Complement Signals Determine Opposite Effects of B Cells in Chemotherapy-Induced Immunity.

Understanding molecular mechanisms that dictate B cell diversity is important for targeting B cells as anti-cancer treatment. Through the single-cell dissection of B cell heterogeneity in longitudinal samples of patients with breast cancer before and after neoadjuvant chemotherapy, we revealed that an ICOSL+ B cell subset emerges after chemotherapy. Using three immunocompetent mouse models, we recapitulated the subset switch of human tumor-infiltrating B cells during chemotherapy. By employing B-cell-specific deletion mice, we showed that ICOSL in B cells boosts anti-tumor immunity by enhancing the effector to regulatory T cell ratio. The signature of ICOSL+ B cells is imprinted by complement-CR2 signaling, which is triggered by immunogenic cell death. Moreover, we identified that CD55, a complement inhibitory protein, determines the opposite roles of B cells in chemotherapy. Collectively, we demonstrated a critical role of the B cell subset switch in chemotherapy response, which has implications in designing novel anti-cancer therapies. VIDEO ABSTRACT.

Deciphering Acclimation to Sublethal Combined and Sequential Abiotic Stresses in Arabidopsis thaliana.

Plants are frequently exposed to environmental challenges. Responses to sub-lethal abiotic stress combinations are complex and often distinct from responses to individual stresses and remain poorly understood. Investigating traits and molecular factors mediating acclimation to stress combinations is essential for the development of climate change-resilient field crops. Here, we studied the morphological, physiological, and molecular responses of Arabidopsis thaliana to i) co-occurring high temperature and drought and ii) flooding followed by drought, both of which have increased in frequency due to climate change, and the individual component stresses: high temperature, drought and flooding. A set of 15 physiological and morphological traits were assessed during single and combined stresses. By combining these comprehensive trait analyses with transcriptome characterization, we established the generally additive negative effects of simultaneous or sequential stresses on plant morphology and physiology compared to the corresponding individual stresses. Although drought had a mild effect on various growth, morphological and physiological traits in both stress combinations, a unique transcriptome signature emerged upon combination with high temperature simultaneously or flooding sequentially. Molecular processes identified as important for multi-stress resilience included plastid-nucleus communication, ABA signaling and photo-acclimation. Based on the RNA-seq data, a set of 39 genes was identified as potential multi-stress response regulators. Mutants were tested to validate the contribution of these genes to plant survival and phenotypic acclimation under combined stress. We confirmed the involvement of several genes in regulating phenotypic acclimation traits. Among the identified factors were EARLY FLOWERING 6 (ELF6) and ARABIDOPSIS TÓXICOS EN LEVADURA 80 (ATL80), with substantial effects on plant growth, leaf development and plant survival (wilting) during high-temperature drought and post-submergence drought, respectively.

Inhibition of complement factor C5a or C5aR for cholesterol crystal embolism-related vascular thrombosis with microvascular injury and its consequences.

Cholesterol crystal embolism (CCE) implies immunothrombosis, tissue necrosis, and organ failure but no specific treatments are available. As CCE involves complement activation, we speculated that inhibitors of the C5a/C5aR axis would be sufficient to attenuate the consequences of CCE like that with systemic vasculitis. Cholesterol microcrystal injection into the kidney artery of wild-type mice initiated intra-kidney immunothrombosis within a few hours followed by a sudden drop of glomerular filtration rate and ischemic kidney necrosis after 24 hours. Genetic deficiency of either C3 or C5aR prevented immunothrombosis, glomerular filtration rate drop, and ischemic necrosis at 24 hours as did preemptive treatment with inhibitors of either C5a or C5aR. Delayed C5a blockade after crystal injection still resolved crystal clots and prevented all consequences. Thus, selective blockade of C5a or C5aR is sufficient to attenuate the consequences of established CCE and prospective inhibition in high-risk patients may be clinically feasible and safe.

Reconstruction method suitable for fast CT imaging.

