Tunable High-Performance Electromagnetic Interference Shielding of VO2 Nanowires-Based Composite.

The unique metal-insulator transition of VO2 is very suitable for dynamic electromagnetic (EM) regulation materials due to its sharp change in electrical conductivity. Here, we have developed an off/on switchable electromagnetic interference (EMI) shielding composite by interconnecting VO2 nanowires (NWs) in poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) to form conductive networks, resulting in outstanding performance at the X and Ku bands with maximum change values of 44.8 and 59.4 dB, respectively. The unique insulator-to-metal transition (IMT) of VO2 NWs has dominated the variation of polarization loss (εp″) and conductivity loss (εσ″) for the composites, which is the mechanism of EMI shielding switching between off and on states. Furthermore, the composite exhibits good cycling stability of the off/on switchable EMI shielding performance and has excellent mechanical properties, especially with 200 times abrasion resistance without obvious weight loss. This study provides a unique approach for dynamic switching of EM response with the potential to construct practical intelligent EM response systems for next-generation smart electromagnetic devices in various scenarios.

Relish involved in immunity and larval survival in the willow leaf beetle Plagiodera versicolora.

BACKGROUND: Insects mainly rely on innate immunity against pathogen infection. Plagiodera versicolora (Coleoptera: Chrysomelidae), is a worldwide leaf-eating forest pest in salicaceous trees. However, the mechanisms behind the immunodeficiency pathway (IMD) remain poorly understood. RESULTS: In this study, we obtained a Relish gene from transcriptome analysis. Tissue and instar expression profiles were subsequently obtained using quantitative real-time polymerase chain reaction analysis. The results showed that Relish has high expression levels in eggs, larvae and adults, and especially in fat bodies. Transcripts of the tested antimicrobial peptides (AMPs), defensin1, defensin2 and attacin2 were downregulated by dsRelish. Knockdown of Relish led to greater mortality in larvae after Staphylococcus aureus infection. In addition, we performed bacterial 16S ribosomal RNA-based high-throughput sequencing. The results showed that the relative abundance of some gut bacteria was significantly altered after dsRelish ingestion. CONCLUSION: This study provides a greater understanding of the IMD signaling pathway, facilitating functional studies of Relish in P. versicolora. Moreover, a genetic pest management technique might be developed using Relish as a lethal gene to control the pest P. versicolora. © 2024 Society of Chemical Industry.

Metagenomic next-generation sequencing for diagnosis of fatal Balamuthia amoebic encephalitis.

INTRODUCTION: Balamuthia amoebic encephalitis (BAE), caused by Balamuthia mandrillaris, is a rare and life-threatening infectious disease with no specific and effective treatments available. The diagnosis of BAE at an early stage is difficult because of the non-specific clinical manifestations and neuroimaging. CASE DESCRIPTION: A 52-year-old male patient, who had no previous history of skin lesions, presented to the emergency department with an acute headache, walking difficulties, and disturbance of consciousness. The patient underwent a series of examinations, including regular cerebrospinal fluid (CSF) studies and magnetic resonance imaging, and tuberculous meningoencephalitis was suspected. Despite being treated with anti-TB drugs, no clinical improvement was observed in the patient. Following corticosteroid therapy, the patient developed a rapid deterioration in consciousness with dilated pupils. Metagenomic next-generation sequencing (mNGS) revealed an unexpected central nervous system (CNS) amoebic infection, and the patient died soon after the confirmed diagnosis. CONCLUSION: This study highlights the application of mNGS for the diagnosis of patients with suspected encephalitis or meningitis, especially those caused by rare opportunistic infections.

Functional Characterization and Putative Regulatory Mechanism of an RNAi Efficiency-Related Nuclease (REase) in the Fall Armyworm, Spodoptera frugiperda.

