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Purpose Milk protein ingestion reduces post-meal glycemia when consumed either before or together with carbohydrate foods. The aim of this study was to compare the effects of dairy and soy milk consumed either before (preload) or together with (co-ingestion) a carbohydrate (bread), on postprandial blood glucose, insulin and gastric emptying in healthy participants. Methods Twelve healthy Chinese male participants were studied on five separate occasions using a randomized crossover design. White wheat bread consumed with water was used as a reference meal. Capillary and venous bloods were sampled pretest and 3.5 h post-test meal for glucose and insulin measurement. Gastric emptying was measured using real-time ultrasonography. Results Co-ingestion of dairy milk or soy milk with bread lowered postprandial blood glucose response and glycemic index. Co-ingesting soy milk with bread increased insulin response and insulinemic index significantly compared to co-ingestion of dairy milk and preload treatments. Preloads (30 min prior to bread) significantly lowered postprandial glycemia and insulinemia compared to co-ingestion. Gastric emptying was slower after co-ingesting dairy milk with bread than after reference meal. Conclusions Preloading either soy milk or dairy milk results in greater reduction in glycemic response compared to co-ingestion alone. This dietary practice may have therapeutic advantage in communities consuming high GI diets. Optimal glucose control may have the potential for increasing the time of transition from prediabetes to type 2 diabetes in Asian communities. Clinical trial registration This trial was registered at clinicaltrials.gov as NCT 02151188.

This study investigated the impact of calcium chloride (CaCl2) and magnesium chloride (MgCl2) at varying concentrations on a model milk formulation’s physical and chemical properties after thermal treatment. The model milk was subjected to two-stage homogenization and pasteurization before being supplemented with different concentrations of CaCl2 or MgCl2. The findings revealed that elevating the concentration of either calcium or magnesium resulted in the milk emulsion having a higher viscosity and median particle size following heating. CaCl2 had a slightly stronger impact than MgCl2, particularly at higher concentrations. The milk samples also exhibited a reduction in the zeta potential as the ionic strength of the salt solution increased, with the CaCl2-fortified milk displaying a slightly lower negative surface charge than the MgCl2-fortified milk at the same dose. The model milk’s viscosity was evaluated after adding various salt concentrations and a temperature ramp from 20 to 80 °C. Notably, the viscosity and particle size changes demonstrated a non-linear relationship with increasing mineral levels, where a significant increase was observed at or above 5.0 mM. An emulsion stability analysis also revealed that the de-stabilization pattern of the high salt concentration sample differed significantly from its low salt concentration counterparts. These findings could serve as a basis for the future development of fortified UHT milk with nutritionally beneficial calcium and magnesium in industrial applications.

PurposeThe magnitude of postprandial lipemia is influenced not only by the amount but also the type of fat and carbohydrate consumed. The aim of this study was to evaluate differences in postprandial glucose and lipid responses after a mixed meal containing low- or high-glycemic-index (GI) carbohydrate and three different types of fat varying in the degree of saturation in healthy subjects.MethodsA randomized, controlled, single-blinded crossover study was conducted in 20 healthy Chinese men. Subjects consumed in random order six experimental isocaloric meals that differed in carbohydrate and fat quality, and contained 40 g of either saturated fat (SFA, butter), monounsaturated fat (MUFA, olive oil) or polyunsaturated fat (PUFA, grapeseed oil), and 50 g of either low-GI (basmati rice) or high-GI (jasmine rice) carbohydrate. Glucose, insulin, c-peptide, triglycerides (TG) and non-esterified fatty acids (NEFA) were measured over 4 h.ResultsFor all substrates evaluated, there were no significant interactions between fat and carbohydrate. The incremental area under the curve (iAUC) for TG was significantly lower after the SFA and PUFA meals compared with the MUFA meal, irrespective of GI. No significant difference was found for NEFA iAUC in all treatments. Glucose, insulin and c-peptide iAUCs were significantly lower after ingestion of low-GI than high-GI meals, independent of the type of fat.ConclusionsA carbohydrate-rich meal (of either low or high GI) that contains butter or grapeseed oil results in lower postprandial TG concentrations relative to olive oil in healthy Chinese males. Glucose, insulin and c-peptide responses, however, are directly dependent on the GI of the meal and not on the degree of saturation of dietary fat.The trial was registered at clinicaltrials.gov as NCT02585427.

