Nonvolatile Reconfigurable Logic Device Based on Photoinduced Interfacial Charge Trapping in van der Waals Gap.

Due to the increasing complexity in miniaturization of electronic devices, reconfigurable field-effect transistors (RFETs) have emerged as a solution. Although the foundational concepts of RFETs have matured over two decades, ongoing breakthroughs are needed to address challenges such as improving the device performance as well as achieving balanced symmetry between n-type and p-type transport modes with long-term stability. Herein, we present a nonvolatile WSe2-based RFET that utilizes photoassisted interfacial charge trapping at the h-BN and SiO2 interface. Unlike typical RFETs with two gate electrodes, our RFETs achieved polarity control with a single operating gate activated exclusively under white-light exposure. The threshold voltage was tunable, ranging from 27.4 (-31.6 V) to 0.9 (+19.5 V), allowing selective activation of n-type (p-type) operation at VGS = 0 V. Additionally, our WSe2-based RFETs show superior repeatability and long-term stability. Leveraging these advantages, various reconfigurable logic circuits were successfully demonstrated, including complementary inverters and switch circuits as well as pull-up and pull-down circuits, highlighting the potential of WSe2 FETs for future advancements of integrated circuits.

The contribution of vitamin D insufficiency to the onset of steatotic liver disease among individuals with metabolic dysfunction.

The interplay between fatty liver disease (FLD) and metabolic dysfunction has given rise to the concept of metabolic associated fatty liver disease (MAFLD). With vitamin D insufficiency frequently co-occurring with FLD and linked to metabolic abnormalities, this study investigates the potential role of vitamin D in the development of MAFLD. In this cross-sectional analysis, 22,476 participants with baseline metabolic dysfunction and known serum 25-OH-vitamin D3 levels were examined. The fatty liver index (FLI) was utilized to predict FLD, dividing subjects into MAFLD and non-MAFLD groups. Further stratification by vitamin D levels (sufficient vs. insufficient) and gender provided a detailed assessment through binary logistic regression to determine the association of vitamin D status with MAFLD incidence. Vitamin D insufficiency correlated with a higher MAFLD incidence in metabolically impaired individuals. Post-adjustment, the correlation was stronger (men: aOR = 1.32, 95% CI = 1.22-1.43, P < 0.001; women: aOR = 1.53, 95% CI = 1.18-1.98, P = 0.001). Lower serum 25-OH-vitamin D3 levels were found in MAFLD patients across genders (men: P = 0.003; women: P = 0.014), with a higher prevalence of insufficiency in MAFLD cases (men: P = 0.007; women: P = 0.003). The vitamin D-MAFLD link was stable across subgroups and using varying FLI criteria. Our findings indicate a clear association between vitamin D insufficiency and increased MAFLD incidence, underscoring the potential of vitamin D as an anti-lipogenic and anti-fibrotic agent.

Strengthening Multi-Factor Authentication Through Physically Unclonable Functions in PVDF-HFP-Phase-Dependent a-IGZO Thin-Film Transistors.

For enhanced security in hardware-based security devices, it is essential to extract various independent characteristics from a single device to generate multiple keys based on specific values. Additionally, the secure destruction of authentication information is crucial for the integrity of the data. Doped amorphous indium gallium zinc oxide (a-IGZO) thin-film transistors (TFTs) using poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) induce a dipole doping effect through a phase-transition process, creating physically unclonable function (PUF) devices for secure user information protection. The PUF security key, generated at VGS = 20 V in a 20 × 10 grid, demonstrates uniformity of 42% and inter-Hamming distance (inter-HD) of 49.79% in the ß-phase of PVDF-HFP. However, in the γ-phase, the uniformity drops to 22.5%, and inter-HD decreases to 35.74%, indicating potential security key destruction during the phase transition. To enhance security, a multi-factor authentication (MFA) system is integrated, utilizing five security keys extracted from various TFT parameters. The security keys from turn-on voltage (VON ), VGS = 20 V, VGS = 30 V, mobility, and threshold voltage (Vth ) exhibit near-ideal uniformities and inter-HDs, with the highest values of 58% and 51.68%, respectively. The dual security system, combining phase transition and MFA, establishes a robust protection mechanism for privacy-sensitive user information.

