Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals.

The World Health Organization has declared SARS-CoV-2 virus outbreak a worldwide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free, and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in eight newly discharged patients. Follow-up analysis on another cohort of six patients 2 weeks post discharge also revealed high titers of immunoglobulin G (IgG) antibodies. In all 14 patients tested, 13 displayed serum-neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It also has implications in developing an effective vaccine to SARS-CoV-2 infection.

Suppression of distracting inputs by visual-spatial cues is driven by anticipatory alpha activity.

A growing body of research demonstrates that distracting inputs can be proactively suppressed via spatial cues, nonspatial cues, or experience, which are governed by more than one top-down mechanism of attention. However, how the neural mechanisms underlying spatial distractor cues guide proactive suppression of distracting inputs remains unresolved. Here, we recorded electroencephalography signals from 110 participants in 3 experiments to identify the role of alpha activity in proactive distractor suppression induced by spatial cues and its influence on subsequent distractor inhibition. Behaviorally, we found novel changes in the spatial proximity of the distractor: Cueing distractors far away from the target improves search performance for the target, while cueing distractors close to the target hampers performance. Crucially, we found dynamic characteristics of spatial representation for distractor suppression during anticipation. This result was further verified by alpha power increased relatively contralateral to the cued distractor. At both the between- and within-subjects levels, we found that these activities further predicted the decrement of the subsequent PD component, which was indicative of reduced distractor interference. Moreover, anticipatory alpha activity and its link with the subsequent PD component were specific to the high predictive validity of distractor cue. Together, our results reveal the underlying neural mechanisms by which cueing the spatial distractor may contribute to reduced distractor interference. These results also provide evidence supporting the role of alpha activity as gating by proactive suppression.

Cell cycle arrest explains the observed bulk 3D genomic alterations in response to long-term heat shock in K562 cells.

Heat shock is a common environmental stress, although the response of the nucleus to it remains controversial in mammalian cells. Acute reaction and chronic adaptation to environmental stress may have distinct internal rewiring in the gene regulation networks. However, this difference remains largely unexplored. Here, we report that chromatin conformation and chromatin accessibility respond differently in short- and long-term heat shock in human K562 cells. We found that chromatin conformation in K562 cells was largely stable in response to short-term heat shock, whereas it showed clear and characteristic changes after long-term heat treatment with little alteration in chromatin accessibility during the whole process. We further show in silico and experimental evidence strongly suggesting that changes in chromatin conformation may largely stem from an accumulation of cells in the M stage of the cell cycle in response to heat shock. Our results represent a paradigm shift away from the controversial view of chromatin response to heat shock and emphasize the necessity of cell cycle analysis when interpreting bulk Hi-C data.

MiR-30a-5p isoform -1|1 promotes the progression of gastric cancer by inhibiting TMEM66 and reducing intratumoral cytotoxic T cells.

Gastric cancer is histologically classified into the intestinal subtype, which forms tubular structures, and the aggressive diffuse subtype, characterized by rapid invasion and poor prognosis. The variety and quantity of miRNA isoforms between different histological subtypes of gastric cancer were unknown. Through systematic filtering, we found that more diverse miR-30a-5p isoforms was present in the diffuse subtype of gastric cancer, and was associated with patients' worse survival independent of tumor stage based on the TCGA miRNA-seq data. Among all nine isoforms of miR-30a-5p, miR-30a-5p -1|1 was more abundant than the archetype of miR-30a-5p. Higher expression of miR-30a-5p -1|1 was observed in patients with advanced tumor stage and poor survival. Furthermore, miR-30a-5p -1|1 could promote the metastasis of gastric cancer cells both in vitro and in vivo by down-regulating TMEM66. In clinical samples, decreased expression of TMEM66 was characteristic of gastric cancer, and the low level of TMEM66 correlated with deceased CD8 positive cells in the tumor microenvironment probably due to decreased cytokines production. In conclusion, the variety of miR-30a-5p isoforms correlates with worse survival in gastric cancer patients. Moreover, miR-30a-5p -1|1 could promote gastric cancer metastasis by inhibiting TMEM66 and the infiltration of intratumoral CD8 positive cells.

Glymphatic dysfunction mediates the influence of choroid plexus enlargement on information processing speed in patients with white matter hyperintensities.