Reconstructing computed tomography (CT) images from an extremely limited set of projections is crucial in practical applications. As the available projections significantly decrease, traditional reconstruction and model-based iterative reconstruction methods become constrained. This work aims to seek a reconstruction method applicable to fast CT imaging when available projections are highly sparse. To minimize the time and cost associated with projections acquisition, we propose a deep learning model, X-CTReNet, which parameterizes a nonlinear mapping function from orthogonal projections to CT volumes for 3D reconstruction. The proposed model demonstrates effective capability in inferring CT volumes from two-view projections compared to baseline methods, highlighting the significant potential for drastically reducing projection acquisition in fast CT imaging.

Engineering Streptomyces sp. CPCC 204095 for the targeted high-level production of isatropolone A by elucidating its pathway-specific regulatory mechanism.

BACKGROUND: Isatropolone A and C, produced by Streptomyces sp. CPCC 204095, belong to an unusual class of non-benzenoid aromatic compounds and contain a rare seven-membered ring structure. Isatropolone A exhibits potent activity against Leishmania donovani, comparable to the only oral drug miltefosine. However, its variably low productivity represents a limitation for this lead compound in the future development of new anti-leishmaniasis drugs to meet unmet clinical needs. RESULTS: Here we first elucidated the regulatory cascade of biosynthesis of isatropolones, which consists of two SARP family regulators, IsaF and IsaJ. Through a series of in vivo and in vitro experiments, IsaF was identified as a pathway-specific activator that orchestrates the transcription of the gene cluster essential for isatropolone biosynthesis. Interestingly, IsaJ was found to only upregulate the expression of the cytochrome P450 monooxygenase IsaS, which is crucial for the yield and proportion of isatropolone A and C. Through targeted gene deletions of isaJ or isaS, we effectively impeded the conversion of isatropolone A to C. Concurrently, the facilitation of isaF overexpression governed by selected promoters, prompted the comprehensive activation of the production of isatropolone A. Furthermore, meticulous optimization of the fermentation parameters was conducted. These strategies culminated in the attainment of an unprecedented maximum yield-980.8 mg/L of isatropolone A-achieved in small-scale solid-state fermentation utilizing the genetically modified strains, thereby establishing the highest reported titer to date. CONCLUSION: In Streptomyces sp. CPCC 204095, the production of isatropolone A and C is modulated by the SARP regulators IsaF and IsaJ. IsaF serves as a master pathway-specific regulator for the production of isatropolones. IsaJ, on the other hand, only dictates the transcription of IsaS, the enzyme responsible for the conversion of isatropolone A and C. By engineering the expression of these pivotal genes, we have devised a strategy for genetic modification aimed at the selective and high-yield biosynthesis of isatropolone A. This study not only unveils the unique regulatory mechanisms governing isatropolone biosynthesis for the first time, but also establishes an essential engineering framework for the targeted high-level production of isatropolone A.

Bioactivity-Based Molecular Networking-Guided Isolation of Epicolidines A-C from the Endophytic Fungus Epicoccum sp. 1-042.

Bioactivity-based molecular networking-guided fractionation enabled the isolation of three new polycyclic tetramic acids bearing cis-decalin, epicolidines A-C (1-3), along with one known compound, PF 1052 (4), from the endophytic fungus Epicoccum sp. 1-042 collected in Tibet, China. Their structures were assigned on the basis of extensive spectroscopic data, partial hydrolysis, advanced Marfey's method, quantum chemistry calculations, and X-ray diffraction analysis. Compounds 2-4 displayed promising activities against Gram-positive bacteria in vitro. Particularly, compound 4 displayed remarkable potential against vancomycin-resistant Enterococcus faecium (VRE) with an MIC value of 0.25 µg/mL, lower than the MIC (0.5 µg/mL) of the antibiotic combination quinupristin/dalfopristin (Q/D). In a further in vivo study, compound 4 increased the survival rate to 100% in the VRE-G. mellonella infection model at a concentration of 10 mg/kg.

