The gut microbiota modifies antibody durability and booster responses after SARS-CoV-2 vaccination.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are pivotal in combating coronavirus disease 2019 (COVID-19); however, the declining antibody titers postvaccination pose challenges for sustained protection and herd immunity. Although gut microbiome is reported to affect the early antibody response after vaccination, its impact on the longevity of vaccine-induced antibodies remains unexplored. METHODS: A prospective cohort study was conducted involving 44 healthy adults who received two doses of either the BNT162b2 or ChAdOx1 vaccine, followed by a BNT162b2 booster at six months. The gut microbiome was serially analyzed using 16S rRNA and shotgun sequencing, while humoral immune response was assessed using a SARS-CoV-2 spike protein immunoassay. RESULTS: Faecalibacterium prausnitzii was associated with robust and persistent antibody responses post-BNT162b2 vaccination. In comparison, Escherichia coli was associated with a slower antibody decay following ChAdOx1 vaccination. The booster immune response was correlated with metabolic pathways involving cellular functions and aromatic amino acid synthesis. CONCLUSIONS: The findings of this study underscored the potential interaction between the gut microbiome and the longevity/boosting effect of antibodies following vaccination against SARS-CoV-2. The identification of specific microbial associations suggests the prospect of microbiome-based strategies for enhancing vaccine efficacy.

Fabrication and Evaluation of Ultrasound-Responsive Emulsion Loading Paclitaxel for Targeted Chemotherapy.

Chemotherapy is the most widely used cancer treatment, but it has several drawbacks such as adverse side effects and low bioavailability. To address these limitations, various drug delivery systems have been investigated, including liposomes, micelles, and emulsions. These drug delivery technologies have been improving the efficacy and safety of conventional chemotherapy. This study presents an emerging drug delivery technology for targeted chemotherapy using drug-loaded ultrasound-responsive emulsion (URE) as a drug carrier and ultrasound technology for external activation. URE was designed to be responsive to ultrasound energy and fabricated by using an emulsification technique. To investigate this technology, paclitaxel, as a model drug, was used and encapsulated into URE. The size distribution, morphology, and drug release behavior of paclitaxel-loaded URE (PTX-URE) were characterized, and the echogenicity of PTX-URE was assessed by using ultrasound imaging equipment. The cellular uptake and cytotoxicity of PTX-URE with ultrasound were evaluated in breast cancer cells (MDA-MB-231). Our in vitro results indicate that the combination of PTX-URE and ultrasound significantly enhanced cellular uptake by 10.6-fold and improved cytotoxicity by 24.1% compared to PTX alone. These findings suggest that the URE platform combined with ultrasound is a promising technology to improve the drug delivery efficiency for chemotherapy.

Condition Monitoring of Railway Bridges Using Vehicle Pitch to Detect Scour.

This study proposes the new condition monitoring concept of using features in the measured rotation, or 'pitch' signal, of a crossing vehicle as an indicator of the presence of foundation scour in a bridge. The concept is explored through two-dimensional vehicle-bridge interaction modelling, with a reduction in stiffness under a pier used to represent the effects of scour. A train consisting of three 10-degree-of-freedom carriages cross the model on a profiled train track, each train varying slightly in terms of mass and velocity. An analysis of the pitch of the train carriages can clearly identify when scour is present. The concept is further tested in a scaled laboratory experiment consisting of a tractor-trailer crossing a four-span simply supported bridge on piers. The foundation support is represented by four springs under each pier, which can be replaced with springs of a reduced stiffness to mimic the effect of scour. The laboratory model also consistently shows a divergence in vehicle pitch between healthy and scoured bridge states.

Eucommia ulmoides Leaves Alleviate Cognitive Dysfunction in Dextran Sulfate Sodium (DSS)-Induced Colitis Mice through Regulating JNK/TLR4 Signaling Pathway.

Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD) that is characterized by systemic immune system activation. This study was performed to assess the alleviative effect of administering an aqueous extract of Eucommia ulmoides leaves (AEEL) on cognitive dysfunction in mice with dextran sulfate sodium (DSS)-induced colitis. The major bioactive compounds of AEEL were identified as a quinic acid derivative, caffeic acid-O-hexoside, and 3-O-caffeoylquinic acid using UPLC Q-TOF/MSE. AEEL administration alleviated colitis symptoms, which are bodyweight change and colon shortening. Moreover, AEEL administration protected intestinal barrier integrity by increasing the tight junction protein expression levels in colon tissues. Likewise, AEEL improved behavioral dysfunction in the Y-maze, passive avoidance, and Morris water maze tests. Additionally, AEEL improved short-chain fatty acid (SCFA) content in the feces of DSS-induced mice. In addition, AEEL improved damaged cholinergic systems in brain tissue and damaged mitochondrial and antioxidant functions in colon and brain tissues caused by DSS. Also, AEEL protected against DSS-induced cytotoxicity and inflammation in colon and brain tissues by c-Jun N-terminal kinase (JNK) and the toll-like receptor 4 (TLR4) signaling pathway. Therefore, these results suggest that AEEL is a natural material that alleviates DSS-induced cognitive dysfunction with the modulation of gut-brain interaction.

Sustained interactions between T cell receptors and antigens promote the differentiation of CD4⁺ memory T cells.

During CD4⁺ T cell activation, T cell receptor (TCR) signals impact T cell fate, including recruitment, expansion, differentiation, trafficking, and survival. To determine the impact of TCR signals on the fate decision of activated CD4⁺ T cells to become end-stage effector or long-lived memory T helper 1 (Th1) cells, we devised a deep-sequencing-based approach that allowed us to track the evolution of TCR repertoires after acute infection. The transition of effector Th1 cells into the memory pool was associated with a significant decrease in repertoire diversity, and the major histocompatibility complex (MHC) class II tetramer off rate, but not tetramer avidity, was a key predictive factor in the representation of individual clonal T cell populations at the memory stage. We conclude that stable and sustained interactions with antigens during the development of Th1 responses to acute infection are a determinative factor in promoting the differentiation of Th1 memory cells.

Sonophoresis with ultrasound-responsive liquid-core nuclei for transdermal drug delivery.

BACKGROUND: Sonophoresis can increase the delivery efficiency of various drugs into the skin. A recent advance in sonophoresis is the use of ultrasound-responsive liquid-core nuclei (URLN) to increase the probability of cavitation. In this study, we developed a URLN and ultrasound device, and demonstrated its effectiveness through in vitro and clinical tests. MATERIALS AND METHODS: Three types of experiments were designed to evaluate the efficiency of sonophoresis with URLN. First, a Franz diffusion cell with cosmetic ingredients was used to analyze quantitatively the amount of drug delivered to the porcine skin. Second, after the application of sonophoresis with URLN, the porcine skin surface was examined using scanning electron microscopy (SEM) to see the changes in morphology. Finally, a clinical test was performed to verify the utility of sonophoresis with URLN. RESULTS: The results indicate that sonophoresis with URLN can increase the amount of compound delivered by approximately 11.9-fold over 6 h for niacinamide and by 7.33-fold over 6 h for adenosine. In addition, we observed approximately 20-30 µm sized pores on porcine skin in SEM images. In clinical testing, the application of sonophoresis with cosmetics containing URLN for 3 min improved the efficiency of transdermal drug delivery by 1.9-fold, the depth of absorption by 2.0-fold, and the speed of absorption by 2.0-fold at 30 min after application. CONCLUSION: We expect that sonophoresis with specialized URLN in transdermal drug delivery could be used widely for various skin-related applications.

First Report of Anthracnose on Juglans regia Caused by Colletotrichum siamense in Korea.

