Enhanced immune reconstitution with albuvirtide in HIV-infected immunological non-responders.

Background: Incomplete immune recovery in people living with HIV/AIDS (PLWHA) remains an important clinical challenge with the lack of an effective strategy currently available to restore their T-cell immune response. This study aimed to evaluate the effect of Albuvirtide (ABT) on immune recovery in immunological non-responders (INRs) and attempted to explore potential mechanisms of ABT on the functionality of immune cells. Methods: In this prospective, open-label, controlled clinical study, participants with incomplete immune reconstitution (continuous ART over 5 years and CD4+T lymphocyte absolute count of <500 cells/µl or ART for 2-5 years and CD4+T cell count of <200 cells/µl with undetectable viral load) were received intensive treatment with ABT or maintained on the original ART regimen at a ratio of 1:1. Immune response and safety were examined within 24 weeks. In the cytological study, T subsets, cell apoptosis and cell autophagy were analyzed using immunofluorescence staining and flow cytometry from 25 blood specimens. Results: Both groups (n=25 each) were comparable in age, gender, and ART duration. At week 12, CD4+T cell count increased significantly in the intensive ABT group compared with control group (the change from baseline in CD4+T cell count: 45 vs. -5 cells/µL, p<0.001). After ABT discontinuation, CD4+T cell counts remained significantly higher in the intensive ABT group at week 24 (55 vs. -5 cells/µL, p=0.012). In laboratory analysis, naïve CD4+ T cell amounts were lowest among participants with unsatisfactory immune response (uIR) to ABT (p=0.001). The proportion of caspase 3+CD45RA+CD31+CD4+ T cells was significantly lower in participants with satisfactory immune response (sIR) to ABT (p<0.05). Conclusion: Significant CD4+T cell count increase suggests ABT enhances immune function in INRs which may be attributed to its antiviral properties as well as its ability to increase thymic cell output and decrease cell apoptosis.

Dynamic imaging of micro-vibrations with an ultra-wide bandwidth and a femtometer noise using switchable pulsed laser interferometry.

Imaging the complex dynamics of micro-vibrations plays a fundamental role in the investigation of microelectromechanical systems (MEMS). However, it remains a challenge for achieving both a wide bandwidth and a low noise due to the high photodetector noise and electromagnetic interference at GHz frequencies. Here, we propose a pulsed laser interferometry system with an adaptable switch to image GHz vibrations based on stroboscopic mixing, while measuring lower-frequency vibrations based on the homodyne scheme. The noise power spectral density is shown in both regions from DC to 10 GHz with an average noise down to 30.8 fm/√Hz at GHz frequencies, which holds the highest resolution to the best of our knowledge. Vibrational amplitude and phase mappings of a kHz comb-drive resonator, a GHz piezoelectric transducer, and a GHz film bulk acoustic resonator are presented with animated visualizations and k-space analysis, paving a new paradigm for the first time to image and analyze various MEMS devices of a bandwidth spanning 10 orders of magnitude.

Follicular CD8+ T cells promote immunoglobulin production and demyelination in multiple sclerosis and a murine model.

Emerging evidence underscores the importance of CD8+ T cells in the pathogenesis of multiple sclerosis (MS), but the precise mechanisms remain ambiguous. This study intends to elucidate the involvement of a novel subset of follicular CD8+ T cells (CD8+CXCR5+ T) in MS and an experimental autoimmune encephalomyelitis (EAE) murine model. The expansion of CD8+CXCR5+ T cells was observed in both MS patients and EAE mice during the acute phase. In relapsing MS patients, higher frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions in the central nervous system (CNS). In EAE mice, frequencies of CD8+CXCR5+ T cells were also positively correlated with clinical scores. These cells were found to infiltrate into ectopic lymphoid-like structures in the spinal cords during the peak of the disease. Furthermore, CD8+CXCR5+ T cells, exhibiting high expression levels of ICOS, CD40L, IL-21, and IL-6, were shown to facilitate B cell activation and differentiation through a synergistic interaction between CD40L and IL-21. Transferring CD8+CXCR5+ T cells into naïve mice confirmed their ability to enhance the production of anti-MOG35-55 antibodies and contribute to the disease progression. Consequently, CD8+CXCR5+ T cells may play a role in CNS demyelination through heightening humoral immune responses.