Molecular detection and characterization of Acanthamoeba infection in dogs and its association with keratitis in Korea.

Acanthamoeba infection is associated with keratitis in humans; however, its association with keratitis in dogs remains unclear. To investigate this possibility, we collected 171 conjunctival swab samples from dogs with eye-related diseases (65 with keratitis and 106 without keratitis) at Chungbuk National University Veterinary Teaching Hospital, Korea, from August 2021 to September 2022. Polymerase chain reaction identified 9 samples (5.3%) as Acanthamoeba positive; of these, 3 were from dogs with keratitis (4.6%) and 6 were from dogs without keratitis (5.7%). Our results indicated no significant association between Acanthamoeba infection and keratitis, season, sex, or age. All Acanthamoeba organisms found in this study had the genotype T4, according to 18S ribosomal RNA analysis. Acanthamoeba infection in dogs might have only a limited association with keratitis.

Comparison of Diagnostic Performance between Classic and Modified Abbreviated Breast MRI and the MRI Features Affecting Their Diagnostic Performance.

Abbreviated breast magnetic resonance imaging (AB-MRI) has emerged as a supplementary screening tool, though protocols have not been standardized. The purpose of this study was to compare the diagnostic performance of modified and classic AB-MRI and determine MRI features affecting their diagnostic performance. Classic AB-MRI included one pre- and two post-contrast T1-weighted imaging (T1WI) scans, while modified AB-MRI included a delayed post-contrast axial T1WI scan and an axial T2-weighted interpolated scan obtained between the second and third post-contrast T1WI scans. Four radiologists (two specialists and two non-specialists) independently categorized the lesions. The MRI features investigated were lesion size, lesion type, and background parenchymal enhancement (BPE). The Wilcoxon rank-sum test, Fisher's exact test, and bootstrap-based test were used for statistical analysis. The average area under the curve (AUC) for modified AB-MRI was significantly greater than that for classic AB-MRI (0.76 vs. 0.70, p = 0.010) in all reader evaluations, with a similar trend in specialist evaluations (0.83 vs. 0.76, p = 0.004). Modified AB-MRI demonstrated increased AUCs and better diagnostic performance than classic AB-MRI, especially for lesion size > 10 mm (p = 0.018) and mass lesion type (p = 0.014) in specialist evaluations and lesion size > 10 mm (p = 0.003) and mild (p = 0.026) or moderate BPE (p = 0.010) in non-specialist evaluations.

The potential of Rhodobacter sphaeroides extract as an alternative supplement for cell culture systems.

It is essential to identify suitable supplements that enhance cell growth, viability, and functional development in cell culture systems. The use of fetal bovine serum (FBS) has been common, but it has limitations, such as batch-to-batch variability, ethical concerns, and risks of environmental contamination. In this study, we explore the potential of Rhodobacter sphaeroides extract, derived from a probiotic photosynthetic bacterium, as an alternative supplement. Our results demonstrate that the extract from R. sphaeroides significantly improves various aspects of cell behavior compared to serum-free conditions. It enhances cell growth and viability to a greater extent than FBS supplementation. Additionally, the extract alleviates oxidative stress by reducing intracellular levels of reactive oxygen species and stimulates lysosomal activity, contributing to cellular processes. The presence of abundant amino acids, glycine and arginine, in the extract may play a role in promoting cell growth. These findings emphasize the potential of R. sphaeroides extract as a valuable supplement for cell culture, offering advantages over the use of FBS.IMPORTANCEThe choice of supplements for cell culture is crucial in biomedical research, but the widely used fetal bovine serum (FBS) has limitations in terms of variability, ethics, and environmental risks. This study explores the potential of an extract from Rhodobacter sphaeroides, a probiotic bacterium, as an alternative supplement. The findings reveal that the R. sphaeroides extract surpasses FBS in enhancing cell growth, viability, and functionality. It also mitigates oxidative stress and stimulates lysosomal activity, critical for cellular health. The extract's abundance of glycine and arginine, amino acids with known growth-promoting effects, further highlights its potential. By providing a viable substitute for FBS, the R. sphaeroides extract addresses the need for consistent, ethical, and environmentally friendly cell culture supplements. This research paves the way for sustainable and reliable cell culture systems, revolutionizing biomedical research and applications in drug development and regenerative medicine.