Walnut (Juglans regia) is one of the main tree crops cultivated for nut production in South Korea with an estimated production of about 1,189 tons per year (Korea Forest Service 2020). In August 2021, anthracnose symptoms, including dark, depressed, irregularly shaped lesions on fruits and leaves of walnut cv. Sinlyeong, were observed at three orchards in Nonsan (36°10'22.5"N 127°06'14.8"E) and Suwon (37°16'04.7"N 126°55'22.3"E and 37°15'10.6"N 126°57'35.6"E). This led to severe yield loss of walnut fruit with a disease incidence of approximately 70 to 80% in each orchard. Three samples, including infected fruits and leaves, were randomly collected per site. Fungal isolates were isolated either from acervuli filled with conidial masses on infected walnut tissues or from plant tissues that were surface-disinfested, followed by plating onto 2% PDA. Colonies were initially white, later became pale brownish to light gray with concentric rings of salmon sporodochia. White to gray aerial mycelia, reaching 65 mm diameter in 5 days, were abundantly produced on PDA at 25 °C. Appressoria were brown, ovoid, and in some cases, clavate, 5.1-8.7 µm in length, and 3.2-5.1 µm in width (n = 50). Conidia were single celled, hyaline, cylindrical with rounded ends and smooth walls, guttulate, 13.6-18.8 µm in length, and 4.4-6.3 µm in width (n = 50). Setae were absent. Three isolates, i.e., one per orchard, were retained and deposited in the culture collection (CDH) of National Institute of Forest Science, Korea (Accession No. CDH052-054). The internal transcribed spacer (ITS) region of rDNA, beta-tubulin (TUB2) and a partial sequence of the actin (ACT) genes were amplified and sequenced for each of the isolates using the pair of primers, ITS1F/ITS4 (Gardes and Bruns 1993; White et al. 1990), T1/Bt2b (ODonnell and Cigelnik 1997; Glass and Donaldson 1995) and ACT-512F/ACT-783R (Carbone and Kohn 1999), respectively. A BLAST search in GenBank revealed that the sequences of ITS (OK631731-733), TUB2 (OK665927-929) and ACT (OK665930-932) showed sequence identities of 98.6 to 99.6% to Colletotrichum siamense sequences (FJ972613, FJ907423, FJ907438). A maximum likelihood tree, based on a combined dataset of ITS, ACT and TUB2 gene sequences for Colletotrichum spp., revealed that the three isolates were clustered with type specimens of C. siamense. To prepare larger quantities of inoculum for the pathogenicity, mycelial plugs bearing acervuli taken from 2% PDA were incubated in a conical flask containing 200 ml of 2% potato dextrose broth at 25°C on a rotary shaker at 150 rpm for two weeks. Spore concentration was adjusted to 1.0 × 104 ml-1 conidia of C. siamense (CDH054). A 10 to 15 ml of spore suspension was then sprayed on each leaf of 12 seedlings of 'Sinlyeong' walnut (three-year-old), while 7 seedlings were treated with sterile distilled water as a control. Each treated seedling was covered by a plastic bag to maintain moisture for one day. Inoculation trials were repeated twice, in August and September 2021. Symptoms identical to those observed in the field developed four to five days after the inoculations from which the inoculated pathogen was successfully re-isolated, fulfilling Koch's postulates. However, no symptoms were observed in the control. To our knowledge, this is the first report of anthracnose on J. regia caused by C. siamense in Korea. This indicates that disease occurrences must be further rigorously surveyed at the nation-wide scale to effectively control the disease in the country.

Walnut Prevents Cognitive Impairment by Regulating the Synaptic and Mitochondrial Dysfunction via JNK Signaling and Apoptosis Pathway in High-Fat Diet-Induced C57BL/6 Mice.

