Stable peptide-assembled nanozyme mimicking dual antifungal actions.

Natural antimicrobial peptides (AMPs) and enzymes (AMEs) are promising non-antibiotic candidates against antimicrobial resistance but suffer from low efficiency and poor stability. Here, we develop peptide nanozymes which mimic the mode of action of AMPs and AMEs through de novo design and peptide assembly. Through modelling a minimal building block of IHIHICI is proposed by combining critical amino acids in AMPs and AMEs and hydrophobic isoleucine to conduct assembly. Experimental validations reveal that IHIHICI assemble into helical ß-sheet nanotubes with acetate modulation and perform phospholipase C-like and peroxidase-like activities with Ni coordination, demonstrating high thermostability and resistance to enzymatic degradation. The assembled nanotubes demonstrate cascade antifungal actions including outer mannan docking, wall disruption, lipid peroxidation and subsequent ferroptotic death, synergistically killing >90% Candida albicans within 10 min on disinfection pad. These findings demonstrate an effective de novo design strategy for developing materials with multi-antimicrobial mode of actions.

Decoding N400m Evoked Component: A Tutorial on Multivariate Pattern Analysis for OP-MEG Data.

Multivariate pattern analysis (MVPA) has played an extensive role in interpreting brain activity, which has been applied in studies with modalities such as functional Magnetic Resonance Imaging (fMRI), Magnetoencephalography (MEG) and Electroencephalography (EEG). The advent of wearable MEG systems based on optically pumped magnetometers (OPMs), i.e., OP-MEG, has broadened the application of bio-magnetism in the realm of neuroscience. Nonetheless, it also raises challenges in temporal decoding analysis due to the unique attributes of OP-MEG itself. The efficacy of decoding performance utilizing multimodal fusion, such as MEG-EEG, also remains to be elucidated. In this regard, we investigated the impact of several factors, such as processing methods, models and modalities, on the decoding outcomes of OP-MEG. Our findings indicate that the number of averaged trials, dimensionality reduction (DR) methods, and the number of cross-validation folds significantly affect the decoding performance of OP-MEG data. Additionally, decoding results vary across modalities and fusion strategy. In contrast, decoder type, resampling frequency, and sliding window length exert marginal effects. Furthermore, we introduced mutual information (MI) to investigate how information loss due to OP-MEG data processing affect decoding accuracy. Our study offers insights for linear decoding research using OP-MEG and expand its application in the fields of cognitive neuroscience.

Expanding the clinical application of OPM-MEG using an effective automatic suppression method for the dental brace metal artifact.

Optically pumped magnetometer magnetoencephalography (OPM-MEG) holds significant promise for clinical functional brain imaging due to its superior spatiotemporal resolution. However, effectively suppressing metallic artifacts, particularly from devices such as orthodontic braces and vagal nerve stimulators remains a major challenge, hindering the wider clinical application of wearable OPM-MEG devices. A comprehensive analysis of metal artifact characteristics from time, frequency, and time-frequency perspectives was conducted for the first time using an OPM-MEG device in clinical medicine. This study focused on patients with metal orthodontics, examining the modulation of metal artifacts by breath and head movement, the incomplete regular sub-Gaussian distribution, and the high absolute power ratio in the 0.5-8 Hz band. The existing metal artifact suppression algorithms applied to SQUID-MEG, such as fast independent component analysis (FastICA), information maximization (Infomax), and algorithms for multiple unknown signal extraction (AMUSE), exhibit limited efficacy. Consequently, this study introduced the second-order blind identification (SOBI) algorithm, which utilized multiple time delays for the component separation of OPM-MEG measurement signals. We modified the time delays of the SOBI method to improve its efficacy in separating artifact components, particularly those in the ultralow frequency range. This approach employs the frequency-domain absolute power ratio, root mean square (RMS) value, and mutual information methods to automate the artifact component screening process. The effectiveness of this method was validated through simulation experiments involving four subjects in both resting and evoked experiments. In addition, the proposed method was also validated by the actual OPM-MEG evoked experiments of three subjects. Comparative analyses were conducted against the FastICA, Infomax, and AMUSE algorithms. Evaluation metrics included normalized mean square error, normalized delta band power error, RMS error, and signal-to-noise ratio, demonstrating that the proposed method provides optimal suppression of metal artifacts. This advancement holds promise for enhancing data quality and expanding the clinical applications of OPM-MEG.

