Broad immunogenicity to prior SARS-CoV-2 strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents.

SARS-CoV-2 vaccination has reduced hospitalization and mortality for nursing home residents (NHRs) but emerging variants and waning immunity challenge vaccine effectiveness. This study assesses the immunogenicity of the most recent XBB.1.5 monovalent vaccine to variant strains among NHRs. Participants were subset of a longitudinal study of consented NHRs and Healthcare workers (HCWs) who have received serial blood draws to assess immunogenicity with each SARS-CoV-2 mRNA vaccine dose. We report data on participants who received the XBB.1.5 monovalent vaccine post-FDA approval in Fall 2023. NHRs were categorized by whether they had an interval SARS-CoV-2 infection between their first bivalent vaccine dose and their XBB.1.5 monovalent vaccination. The sample included 61 NHRs [median age 76 (IQR 68-86), 51% female] and 28 HCWs [median age 45 (IQR 31-58), 46% female). After XBB.1.5 vaccination, a robust geometric mean fold rise (GMFR) in XBB.1.5-specific neutralizing antibody titers was observed:17.3 (95% confidence interval [CI] 9.3, 32.4) and NHRs with interval infection and 11.3 (95% CI 5, 25.4) in those without and 13.6 (95% CI 8.4,22) in HCWs. For JN.1-specific titers, GMFRs were 14.9 (95% CI 7.9, 28) and 6.5 (95% CI 3.3, 13.1) in NHRs with and without interval infection, and 11.4 (95% CI 6.2, 20.9) in HCWs. NHRs with interval SARS-CoV-2 infection had higher titers across all analyzed strains analyzed. The XBB.1.5 vaccine significantly elevates Omicron-specific neutralizing antibody titers to XBB.1.5 and JN.1 strains in both NHRs and HCWs with more pronounced in those previously infected with SARS-CoV-2 since bivalent vaccination.

Gut Bacteroides ovatus ameliorates renal fibrosis by promoting the production of HDCA through upregulation of Clostridium scindens.

Renal fibrosis, inflammation, and gut dysbiosis are all linked to chronic kidney disease (CKD). Here we show that Bacteroides ovatus protects against renal fibrosis. Mechanistically, B. ovatus enhances intestinal hyodeoxycholic acid (HDCA) levels by upregulating a strain of intestinal bacteria, Clostridium scindens, that has the capacity for direct HDCA production in mice. HDCA significantly promoted GLP-1 secretion by upregulating the expression of TGR5 and downregulating the expression of farnesoid X receptor (FXR) in the gut. Activation of renal GLP-1R attenuates renal fibrosis while delaying the subsequent development of CKD. In addition, HDCA can also protect against renal fibrosis by directly upregulating renal TGR5. The natural product neohesperidin (NHP) was found to exert its anti-renal fibrotic effects by promoting the growth of B. ovatus. Our findings provide mechanistic insights into the therapeutic potential of B. ovatus, C. scindens, and HDCA in treating CKD.

Cis-3-Indoleacrylic Acid: A Nematicidal Compound from Streptomyces youssoufiensis YMF3.862 as V-ATPase Inhibitor on Meloidogyne incognita.

The application of the bionematicides derived from microorganisms and their secondary metabolites represents a promising strategy for managing root-knot nematodes. In this study, a nematicidal compound, cis-3-indoleacrylic acid, was isolated from Streptomyces youssoufiensis YMF3.862. This compound caused Meloidogyne incognita juveniles to have swollen bodies with apparent cracks on the cuticle surface. The LC50 value of cis-3-indoleacrylic acid against juveniles was 16.31 µg/mL 24 h of post-treatment. Cis-3-indoleacrylic acid at 20 µg/mL significantly inhibited V-ATPase expression and remarkably decreased enzyme activity by 84.41%. As an inhibitor of V-ATPase, cis-3-indoleacrylic acid caused significant H+ accumulation in nematode bodies, resulting in lower intracellular pH values and higher extracellular pH values of M. incognita. Application of 50 µg/mL cis-3-indoleacrylic acid generated a 71.06% control efficiency against M. incognita on tomatoes. The combination results of this study indicated that cis-3-indoleacrylic acid can be developed as a natural nematicide for controlling M. incognita.