Enhanced Arsenate Immobilization by Kaolinite via Heterogeneous Pathways during Ferrous Iron Oxidation.

Clay minerals are ubiquitous in subsurface environments and have long been recognized as having a limited or negligible impact on the fate of arsenic (As) due to their negatively charged surfaces. Here, we demonstrate the significant role of kaolinite (Kln), a pervasive clay mineral, in enhancing As(V) immobilization during ferrous iron (Fe(II)) oxidation at near-neutral pH. Our results showed that Fe(II) oxidation alone was not capable of immobilizing As(V) at relatively low Fe/As molar ratios (≤2) due to the generation of Fe(III)-As(V) nanocolloids that could still migrate easily as truly dissolved As did. In the presence of kaolinite, dissolved As(V) was significantly immobilized on the kaolinite surfaces via forming Kln-Fe(III)-As(V) ternary precipitates, which had large sizes (at micrometer levels) to reduce the As mobility. The kaolinite-induced heterogeneous pathways for As(V) immobilization involved Fe(II) adsorption, heterogeneous oxidation of adsorbed Fe(II), and finally heterogeneous nucleation/precipitation of Fe(III)-As(V) phases on the edge surfaces of kaolinite. The surface precipitates were mixtures of amorphous basic Fe(III)-arsenate and As-rich hydrous ferric oxide. Our findings provide new insights into the role of clay minerals in As transformation, which is significant for the fate of As in natural and engineered systems.

L-theanine alleviates myocardial ischemia/reperfusion injury by suppressing oxidative stress and apoptosis through activation of the JAK2/STAT3 pathway in mice.

BACKGROUND: L-theanine is a unique non-protein amino acid in tea that is widely used as a safe food additive. We investigated the cardioprotective effects and mechanisms of L-theanine in myocardial ischemia-reperfusion injury (MIRI). METHODS: The cardioprotective effects and mechanisms of L-theanine and the role of Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling were investigated in MIRI mice using measures of cardiac function, oxidative stress, and apoptosis. RESULTS: Administration of L-theanine (10 mg/kg, once daily) suppressed the MIRI-induced increase in infarct size and serum creatine kinase and lactate dehydrogenase levels, as well as MIRI-induced cardiac apoptosis, as evidenced by an increase in Bcl-2 expression and a decrease in Bax/caspase-3 expression. Administration of L-theanine also decreased the levels of parameters reflecting oxidative stress, such as dihydroethidium, malondialdehyde, and nitric oxide, and increased the levels of parameters reflecting anti-oxidation, such as total antioxidant capacity (T-AOC), glutathione (GSH), and superoxide dismutase (SOD) in ischemic heart tissue. Further analysis showed that L-theanine administration suppressed the MIRI-induced decrease of phospho-JAK2 and phospho-STAT3 in ischemic heart tissue. Inhibition of JAK2 by AG490 (5 mg/kg, once daily) abolished the cardioprotective effect of L-theanine, suggesting that the JAK2/STAT3 signaling pathway may play an essential role in mediating the anti-I/R effect of L-theanine. CONCLUSIONS: L-theanine administration suppresses cellular apoptosis and oxidative stress in part via the JAK2/STAT3 signaling pathway, thereby attenuating MIRI-induced cardiac injury. L-theanine could be developed as a potential drug to alleviate cardiac damage in MIRI.