Hepatic-derived BMP9 is involved in hepatic fibrosis-induced kidney injury through inhibition of renal VEGFA.

Clinical observations suggest that acute kidney injury (AKI) occurs in approximately 20-50% of hospitalized cirrhotic patients, suggesting a link between the liver and kidney. Bone morphogenetic protein 9 (BMP9) is a protein produced primarily by the liver and can act on other tissues at circulating systemic levels. Previous studies have demonstrated that controlling abnormally elevated BMP9 in acute liver injury attenuates liver injury; however, reports on whether BMP9 plays a role in liver injury-induced AKI are lacking. By testing we found that liver injury in mice after bile duct ligation (BDL) was accompanied by a significant upregulation of the kidney injury marker kidney injury molecule (KIM-1). Interestingly, all these impairments were alleviated in the kidneys of hepatic BMP9 knockout (BMP9-KO) mice. Peritubular capillary injury is a key process leading to the progression of AKI, and previous studies have demonstrated that vascular endothelial growth factor A (VEGFA) plays a key role in maintaining the renal microvascular system. In animal experiments, we found that high levels of circulating BMP9 had an inhibitory effect on VEGFA expression, while renal tubular epithelial cell injury was effectively attenuated by VEGFA supplementation in the hypoxia-enriched-oxygen (H/R) constructs of the AKI cell model in both humans and mice. Overall, we found that elevated BMP9 in hepatic fibrosis can affect renal homeostasis by regulating VEGFA expression. Therefore, we believe that targeting BMP9 therapy may be a potential means to address the problem of clinical liver fibrosis combined with AKI.

Extraction of Proteins from Soil.

Soil metaproteomics could explore the proteins involved in life activities and their abundance in the soils to overcome the difficulty in pure cultures of soil microorganisms and the limitations of proteomics of pure cultures. However, the complexity and heterogeneity of soil composition, the low abundance of soil proteins, and the presence of massive interfering substances (including humic compounds) generally lead to an extremely low extraction efficiency of soil proteins. Therefore, the efficient extraction of soil proteins is a prerequisite and bottleneck problem in soil metaproteomics. In this chapter, a soil protein extraction method suitable for most types of soils with low cost and enabling simple operation (about 150 µg protein can be extracted from 5.0 g soil) is described. The quantity and purity of the extracted soil proteins could meet the requirements for further analysis using routine mass spectrometry-based proteomics.

Fungal Secretomics Through iTRAQ-Based Analysis.

Our understanding of how fungi respond and adapt to external environments can be increased by the comprehensive data sets of fungal-secreted proteins. Fungi produce a variety of secreted proteins, and environmental conditions can easily influence the fungal secretome. However, the low abundance of secreted proteins and their post-translational modifications make protein extraction more challenging. Hence, the enrichment of secreted proteins is a crucial procedure for secretome analysis. This chapter illustrates a protocol for iTRAQ-based quantitative secretome analysis describing the example of fungi exposed to different environmental conditions. The fungal-secreted proteins can be extracted by combining ultrafiltration and TCA-acetone precipitation. Subsequently, the secreted proteins can be identified and quantified by the iTRAQ-based quantitative proteomics approach.

Exosomal circ_CCDC7/gga-miR-6568-3p/Pax7 axis accelerates the differentiation of chicken embryonic stem cells infected with subgroup J avian leukosis virus.

