Associations of E-proteinoid 3 receptor genetic polymorphisms with salt sensitivity, longitudinal blood pressure changes, and hypertension incidence in Chinese adults.

The E-proteinoid 3 receptor (PTGER3), a member of the prostaglandin E2 (PGE2) subtype receptor, belongs to the G-protein-coupled superfamily of receptors. Animal studies have demonstrated its involvement in salt sensitivity by regulating sodium reabsorption. This study aimed to investigate the association between genetic variants of PTGER3 and salt sensitivity, longitudinal blood pressure (BP) changes, and the incidence of hypertension in Chinese adults. A chronic salt intake intervention was conducted involving 514 adults from 124 families in the 2004 Baoji Salt-Sensitivity Study Cohort in northern China. These participants followed a 3-day regular baseline diet, followed by a 7-day low-salt diet (3.0 g/d) and a 7-day high-salt diet (18 g/d), and were subsequently followed for 14 years. The findings revealed a significant relationship between the single nucleotide polymorphism (SNP) rs17482751 of PTGER3 and diastolic blood pressure (DBP) response to high salt intervention. Additionally, SNPs rs11209733, rs3765894, and rs2268062 were significantly associated with longitudinal changes in systolic blood pressure (SBP), DBP, and mean arterial pressure (MAP) during the 14-year follow-up period. SNP rs6424414 was significantly associated with longitudinal changes in DBP over 14 years. Finally, SNP rs17482751 showed a significant correlation with the incidence of hypertension over 14 years. These results emphasize the significant role of PTGER3 gene polymorphism in salt sensitivity, longitudinal BP changes, and the development of hypertension in the Chinese population.

Ni/Graphene Coating for Enhanced Corrosion Resistance of Metal Foam Flow Field in Simulated PEMFC Cathode Environment.

Metal foam flow field suffers serious corrosion issues in proton exchange membrane fuel cells due to its large surface area. Ni and Ni/graphene coatings are prepared under constant and gradient current modes, respectively, to improve the corrosion resistance. The effect of the electrodeposition current mode and the deposition mechanism is studied. Compared with Ni coating, Ni/graphene coating brings low corrosion current density and high coating resistance, effectively enhancing the stability of Ni foam in an acidic environment. Different from Ni coating with a single layer, Ni/graphene deposits have core-shell structure, with graphene coated on the surface of Ni nanoparticles. It is shown that graphene deposits cover the Ni particles during the electrodeposition, which protects nickel particles from agglomeration and forms an inert film on the surface of the porous structure. After an 8 h constant potential test, no significant pitting is observed on the surface of Ni/graphene coating, showing excellent anticorrosion performance. As to the effect of the deposition current mode, it is shown that more composite particles deposit on the upper layer under the gradient current mode, which brings denser protective film and fewer surface defects on the surface. Ni/graphene coating electrodeposited under a gradient current mode between 0 and 10 mA·cm-2 exhibits the lowest corrosion current densities. The values at 50 and 80 °C are only 62.9 and 26.0% of those of uncoated Ni foam, respectively.

BI-2865, a pan-KRAS inhibitor, reverses the P-glycoprotein induced multidrug resistance in vitro and in vivo.