The ratio of circulating CD56dim NK cells to follicular T helper cells as a promising predictor for disease activity of relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system primarily mediated by CD4+ T helper cells. This study investigated the dynamic changes of natural killer (NK) cells and follicular T helper (Tfh) cells and their associations in relapsing-remitting MS patients. The findings revealed inverse relationships between NK cells and CD4+ T cells or Tfh cells. Specifically, CD56dim NK cells, not CD56bright NK cells, were negatively correlated with CD4+ T cells and Tfh cells. However, no significant correlations were found between NK cells and sNfL levels or EDSS scores. The ratio of CD56dim NK cells to circulating Tfh (cTfh) cells demonstrated superior discriminatory ability in distinguishing relapsing MS patients from healthy controls (HCs) and remitting patients, as determined by receiver operating characteristic (ROC) analysis. Following treatment with immunosuppressants or disease-modifying therapies (DMTs), a significant increase in the CD56dim NK/cTfh ratio was observed. These findings suggest that the CD56dim NK/cTfh ratio holds promise as a prognostic indicator for clinical relapse and treatment response in MS.

Promoting Alzheimer's disease research and therapy with stem cell technology.

BACKGROUND: Alzheimer's disease (AD) is a prevalent form of dementia leading to memory loss, reduced cognitive and linguistic abilities, and decreased self-care. Current AD treatments aim to relieve symptoms and slow disease progression, but a cure is elusive due to limited understanding of the underlying disease mechanisms. MAIN CONTENT: Stem cell technology has the potential to revolutionize AD research. With the ability to self-renew and differentiate into various cell types, stem cells are valuable tools for disease modeling, drug screening, and cell therapy. Recent advances have broadened our understanding beyond the deposition of amyloidß (Aß) or tau proteins in AD to encompass risk genes, immune system disorders, and neuron-glia mis-communication, relying heavily on stem cell-derived disease models. These stem cell-based models (e.g., organoids and microfluidic chips) simulate in vivo pathological processes with extraordinary spatial and temporal resolution. Stem cell technologies have the potential to alleviate AD pathology through various pathways, including immunomodulation, replacement of damaged neurons, and neurotrophic support. In recent years, transplantation of glial cells like oligodendrocytes and the infusion of exosomes have become hot research topics. CONCLUSION: Although stem cell-based models and therapies for AD face several challenges, such as extended culture time and low differentiation efficiency, they still show considerable potential for AD treatment and are likely to become preferred tools for AD research.

The Indispensable Roles of GMDS and GMDS-AS1 in the Advancement of Cancer: Fucosylation, Signal Pathway and Molecular Pathogenesis.

Fucosylation is facilitated by converting GDP-mannose to GDP-4-keto-6-deoxymannose, which GDP-mannose 4,6-dehydratase, a crucial enzyme in the route, carries out. One of the most prevalent glycosylation alterations linked to cancer has reportedly been identified as fucosylation. There is mounting evidence that GMDS is intimately linked to the onset and spread of cancer. Furthermore, the significance of long-chain non-coding RNAs in the development and metastasis of cancer is becoming more well-recognized, and the regulatory mechanism of lncRNAs has emerged as a prominent area of study in the biological sciences. GMDS-AS1, an antisense RNA of GMDS, was discovered to have the potential to be an oncogene. We have acquired and analyzed relevant data to understand better how GMDS-AS1 and its lncRNA work physiologically and in tumorigenesis and progression. Additionally, we have looked into the possible effects of these molecules on cancer treatment approaches and patient outcomes. The physiological roles and putative processes of GMDS and lncRNA GMDS-AS1 throughout the development and progression of tumors have been assembled and examined. We also examined how these chemicals might affect patient prognosis and cancer therapy approaches. GMDS and GMDS-AS1 were determined to be research subjects by searching and gathering pertinent studies using the PubMed system. The analysis of these research articles demonstrated the close relationship between GMDS and GMDS-AS1 and tumorigenesis and the factors that influence them. GMDS plays a vital role in regulating fucosylation. The related antisense gene GMDS-AS1 affects the biological behaviors of cancer cells through multiple pathways, including the key processes of proliferation, migration, invasion, and apoptosis, providing potential biomarkers and therapeutic targets for cancer treatment and prognosis assessment.

Burdock miR8175 in diet improves insulin resistance induced by obesity in mice through food absorption.