Split-Gate: Harnessing Gate Modulation Power in Thin-Film Electronics.

With the increase in electronic devices across various applications, there is rising demand for selective carrier control. The split-gate consists of a gate electrode divided into multiple parts, allowing for the independent biasing of electric fields within the device. This configuration enables the potential formation of both p- and n-channels by injecting holes and electrons owing to the presence of the two gate electrodes. Applying voltage to the split-gate allows for the control of the Fermi level and, consequently, the barrier height in the device. This facilitates band bending in unipolar transistors and allows ambipolar transistors to operate as if unipolar. Moreover, the split-gate serves as a revolutionary tool to modulate the contact resistance by controlling the barrier height. This approach enables the precise control of the device by biasing the partial electric field without limitations on materials, making it adaptable for various applications, as reported in various types of research. However, the gap length between gates can affect the injection of the electric field for the precise control of carriers. Hence, the design of the gap length is a critical element for the split-gate structure. The primary investigation in this review is the introduction of split-gate technology applied in various applications by using diverse materials, the methods for forming the split-gate in each device, and the operational mechanisms under applied voltage conditions.

Anion Engineering for Stabilizing Li Interstitial Sites in Halide Solid Electrolytes for All-Solid-State Li Batteries.

Halide solid electrolytes (SEs) have been highlighted for their high-voltage stability. Among the halide SEs, the ionic conductivity has been improved by aliovalent metal substitutions or choosing a ccp-like anion-arranged monoclinic structure (C2/m) over hcp- or bcc-like anion-arranged structures. Here, we present a new approach, hard-base substitution, and its underlying mechanism to increase the ionic conductivity of halide SEs. The oxygen substitution to Li2ZrCl6 (trigonal, hcp) increased the ionic conductivity from 0.33 to 1.3 mS cm-1 at Li3.1ZrCl4.9O1.1 (monoclinic, ccp), while the sulfur and fluorine substitutions were not effective. A systematic comparison study revealed that the energetic stabilization of interstitial sites for Li migration plays a key role in improving the ionic conductivity, and the ccp-like anion sublattice is not sufficient to achieve high ionic conductivity. We further examined the feasibility of the oxyhalide SE for practical and all-solid-state battery applications.

Exploring shared neural substrates underlying cognition and gait variability in adults without dementia.

BACKGROUND: High gait variability is associated with neurodegeneration and cognitive impairments and is predictive of cognitive impairment and dementia. The objective of this study was to identify cortical or subcortical structures of the brain shared by gait variability measured using a body-worn tri-axial accelerometer (TAA) and cognitive function. METHODS: This study is a part of a larger population-based cohort study on cognitive aging and dementia. The study included 207 participants without dementia, with a mean age of 72.6, and 45.4% of them are females. We conducted standardized diagnostic interview including a detailed medical history, physical and neurological examinations, and laboratory tests for cognitive impairment. We obtained gait variability during walking using a body-worn TAA along and measured cortical thickness and subcortical volume from brain magnetic resonance (MR) images. We cross-sectionally investigated the cortical and subcortical neural structures associated with gait variability and the shared neural substrates of gait variability and cognitive function. RESULTS: Higher gait variability was associated with the lower cognitive function and thinner cortical gray matter but not smaller subcortical structures. Among the clusters exhibiting correlations with gait variability, one that included the inferior temporal, entorhinal, parahippocampal, fusiform, and lingual regions in the left hemisphere was also associated with global cognitive and verbal memory function. Mediation analysis results revealed that the cluster's cortical thickness played a mediating role in the association between gait variability and cognitive function. CONCLUSION: Gait variability and cognitive function may share neural substrates, specifically in regions related to memory and visuospatial navigation.