BACKGROUND: Multidrug resistance (MDR) limits successful cancer chemotherapy. P-glycoprotein (P-gp), BCRP and MRP1 are the key triggers of MDR. Unfortunately, no MDR modulator was approved by FDA to date. Here, we will investigate the effect of BI-2865, a pan-KRAS inhibitor, on reversing MDR induced by P-gp, BCRP and MRP1 in vitro and in vivo, and its reversal mechanisms will be explored. METHODS: The cytotoxicity of BI-2865 and its MDR removal effect in vitro were tested by MTT assays, and the corresponding reversal function in vivo was assessed through the P-gp mediated KBv200 xenografts in mice. BI-2865 induced alterations of drug discharge and reservation in cells were estimated by experiments of Flow cytometry with fluorescent doxorubicin, and the chemo-drug accumulation in xenografts' tumor were analyzed through LC-MS. Mechanisms of BI-2865 inhibiting P-gp substrate's efflux were analyzed through the vanadate-sensitive ATPase assay, [125I]-IAAP-photolabeling assay and computer molecular docking. The effects of BI-2865 on P-gp expression and KRAS-downstream signaling were detected via Western blotting, Flow cytometry and/or qRT-PCR. Subcellular localization of P-gp was visualized by Immunofluorescence. RESULTS: We found BI-2865 notably fortified response of P-gp-driven MDR cancer cells to the administration of chemo-drugs including paclitaxel, vincristine and doxorubicin, while such an effect was not observed in their parental sensitive cells and BCRP or MRP1-driven MDR cells. Importantly, the mice vivo combination study has verified that BI-2865 effectively improved the anti-tumor action of paclitaxel without toxic injury. In mechanism, BI-2865 prompted doxorubicin accumulating in carcinoma cells by directly blocking the efflux function of P-gp, which more specifically, was achieved by BI-2865 competitively binding to the drug-binding sites of P-gp. What's more, at the effective MDR reversal concentrations, BI-2865 neither varied the expression and location of P-gp nor reduced its downstream AKT or ERK1/2 signaling activity. CONCLUSIONS: This study uncovered a new application of BI-2865 as a MDR modulator, which might be used to effectively, safely and specifically improve chemotherapeutic efficacy in the clinical P-gp mediated MDR refractory cancers.

Research on roller monitoring technology based on distributed fiber optic sensing system.

As one of the key components of the belt conveyor, the roller bears the task of supporting and rolling the conveyor belt, and monitoring its condition is very important. The traditional monitoring of the conveyor roller group adopts worker inspection, which has strong subjectivity. Monitoring using sensors necessitates the use of numerous sensors, which can pose wiring challenges. The use of inspection robots for monitoring results can be discontinuous, and their performance may be limited. This study proposes a fault diagnosis method for rollers based on a distributed fiber optic sensing system. By improving the traditional Isolation Forest (IForest), a framework called Incremental Majority Voting Isolation Forest (IMV-IForest) is proposed. By analyzing the optical signal, we extracted the variation patterns of roller faults over time and space, and analyzed the abnormal score distribution between fault data and normal data. Using the dataset collected on-site, we compared and analyzed IMV-IForest with the traditional IForest and the Extended Isolation Forest (E-iForest). The results indicate that the variation of the fault of the faulty roller with time and space can be used for early prediction of roller faults; determine an anomaly score threshold of 0.6; improved IForest have faster computation time and higher accuracy. Finally, to verify the effectiveness of the proposed scheme, a 3-month experiment was conducted on a 600 m long belt conveyor in a certain mine, and on-site monitoring results were obtained. By comparing with manual detection results, it was shown that the proposed method has high recognition rate for faulty idlers, with an accuracy rate of 97.92%, and can effectively diagnose faulty idlers.

Coffee, tea, and cocoa in obesity prevention: Mechanisms of action and future prospects.

Obesity, a major public health problem, causes numerous complications that threaten human health and increase the socioeconomic burden. The pathophysiology of obesity is primarily attributed to lipid metabolism disorders. Conventional anti-obesity medications have a high abuse potential and frequently deliver insufficient efficacy and have negative side-effects. Hence, functional foods are regarded as effective alternatives to address obesity. Coffee, tea, and cocoa, three widely consumed beverages, have long been considered to have the potential to prevent obesity, and several studies have focused on their intrinsic molecular mechanisms in past few years. Therefore, in this review, we discuss the mechanisms by which the bioactive ingredients in these three beverages counteract obesity from the aspects of adipogenesis, lipolysis, and energy expenditure (thermogenesis). The future prospects and challenges for coffee, tea, and cocoa as functional products for the treatment of obesity are also discussed, which can be pursued for future drug development and prevention strategies against obesity.

Chronic exposure to PM10 induces anxiety-like behavior via exacerbating hippocampal oxidative stress.

