Current research efforts, although limited, clearly indicate that the gut microbiota may be implicated in bone metabolism, and therefore, further exploration of this relationship is a promising area of focus in bone health and osteoporosis research. Although most existing studies investigate this relationship using animal models, human studies are both needed and on the horizon.

Calcium is an important integrative component of the human body and critical for human health. It has been well established that calcium intake is helpful in the prevention and treatment of osteoporosis, which has become one of the most serious public health problems across the world. However, community-dwelling adults with and without osteoporosis are rarely concerned or even not aware of the potential side effects of high or inappropriate doses of calcium intake. Some recent studies have revealed that excessive calcium intake might increase the risks of cardiovascular diseases. The purpose of this article was to review the health benefits, costs, and consequences of calcium supplementation on osteoporosis/osteoporotic fractures, cardiovascular events, kidney stones, gastrointestinal diseases, and other important diseases. In the end, we suggest that calcium supplementation should be prescribed and taken cautiously, accounting for individual patients’ risks and benefits. Clearly, further studies are needed to examine the health effects of calcium supplementation to make any solid recommendations for people of different genders, ages, and ethnicities.

BACKGROUND AND PURPOSE Intracellular pharmacokinetics of anticancer drugs in multi‐drug resistance (MDR) cancer cells is hugely important in the evaluation and improvement of drug efficacy. By using adriamycin as a probe drug in MDR cancer cells, we developed a cellular pharmacokinetic‐pharmacodynamic (PK‐PD) model to reveal the correlation between cellular pharmacokinetic properties and drug resistance. In addition, the ability of 20(S)‐ginsenoside Rh2 (20(S)‐Rh2) to reverse MDR was further investigated. EXPERIMENTAL APPROACH The cellular pharmacokinetics of adriamycin were analysed visually and quantitatively in human breast cancer cells MCF‐7 and in adriamycin‐resistant MCF‐7 (MCF‐7/Adr) cells. Mitochondria membrane potential was assayed to evaluate the apoptotic effect of adriamycin. Subsequently, a PK‐PD model was developed via MATLAB. KEY RESULTS Visual and quantitative data of the dynamic subcellular distribution of adriamycin revealed that it accumulated in cells, especially nuclei, to a lesser and slower extent in MCF‐7/Adr than in MCF‐7 cells. 20(S)‐Rh2 increased the rate and amount of adriamycin entering cellular/subcellular compartments in MCF‐7/Adr cells through inhibition of P‐glycoprotein (P‐gp) activity, in turn augmenting adriamycin‐induced apoptosis. The integrated PK‐PD model mathematically revealed the pharmacokinetic mechanisms of adriamycin resistance in MCF‐7/Adr cells and its reversal by 20(S)‐Rh2. CONCLUSIONS AND IMPLICATIONS P‐gp, which is overexpressed and functionally active at cellular/subcellular membranes, influences the cellular pharmacokinetic and pharmacological properties of adriamycin in MCF‐7/Adr cells. Inhibition of P‐gp activity represents a key mechanism by which 20(S)‐Rh2 attenuates adriamycin resistance. Even more importantly, our findings provide a new strategy to explore the in‐depth mechanisms of MDR and evaluate the efficacy of MDR modulators.

Hierarchical Fe2O3 and SnO2 nanostructures have shown great potential for applications in high-performance ion batteries because of their superiority, including wide resources, facile preparation, environmental friendliness, and high energy density. However, some severe challenges, such as rapid capacity decay due to volume expansion upon cycling and poor conductivity, limit their rate performance. To address this issue, multishelled Fe2O3@SnO2@C (FSC) nanotubes were designed and synthesized by using a template method and Ostwald interaction. The as-prepared FSC nanotubes can deliver a high capacity of 1659 mA h g–1 at a current density of 200 mA g–1 and a high reversible capacity of 818 mA h g–1 at 2000 mA g–1 for lithium-ion batteries. Particularly, a high specific capacity of 1024 mA h g–1 is still maintained after 100 charging/discharging cycles at 200 mA g–1. Applied in sodium-ion batteries, the multishelled FSC nanotubes manifest a high specific capacity of 449 mA h g–1 after 180 cycles at 50 mA g–1. Such excellent performances of the as-fabricated FSC nanotubes may be due to the unique multishelled tubular structure, porous characteristics, and high specific surface area. Therefore, the present work provides an outstanding method to improve the energy storage performance of metal oxide composites and other types of nanocomposites.