A Metalgel with Liquid Metal Continuum Immobilized in Polymer Network.

Gels are formed by fluids that expand throughout the whole volume of 3D polymer networks. To unlock unprecedented properties, exploring new fluids immobilized in polymer networks is crucial. Here, a new liquid metal-polymer gel material termed "metalgel" is introduced via fluid replacement strategy, featuring 92.40% vol liquid metal fluid as a continuum immobilized by interconnected nanoscale polymer network. The unique structure endows metalgel with high electrical conductivity (up to 3.18 × 106 S·m‒1), tissue-like softness (Young's modulus as low as 70 kPa), and low gas permeability (4.50 × 10‒22 m2·s‒1·Pa‒1). Besides, metalgel demonstrates electrical stability under extreme deformations, such as being run over by a 4.5-metric-tonne truck, and maintains its integrity in various environments for up to 180 days. The immobilization of high-volume-fraction liquid metal fluid is realized by electrostatic interactions is further revealed. Potential applications for metalgel are diverse and include soft electromagnetic shielding, hermetic sealing, and stimulating/sensing electrodes in implantable bioelectronics, underscoring its broad applicability.

Transcription factor networks drive perforin activity in the anti-bacterial immune response of tilapia.

Perforin, produced by natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), is one of the effectors of cell-mediated cytotoxicity (CMC) in vertebrates, playing a paramount role in killing target cells. However, whether and how perforin is involved in adaptive immune responses in early vertebrates remains unclear. Using Nile tilapia (Oreochromis niloticus) as a model, we investigated the characteristics of perforin in early vertebrates. Oreochromis niloticus perforin (OnPRF) possesses 2 conserved functional domains, membrane attack complex/perforin (MACPF) and protein kinase C conserved region 2 (C2) domains, although they share low amino acid sequence similarity with other homologs. OnPRF was widely expressed in various immune tissues and could respond to lymphocyte activation and T-cell activation in vitro at both the transcriptional and protein levels, indicating that it may be involved in adaptive immune responses. Furthermore, after infection with Edwardsiella piscicida and Aeromonas hydrophila, the mRNA and protein levels of OnPRF were significantly up-regulated within the adaptive immune response period. Additionally, we revealed that many transcription factors were involved in the transcriptional regulation of OnPRF, including p65, c-Fos, c-Jun, STAT1 and STAT4, and there was a synergy among these transcription factors. Overall, these findings demonstrate the involvement of OnPRF in T-cell activation and adaptive immune response in tilapia, thus providing new evidence for comprehending the evolution of immune response in early vertebrates.

Multifunctional ICG-SB@Lip-ZA Nanosystem Focuses on Remodeling the Inflammatory-Immunosuppressive Microenvironment After Photothermal Therapy to Potentiate Cancer Photothermal Immunotherapy.

Achieving full eradication of residual tumors post photothermal therapy (PTT) hinges on the immune system's activation and response. Nevertheless, the resultant local inflammation attracts a significant influx of aberrant immune cells and fibroblasts, such as tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), following tumor PTT. This phenomenon exacerbates immune evasion and the persistence of residual tumor cells, culminating in tumor recurrence and advancement. To tackle this challenge, a combined therapeutic approach utilizing multifunctional ICG-SB@Lip-ZA nanosystem has been introduced. Indocyanine green (ICG) as a photothermal-transducer ablated tumor cells, zoledronic acid (ZA) depletes TAMs recruited by the inflammatory tumor microenvironment (mostly M2-like phenotype), SB-505124 affects CAFs proliferation in the tumor microenvironment (TME) by inhibiting the transforming growth factor-ß ï¼ˆTGF-ß） pathway, thereby removing physical barriers to T cell infiltration. In a breast cancer model, these immunomodulatory nanoliposomes markedly decrease the population of M2-like TAMs in the TME, eliminate physical barriers hindering T cell infiltration, reshape the inflammatory immune-suppressive tumor microenvironment, eventually leading to a rate of tumor eradication of 94%. This multifunctional ICG-SB@Lip-ZA nanosystem (including photothermal conversion, TAM depletion, and TGF-ß pathway blockade) offers a promising strategy for mitigating the deteriorating tumor microenvironment following PTT and presents a more efficient approach for clinical photothermal-immune combination therapy.