Glymphatic dysfunction has been correlated with cognitive decline, with a higher choroid plexus volume (CPV) being linked to a slower glymphatic clearance rate. Nevertheless, the interplay between CPV, glymphatic function, and cognitive impairment in white matter hyperintensities (WMHs) has not yet been investigated. In this study, we performed neuropsychological assessment, T1-weighted three-dimensional (3D-T1) images, and diffusion tensor imaging (DTI) in a cohort of 206 WMHs subjects and 43 healthy controls (HCs) to further explore the relationship. The DTI analysis along the perivascular space (DTI-ALPS) index, as a measure of glymphatic function, was calculated based on DTI. Severe WMHs performed significantly worse in information processing speed (IPS) than other three groups, as well as in executive function than HCs and mild WMHs. Additionally, severe WMHs demonstrated lower DTI-ALPS index and higher CPV than HCs and mild WMHs. Moderate WMHs displayed higher CPV than HCs and mild WMHs. Mini-Mental State Examination, IPS, and executive function correlated negatively with CPV but positively with DTI-ALPS index in WMHs patients. Glymphatic function partially mediated the association between CPV and IPS, indicating a potential mechanism for WMHs-related cognitive impairment. CPV may act as a valuable prognostic marker and glymphatic system as a promising therapeutic target for WMHs-related cognitive impairment.

Symmetric control of sister chromatid cohesion establishment.

Besides entrapping sister chromatids, cohesin drives other high-order chromosomal structural dynamics like looping, compartmentalization and condensation. ESCO2 acetylates a subset of cohesin so that cohesion must be established and only be established between nascent sister chromatids. How this process is precisely achieved remains unknown. Here, we report that GSK3 family kinases provide higher hierarchical control through an ESCO2 regulator, CRL4MMS22L. GSK3s phosphorylate Thr105 in MMS22L, resulting in homo-dimerization of CRL4MMS22L and ESCO2 during S phase as evidenced by single-molecule spectroscopy and several biochemical approaches. A single phospho-mimicking mutation on MMS22L (T105D) is sufficient to mediate their dimerization and rescue the cohesion defects caused by GSK3 or MMS22L depletion, whereas non-phosphorylable T105A exerts dominant-negative effects even in wildtype cells. Through cell fractionation and time-course measurements, we show that GSK3s facilitate the timely chromatin association of MMS22L and ESCO2 and subsequently SMC3 acetylation. The necessity of ESCO2 dimerization implicates symmetric control of cohesion establishment in eukaryotes.

Intracranial neural representation of phenomenal and access consciousness in the human brain.

After more than 30 years of extensive investigation, impressive progress has been made in identifying the neural correlates of consciousness (NCC). However, the functional role of spatiotemporally distinct consciousness-related neural activity in conscious perception is debated. An influential framework proposed that consciousness-related neural activities could be dissociated into two distinct processes: phenomenal and access consciousness. However, though hotly debated, its authenticity has not been examined in a single paradigm with more informative intracranial recordings. In the present study, we employed a visual awareness task and recorded the local field potential (LFP) of patients with electrodes implanted in cortical and subcortical regions. Overall, we found that the latency of visual awareness-related activity exhibited a bimodal distribution, and the recording sites with short and long latencies were largely separated in location, except in the lateral prefrontal cortex (lPFC). The mixture of short and long latencies in the lPFC indicates that it plays a critical role in linking phenomenal and access consciousness. However, the division between the two is not as simple as the central sulcus, as proposed previously. Moreover, in 4 patients with electrodes implanted in the bilateral prefrontal cortex, early awareness-related activity was confined to the contralateral side, while late awareness-related activity appeared on both sides. Finally, Granger causality analysis showed that awareness-related information flowed from the early sites to the late sites. These results provide the first LFP evidence of neural correlates of phenomenal and access consciousness, which sheds light on the spatiotemporal dynamics of NCC in the human brain.

DeNOPA: decoding nucleosome positions sensitively with sparse ATAC-seq data.