Exosome-mediated horizontal and vertical transmission of subgroup J avian leukosis virus (ALV-J) in poultry flocks can lead to growth inhibition and severe immunosuppression. However, there are few reports on the early infection of chicken embryonic stem cells (cESCs) with ALV-J. In this study, we confirmed that early infection with ALV-J can accelerate the differentiation of cESCs and promote the secretion of exosomes. To investigate the modulation strategy of ALV-J in cESCs, circRNA sequencing was performed for further analysis. A total of 305 differentially expressed circRNAs (DECs) were obtained, including 71 upregulated DECs. Circ-CCDC7 was found to be the most upregulated DEC and was assessed by qRT-PCR, with the result consistent with the result of circRNA-seq. Based on qRT-PCR, gga-miR-6568-3p was found to be the target of the top 3 DECs, including circ-CCDC7, and the stem cell marker gene Pax7 was identified as the target gene of gga-miR-6568-3p. This study demonstrated that exosomal circ-CCDC7/gga-miR-6568-3p/Pax7 accelerates the differentiation of cESCs after early infection with ALV-J.

Monomolecular Membrane-Assisted Growth of Antimony Halide Perovskite/MoS2 Van der Waals Epitaxial Heterojunctions with Long-Lived Interlayer Exciton.

Epitaxial growth stands as a key method for integrating semiconductors into heterostructures, offering a potent avenue to explore the electronic and optoelectronic characteristics of cutting-edge materials, such as transition metal dichalcogenide (TMD) and perovskites. Nevertheless, the layer-by-layer growth atop TMD materials confronts a substantial energy barrier, impeding the adsorption and nucleation of perovskite atoms on the 2D surface. Here, we epitaxially grown an inorganic lead-free perovskite on TMD and formed van der Waals (vdW) heterojunctions. Our work employs a monomolecular membrane-assisted growth strategy that reduces the contact angle and simultaneously diminishing the energy barrier for Cs3Sb2Br9 surface nucleation. By controlling the nucleation temperature, we achieved a reduction in the thickness of the Cs3Sb2Br9 epitaxial layer from 30 to approximately 4 nm. In the realm of inorganic lead-free perovskite and TMD heterojunctions, we observed long-lived interlayer exciton of 9.9 ns, approximately 36 times longer than the intralayer exciton lifetime, which benefited from the excellent interlayer coupling brought by direct epitaxial growth. Our research introduces a monomolecular membrane-assisted growth strategy that expands the diversity of materials attainable through vdW epitaxial growth, potentially contributing to future applications in optoelectronics involving heterojunctions.

Development and characterization of a novel specific monoclonal antibody against mink enteritis virus and its antigen epitope analysis.

This study prepared a novel monoclonal antibody (MAb) against mink enteritis parvovirus (MEV) and identified its antigen epitope. The antibody subclass is identified as IgG1, the titers of the MAb is up to 1:1 × 106 and keeps stably after low-temperature storage for 9 months or 11 passages of the MAb cells. The MAb can specifically recognize MEV in the cells in IFA, but not Aleutian disease virus (ADV) or canine distemper virus (CDV). Its antigen epitope was identified as a polypeptide containing 5 key amino acids (378YAFGR382) and the homology in 20 MEV strains, 4 canine parvovirus strains, and 4 feline panleukopenia virus strains was 100%. This study supplies a biological material for developing new methods to detect MEV.

A novel dual near-infrared fluorescent probe for bioimaging and visualization of viscosity in acute alcoholic liver injury.

A dual NIR fluorescent probe Cy-ND is developed for viscosity sensing with λex/em = 766/806 nm, making it apt for biological analysis, whose response is validated through DFT and TDDFT computations. Cy-ND successfully detected viscosity changes amidst acute alcohol-induced liver injury and liver ischemia-reperfusion injury.

Automatic Estimation of the Interference Subspace Dimension Threshold in the Subspace Projection Algorithms of Magnetoencephalography Based on Evoked State Data.

