Correlation between serum trimethylamine-N-oxide and body fat distribution in middle-aged and older adults: a prospective cohort study.

BACKGROUND: Trimethylamine-N-oxide (TMAO) is linked with obesity, while limited evidence on its relationship with body fat distribution. Herein, we investigated the associations between serum TMAO and longitudinal change of fat distribution in this prospective cohort study. METHODS: Data of 1964 participants (40-75y old) from Guangzhou Nutrition and Health Study (GNHS) during 2008-2014 was analyzed. Serum TMAO concentration was quantified by HPLC-MS/MS at baseline. The body composition was assessed by dual-energy X-ray absorptiometry at each 3-y follow-up. Fat distribution parameters were fat-to-lean mass ratio (FLR) and trunk-to-leg fat ratio (TLR). Fat distribution changes were derived from the coefficient of linear regression between their parameters and follow-up duration. RESULTS: After an average of 6.2-y follow-up, analysis of covariance (ANCOVA) and linear regression displayed women with higher serum TMAO level had greater increments in trunk FLR (mean ± SD: 1.47 ± 4.39, P-trend = 0.006) and TLR (mean ± SD: 0.06 ± 0.24, P-trend = 0.011). Meanwhile, for women in the highest TMAO tertile, linear mixed-effects model (LMEM) analysis demonstrated the annual estimated increments (95% CI) were 0.03 (95% CI: 0.003 - 0.06, P = 0.032) in trunk FLR and 1.28 (95% CI: -0.17 - 2.73, P = 0.083) in TLR, respectively. In men, there were no similar significant observations. Sensitivity analysis yielded consistent results. CONCLUSION: Serum TMAO displayed a more profound correlation with increment of FLR and TLR in middle-aged and older community-dwelling women in current study. More and further studies are still warranted in the future. TRIAL REGISTRATION: NCT03179657.

Dietary inflammatory index, mediating biomarkers and incident frailty in Chinese community-dwelling older adults.

OBJECTIVES: Diet can modulate systemic inflammation, while inflammation is a critical contributory factor of frailty. However, longitudinal data on the association between dietary inflammatory index (DII) and frailty are limited, and the intermediate mechanisms remain unclear. This study aimed to examine the association between DII and incident frailty and the potential mediating roles of frailty-related biomarkers. DESIGN: Prospective cohort study. SETTING: The Mr. OS and Ms. OS (Hong Kong) study. PARTICIPANTS: A total of 3,035 community-dwelling men and women aged above 65 years without frailty at baseline were included. MEASUREMENTS: DII scores were calculated using the locally validated food frequency questionnaire. Incident frailty at year four was defined using the Fried frailty phenotype. Logistic regression was used to examine the association between DII and frailty onset. Mediation analysis was used to explore the mediating roles of frailty-related biomarkers in the DII-frailty association. RESULTS: During four years of follow-up, 208 individuals developed frailty. Compared with the lowest tertile of DII, the highest tertile was associated with an increased risk of incident frailty (OR: 1.82; 95% CI: 1.17-2.82; p = 0.008) after adjustment for relevant confounders. The DII-frailty association was significant in men but not in women. Furthermore, increasing serum homocysteine, decreasing serum folate, and reducing estimated glomerular filtration rate (eGFR) mediated 11.6%, 7.1%, and 9.6 % of the total relation between DII and frailty onset, respectively. CONCLUSION: In this cohort study, a pro-inflammatory diet was associated with a higher risk of frailty onset, mediated by homocysteine, folate, and renal function.

Using Quercetin to Construct Molecularly Imprinting Polymer in the Preparation and Enrichment of Flavonol and Flavonoid Compounds.