As the basal bricks, the dynamics and arrangement of nucleosomes orchestrate the higher architecture of chromatin in a fundamental way, thereby affecting almost all nuclear biology processes. Thanks to its rather simple protocol, assay for transposase-accessible chromatin using sequencing (ATAC)-seq has been rapidly adopted as a major tool for chromatin-accessible profiling at both bulk and single-cell levels; however, to picture the arrangement of nucleosomes per se remains a challenge with ATAC-seq. In the present work, we introduce a novel ATAC-seq analysis toolkit, named decoding nucleosome organization profile based on ATAC-seq data (deNOPA), to predict nucleosome positions. Assessments showed that deNOPA outperformed state-of-the-art tools with ultra-sparse ATAC-seq data, e.g. no more than 0.5 fragment per base pair. The remarkable performance of deNOPA was fueled by the short fragment reads, which compose nearly half of sequenced reads in the ATAC-seq libraries and are commonly discarded by state-of-the-art nucleosome positioning tools. However, we found that the short fragment reads enrich information on nucleosome positions and that the linker regions were predicted by reads from both short and long fragments using Gaussian smoothing. Last, using deNOPA, we showed that the dynamics of nucleosome organization may not directly couple with chromatin accessibility in the cis-regulatory regions when human cells respond to heat shock stimulation. Our deNOPA provides a powerful tool with which to analyze the dynamics of chromatin at nucleosome position level with ultra-sparse ATAC-seq data.

CMMS-GCL: cross-modality metabolic stability prediction with graph contrastive learning.

MOTIVATION: Metabolic stability plays a crucial role in the early stages of drug discovery and development. Accurately modeling and predicting molecular metabolic stability has great potential for the efficient screening of drug candidates as well as the optimization of lead compounds. Considering wet-lab experiment is time-consuming, laborious, and expensive, in silico prediction of metabolic stability is an alternative choice. However, few computational methods have been developed to address this task. In addition, it remains a significant challenge to explain key functional groups determining metabolic stability. RESULTS: To address these issues, we develop a novel cross-modality graph contrastive learning model named CMMS-GCL for predicting the metabolic stability of drug candidates. In our framework, we design deep learning methods to extract features for molecules from two modality data, i.e. SMILES sequence and molecule graph. In particular, for the sequence data, we design a multihead attention BiGRU-based encoder to preserve the context of symbols to learn sequence representations of molecules. For the graph data, we propose a graph contrastive learning-based encoder to learn structure representations by effectively capturing the consistencies between local and global structures. We further exploit fully connected neural networks to combine the sequence and structure representations for model training. Extensive experimental results on two datasets demonstrate that our CMMS-GCL consistently outperforms seven state-of-the-art methods. Furthermore, a collection of case studies on sequence data and statistical analyses of the graph structure module strengthens the validation of the interpretability of crucial functional groups recognized by CMMS-GCL. Overall, CMMS-GCL can serve as an effective and interpretable tool for predicting metabolic stability, identifying critical functional groups, and thus facilitating the drug discovery process and lead compound optimization. AVAILABILITY AND IMPLEMENTATION: The code and data underlying this article are freely available at https://github.com/dubingxue/CMMS-GCL.

Single domain antibodies against enteric pathogen virulence factors are active as curli fiber fusions on probiotic E. coli Nissle 1917.

Enteric microbial pathogens, including Escherichia coli, Shigella and Cryptosporidium species, take a particularly heavy toll in low-income countries and are highly associated with infant mortality. We describe here a means to display anti-infective agents on the surface of a probiotic bacterium. Because of their stability and versatility, VHHs, the variable domains of camelid heavy-chain-only antibodies, have potential as components of novel agents to treat or prevent enteric infectious disease. We isolated and characterized VHHs targeting several enteropathogenic E. coli (EPEC) virulence factors: flagellin (Fla), which is required for bacterial motility and promotes colonization; both intimin and the translocated intimin receptor (Tir), which together play key roles in attachment to enterocytes; and E. coli secreted protein A (EspA), an essential component of the type III secretion system (T3SS) that is required for virulence. Several VHHs that recognize Fla, intimin, or Tir blocked function in vitro. The probiotic strain E. coli Nissle 1917 (EcN) produces on the bacterial surface curli fibers, which are the major proteinaceous component of E. coli biofilms. A subset of Fla-, intimin-, or Tir-binding VHHs, as well as VHHs that recognize either a T3SS of another important bacterial pathogen (Shigella flexneri), a soluble bacterial toxin (Shiga toxin or Clostridioides difficile toxin TcdA), or a major surface antigen of an important eukaryotic pathogen (Cryptosporidium parvum) were fused to CsgA, the major curli fiber subunit. Scanning electron micrographs indicated CsgA-VHH fusions were assembled into curli fibers on the EcN surface, and Congo Red binding indicated that these recombinant curli fibers were produced at high levels. Ectopic production of these VHHs conferred on EcN the cognate binding activity and, in the case of anti-Shiga toxin, was neutralizing. Taken together, these results demonstrate the potential of the curli-based pathogen sequestration strategy described herein and contribute to the development of novel VHH-based gut therapeutics.