The lepidopteran-specific RNAi efficiency-related nuclease (REase) has been shown to contribute to double-strand RNA (dsRNA) degradation in several lepidopteran insects. However, little is known about its regulatory mechanism. In this study, we identified and characterized SfREase in Spodoptera frugiperda. The exposure of the third-instar larvae to dsEGFP and high temperature led to the upregulation of SfREase, whereas starvation treatment resulted in the downregulation of SfREase. Further experiments revealed that dsRNA degraded more slowly in the hemolymph or midgut fluid extracted from dsSfREase-injected or dsSfREase-ingested larvae compared with those from dsEGFP-treated larvae, and the recombinant SfREase degraded dsRNA in a concentration-dependent manner. Additionally, the knockdown of SfREase improved RNAi efficiency. Finally, both RNAi and dual-luciferase reporter assay in Sf9 cells revealed that SfREase is negatively regulated by FOXO. These data provide insights into the function and regulatory mechanism of REase and have applied implications for the development of an RNAi-based control strategy of S. frugiperda.

Engineering a transposon-associated TnpB-ωRNA system for efficient gene editing and phenotypic correction of a tyrosinaemia mouse model.

Transposon-associated ribonucleoprotein TnpB is known to be the ancestry endonuclease of diverse Cas12 effector proteins from type-V CRISPR system. Given its small size (408 aa), it is of interest to examine whether engineered TnpB could be used for efficient mammalian genome editing. Here, we showed that the gene editing activity of native TnpB from Deinococcus radiodurans (ISDra2 TnpB) in mouse embryos was already higher than previously identified small-sized Cas12f1. Further stepwise engineering of noncoding RNA (ωRNA or reRNA) component of TnpB significantly elevated the nuclease activity of TnpB. Notably, an optimized TnpB-ωRNA system could be efficiently delivered in vivo with single adeno-associated virus (AAV) and corrected the disease phenotype in a tyrosinaemia mouse model. Thus, the engineered miniature TnpB system represents a new addition to the current genome editing toolbox, with the unique feature of the smallest effector size that facilitate efficient AAV delivery for editing of cells and tissues.

Corrigendum: Case report: early recognition, treatment, and occupational safety protection are crucial for methanol toxicity.

[This corrects the article DOI: 10.3389/fmed.2022.918812.].

Case report: Desquamating dermatitis, bilateral cerebellar lesions in a late-onset methylmalonic acidemia patient.

Introduction: Cobalamin C (cblC) deficiency is a rare hereditary disorder affecting intracellular cobalamin metabolism, primarily caused by mutations in MMACHC. This condition is characterized by combined methylmalonic acidemia and hyperhomocysteinemia, displaying a wide range of clinical manifestations involving multiple organs. Owing to its uncommon occurrence and diverse clinical phenotypes, diagnosing cblC deficiency is challenging and often leads to delayed or missed diagnoses. Case description: In this report, we present a case of late-onset cblC deficiency with brown desquamating dermatitis on the buttocks. Magnetic resonance imaging (MRI) of the brain revealed bilateral cerebellar abnormalities. The suspicion of an inherited metabolic disorder was raised by abnormal serum amino acid and acylcarnitine levels, along with increased urine methylmalonic acid and serum homocysteine levels. Whole-exome sequencing helped identify a homozygous variant (c.482G>A) in MMACHC, confirming the diagnosis of cblC deficiency. However, despite receiving treatment with hydroxocobalamin and betaine, the patient did not experience clinical improvement, which may be attributed to the delayed diagnosis as indicated by the declining homocysteine and methylmalonic acid levels. Conclusion: Collectively, we emphasize the significance of recognizing the skin lesions and observing serial MRI changes in patients with cblC deficiency. Our case underscores the importance of early diagnosis and timely therapeutic intervention for this severe yet frequently manageable condition.

Transcriptome analysis and expression profiles of odorant binding proteins and chemosensory proteins in Orius sauteri.