CCRL2 promotes antitumor T-cell immunity via amplifying TLR4-mediated immunostimulatory macrophage activation.

Macrophages are the key regulator of T-cell responses depending on their activation state. C-C motif chemokine receptor-like 2 (CCRL2), a nonsignaling atypical receptor originally cloned from LPS-activated macrophages, has recently been shown to regulate immune responses under several inflammatory conditions. However, whether CCRL2 influences macrophage function and regulates tumor immunity remains unknown. Here, we found that tumoral CCRL2 expression is a predictive indicator of robust antitumor T-cell responses in human cancers. CCRL2 is selectively expressed in tumor-associated macrophages (TAM) with immunostimulatory phenotype in humans and mice. Conditioned media from tumor cells could induce CCRL2 expression in macrophages primarily via TLR4, which is negated by immunosuppressive factors. Ccrl2-/- mice exhibit accelerated melanoma growth and impaired antitumor immunity characterized by significant reductions in immunostimulatory macrophages and T-cell responses in tumor. Depletion of CD8+ T cells or macrophages eliminates the difference in tumor growth between WT and Ccrl2-/- mice. Moreover, CCRL2 deficiency impairs immunogenic activation of macrophages, resulting in attenuated antitumor T-cell responses and aggravated tumor growth in a coinjection tumor model. Mechanically, CCRL2 interacts with TLR4 on the cell surface to retain membrane TLR4 expression and further enhance its downstream Myd88-NF-κB inflammatory signaling in macrophages. Similarly, Tlr4-/- mice exhibit reduced CCRL2 expression in TAM and accelerated melanoma growth. Collectively, our study reveals a functional role of CCRL2 in activating immunostimulatory macrophages, thereby potentiating antitumor T-cell response and tumor rejection, and suggests CCLR2 as a potential biomarker candidate and therapeutic target for cancer immunotherapy.

Novel series of tunable µOR modulators with enhanced brain penetration for the treatment of opioid use disorder, pain and neuropsychiatric indications.

Structural optimization of a previously reported agonist of µOR, PZM21 is described resulting in the discovery of a novel series of amides with at least 4-folds enhanced CNS penetration in rat. Furthermore, these efforts yielded compounds with varying levels of efficacy on the receptor ranging from high efficacy agonists such as compound 20 to antagonists, such as 24. The correlation between in vitro activation of µOR and relative activity in models of analgesia for these compounds is discussed. The compelling results obtained in these studies demonstrate the potential utility of these newly discovered compounds in the treatment of pain and opioid use disorder.

A hierarchical intervention scheme based on epidemic severity in a community network.

As there are no targeted medicines or vaccines for newly emerging infectious diseases, isolation among communities (villages, cities, or countries) is one of the most effective intervention measures. As such, the number of intercommunity edges ([Formula: see text]) becomes one of the most important factor in isolating a place since it is closely related to normal life. Unfortunately, how [Formula: see text] affects epidemic spread is still poorly understood. In this paper, we quantitatively analyzed the impact of [Formula: see text] on infectious disease transmission by establishing a four-dimensional [Formula: see text] edge-based compartmental model with two communities. The basic reproduction number [Formula: see text] is explicitly obtained subject to [Formula: see text] [Formula: see text]. Furthermore, according to [Formula: see text] with zero [Formula: see text], epidemics spread could be classified into two cases. When [Formula: see text] for the case 2, epidemics occur with at least one of the reproduction numbers within communities greater than one, and otherwise when [Formula: see text] for case 1, both reproduction numbers within communities are less than one. Remarkably, in case 1, whether epidemics break out strongly depends on intercommunity edges. Then, the outbreak threshold in regard to [Formula: see text] is also explicitly obtained, below which epidemics vanish, and otherwise break out. The above two cases form a severity-based hierarchical intervention scheme for epidemics. It is then applied to the SARS outbreak in Singapore, verifying the validity of our scheme. In addition, the final size of the system is gained by demonstrating the existence of positive equilibrium in a four-dimensional coupled system. Theoretical results are also validated through numerical simulation in networks with the Poisson and Power law distributions, respectively. Our results provide a new insight into controlling epidemics.

