Influenza viruses and SARS-CoV-2 diagnosis via sensitive testing methods in clinical application.

The identification of influenza viruses and SARS-CoV-2 has garnered increasing attention due of their longstanding global menace to human life and health. The point-of-care test is a potential approach for identifying influenza viruses and SARS-CoV-2 in clinical settings, leading to timely discovery, documentation, and treatment. The primary difficulties encountered with conventional detection techniques for influenza viruses and SARS-CoV-2 are the limited or inadequate ability to identify the presence of the viruses, the lack of speed, precision, accuracy, sensitivity, and specificity, often resulting in a failure to promptly notify disease control authorities. Recently, point-of-care test methods, along with nucleic acid amplification, optics, electrochemistry, lateral/vertical flow, and minimization, have been demonstrated the characteristics of reliability, sensitivity, specificity, stability, and portability. A point-of-care test offers promising findings in the early detection of influenza viruses and SARS-CoV-2 in both scientific research and practical use. In this review, we will go over the principles, advantages, limitations, and real-world applications of point-of-care diagnostics. The significance of constraints of detection, throughput, sensitivity, and specificity in the analysis of clinical samples in settings with restricted resources is underscored. This discussion concludes with their prospects and challenges.

Insight into the enhancement and mechanism of saltiness perception by salty peptides from bovine bone.

Food-derived salty peptides have been considered promising substitutes for sodium salt. In this work, three novel salty dipeptides Asp-Pro (DP), Asp-Arg (DR), and Arg-Glu (RE) were identified from bovine bone hydrolysates. The salt reduction rates were 76.85 %, 77.28 %, and 73.72 % by the three peptides (2 mg/mL) in a NaCl concentration of 0.203 g/100 mL, respectively. According to Stevens' law, a non-linear relationship between saltiness intensity and concentration was quantified, showing a slower increase in the sensory intensity perception compared with the changes in physical concentration (ß < 1). In molecular detail, electrostatic energy and van der Waals energy were the main energetic contributions to forming stable complexes. The binding of salty peptides to TMC4 was driven by hydrogen bonding and salt bridge, and the main binding sites were Glu319, Ala579, and Thr581. These results could provide new insight into the salt-enhancing property and interaction mechanism of salty peptides as novel sodium substitutes.

Epitope prime editing shields hematopoietic cells from CD123 immunotherapy for acute myeloid leukemia.

Acute myeloid leukemia (AML) is a malignant cancer characterized by abnormal differentiation of hematopoietic stem and progenitor cells (HSPCs). While chimeric antigen receptor T (CAR-T) cell immunotherapies target AML cells, they often induce severe on-target/off-tumor toxicity by attacking normal cells expressing the same antigen. Here, we used base editors (BEs) and a prime editor (PE) to modify the epitope of CD123 on HSPCs, protecting healthy cells from CAR-T-induced cytotoxicity while maintaining their normal function. Although BE effectively edits epitopes, complex bystander products are a concern. To enhance precision, we optimized prime editing, increasing the editing efficiency from 5.9% to 78.9% in HSPCs. Epitope-modified cells were resistant to CAR-T lysis while retaining normal differentiation and function. Furthermore, BE- or PE-edited HSPCs infused into humanized mice endowed myeloid lineages with selective resistance to CAR-T immunotherapy, demonstrating a proof-of-concept strategy for treating relapsed AML.

Extending Dynamic Blind Interaction: Microgap Discharge-Induced Flexible Virtual Electrotactile Braille.

Braille is an essential implement for the blind to communicate with outside, but traditional Braille is limited to a paper-based format that cannot directly provide real-time word information. In this work, a flexible virtual electrotactile Braille is proposed that can benefit the blind from blocked interaction. The Braille interface, S-shaped wires and a sphere electrode with a textile fingerstall integrated by silicone, offers flexibility and simultaneously generates the microgap through textile cracks, which achieves virtual electrotactile sensation by electrostatic discharge. Powered by a high-voltage triboelectric generator of 10.2 kV designed through the charge accumulation and induction strategy, the electrotactile stimulation is realized with a microgap discharge of only 40 µA current induced on the finger. A dynamic electrotactile Braille is finally assembled, controlled by a programmable relay array. The strategies of short circuit and voice reminder are employed, so that the recognition of dynamic Braille letters is realized with spatiotemporal electrotactile stimulation and high recognition accuracy. This virtual electrotactile Braille brings convenience for the blind to access the information world and illustrates its applications to promote virtual electrotactility in this special community.

