to the SCD or Control group. Results The SCD and Control groups showed comparable performance on the neuropsychological tests and DMS task. The SCD group showed an enhanced right frontal target-related P300 effect during working memory retrieval and higher frontal theta power during rest. Higher theta power was associated with worse working memory performance and greater left frontal nontarget-related positivity across all older adults. Discussion and Implications Our findings suggest that older people with SCD have subtle pathophysiological changes in working memory–related potentials and intrinsic theta power, which has important implications for predicting risks and early interventions in older adults in the preclinical stage of ADRD.

Pure red-cell aplasia (PRCA) is a syndrome associated with reduced erythroid precursors. This report presents the case of an elderly PRCA patient with significantly proliferated γδT cells and clonal T-cell receptor (TCR) gene rearrangement. The cause of this patient’s PRCA was confirmed to be an autoimmune disorder rather than malignancy on the basis of flow cytometry, TCR gene rearrangement, and positron emission tomography/computed tomography (PET/CT) findings. Moreover, the γδT cell group identified in this case was captured for the first time under the microscope; this CD4+/CD8− (extremely high CD4/CD8 ratio) population is rare in PRCA patients. Our patient with a monoclonal and polyclonal hybrid of TCR gene rearrangement was sensitive to cyclosporin A (CsA), despite previous reports suggesting that patients with TCR clonal rearrangement may respond poorly to this drug. Overall, this case presents valuable clinical findings for the future diagnosis and management of PRCA caused by autoimmune conditions and further research on γδT cells’ autoimmune pathophysiology and gene rearrangement.

We demonstrate gapless and real-time spectral analysis of broadband waveforms with >250 analysis points per spectrum. The concept is based on a discretization of an electro-optic time-lens to implement a phase modulation equivalent to 206.25π.

Rapid and accurate detection of pathogen spores is an important step to achieve early diagnosis of diseases in precision agriculture. Traditional detection methods are time-consuming, laborious, and subjective, and image processing methods mainly rely on manually designed features that are difficult to cope with pathogen spore detection in complex scenes. Therefore, an MG-YOLO detection algorithm ( M ulti-head self-attention and G host-optimized YOLO ) is proposed to detect gray mold spores rapidly. Firstly, Multi-head self-attention is introduced in the backbone to capture the global information of the pathogen spores. Secondly, we combine weighted Bidirectional Feature Pyramid Network (BiFPN) to fuse multiscale features of different layers. Then, a lightweight network is used to construct GhostCSP to optimize the neck part. Cucumber gray mold spores are used as the study object. The experimental results show that the improved MG-YOLO model achieves an accuracy of 0.983 for detecting gray mold spores and takes 0.009 s per image, which is significantly better than the state-of-the-art model. The visualization of the detection results shows that MG-YOLO effectively solves the detection of spores in blurred, small targets, multimorphology, and high-density scenes. Meanwhile, compared with the YOLOv5 model, the detection accuracy of the improved model is improved by 6.8%. It can meet the demand for high-precision detection of spores and provides a novel method to enhance the objectivity of pathogen spore detection.

We experimentally demonstrate electronically programmable, user-defined time-varying frequency filtering of continuous broadband signals, over a 22 GHz frequency tuning range and with >1 GHz reconfiguration speed, using electro-optic modulation of a reversible time-mapped spectrogram.

Lysinibacillus sp. is a spore-forming gram-positive bacterium showing excellent adaptive capacity to environment, convenience to storage and antimicrobial properties. Thus, it has appeared a huge potential as probiotics in application, but related studies remain limited. This study was conducted to determine the effects of supplementary Lysinibacillus (L.) macroides 38328 in drinking water on antioxidant capacity and avian influenza virus vaccine immune response of laying hens. Hereon, layers were fed with drinking water with or without supplementary L. macroides 38328 at the dose of 7×109 colony-forming units per milliliter (CFU/mL). The results showed that supplementation with L. macroides 38328 significantly improved the layers’ productive performance while enhancing their antioxidant capacity and immunity. According to the testing results, the rise of serum T-AOC and the downtrend of serum MDA were significant (P L. macroides 38328 had positive effects on layers’ heath condition and productivity, indicating great applied potential as a new probiotics strain.

End-stage kidney disease (ESKD) is associated with cognitive impairment (CI) and affects different aspects of cortical morphometry, but where these changes converge remains unclear. Fractal dimension (FD) is used to represent cortical complexity (CC), which describes the structural complexity of the cerebral cortex by integrating different cortical morphological measures. This study aimed to investigate changes in CC in patients with ESKD prior to initiation of dialysis and to evaluate the relationship between changes in CC, cognitive performance, and uremic toxins. Forty-nine patients with ESKD naive to dialysis and 31 healthy controls (HCs) were assessed using structural magnetic resonance imaging (MRI) and cognitive tests, including evaluations of global cognitive function, memory, and executive function. Clinical laboratory blood tests were performed on all patients with ESKD, including measurement of nine uremic toxin-related indices. CC was measured using MRI data to determine regional FD values. We estimated the association between cognitive performance, uremic toxin levels, and CC changes. Compared to HCs, patients with ESKD showed significantly lower CC in the left precuneus (p = 0.006), left middle temporal cortex (p = 0.010), and left isthmus cingulate cortex (p = 0.018). Furthermore, lower CC in the left precuneus was associated with impaired long-term delayed memory (Pearson r = 0.394, p = 0.042) in patients with ESKD. Our study suggests that regional decreases in CC are an additional characteristic of patients with ESKD naive to dialysis, related to impaired long-term memory performance. These findings may help further understand the underlying neurobiological mechanisms between brain structural changes and CI in patients with ESKD.