Flavonol and flavonoid compounds are important natural compounds with various biomedical activities. Therefore, it is of great significance to develop a strategy for the specific extraction of flavonol and flavonoid compounds. Quercetin is a well-studied flavonoid possessing many health benefits. This compound is a versatile antioxidant known to possess protective abilities against body tissue injury induced by pathological situations and various drug toxicities. Although quercetin is widely distributed in many plants, its content generally is not very high. Therefore, the specific extraction of quercetin as well as other flavonol and flavonoid compounds has profound significance. In this work, the quercetin molecularly imprinting polymer (QMIP) was successfully prepared, in which a typical flavonol quercetin was selected as the template molecule. QMIP was synthesized by performing the surface molecular imprinting technology on the surface of NH2-MIL-101(Fe). Our study results showed that QMIP exhibited quick binding kinetic behavior, a high adsorption capacity (57.04[Formula: see text]mg/g), and the specific recognition ability toward quercetin compared with structurally distinct compounds (selective [Formula: see text]). The specific adsorption ability of quercetin by QMIP was further explained using computation simulation that molecules with non-planar 3D conformations hardly entered the molecularly imprinted cavities on QMIP. Finally, QMIP was successfully used for the specific extraction of quercetin and five other flavonol and flavonoid compounds in the crude extracts from Sapium sebiferum. This study proposes a new strategy to synthesize the molecularly imprinted polymer based on a single template for enriching and loading a certain class of active ingredients with similar core structures from variable botanicals.

α4 nicotinic receptors on GABAergic neurons mediate a cholinergic analgesic circuit in the substantia nigra pars reticulata.

Nicotinic acetylcholine receptors (nAChRs) regulate pain pathways with various outcomes depending on receptor subtypes, neuron types, and locations. But it remains unknown whether α4ß2 nAChRs abundantly expressed in the substantia nigra pars reticulata (SNr) have potential to mitigate hyperalgesia in pain states. We observed that injection of nAChR antagonists into the SNr reduced pain thresholds in naïve mice, whereas injection of nAChR agonists into the SNr relieved hyperalgesia in mice, subjected to capsaicin injection into the lower hind leg, spinal nerve injury, chronic constriction injury, or chronic nicotine exposure. The analgesic effects of nAChR agonists were mimicked by optogenetic stimulation of cholinergic inputs from the pedunculopontine nucleus (PPN) to the SNr, but attenuated upon downregulation of α4 nAChRs on SNr GABAergic neurons and injection of dihydro-ß-erythroidine into the SNr. Chronic nicotine-induced hyperalgesia depended on α4 nAChRs in SNr GABAergic neurons and was associated with the reduction of ACh release in the SNr. Either activation of α4 nAChRs in the SNr or optogenetic stimulation of the PPN-SNr cholinergic projection mitigated chronic nicotine-induced hyperalgesia. Interestingly, mechanical stimulation-induced ACh release was significantly attenuated in mice subjected to either capsaicin injection into the lower hind leg or SNI. These results suggest that α4 nAChRs on GABAergic neurons mediate a cholinergic analgesic circuit in the SNr, and these receptors may be effective therapeutic targets to relieve hyperalgesia in acute and chronic pain, and chronic nicotine exposure.

Association of dietary protein intake, inflammation with muscle mass, physical performance and incident sarcopenia in Chinese community-dwelling older adults.

OBJECTIVES: Inflammation and impaired muscle synthesis are important factors of sarcopenia. Plant protein may reduce inflammation but may not be as efficient as animal protein in providing essential amino acids. We therefore examined the associations between dietary protein intake and changes in muscle mass and physical performance, incident sarcopenia, and the interaction effect of inflammation. DESIGN: Prospective cohort study. SETTING: The Mr. OS and Ms. OS (Hong Kong) cohort. PARTICIPANTS: A total of 2,811 sarcopenia-free participants and 569 sarcopenia participants aged ≥65 years were recruited from communities. MEASUREMENTS: Dietary protein intake was assessed using a validated food frequency questionnaire. Serum high-sensitivity C-reactive protein (hs-CRP) was measured. Linear regression examined the associations between dietary protein intake and 4-year changes in muscle mass and physical performance. Cox regression examined the association between dietary protein intake and incident sarcopenia. RESULTS: Higher plant protein intake, but not total and animal protein, was associated with less decline in muscle mass and gait speed among sarcopenia-free participants. Conversely, higher ratio of animal-to-plant protein was associated with reduced muscle mass loss among participants with sarcopenia. The highest tertile of plant protein intake was associated with lower incident sarcopenia risk (HR: 0.75, 95% CI: 0.57-0.98; P-trend = 0.034) compared to the lowest tertile. Notably, this association was observed among participants with higher serum hs-CRP levels (HR: 0.57, 95% CI: 0.34-0.95), but not in those with lower hs-CRP levels. CONCLUSION: Dietary animal and plant protein intake have differential associations with muscle mass and physical performance in older adults with and without sarcopenia. The role of plant protein in preventing sarcopenia involves modulation of inflammation.

