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In order to explore the effect of different distillation methods on the key aroma compounds of whisky, the aroma composition of base whisky produced by two different distillation methods: double distillation in pot stills and continuous distillation in tower stills, and whisky aged with oak chips was detected by headspace-solid phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS). The characteristic aroma compounds were determined by odor activity values (OAVs), and the effect of distillation methods on the characteristic aroma of whisky was investigated by sensory evaluation. The results demonstrated that the distillation methods led to significant differences in the raw material-like, fermented and distilled aromas of base whisky. Pot-distilled whisky retained more aroma characteristics of the raw material. The difference in fermented aroma was mainly reflected by the ethyl ester content. More medium-chain and long-chain fatty acid ethyl esters were retained during pot distillation, while more short-chain fatty acid ethyl esters contributing to the fermented aroma were retained during tower distillation. The aroma differences brought about by the distillation methods affected the change of aroma compounds during subsequent aging. After aging, more fermented aroma compounds in pot-distilled whisky were lost, but the distilled aroma and the aged aroma from oak chips were more prominent. Although the aged aroma could attenuate the aroma difference between base whisky produced by different distillation methods, the effect of the distillation methods on the aroma was still evident. The choice of the appropriate distillation process is essential for the production of whisky.

Background: Galectin‐9 (Gal‐9) has been implicated in allergic and autoimmune diseases, but its role and relevance in chronic spontaneous urticaria (CSU) are unclear. Objectives: To characterize the role and relevance of Gal‐9 in the pathogenesis of CSU. Methods: We assessed 60 CSU patients for their expression of Gal‐9 on circulating eosinophils and basophils as well as T cell expression of the Gal‐9 receptor TIM‐3, compared them with 26 healthy controls (HCs), and explored possible links with disease features including disease activity (urticaria activity score, UAS), total IgE, basophil activation test (BAT), and response to omalizumab treatment. We also investigated potential drivers of Gal‐9 expression by eosinophils and basophils. Results: Our CSU patients had markedly increased rates of circulating Gal‐9+ eosinophils and basophils and high numbers of lesional Gal‐9+ cells. High rates of blood Gal‐9+ eosinophils/basophils were linked to high disease activity, IgE levels, and BAT negativity. Serum levels of TNF‐α were positively correlated with circulating Gal‐9+ eosinophils/basophils, and TNF‐α markedly upregulated Gal‐9 on eosinophils. CSU patients who responded to omalizumab treatment had more Gal‐9+ eosinophils/basophils than non‐responders, and omalizumab reduced blood levels of Gal‐9+ eosinophils/basophils in responders. Gal‐9+ eosinophils/basophils were negatively correlated with TIM‐3+TH17 cells. Conclusion: Our findings demonstrate a previously unrecognized involvement of the Gal‐9/TIM‐3 pathway in the pathogenesis CSU and call for studies that explore its relevance. [ABSTRACT FROM AUTHOR]

Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV‐1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion‐stabilized HIV‐1 envelope (Env) trimer, BG505 DS‐SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4‐binding site (CD4bs) of vulnerability. Two of the vaccine‐elicited CD4bs‐targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a‐hinge region and human IgG1‐constant region (G36×3‐IgG2a and R27×3‐IgG2a), neutralized 96% of a multiclade 208‐strain panel at geometric mean IC80s of 0.314 and 0.033 µg mL−1, respectively. Cryo‐EM structures of these nanobodies in complex with Env trimer revealed the two nanobodies to neutralize HIV‐1 by mimicking the recognition of the CD4 receptor. To enhance their neutralizing potency and breadth, nanobodies are linked to the light chain of the V2‐apex‐targeting broadly neutralizing antibody, CAP256V2LS. The resultant human‐llama bispecific antibody CAP256L‐R27×3LS exhibited ultrapotent neutralization and breadth exceeding other published HIV‐1 broadly neutralizing antibodies, with pharmacokinetics determined in FcRn‐Fc mice similar to the parent CAP256V2LS. Vaccine‐elicited llama nanobodies, when combined with V2‐apex broadly neutralizing antibodies, may therefore be able to fulfill anti‐HIV‐1 therapeutic and prophylactic clinical goals. [ABSTRACT FROM AUTHOR]