The flower bug Orius sauteri (Heteroptera: Anthocoridae), is a polyphagous predator and a natural enemy widely used in biological pest control to micro-pests including aphids, spider mites, thrips and so on. In the present study, the transcriptome analysis of adult heads in O. sauteri were performed and identified a total of 38 chemosensory genes including 24 odorant binding proteins (OBPs) and 14 chemosensory proteins (CSPs). Subsequently, we conducted quantitative real-time PCR to detect the tissue expression level of 18 OBPs and 8 CSPs. The results showed that almost all OsauOBPs and OsauCSPs have a high expression level in the adult heads of both sexes. In addition, 5 OsauOBPs (OBP1, OBP2, OBP3, OBP4 and OBP14) have a significantly higher expressed in male heads than female, indicating that these chemosensory proteins might be involved in the male-specific behaviors such as pheromone reception and mate-seeking. This study will provide helpful reference for subsequent understanding of chemoreception mechanism in O. sauteri.

Involvement of Glutamate Cysteine Ligase Genes in Tolerance to Emamectin Benzoate in Spodoptera frugiperda and Their Putative Regulatory Mechanisms.

As the rate-limiting enzyme in de novo Glutathione (GSH) biosynthesis, the mammalian glutamate cysteine ligase (Gcl) catalytic (Gclc) and modifier (Gclm) subunits are regulated at multiple levels, whereas the function and regulatory mechanism of insect Gcl remain to be explored. In this study, we identified and characterized SfGclc and SfGclm in Spodoptera frugiperda. SfGclc and SfGclm were highly expressed in the hindgut and relatively less expressed in other tissues. The exposure of the third instar larvae to LC30 of emamectin benzoate (EMB) significantly reduced the GSH content with a concomitant upregulation of SfGclc and SfGclm. Further in vivo pretreatment with L-BSO, the Gcl inhibitor, increased the susceptibility of S. frugiperda to EMB. Consistently, overexpression of SfGclc and SfGclm increased the Sf9 cell viability under EMB treatment. Finally, both RNAi and the dual-luciferase reporter assay in Sf9 cells revealed that SfGclc is regulated by transcription factor CncC. These data provide insights into the function and regulatory mechanism of insect Gcl, and they imply that disruption of the redox homeostasis might be a practical strategy to enhance the insecticidal activity of EMB and other insecticides.

Characteristics of aseptic meningitis-like attack-an underestimated phenotype of myelin oligodendrocyte glycoprotein antibody-associated disease.

INTRODUCTION: Aseptic meningitis was recently reported and recognized as a novel phenotype of Myelin oligodendrocyte glycoprotein antibody-associated disease (MOG-AD). However, the frequency and clinical features of this specific subtype remain unclear. METHODS: We reported sixteen MOG-AD cases with aseptic meningitis from June 2018 to June 2022. Moreover, systematic literature of 17 reported cases was conducted. RESULTS: Upon reviewing the records of 91 patients diagnosed with MOG-AD in our center, we identified 16 patients (17.6%; 9 men and 7 women) with aseptic meningitis-like MOG-AD. The median age at onset was 23.5 ± 15.7 years. The common clinical presentations were fever (87.5%), headache (75.0%) and seizure (18.8%). Most patients had leukocytosis (62.5%) and a significantly elevated neutrophil-lymphocyte ratio (NLR, ≥3.0). Cerebrospinal fluid showed elevated intracranial hypertension (43.8%), elevated leukocytes (100%) and protein (56.3%). Negative brain magnetic resonance images were observed in 6 patients and only meningeal enhancement was observed in 8 patients at first. Almost all patients had a prolonged fever (over 2 weeks) and ineffectual antibiotic treatment. All patients experienced an effective response to immunotherapy. The majority had a benign course (low Expanded Disability Status Scale score and relapsing rate). Five patients (31.3%) progressed and four patients (25.0%) experienced recurrence. Aseptic meningitis-like MOG-AD of 17 cases reported in previous studies showed similar clinical features to our cases. CONCLUSION: Aseptic meningitis could be an initial or isolated manifestation of MOG-AD. It is an underestimated phenotype of MOG-AD.

