The progress of small molecules against cannabinoid 2 receptor (CB2R).

The two subtypes of cannabinoid receptors (CBR), namely CB1R and CB2R, belong to the G protein-coupled receptor (GPCR) superfamily and are confirmed as potential therapeutic targets for a variety of diseases such as inflammation, neuropathic pain, and immune-related disorders. Since CB1R is mainly distributed in the central nervous system (CNS), it could produce severe psychiatric adverse reactions and addiction. In contrast, CB2R are predominantly distributed in the peripheral immune system with minimal CNS-related side effects. Therefore, more attention has been devoted to the discovery of CB2R ligands. In view of the favorable profile of CB2R, many high-binding affinity and selectivity CB2R ligands have been developed recently. This paper reviews recent research progress on CB2R ligands, including endogenous CB2R ligands, natural compounds, and novel small molecules, in order to provide a reference for subsequent CB2R ligand development.

Two-color attosecond chronoscope.

We study ionization of atoms in strong orthogonal two-color (OTC) laser fields numerically and analytically. The calculated photoelectron momentum distribution shows two typical structures: a rectangular-like one and a shoulder-like one, the positions of which depend on the laser parameters. Using a strong-field model which allows us to quantitatively evaluate the Coulomb effect, we show that these two structures arise from attosecond response of electron inside an atom to light in OTC-induced photoemission. Some simple mappings between the locations of these structures and response time are derived. Through these mappings, we are able to establish a two-color attosecond chronoscope for timing electron emission, which is essential for OTC-based precise manipulation.

Band Structure Engineering of Single Pt Atoms on Fe-TiO2 for Enhanced Photocatalytic Performance.

Single atomic site catalysts display the maximal atom-utilization efficiency, unique structural properties, and remarkable enhancements on catalytic activity. Herein, single Pt atoms loaded Fe-TiO2 catalysts were prepared. Fe3+ doping leads to the formation of oxygen vacancies and improve the interaction between TiO2 and Pt. Single Pt atoms are thus anchored and effectively modify the local energy band structure of TiO2 . The optimized local band structures improve the intrinsic photoexcitation of Pt/Fe-TiO2 , promote the separation of photogenerated carriers, and extend the lifetime of photogenerated carriers. Meanwhile, the electrons transfer from the excited dyes to the conduction band edge of Pt/Fe-TiO2 is also facilitated due to the shift-down of the conduction band edge. Therefore, with the increase of the Pt content (till up to 0.6 wt%), the photocatalytic performance of Pt/ Fe-TiO2 with the confined single Pt atoms is significantly boosted in either the intrinsic or the sensitized photocatalytic process.

Targeting anticancer immunity in oral cancer: Drugs, products, and nanoparticles.

Oral cavity carcinomas are the most frequent malignancies among head and neck malignancies. Oral tumors include not only oral cancer cells with different potency and stemness but also consist of diverse cells, containing anticancer immune cells, stromal and also immunosuppressive cells that influence the immune system reactions. The infiltrated T and natural killer (NK) cells are the substantial tumor-suppressive immune compartments in the tumor. The infiltration of these cells has substantial impacts on the response of tumors to immunotherapy, chemotherapy, and radiotherapy. Nevertheless, cancer cells, stromal cells, and some other compartments like regulatory T cells (Tregs), macrophages, and myeloid-derived suppressor cells (MDSCs) can repress the immune responses against malignant cells. Boosting anticancer immunity by inducing the immune system or repressing the tumor-promoting cells is one of the intriguing approaches for the eradication of malignant cells such as oral cancers. This review aims to concentrate on the secretions and interactions in the oral tumor immune microenvironment. We review targeting tumor stroma, immune system and immunosuppressive interactions in oral tumors. This review will also focus on therapeutic targets and therapeutic agents such as nanoparticles and products with anti-tumor potency that can boost anticancer immunity in oral tumors. We also explain possible future perspectives including delivery of various cells, natural products and drugs by nanoparticles for boosting anticancer immunity in oral tumors.