Meropenem is used to manage postneurosurgical meningitis, but its population pharmacokinetics (PPK) in plasma and cerebrospinal fluid (CSF) in this patient group are not well-known. Our aims were to (i) characterize meropenem PPK in plasma and CSF and (ii) recommend favorable dosing regimens in postneurosurgical meningitis patients. Eighty-two patients were enrolled to receive meropenem infusions of 2 g every 8 h (q8h), 1 g q8h, or 1 g q6h for at least 3 days. Serial blood and CSF samples were collected, and concentrations were determined and analyzed via population modeling. Probabilities of target attainment (PTA) were predicted via Monte Carlo simulations, using the target of unbound meropenem concentrations above the MICs for at least 40% of dosing intervals in plasma and at least of 50% or 100% of dosing intervals in CSF. A two-compartment model plus another CSF compartment best described the data. The central, intercentral/peripheral, and intercentral/CSF compartment clearances were 22.2 liters/h, 1.79 liters/h, and 0.01 liter/h, respectively. Distribution volumes of the central and peripheral compartments were 17.9 liters and 3.84 liters, respectively. The CSF compartment volume was fixed at 0.13 liter, with its clearance calculated by the observed drainage amount. The multiplier for the transfer from the central to the CSF compartment was 0.172. Simulation results show that the PTAs increase as infusion is prolonged and as the daily CSF drainage volume decreases. A 4-hour infusion of 2 g q8h with CSF drainage of less than 150 ml/day, which provides a PTA of >90% for MICs of ≤8 mg/liter in blood and of ≤0.5 mg/liter or 0.25 mg/liter in CSF, is recommended. (This study has been registered at ClinicalTrials.gov under identifier NCT02506686.)

Our study provided evidence for shared genetic loci between T2D and AD in European subjects by using cFDR and ccFDR analyses. These results may provide novel insight into the etiology and potential therapeutic targets of T2D and/or AD.

Background Clinical and epidemiological findings point to an association between type 2 diabetes (T2D) and low birth weight. However, the nature of the relationship is largely unknown. The aim of this study was to identify novel single nucleotide polymorphisms (SNPs) in T2D and birth weight, and their pleiotropic loci. Methods A pleiotropy-informed conditional false discovery rate (cFDR) method was applied to two independent genome-wide association studies (GWAS) summary statistics of T2D (n = 149 821) and birth weight (n = 26 836). Results A conditional Q–Q plot showed strong enrichment of genetic variants in T2D conditioned on different levels of association with birth weight. 133 T2D-associated SNPs, including 120 novel SNPs, were identified with a significance threshold of cFDR < 0.05; 13 significant birth weight-associated SNPs, including 12 novel SNPs (cFDR < 0.05) were identified. Conjunctional cFDR (ccFDR) analysis identified nine pleiotropic loci, including seven novel loci, shared by both T2D and birth weight (ccFDR < 0.05). Two novel SNPs located at the CDK5 regulatory subunit-associated protein 1-like 1 (CDKAL1; rs1012635; cFDR < 0.05) and adenylate cyclase 5 (ADCY5; rs4677887; cFDR < 0.05) genes are of note. These two genes increase the risk of T2D and low birth weight through the pathway of the “fetal insulin hypothesis.” Conclusion Several pleiotropic loci were identified between T2D and birth weight by leveraging GWAS results. The results make it possible to explain a greater proportion of trait heritability and improve our understanding of the shared pathophysiology between T2D and birth weight.

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