Mnemonic training can improve episodic memory function, the most aging-sensitive functional domain in older adults. However, it remains unclear whether memory training gains can be maintained over time. In this meta-analysis, we aimed to investigate the long-term effects (pretest to follow-up) of mnemonic training in improving memory among older adults. Eligible studies were randomized controlled trials of mnemonic training with follow-up assessments (ranging from 0.5 to 32 months, median follow-up duration = 4 months) in healthy older adults (aged ≥ 50 years) without known cognitive impairment. Twenty-one studies, with a total of 4,149 participants, were identified. The three-level meta-analyses indicated that the immediate (pre- to post-test) and long-term effect sizes on episodic memory were 0.408 and 0.418 (Hedges'

It is known that schistosome-derived antigens induce innate and adaptive immune responses that are essential for the formation of hepatic immunopathology. Here, we screened and synthesized four peptides derived from Schistosoma japonicum (S. japonicum) heat shock protein 90α (Sjp90α-1, -2, -3, and -4), which is widely expressed in adults and eggs of the genus S. japonicum and induces remarkable immune reactions. To define the antigenicity of these peptides, we stimulated splenocytes with peptides, and the results showed that only the Sjp90α-1 peptide could predominately induce the activation of dendritic cells (DCs) and macrophages as well as alter the proportion of follicular helper T (Tfh) cells. Next, CD4+ T cells were purified and cocultured with mouse bone-marrow-derived DCs (BMDCs) with or without Sjp90α-1 peptide stimulation in vitro, and the results showed that Sjp90α-1-stimulated BMDCs can significantly induce CD4+ T-cell differentiation into Tfh cells, while the direct stimulation of CD4+ T cells with Sjp90α-1 did not induce Tfh cells, indicating that the Sjp90α-1 peptide promotes Tfh cell differentiation depending on the presence of DCs. Furthermore, we selected and prepared an Sjp90α-1-peptide-based antibody and illustrated that it has excellent reactivity with the immunizing peptide and detects a single band of 29 kDa corresponding to the Sjp90α protein. The immunolocalization results showed that the protein recognized by this Sjp90α-1-peptide-based antibody is present in the mature eggs and the tegument of adults, implying that the parasite-derived peptide has a potential interaction with the host immune system. Finally, we evaluated antipeptide IgG antibodies and revealed a significantly higher level of anti-Sjp90α-1 peptide IgG antibodies in mice 3 weeks after S. japonicum infection. In conclusion, we illustrate that these synthetic peptides warrant further investigation by evaluating their antigen-specific immune response and their ability to efficiently induce Tfh cells. Moreover, they may constitute a potentially helpful method for the laboratory diagnosis of schistosomiasis japonica.

Neurovascular (NV) decoupling is a potential neuropathologic mechanism of cognitive impairment in patients with end-stage renal disease (ESRD). Hemodialysis improves cognitive impairment at 24 h post-dialysis, which suggests a potential neuroprotective effect of hemodialysis treatment on the brain. We investigated the effects of hemodialysis treatment on the reversal of NV decoupling associated with cognitive improvement. A total of 39 patients with ESRD and 39 healthy controls were enrolled. All patients were imaged twice during a dialysis session: before hemodialysis (T1

ObjectiveTo investigate the effect of weight loss on pregnancy outcomes, PCOS related neuronal-reproductive-metabolic hormones and ovarian granulosa cell gene expression profiles in obese PCOS infertile patients undergoing in vitro fertilization-embryo transfer (IVF-ET).Methods75 patients undergoing IVF-ET due to tubal factors alone collected as the control group (group A), and 352 patients with obese PCOS infertility were divided into four groups according to the amount of weight loss before IVF: 0 kg (group B), 1-5 kg (group C), 5-10 kg (group D), and >10 kg (group E). Six cases of ovarian granulosa cells were collected randomly with the random number table method in each group for detecting mRNA profiling. Pathway networks and biological functions of the differentially expressed genes were analyzed. Validation by RT-PCR was performed.Results(1) The levels of luteinizing hormone(LH), testosterone(T) and homeostasis model assessment insulin resistance(HOMA-IR) in group E were significantly lower than those in groups B and C (PP2 level on trigger day and number of oocytes obtained in group B was significantly less than that in group E (PPPConclusionWeight loss more than 5kg may regulate the neuroreproductive endocrine hormone secretion, insulin resistance and gene expression profiles of ovarian granulosa cells, so as to improve the ovarian responsiveness to Gn, the embryo quality, embryo implantation rate, clinical pregnancy rate, live birth rate, and reduce the spontaneous abortion rate in obese infertile PCOS patients undergoing IVF-ET.Clinical trial registrationwww.chictr.org.cn, identifier ChiCTR1800018298.