Covalent Binding of Reactive Anhydride of Cantharidin to Biological Amines.

Cantharidin is a terpenoid from coleoptera beetles. Cantharidin has been used to treat molluscum contagiosum and some types of tumors. Cantharidin is highly toxic, and cantharidin poisoning and fatal cases have been reported worldwide. The mechanisms underlying cantharidin-induced toxicity remain unclear. Cantharidin contains anhydride, which may react with biologic amines. This study aimed to examine the chemical reactivity of cantharidin toward nucleophiles and characterize adducts of cantharidin with biologic amines in vitro and in mice. Here two types of conjugates were formed in the incubation of cantharidin under physiologic conditions with free amino acids, a mimic peptide, or amine-containing compounds, respectively. Amide-type conjugates were produced by the binding of cantharidin anhydride with the primary amino group of biologic amines. Imide-type conjugates were generated from the dehydration and cyclization of amide-type conjugates. The structure of the conjugates was characterized by using high-resolution mass spectrometry. We introduced the 14N/15N and 79Br/81Br isotope signatures to confirm the formation of conjugates using L-(ε)15N-lysine, L-lysine-15N2, and bromine-tagged hydrazine, respectively. The structure of imide conjugate was also confirmed by nuclear magnetic resonance experiments. Furthermore, the amide and imide conjugates of cantharidin with amino acids or N-acetyl-lysine were detected in mouse liver and urine. Cantharidin was found to modify lysine residue proteins in mouse liver. Pan-cytochrome P450 inhibitor 1-aminobenzotriazole significantly increased the urine cantharidin-N-acetyl-lysine conjugates, whereas it decreased cantharidin metabolites. In summary, cantharidin anhydride can covalently bind to biologic amines nonenzymatically, which facilitates a better understanding of the role of nonenzymatic reactivity in cantharidin poisoning. SIGNIFICANCE STATEMENT: Anhydride moiety of cantharidin can covalently bind to the primary amino group of biological amines nonenzymatically. Amide and imide conjugates were generated after the covalent binding of cantharidin anhydride with the primary amino groups of amino acids, a mimic peptide, and protein lysine residues. The structure of conjugates was confirmed by 14N/15N and 79Br/81Br isotope signatures using isotope-tagged reagents and nuclear magnetic resonance experiments. This study will facilitate the understanding of the role of nonenzymatic reactivity in cantharidin poisoning.

Isolation, identification, and pathogenicity of Pseudomonas glycinae causing ginseng bacterial soft rot in China.

By tissue separation method, tie-back experiment, and hypersensitive response test in potato, strain XJFL-1 was isolated and identified as the pathogen of ginseng bacterial soft rot in Liaoning Provence, China. The morphological characteristics of XJFL-1 were conformed to the Pseudomonads genus. Microbial fatty acid identification showed the principal cellular fatty acid traits of XLFJ-1 corresponded with Pseudomonas spp. API 50CH test results allowed the differentiation of strain XJFL-1 and MS586T from other closely related Pseudomonas species. The molecular identification, including 16S rRNA analysis and multilocus sequence typing (MLST) analysis, showed that XJFL-1 was in the same branch as P. glycinae MS586T. The genome of XJFL-1 was 6,296,473 bp, with an average guanine/cytosine (G + C) content of 60.72 %. Comparative genomics analysis using ANIb and GGDC algorithms indicated that the maximum value was observed between XJFL-1 and P. glycinae MS586T. The above morphological, cell morphology, and molecular biological identification results supported to identification of XJFL-1 as P. glycinae. This is the first report of P. glycinae as the plant pathogen causing ginseng bacterial root rot in China, which complements the biological significance of the species to a certain extent, enriches the pathogens of ginseng bacterial soft rot, and provides a theoretical basis for further investigation.