As one of the most environmental concerns, inhaled particulate matter (PM10) causes numerous health problems. However, the associations between anxiety behavior and toxicity caused by PM10 have rarely been reported so far. To investigate the changes of behavior after PM10 exposure and to identify the potential mechanisms of toxicity, PM10 samples (with doses of 15 mg/kg and 30 mg/kg) were intratracheally instilled into rats to simulate inhalation of polluted air by the lungs. After instillation for eight weeks, anxiety-like behavior was evaluated, levels of oxidative stress and morphological changes of hippocampus were measured. The behavioral results indicated that PM10 exposure induced obvious anxiety-like behavior in the open field and elevated plus maze tests. Both PM10 concentrations tested could increase whole blood viscosity and trigger hippocampal neuronal damage and oxidative stress by increasing superoxide dismutase (SOD) activities and malondialdehyde levels, and decreasing the expressions of antioxidant-related proteins (e.g., nuclear factor erythroid 2-related factor 2 (Nrf2), SOD1 and heme oxygenase 1). Furthermore, through collecting and analyzing questionnaires, the data showed that the participants experienced obvious anxiety-related emotions and negative somatic responses under heavily polluted environments, especially PM10 being the main pollutant. These results show that PM10 exposure induces anxiety-like behavior, which may be related to suppressing the Nrf2/Keap1-SOD1 pathway.

Effects of Inhomogeneous Gas Diffusion Layer Properties on the Transportation Phenomenon and Performances of Proton-Exchange Membrane Fuel Cells.

The encapsulation of the proton-exchange membrane fuel cell (PEMFC) is an essential step of fuel cell stack assembly. The selection of the assembly pressure is very important to the stack performance and life. Based on that, this paper presents a method to describe the internal physical deformation of the gas diffusion layer (GDL) after inhomogeneous pressure by using user-defined functions (UDFs). The results show that the transmission difference caused by the nonuniform GDL deformation can be clearly seen by the UDFs method, and there is an obvious transition of GDL at the interface of the channel and the rib. A three-dimensional single-channel PEMFC model is established, and an optimal assembly pressure range is obtained, between 1.5 and 2.0 MPa. The maximum thermal stress inside the cell occurs in the middle of the membrane electrode assembly and decreases as the assembly pressure increases. Furthermore, the influence of rib-channel ratios is discussed. Compared to the fuel cells with ratios of 2:1, 2:3, and 1:2, the one with 1:1 exhibits the maximum current density and the highest power density.

Self-Assembly of Wheel-Shaped Nanographdiynes and Self-Template Growth of Graphdiyne.

Graphdiyne (GDY) multilayers show stacking-style-dependent physical properties; thus, controlling the stacking style of nanostructures is crucial for utilizing their electrical, optical, and transport properties in electro-optical devices. Herein, we report the assemblies of nanographdiynes decorated with substituents with different steric hindrances to adjust the stacking style. We show that the π-stacked aggregates were influenced by peripheral substituents and the substrate. Steric hexaterphenyl-substituted nanoGDY scaffolds led to dimer structures stacked in the AB-3 configuration with a twist angle of 26.01° or the AB-1 configuration with an in-plane shift along one diyne link. With the interval replacement of steric substituents with long C12 alkyl chains, nanoGDYs were stacked in the AB-2 configuration to decrease the steric congestion, eventually leading to one-dimensional (1D) nanofibrous aggregates. Self-assembly in the presence of substrates can result in ABC-stacked nanoGDYs, which endowed us with the possibility of using nanoGDY as the template for GDY growth in a homogeneous reaction. High-resolution transmission electron microscopy (HRTEM), powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and near-infrared-ultraviolet-visible (NIR-UV-vis) absorption spectroscopy indicate that the crystalline GDY prepared in this way is a 1.18 eV bandgap semiconductor.

Associations of genetic variations in the M3 receptor with salt sensitivity, longitudinal changes in blood pressure and the incidence of hypertension in Chinese adults.