IRF5 plays a crucial role in the development of lupus. GWAS has identified several SLE risk SNPs enriched in the IRF5 locus. However, no comprehensive genome editing-based functional analysis exists to establish a direct link between these variants and altered IRF5 expression, particularly for enhancer variants. This study aims to dissect the regulatory function and mechanisms of SLE IRF5 enhancer risk variants and to explore the utilization of CRISPRi to regulate the expression of disease risk gene to intervene in the disease.Epigenomic profiles and eQTL analysis were applied to prioritize putative functional variants in IRF5 locus. CRISPR-mediated deletion, activation, and interference were performed to investigate the genetic function of rs4728142. AS-ChIP-qPCR and FAIRE-qPCR were used to decipher the mechanism of alleles differentially regulating IRF5 expression. CRISPRi approach was used to evaluate the intervention effect in SLE patients' monocytes.SLE risk SNP rs4728142 was located in an enhancer region, indicating a disease-related regulatory function, and rs4728142 A risk allele was closely associated with increased IRF5 expression. We demonstrated that rs4728142-containing region could act as an enhancer to regulate the expression of IRF5. Moreover, rs4728142 affected the binding affinity of ZBTB3, a transcription factor involved in regulation. Furthermore, in monocytes from SLE patients, CRISPR-based interference with the regulation of this enhancer attenuated the production of disease-associated cytokines.These results demonstrate that rs4728142-A allele increases the SLE risk by affecting ZBTB3 binding, chromatin status, and regulating IRF5 expression, establishing a biological link between genetic variation and lupus pathogenesis.

It is known that schistosome-derived antigens induce innate and adaptive immune responses that are essential for the formation of hepatic immunopathology. Here, we screened and synthesized four peptides derived from

GSK3335065 is an inhibitor of kynurenine monooxygenase (KMO) being developed for the treatment of acute pancreatitis. Healthy male volunteers were administered ascending doses of GSK3335065 or matched placebo as a single intravenous bolus injection to assess safety, tolerability, pharmacokinetics and pharmacodynamics. GSK3335065 displayed an apparent volume of distribution between 20.6 L and 44.6 L, a clearance between 0.462 L/h and 0.805 L/hr and a terminal half-life between 31.3 and 34.5 hr. In the single subject who received 1.3 mg GSK3335065, changes in tryptophan pathway metabolites were observed consistent with the changes seen in preclinical species suggesting that KMO enzyme activity was partially inhibited. However, a broad complex ventricular tachycardia was observed in this subject, which was judged to be a Serious Adverse Event (SAE) and resulted in early termination of the study. While development of GSK3335065 was subsequently discontinued, significant confounding factors hinder a clear interpretation that the tachycardia was directly related to administration of the compound.

The storage of dynamic information in hydrogel is extremely interesting due to the reprogrammable and responsive features of hydrogel. Here, we report that structural information can be stored in polysaccharide hydrogel by electrically induced covalent cross-linking, and the imbedded information can be retrieved by different means (dye adsorption, protonation of chitosan, and acid dissolution). Taking the advantage of diffusible feature of hydrogel, OH- was generated from the contacting area of the electrode and controllably diffused by electrical writing, thus the high pH domain (pH ∼ 10) triggered covalent cross-linking of the hydrogel. The written area exhibits different micromorphology, chemical properties, and pH sensitivity, allowing dynamic 2D and 3D information to be stored and read when necessary. This work demonstrates the use of stable electrical inputs to store dynamic structural information in a biopolymer-based hydrogel and how the chemical and physical varies allow eye recognition to the embedded information.

For 1-MHz GaN LLC converters with 1-kV input, the switching speed of eGaN high-electron mobility transistors (HEMTs) is as fast as 6 ns, which results in dv / dt up to 200 kV/ μ s. It poses serious challenge for synchronous rectification (SR). A sensorless model-based SR driving scheme for high voltage applications is proposed to optimize the efficiency at steady state and the complementary control as an interlock mechanism is applied during the transients to ensure safety. A mathematic model is built to determine the turn- on instant and conduction time related to the switching frequency and load condition so that the driving signals are adjusted adaptively. The proposed method provides reliable gate driving signals without any detection circuits and is immune to high frequency noise. The transient response is analyzed and the tolerance effects of the resonant components are analyzed quantitatively. This control is fully transparent to design engineers compared to SR drive ICs, and is convenient to implement in high voltage and high frequency applications. A 1-MHz prototype with 1-kV input and 32 V/3 kW output is built, which achieves the power density of 103 W/in3 and peak efficiency of 95.92% with an improvement of 2.0% at full load compared to the conventional SR driving scheme.