Hyperechoic spots in the renal medulla as a potential indicator of early gouty nephropathy.

INTRODUCTION: To explore the causes and clinical significance of hyperechoic renal medulla observed by ultrasonography in patients with primary gout. METHODS: This study included 2107 patients with primary gout treated in the Gout Clinic of our hospital from 2016 to 2022. The clinical data and biochemical data of these patients were collected and analyzed. According to the presence or absence of punctate hyper-echogenicity in the renal medulla on ultrasound examination, the patients were divided into the hyperechoic medulla (HM) and the normal hypoechoic medulla (NM) groups, and the HM group was further divided into the partial HM (P-HM) and fulfilled-HM (F-HM) subgroups according to the distribution range of hyper-echogenicity. RESULTS: Among the 2107 patients with primary gout, 380 had hyperechoic renal medulla on renal ultrasound, including 106 patients with F-HM and 274 with P-HM. There were significant differences in the gout duration, urate arthropathies number, serum urate (SU) level, clinical tophi number, blood urea nitrogen (BUN), sCr, and eGFR between the HM and NM groups or between the F-HM and P-HM subgroups (P < 0.05). Multivariate regression analysis showed that the presence of hyperechoic medulla was positively correlated with gout duration, urate arthropathy number, gout attack frequency, SU, and sCr. The number of clinical tophi and sCr were closely related to F-HM. CONCLUSION: Ultrasound examination showed that a high medulla echo in patients with gout was often related to renal function damage. P-HM may be a transitory condition between NM and F-HM in patients with gout.

Comparison of efficacy of eltrombopag combined with immunosuppression in the treatment of severe aplastic anemia and very severe aplastic anemia: real-world data and evidence.

Eltrombopag combined with immunosuppressive therapy (IST) was superior to IST alone for severe aplastic anemia (SAA) in the previous studies. But in China, horse antithymocyte globulin (hATG) is not available, instead, we use rabbit ATG (rATG). Here, we compared the efficacy and safety of IST (rATG combined with cyclosporine) combined with or without eltrombopag for the first-line treatment of SAA and very severe aplastic anemia (VSAA). A total of 371 patients in ten institutions in China from April 1, 2017 to December 1, 2022 were enrolled. The overall response (OR) rate at 3 months (54.2% vs. 41%; P = 0.046), the complete response (CR) (31.3% vs. 19.4%; P = 0.041) and OR (78.3% vs. 51.1%; P < 0.0001) rates at 6 months were significantly higher with IST combined with eltrombopag than with IST alone in SAA patients. While in VSAA patients, the addition of eltrombopag to IST only increased the CR rate at 6 months (29.8% vs. 9.43%; P = 0.010). Liver injury increased significantly in groups treated with IST combined with eltrombopag (P < 0.05). Serious treatment-related toxicities were similar (P > 0.05). In patients with SAA, 3-year failure-free survival (FFS) of eltrombopag combined with IST group was significantly higher than that of IST group (70.7 ± 5.3% vs. 50.3 ± 3.9%; P = 0.007). In patients with VSAA, the addition of eltrombopag significantly improved 3-year overall survival (OS) (82.2 ± 5.7% vs. 57.3 ± 7.2%; P = 0.020). Our findings suggested that IST combined with eltrombopag could improve the hematological recovery of newly diagnosed SAA without increasing severe toxicities. But in VSAA, the addition of eltrombopag seemed to show no other improvement to efficacy except the CR rate at 6 months.

Halogen-Free Functional Quaternary Ammonium-Based Ionic Liquid as an Ecofriendly Corrosion Inhibitor for Q235 Steel in Acids.