LFIR-YOLO: Lightweight Model for Infrared Vehicle and Pedestrian Detection.

The complexity of urban road scenes at night and the inadequacy of visible light imaging in such conditions pose significant challenges. To address the issues of insufficient color information, texture detail, and low spatial resolution in infrared imagery, we propose an enhanced infrared detection model called LFIR-YOLO, which is built upon the YOLOv8 architecture. The primary goal is to improve the accuracy of infrared target detection in nighttime traffic scenarios while meeting practical deployment requirements. First, to address challenges such as limited contrast and occlusion noise in infrared images, the C2f module in the high-level backbone network is augmented with a Dilation-wise Residual (DWR) module, incorporating multi-scale infrared contextual information to enhance feature extraction capabilities. Secondly, at the neck of the network, a Content-guided Attention (CGA) mechanism is applied to fuse features and re-modulate both initial and advanced features, catering to the low signal-to-noise ratio and sparse detail features characteristic of infrared images. Third, a shared convolution strategy is employed in the detection head, replacing the decoupled head strategy and utilizing shared Detail Enhancement Convolution (DEConv) and Group Norm (GN) operations to achieve lightweight yet precise improvements. Finally, loss functions, PIoU v2 and Adaptive Threshold Focal Loss (ATFL), are integrated into the model to better decouple infrared targets from the background and to enhance convergence speed. The experimental results on the FLIR and multispectral datasets show that the proposed LFIR-YOLO model achieves an improvement in detection accuracy of 4.3% and 2.6%, respectively, compared to the YOLOv8 model. Furthermore, the model demonstrates a reduction in parameters and computational complexity by 15.5% and 34%, respectively, enhancing its suitability for real-time deployment on resource-constrained edge devices.

[Effects of simulated repeated transcranial acupuncture on learning and memory and cerebral microvascular flow in vascular dementia rats]. / æ¨¡æ‹Ÿç»é¢ é‡å¤é’ˆåˆºæ‰‹æ³•å¯¹è¡€ç®¡æ€§ç—´å‘†å¤§é¼ å­¦ä¹ è®°å¿†åŠè„‘å¾®è¡€æµçš„å½±å“.

OBJECTIVES: To observe the effect of simulated repeated transcranial acupuncture (rTAS) on learning and memory abilities and cerebral microvascular flow in vascular dementia (VD) model rats, so as to explore the potential mechanism of rTAS in treating VD. METHODS: Thirty-two Wistar rats were randomly divided into normal, model, acupuncture and rTAS groups (n=8 rats in each group). The VD model was established by permanent ligation of bilateral common carotid arteries. For rats of the acupuncture group, "Baihui" (GV20) and "Shenting" (GV24) were needled, and for rats of the rTAS group, GV20 and GV24 were stimulated by simulated repeated transcranial manipulation (200 r/min, for 5 min). The treatment was conducted once daily for 14 days. After the intervention, learning and memory abilities were evaluated using the Morris water maze test. Laser speckle technology was used to measure the average cerebral microvascular flow. ELISA was performed to measure the contents of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), nitric oxide (NO), and inducible nitric oxide synthase (iNOS) in the hippocampal tissues. RESULTS: In comparison with the normal group, the escape latency of rats in the model group was prolonged (P<0.01), and the times of crossing the platform were decreased (P<0.01). The average cerebral microvascular flow and the VEGF content in the hippocampus were significantly decreased, while the contents of NO, iNOS, and ET-1 were significantly increased (P<0.01). In comparison with the model group, the escape latency was significantly shortened (P<0.01), the average cerebral microvascular flow and VEGF content in the hippocampus were significantly increased (P<0.05, P<0.01), while contents of iNOS were significantly decreased (P<0.05, P<0.01) in both acupuncture and rTAS groups；and the times of crossing the platform were increased (P<0.01), the contents of NO and ET-1 in hippocampus were significantly decreased (P<0.01) in the rTAS group. The effects of rTAS were significantly superior to those of acupuncture in up-regulating the average cerebral microvascular flow (P<0.05) and VEGF content (P<0.01), and down-regulating the NO, iNOS and ET-1 contents (P<0.01, P<0.05). CONCLUSIONS: rTAS can increase cerebral microvascular flow, improve spatial cognition and enhance learning and memory abilities of VD rats. The underlying mechanism may be involved in promoting angiogenesis, improving endothelial function and mitigating oxidative stress.