A class of algorithms based on subspace projection is widely used in the denoising of magnetoencephalography (MEG) signals. Setting the dimension of the interference (external) subspace matrix of these algorithms is the key to balancing the denoising effect and the degree of signal distortion. However, most current methods for estimating the dimension threshold rely on experience, such as observing the signal waveforms and spectrum, which may render the results too subjective and lacking in quantitative accuracy. Therefore, this study proposes a method to automatically estimate a suitable threshold. Time-frequency transformations are performed on the evoked state data to obtain the neural signal of interest and the noise signal in a specific time-frequency band, which are then used to construct the objective function describing the degree of noise suppression and signal distortion. The optimal value of the threshold in the selected range is obtained using the weighted-sum method. Our method was tested on two classical subspace projection algorithms using simulation and two sensory stimulation experiments. The thresholds estimated by the proposed method enabled the algorithms to achieve the best waveform recovery and source location error. Therefore, the threshold selected in this method enables subspace projection algorithms to achieve the best balance between noise removal and neural signal preservation in subsequent MEG analyses.

A novel electrochemical aptasensor based on AgPdNPs/PEI-GO and hollow nanobox-like Pt@Ni-CoHNBs for procymidone detection.

Herein, an aptasensor based on a signal amplification strategy was developed for the sensitive detection of procymidone (PCM). AgPd nanoparticles/Polenimine Graphite oxide (AgPdNPs/PEI-GO) was weaned as electrode modification material to facilitate electron transport and increase the active sites on the electrode surface. Besides, Pt@Ni-Co nanoboxes (Pt@Ni-CoHNBs) were utilized to be carriers for signaling tags, after hollowing ZIF-67 and growing Pt, the resulting Pt@Ni-CoHNBs has a tremendous amounts of folds occurred on the surface, enables it to carry a larger quantity of thionine, thus amplify the detectable electrochemical signal. In the presence of PCM, the binding of PCM to the signal probe would trigger a change in electrical signal. The aptasensor was demonstrated with excellent sensitivity and a low detection limit of 0.98 pg·mL-1, along with a wide linear range of 1 µg·mL-1 to 1 pg·mL-1. Meanwhile, the specificity, stability and reproducibility of the constructed aptasensor were proved to be satisfactory.

Smad4 deficiency inhibits lung metastases through enhancing phagocytosis of lung interstitial macrophages.

Smad4, a critical mediator of TGF-ß signaling, plays a pivotal role in regulating various cellular functions, including immune responses. In this study, we investigated the impact of Smad4 knockout specifically in macrophages on anti-tumor immunity, focusing on lung metastasis of B16 melanoma cells. Using a mouse model with Smad4 knockout in macrophages established via Lyz2-cre mice and Smad4 flox/flox mice, we demonstrated a significant inhibition of B16 metastasis in the lungs. Interestingly, the inhibition of tumor growth was found to be independent of adaptive immunity, as no significant changes were observed in the numbers or activities of T cells, B cells, or NK cells. Instead, Smad4 knockout led to the emergence of an MCHIIlow CD206high subset of lung interstitial macrophages, characterized by enhanced phagocytosis function. Our findings highlight the crucial role of Smad4 in modulating the innate immune response against tumors and provide insights into potential therapeutic strategies targeting lung interstitial macrophages to enhance anti-tumor immunity.

Nonlocal erasing and writing of ferroelectric domains using a femtosecond laser in lithium niobate.

We experimentally demonstrate the highly-efficient nonlocal erasing and writing of ferroelectric domains using a femtosecond laser in lithium niobate. Based on the induction of a focused infrared femtosecond laser without any relative displacement or additional treatment, the original multiple ferroelectric domains can be either erased (erasing operation) or elongated (writing operation) simultaneously in the crystal, depending on the laser focusing depth and the laser pulse energy. In the erasing operation, the original multiple ferroelectric domains can be cleared completely by just one laser induction, while in the writing operation, the average length of the ferroelectric domains can be elongated up to 235 µm by three laser inductions. A model has been proposed in which a thermoelectric field and a space charge field are used cooperatively to successfully explain the mechanism of nonlocal erasing and writing. This method greatly improves the efficiency and flexibility of tailoring ferroelectric domain structures, paving the way to large-scale all-optical industrial production for nonlinear photonic crystals and nonvolatile ferroelectric domain wall memories.