Textural and Volumetric Changes of the Temporal Lobes in Semantic Variant Primary Progressive Aphasia and Alzheimer's Disease.

BACKGROUND: Texture analysis may capture subtle changes in the gray matter more sensitively than volumetric analysis. We aimed to investigate the patterns of neurodegeneration in semantic variant primary progressive aphasia (svPPA) and Alzheimer's disease (AD) by comparing the temporal gray matter texture and volume between cognitively normal controls and older adults with svPPA and AD. METHODS: We enrolled all participants from three university hospitals in Korea. We obtained T1-weighted magnetic resonance images and compared the gray matter texture and volume of regions of interest (ROIs) between the groups using analysis of variance with Bonferroni posthoc comparisons. We also developed models for classifying svPPA, AD and control groups using logistic regression analyses, and validated the models using receiver operator characteristics analysis. RESULTS: Compared to the AD group, the svPPA group showed lower volumes in five ROIs (bilateral temporal poles, and the left inferior, middle, and superior temporal cortices) and higher texture in these five ROIs and two additional ROIs (right inferior temporal and left entorhinal cortices). The performances of both texture- and volume-based models were good and comparable in classifying svPPA from normal cognition (mean area under the curve [AUC] = 0.914 for texture; mean AUC = 0.894 for volume). However, only the texture-based model achieved a good level of performance in classifying svPPA and AD (mean AUC = 0.775 for texture; mean AUC = 0.658 for volume). CONCLUSION: Texture may be a useful neuroimaging marker for early detection of svPPA in older adults and its differentiation from AD.

Cortical Iron Accumulation as an Imaging Marker for Neurodegeneration in Clinical Cognitive Impairment Spectrum: A Quantitative Susceptibility Mapping Study.

OBJECTIVE: Cortical iron deposition has recently been shown to occur in Alzheimer's disease (AD). In this study, we aimed to evaluate how cortical gray matter iron, measured using quantitative susceptibility mapping (QSM), differs in the clinical cognitive impairment spectrum. MATERIALS AND METHODS: This retrospective study evaluated 73 participants (mean age ± standard deviation, 66.7 ± 7.6 years; 52 females and 21 males) with normal cognition (NC), 158 patients with mild cognitive impairment (MCI), and 48 patients with AD dementia. The participants underwent brain magnetic resonance imaging using a three-dimensional multi-dynamic multi-echo sequence on a 3-T scanner. We employed a deep neural network (QSMnet+) and used automatic segmentation software based on FreeSurfer v6.0 to extract anatomical labels and volumes of interest in the cortex. We used analysis of covariance to investigate the differences in susceptibility among the clinical diagnostic groups in each brain region. Multivariable linear regression analysis was performed to study the association between susceptibility values and cognitive scores including the Mini-Mental State Examination (MMSE). RESULTS: Among the three groups, the frontal (P < 0.001), temporal (P = 0.004), parietal (P = 0.001), occipital (P < 0.001), and cingulate cortices (P < 0.001) showed a higher mean susceptibility in patients with MCI and AD than in NC subjects. In the combined MCI and AD group, the mean susceptibility in the cingulate cortex (ß = -216.21, P = 0.019) and insular cortex (ß = -276.65, P = 0.001) were significant independent predictors of MMSE scores after correcting for age, sex, education, regional volume, and APOE4 carrier status. CONCLUSION: Iron deposition in the cortex, as measured by QSMnet+, was higher in patients with AD and MCI than in NC participants. Iron deposition in the cingulate and insular cortices may be an early imaging marker of cognitive impairment related neurodegeneration.