New mitogenomes from the genus Cricotopus (Diptera: Chironomidae, Orthocladiinae): Characterization and phylogenetic implications.

Cricotopus is a large and diverse genus of non-biting midges composed of several subgenera. Complete mitogenome sequences are available for very few Cricotopus species. The subgenus Pseudocricotopus unites species with unusual morphological structures in adult male and pupal stages, however, molecular methods are needed to verify the placement of this subgenus within Cricotopus. We obtained mitogenomes of C. (Pseudocricotopus) cf. montanus and nine other Cricotopus species for phylogenetic analysis, coupled with two Rheocricotopus species and one Synorthocladius species as outgroups. The structure of the mitogenome was similar among these Cricotopus species, exhibiting A+T bias and retaining ancestral gene order. Mutation rate, estimated as Ka/Ks, varied among genes, and was highest for ATP8 and lowest for COI. The phylogenetic relationships among species of Cricotopus, Rheocricotopus and Synorthocladius was reconstructed using Bayesian inference and maximum likelihood estimation. The phylogenetic trees confirmed placement of subgenus Pseudocricotopus, represented by Cricotopus cf. montanus, within Cricotopus. Our study increases the library of chironomid mitogenomes and provides insight into the properties of their constituent genes.

DNA barcodes and morphology reveal new species within the Rheotanytarsus guineensis species group from China (Diptera: Chironomidae).

The Rheotanytarsus guineensis species group (Diptera: Chironomidae) is a species diverse and taxonomically difficult group. Using DNA barcodes, we found five new species within the R. guineensis species group and reviewed the species group based on adult males from China. Rheotanytarsus guoae Lin & Yao sp. n., Rheotanytarsus miaoae Lin & Yao sp. n., Rheotanytarsus qiangi Lin & Yao sp. n., Rheotanytarsus yueqingensis Lin & Yao sp. n., and Rheotanytarsus yui Lin & Yao sp. n. are all described and figured. A key to known adult males of the R. guineensis species group worldwide is provided for the first time.

Quantity and Variety of Fruit and Vegetable Intake with Changes in Measures of Adiposity among Community-Dwelling Chinese Older Adults.

BACKGROUND: The association between fruit and vegetable intake, considering both quantity and variety, and weight change among older adults remains controversial. We aimed to investigate the association between fruit and vegetable intake, variety, and changes in adiposity measures among community-dwelling Chinese older adults. METHODS: A total of 2944 participants aged ≥65 years from Hong Kong communities were included. Fruit and vegetable intake was estimated by a locally validated food frequency questionnaire. Adiposity measures (weight, body mass index (BMI), waist circumference, fat and lean mass) were assessed at baseline and the year four follow-up. Restricted cubic spline and logistic models were performed to estimate the associations between fruit and vegetable intake, variety, and changes in adiposity measures. RESULTS: A nonlinear association between vegetable intake and weight change was found, following a J-shape curve. Increased vegetable intake was associated with less increases in weight, BMI, and fat mass among those below median intakes. However, these associations became insignificant at higher intakes (all P-nonlinearity < 0.05). The ORs (95% CIs) for weight gain across the quartiles of vegetable intake were as follows: 1.00 (reference), 0.81 (0.56, 1.17), 0.55 (0.36, 0.83), and 0.88 (0.58, 1.33). Similar patterns were observed in overweight and normal weight participants, but not in those with low body weight. No associations with weight change were found for fruit intake or fruit and vegetable variety. CONCLUSIONS: Moderate vegetable intake was associated with less weight gain among community-dwelling Chinese older adults, but not in those with low body weight. No association was observed between fruit intake or variety with weight change.

Improved emission performance of benzo[a]phenoxazine in aqueous solution through host-guest interaction.

To evaluate the contribution of host-guest chemistry in fluorescence enhancement under aqueous conditions, two benzo[a]phenoxazine derivatives with the adamantyl group were prepared. After they formed stable complexes with methyl-ß-cyclodextrin, their emissions at 625-825 nm were greatly increased and fluorescence quantum yields reached 11.5-12.6% in aqueous solution. Furthermore, they were successfully applied in fluorescence labeling of organelles in HeLa cells.

Pogocablenes A-O, fifteen undescribed sesquiterpenoids with structural diversity from Pogostemon cablin.