Meta-analysis of corneal endothelial changes after phacoemulsification in diabetic and non-diabetic patients.

BACKGROUND: Currently, there is still controversy about the differential changes in corneal endothelium function and morphology after phacoemulsification between Diabetes Mellitus (DM) and non-Diabetes Mellitus (non-DM) patients. In this study, we aimed to evaluate the influence of phacoemulsification on the corneal endothelium in DM and non-DM patients. METHODS: Databases of PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies published between January 1, 2011 and December 25, 2021. The weighted mean difference and 95% confidence interval were used to estimate the outcomes of statistical analyses performed. RESULTS: Thirteen studies involving 1744 eyes were included in this meta-analysis. No significant difference was observed in the central corneal thickness (CCT), endothelial cell density (ECD), coefficients of variation (CV), or hexagonal cell percentage (HCP) between the DM and non-DM groups (CCT: P = 0.91; ECD: P = 0.07; CV: P = 0.06; HCP: P = 0.09) preoperatively. The CCT was significantly thicker in the DM group at 1 month (P = 0.003) and 3 months (P = 0.0009) postoperatively, and there was no significant difference at 6 months postoperatively (P = 0.26) than non-DM group. The CV was significantly higher and HCP was significantly lower in the DM group at 1 month (CV:P < 0.0001, HCP: P = 0.002), with no significant difference at 3 months (CV: P = 0.09, HCP: P = 0.36) and 6 months (CV: P = 0.32, HCP: P = 0.36) postoperatively than non-DM group. DM patients had lower ECD than non-DM patients at all postoperative time points (1 month, 3 months: P < 0.00001, 6 months: P < 0.0001). CONCLUSIONS: The influence of phacoemulsification on corneal endothelial damage is greater in diabetic patients. Moreover, the recovery of corneal endothelial function and morphology is delayed in these patients. Clinicians should be more attentive to the corneal health of DM patients when considering phacoemulsification.

Oral and gastric microbiome in relation to gastric intestinal metaplasia.

Evidence suggests that Helicobacter pylori plays a role in gastric cancer (GC) initiation. However, epidemiologic studies on the specific role of other bacteria in the development of GC are lacking. We conducted a case-control study of 89 cases with gastric intestinal metaplasia (IM) and 89 matched controls who underwent upper gastrointestinal endoscopy at three sites affiliated with NYU Langone Health. We performed shotgun metagenomic sequencing using oral wash samples from 89 case-control pairs and antral mucosal brushing samples from 55 case-control pairs. We examined the associations of relative abundances of bacterial taxa and functional pathways with IM using conditional logistic regression with and without elastic-net penalty. Compared with controls, oral species Peptostreptococcus stomatis, Johnsonella ignava, Neisseria elongata and Neisseria flavescens were enriched in cases (odds ratios [ORs] = 1.29-1.50, P = .004-.01) while Lactobacillus gasseri, Streptococcus mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.66-0.76, P = .006-.042) in cases. Species J ignava and Filifactor alocis in the gastric microbiota were enriched (ORs = 3.27 and 1.43, P = .005 and .035, respectively), while S mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.61-0.75, P = .024-.046), in cases compared with controls. The lipopolysaccharide and ubiquinol biosynthesis pathways were more abundant in IM, while the sugar degradation pathways were under-represented in IM. The findings suggest potential roles of certain oral and gastric microbiota, which are correlated with regulation of pathways associated with inflammation, in the development of gastric precancerous lesions.

Lactobacilli and human dental caries: more than mechanical retention.