Photo-tunable hydrogels reveal cellular sensing of rapid rigidity changes through the accumulation of mechanical signaling molecules.

Cells use traction forces to sense mechanical cues in their environment. While the molecular clutch model effectively explains how cells exert more forces on stiffer substrates, it falls short in addressing their adaptation to dynamic mechanical fluctuations prevalent in tissues and organs. Here, using hydrogel with photo-responsive rigidity, we show that cells' response to rigidity changes is frequency dependent. Strikingly, at certain frequencies, cellular traction forces exceed those on static substrates 4-fold stiffer, challenging the established molecular clutch model. We discover that the discrepancy between the rapid adaptation of traction forces and the slower deactivation of mechanotransduction signaling proteins results in their accumulation, thereby enhancing long-term cellular traction in dynamic settings. Consequently, we propose a new model that melds immediate mechanosensing with extended mechanical signaling. Our study underscores the significance of dynamic rigidity in the development of synthetic biomaterials, emphasizing the importance of considering both immediate and prolonged cellular responses.

Single-cell transcriptomic profiling uncovers cellular complexity and microenvironment in gastric tumorigenesis associated with Helicobacter pylori.

INTRODUCTION: Helicobacter pylori (H. pylori) infection is the main risk for gastric cancer (GC). However, the cellular heterogeneity and underlying molecular mechanisms in H. pylori-driven gastric tumorigenesis are poorly understood. OBJECTIVE: Here, we generated a single-cell atlas of gastric tumorigenesis comprising 18 specimens of gastritis, gastric intestinal metaplasia (IM) and GC with or without H. pylori infection. METHODS: Single-cell RNA sequencing (scRNA-seq) was performed. Immunofluorescence, immunohistochemistry and qRT-PCR analysis were applied in a second human gastric tissues cohort for validation. Bioinformatics analyses of public TCGA and GEO datasets were applied. RESULTS: Single-cell RNA profile highlights cellular heterogeneity and alterations in tissue ecology throughout the progression of gastric carcinoma. Various cell lineages exhibited unique cancer-associated expression profiles, such as tumor-like epithelial cell subset (EPC), inflammatory cancer-associated fibroblasts (iCAFs) and Tumor-associated macrophage (TAM). Notably, we revealed that the specific epithelial subset enterocytes from the precancerous lesion GIM, exhibited elevated expression of genes related to lipid metabolism, and HNF4G was predicted as its specific transcription factor. Furthermore, we identified differentially expressed genes in H. pylori-positive and negative epithelial cells, fibroblasts and myeloid cells were identified. Futhermore, H. pylori-positive specimens exhibited enriched cell-cell communication, characterized by significantly active TNF, SPP1, and THY1 signaling networks. CONCLUSIONS: Our study provides a comprehensive landscape of the gastric carcinogenesis ecosystem and novel insights into the molecular mechanisms of different cell types in H. pylori-induced GC.

Bidirectional Allostery Mechanism in Catch-Bond Formation of CD44 Mediated Cell Adhesion.

Catch-bonds, whereby noncovalent ligand-receptor interactions are counterintuitively reinforced by tensile forces, play a major role in cell adhesion under mechanical stress. A basic prerequisite for catch-bond formation, as implicated in classic catch-bond models, is that force-induced remodeling of the ligand binding interface occurs prior to bond rupture. However, what strategy receptor proteins utilize to meet such specific kinetic control remains elusive. Here we report a bidirectional allostery mechanism of catch-bond formation based on theoretical and molecular dynamics simulation studies. Binding of ligand allosterically reduces the threshold force for unlocking of otherwise stably folded force-sensing element (i.e., forward allostery), so that a much smaller tensile force can trigger the conformational switching of receptor protein to high binding-strength state via backward allosteric coupling before bond rupture. Such bidirectional allostery fulfills the specific kinetic control required by catch-bond formation and is likely to be commonly utilized in cell adhesion. The essential thermodynamic and kinetic features of receptor proteins essential for catch-bond formation were identified.

Comparative analysis of T-cell immunity between Streptococcus agalactiae susceptible and resistant tilapia (Oreochromis niloticus).