Fifteen previously undescribed sesquiterpenoids (pogocablenes A-O), three first discovered natural patchoulol-type ones, coupled with fourteen known ones, were isolated from the aerial parts of Pogostemon cablin. Among them, pogocablenes A and B, a pair of C2 epimers, possessed an unusual carbon skeleton with bicyclo[4.3.1]decane core. Pogocablene C, originated from eudesmane-type sesquiterpenoid, had an unprecedented bicyclo[5.4.0]undecane scaffold with a peroxy hemiactetal moiety. Pogocablene D possessed a rare tricyclo[5.2.2.01,5]undecane carbon skeleton derived from guaiane-type sesquiterpenoid. Pogocablene E was a 4,5-seco-guaiane derivative owning a peroxy hemiactetal unit and a spirocyclic skeleton. Pogocablene M was a nor-patchoulol-type sesquiterpenoid with α,ß-unsaturated ketone moiety. Their structures with absolute configuration were determined by extensive spectroscopic analysis, in combination with quantum chemical calculation. In addition, the plausible biogenetic pathways of pogocablenes A-E were proposed. Furthermore, all isolates were evaluated for anti-influenza virus and anti-inflammatory effects.

Pore Environmental Modification by Alkoxy Groups in Pore-Space-Partitioned Metal-Organic Frameworks to Achieve Gas Uptake-Selectivity Balance.

Due to the trade-off barrier between high storage capacity and high selectivity, the controllable and systematic design of metal-organic frameworks (MOFs) aiming at performance optimization is still challenging. Herein, considering the effectiveness of alkoxy group functionalization and a pore-space partition strategy, a series of rigid Mg-pacs-MOFs (SNNU-10-n, n = 1-6) with flexible side chains are built for the first time, realizing systematic pore environmental modification. The steric hindrance effects, electron-donating ability, and the flexibility of alkoxy groups are considered as key factors, which lead to a regular change of gas adsorption capacity and selectivity. Notably, methoxy-modified SNNU-10-1 with moderately high storage capacities of C2H2 (139.4 cm3 g-1), C2H4 (100.4 cm3 g-1), CO2 (105.0 cm3 g-1), and high selectivity values for equimolar C2H2/CH4 (431.8), C2H4/CH4 (164.2), and CO2/CH4 (16.1) mixture separation at 273 K and 100 kPa achieves an ideal gas uptake-selectivity balance. Breakthrough experiments verified that it could effectively separate the above-mentioned mixtures under ambient conditions, and GCMC simulation provides a deep understanding of methoxy group functionalization. Undoubtedly, this work not only realizes controllable regulation of gas adsorption behavior but also proves the validity of improving selectivity by alkoxy groups in those platforms with high gas-uptake potential to overcome the trade-off barrier.

Increased Dietary Intakes of Total Protein, Animal Protein and White Meat Protein Were Associated with Reduced Bone Loss-A Prospective Analysis Based on Guangzhou Health and Nutrition Cohort, South China.

In this study, we aimed to prospectively investigate the relationships between different types of dietary protein and changes in bone mass in Chinese middle-aged and elderly people. Dietary intakes were evaluated by means of a validated food frequency questionnaire. Bone mineral density (BMD) was measured using a dual-energy bone densitometer at multiple bone sites. Multivariable regression models were applied to investigate the associations of the participants' dietary intakes of total protein, intakes of protein from various sources, and amino acid intakes with the annualized changes in BMD during a 3-year follow-up. A total of 1987 participants aged 60.3 ± 4.9 years were included in the analyses. Multivariable linear regression results showed that dietary intakes of total protein, animal protein, and protein from white meat were positively correlated with BMD changes, with standardized coefficients (ß) of 0.104, 0.073, and 0.074 at the femur neck (p < 0.01) and 0.118, 0.067, and 0.067 at the trochanter (p < 0.01), respectively. With each increase of 0.1g·kg-1·d-1 in animal protein and white meat protein intakes, the BMD losses were reduced by 5.40 and 9.24 mg/cm2 at the femur neck (p < 0.05) and 1.11 and 1.84 mg/cm2 at the trochanter (p < 0.01), respectively. Our prospective data, obtained from Chinese adults, showed that dietary total and animal protein, especially protein from white meat, could significantly reduce bone loss at the femur neck and trochanter.

Effects of low-dose B vitamins plus betaine supplementation on lowering homocysteine concentrations among Chinese adults with hyperhomocysteinemia: a randomized, double-blind, controlled preliminary clinical trial.