Objective: Bone mesenchymal stem cells (BMSCs) have been tentatively applied in the treatment of glucocorticoid‐induced osteoporosis (GIOP) and systemic lupus erythematosus (SLE). However, the effects of BMSCs on osteoporosis within the context of glucocorticoid (GC) application in SLE remain unclear. Our aim was to explore the roles of BMSCs and different doses of GC interventions on osteoporosis in SLE murine models. Methods: MRL/MpJ‐Faslpr mice were divided into eight groups with BMSC treatment and different dose of GC intervention. Three‐dimensional imaging analysis and hematoxylin and eosin (H&E) staining were performed to observe morphological changes. The concentrations of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in serum were measured by enzyme‐linked immunosorbent assay (ELISA). The subpopulation of B cells and T cells in bone marrows and spleens were analyzed by flow cytometry. Serum cytokines and chemokines were assessed using Luminex magnetic bead technology. Results: BMSCs ameliorated osteoporosis in murine SLE models by enhancing bone mass, improving bone structure, and promoting bone formation through increased bone mineral content and optimization of trabecular morphology. BMSC and GC treatments reduced the number of B cells in bone marrows, but the effect was not significant in spleens. BMSCs significantly promoted the expression of IL‐10 while reducing IL‐18. Moreover, BMSCs exert immunomodulatory effects by reducing Th17 expression and rectifying the Th17/Treg imbalance. Conclusion: BMSCs effectively alleviate osteoporosis induced by SLE itself, as well as osteoporosis resulting from SLE combined with various doses of GC therapy. The therapeutic effects of BMSCs appear to be mediated by their influence on bone marrow B cells, T cell subsets, and associated cytokines. High‐dose GC treatment exerts a potent anti‐inflammatory effect but may hinder the immunotherapeutic potential of BMSCs. Our research may offer valuable guidance to clinicians regarding the use of BMSC treatment in SLE and provide insights into the judicious use of GCs in clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to examine the proportion of CD161 on CD56+ natural killer (NK) cells in peripheral blood of primary Sjögren's syndrome (pSS) and investigate its clinical relevance of pSS. Methods: The proportion of CD56+ NK cells and CD161 on CD56+ NK cells was detected by flow cytometry in 31 pSS patients and 29 healthy controls (HCs). The correlations between the proportion of CD161+CD56+ NK cells and clinical features and disease activity of pSS were further analyzed. Meanwhile, we drew the receiver operating characteristic curve to evaluate the diagnostic value of CD161+CD56+ NK cells in pSS. In addition, we evaluated the differences in the effects of CD161+ cells and CD161− cells in peripheral blood on the function of CD56+ NK cells in 5 pSS patients. Results: The proportion of CD56+ NK cells and CD161+CD56+ NK cells decreased markedly in pSS patients compared to HCs. The correlation analysis showed that the proportion of CD161+CD56+ NK cells negatively correlated with white blood cells, Immunoglobulin A (IgA), IgM, IgG, European League Against Rheumatism Sjogren's Syndrome Patient Reported Index and European League Against Rheumatism Sjogren's Syndrome Disease Activity Index, and positively correlated with complement C4. The proportion of CD161+CD56+ NK cells in pSS patients with decayed tooth, fatigue, arthralgia, skin involvement, primary biliary cirrhosis, interstitial lung disease, anti‐SSA/Ro60 positive, anti‐SSB positive and high IgG was lower than that in negative patients. Furthermore, compared with inactive patients, the proportion of CD161+CD56+ NK cells decreased obviously in active patients. The area under the curve was 0.7375 (p =.0016), the results indicated that CD161+CD56+ NK cells had certain diagnostic values for pSS. In addition, the proportion of CD86, HLA‐DR, Ki67, FasL, TNF‐α, and IFN‐γ on CD161+CD56+ NK cells was lower than that on CD161−CD56+ NK cells in the peripheral blood of pSS patients. Conclusion: This study suggested that the proportion of CD56+ NK cells and CD161+CD56+ NK cells decreased significantly in pSS patients, and the proportion of CD161+CD56+ NK cells negatively associated with the clinical features and disease activity of pSS patients. CD161 expression inhibited the function of CD56+ NK cells in peripheral blood of pSS patients. The CD161+CD56+ NK cells may present as a potential target for therapy and a biomarker of disease activity in pSS. [ABSTRACT FROM AUTHOR]

A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans. However, the degree and extent to which such bNAbs interact with primary lymphocytes have not been fully delineated. Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals. Binding of these bNAbs, particularly PGT121 and PGT151, to activated [CD4.sup.+] and [CD8.sup.+] T cells was mediated by complex-type glycans and was abrogated by enzymatic inhibition of N-linked glycosylation. In addition, a short-term incubation of PGT151 and primary NK cells led to degranulation and cellular death. Our data suggest that the propensity of certain bNAbs to bind uninfected/bystander cells has the potential for unexpected outcomes in passive-transfer studies and underscore the importance of antibody screening against primary lymphocytes., Introduction Recent advances in antibody cloning technologies have led to the isolation of a number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV). Some [...]