Case report: Reversible encephalopathy caused by dyskinesia-hyperpyrexia syndrome.

Parkinson's disease (PD) is a common neurodegenerative disorder. Some patients with advanced-stage disease are accompanied by emergencies and critical issues such as dyskinesia-hyperpyrexia syndrome (DHS), parkinsonism-hyperpyrexia syndrome (PHS), and serotonin syndrome (SS). In this study, we report a patient with reversible encephalopathy caused by DHS who presented with an acute onset of fidgetiness, dyskinesia, and hyperpyrexia after antiparkinsonian drug abuse. In the present case, brain magnetic resonance imaging (MRI) showed multiple abnormal signals in the cortex and subcortex of the bilateral parietal and occipital lobes that resolved within weeks, which coincided with the characteristic MRI findings in posterior reversible encephalopathy (PRES). Our report expands on the neuroimaging features of DHS and highlights the importance of early identification, diagnosis, and treatment to improve patient prognosis.

Programmable deaminase-free base editors for G-to-Y conversion by engineered glycosylase.

Current DNA base editors contain nuclease and DNA deaminase that enables deamination of cytosine (C) or adenine (A), but no method for guanine (G) or thymine (T) editing is available at present. Here we developed a deaminase-free glycosylase-based guanine base editor (gGBE) with G editing ability, by fusing Cas9 nickase with engineered N-methylpurine DNA glycosylase protein (MPG). By several rounds of MPG mutagenesis via unbiased and rational screening using an intron-split EGFP reporter, we demonstrated that gGBE with engineered MPG could increase G editing efficiency by more than 1500 fold. Furthermore, this gGBE exhibited high base editing efficiency (up to 81.2%) and high G-to-T or G-to-C (i.e. G-to-Y) conversion ratio (up to 0.95) in both cultured human cells and mouse embryos. Thus, we have provided a proof-of-concept of a new base editing approach by endowing the engineered DNA glycosylase the capability to selectively excise a new type of substrate.

Development of miniature base editors using engineered IscB nickase.

As a miniature RNA-guided endonuclease, IscB is presumed to be the ancestor of Cas9 and to share similar functions. IscB is less than half the size of Cas9 and thus more suitable for in vivo delivery. However, the poor editing efficiency of IscB in eukaryotic cells limits its in vivo applications. Here we describe the engineering of OgeuIscB and its corresponding ωRNA to develop an IscB system that is highly efficient in mammalian systems, named enIscB. By fusing enIscB with T5 exonuclease (T5E), we found enIscB-T5E exhibited comparable targeting efficiency to SpG Cas9 while showing reduced chromosome translocation effects in human cells. Furthermore, by fusing cytosine or adenosine deaminase with enIscB nickase, we generated miniature IscB-derived base editors (miBEs), exhibiting robust editing efficiency (up to 92%) to induce DNA base conversions. Overall, our work establishes enIscB-T5E and miBEs as versatile tools for genome editing.

A mini-review of the role of vesicular glutamate transporters in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease implicated in multiple interacting neurotransmitter pathways. Glutamate is the central excitatory neurotransmitter in the brain and plays critical influence in the control of neuronal activity. Impaired Glutamate homeostasis has been shown to be closely associated with PD. Glutamate is synthesized in the cytoplasm and stored in synaptic vesicles by vesicular glutamate transporters (VGLUTs). Following its exocytotic release, Glutamate activates Glutamate receptors (GluRs) and mediates excitatory neurotransmission. While Glutamate is quickly removed by excitatory amino acid transporters (EAATs) to maintain its relatively low extracellular concentration and prevent excitotoxicity. The involvement of GluRs and EAATs in the pathophysiology of PD has been widely studied, but little is known about the role of VGLUTs in the PD. In this review, we highlight the role of VGLUTs in neurotransmitter and synaptic communication, as well as the massive alterations in Glutamate transmission and VGLUTs levels in PD. Among them, adaptive changes in the expression level and function of VGLUTs may exert a crucial role in excitatory damage in PD, and VGLUTs are considered as novel potential therapeutic targets for PD.