Establishment of a Seven-Gene Signature Associated with CD8+ T Cells through the Utilization of Both Single-Cell and Bulk RNA-Sequencing Techniques in Clear Cell Renal Cell Carcinoma.

Tumor immune microenvironment constituents, such as CD8+ T cells, have emerged as crucial focal points for cancer immunotherapy. Given the absence of reliable biomarkers for clear cell renal cell carcinoma (ccRCC), we aimed to ascertain a molecular signature that could potentially be linked to CD8+ T cells. The differentially expressed genes (DEGs) linked to CD8+ T cells were identified through an analysis of single-cell RNA sequencing (scRNA-seq) data obtained from the Gene Expression Omnibus (GEO) database. Subsequently, immune-associated genes were obtained from the InnateDB and ImmPort datasets and were cross-referenced with CD8+ T-cell-associated DEGs to generate a series of DEGs linked to immune response and CD8+ T cells. Patients with ccRCC from the Cancer Genome Atlas (TCGA) were randomly allocated into testing and training groups. A gene signature was established by conducting LASSO-Cox analysis and subsequently confirmed using both the testing and complete groups. The efficacy of this signature in evaluating immunotherapy response was assessed on the IMvigor210 cohort. Finally, we employed various techniques, including CIBERSORT, ESTIMATE, ssGSEA, and qRT-PCR, to examine the immunological characteristics, drug responses, and expression of the signature genes in ccRCC. Our findings revealed 206 DEGs linked to immune response and CD8+ T cells, among which 65 genes were correlated with overall survival (OS) in ccRCC. A risk assessment was created utilizing a set of seven genes: RARRES2, SOCS3, TNFSF14, XCL1, GRN, CLDN4, and RBP7. The group with a lower risk showed increased expression of CD274 (PD-L1), suggesting a more favorable response to anti-PD-L1 treatment. The seven-gene signature demonstrated accurate prognostic prediction for ccRCC and holds potential as a clinical reference for treatment decisions.

Chaotic Color Image Encryption Based on Eight-Base DNA-Level Permutation and Diffusion.

Images, as a crucial information carrier in the era of big data, are constantly generated, stored, and transmitted. Determining how to guarantee the security of images is a hot topic in the information security community. Image encryption is a simple and direct approach for this purpose. In order to cope with this issue, we propose a novel scheme based on eight-base DNA-level permutation and diffusion, termed as EDPD, for color image encryption in this paper. The proposed EDPD integrates secure hash algorithm-512 (SHA-512), a four-dimensional hyperchaotic system, and eight-base DNA-level permutation and diffusion that conducts on one-dimensional sequences and three-dimensional cubes. To be more specific, the EDPD has four main stages. First, four initial values for the proposed chaotic system are generated from plaintext color images using SHA-512, and a four-dimensional hyperchaotic system is constructed using the initial values and control parameters. Second, a hyperchaotic sequence is generated from the four-dimensional hyperchaotic system for consequent encryption operations. Third, multiple permutation and diffusion operations are conducted on different dimensions with dynamic eight-base DNA-level encoding and algebraic operation rules determined via the hyperchaotic sequence. Finally, DNA decoding is performed in order to obtain the cipher images. Experimental results from some common testing images verify that the EDPD has excellent performance in color image encryption and can resist various attacks.

Early diagnosis of diabetic peripheral neuropathy based on infrared thermal imaging technology.