Development and application of novel peptide-formulated nanoparticles for treatment of atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin condition that is characterized by skin inflammation, itching, and redness. Although various treatments can alleviate symptoms, they often come with side effects, highlighting the need for new treatments. Here, we discovered a new peptide-based therapy using the intra-dermal delivery technology (IDDT) platform developed by Remedi Co., Ltd (REMEDI). The platform screens and identifies peptides derived from proteins in the human body that possess cell-penetrating peptide (CPP) properties. We screened over 1000-peptides and identified several derived from the Speckled protein (SP) family that have excellent CPP properties and have anti-inflammatory effects. We assessed these peptides for their potential as a treatment for atopic dermatitis. Among them, the RMSP1 peptide showed the most potent anti-inflammatory effects by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription 3 (STAT3) signaling pathways while possessing CPP properties. To further improve efficacy and stability, we developed a palmitoylated version called Pal-RMSP1. Formulation studies using liposomes (Pal-RMSP1 LP) and micelles (Pal-RMSP1 DP) demonstrated improved anti-inflammatory effects in vitro and enhanced therapeutic effects in vivo. Our study indicates that nano-formulated Pal-RMSP1 could have the potential to become a new treatment option for atopic dermatitis.

Machine Learning Attacks-Resistant Security by Mixed-Assembled Layers-Inserted Graphene Physically Unclonable Function.

Mixed layers of octadecyltrichlorosilane (ODTS) and 1H,1H,2H,2H-perfluorooctyltriethoxysilane (FOTS) on an active layer of graphene are used to induce a disordered doping state and form a robust defense system against machine-learning attacks (ML attacks). The resulting security key is formed from a 12 × 12 array of currents produced at a low voltage of 100 mV. The uniformity and inter-Hamming distance (HD) of the security key are 50.0 ± 12.3% and 45.5 ± 16.7%, respectively, indicating higher security performance than other graphene-based security keys. Raman spectroscopy confirmed the uniqueness of the 10,000 points, with the degree of shift of the G peak distinguishing the number of carriers. The resulting defense system has a 10.33% ML attack accuracy, while a FOTS-inserted graphene device is easily predictable with a 44.81% ML attack accuracy.

Chlorella vulgaris Modulates Gut Microbiota and Induces Regulatory T Cells to Alleviate Colitis in Mice.

Chlorella vulgaris (C. vulgaris) is unicellular green algae consumed worldwide as a functional food. The immune stimulatory function of C. vulgaris is known; however, no study has elucidated its immune regulatory potential and associated microbiome modulation. In the current study, we aimed to validate the immune regulatory role of C. vulgaris mediated through two mechanisms. Initially, we assessed its ability to promote the expansion of the regulatory T cell (Treg) population. Subsequently, we investigated its impact on gut microbiota composition and associated metabolites. The supplementation of C. vulgaris altered the gut microbiota composition, accompanied by increased short-chain fatty acid (SCFAs) production in mice at homeostasis. We later used C. vulgaris in the treatment of a DSS-induced colitis model. C. vulgaris intervention alleviated the pathological symptom of colitis in mice, with a corresponding increase in Treg levels. As C. vulgaris is a safe and widely used food supplement, it can be a feasible strategy to instigate cross-talk between the host immune system and the intestinal flora for the effective management of inflammatory bowel disease (IBD).

Room temperature processed protective layer for printed silver electrodes.