Nile tilapia (Oreochromis niloticus) is one of the important economic fish species cultured worldwide. However, Streptococcus agalactiae has emerged as a significant bacterial threat, severely impacting the economy of tilapia industry. The immune response underlying the resistance of tilapia to S. agalactiae are not well understood, hindering the reasonable evaluation of breeding and the formulation of effective strategies. In this study, we investigated the differences in T-cell immunity between S. agalactiae-resistant and -susceptible tilapia. Compared with susceptible tilapia, resistant tilapia exhibited a higher percentage of T cells and BrdU+ T cells during infection, indicating a superior proliferative capacity. Whether infected or not, T cells from resistant fish demonstrated a greater ability to resist apoptosis. Additionally, T cell effector genes, including interleukin (IL)-2, interferon (IFN)-γ, perforin A, and granzyme B were expressed at higher levels in resistant tilapia after infection. Along with these T-cell immune responses, resistant fish showed more effective clearance of infection. Our study elucidates the T-cell immune responses in resistant tilapia, which may contribute to the high resistance of tilapia to S. agalactiae, and provide valuable theoretical references for the selection and evaluation of disease-resistant fish strains in the future.

Few-shot meta-learning applied to whole brain activity maps improves systems neuropharmacology and drug discovery.

In this study, we present an approach to neuropharmacological research by integrating few-shot meta-learning algorithms with brain activity mapping (BAMing) to enhance the discovery of central nervous system (CNS) therapeutics. By utilizing patterns from previously validated CNS drugs, our approach facilitates the rapid identification and prediction of potential drug candidates from limited datasets, thereby accelerating the drug discovery process. The application of few-shot meta-learning algorithms allows us to adeptly navigate the challenges of limited sample sizes prevalent in neuropharmacology. The study reveals that our meta-learning-based convolutional neural network (Meta-CNN) models demonstrate enhanced stability and improved prediction accuracy over traditional machine-learning methods. Moreover, our BAM library proves instrumental in classifying CNS drugs and aiding in pharmaceutical repurposing and repositioning. Overall, this research not only demonstrates the effectiveness in overcoming data limitations but also highlights the significant potential of combining BAM with advanced meta-learning techniques in CNS drug discovery.

Restricting Linker Rotation in Nanocages of ZIF-8 Membranes using Crown Ether "Molecular Locks" for Enhanced Propylene/Propane Separation.

ZIF-8 membranes have long been prized for their exceptional C3H6/C3H8 separation performance. On the other hand, ZIF-8 has structural flexibility, where the external pressure triggers channel expansion, potentially deteriorating the molecular sieving ability. Here, we demonstrate a reliable strategy to fine-tune the flexible pore structure of ZIF-8 by embedding crown ether within a ZIF-8 membrane. Benzo-15-crown-5 (15C5) was selected as the cavity occupant and perfectly confined in the sodalite (SOD) cage of ZIF-8. The 15C5 molecules, which have a size comparable to the nanocage, impose a spatial constraint on linker rotation, enabling the phase transition to a rigid structure in the flexible ZIF-8. The corresponding 15C5@ZIF-8 membranes achieve an ultrahigh C3H6/C3H8 selectivity of 220, outperforming that of most membranes. Unlike their flexible counterparts, the resulting membranes manifest a positive increase in the C3H6/C3H8 separation factor with elevated pressure, securing a record-high C3H6/C3H8 separation factor of 331 under 7 bar. More importantly, extraordinary separation stability was demonstrated with continuous measurement, which is highly desirable for practical applications.

Non-discriminating engineered masking of immuno-evasive ligands on tumour-derived extracellular vesicles enhances tumour vaccination outcomes.

The success of personalized cancer immunotherapy depends on the initial tumour antigenic presentation to dendritic cells and macrophages. Tumour-derived extracellular vesicles (TEVs) contain abundant tumour antigenic molecules. The presence of anti-phagocytotic signals such as cluster of differentiation 47 (CD47) on the surface of the TEVs, however, leads to evasion of the same dendritic cells and macrophages. Here we show that iron oxide hydroxide nanocomposites can successfully mask TEV surfaces and unblock phagocytosis without affecting extracellular vesicles' elicited immune goals. After internalization, the mask disintegrates in the lysosome, releasing the tumour antigenic cargo. This triggers antigen presentation and promotes dendritic cell activation and maturation and macrophage reprogramming in animal models, leading to a drastic reduction of tumour volume and metastasis, and in human malignant pleural effusion clinical samples. This straightforward masking strategy eliminates the ubiquitous anti-phagocytosis block found in clinical samples and can be applied universally across all patient-specific TEVs as tumour antigenic agents for enhanced immunotherapy.