AIMS: The purpose of this study was to detect and compare the surface temperature of plantar vessels in mild diabetic peripheral neuropathy (DPN) patients and healthy controls, to explore a simple, convenient and reliable method for early diagnosis of DPN, and to explore the influence of sex and age on vascular surface temperature. MATERIALS AND METHODS: In this study, 60 mild DPN patients (30 males and 30 females) and 60 healthy volunteers were randomly recruited according to their age and sex. Intra-class correlation coefficient was used to evaluate the repeatability of skin temperature measurement in the vascular area. A general linear model was used to analyse the difference of skin temperature between mild DPN patients and healthy controls. RESULTS: The infrared detection results of skin temperature corresponding to blood vessels showed excellent test-retest reliability. There was no significant difference in skin temperature between sex and age. But there were significant differences in skin temperature between mild DPN patients and healthy controls, except for the posterior tibial artery. CONCLUSIONS: For mild DNP patients, in case of no obvious abnormality in the infrared detection of lower extremity arterial surface temperature, the small vessels have shown early abnormal body surface temperature, that is, the surface temperature of related vessels increased. The research conclusions of this article not only enable us to better understand the correlation between body surface temperature and hemodynamic parameters, but also provide an in vivo, non-invasive, and convenient way of thinking and methods for early diagnosis of DPN.

Monte Carlo study of TG-43 dosimetry parameters of GammaMed Plus high dose rate 192 Ir brachytherapy source using TOPAS.

PURPOSE: To develop a simulation model for GammaMed Plus high dose rate 192 Ir brachytherapy source in TOPAS Monte Carlo software and validate it by calculating the TG-43 dosimetry parameters and comparing them with published data. METHODS: We built a model for GammaMed Plus high dose rate brachytherapy source in TOPAS. The TG-43 dosimetry parameters including air-kerma strength SK , dose-rate constant Λ, radial dose function gL (r), and 2D anisotropy function F(r,θ) were calculated using Monte Carlo simulation with Geant4 physics models and NNDC 192 Ir spectrum. Calculations using an old 192 Ir spectrum were also carried out to evaluate the impact of incident spectrum and cross sections. The results were compared with published data. RESULTS: For calculations using the NNDC spectrum, the air-kerma strength per unit source activity SK /A and Λ were 1.0139 × 10-7 U/Bq and 1.1101 cGy.h-1 .U-1 , which were 3.56% higher and 0.62% lower than the reference values, respectively. The gL (r) agreed with reference values within 1% for radial distances from 2 mm to 20 cm. For radial distances of 1, 3, 5, and 10 cm, the agreements between F(r,θ) from this work and the reference data were within 1.5% for 15° < Î¸ < 165°, and within 4% for all θ values. The discrepancies were attributed to the updated source spectrum and cross sections. They caused deviations of the SK /A of 2.90% and 0.64%, respectively. As for gL (r), they caused average deviations of -0.22% and 0.48%, respectively. Their impact on F(r,θ) was not quantified for the relatively high statistical uncertainties, but basically they did not result in significant discrepancies. CONCLUSION: A model for GammaMed Plus high dose rate 192 Ir brachytherapy source was developed in TOPAS and validated following TG-43 protocols, which can be used for future studies. The impact of updated incident spectrum and cross sections on the dosimetry parameters was quantified.

Polysaccharides from the Edible Mushroom Agaricus bitorquis (Quél.) Sacc. Chaidam Show Anti-hypoxia Activities in Pulmonary Artery Smooth Muscle Cells.

Three kinds of new water-soluble polysaccharides (FA, FB and FC) were isolated from wild mushroom Agaricus bitorquis (Quél.) Sacc. Chaidam by the classical method "water extraction and alcohol precipitation" and purified by column chromatography. The Mw of FA, FB and FC ranged from 5690 Da to 38,340 Da. The three polysaccharide fractions in the fruiting body were mainly composed of 4 kinds of monosaccharides, including glucose, galactose, mannose, and arabinose, among which glucose and galactose were the major monosaccharides. The FTIR and NMR spectroscopy indicated that the skeleton of three fractions composed of a (1→4)-α-D-glycosidic backbone containing α-D-mannopyranose. In vitro anti-hypoxia activity data showed that three polysaccharide fractions possessed a significant effect on inhibiting PASM cells apoptosis under hypoxia. Among them, FC at the concentration of 200 µg/mL revealed a significant anti-hypoxia effect. These results revealed that the intracellular polysaccharides possessed potent anti-hypoxic activity, which might be related to inhibiting LDH and NADPH oxidase expression and promoting the formation of 5-hydroxytryptamine, dopamine, endothelins, acetylcholine. More importantly, FC showed good performance inducing KV1.5 expression and prohibiting KIR6.2 formation at protein level.