Lactobacilli have been considered as major contributors to human dental caries for over a century. Recent in vitro model studies have shown that when compared to Streptococcus mutans, a keystone pathogen of human dental caries, the ability of lactobacilli to form biofilms is poor, although differences exist between the different major species. Further studies using molecular and bioinformatics approaches provide evidence that multiple mechanisms, including adhesin-receptor mediated physical contact with S. mutans, facilitate the adherence and establishment of lactobacilli on the tooth surface. There is also evidence that under conditions like continuous sugar consumption, weak acids and other antimicrobials such as bacteriocins from lactobacilli can become detrimental to the microbial community, especially those in the proximity. Details on the underlying mechanisms of how different Lactobacillus sp. establish and persist in the highly complex microbiota on the tooth surface await further investigation.

Statistical iterative spectral CT imaging method based on blind separation of polychromatic projections.

Spectral computed tomography (CT) can provide narrow-energy-width reconstructed images, thereby suppressing beam hardening artifacts and providing rich attenuation information for component characterization. We propose a statistical iterative spectral CT imaging method based on blind separation of polychromatic projections to improve the accuracy of narrow-energy-width image decomposition. For direct inversion in blind scenarios, we introduce the system matrix into the X-ray multispectral forward model to reduce indirect errors. A constrained optimization problem with edge-preserving regularization is established and decomposed into two sub-problems to be alternately solved. Experiments indicate that the novel algorithm obtains more accurate narrow-energy-width images than the state-of-the-art method.

Integrated Surveillance System for Controlling COVID-19 on a University Campus, 2020‒2021.

To minimize the impacts of COVID-19 and to keep campus open, Cornell University's Ithaca, NY, campus implemented a comprehensive process to monitor COVID-19 spread, support prevention practices, and assess early warning indicators linked to knowledge, behaviors, and attitudes of campus community members. The integrated surveillance approach informed leadership and allowed for prompt adjustments to university policies and practices through evidence-based decisions. This approach enhanced healthy behaviors and promoted the well-being and safety of all community members. (Am J Public Health. 2022;112(7):980-984. https://doi.org/10.2105/AJPH.2022.306838).

Molecular Networking-Based Screening Led to the Discovery of a Cyclic Heptadepsipeptide from an Endolichenic Xylaria sp.

MS/MS-based molecular networking strain prioritization led to the discovery of a group of cyclic depsipeptides from an endolichenic Xylaria sp. The main component, xylaroamide A (1), was obtained by LC-MS-guided isolation. The planar structure of compound 1 was elucidated via 1D and 2D NMR, as well as MS/MS data. The configurations were fully determined by the combination of advanced Marfey's analysis, partial hydrolysis, Mosher's reaction, and GIAO NMR calculation based on a restricted conformational search. A plausible biosynthetic pathway for xylaroamide A (1) involving a rare trans-acting N-methyltransferase is proposed based on bioinformatics analysis. Xylaroamide A (1) exhibited inhibitory activity against cancer cell lines BT-549 and RKO with IC50 values of 2.5 and 9.5 µM, respectively.

Infection by the parasitic helminth Trichinella spiralis activates a Tas2r-mediated signaling pathway in intestinal tuft cells.

The parasitic helminth Trichinella spiralis, which poses a serious health risk to animals and humans, can be found worldwide. Recent findings indicate that a rare type of gut epithelial cell, tuft cells, can detect the helminth, triggering type 2 immune responses. However, the underlying molecular mechanisms remain to be fully understood. Here we show that both excretory-secretory products (E-S) and extract of T. spiralis can stimulate the release of the cytokine interleukin 25 (IL-25) from the mouse small intestinal villi and evoke calcium responses from tuft cells in the intestinal organoids, which can be blocked by a bitter-taste receptor inhibitor, allyl isothiocyanate. Heterologously expressed mouse Tas2r bitter-taste receptors, the expression of which is augmented during tuft-cell hyperplasia, can respond to the E-S and extract as well as to the bitter compound salicin whereas salicin in turn can induce IL-25 release from tuft cells. Furthermore, abolishment of the G-protein γ13 subunit, application of the inhibitors for G-protein αo/i, Gßγ subunits, and phospholipase Cß2 dramatically reduces the IL-25 release. Finally, tuft cells are found to utilize the inositol triphosphate receptor type 2 (Ip3r2) to regulate cytosolic calcium and thus Trpm5 activity, while potentiation of Trpm5 by a sweet-tasting compound, stevioside, enhances tuft cell IL-25 release and hyperplasia in vivo. Taken together, T. spiralis infection activates a signaling pathway in intestinal tuft cells similar to that of taste-bud cells, but with some key differences, to initiate type 2 immunity.