Automated kapok fiber-based pipette-tip solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry for rapid and sensitive analysis of tyrosine kinase inhibitors in plasma.

This study delineates the development of a novel automated pipette-tip solid-phase extraction (SPE) methodology, employing kapok fiber as a naturally efficient and cost-effective adsorbent for the selective extraction of eleven tyrosine kinase inhibitors (TKIs) from plasma. The uniqueness of this method lies in its assembly, where kapok fibers are ingeniously wrapped around a stainless-steel spring within the pipette tip, ensuring an obstruction-free central space for effortless solution aspiration and dispensation. This design significantly minimizes backpressure, enhancing operational efficiency and ensuring compatibility with pipettors, including the implementation of an electric pipettor to streamline the sample preparation process and facilitate automation. The method's analytical performance, rigorously validated through liquid chromatography-tandem mass spectrometry, exhibits outstanding linearity in ranges of 0.1/0.5-200 ng mL-1 (R² > 0.993), commendable accuracy (86.3%-114.8%), and consistent precision (3.4-11.3%), alongside remarkably low detection limits that span from 0.024 to 0.130 ng mL-1. The assembly of kapok fiber within the pipette tip, in this unique configuration, results in a practical, cost-effective, eco-friendly, and automated pipette-tip SPE method. This innovation signifies a significant advancement in bioanalytical methodologies, offering an efficient and sustainable approach for extracting analytes from complex biological samples. This process notably enhances both the sensitivity and selectivity of subsequent instrumental analyses.

Rapid yet Controlled Synthesis of 2D Covalent Organic Framework Nanocapsules as High-Performance Photocatalytic Carriers.

Synthesis and assembly of two-dimensional (2D) polymeric materials present a tricky trade-off between the high reaction rate and precise morphology control. Here we report a nanoconfined synthesis of imine-based 2D covalent organic frameworks (COFs) at the interface of oil-in-water (O/W) emulsion droplets stabilized by cationic surfactants. Highly uniform nanocapsules (NCs) could be prepared without adding extra catalysts at room temperature in just 4.5 h at a yield of 86%. The NCs have tunable average diameters and shell thicknesses, depending on the monomer and surfactant types/concentrations. Their BET-specific surface areas are up to 139.0 m2/g, mainly contributed by narrowly-distributed mesopores at ~5.0 nm and micropores at 1.4 nm. The surfactant plays the role of a catalyst during the reaction and interestingly, it also regulates the formation of mesopores and their sizes. Both theoretical and experimental studies confirm that the reaction has been accelerated by two orders of magnitude at the microdroplet interface, compared to that without emulsification. The resulting NCs could be well dispersed in water, and they have been demonstrated to be highly efficient nanocatalysts in application of water-based hydrogen evolution. Such microdroplet interface-confined synthesis may facilitate the future development of 2D polymeric materials for more advanced applications.

Maternal infection with SARS-CoV-2 during early pregnancy induces hypoxia at the maternal-fetal interface.