PURPOSE: To test the hypothesis that daily supplementation with low-dose B vitamins plus betaine could significantly reduce plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia and free from background mandatory folic acid fortification. METHODS: One hundred apparently healthy adults aged 18-65 years with hyperhomocysteinemia were recruited in South China from July 2019 to June 2021. They were randomly assigned to either the supplement group (daily supplementation: 400 µg folic acid, 8 mg vitamin B6, 6.4 µg vitamin B12 and 1 g betaine) or the placebo group for 12 weeks. Fasting venous blood was collected at baseline, week 4 and week 12 to determine the concentrations of homocysteine, folate, vitamin B12 and betaine. Generalized estimation equations were used for statistical analysis. RESULTS: Statistically significant increments in blood concentrations of folate, vitamin B12 and betaine after the intervention in the supplement group indicated good participant compliance. At baseline, there were no significant differences in plasma homocysteine concentration between the two groups (P = 0.265). After 12-week supplementation, compared with the placebo group, there was a significant reduction in plasma homocysteine concentrations in the supplement group (mean group difference - 3.87; covariate-adjusted P = 0.012; reduction rate 10.1%; covariate-adjusted P < 0.001). In the supplement group, the decreased concentration of plasma homocysteine was associated with increments of blood concentrations of both folate (ß = -1.680, P = 0.004) and betaine (ß = -1.421, P = 0.020) after 12 weeks of supplementation. CONCLUSIONS: Daily supplementation with low-dose B vitamins plus betaine for 12 weeks effectively decreased plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT03720249 on October 25, 2018. Website: https://clinicaltrials.gov/ct2/show/NCT03720249 .

Greater habitual resveratrol intakes were associated with lower risk of hip fracture- a 1:1 matched case-control study in Chinese elderly.

The aim of the study was to testify the association of dietary resveratrol (RSV) intakes with hip fracture risk in Chinese elderly. This was a 1:1 age- and gender- matched case-control study. Eligible cases were newly diagnosed patients of hip fracture. Dietary assessment was made by a 79-item validated food frequency questionnaire. Habitual RSV intakes were estimated as the sum of trans- and cis- isomers of resveratrol and piceid according to the available database. Multivariable conditional logistic regression was applied to examine the relationship of dietary RSV and RSV-rich foods with hip fracture risk. A total of 1,070 pairs of hip fracture incident cases and controls were recruited and 1,065 were included for analysis. Compared with the lowest group, total RSV in the highest quartile group had significantly reduced hip fracture risk by 66.3% (OR: 0.337, 0.222 ~ 0.571, ptrend < 0.001). Similar findings were observed for cis- and trans-RSV, cis- and trans-Piceid, as well as RSV-rich foods (grapes, apples and nuts) respectively. Subgroup analysis suggested more evident findings among female and less obese participants. Our findings demonstrated that higher habitual RSV intakes and RSV-rich foods, even in a relatively low amount, were associated with reduced risk of hip fracture in Chinese elderly.

Comparative Analysis of Mitogenomes of Chironomus (Diptera: Chironomidae).

(1) Background: Chironomids are biological indicators, playing an important role in monitoring and assessing the changes in water ecosystems. Mitochondrial genomes have been widely applied as a molecular marker to analyze the taxonomy and phylogeny of insects. However, knowledge of the mitogenomes of Chironomus species is scarce at present, which limits our understanding of the evolutionary relationships among Chironomus. (2) Methods: In our study, the mitogenomes and their basic structure of 12 Chironomus species and one Microchironomus species were newly sequenced. Combined with reported mitogenomes, a total of 15 mitogenomes of Chironomus were selected for a comparative mitogenomic analysis and phylogenetic reconstruction of Chironomus. (3) Results: Each mitogenome of the Chironomus species has the typical 37 genes and a control region. The basic structure of the whole mitogenomes of Chironomus species is relatively conservative, and the genetic arrangements stay the same as the ancestral mitogenome. (4) Conclusions: Our study enriches the library of mitogenomes of chironomids and provides a valuable resource for understanding the evolutionary history of Chironomus.

High-Performance Turn-On Fluorescent Metal-Organic Framework for Detecting Trace Water in Organic Solvents Based on the Excited-State Intramolecular Proton Transfer Mechanism.

