Ethyl 2-[(tert-but­oxy­carbon­yl)amino]­thia­zole-5-carboxyl­ate

In the crystal of the title compound, C11H16N2O4S, molecules are linked via pairs of N—H⋯N hydrogen bonds to form inversion dimers. The dimers are linked by a weak C—H⋯O interaction to form chains propagating along direction [100]

Effects of high-intensity interval training, moderate-intensity continuous training, and guideline-based physical activity on cardiovascular metabolic markers, cognitive and motor function in elderly sedentary patients with type 2 diabetes (HIIT-DM): a protocol for a randomized controlled trial

Background and objectiveSedentary behavior is of increasing concern in older patients with type 2 diabetes mellitus (T2DM) due to its potential adverse effects on cardiovascular health, cognitive function, and motor function. While regular exercise has been shown to improve the health of individuals with T2DM, the most effective exercise program for elderly sedentary patients with T2DM remains unclear. Therefore, the objective of this study was to assess the impact of high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and guideline-based physical activity programs on the cardiovascular health, cognitive function, and motor function of this specific population.MethodsThis study will be a randomized, assessor-blind, three-arm controlled trial. A total of 330 (1:1:1) elderly sedentary patients diagnosed with T2DM will be randomly assigned the HIIT group (10 × 1-min at 85–95% peak HR, intersperse with 1-min active recovery at 60–70% peak HR), MICT (35 min at 65–75% peak HR), and guideline-based group (guideline group) for 12 weeks training. Participants in the guideline group will receive 1-time advice and weekly remote supervision through smartphones. The primary outcomes will be the change in glycosylated hemoglobin (HbA1c) and brain-derived neurotrophic factor (BDNF) after 12-weeks. Secondary outcomes will includes physical activity levels, anthropometric parameters (weight, waist circumference, hip circumference, and body mass index), physical measurements (fat percentage, muscle percentage, and fitness rate), cardiorespiratory fitness indicators (blood pressure, heart rate, vital capacity, and maximum oxygen), biochemical markers (high-density lipoprotein, low-density lipoprotein, triglycerides, total cholesterol, and HbA1c), inflammation level (C-reactive protein), cognitive function (reaction time and dual-task gait test performance), and motor function (static balance, dynamic balance, single-task gait test performance, and grip strength) after 12 weeks.DiscussionThe objective of this study is to evaluate the effect of 12 weeks of HIIT, MICT, and a guideline-based physical activity program on elderly sedentary patients diagnosed with T2DM. Our hypothesis is that both HIIT and MICT will yield improvements in glucose control, cognitive function, cardiopulmonary function, metabolite levels, motor function, and physical fitness compared to the guideline group. Additionally, we anticipate that HIIT will lead to greater benefits in these areas. The findings from this study will provide valuable insights into the selection of appropriate exercise regimens for elderly sedentary individuals with T2DM.Ethics and disseminationThis study has been approved by the Ethics Review Committee of the Reproductive Hospital Affiliated with China Medical University (approval number: 202203). Informed consent will be obtained from all participants or their guardians. Upon completion, the authors will submit their findings to a peer-reviewed journal or academic conference for publication.Clinical trial registrationChinese Clinical Trial Registry, identifier ChiCTR2200061573

Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain

The α-aminoamide family of sodium ion channel blockers have exhibited analgesic effects on neuropathic pain. Here, a series of novel α-aminoamides containing an indole ring were designed and synthesized. These compounds were evaluated in mice using a formalin test and they exhibited significant anti-allodynia activities. However, the analgesic mechanism of these compounds remains unclear; a subset of the synthesized compounds can only moderately inhibit the sodium ion channel, Nav1.7, in a whole-cell patch clamp assay. Overall, these results suggest that introduction of an indole moiety to α-aminoamide derivatives can significantly improve their bioactivity and further study is warranted

Synthesis and Evaluation of Novel Biased μ-Opioid-Receptor (μOR) Agonists

‘Biased’ ligands of G protein-coupled receptors (GPCRs) represent a type of promising analgesic with reduced on-target side effects. PZM21, a potent μ-opioid-receptor (μOR)-biased agonist with a new chemical scaffold compared to classic opioids, has been identified as a therapeutic lead molecule for treating pain. In the current study, novel PZM21 analogues were synthesized and evaluated for their in vitro and in vivo efficacy. Novel compound 7a and PZM21 demonstrated undetectable β-arrestin-2 recruitment, however, their analgesic effects need to be further confirmed. Compounds 7b, 7d, and 7g were stronger analgesics than PZM21 in both the mouse formalin injection assay and the writhing test. Compound 7d was the most potent analogue, requiring a dose that was 1/16th to 1/4th of that of PZM21 for its analgesic activity in the two assays, respectively. Therefore, compound 7d could serve as a lead to develop new biased μOR agonists for treating pain