A halogen-free quaternary ammonium-based ionic liquid functionalized with benzotriazole, BTA-16-BTA, was synthesized. Its anticorrosion effects on Q235 steel were evaluated in two different acids (6 M HCl or 1 M H3PO4) by weight loss and electrochemical tests. BTA-16-BTA shows the best performance at 30 °C with the highest inhibition efficiencies of 98.84% in 6 M HCl and 96.40% in 1 M H3PO4. The adsorption behavior of BTA-16-BTA molecules on Q235 steel in HCl solution obeys the Langmuir isotherm with an adsorption energy of about -40 kJ·mol-1, which implies chemisorption. Quantum chemistry calculation indicates that the chemical adsorption originated from the injection of π-electrons from inhibitor molecules into empty 3d orbitals of Fe atoms. The tight adsorption of inhibitor molecules and associated dehydration of the steel surface promoted the corrosion inhibition in HCl solutions. In H3PO4 solutions, passivation by phosphate anions and adsorption of inhibitor molecules contributed synergistically to the excellent anticorrosion performance.

State-related Electroencephalography Microstate Complexity during Propofol- and Esketamine-induced Unconsciousness.

BACKGROUND: Identifying the state-related "neural correlates of consciousness" for anesthetics-induced unconsciousness is challenging. Spatiotemporal complexity is a promising tool for investigating consciousness. The authors hypothesized that spatiotemporal complexity may serve as a state-related but not drug-related electroencephalography (EEG) indicator during an unconscious state induced by different anesthetic drugs (e.g., propofol and esketamine). METHODS: The authors recorded EEG from patients with unconsciousness induced by propofol (n = 10) and esketamine (n = 10). Both conventional microstate parameters and microstate complexity were analyzed. Spatiotemporal complexity was constructed by microstate sequences and complexity measures. Two different EEG microstate complexities were proposed to quantify the randomness (type I) and complexity (type II) of the EEG microstate series during the time course of the general anesthesia. RESULTS: The coverage and occurrence of microstate E (prefrontal pattern) and the duration of microstate B (right frontal pattern) could distinguish the states of preinduction wakefulness, unconsciousness, and recovery under both anesthetics. Type I EEG microstate complexity based on mean information gain significantly increased from awake to unconsciousness state (propofol: from mean ± SD, 1.562 ± 0.059 to 1.672 ± 0.023, P < 0.001; esketamine: 1.599 ± 0.051 to 1.687 ± 0.013, P < 0.001), and significantly decreased from unconsciousness to recovery state (propofol: 1.672 ± 0.023 to 1.537 ± 0.058, P < 0.001; esketamine: 1.687 ± 0.013 to 1.608 ± 0.028, P < 0.001) under both anesthetics. In contrast, type II EEG microstate fluctuation complexity significantly decreased in the unconscious state under both drugs (propofol: from 2.291 ± 0.771 to 0.782 ± 0.163, P < 0.001; esketamine: from 1.645 ± 0.417 to 0.647 ± 0.252, P < 0.001), and then increased in the recovery state (propofol: 0.782 ± 0.163 to 2.446 ± 0.723, P < 0.001; esketamine: 0.647 ± 0.252 to 1.459 ± 0.264, P < 0.001). CONCLUSIONS: Both type I and type II EEG microstate complexities are drug independent. Thus, the EEG microstate complexity measures that the authors proposed are promising tools for building state-related neural correlates of consciousness to quantify anesthetic-induced unconsciousness.

A nature-inspired multifunctional adhesive for cartilage tissue-biomaterial integration.

Surgical adhesives play a crucial role in tissue integration and repair, yet their application in wet conditions has been severely limited by inadequate adhesive strength and subpar biocompatibility. Furthermore, tissue adhesives have rarely been reported in cartilage tissue repair. In this study, a three-armed dopamine-modified hyaluronic acid derivative adhesive was prepared to function as a bio-inspired adhesive in moist environments. To meet the clinical requirements for cartilage tissue adhesion, we studied its chemical structure, including microscopic morphology, adhesion properties with materials and tissues, in vivo degradation rules, and biological evaluation. The OGMHA8-DOPA adhesive with the optimal aldehyde substitution degree and dopamine-grafting rate was determined by analyzing the experimental conditions. SEM results revealed that the cartilage tissue adhered to a porous interconnected structure. The excellent biocompatibility of the material not only facilitated chondrocyte adhesion but also supported their proliferation on its surface. Animal experiments have demonstrated that this material has no observable inflammatory response or incidence of fibrous capsule formation. The degradation timeline of the material extends beyond the duration of two weeks. The dopamine-modified adhesive exhibited a tight interfacial binding force between the biomaterial and cartilage tissue and excellent biocompatibility in watery tissue, revealing its potential for application in cartilage tissue repair and minimally invasive surgery.