Local resection via partial lamellar sclerouvectomy for ciliary body tumors - a case series.

BACKGROUND: Ciliary body tumor is extremely rare and treatment is challenging. The aim of this study is to present our experience in treating this rare entity, especially large tumors with more than 5 clock hours of involvement, and to evaluate the surgical outcomes and complications of local resection via partial lamellar sclerouvectomy in four cases of ciliary body tumors in China. METHODS: Four patients with ciliary body tumors underwent partial lamellar sclerouvectomy between October 2019 and April 2023 in Shanghai General Hospital, China. Tumor features, histopathologic findings, complications, visual acuity, and surgical outcomes were reviewed at a mean follow-up of 20.8 months. RESULTS: Four patients with a mean age of 31.8 years were included in this study. The histopathological diagnosis was adenoma of non-pigmented ciliary epithelium (ANPCE), schwannoma, and multiple ciliary body pigment epithelial cysts. The mean largest tumor base diameter was 6.00 mm (range: 2.00-10.00) and the mean tumor thickness was 3.50 mm (range: 2.00-5.00). Preoperative complications included cataract in 3 (75%) eyes, lens dislocation in 2 (50%), and secondary glaucoma in 1 (25%). Temporary ocular hypotonia was observed in one case and no other postoperative complications were observed. At a mean follow-up of 20.8 months, the best corrected visual acuity increased in 3 eyes and was stable in 1 eye. Tumor recurrence was absent in all eyes. All patients were alive at the end of follow-up. CONCLUSIONS: Local tumor resection via PLSU is useful in the treatment of ciliary body tumors, including large tumors occupying more than five clock hours of pars plicata. Surgery-related complications were manageable with adequate preoperative assessment and careful operation during surgery.

A Multivariate analysis on evoked components of Chinese semantic congruity: an OP-MEG study with EEG.

The application of wearable magnetoencephalography using optically-pumped magnetometers has drawn extensive attention in the field of neuroscience. Electroencephalogram system can cover the whole head and reflect the overall activity of a large number of neurons. The efficacy of optically-pumped magnetometer in detecting event-related components can be validated through electroencephalogram results. Multivariate pattern analysis is capable of tracking the evolution of neurocognitive processes over time. In this paper, we adopted a classical Chinese semantic congruity paradigm and separately collected electroencephalogram and optically-pumped magnetometer signals. Then, we verified the consistency of optically-pumped magnetometer and electroencephalogram in detecting N400 using mutual information index. Multivariate pattern analysis revealed the difference in decoding performance of these two modalities, which can be further validated by dynamic/stable coding analysis on the temporal generalization matrix. The results from searchlight analysis provided a neural basis for this dissimilarity at the magnetoencephalography source level and the electroencephalogram sensor level. This study opens a new avenue for investigating the brain's coding patterns using wearable magnetoencephalography and reveals the differences in sensitivity between the two modalities in reflecting neuron representation patterns.

Acute exposure to tris(2,4-di-tert-butylphenyl)phosphate elicits cardiotoxicity in zebrafish (Danio rerio) larvae via inducing ferroptosis.

