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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., (© 2024. The Author(s).)

Nicotinic acetylcholine receptors (nAChRs) regulate pain pathways with various outcomes depending on receptor subtypes, neuron types, and locations. But it remains unknown whether α4β2 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-β-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., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

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-β-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.

Aim: To assess "top-down" treatment for deep remission of early moderate to severe Crohn's disease (CD) by double balloon enteroscopy., Methods: Patients with early active moderate to severe ileocolonic CD received either infusion of infliximab 5 mg/kg at weeks 0, 2, 6, 14, 22 and 30 with azathioprine from week 6 onwards (Group I), or prednisone from week 0 as induction therapy with azathioprine from week 6 onwards (Group II). Endoscopic evaluation was performed at weeks 0, 30, 54 and 102 by double balloon enteroscopy. The primary endpoints were deep remission rates at weeks 30, 54 and 102. Secondary endpoints included the time to achieve clinical remission, clinical remission rates at weeks 2, 6, 14, 22, 30, 54 and 102, and improvement of Crohn's Disease Endoscopic Index of Severity scores at weeks 30 and 54 relative to baseline. Intention-to-treat analyses of the endpoints were performed., Results: Seventy-seven patients were enrolled, with 38 in Group I and 39 in Group II. By week 30, deep remission rates were 44.7% and 17.9% in Groups I and II, respectively (P = 0.011). The median time to clinical remission was longer for patients in Group II (14.2 wk) than for patients in Group I (6.8 wk, P = 0.009). More patients in Group I were in clinical remission than in Group II at weeks 2, 6, 22 and 30 (2 wk: 26.3% vs 2.6%; 6 wk: 65.8% vs 28.2%; 22 wk: 71.1% vs 46.2%; 30 wk: 68.4% vs 43.6%, P < 0.05). The rates of clinical remission and deep remission were greater at weeks 54 and 102 in Group I, but the differences were insignificant., Conclusion: Top-down treatment with infliximab and azathioprine, as compared with corticosteroid and azathioprine, results in higher rates of earlier deep remission in early CD.

Variable-charge (v-c) soils in subtropical areas contain considerable amounts of iron/aluminum (Fe/Al) oxides that can strongly influence the fate of heavy metals in agricultural ecosystems. However, the relationship between heavy metal accumulation in vegetables and the geochemical factors associated with v-c soils in subtropical regions remains unknown. The present study investigated heavy metal accumulation under field conditions in the Pearl River Delta (PRD) by measuring the content of 8 heavy metals (zinc (Zn), arsenic (As), copper (Cu), mercury (Hg), lead (Pb), chromium (Cr), nickel (Ni) and cadmium (Cd)) in 43 pairs of v-c soil and vegetable (balsam pear and cowpea) samples. Soil physicochemical properties including pH, texture, organic matter and oxide minerals (Fe2O3, SiO2, Al2O3, CaO, MgO, K2O and Na2O) were also analyzed. Heavy metal accumulation from soil to vegetables was assessed based on bioconcentration factors (BCFs). The results showed that soil extractable Fe, oxide minerals and chemical weathering indices of v-c soils strongly affected heavy metal accumulation, whereas the content of Zn, Cu, Cr and Ni in vegetables was strongly affected by the soil clay content. Significant correlations were found between the BCFs of heavy metals and oxide minerals. However, no significant relationship was found between pH and heavy metal accumulation (except for Cu) in balsam pear and cowpea. Correlation analyses showed that a lower oxalate/DCB- extractable Fe content might indicate greater heavy metal (Zn, Cu, Hg, Cr and Ni) accumulation in vegetables. Therefore, it can be deduced that oxalate/DCB- extractable Fe content is a critical geochemical factor that determines the bioavailability of heavy metals and that iron biogeochemical cycles play vital roles in the fate of heavy metals in vegetable fields in this area. These findings provide new insights into the behaviors and fate of heavy metals in subtropical v-c soils and can be used to develop possible guidelines for vegetable safety management.