Low-temperature processed printed silver electrodes pave the way for electrical connections in flexible substrates with reduced energy consumption. Despite their excellent performance and simple process, printed silver electrodes' poor stability limits their applications. This study demonstrates a transparent protective layer without thermal annealing for printed silver electrodes, which maintains its electrical properties for a long period of time. A fluoropolymer, specifically a cyclic transparent optical polymer (CYTOP), was used as a protective layer for silver. The CYTOP is room temperature processable and chemically stable against carboxyl acid. The introduction of the CYTOP film on the printed silver electrodes mitigates the chemical reaction between silver and carboxyl acid, thereby elongating its lifetime. Under heated acetic acid, the printed silver electrodes with a CYTOP protective layer maintained their initial resistance for up to 300 hours, while the electrodes without a protective layer were damaged within a few hours. A microscopic image shows that the protective layer enables printed electrodes to maintain their shape without damage. Hence, the protective layer guarantees the accurate and reliable performance of electronic devices with printed electrodes under actual operating conditions. This research will contribute to designing chemically reliable flexible devices in the near future.

Magnetic resonance texture analysis reveals stagewise nonlinear alterations of the frontal gray matter in patients with early psychosis.

Although gray matter (GM) abnormalities are present from the early stages of psychosis, subtle/miniscule changes may not be detected by conventional volumetry. Texture analysis (TA), which permits quantification of the complex interrelationship between contrasts at the individual voxel level, may capture subtle GM changes with more sensitivity than does volume or cortical thickness (CTh). We performed three-dimensional TA in nine GM regions of interest (ROIs) using T1 magnetic resonance images from 101 patients with first-episode psychosis (FEP), 85 patients at clinical high risk (CHR) for psychosis, and 147 controls. Via principal component analysis, three features of gray-level cooccurrence matrix - informational measure of correlation 1 (IMC1), autocorrelation (AC), and inverse difference (ID) - were selected to analyze cortical texture in the ROIs that showed a significant change in volume or CTh in the study groups. Significant reductions in GM volume and CTh of various frontotemporal regions were found in the FEP compared with the controls. Increased frontal AC was found in the FEP group compared to the controls after adjusting for volume and CTh changes. While volume and CTh were preserved in the CHR group, a stagewise nonlinear increase in frontal IMC1 was found, which exceeded both the controls and FEP group. Increased frontal IMC1 was also associated with a lesser severity of attenuated positive symptoms in the CHR group, while neither volume nor CTh was. The results of the current study suggest that frontal IMC1 may reflect subtle, dynamic GM changes and the symptomatology of the CHR stage with greater sensitivity, even in the absence of gross GM abnormalities. Some structural mechanisms that may contribute to texture changes (e.g., macrostructural cortical lamina, neuropil/myelination, cortical reorganization) and their possible implications are explored and discussed. Texture may be a useful tool to investigate subtle and dynamic GM abnormalities, especially during the CHR period.

Outbreak of severe diarrhea due to zoonotic Cryptosporidium parvum and C. xiaoi in goat kids in Chungcheongbuk-do, Korea.

Severe diarrhea was reported in goat kids in Chungcheongbuk-do, Korea, from 2021 to 2023, and Cryptosporidium infection was suspected. To confirm the cause of this outbreak, fecal samples were collected from goat farms where diarrhea had been reported and analyzed for Cryptosporidium infection using a molecular assay. A total of 65 fecal samples, including 37 from goats with diarrhea and 28 from goats without diarrhea, were collected from six goat farms. Forty-eight of the goats were kids (<2 months) and 17 were adults (>1 year). Cryptosporidium was identified in 53.8% (35/65) of total samples. Overall, 86.5% (32/37) of the diarrheic fecal samples tested positive; however, Cryptosporidium was not detected in any fecal sample from non-diarrheic adult goats. Therefore, cryptosporidiosis was significantly associated with diarrhea in goat kids, and adult goats were not responsible for transmission of Cryptosporidium to them. Phylogenetic analysis and molecular characterization revealed two Cryptosporidium species, namely, C. parvum (n = 28) and C. xiaoi (n = 7). In the C. parvum-positive samples, gp60 gene analysis revealed three zoonotic subtypes-IIaA18G3R1, IIdA15G1, and IIdA16G1. To the best of our knowledge, this study is the first to identify C. parvum IIaA18G3R1 and IIdA16G1 in goats, as well as the first to identify C. xiaoi in goats in Korea. These results suggest that goat kids play an important role as reservoir hosts for different Cryptosporidium species and that continuous monitoring with biosecurity measures is necessary to control cryptosporidiosis outbreaks.