Recent studies have reported the role of the M3 muscarinic acetylcholine receptor (M3R), a member of the G-protein coupled receptor superfamily, encoded by the CHRM3 gene, in cardiac function and the regulation of blood pressure (BP). The aim of this study was to investigate the associations of CHRM3 genetic variants with salt sensitivity, longitudinal BP changes, and the development of hypertension in a Chinese population. We conducted a chronic dietary salt intervention experiment in a previously established Chinese cohort to analyze salt sensitivity of BP. Additionally, a 14-year follow-up was conducted on all participants in the cohort to evaluate the associations of CHRM3 polymorphisms with longitudinal BP changes, as well as the incidence of hypertension. The single nucleotide polymorphism (SNP) rs10802811 within the CHRM3 gene displayed significant associations with low salt-induced changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), while rs373288072, rs114677844, and rs663148 exhibited significant associations with SBP and MAP responses to a high-salt diet. Furthermore, the SNP rs58359377 was associated with changes in SBP and pulse pressure (PP) over the course of 14 years. Additionally, the 14-year follow-up revealed a significant association between the rs619288 polymorphism and an increased risk of hypertension (OR = 1.74, 95% CI: 1.06-2.87, p = .029). This study provides evidence that CHRM3 may have a role in salt sensitivity, BP progression, and the development of hypertension.

Identification of New Diterpenoids from the Pulp of Coffea arabica and Their α-Glucosidase Inhibition Activity.

Six new (1, 2, 3, 5, 6, and 8) and seven known (4, 7, 9, 10, 11, 12, and 13) diterpenoids have been identified in the pulp of Coffea arabica. The structures of new diterpenoids were elucidated by extensive spectroscopic analysis, including 1D, 2D NMR (HSQC, HMBC, 1H-1H COSY, and ROESY), HRESIMS, IR, DP4+, electronic circular dichroism, and X-ray crystallography analysis. Compound 1 is ent-labdane-type diterpenoid, whereas compounds (2-13) are ent-kaurane diterpenoids. The result of α-glucosidase inhibitory assay demonstrated that compounds (1, 3, 5, 7, and 10) have moderate inhibitory activity with IC50 values of 55.23 ± 0.84, 74.02 ± 0.89, 66.46 ± 1.05, 49.70 ± 1.02, and 76.34 ± 0.46 µM, respectively, compared to the positive control (acarbose, 51.62 ± 0.21 µM). Furthermore, molecular docking analysis has been conducted to investigate the interaction between the compounds and the receptors of α-glucosidase to interpret their mechanism of activity. This study is the first investigation that successfully discovered the presence of diterpenoids within the coffee pulp.

Association of high-normal albuminuria and vascular aging: Hanzhong adolescent hypertension study.

Normoalbuminuria has recently been associated with increased cardiovascular risk, and vascular aging is proposed as the early manifestation of cardiovascular disease. Here, the authors aimed to examine the association of high-normal albuminuria and vascular aging in a Chinese cohort. From our previously established cohort, 1942 participants with estimated glomerular filtration rate ≥60 mL/min/1.73 m2 or urinary albumin-creatinine ratio (UACR) <30 mg/g were enrolled. Brachial-ankle pulse wave velocity (baPWV) ≥1400 cm/s and/or carotid intima-media thickness (CIMT) ≥0.9 mm were used as indicators of vascular aging. Multivariate regression and receiving operating characteristic curve analysis were performed to examine the relationship between continuous and categorical UACR with vascular aging. We found an average UACR value of 8.08 (5.45-12.52) mg/g in this study. BaPWV and CIMT demonstrated positive correlations with lg-UACR (p < .05). High-normal albuminuria (10-29 mg/g) was significantly associated with the presence of vascular aging after adjusting for multiple cardiovascular confounders (OR = 1.540, 95% CI = 1.203-1.972, p = .001). In addition, a lg-UACR cutoff point of 0.918 lg(mg/g) (equal to UACR of 8.285 mg/g) was significantly associated with the presence of vascular aging and its components for all participants and those without hypertension or diabetes and without medication (p < .05). Briefly, high-normal albuminuria was significantly associated with vascular aging in this sample of Chinese adults. These findings implied the warning of elevated UACR even within normal range in clinical practice and the importance of UACR screening in normoalbuminuria for early detection and prevention of cardiovascular disease in otherwise healthy participants.