Higher erythrocyte n-3 polyunsaturated fatty acid were associated with a better profile of DXA-derived body fat and fat distribution in adults.

BACKGROUND: Previous studies have reported that high-dose supplementation of n-3 polyunsaturated fatty acids (PUFAs) may reduce the risk of metabolic diseases, but there is limited evidence of an effect on body fat. We examined the associations of erythrocyte n-3 PUFAs with body fat and fat distribution in a general population consuming a normal diet. METHODS: This community-based cross-sectional study included 3075 Chinese (68% women, 40-75 years) recruited between 2008 and 2013. We collected general information and measured anthropometric indices; erythrocyte n-3 PUFAs (including α-C18:3, C20:5, C22:5 and C22:6) by gas-chromatography, and fat mass (FM) and %FM at the total body (TB), android (A) and gynoid (G) regions by dual-energy X-ray absorptiometry (DXA). RESULTS: Both minimally and maximally adjusted models showed dose-dependent inverse associations of total and individual levels of erythrocyte n-3 PUFAs (except C20:5 n-3[EPA]) with adiposity indices. In the full model, the mean differences between quartiles 4 and 1 of total n-3 PUFAs were -1.60% (BMI), -4.06% (TB FM), -5.38% (A FM), -2.05% (G FM), -2.05% (TB %FM), -3.39% (A %FM) and -2.50% (% A/G); the ORs (95% CI) of %FM-derived obesity (≥25% for men, ≥35% for women) for the highest (vs. lowest) quartile were 0.70 (0.57, 0.86) for total n-3 PUFAs and 0.71 (0.58, 0.87), 0.96(0.78, 1.18), 0.82(0.67, 1.00), 0.66 (0.54, 0.81) for α-C18:3/C20:5/C22:5/C22:6 n-3, respectively. The favourable associations were more pronounced for the DXA-derived FM indices, measurements at the android region and for C22:6 n-3. No significant associations between C20:5 n-3 and the adiposity indices were observed. CONCLUSIONS: Higher levels of circulating n-3 PUFAs were dose-dependently associated with better profiles of body fat and fat distribution, particularly in the abdominal regions in this population.

Erythrocyte Membrane Polyunsaturated Fatty Acids Are Associated with Incidence of Metabolic Syndrome in Middle-Aged and Elderly People-An 8.8-Year Prospective Study.

BACKGROUND: The total and specific types of polyunsaturated fatty acids (PUFAs) related to metabolic syndrome (MetS) remain inconsistent. OBJECTIVE: We assessed the association of erythrocyte n-3 and n-6 PUFAs with MetS and the components of MetS in a cohort population. METHODS: This prospective analysis included 2754 participants (aged 40-75 y) from the Guangzhou Nutrition and Health Study (2008-2019) in China. Erythrocyte PUFAs at baseline were measured using gas chromatography. MetS was assessed every 3 y according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria. Multivariable Cox proportional hazard models were used to evaluate HRs and 95% CIs. RESULTS: We identified 716 incident cases of MetS. The primary analyses showed that the HRs (95% CIs) of MetS (tertile 3 versus 1) were 0.67 (0.56, 0.80) for n-3 PUFAs and 0.70 (0.58, 0.85) for n-6 PUFAs (all Ps trend <0.001). The secondary outcomes showed that, higher erythrocyte very-long-chain (VLC) PUFAs [20:3n-3, docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), arachidonic acid (ARA), and 22:4n-6], but lower α-linolenic acid (ALA) and γ-linolenic acid (GLA), tended to be associated with lower incidences of MetS and its components; among individual MetS components, the associations of PUFAs were more pronounced for hypertriglyceridemia (HTG) and hypertension, followed by low high-density lipoproten (HDL) cholesterol. Significantly higher concentrations of n-3 PUFAs (total, DPA, and DHA) and n-6 PUFAs (total, ARA, and 22:4) were observed in participants with improved (versus progressed) status of MetS (all Ps trend ≤0.003). CONCLUSION: This study reveals that higher erythrocyte VLC n-3 and n-6 PUFAs, but lower 18-carbon PUFAs (ALA and GLA), are associated with lower risks of MetS components (HTG, hypertension, and low HDL cholesterol) and thereby lower MetS incidence in Chinese adults.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated with lower presence of non-alcoholic fatty liver disease in middle-aged and elderly adults.