Simple, fast, and sensitive detection of trace water in organic solvents is an urgent requirement for chemical industries. Herein, combining the unusual excited-state intramolecular proton transfer (ESIPT) mechanism with the effective strategy of pore space partition, for the first time, we construct a powerful fluorescent metal-organic framework (SNNU-301) probe with excellent water stability. The SNNU-301 probe shows a remarkable performance for turn-on ESIPT-based fluorescence response to water in nine common organic solvents, exhibiting wide linear ranges, low limit of detection values, and ultrafast response, especially in dimethyl sulfoxide (0-5.2%; 0.011%, v/v; 110 s). The typical ESIPT-sensitive linker 2,5-dihydroxyterephthalate (DHBDC) imparts it with discriminative detection properties via enol-keto tautomerism, and light-responsive triangular tri(pyridin-4-yl)-amine (TPA) realizes pore space partition. The theoretical calculation gives an in-depth explanation about the proton transfer mechanism. Comparative experiments and GCMC simulation provide evidence that the synergy of the ESIPT process and TPA of the framework further boosts its performance effectively. Definitely, this work not only offers a promising candidate with fast detection speed, high sensitivity, excellent universality, and visual observation for the determination of water in organic solvents but also provides valuable guidance for the design of high-performance fluorescent probes.

Triterpenoids, steroids and other constituents from Euphorbia kansui and their anti-inflammatory and anti-tumor properties.

Six undescribed triterpenoids (euphokanols A-F), two undescribed C21-steroidal glycosides (euphokanosides A and B), together with fifty-four known compounds were isolated from the roots of Euphorbia kansui. Their structures were demonstrated by extensive spectroscopic data (1D, 2D NMR and HR-ESI-MS), and the absolute configuration of euphokanol A was elucidated based on electronic circular dichroism (ECD) calculation. Among them, euphokanol A was a tetracyclic triterpenoid with a 5,10-epoxy moiety and concurrent rearrangement of Me-19(10 â†’ 9) and Me-30 (14 â†’ 8), while euphokanols B and C were rare 19(10 â†’ 9) abeo-tirucallane-type triterpenoids with Δ5(10) double bonds and 7,8-epoxy moieties. In addition, ten C21-steroidal glycosides were isolated from Euphorbia plants for the first time. Moreover, cynotophylloside B, caudatin, 5α,8α-epidioxy-22E-ergosta-6,22-diene-3ß-ol, 6ß,7ß-epoxy-3ß,4ß,5ß-trihydroxyl-20-deoxyingenol, 13-hydroxyingenol-3-(2,3- dimethylbutanoate)-13-dodecanoate, ingenol, 3-O-benzoyl-13-O-dodecanoateingenol, 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol, 20-O-acetylingenol and 20- deoxyingenol exhibited significant inhibition on NO production with IC50 values of 9.10, 17.38, 1.71, 0.55, 0.57, 12.22, 0.56, 0.30, 11.21 and 2.98 µM, respectively. Furthermore, wilfoside KIN, cynsaccatol L, kanesulone A, and 3ß,7ß,15ß-triacetyloxy-5α-benzoyloxy-2α,8α-dihydroxyjatropha-6(17),11E-diene-9, 14-dione showed cytotoxicity against HepG2 cell line, with IC50 values of 12.55, 12.61, 18.24 and 18.26 µM, respectively. 13-Hydroxyingenol-3-(2,3-dimethylbutanoate)-13- dodecanoate exhibited anti-proliferation activity on MCF-7 cell line with an IC50 value of 17.12 µM. Specifically, euphol selectively inhibited the growth of human glioma stem cells (GSC-3# and GSC-12#), with IC50 values of 8.89 and 13.00 µM, respectively.

Serum trimethylamine-N-oxide is associated with incident type 2 diabetes in middle-aged and older adults: a prospective cohort study.