The coronavirus disease 2019 (COVID-19) pandemic increases the risk of adverse fetal outcomes during pregnancy. Maternal infection during pregnancy, particularly with cytomegalovirus (CMV), hepatitis B and C virus, and human immunodeficiency virus can have detrimental effects on both mother and fetus, potentially leading to adverse outcomes such as spontaneous abortion or neonatal infection. However, the impact of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection on the maternal-fetal interface remains poorly understood. In this study, we initially utilised immunofluorescence and immunohistochemical to investigate placental samples from pregnant women who were infected with SARS-CoV-2 during the first trimester. Our data indicate that infection in the first trimester induces an upregulation of hypoxia inducible factor (HIF) levels at the maternal-fetal interface. Subsequently, single-cell RNA sequencing and metabolomics sequencing analyses reveal alterations in maternal-fetal interface. Remarkably, immune cells exhibited low expression levels of HIF possibly associated with immune activation. Furthermore, our findings demonstrate a gradual reduction in transcriptome and metabolic changes as gestation progressed beyond 12-16 weeks compared to samples obtained at 6-8 weeks gestation. Overall, our study suggests that early-stage SARS-CoV-2 infection during the first trimester leads to severe hypoxia and aberrant cell metabolism at the maternal-fetal interface which gradually resolves as pregnancy progresses. Nevertheless, these abnormal changes may have long-term implications for maternal-fetal interface development.

Pipette-tip kapok fiber-based solid-phase extraction/in-situ derivatization for the rapid and green analysis of furfural compounds.

Furfural compounds, including 5-hydroxymethylfurfural, furfural, and 5-methylfurfural, are common in foods and pose health risks. This study presents a pipette-tip solid-phase extraction with in-situ derivatization (PT-KF-SPE/ISD) method for rapid analysis of furfural compounds in various food matrices. Utilizing natural kapok fiber as an efficient adsorbent, this method integrates extraction and derivatization into a single step via a simple pull-push operation. Derivatization with 2,4-dinitrophenylhydrazine increases the hydrophobicity and ultraviolet absorption of furfural compounds, enabling sensitive liquid chromatography-ultraviolet detection. The method shows good linearity, sensitivity, and reproducibility, with limits of detection in ranges of 3.9-6.0 ng/mL. Real sample analysis confirms its applicability in detecting furfural compounds in beverages and herbal products, offering a reliable and eco-friendly solution for food safety and quality control. Five greenness assessment metrics demonstrate the method's excellent environmental friendliness. This approach highlights the advantages of combining natural adsorbents with in-situ derivatization for efficient food analysis.

Aperiodic Component Analysis in Quantification of Steady-State Visually Evoked Potentials.

OBJECTIVE: In this study, we aimed to investigate whether and how the aperiodic component in electroencephalograms affects different quantitative processes of steady-state visually evoked potentials and the performance of corresponding brain-computer interfaces. METHODS: We applied the Fitting Oscillations & One-Over-F method to parameterize power spectra as a combination of periodic oscillations and an aperiodic component. Electroencephalographic responses and system performance were measured and compared using four prevailing methods: power spectral density analysis, canonical correlation analysis, filter bank canonical correlation analysis and the state-of-the-art method, task discriminant component analysis. RESULTS: We found that controlling for the aperiodic component prominently downgraded the performance of brain-computer interfaces measured by canonical correlation analysis (94.9% to 82.8%), filter bank canonical correlation analysis (94.1% to 87.6%), and task discriminant component analysis (96.5% to 70.3%). However, it had almost no effect on that measured by power spectral density analysis (80.4% to 78.7%). This was accompanied by a differential aperiodic impact between power spectral density analysis and the other three methods on the differentiation of the target and non-target stimuli. CONCLUSION: The aperiodic component distinctly impacts the quantification of steady-state visually evoked potentials and the performance of corresponding brain-computer interfaces. SIGNIFICANCE: Our work underscores the significance of taking into account the dynamic nature of aperiodic activities in research related to the quantification of steady-state visually evoked potentials. The source code for our approach is available at https://github.com/didi226/scut_ssvep_aperiod.

Identification of salty peptides from enzymolysis extract of oyster by peptidomics and virtual screening.

Salty peptide as an important sodium substitute, which could reduce the risk of cardiovascular disease caused by excessive sodium intake. In this study, novel salty peptides were prepared and identified from enzymolysis extract of oysters by peptitomic identification, virtual screening and solid phase synthesis. Additionally, molecular simulation was used to study the taste mechanism of salty peptides. 316 peptides were identified in the enzymatic hydrolysates of oysters. 6 peptides, selected through virtual screening, were synthesized using solid-phase synthesis, and EK, LFE, LEY and DR were confirmed to possess a pleasing salty taste through electronic tongue evaluation. Molecular docking results indicated that these 4 peptides could enter the binding pocket within the transmembrane channel-like 4 (TMC4) cavity, wherein salt bridges, hydrogen bonds and attractive charges were the main binding forces. This study provides a rapid screening method for salty peptides in sea food products but possibly applied for other sources.