Associations of lipid accumulation product, visceral adiposity index, and triglyceride-glucose index with subclinical organ damage in healthy Chinese adults.

Background and aims: Obesity is an independent risk factor for cardiovascular disease development. Here, we aimed to examine and compare the predictive values of three novel obesity indices, lipid accumulation product (LAP), visceral adiposity index (VAI), and triglyceride-glucose (TyG) index, for cardiovascular subclinical organ damage. Methods: A total of 1,773 healthy individuals from the Hanzhong Adolescent Hypertension Study cohort were enrolled. Anthropometric, biochemical, urinary albumin-to-creatinine ratio (uACR), brachial-ankle pulse wave velocity (baPWV), and Cornell voltage-duration product data were collected. Furthermore, the potential risk factors for subclinical organ damage were investigated, with particular emphasis on examining the predictive value of the LAP, VAI, and TyG index for detecting subclinical organ damage. Results: LAP, VAI, and TyG index exhibited a significant positive association with baPWV and uACR. However, only LAP and VAI were found to have a positive correlation with Cornell product. While the three indices did not show an association with electrocardiographic left ventricular hypertrophy, higher values of LAP and TyG index were significantly associated with an increased risk of arterial stiffness and albuminuria. Furthermore, after dividing the population into quartiles, the fourth quartiles of LAP and TyG index showed a significant association with arterial stiffness and albuminuria when compared with the first quartiles, in both unadjusted and fully adjusted models. Additionally, the concordance index (C-index) values for LAP, VAI, and TyG index were reasonably high for arterial stiffness (0.856, 0.856, and 0.857, respectively) and albuminuria (0.739, 0.737, and 0.746, respectively). Lastly, the analyses of continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) demonstrated that the TyG index exhibited significantly higher predictive values for arterial stiffness and albuminuria compared with LAP and VAI. Conclusion: LAP, VAI, and, especially, TyG index demonstrated utility in screening cardiovascular subclinical organ damage among Chinese adults in this community-based sample. These indices have the potential to function as markers for early detection of cardiovascular disease in otherwise healthy individuals.

Discovery of ACE Inhibitory Peptides Derived from Green Coffee Using In Silico and In Vitro Methods.

Inhibition of angiotensin-I converting enzyme (ACE) is an important means of treating hypertension since it plays an important regulatory function in the renin-angiotensin system. The aim of this study was to investigate the ACE inhibitory effect of bioactive peptides from green coffee beans using in silico and in vitro methods. Alcalase and thermolysin were employed to hydrolyze protein extract from coffee beans. Bioactive peptides were identified by LC-MS/MS analysis coupled with database searching. The potential bioactivities of peptides were predicted by in silico screening, among which five novel peptides may have ACE inhibitory activity. In vitro assay was carried out to determine the ACE inhibitory degree. Two peptides (IIPNEVY, ITPPVMLPP) were obtained with IC50 values of 57.54 and 40.37 µM, respectively. Furthermore, it was found that two inhibitors bound to the receptor protein on similar sites near the S1 active pocket of ACE to form stable enzyme-peptide complexes through molecular docking, and the Lineweaver-Burk plot showed that IIPNEVY was a noncompetitive inhibitor, and ITPPVMLPP was suggested to be a mixed-type inhibitor. Our study demonstrated that two peptides isolated from coffee have potential applications as antihypertensive agents.

Dual-Interface Engineering in Perovskite Solar Cells with 2D Carbides.