This study was conducted to evaluate the protective effect of Juglans regia (walnut, Gimcheon 1ho cultivar, GC) on high-fat diet (HFD)-induced cognitive dysfunction in C57BL/6 mice. The main physiological compounds of GC were identified as pedunculagin/casuariin isomer, strictinin, tellimagrandin I, ellagic acid-O-pentoside, and ellagic acid were identified using UPLC Q-TOF/MS analysis. To evaluate the neuro-protective effect of GC, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 2',7'-dichlorodihydrofluorecein diacetate (DCF-DA) analysis were conducted in H2O2 and high glucose-induced neuronal PC12 cells and hippocampal HT22 cells. GC presented significant cell viability and inhibition of reactive oxygen species (ROS) production. GC ameliorated behavioral and memory dysfunction through Y-maze, passive avoidance, and Morris water maze tests. In addition, GC reduced white adipose tissue (WAT), liver fat mass, and serum dyslipidemia. To assess the inhibitory effect of antioxidant system deficit, lipid peroxidation, ferric reducing antioxidant power (FRAP), and advanced glycation end products (AGEs) were conducted. Administration of GC protected the antioxidant damage against HFD-induced diabetic oxidative stress. To estimate the ameliorating effect of GC, acetylcholine (ACh) level, acetylcholinesterase (AChE) activity, and expression of AChE and choline acetyltransferase (ChAT) were conducted, and the supplements of GC suppressed the cholinergic system impairment. Furthermore, GC restored mitochondrial dysfunction by regulating the mitochondrial ROS production and mitochondrial membrane potential (MMP) levels in cerebral tissues. Finally, GC ameliorated cerebral damage by synergically regulating the protein expression of the JNK signaling and apoptosis pathway. These findings suggest that GC could provide a potential functional food source to improve diabetic cognitive deficits and neuronal impairments.

Immature Persimmon Suppresses Amyloid Beta (Aß) Mediated Cognitive Dysfunction via Tau Pathology in ICR Mice.

This study confirmed the ameliorating effect of immature persimmon (Diospyros kaki) ethanolic extract (IPEE) on neuronal cytotoxicity in amyloid beta (Aß)1-42-induced ICR mice. The administration of IPEE ameliorated the cognitive dysfunction in Aß1-42-induced mice by improving the spatial working memory, the short-term and long-term memory functions. IPEE protected the cerebral cholinergic system, such as the acetylcholine (ACh) level and acetylcholinesterase (AChE) activity, and antioxidant system, such as the superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA) contents. In addition, mitochondrial dysfunction against Aß1-42-induced toxicity was reduced by regulating the reactive oxygen species (ROS), mitochondrial membrane potential and ATP contents. In addition, IPEE regulated the expression levels of tau signaling, such as TNF-α, p-JNK, p-Akt, p-GSK3ß, p-tau, p-NF-κB, BAX and caspase 3. Finally, gallic acid, ellagic acid and quercetin 3-O-(6″-acetyl-glucoside) were identified as the physiological compounds of IPEE using ultra-performance liquid chromatography ion mobility separation quadrupole time-of-flight/tandem mass spectrometry (UPLC IMS Q-TOF/MS2).

miR-181a-regulated pathways in T-cell differentiation and aging.

MicroRNAs (miRNAs) are regulatory noncoding RNAs important for many aspects of cellular processes including cell differentiation and proliferation. Functions of numerous miRNAs have been identified in T cells, with miR-181a regulating T cell activation thresholds during thymic T cell development and during activation of peripheral T cells. Intriguingly, miR-181a is implicated in defective antiviral and vaccine responses in older individuals, as its expression declines in naïve T cells with increasing age. Here, we review the pathways that are regulated by miR-181a and that explain the unique role of miR-181a in T cell development, T cell activation and antiviral T cell responses. These studies provide a framework for understanding how a decline in miR-181a expression in T cells could contribute to age-related defects in adaptive immunity. We furthermore review the mechanisms that cause the age-related decline in miR-181a expression and discuss the potential of restoring miR-181a expression or targeting miR-181a-regulated pathways to improve impaired T cell responses in older individuals.