Specific pupylation as IDEntity reporter (SPIDER) for the identification of protein-biomolecule interactions.

Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired. By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin (SA)-biotin system, we developed the Specific Pupylation as IDEntity Reporter (SPIDER) method for identifying protein-biomolecule interactions. Using SPIDER, we validated the interactions between the known binding proteins of protein, DNA, RNA, and small molecule. We successfully applied SPIDER to construct the global protein interactome for m6A and mRNA, identified a variety of uncharacterized m6A binding proteins, and validated SRSF7 as a potential m6A reader. We globally identified the binding proteins for lenalidomide and CobB. Moreover, we identified SARS-CoV-2-specific receptors on the cell membrane. Overall, SPIDER is powerful and highly accessible for the study of protein-biomolecule interactions.

Engineered CRISPR-OsCas12f1 and RhCas12f1 with robust activities and expanded target range for genome editing.

The type V-F CRISPR-Cas12f system is a strong candidate for therapeutic applications due to the compact size of the Cas12f proteins. In this work, we identify six uncharacterized Cas12f1 proteins with nuclease activity in mammalian cells from assembled bacterial genomes. Among them, OsCas12f1 (433 aa) from Oscillibacter sp. and RhCas12f1 (415 aa) from Ruminiclostridium herbifermentans, which respectively target 5' T-rich Protospacer Adjacent Motifs (PAMs) and 5' C-rich PAMs, show the highest editing activity. Through protein and sgRNA engineering, we generate enhanced OsCas12f1 (enOsCas12f1) and enRhCas12f1 variants, with 5'-TTN and 5'-CCD (D = not C) PAMs respectively, exhibiting much higher editing efficiency and broader PAMs, compared with the engineered variant Un1Cas12f1 (Un1Cas12f1_ge4.1). Furthermore, by fusing the destabilized domain with enOsCas12f1, we generate inducible-enOsCas12f1 and demonstate its activity in vivo by single adeno-associated virus delivery. Finally, dead enOsCas12f1-based epigenetic editing and gene activation can also be achieved in mammalian cells. This study thus provides compact gene editing tools for basic research with remarkable promise for therapeutic applications.

High-Intensity Ultraviolet-C Irradiation Efficiently Inactivates SARS-CoV-2 Under Typical Cold Chain Temperature.

SARS-CoV-2 contaminated items in the cold chain becomes a threat to public health, therefore the effective and safe sterilization method fit for the low temperature is needed. Ultraviolet is an effective sterilization method while its effect on SARS-CoV-2 under low-temperature environment is unclear. In this research, the sterilization effect of high-intensity ultraviolet-C (HIUVC) irradiation against SARS-CoV-2 and Staphylococcus aureus on different carriers at 4 °C and - 20 °C was investigated. The results showed that dose of 15.3 mJ/cm2 achieved more than 3 log reduction of SARS-CoV-2 on gauze at 4 °C and - 20 °C. The vulnerability of coronavirus to HIUVC under - 20 °C was not significantly different than those under 4 °C. Four models including Weibull, biphasic, log-linear tail and log linear were used to fit the survival curves of SARS-CoV-2 and Staphylococcus aureus. The biphasic model fitted best with R2 ranging from 0.9325 to 0.9878. Moreover, the HIUVC sterilization correlation between SARS-CoV-2 and Staphylococcus aureus was established. This paper provides data support for the employment of HIUVC under low-temperature environment. Also, it provides a method of using Staphylococcus aureus as a marker to evaluate the sterilization effect of cold chain sterilization equipment.