The incidence of type 2 diabetes mellitus (T2DM) induced by obesity is rapidly increasing. Although there are many synthetic drugs for treating T2DM, they have various side effects. Here, we report that miR8175, a plant miRNA from burdock root, has effective antidiabetic activity. After administration of burdock decoction or synthetic miR8175 by gavage, both burdock decoction and miR8175 can significantly improve the impaired glucose metabolism of diabetic mice induced by a high-fat diet (HFD). Our results demonstrate that burdock decoction and miR8175 enhance the insulin sensitivity of the hepatic insulin signaling pathway by targeting Ptprf and Ptp1b, which may be the reason for the improvement in metabolism. This study provides a theoretical basis for the main active component and molecular mechanism of burdock to improve insulin resistance. And the study also suggests that plant miRNA may be an indispensable nutrient for maintaining human health.

[Study on allergen components of birch pollen in Beijing area].

Objective:To explore the allergen components of birch pollen in the Beijing area and interpret its clinical significance. Methods:A total of 58 patients with birch pollen allergy were included in the cross-sectional study and divided into allergic rhinitis（AR） and allergic asthma（AA） groups according to clinical manifestations. Concentration of birch pollen allergen sIgE, as well as Bet v 1, Bet v 2, Bet v 4 and Bet v 6 sIgE were detected by ImmunoCAP immunolinked immunoassay. Differences of sIgE concentration of birch pollen allergen component in AR and AA were analyzed. Results:There were 44（75.9%） cases of AR and 14（24.1%） cases of AA were enrolled. All the 18 patients with spring pollen allergy were AR patients without AA. There were 40 cases with both spring and autumn pollen allergy, of which 26 cases（65%） were AR and 14 cases（35%） were AA. The sIgE of birch pollen allergen was level 2 or above in all subjects. 94.8% were positive for any four allergen components. 77.6% were mono-sensitized to any allergen component while 17.2% were dual-sensitized. The positive rate of Bet v 1 and/or Bet v 2 was 93.1%. The positive rates of four protein components were: Bet v 1（82.8%）, Bet v 2（29.3%）, Bet v 6（1.7%）, Bet v 4（0%）. sIgE of birch pollen was positively correlated with sIgE level of Betv 1（r=0.898, P<0.001）. The sIgE concentration of Bet v2 in AA group was significantly higher than that in AR group（[4.34±14.35] kUA/L vs [1.56±3.26] kUA/L, P<0.05）. There was no significant difference in other components. Conclusion:Bet v 1 is the main allergen component of birch pollen in the Beijing area, and Bet v 1 plus Bet v 2 can diagnose more than 90% of birch pollen allergy.

Ultrasound assisted fabrication of the yeast protein-chitooligosaccharide-betanin composite for stabilization of betanin.

Betanin, a water-soluble colorant, is sensitive to light and temperature and is easily faded and inactivated. This study investigated the formation of yeast protein-chitooligosaccharide-betanin complex (YCB) induced by ultrasound treatment, and evaluated its protective effect on the colorant betanin. Ultrasound (200-600 W) increased the surface hydrophobicity and solubility of yeast protein, and influenced the protein's secondary structure by decreasing the α-helix content and increasing the contents of ß-sheet and random coil. The ultrasound treatment (200 W, 15 min) facilitated binding of chitooligosaccharide and betanin to the protein, with the binding numbers of 4.26 ± 0.51 and 0.61 ± 0.06, and the binding constant of (2.73 ± 0.25) × 105 M-1 and (3.92 ± 0.10) × 104 M-1, respectively. YCB could remain the typical color of betanin, and led to a smaller and disordered granule morphology. Moreover, YCB exhibited enhanced thermal-, light-, and metal irons (ferric and copper ions) -stabilities of betanin, protected the betanin against color fading, and realized a controlled release in simulated gastrointestinal tract. This study extends the potential application of the fungal proteins for stabilizing bioactive molecules.

IGF2BP3 enhances lipid metabolism in cervical cancer by upregulating the expression of SCD.