Passivating the interfaces between the perovskite and charge transport layers is crucial for enhancing the power conversion efficiency (PCE) and stability in perovskite solar cells (PSCs). Here we report a dual-interface engineering approach to improving the performance of FA0.85 MA0.15 Pb(I0.95 Br0.05 )3 -based PSCs by incorporating Ti3 C2 Clx Nano-MXene and o-TB-GDY nanographdiyne (NanoGDY) into the electron transport layer (ETL)/perovskite and perovskite/ hole transport layer (HTL) interfaces, respectively. The dual-interface passivation simultaneously suppresses non-radiative recombination and promotes carrier extraction by forming the Pb-Cl chemical bond and strong coordination of π-electron conjugation with undercoordinated Pb defects. The resulting perovskite film has an ultralong carrier lifetime exceeding 10 µs and an enlarged crystal size exceeding 2.5 µm. A maximum PCE of 24.86 % is realized, with an open-circuit voltage of 1.20 V. Unencapsulated cells retain 92 % of their initial efficiency after 1464 hours in ambient air and 80 % after 1002 hours of thermal stability test at 85 °C.

Machine learning-assisted structure annotation of natural products based on MS and NMR data.

Covering: up to March 2023Machine learning (ML) has emerged as a popular tool for analyzing the structures of natural products (NPs). This review presents a summary of the recent advancements in ML-assisted mass spectrometry (MS) and nuclear magnetic resonance (NMR) data analysis to establish the chemical structures of NPs. First, ML-based MS/MS analyses that rely on library matching are discussed, which involves the utilization of ML algorithms to calculate similarity, predict the MS/MS fragments, and form molecular fingerprint. Then, ML assisted MS/MS structural annotation without library matching is reviewed. Furthermore, the cases of ML algorithms in assisting structural studies of NPs based on NMR are discussed from four perspectives: NMR prediction, functional group identification, structural categorization and quantum chemical calculation. Finally, the review concludes with a discussion of the challenges and the trends associated with the structural establishment of NPs based on ML algorithms.

Water Management Capacity of Metal Foam Flow Field for PEMFC under Flooding Situation.

Porous metal foam with complex opening geometry has been used as a flow field to enhance the distribution of reactant gas and the removal of water in polymer electrolyte membrane fuel cells. In this study, the water management capacity of a metal foam flow field is experimentally investigated by polarization curve tests and electrochemical impedance spectroscopy measurements. Additionally, the dynamic behavior of water at the cathode and anode under various flooding situations is examined. It is found that obvious flooding phenomena are observed after water addition both into the anode and cathode, which are alleviated during a constant-potential test at 0.6 V. Greater abilities of anti-flooding and mass transfer and higher current densities are found as the same amount of water is added at the anode. No diffusion loop is depicted in the impedance plots although a 58.3% flow volume is occupied by water. The maximum current density of 1.0 A cm-2 and the lowest Rct around 17 mΩ cm2 are obtained at the optimum state after 40 and 50 min of operation as 2.0 and 2.5 g of water are added, respectively. The porous metal pores store a certain amount of water to humidify the membrane and achieve an internal "self-humidification" function.

Comparative studies of fermented coffee fruits post-treatments on chemical and sensory properties of roasted beans in Yunnan, China.

In this study, medium roasted coffee with four different fermented coffee fruits post-treatments (dry, wet, semi-dry and hot air dry) was used as the material. Chemical profile and sensorial analysis were used to comprehensively analyze the effects of post-treatments on coffee flavor characteristics from multiple dimensions. A total of 31 water-soluble chemical components and 39 volatile compounds were identified in roasted coffee, and distinct post-treatments based on chemical orientation make coffee highly differentiated. In addition, the principal component analysis (PCA) of the chemical composition integrated data set showed that the first two principal components could explain 54.9% of the sample variability. All four post-treatments can be classified as "specialty coffees" according to the Specialty Coffee Association (SCA) protocol, with various organoleptic characteristics and flavor attributes. As a result, the fermented coffee fruits post-treatment method further determines the quality characteristics of coffee, thus meeting the needs of different niche markets.