A low-glycaemic-index (GI) breakfast has been shown to lower blood glucose levels throughout the day. A wide variety of breakfast foods are consumed, but their GI values are largely unknown, hence limiting consumers’ ability to select healthier options. This study investigated the GI values of ten common breakfast (five Asian and five Western) foods in this region using a randomised, cross-over study design. Participants arrived after an overnight fast, and fasting blood sample was taken before participants consumed test foods. Next, blood samples were taken at fixed intervals for 180 min. Glycaemic and insulinaemic responses to test foods were calculated as incremental AUC over 120 min, which were subsequently reported as glycaemic and insulinaemic indices. In all, nineteen healthy men (nine Chinese and ten Indians) aged 24·7 (sem 0·4) years with a BMI of 21·7 (sem 0·4) kg/m2 completed the study. Asian breakfast foods were of medium (white bun filled with red bean paste=58 (sem 4); Chinese steamed white bun=58 (sem 3)) to high GI (rice idli=85 (sem 4); rice dosa=76 (sem 5); upma=71 (sem 6)), whereas Western breakfast foods were all of low GI (whole-grain biscuit=54 (sem 5); whole-grain biscuit filled with peanut butter=44 (sem 3); whole-grain oat muesli=55 (sem 4); whole-grain oat protein granola=51 (sem 4); whole-grain protein cereal=49 (sem 3)). The GI of test foods negatively correlated with protein (r s −0·366), fat (r s −0·268) and dietary fibre (r s −0·422) (all P<0·001). GI values from this study contribute to the worldwide GI database, and may assist healthcare professionals in recommending low-GI breakfast to assist in lower daily glycaemia among Asians who are susceptible to type 2 diabetes mellitus.

Apart from the well-known action of insulin, the mechanism by which soya and cows’ milk improve postprandial glycaemia control was examined. In total, twelve healthy, young, Chinese men were studied on three separate occasions, in random order with isovolumetric (322 ml) control water, soya milk and cows’ milk. Plasma total amino acid concentrations increased 30 min after test meals consumption and were higher after soya milk (230 %) and cow milk (240 %) consumption compared with water. Cows’ milk ingestion induced higher branched-chain amino acids (BCAA) (40 %) than soya milk. Postprandial incretin concentrations increased after meal consumption. Cows’ milk meal was accompanied by higher incremental AUC (iAUC) (170 %) for glucagon-like peptide-1 (GLP-1) compared with soya milk and control (P=0·06). However, glucose-dependent insulinotropic polypeptide (GIP) concentrations increased to significantly greater levels after soya milk consumption (iAUC 60 % higher) compared with cows’ milk and control. Consumption of both soya and cows’ milk with carbohydrates induced a similar reduction in glycaemic response through a different mechanism, beyond insulin action. Plasma amino acids (alanine and arginine), and incretins in particular (GIP was stimulated), may be involved in the hyperinsulinaemia after soya milk meals. However, BCAA and GLP-1 release may be responsible for the reduced glycaemia after cows’ milk consumption by delaying gastric emptying. This could be the result of different milk protein/amino acid composition, but also differences in milk carbohydrate composition (i.e. lactose v. sucrose). It can be concluded that soya milk is a good alternative to cows’ milk with regard to glycaemic regulation, with different mechanisms involved.

The objective of the present study was to determine the glycaemic index (GI) and glycaemic load (GL) values of standard portion sizes of Southeast Asian traditional foods. A total of fifteen popular Southeast Asian foods were evaluated. Of these foods, three were soft drinks, while the other twelve were solid foods commonly consumed in this region. In total, forty-seven healthy participants (eighteen males and twenty-nine females) volunteered to consume either glucose at least twice or one of the fifteen test foods after a 10–12 h overnight fast. Blood glucose concentrations were analysed before consumption of the test food, and 15, 30, 45, 60, 90 and 120 min after food consumption, using capillary blood samples. The GI value of each test food was calculated by expressing the incremental area under the blood glucose response curve (IAUC) value of the test food as a percentage of each participant's average IAUC value, with glucose as the reference food. Among the fifteen foods tested, six belonged to low-GI foods (Ice Green Tea, Beehoon, Pandan Waffle, Curry Puff, Youtiao and Kaya Butter Toast), three belonged to medium-GI foods (Barley Drink, Char Siew Pau and Nasi Lemak), and the other six belonged to high-GI foods (Ice Lemon Tea, Chinese Carrot Cake, Chinese Yam Cake, Chee Cheong Fun, Lo Mai Gai and Pink Rice Cake). The GI and GL values of these traditional foods provide valuable information to consumers, researchers and dietitians on the optimal food choice for glycaemic control. Moreover, our dataset provides GI values of fifteen foods that were not previously tested extensively, and it presents values of foods commonly consumed in Southeast Asia.