Tris(2,4-di-tert-butylphenyl)phosphate (AO168 =O), a novel organophosphate ester, is prevalent and abundant in the environment, posing great exposure risks to ecological and public health. Nevertheless, the toxicological effects of AO168 =O remain entirely unknown to date. The results in this study indicated that acute exposure to AO168 =O at 10 and 100 µg/L for 5 days obviously impaired cardiac morphology and function of zebrafish larvae, as proofed by decreased heartbeat, stroke volume, and cardiac output and the occurrence of pericardial edema and ventricular hypertrophy. Transcriptomics, polymerase chain reaction, and molecular docking revealed that the strong interaction of AO168 =O and transferrin receptor 1 activated the transportation of ferric iron into intracellular environment. The release of free ferrous ion to cytoplasmic iron pool also contributed to the iron overload in heart region, thus inducing ferroptosis in larvae via generation of excessive reactive oxygen species, glutathione peroxidase 4 inhibition, glutathione depletion and lipid peroxidation. Ferroptosis inhibitor (Fer-1) co-exposure effectively relieved the cardiac dysfunctions of zebrafish, verifying the dominant role of ferroptosis in the cardiotoxicity caused by AO168 =O. This research firstly reported the adverse impact and associated mechanisms of AO168 =O in cardiomyogenesis of vertebrates, underlining the urgency of concerning the health risks of AO168 =O.

A fluorescence-electrochemical dual-mode aptasensor based on novel DNA-dependent PBNFs@PtPd for highly selective and sensitive detection of procymidone through hybridization chain reaction.

Herein, a study for the first application of a hybridization chain reaction, a 1,8-naphthalimides-DNA (NDs) intercalator, and DNA-dependent Prussian blue nanoflowers@PtPd materials (PBNFs@PtPd) in the development of a fluorescence-electrochemical (FL-EC) aptasensor. This construction establishes an efficient sensing platform for the detection of procymidone (PCM). In the context of the described experiment, dual-mode detection is achieved through the generation of FL signals by an aptamer labeled with a Cy5 moiety and the formation of DPV signals by the modification of a thionine-appended 1,8-naphthalimide (Thi-NDs). In the presence of PCM, specific recognition occurs, followed by the utilization of magnetic separation technology to release DNA1 (S1) and aptamer-Cy5 (Apt-Cy5), subsequently introducing them onto both fluorescence and EC platforms. The presence of S1 effectively activates hybridization chain reaction (HCR) for the electrode surface, thereby significantly increasing the binding sites for Thi-NDs and consequently greatly amplifying the response signal of differential pulse voltammetry (DPV). The developed FL-EC dual-mode sensing platform demonstrates high sensitivity in the detection of PCM, with the detection limits of 0.173 µg·ml-1 (within the detection range of 500 pg·ml-1 to 500 ng·ml-1) and 0.074 ng·ml-1 (within the detection range of 100 pg·ml-1 to 100 ng·ml-1), respectively. The designed dual-mode sensor exhibits notable characteristics, including high selectivity, reproducibility, synergy, and reliable monitoring/capability for PCM in real samples.

Discovery of Selective and Potent ATR Degrader for Exploration its Kinase-Independent Functions in Acute Myeloid Leukemia Cells.

ATR has emerged as a promising target for anti-cancer drug development. Several potent ATR inhibitors are currently undergoing various stages of clinical trials, but none have yet received FDA approval due to unclear regulatory mechanisms. In this study, we discovered a potent and selective ATR degrader. Its kinase-independent regulatory functions in acute myeloid leukemia (AML) cells were elucidated using this proteolysis-targeting chimera (PROTAC) molecule as a probe. The ATR degrader, 8 i, exhibited significantly different cellular phenotypes compared to the ATR kinase inhibitor 1. Mechanistic studies revealed that ATR deletion led to breakdown in the nuclear envelope, causing genome instability and extensive DNA damage. This would increase the expression of p53 and triggered immediately p53-mediated apoptosis signaling pathway, which was earlier and more effective than ATR kinase inhibition. Based on these findings, the in vivo anti-proliferative effects of ATR degrader 8 i were assessed using xenograft models. The degrader significantly inhibited the growth of AML cells in vivo, unlike the ATR inhibitor. These results suggest that the marked anti-AML activity is regulated by the kinase-independent functions of the ATR protein. Consequently, developing potent and selective ATR degraders could be a promising strategy for treating AML.