Cervical cancer (CC) is the most common gynecologic malignancy, which seriously threatens the health of women. Lipid metabolism is necessary for tumor proliferation and metastasis. However, the molecular mechanism of the relationship between CC and lipid metabolism remains poorly defined. We revealed the expression of IGF2BP3 in CC exceeded adjacent tissues, and was positively associated with tumor stage using human CC tissue microarrays. The Cell Counting Kit-8, colony formation assay, 5-ethynyl-2'-deoxyuridine assay, transwell assays, wound-healing assays, and flow cytometry assessed the role of IGF2BP3 in proliferation and metastasis of CC cells. Besides, exploring the molecular mechanism participating in IGF2BP3-driven lipid metabolism used RNA-seq, which determined SCD as the target of IGF2BP3. Further, lipid droplets, cellular triglyceride (TG) contents, and fatty acids were accessed to discover that IGF2BP3 can enhance lipid metabolism in CC. Moreover, RIP assay and methylated RNA immunoprecipitation experiments seeked the aimed-gene-binding specificity. Lastly, the IGF2BP3 knockdown restrained CC growth and lipid metabolism, after which SCD overexpression rescued the influence in vitro and in vivo using nude mouse tumor-bearing model. Mechanistically, IGF2BP3 regulated SCD mRNA m6A modifications via IGF2BP3-METTL14 complex, thereby enhanced CC proliferation, metastasis, and lipid metabolism. Our study highlights IGF2BP3 plays a crucial role in CC progression and represents a therapeutic latent strategy. It is a potential tactic that blocks the metabolic pathway relevant to IGF2BP3 with the purpose of treating CC.

Physiologically based toxicokinetic modelling of Tri(2-chloroethyl) phosphate (TCEP) in mice accounting for multiple exposure routes.

Exposure routes are important for health risk assessment of chemical risks. The application of physiologically based toxicokinetic (PBTK) models to predict concentrations in vivo can determine the effects of harmful substances and tissue accumulation on the premise of saving experimental costs. In this study, Tri(2-chloroethyl) phosphate (TCEP), an organophosphate ester (OPE), was used as an example to study the PBTK model of mice exposed to different exposure doses by multiple routes. Different routes of exposure (gavage and intradermal injection) can cause differences in the concentration of chemicals in the organs. TCEP that enters the body through the mouth is mainly concentrated in the gastrointestinal tract and liver. However, the concentrations of chemicals that enter the skin into the mice are higher in skin, rest of body, and blood. In addition, TCEP was absorbed and accumulated very rapidly in mice, within half an hour after a single exposure. We have successfully established a mouse PBTK model of the TCEP accounting for multiple exposure Routes and obtained a series of kinetic parameters. The model includes blood, liver, kidney, stomach, intestine, skin, and rest of body compartments. Oral and dermal exposure route was considered for PBTK model. The PBTK model established in this study has a good predictive ability. More than 70% of the predicted values deviated from the measured values by less than 5-fold. In addition, we extrapolated the model to humans. A human PBTK model is built. We performed a health risk assessment for world populations based on human PBTK model. The risk of TCEP in dust is greater through mouth than through skin. The risk of TCEP in food of Chinese population is greater than dust.

Unraveling the underlying mechanism of good electrochemical performance of hard carbon in PC/EC-Based electrolyte.

Although hard carbon in propylene carbonate / ethylene carbonate (PC/EC)-based electrolytes possesses favorable electrochemical characteristics in rechargeable sodium-ion batteries, the underlying mechanism is still vague. Numerous hypotheses have been proposed to solve the puzzle, but none of them have satisfactorily unraveled the reason at the molecular-level. In this study, we firstly attempted to address this mystery through a profound insight into the disparity of the ion solvation/desolvation behavior in electrolyte. Combining the results of density functional theory (DFT) calculations and experiments, the work explains that compared to the sole PC-based electrolyte, Na+-EC4 molecules in the PC/EC-based electrolyte preferentially undergo reduction and contribute to the emergence of a more stable protective film on the surface of hard carbon, leading to the preferable durability and rate capability of the cell. Nevertheless, applying the ion solvation/desolvation model, it also reveals that Na+-(solvent)n molecules in the PC/EC-based electrolyte can achieve faster Na+ desolvation processes than in the PC-based electrolyte alone, contributing to the enhancement of charge transfer kinetics. This research holds great importance in uncovering the possible mechanism of the remarkable electrochemical- properties of hard carbon in PC/EC-based electrolytes, and advancing its practical utilization in future sodium-ion batteries.