Corrigendum: Association between weight-adjusted waist index and kidney stones: a propensity score matching study.

[This corrects the article DOI: 10.3389/fendo.2024.1266761.].

Causal Association Between Atopic Dermatitis and Keratoconus: A Mendelian Randomization Study.

Purpose: Although many studies have indicated that atopic dermatitis (AD) could contribute to the risk of keratoconus (KC), the causality between AD and KC remains controversial. This study aimed to explore the potential causal associations between AD and KC. Methods: Instrumental variables for both exposures and outcomes were obtained from large-scale genome-wide association study summary statistics from previous meta-analyses. Mendelian randomization (MR) was applied to infer causal associations between AD and KC. Our main analyses were conducted by inverse-variance weighted (IVW) method multiplicative random effect model, complemented with additional five models and sensitivity analyses. Reverse MR analysis was applied to determine the direction of the causal association between AD and KC. Results: Both IVW and weighted median methods revealed a causal effect of AD on KC (IVW odds ratio [OR], 1.475; P = 4.16 × 10-4; weighted median OR, 1.351; P = 7.65 × 10-3). The weighted mode, simple mode, and MR Egger methods demonstrated consistent direction of causality. Evidence from all sensitivity analyses further supported these associations. Reverse MR analyses did not suggest causal effects of KC on AD. Conclusions: This study supported a significant causal effect of AD on KC, and reverse MR analysis proved that the causal association was unilateral. Translational Relevance: This study provides valid evidence that regular ophthalmic examinations are recommended for patients with AD to detect and prevent KC at an early stage.

Unveiling the functional roles of patient-derived tumour organoids in assessing the tumour microenvironment and immunotherapy.

Recent studies have established the pivotal roles of patient-derived tumour organoids (PDTOs), innovative three-dimensional (3D) culture systems, in various biological and medical applications. PDTOs, as promising tools, have been established and extensively used for drug screening, prediction of immune response and assessment of immunotherapeutic effectiveness in various cancer types, including glioma, ovarian cancer and so on. The overarching goal is to facilitate the translation of new therapeutic modalities to guide personalised immunotherapy. Notably, there has been a recent surge of interest in the co-culture of PDTOs with immune cells to investigate the dynamic interactions between tumour cells and immune microenvironment. A comprehensive and in-depth investigation is necessary to enhance our understanding of PDTOs as promising testing platforms for cancer immunotherapy. This review mainly focuses on the latest updates on the applications and challenges of PDTO-based methods in anti-cancer immune responses. We strive to provide a comprehensive understanding of the potential and prospects of PDTO-based technologies as next-generation strategies for advancing immunotherapy approaches.

Reading the m6A-encoded epitranscriptomic information in development and diseases.

N6-methyladenosine (m6A) represents the most prevalent internal and reversible modification on RNAs. Different cell types display their unique m6A profiles, which are determined by the functions of m6A writers and erasers. M6A modifications lead to different outcomes such as decay, stabilization, or transport of the RNAs. The m6A-encoded epigenetic information is interpreted by m6A readers and their interacting proteins. M6A readers are essential for different biological processes, and the defects in m6A readers have been discovered in diverse diseases. Here, we review the latest advances in the roles of m6A readers in development and diseases. These recent studies not only highlight the importance of m6A readers in regulating cell fate transitions, but also point to the potential application of drugs targeting m6A readers in diseases.

Axin1 regulates tooth root development by inhibiting AKT1-mTORC1 activation and Shh translation in Hertwig's epithelial root sheath.