Synthesis, Characterization of Liposomes Modified with Biosurfactant MEL-A Loading Betulinic Acid and Its Anticancer Effect in HepG2 Cell.

As a novel natural compound delivery system, liposomes are capable of incorporating lipophilic bioactive compounds with enhanced compound solubility, stability and bioavailability, and have been successfully translated into real-time clinical applications. To construct the soy phosphatidylcholine (SPC)-cholesterol (Chol) liposome system, the optimal formulation was investigated as 3:1 of SPC to Chol, 10% mannosylerythritol lipid-A (MEL-A) and 1% betulinic acid. Results show that liposomes with or without betulinic acid or MEL-A are able to inhibit the proliferation of HepG2 cells with a dose-effect relation remarkably. In addition, the modification of MEL-A in liposomes can significantly promote cell apoptosis and strengthen the destruction of mitochondrial membrane potential in HepG2 cells. Liposomes containing MEL-A and betulinic acid have exhibited excellent anticancer activity, which provide factual basis for the development of MEL-A in the anti-cancer applications. These results provide a design thought to develop delivery liposome systems carrying betulinic acid with enhanced functional and pharmaceutical attributes.

Hypothalamus-pituitary-adrenal axis involves in anti-viral ability through regulation of immune response in piglets infected by highly pathogenic porcine reproductive and respiratory syndrome virus.

BACKGROUND: The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has been responsible for several viral attacks in the Asian porcine industry, since the first outbreak in China in 2006. During the early stages of the HP-PRRSV infection, high levels of proinflammatory cytokines are noted in the host peripheral blood, which are accompanied by severe lesions in the lungs and immune system organs; these are considered as the greatest contributors to the overall disease burden. We hypothesized that the anti-PRRSV response in piglets might be mediated by the hypothalamus-pituitary-adrenal (HPA) axis, which led to a decrease in the psycho-neuroendocrinological manifestation of HP-PRRSV etiology via immune response regulation. RESULTS: We investigated the regulation of the HPA axis in HP-PRRSV-infected piglets that were treated with 1 mg/kg body weight (b. w.)/day mifepristone (RU486) or 2 mg/kg b.w./day dexamethasone (DEX). Both RU486 and DEX enhanced the disease status of the piglets infected by the HP-PRRSV HuN4 strain, resulting in high mortality and more severe pathological changes in the lungs. CONCLUSIONS: HP-PRRSV infection activates the HPA axis, and artificial regulation of the immune-endocrine system enhances disease severity in HP-PRRSV-infected piglets. Thus, DEX and RU486 should be avoided in the clinical treatment of HP-PRRS.

Treating tuberculosis with high doses of anti-TB drugs: mechanisms and outcomes.

Tuberculosis (TB) is considered as one of the most serious threats to public health in many parts of the world. The threat is even more severe in the developing countries where there is a lack of advanced medical amenities and contemporary anti-TB drugs. In such situations, dosage optimization of existing medication regimens seems to be the only viable option. Therapeutic drug monitoring study results suggest that high-dose treatment regimens can compensate the low serum concentration of anti-TB drugs and shorten the therapy duration. The article presents a critical review on the possible changes that occur in the host and the pathogen upon the administration of standard and high-dose regimens. Some of the most common factors that are responsible for low anti-TB drug concentrations in the serum are differences in hosts' body weight, metabolic processing of the drug, malabsorption and/or drug-drug interaction. Furthermore, failure to reach the cavitary pulmonary and extrapulmonary tissues also contributes to the therapeutic inefficiency of the drugs. In such conditions, administration of higher doses can help in compensating the pathogenic outcomes of enhancement of the pathogen's physical barriers, efflux pumps and genetic mutations. The present article also presents a summary of the recorded treatment outcomes of clinical trials that were conducted to test the efficacy of administration of high dose of anti-tuberculosis drugs. This review will help physicians across the globe to understand the underlying pathophysiological changes (including side effects) that dictate the clinical outcomes in patients administered with standard and/or high dose anti-TB drugs.