Clinical and epidemiological features of imported loiasis in Beijing: a report from patients returned from Africa.

BACKGROUND: Loiasis is one of the significant filarial diseases for people living in West and Central Africa with wide endemic area but is not seen in China. As economy booms and international traveling increase, China faces more and more imported parasitic diseases that are not endemic locally. Loiasis is one of the parasitic diseases that enter China by travelers infected in Africa. The better understanding of the clinical and laboratory features of loa loa infection will facilitate the diagnosis and treatment of loiasis in China. METHODS: The study targeted travelers who were infected with L. loa in endemic Africa regions and returned to Beijing between 2014 and 2023. Epidemiological, clinical, and biological data as well as treatment of these patients were collected. RESULTS: Total 21 cases were identified as L. loa infection based on their typical clinical manifestations and parasite finding. All cases had a history of travel to Africa for more than 6 months, most of them are the construction workers dispatched to West Africa with outdoor activities. Calabar swelling (n = 19; 90.5%) and pruritus (n = 11; 52.4%) were among the most common clinical symptoms followed by muscle pain (n = 7; 33.3%) and skin rash (n = 2; 9.5%). The adult worms were observed in the eyelid or subconjunctiva (n = 2; 9.5%) and subcutaneous tissues (n = 2; 9.5%). Although all patients presented with a high eosinophil count (> 0.52 × 109/L), only two cases displayed microfilariae in fresh venous blood and positive for filarial antigen. A cut section of adult worm was observed through biopsy on a skin nodule surrounded by lymphocytes, plasma cells and eosinophils. All subjects were positive in PCR targeting L. loa ITS-1. The constructed phylogenetic tree based on the amplified ITS-1 sequences identified their genetical relation to the L. Loa from Africa. All patients treated with albendazole and diethylcarbamazine were recovered without relapse. CONCLUSION: This study provides useful information and guideline for physicians and researchers in non-endemic countries to diagnose and treat loiasis and L. loa infections acquired from endemic regions.

Silver nanowires/cellulose flexible transparent conductive films for electromagnetic interference shielding and electrothermal conversion.

Currently, electromagnetic shielding materials need to meet the characteristics of lightweight, high transmittance, and robust conductivity. Silver nanowires (AgNWs) have progressively found applications in recent years owing to their excellent aspect ratio, conductivity, and flexibility. The properties of AgNWs vary with different aspect ratios, and the length and diameter of AgNWs often exert diverse influences on the photoelectric properties of conductive films. In this study, we combined AgNWs with hydroxypropyl methylcellulose (HPMC) and employed a directional stacking arrangement method to apply AgNWs onto the PET substrate, investigating the properties of four distinct aspect ratios of AgNWs (1000, 750, 625, and 531). Ultimately, the prepared four films achieved electromagnetic shielding capabilities ranging from 26.6 dB to 32.8 dB, with a transmittance range of 89.8% to 94.6%, showing excellent electromagnetic shielding properties. Moreover, the prepared films showed an exceedingly low roughness value (RMS = 7.07 nm), remarkable flexibility, and superior oxidation resistance with the facilitation of HPMC. The films also showed exceptional electrothermal conversion prowess, achieving saturation temperature within a mere 8 seconds, thereby displaying a rapid thermal response. Furthermore, when a voltage of 4 V was applied, the temperature of the thin film remained essentially constant for a duration of 2500 seconds, highlighting its admirable thermal stability, which is of great significance for the development of flexible and transparent electromagnetic shielding materials in the future.

Protoilludane-Type and Related Nor-Sesquiterpenes from Phellinus hartigii and Their Anti-Hypertrophic Activities in Rat Cardiomyocytes.

Three nor-sesquiterpenes, phellinharts A-C (1-3), isolated from Phellinus hartigii, exhibited unprecedented protoilludane and cerapicane-type structures. The structures of compounds 1-3 were elucidated via spectroscopic analysis, quantum chemical calculations, and X-ray diffraction. Potential biogenic pathways involving demethylation, ring cleavage, and rearrangement were proposed. Compounds 1-3 displayed potent anti-hypertrophic activities with low cytotoxicity (CC50 > 50 µM) in rat cardiomyocytes, underscoring their therapeutic potential.