Hertwig's epithelial root sheath (HERS) interacts with dental apical mesenchyme and guides development of the tooth root, which is an integral part for the function of the whole tooth. However, the key genes in HERS essential for root development are understudied. Here we show that Axin1, a scaffold protein that negatively regulates canonical Wnt signaling, is strongly expressed in the HERS. Axin1 ablation in the HERS of mice leads to defective root development but in a manner independent of canonical Wnt signaling. Further studies reveal that Axin1 in the HERS negatively regulates the AKT1-mTORC1 pathway through binding to AKT1, leading to inhibition of ribosomal biogenesis and mRNA translation. Sonic hedgehog (Shh) protein, a morphogen essential for root development, is over synthesized by upregulated mTORC1 activity upon Axin1 inactivation. Importantly, either haploinsufficiency of mTORC1 subunit Raptor or pharmacologic inhibition of Shh signaling can rescue the root defects in Axin1 mutant mice. Collectively, our data suggest that, independent of canonical Wnt signaling, Axin1 controls ribosomal biogenesis and selective mRNA translation programs via AKT1-mTORC1 signaling during tooth root development.

Study on the formation and characteristics of unstable sheet cavitation on hydrofoils.

Hydrofoils, as fundamental components of hydraulic machinery, directly influence the performance of such machinery. This study conducted an analysis of the cavitation characteristics of hydrofoils at a + 4° angle of attack under various cavitation numbers using numerical simulation and experimental research methods. The focus of the research was to explore the phenomenon of unstable sheet cavitation and its causes, as well as to reveal the characteristics of the re-entrant jet. The large eddy simulation method was employed to calculate the cavitation morphology under three different cavitation numbers. The method is highly consistent with the experimental results in simulating the small-scale detachment at the tail of unstable sheet cavitation and the large-scale shedding of cloud cavitation. The study found that the detachment of unstable sheet cavitation is closely related to the re-entrant jet, which exhibits transient and abrupt characteristics during the unstable sheet cavitation phase. Furthermore, by applying FFT processing to the distribution of maximum reverse velocity and the spatiotemporal changes of Ux on characteristic lines, eigenfrequency of the detachment of unstable sheet cavitation were identified. The research results indicate that cavitation mainly show as sheet cavitation when the cavitation closure point does not exceed the zero-slope point. Beyond this point, it transitions to cloud cavitation. This study provides new insights into the cavitation phenomenon of hydrofoils and offers quantitative research on the phenomenon of unstable sheet cavitation.

Facile Synthesis of Aptamer-Functionalized Polydopamine-Coated Magnetic Graphene Oxide Nanocomposites for Highly Efficient Purification of His-Tagged Proteins.

Recombinant proteins hold significant importance in numerous disciplines. As the demand for expressing and purifying these proteins grows, the scientific community is in dire need of a simple yet versatile methodology that can efficiently purify these proteins. Aptamers as synthetic nucleic acid-based ligands with high affinity have shown promise in this regard, as they can capture targets through molecular recognition. In this study, novel aptamer-functionalized polydopamine-coated magnetic graphene oxide nanocomposites were facilely prepared, achieving an impressive average aptamer coverage density (45 nmol/mg). These nanocomposites exhibited a uniform structure and robust magnetic responsiveness. The findings indicated that they possess several advantages, such as rapid adsorption, substantial capacity (171.4 mg/g), and excellent reusability. Notably, due to the inherent properties of nucleic acids, the immobilized aptamer-magnetic beads can be utilized repeatedly with high purification efficiency. Finally, the nanocomposites were further employed to purify His-tagged proteins from actual samples. Remarkably, they were able to selectively and efficiently isolate His-tagged retinoid X receptor alpha protein from complex Escherichia coli lysate. The purified His-tagged retinoid X receptor alpha protein was analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. This confirmed the efficacy of developed nanocomposites, reinforcing their vast potential for purification of His-tagged recombinant proteins.