Fusion Dynamics and Size-Dependence of Droplet Microstructure in ssDNA-Mediated Protein Phase Separation.

Biomolecular condensation involving proteins and nucleic acids has been recognized to play crucial roles in genome organization and transcriptional regulation. However, the biophysical mechanisms underlying the droplet fusion dynamics and microstructure evolution during the early stage of liquid-liquid phase separation (LLPS) remain elusive. In this work, we study the phase separation of linker histone H1, which is among the most abundant chromatin proteins, in the presence of single-stranded DNA (ssDNA) capable of forming a G-quadruplex by using molecular simulations and experimental characterization. We found that droplet fusion is a rather stochastic and kinetically controlled process. Productive fusion events are triggered by the formation of ssDNA-mediated electrostatic bridges within the droplet contacting zone. The droplet microstructure is size-dependent and evolves driven by maximizing the number of electrostatic contacts. We also showed that the folding of ssDNA to the G-quadruplex promotes LLPS by increasing the multivalency and strength of protein-DNA interactions. These findings provide deep mechanistic insights into the growth dynamics of biomolecular droplets and highlight the key role of kinetic control during the early stage of ssDNA-protein condensation.

Radiofrequency field inhibits RANKL-induced osteoclast differentiation in RAW264.7 cells via modulating the NF-κB signaling pathway.

In this study, we investigated the inhibitory effects of radiofrequency exposure on RANKL-induced osteoclast differentiation in RAW264.7 cells, along with the underlying mechanisms. RAW264.7 cells were subjected to radiofrequency exposure at three distinct power densities: 50 µW/cm2, 150 µW/cm2, and 450 µW/cm2. The results showed that, among the three dosage levels, exposure to 150 µW/cm2 of radiofrequency radiation significantly reduced the proliferation capacity of RAW264.7 cells. RF exposure at three power densities resulted in significant increases in the level of osteoclast apoptosis and notable decreases in osteoclast differentiation. Notably, the most pronounced effects on apoptosis, differentiation in RAW 264.7 cells were observed at the 150 µW/cm2 power density. These effects were accompanied by concurrent decreases in mRNA and protein levels of osteoclast-specific genes, including RANK, NFATc1, and TRACP. Furthermore, radiofrequency exposure at power density of 150 µW/cm2 induced a significant decrease in cytoplasmic NF-κB protein levels while increasing its nuclear fraction, thereby counteracting the effects of RANKL-induced NF-κB activation. These data suggest that radiofrequency exerts inhibitory properties on RANKL-induced NF-κB transcriptional activity, subsequently indirectly suppressing the expression of downstream NF-κB target genes, such as NFATc1 and TRACP. In conclusion, our study demonstrates that radiofrequency radiation effectively inhibits osteoclast differentiation by modulating the NF-κB signaling pathway. These findings have important implications for potential therapeutic interventions in osteoporosis.

Osteoporosis is a common bone disease where bones become weak and brittle, often leading to fractures. It frequently occurs in older adults, especially postmenopausal women, due to low estrogen levels and inadequate calcium intake. This causes increased activity of bone cells called osteoclasts which break down bone tissue, resulting in severe bone loss. Currently, the primary treatment is long-term use of medications like bisphosphonates. However, these drugs can have side effects. The main adverse reactions include fever, vomiting, rash, diarrhea, dizziness, abdominal pain, musculoskeletal pain, headache, allergic-like reactions, indigestion, edema, and ocular symptoms.This study explored using radiofrequency (RF) radiation as a safe, non-invasive alternative therapy for osteoporosis. RF radiation is a type of energy used in communications like cell phones and WiFi. We tested whether exposure to 900MHz RF radiation could inhibit the formation and activity of osteoclasts to prevent excessive bone breakdown.We treated osteoclast precursor cells with RANKL, a protein that stimulates osteoclast formation. Cells were then exposed to RF radiation at various intensities. The results showed that medium-level RF radiation (150 µW/cm²) significantly suppressed RANKL-induced osteoclast differentiation and bone resorption capacity. This effect was like the osteoclast inhibition seen with estrogen treatment.Further analysis revealed that RF radiation blocks the activation of NF-κB, a key signaling molecule that promotes osteoclast formation when RANKL is present. This in turn reduced production of downstream signals like NFATc1 and TRACP which are essential for osteoclast differentiation.In summary, this study demonstrates that medium-intensity RF radiation could potentially prevent excessive osteoclastic bone resorption in osteoporosis patients by interfering with NF-κB signaling cascade. The research highlights RF radiation's promise as a novel, non-invasive osteoporosis therapy.