Optimization of EPS Production and Characterization by a Halophilic Bacterium, Kocuria rosea ZJUQH from Chaka Salt Lake with Response Surface Methodology.

With the rising awareness of microbial exopolysaccharides (EPSs) application in various fields, halophilic microorganisms which produce EPSs have received broad attention. A newly identified Kocuria rosea ZJUQH CCTCC M2016754 was determined to be a moderate halobacterium on account of its successful adaption to the environment containing 10% NaCl. The optimal combination of fermentation medium compositions on EPS production was studied. In this work, a fractional factorial design was adopted to investigate the significant factors that affected EPS production. The factors of KCl and MgSO4 were found to have a profound impact on EPS production. We utilized central composite design and response surface methodology to derive a statistical model for optimizing the submerged culture medium composition. Judging from these experimental results, the optimum culture medium for producing EPSs was composed of 0.50% casein hydrolysate, 1.00% sodium citrate, 0.30% yeast extract, 0.50% KCl, 0.50% peptone, and 5.80% MgSO4 (initial pH 7.0). The maximal EPS was 48.01 g/L, which is close to the predicted value (50.39 g/L). In the validation experiment, the highest concentration of 70.64 g/L EPSs was obtained after 120 h under the optimized culture medium in a 5-L bioreactor. EPS from this bacterium was also characterized by differential scanning calorimetry (DSC) and Fourier transform infrared analysis (FT-IR). The findings in this study imply that Kocuria rosea ZJUQH has great potential to be exploited as a source of EPSs utilized in food, the pharmaceutical and agriculture industry, and in the biotreatment of hypersaline environments.

Cell-Free Production of Pentacyclic Triterpenoid Compound Betulinic Acid from Betulin by the Engineered Saccharomyces cerevisiae.

Betulinic acid is a product of plant secondary metabolism which has shown various bioactivities. Several CYP716A subfamily genes were recently characterized encoding multifunctional oxidases capable of C-28 oxidation. CYP716A12 was identified as betulin C-28 oxidase, capable of modifying betulin. This study aimed to induce the transformation of betulin to betulinic acid by co-expressing enzymes CYP716A12 from Medicago truncatula and ATR1 from Arabidopsis thaliana in Saccharomyces cerevisiae. The microsome protein extracted from the transgenic yeast successfully catalyzed the transformation of betulin to betulinic acid. We also characterized the optimization of cell fragmentation, protein extraction method, and the conversion conditions. Response surface methodology was implemented, and the optimal yield of betulinic acid reached 18.70%. After optimization, the yield and the conversion rate of betulin were increased by 83.97% and 136.39%, respectively. These results may present insights and strategies for the sustainable production of betulinic acid in multifarious transgenic microbes.

[The Trace Methane Sensor Based on TDLAS-WMS].