Elucidating the toxicity mechanisms of organophosphate esters by adverse outcome pathway network.

With the widespread use of organophosphate esters (OPEs), the accumulation and toxicity effect of OPEs in biota are attracting more and more concern. In order to clarify the mechanism of toxicity of OPEs to organisms, this study reviewed the OPEs toxicity and systematically identified the mechanism of OPEs toxicity under the framework of adverse outcome pathway (AOP). OPEs were divided into three groups (alkyl-OPEs, aryl-OPEs, and halogenated-OPEs) and biota was divided into aquatic organism and mammals. The results showed that tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) mainly caused neurotoxicity, reproductive, and hepatotoxicity in different mechanisms. According to the constructed AOP network, the toxicity mechanism of OPEs on aquatic organisms and mammals is different, which is mainly attributed to the different biological metabolic systems of aquatic organisms and mammals. Interestingly, our results indicate that the toxicity effect of the three kinds of OPEs on aquatic organisms is different, while there was no obvious difference in the mechanism of toxicity of OPEs on mammals. This study provides a theoretical basis for OPEs risk assessment in the future.

Loganin protects against myocardial ischemia-reperfusion injury by modulating oxidative stress and cellular apoptosis via activation of JAK2/STAT3 signaling.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is a pathological process that follows immediate revascularization of myocardial infarction and is characterized by exacerbation of cardiac injury. Loganin, a monoterpene iridoid glycoside derived from Cornus officinalis Sieb. Et Zucc, can exert cardioprotective effects in cardiac hypertrophy and atherosclerosis. However, its role in ischemic heart disease remains largely unknown. METHODS: Considering that Janus kinase 2 (JAK2)/ signal transducer and activator of transcription 3 (STAT3) has a protective effect on the heart, we developed a mouse model of MIRI to investigate the potential role of this pathway in loganin-induced cardioprotection. RESULTS: Our results showed that treatment with loganin (20 mg/kg) prevented the enlargement of myocardial infarction, myocyte destruction, serum markers of cardiac injury, and deterioration of cardiac function induced by MIRI. Myocardium subjected to I/R treatment exhibited higher levels of oxidative stress, as indicated by an increase in malondialdehyde (MDA) and dihydroethidium (DHE) density and a decrease in total antioxidant capacity (T-AOC), glutathione (GSH), and superoxide dismutase (SOD), whereas treatment with loganin showed significant attenuation of I/R-induced oxidative stress. Loganin treatment also increased the expression of anti-apoptotic Bcl-2 and reduced the expression of caspase-3/9, Bax, and the number of TUNEL-positive cells in ischemic cardiac tissue. Moreover, treatment with loganin triggered JAK2/STAT3 phosphorylation, and AG490, a JAK2/STAT3 inhibitor, partially abrogated the cardioprotective effects of loganin, indicating the essential role of JAK2/STAT3 signaling in the cardioprotective effects of loganin. CONCLUSIONS: Our data demonstrate that loganin protects the heart from I/R injury by inhibiting I/R-induced oxidative stress and cellular apoptosis via activation of JAK2/STAT3 signaling.

Exploring Route-Specific Pharmacokinetics of PFAS in Mice by Coupling in Vivo Tests and Physiologically Based Toxicokinetic Models.