Improved methodology for protein NMR structure calculation using hydrogen bond restraints and ANSURR validation: The SH2 domain of SH2B1.

Protein structures calculated using NMR data are less accurate and less well-defined than they could be. Here we use the program ANSURR to show that this deficiency is at least in part due to a lack of hydrogen bond restraints. We describe a protocol to introduce hydrogen bond restraints into the structure calculation of the SH2 domain from SH2B1 in a systematic and transparent way and show that the structures generated are more accurate and better defined as a result. We also show that ANSURR can be used as a guide to know when the structure calculation is good enough to stop.

Development of a sorafenib-loaded solid self-nanoemulsifying drug delivery system: Formulation optimization and characterization of enhanced properties.

Sorafenib, marketed under the brand name Nexavar®, is a multiple tyrosine kinase inhibitor drug that has been actively used in the clinical setting for the treatment of several cancers. However, the low solubility and bioavailability of sorafenib constitute a significant barrier to achieving a good therapeutic outcome. We developed a sorafenib-loaded self-nanoemulsifying drug delivery system (SNEDDS) formulation composed of capmul MCM, tween 80, and tetraglycol, and demonstrated that the SNEDDS formulation could improve drug solubility with excellent self-emulsification ability. Moreover, the sorafenib-loaded SNEDDS exhibited anticancer activity against Hep3B and KB cells, which are the most commonly used hepatocellular carcinoma and oral cancer cell lines, respectively. Subsequently, to improve the storage stability and to increase the possibility of commercialization, a solid SNEDDS for sorafenib was further developed through the spray drying method using Aerosil® 200 and PVP K 30. X-ray diffraction and differential scanning calorimeter data showed that the crystallinity of the drug was markedly reduced, and the dissolution rate of the drug was further improved in formulation in simulated gastric and intestinal fluid conditions. In vivo study, the bioavailability of the orally administered formulation increases dramatically compared to the free drug. Our results highlight the use of the solid-SNEDDS formulation to enhance sorafenib's bioavailability and outlines potential translational directions for oral drug development.

Murine Coronavirus Disease 2019 Lethality Is Characterized by Lymphoid Depletion Associated with Suppressed Antigen-Presenting Cell Functionality.

The disease severity of coronavirus disease 2019 (COVID-19) varies considerably from asymptomatic to serious, with fatal complications associated with dysregulation of innate and adaptive immunity. Lymphoid depletion in lymphoid tissues and lymphocytopenia have both been associated with poor disease outcomes in patients with COVID-19, but the mechanisms involved remain elusive. In this study, human angiotensin-converting enzyme 2 (hACE2) transgenic mouse models susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were used to investigate the characteristics and determinants of lethality associated with the lymphoid depletion observed in SARS-CoV-2 infection. The lethality of Wuhan SARS-CoV-2 infection in K18-hACE2 mice was characterized by severe lymphoid depletion and apoptosis in lymphoid tissues related to fatal neuroinvasion. The lymphoid depletion was associated with a decreased number of antigen-presenting cells (APCs) and their suppressed functionality below basal levels. Lymphoid depletion with reduced APC function was a specific feature observed in SARS-CoV-2 infection but not in influenza A infection and had the greatest prognostic value for disease severity in murine COVID-19. Comparison of transgenic mouse models resistant and susceptible to SARS-CoV-2 infection revealed that suppressed APC function could be determined by the hACE2 expression pattern and interferon-related signaling. Thus, we demonstrated that lymphoid depletion associated with suppressed APC function characterizes the lethality of COVID-19 mouse models. Our data also suggest a potential therapeutic approach to prevent the severe progression of COVID-19 by enhancing APC functionality.