BACKGROUND: The role of trimethylamine-N-oxide (TMAO) in the development of diabetes remains controversial, and prospective data are few. We aimed to investigate the association between serum TMAO and incident type 2 diabetes in middle-aged and older adults. METHODS: This study was based on the Guangzhou Nutrition and Health Study (GNHS), a community-based prospective cohort study in China. A total of 2088 diabetes-free participants aged 40-75 years were included from 2008 to 2010. Incident type 2 diabetes was ascertained during follow-up visits. Baseline serum TMAO was measured by high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for diabetes across tertiles of serum TMAO were calculated using Cox proportional hazard models. Prospective associations of serum TMAO with changes in glycemic traits (fasting glucose, HbA1c, insulin, HOMA-IR) over time were estimated using linear mixed-effects models (LMEMs). RESULTS: We ascertained 254 incident type 2 diabetes cases during a median follow-up of 8.9 years. The median (interquartile range) of serum TMAO was 1.54 (0.86-2.91) µmol/L. From the first to the third tertile of serum TMAO, the multivariable-adjusted HRs for diabetes were 1.00 (reference), 1.17 (95% CI: 0.84-1.61), and 1.42 (95% CI: 1.03-1.96) (P-trend = 0.031). LMEMs showed that the estimated yearly change in fasting glucose was 0.011 (0.001-0.022) mmol/L/y in the highest tertile of serum TMAO, compared with the lowest tertile (P-interaction = 0.044). Serum TMAO was not associated with longitudinal changes in HbA1c, insulin or HOMA-IR. CONCLUSIONS: Our findings suggested that higher serum TMAO was associated with a higher risk of type 2 diabetes and an increase in fasting glucose among middle-aged and older Chinese adults. TRIAL REGISTRATION: NCT03179657. https://clinicaltrials.gov/ct2/show/NCT03179657?term=NCT03179657&draw=2&rank=1.

Prefabricated 3D-Printed Tissue-Engineered Bone for Mandibular Reconstruction: A Preclinical Translational Study in Primate.

The advent of three dimensionally (3D) printed customized bone grafts using different biomaterials has enabled repairs of complex bone defects in various in vivo models. However, studies related to their clinical translations are truly limited. Herein, 3D printed poly(lactic-co-glycolic acid)/ß-tricalcium phosphate (PLGA/TCP) and TCP scaffolds with or without recombinant bone morphogenetic protein -2 (rhBMP-2) coating were utilized to repair primate's large-volume mandibular defects and compared efficacy of prefabricated tissue-engineered bone (PTEB) over direct implantation (without prefabrication). 18F-FDG PET/CT was explored for real-time monitoring of bone regeneration and vascularization. After 3-month's prefabrication, the original 3D-architecture of the PLGA/TCP-BMP scaffold was found to be completely lost, while it was properly maintained in TCP-BMP scaffolds. Besides, there was a remarkable decrease in the PLGA/TCP-BMP scaffold density and increase in TCP-BMP scaffolds density during ectopic (within latissimus dorsi muscle) and orthotopic (within mandibular defect) implantation, indicating regular bone formation with TCP-BMP scaffolds. Notably, PTEB based on TCP-BMP scaffold was successfully fabricated with pronounced effects on bone regeneration and vascularization based on radiographic, 18F-FDG PET/CT, and histological evaluation, suggesting a promising approach toward clinical translation.

Perilla Leaf Extract Attenuates Asthma Airway Inflammation by Blocking the Syk Pathway.

Perilla frutescens (L.) Britton is a classic herbal plant used widely against asthma in China. But its mechanism of beneficial effect remains undermined. In the study, the antiallergic asthma effects of Perilla leaf extract (PLE) were investigated, and the underlying mechanism was also explored. Results showed that PLE treatment significantly attenuated airway inflammation in OVA-induced asthma mice, by ameliorating lung pathological changes, inhibiting recruitment of inflammatory cells in lung tissues and bronchoalveolar lavage fluid (BALF), decreasing the production of inflammatory cytokines in the BALF, and reducing the level of immunoglobulin in serum. PLE treatment suppressed inflammatory response in antigen-induced rat basophilic leukemia 2H3 (RBL-2H3) cells as well as in OVA-induced human peripheral blood mononuclear cells (PBMCs). Furthermore, PLE markedly inhibited the expression and phosphorylation of Syk, NF-κB, PKC, and cPLA2 both in vivo and in vitro. By cotreating with inhibitors (BAY61-3606, Rottlerin, BAY11-7082, and arachidonyl trifluoromethyl ketone) in vitro, results revealed that PLE's antiallergic inflammatory effects were associated with the inhibition of Syk and its downstream signals NF-κB, PKC, and cPLA2. Collectively, the present results suggested that PLE could attenuate allergic inflammation, and its mechanism might be partly mediated through inhibiting the Syk pathway.