BACKGROUND: Oral ingestion, inhalation, and skin contact are important exposure routes for humans to uptake per- and polyfluoroalkyl substances (PFAS). However, nasal and dermal exposure to PFAS remains unclear, and accurately predicting internal body burden of PFAS in humans via multiple exposure pathways is urgently required. OBJECTIVES: We aimed to develop multiple physiologically based toxicokinetic (PBTK) models to unveil the route-specific pharmacokinetics and bioavailability of PFAS via respective oral, nasal, and dermal exposure pathways using a mouse model and sought to predict the internal concentrations in various tissues through multiple exposure routes and extrapolate it to humans. METHODS: Mice were administered the mixed solution of perfluorohexane sulfonate, perfluorooctane sulfonate, and perfluorooctanoic acid through oral, nasal, and dermal exposure separately or jointly. The time-dependent concentrations of PFAS in plasma and tissues were determined to calibrate and validate the individual and combined PBTK models, which were applied in single- and repeated-dose scenarios. RESULTS: The developed route-specific PBTK models successfully simulated the tissue concentrations of PFAS in mice following single or joint exposure routes as well as long-term repeated dose scenarios. The time to peak concentration of PFAS in plasma via dermal exposure was much longer (34.1-83.0 h) than that via nasal exposure (0.960 h). The bioavailability of PFAS via oral exposure was the highest (73.2%-98.0%), followed by nasal (33.9%-66.8%) and dermal exposure (4.59%-7.80%). This model was extrapolated to predict internal levels in human under real environment. DISCUSSION: Based on these data, we predict the following: PFAS were absorbed quickly via nasal exposure, whereas a distinct hysteresis effect was observed for dermal exposure. Almost all the PFAS to which mice were exposed via gastrointestinal route were absorbed into plasma, which exhibited the highest bioavailability. Exhalation clearance greatly depressed the bioavailability of PFAS via nasal exposure, whereas the lowest bioavailability in dermal exposure was because of the interception of PFAS within the skin layers. https://doi.org/10.1289/EHP11969.

Profiles of Birch Allergen Component Sensitization and Its Association with Pollen Food Allergy Syndrome in Northern China.

Purpose: To investigate the major allergen components associated with birch pollen allergy in northern China and elucidate clinical relevance to pollen food allergy syndrome (PFAS). Methods: Fifty-eight patients were recruited for a cross-sectional study and categorized into two groups: PFAS group and non-PFAS group, as well as apple allergy group and non-apple allergy group. The sIgE levels of birch pollen and its components, namely Bet v 1, Bet v 2, Bet v 4, and Bet v 6, were analyzed. Results: Among 58 participants, 44 individuals (75.9%) reported PFAS. 32 out of 44 (72.7%) participants reported apple allergy. Bet v 1 exhibited the highest sensitization rate at 82.8%, followed by Bet v 2 (29.3%) and Bet v 6 (1.7%). The combined sensitization rate for Bet v 1 and/or Bet v 2 was 93.1%. A total of 77.6% of the subjects demonstrated sensitization to single component, while 19.0% exhibited sensitization to two components. The sIgE levels of birch pollen and Bet v 1 were significantly elevated in PFAS group compared to non-PFAS group (p=0.001, p<0.001, respectively), as well as in apple-allergic and non-apple-allergic group (p<0.001, p<0.001, respectively). The optimal cut-off values for birch pollen and Bet v 1 sIgE were determined to be 7.09 kUA/L (with a sensitivity of 84.1% and specificity of 78.6%) and 5.11 kUA/L (with a sensitivity of 75.0% and specificity of 85.7%) when diagnosing PFAS. In terms of apple allergy, the optimal cut-off value were 9.40 kUA/L (with a sensitivity of 81.3% and specificity of 76.9%) and 6.53 kUA/L (with a sensitivity of 84.4% and specificity of 84.6%), respectively. Conclusion: The predominant sensitization pattern is mono-sensitization to Bet v 1, but when considering immunotherapy, Bet v 2 should also be taken into account. Bet v 1 serves as a valuable biomarker for diagnosing PFAS and apple allergy.

Joint geoacoustic inversion based on Pearson correlation coefficient constraints.

This Letter proposes a joint geoacoustic inversion method for modal group velocity dispersion and amplitudes of waveform by incorporating a Pearson correlation constraint. Numerical simulations show that this joint inversion leads to improved geoacoustic inversion performance with smaller uncertainties compared to separate inversion methods when applied to data from a single receiver. Additionally, the effective use of the Wasserstein metric from optimal transport theory is explored and compared to the more-common L2 norm misfit measure. The Letter also presents a qualitative representation of joint inversion convergence obtained through multiple independent runs of genetic algorithms. The algorithm is applied to simulated data.