Methane is a colorless, odorless, flammable and explosive gas, which not only is the cause to induce significant security risk in coal mining operation, but also one of the important greenhouse gases, so the monitoring of methane is extremely critical. A trace methane gas sensor is designed and developed using the combination of tunable diode laser absorption spectroscopy (TDLAS) and wavelength modulation spectroscopy (WMS) detection technology, which is based on the methane R(3) absorption branch in 2v3 second harmonic band. Through tuning parameters -0.591 cm(-1) x K(-1), using the method that change the working temperature of distributed feedback (DFB) laser to obtain the best absorption wavelength of methane at 1.654 µm. When the mid-wavelength of DFB laser is selected, the appropriate emitting intension can be obtained via adjusting the amplitude of inject current of DFB laser. Meanwhile, combining the frequency modulation technology to move the bandwidth of detection signal from low frequency to high frequency to reduce the 1/f noise. With aspect to the optical structure, utilizing herriott cell with 76 m effective optical path to guarantee the detection of trace methane is successful. Utilizing the proposed trace methane sensor to extract the second harmonic signal of detected methane in the range of 50 to 5 000 µmol x mol(-1), and adopting minimum mean square error criterion to fit the relationship between methane concentration and signal noise ratio, harmonic peak signal and methane concentration, respectively. In addition, the minimum detection limit is 1.4 µmol x mol(-1). The experiment results show the symmetry of harmonic waveform is good, no intensity modulation, and the factor of intensity-modulated impacts on harmonic detection is eliminated.

Role of the ehxA gene from Escherichia coli serotype O82 in hemolysis, biofilm formation, and in vivo virulence.

Enterohemorrhagic Escherichia coli (EHEC) strains cause serious gastrointestinal disease, which can lead to potentially life-threatening systemic complications such as hemolytic uremic syndrome. Although the ehx gene is established as a major virulence factor of EHEC, the role of this gene in colonization and biofilm formation remains to be elucidated. We constructed recombinant isogenic mutants of the ehxA locus of E. coli HLJ1122 (serotype O82) using the λ Red homologous recombination system. Significantly higher levels of adherence to human epithelial cells (HEp-2) cells were observed for strain HLJ1122 compared with the mutant strain HLJ1122-ΔehxA (P < 0.05). Strain HLJ1122 also exhibited significantly higher levels of biofilm formation than strain HLJ1122-ΔehxA (P < 0.05). Mice infected with strain HLJ1122 showed severe destruction of the intestinal and gastric mucosa; in contrast, mice infected with HLJ1122-ΔehxA showed limited intestinal pathology, displaying minimal inflammatory infiltrates compared with mock-infected mice. These results showed the multifunctional role of Ehx in E. coli virulence.

Non-invasive in vivo study of morphology and mechanical properties of the median nerve.

The current literature studied the median nerve (MN) at specific locations during joint motions. As only a few particular parts of the nerve are depicted, the relevant information available is limited. This experiment investigated the morphological and biomechanical properties of the MN. The effects of the shoulder and wrist motions on MN were explored as well. Eight young healthy female individuals were tested with two-dimensional ultrasound and shear wave elastography (SWE). The morphological and biomechanical properties were examined in limb position 1, with the wrist at the neutral position, the elbow extended at 180°, and the shoulder abducted at 60°. In addition, the experiment assessed the differences among the wrist, forearm, elbow, and upper arm with Friedman's test and Bonferroni post hoc analysis. Two groups of limb positions were designed to explore the effects of shoulder movements (shoulder abducted at 90° and 120°) and wrist movements (wrist extended at 45° and flexed at 45°) on the thickness and Young's modulus. Differences among the distributions of five limb positions were tested as well. The ICC3, 1 values for thickness and Young's modulus were 0.976 and 0.996, respectively. There were differences among the MN thicknesses of four arm locations in limb position 1, while Young's modulus was higher at the elbow and wrist than at the forearm and upper arm. Compared to limb position 1, only limb position 4 had an effect on MN thickness at the wrist. Both shoulder and wrist motions affected MN Young's modulus, and the stiffness variations at typical locations all showed a downward trend proximally in all. The distributions of MN thickness and Young's modulus showed fold line patterns but differed at the wrist and the pronator teres. The MN in the wrist is more susceptible to limb positions, and Young's modulus is sensitive to nerve changes and is more promising for the early diagnosis of neuropathy.

Evolutionary trajectory of TRPM2 channel activation by adenosine diphosphate ribose and calcium.