Comprehensive analysis of POLH-AS1 as a prognostic biomarker in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC), a prevalent primary malignant tumor, is notorious for its high mortality rate. Despite advancements in HCC treatment, patient outcomes remain suboptimal. This study endeavors to assess the potential prognostic significance of POLH-AS1 in HCC. METHODS: In this research, we gathered RNA-Seq information from individuals with HCC in The Cancer Genome Atlas (TCGA). We analyzed the levels of POLH-AS1 expression in both HCC cells and tissues using statistical tests. Additionally, we examined various prognostic factors in HCC using advanced methodologies. Furthermore, we employed Spearman's rank correlation analysis to examine the association between POLH-AS1 expression and the tumor's immune microenvironment. Finally, the functional roles of POLH-AS1 in HCC were validated in two HCC cell lines (HEP3B and HEPG2). RESULTS: Our analysis revealed elevated POLH-AS1 expression across various cancers, including HCC, with heightened expression correlating with HCC progression. Notably, POLH-AS1 expression emerged as a potential biomarker for HCC patient survival and prognosis. Mechanistically, we identified the involvement of POLH-AS1 in tumorigenesis pathways such as herpes simplex virus 1 infection, interactions with neuroactive receptors, and the cAMP signaling pathway. Lastly, inhibition of POLH-AS1 was discovered to hinder the proliferation, invasion and migration of HEP3B and HEPG2 HCC cells. CONCLUSIONS: POLH-AS1 emerges as a promising prognostic biomarker and therapeutic target for HCC, offering potential avenues for enhanced patient management and treatment strategies.

Sortilin is associated with progranulin deficiency and autism-like behaviors in valproic acid-induced autism rats.

INTRODUCTION: Neuroinflammation and microglial activation-related dendritic injury contribute to the pathogenesis of Autism Spectrum Disorder (ASD). Previous studies show that Progranulin (PGRN) is a growth factor associated with inflammation and synaptic development, but the role of PGRN in autism and the mechanisms underlying changes in PGRN expression remain unclear. AIMS: To investigate the impact of PGRN in autism, we stereotactically injected recombinant PGRN into the hippocampus of ASD model rats. Additionally, we explored the possibility that sortilin may be the factor behind the alterations in PGRN by utilizing SORT1 knockdown. Ultimately, we aimed to identify potential targets for the treatment of autism. RESULTS: PGRN could alleviate inflammatory responses, protect neuronal dendritic spines, and ameliorate autism-like behaviors. Meanwhile, elevated expression of sortilin and decreased levels of PGRN were observed in both ASD patients and rats. Enhanced sortilin levels facilitated PGRN internalization into lysosomes. Notably, suppressing SORT1 expression amplified PGRN levels, lessened microglial activation, and mitigated inflammation, thereby alleviating autism-like behaviors. CONCLUSION: Collectively, our findings highlight elevated sortilin levels in ASD rat brains, exacerbating dendrite impairment by affecting PGRN expression. PGRN supplementation and SORT1 knockdown hold potential as therapeutic strategies for ASD.

Real-Time Attention Regulation and Cognitive Monitoring Using a Wearable EEG-based BCI.

OBJECTIVE: Attention regulation is an essential ability in daily life that affects learning and work efficiency and is closely related to mental health. The effectiveness of brain-computer interface (BCI) systems in attention regulation has been proven, but most of these systems rely on bulky and expensive equipment and are still in the experimental stage. This study proposes a wearable BCI system for real-time attention regulation and cognitive monitoring. METHODS: The BCI system integrates a wearable singlechannel electroencephalogram (EEG) headband with wireless data streaming for real-time analysis. Twenty healthy subjects participated in the long-term attention regulation experiment and were evenly divided into an experimental group and a control group based on the presence of realtime neurofeedback. The neurofeedback is represented by output value of attention, which calculated from singlechannel EEG data. Before and after the regulation sessions, baseline assessments were conducted for each subject, incorporating multi-channel EEG data analysis and cognitive behavioral evaluations, to verify the effectiveness of system for attention regulation. RESULTS: The online experimental results indicate that the average attention level in the experimental group increased from 0.625 to 0.812, while no significant improvement was observed in the control group. Further comparative analysis revealed the reasons for the enhancement of attention regulation ability in terms of both brain network patterns and cognitive performance. SIGNIFICANCE: The proposed wearable BCI system is effective at improving attention regulation ability and could be a promising tool for assisting people with attention disorders.