Cationic polymers have emerged as promising next-generation antimicrobial agents, albeit with inherent limitations such as low potency and limited biocompatibility. Classical cationic polymers kill bacteria via physical membrane disruption. We propose a non-classical mechanism of crossing the bacterial plasma membrane barrier, a step required for subsequent inhibition of intracellular targets, by cationic polymers which are carbon acids. Oligoimidazolium (OIM) carbon acids, instead of lysing bacteria, transiently deprotonate in water to form hydrophobic N-heterocyclic carbenes (NHCs) and exhibit efficient plasma membrane translocation. Only OIMs that are carbon acids have potent antibacterial activities against even colistin- and multidrug-resistant bacteria. OIM amide derivatives exhibit excellent antibacterial efficacy in murine sepsis and thigh infection models, while a polymeric version acts as a prophylactic agent against bovine mastitis, which is a global agricultural problem. This study unveils a promising path for the development of an alternative class of potent antimicrobial agents. Cationic polymers conventionally kill bacteria via physical membrane disruptions. Here, the authors report the development of carbon acid cationic polymers that show potent activity against multidrug-resistant strains in murine infection models and prevent bovine mastitis, and present evidence that these polymers translocate across bacterial membrane aided by N-heterocyclic carbene.

Dongxin Lin, Philip Taylor, Li-Dong Wang and colleagues have now pooled three genome-wide association analyses of esophageal squamous cell carcinoma, finding two new risk loci at genome-wide significance and an HLA class II locus of significance in high-risk populations. They reanalyze the strength of evidence for previously published risk loci. We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1 , 2 , 3 of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82–0.88; P = 7.72 × 10 −20 ) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85–0.91; P = 3.10 × 10 −13 ). rs7447927 is a synonymous SNP in TMEM173 , and rs1642764 is an intronic SNP in ATP1B2 , near TP53 . Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22–1.46; P = 1.99 × 10 −10 ). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC.

Intranasal delivery of mRNA vaccines offers promising opportunities to combat airborne viruses like SARS‐CoV‐2 by provoking mucosal immunity, which not only defends against respiratory infection but also prevents contagious transmission. However, the development of nasal mRNA vaccines has been hampered by the lack of effective means to overcome the mucus barrier. Herein, ionizable lipid‐incorporated liquid lipid nanoparticles (iLLNs) capable of delivering mRNA cargo across airway mucosa are designed. Adjusting the ratios of ionizable and cationic lipids allows fine‐tuning of the pKa of iLLNs to the range of nasal mucosal pH (5.5–6.5), thus facilitating mucus penetration via the formation of near‐neutral, PEGylated muco‐inert surfaces. When nasally administered to mice, the top candidate iLLN‐2/mRNA complexes enable about 60‐fold greater reporter gene expression in the nasal cavity, compared to the benchmark mRNA‐lipid nanoparticles (ALC‐LNP) having the same lipid composition as that of BNT162b2 vaccine. Moreover, a prime‐boost intranasal immunization of iLLN‐2/mRNA complexes elicits a greater magnitude of SARS‐CoV‐2 spike‐specific mucosal IgA and IgG response than ALC‐LNP, without triggering any noticeable inflammatory reactions. Taken together, these results provide useful insights for the design of nasally deliverable mRNA formulations for prophylactic applications. Muco‐penetrating, ionizable lipid‐incorporated liquid lipid nanoparticles (iLLNs) with tunable pKa values are designed for enhanced intranasal mRNA delivery. The top candidate iLLN‐2/mRNA complexes demonstrate superior transgene expression in the nasal cavity and antigen‐specific mucosal immunity in mice over the benchmark mRNA‐lipid nanoparticles while avoiding harmful proinflammatory responses, showing promise as a safer and more effective nasal mRNA formulation.

Breast fibroepithelial lesions (FEL) are biphasic tumors which consist of benign fibroadenomas (FAs) and the rarer phyllodes tumors (PTs). FAs and PTs have overlapping features, but have different clinical management, which makes correct core biopsy diagnosis important. This study used whole-slide images (WSIs) of 187 FA and 100 PT core biopsies, to investigate the potential role of artificial intelligence (AI) in FEL diagnosis. A total of 9228 FA patches and 6443 PT patches was generated from WSIs of the training subset, with each patch being 224 × 224 pixel in size. Our model employed a two-stage architecture comprising a convolutional neural network (CNN) component for feature extraction from the patches, and a recurrent neural network (RNN) component for whole-slide classification using activation values from the global average pooling layer in the CNN model. It achieved an overall slide-level accuracy of 87.5%, with accuracies of 80% and 95% for FA and PT slides respectively. This affirms the potential role of AI in diagnostic discrimination between FA and PT on core biopsies which may be further refined for use in routine practice. An artificial intelligence (AI) model was developed to discriminate between fibroadenomas and phyllodes tumors on core biopsy images. It employed a two-stage architecture comprising a convolutional neural network (CNN) component for feature extraction, and a recurrent neural network (RNN) component for whole-slide classification, with an overall slide-level accuracy of 87.5%.