Synthesis and characterization of the trans- and cis-isomers of N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine and their attempted detection in human urine.

1,3-Butadiene (BD) is a carcinogenic air pollutant. N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine (MHBMA3 or 4HBeMA), an urinary BD metabolite with unspecified configuration, is considered the most sensitive BD biomarker and has been used in routine biomonitoring since 2012. However, two issues remain unaddressed: why its concentrations are unusually high relative to other urinary BD biomarkers and why some authors reported no detection of the biomarker whereas other authors readily quantitated it. To address the issues, we synthesized and structurally characterized the authentic trans- and cis-isomers of MHBMA3 (designated NE and NZ, respectively), developed an isotope-dilution LC-MS/MS method for their quantification, and examined 67 urine samples from barbecue restaurant personnel (n = 47) and hotel administrative staff (n = 20). The restaurant personnel were exposed to barbecue fumes, which contain relatively high concentrations of BD. The results showed that NE and NZ had highly similar NMR spectra, and were difficult to be well separated chromatographically. The NMR data showed that the MHBMA3 isomer investigated in most previous studies was NE. We did not detect NE and NZ in any samples; however, an interfering peak with varying heights was observed in most samples. Notably, under the chromatographic conditions used in the literature, the peak exhibited indistinguishable retention time from that of NE. Thus, it is highly likely that the interfering peak has been mis-identified as NE in previous studies, providing a reasonable explanation for the high MHBMA3 concentration in urine. The contradiction in the presence of MHBMA3 in urine was also caused by the mis-identification, because the researchers who reported the absence of MHBMA3 were actually detecting NZ. Thus, we clarified the confusion on MHBMA3 in previous studies through correctly identifying the two MHBMA3 isomers. The presence of NE and NZ in human urine warrants further investigations.

Correction: Cao et al. Effective Functional Immunogenicity of a DNA Vaccine Combination Delivered via In Vivo Electroporation Targeting Malaria Infection and Transmission. Vaccines 2022, 10, 1134.

The authors would like to make the following corrections to this published paper [...].

Investigation of oral toxicity of WS2 nanosheets to mouse intestine: Pathological injury, trace element balance, lipid profile changes, and autophagy.

The success of graphene oxides has gained extensive research interests in developing novel 2D nanomaterials (NMs). WS2 nanosheets (NSs) are novel transition metal-based 2D NMs, but their toxicity is unclear. In this study, we investigated the oral toxicity of WS2 NSs to mouse intestines. Male mice were administrated with vehicles, 1, 10, or 100 mg/kg NSs via intragastric route, once a day, for 5 days. The results indicate that the NSs did not induce pathological or ultrastructural changes in intestines. There were minimal changes of trace elements that the exposure did not induce W accumulation, and only Co levels were dose-dependently increased. Lipid droplets were observed in all groups of mice, but lipidomics data indicate that WS2 NSs only significantly decreased four lipid species, all belonging to phosphatidylcholine (PC). The levels of proteins regulating autophagic lipolysis, namely, LC3, lysosomal associated membrane protein 2 (LAMP2) and perilipin 2 (PLIN2), were increased, but it was only statistically significantly different for LC3. The results of this study suggest that repeated intragastric exposure to WS2 NSs only induced minimal influences on pathological injury, trace element balance, autophagy, and lipid profiles in mouse intestines, indicating relatively high biocompatibility of WS2 NSs to mouse intestine via oral route.