OBJECTIVE: Previous studies have shown that the Dietary Approaches to Stop Hypertension (DASH) diet might contribute to managing risk factors of non-alcoholic fatty liver disease (NAFLD), but evidence is limited. We examined the association of DASH diet score (DASH-DS) with NAFLD, as well as the intermediary effects of serum retinol-binding protein-4 (RBP4), serum high-sensitivity C-reactive protein (hs-CRP), serum TAG, homeostasis model assessment of insulin resistance (HOMA-IR) and BMI. DESIGN: We performed a cross-sectional analysis of a population-based cohort study. Dietary data and lifestyle factors were assessed by face-to-face interviews and the DASH-DS was then calculated. We assessed serum RBP4, hs-CRP and TAG and calculated HOMA-IR. The presence and degree of NAFLD were determined by abdominal sonography. SETTING: Guangzhou, China. PARTICIPANTS: Guangzhou Nutrition and Health Study participants, aged 40-75 years at baseline (n 3051). RESULTS: After adjusting for potential covariates, we found an inverse association between DASH-DS and the presence of NAFLD (Ptrend = 0·009). The OR (95 % CI) of NAFLD for quintiles 2-5 were 0·78 (0·62, 0·98), 0·74 (0·59, 0·94), 0·69 (0·55, 0·86) and 0·77 (0·61, 0·97), respectively. Path analyses indicated that a higher DASH-DS was associated with lower serum RBP4, hs-CRP, TAG, HOMA-IR and BMI, which were positively associated with the degree of NAFLD. CONCLUSIONS: Adherence to the DASH diet was independently associated with a marked lower prevalence of NAFLD in Chinese adults, especially in women and those without abdominal obesity, and might be mediated by reducing RBP4, hs-CRP, TAG, HOMA-IR and BMI.

Urinary equol is associated with bioavailable testosterone but not total testosterone in women.

Little is known about the association between equol and bioavailable testosterone (BT) in adults. In this study, we examined the associations of urinary equol concentrations with serum concentrations of total, bioavailable and free testosterone (FT), dehydroepiandrosterone sulfide (DHEAS), free androgen index (FAI) and sex hormone-binding globulin (SHBG). This cross-sectional study included 1,904 women with a mean age of 59.7 years. Urinary equol concentrations were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The serum androgenic indices and SHBG were also determined. Overall, urinary equol tended to be inversely associated with bioactive forms of androgenic indices (BT, FT or FAI) but not with total testosterone (TT) or DHEAS. Urinary equol was also positively associated with SHBG. In multi-covariate-adjusted analyses stratified by menopausal status, graded and inverse associations between urinary equol and bioactive forms of androgenic indices (BT, FT and FAI) were observed in postmenopausal women (all p-trends < 0.05), but not in premenopausal women. A significant positive association between urinary equol and SHBG was observed only in postmenopausal women. No significant associations were observed between urinary equol and TT or DHEAS in either group. A path analysis indicated that these associations of equol with androgens in postmenopausal women might be mediated by SHBG. In conclusion, urinary equol exhibited graded and inverse associations with BT or FT, but not TT in women. However, further longitudinal studies of human patients are needed to confirm these results and overcome the limitations of cross-sectional studies.