Ion channel activation upon ligand gating triggers a myriad of biological events and, therefore, evolution of ligand gating mechanism is of fundamental importance. TRPM2, a typical ancient ion channel, is activated by adenosine diphosphate ribose (ADPR) and calcium and its activation has evolved from a simple mode in invertebrates to a more complex one in vertebrates, but the evolutionary process is still unknown. Molecular evolutionary analysis of TRPM2s from more than 280 different animal species has revealed that, the C-terminal NUDT9-H domain has evolved from an enzyme to a ligand binding site for activation, while the N-terminal MHR domain maintains a conserved ligand binding site. Calcium gating pattern has also evolved, from one Ca2+-binding site as in sea anemones to three sites as in human. Importantly, we identified a new group represented by olTRPM2, which has a novel gating mode and fills the missing link of the channel gating evolution. We conclude that the TRPM2 ligand binding or activation mode evolved through at least three identifiable stages in the past billion years from simple to complicated and coordinated. Such findings benefit the evolutionary investigations of other channels and proteins.

Antibody responses to respiratory syncytial virus: a population-based cross-sectional serological study in Southern China, 2021.

OBJECTIVES: With remarkable progress in the field of respiratory syncytial virus (RSV) prophylaxis, it is critical to understand population immunity against RSV. We aim to describe the RSV pre-F IgG antibodies across all age groups in Southern China and to evaluate the risk factors associated with lower antibody levels. METHODS: We performed a community-based cross-sectional sero-epidemiological study in Anhua County, Hunan Province, Southern China, from July 15, 2021, to November 5, 2021. Serum samples were tested for IgG antibodies against the RSV prefusion F (pre-F) protein using an enzyme-linked immunosorbent assay. We estimated the geometric mean titres (GMTs) and seropositivity rates across all age groups. The generalized linear models were built to identify factors associated with antibody levels. RESULTS: A total of 890 participants aged 4 months to older than 89 years were enrolled. The lowest RSV pre-F IgG GMTs were observed in infants and toddlers aged 4 months to younger than 2 years (3.0; 95% CI, 2.6-3.5). With increasing age, the RSV pre-F IgG GMT increased to 4.3 (95% CI, 4.1-4.4) between the ages of 2 and younger than 5 years and then stabilized at high levels throughout life. All the children had serological evidence of RSV infection by the age of 5 years. Age was associated with RSV pre-F antibody levels in children, with an estimated 1.9-fold (95% CI, 0.8-3.6) increase in titre per year before 5 years of age, although it was not significantly associated with antibody levels in adults aged older than 60 years. DISCUSSION: Our findings could provide a comprehensive understanding of the gaps in RSV immunity at the population level and inform the prioritization of immunization platforms.

Dubosiella newyorkensis modulates immune tolerance in colitis via the L-lysine-activated AhR-IDO1-Kyn pathway.

Commensal bacteria generate immensely diverse active metabolites to maintain gut homeostasis, however their fundamental role in establishing an immunotolerogenic microenvironment in the intestinal tract remains obscure. Here, we demonstrate that an understudied murine commensal bacterium, Dubosiella newyorkensis, and its human homologue Clostridium innocuum, have a probiotic immunomodulatory effect on dextran sulfate sodium-induced colitis using conventional, antibiotic-treated and germ-free mouse models. We identify an important role for the D. newyorkensis in rebalancing Treg/Th17 responses and ameliorating mucosal barrier injury by producing short-chain fatty acids, especially propionate and L-Lysine (Lys). We further show that Lys induces the immune tolerance ability of dendritic cells (DCs) by enhancing Trp catabolism towards the kynurenine (Kyn) pathway through activation of the metabolic enzyme indoleamine-2,3-dioxygenase 1 (IDO1) in an aryl hydrocarbon receptor (AhR)-dependent manner. This study identifies a previously unrecognized metabolic communication by which Lys-producing commensal bacteria exert their immunoregulatory capacity to establish a Treg-mediated immunosuppressive microenvironment by activating AhR-IDO1-Kyn metabolic circuitry in DCs. This metabolic circuit represents a potential therapeutic target for the treatment of inflammatory bowel diseases.