Molecular phylogeny, divergence time, biogeography and trends in host plant usage in the agriculturally important tortricid tribe Grapholitini (Lepidoptera: Tortricidae: Olethreutinae).

The leaf-roller moth tribe Grapholitini comprises about 1200 described species and contains numerous notorious pests of fruits and seeds. The phylogeny of the tribe has been little studied using contemporary methods, and the monophyly of several genera remains questionable. In order to provide a more robust phylogenetic framework for the group, we conducted a multiple-gene phylogenetic analysis of 104 species representing 27 genera of Grapholitini and 29 outgroup species. Divergence time, ancestral area, and host plant usage were also inferred to explore evolutionary trends in the tribe. Our analyses indicate that Larisa and Corticivora, traditionally assigned to Grapholitini, are best excluded from the tribe. After removal of these two genera, the tribe is found to be monophyletic, represented by two major lineages-a Dichrorampha clade and a Cydia clade, the latter of which can be divided into seven generic groups. The genus Grapholita was found to be polyphyletic, comprising three different clades, and we propose three genera to accommodate these groups: Grapholita (sensu stricto), Aspila (formerly a subgenus of Grapholita) and Ephippiphora (formerly considered a synonym of Grapholita). We summarize each generic group, including related genera not included in our analysis, providing morphological, pheromone and food plant characters that support particular branches within the molecular hypotheses. Biogeographical analyses indicate that Grapholitini probably originated in the Nearctic, Afrotropical and Neotropical regions in the Lutetian of the middle Eocene (ca. 44.3 Ma). Our results also indicate that most groups in Grapholitini originated from Fabaceae-feeding monophagous or oligophagous ancestors, and that host plant shifts probably promoted species diversification within the tribe.

Identification and screening of novel diterpenoids from roasted arabica coffee in the regulation of lipid content in white adipocytes.

Previous studies have shown that coffee has a role in regulating lipid metabolism. However, the active compounds and pharmacological mechanism(s) are still unclear. Here, four new coffee diterpenoids (1-4) were identified from roasted arabica coffee (Coffea arabica L.) beans, and together with 31 known coffee diterpenoids (5-35), their bioactivities in the regulation of lipid content in white adipocytes were evaluated. Based on their structures and correlated bioactivities, we proposed that the α,ß-unsaturated-γ-lactone moiety and hydroxyl group at C-3 are required for the bioactivity. Furthermore, the pharmacological approaches revealed that the active new diterpenoid, dehydrocaffarolide B, inhibited the Akt/mTOR/GSK3ß pathway and arrested cells in the G0/G1 phase of the mitotic clonal expansion process during the adipocyte differentiation and maturation, eventually resulting in the blunting of lipid accumulation in the adipocytes. Collectively, our findings identified four new diterpenoids of arabica coffee and elucidated a mechanism of an active lactone-type diterpenoid in the regulation of lipid content in white adipocytes.

Associations of SGLT2 genetic polymorphisms with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors lowers blood pressure (BP) and exert a salutary effect on the salt sensitivity of BP. This study aimed to examine the associations of SGLT2 genetic variants with salt sensitivity, longitudinal BP changes and the risk of incident hypertension in Baoji Salt-Sensitive Study. A total of 514 participants were recruited when the cohort was established in 2004, and 333 participants received a dietary intervention that consisted of a 3-day usual diet followed sequentially by a 7-day low-salt diet and a 7-day high-salt diet. The cohort was then followed up for 14 years to evaluate the longitudinal BP changes and development of hypertension. We found that SGLT2 SNP rs3813007 was significantly associated with the systolic BP (SBP) responses to the low-salt diet. Over the 14 years of follow-up, SNPs rs3116149 and rs3813008 were significantly associated with the longitudinal SBP changes, and SNPs rs3116149, rs3813008, rs3813007 in SGLT2 were significantly associated with incidence of hypertension. Furthermore, gene-based analyses revealed that SGLT2 was significantly associated with hypertension incidence. Our study suggests that SGLT2 genetic polymorphisms may be involved in salt sensitivity and development of hypertension.