Greatly enhanced dielectric charge storage capabilities of layered polymer composites incorporated with low loading fractions of ultrathin amorphous iron phosphate nanosheets

Two-dimensional nanomaterials are promising fillers for dielectric nanocomposites because of their high specific surface areas which can induce strong interfacial polarization and result in improved dielectric permittivity. In this work, ultrathin amorphous FePO4 nanosheets with a thickness of about 3.7 nm are successfully obtained using a one-step solvothermal method and are further dispersed into a P(VDF-HFP) matrix, forming FePO4/P(VDF-HFP) nanocomposites. Obviously enhanced dielectric permittivities are achieved owing to the strong interfacial polarization at the huge interfaces between the FePO4 nanosheets and the P(VDF-HFP) matrix. A greatly enhanced dielectric permittivity of 18.5@10 kHz, which is about 240% that of the P(VDF-HFP) matrix, is obtained in the composite with merely 2 wt% FePO4 nanosheets. Furthermore, bilayer paraelectric/ferroelectric composites, in which pure polyetherimide acts as the paraelectric layer and the FePO4/P(VDF-HFP) composite as the ferroelectric layer, are fabricated. It is found that, the synergistic effect between the two layers results in a substantially suppressed loss and elevated breakdown strengths, as well as obviously improved energy density and discharge efficiency in comparison with the single layer FePO4/P(VDF-HFP) composites. Consequently, a high energy density of 7.58 J cm(-3) and a high discharge efficiency of 81.6% are concurrently achieved in the bilayer composite with merely 0.5 wt% FePO4 nanosheets. The excellent dielectric energy storage performances make these composites promising candidates for advanced electrostatic capacitors

Electrode design for multimode suppression of aluminum nitride tuning fork resonators

This paper is focused on electrode design for piezoelectric tuning fork resonators. The relationship between the performance and electrode pattern of aluminum nitride piezoelectric tuning fork resonators vibrating in the in-plane flexural mode is investigated based on a set of resonators with different electrode lengths, widths, and ratios. Experimental and simulation results show that the electrode design impacts greatly the multimode effect induced from torsional modes but has little influence on other loss mechanisms. Optimizing the electrode design suppresses the torsional mode successfully, thereby increasing the ratio of impedance at parallel and series resonant frequencies (Rp/Rs) by more than 80% and achieving a quality factor (Q) of 7753, an effective electromechanical coupling coefficient (kteff2) of 0.066%, and an impedance at series resonant frequency (Rm) of 23.6 kΩ. The proposed approach shows great potential for high-performance piezoelectric resonators, which are likely to be fundamental building blocks for sensors with high sensitivity and low noise and power consumption

Effects of Dietary Phytosterol Supplementation on the Productive Performance, Egg Quality, Length of Small Intestine, and Tibia Quality in Aged Laying Hens

This study aimed at investigating the effects of phytosterols on the productive performance, egg quality, length of small intestine, and tibia quality in aged laying hens. A total of 960 Dawu Jinfeng commercial laying hens (75 weeks of age) were randomly assigned to three groups. Each group had 16 replicates and every replicate contained four cages (five birds/cage). The control group hens received the basal diet without phytosterols. The hens in the experimental groups received a diet containing phytosterols at concentrations of 20 mg/kg and 40 mg/kg for 7 weeks. The results showed that phytosterols had a linearly increasing effect on egg weight, eggshell surface area, albumen height, and haugh unit at week 5 of experiment (p p p p > 0.1). The results of tibia quality detected by micro-CT also showed no difference in the treatment of phytosterols. Therefore, supplementation with 20 mg/kg phytosterols in the diet improves egg quality and increases the length of small intestine, but has no effects on the quality of the tibia

Synthesis and Biological Evaluation of Novel 10-Substituted-7-ethyl-10-hydroxycamptothecin (SN-38) Prodrugs

In an attempt to improve the antitumor activity and reduce the side effects of irinotecan (2), novel prodrugs of SN-38 (3) were prepared by conjugating amino acids or dipeptides to the 10-hydroxyl group of SN-38 via a carbamate linkage. The synthesized compounds completely generated SN-38 in pH 7.4 buffer or in human plasma, while remaining stable under acidic conditions. All prodrug compounds demonstrated much greater in vitro antitumor activities against HeLa cells and SGC-7901 cells than irinotecan. The most active compounds, 5h, 7c, 7d, and 7f, exhibited IC50 values that were 1000 times lower against HeLa cells and 30 times lower against SGC-7901 cells than those of irinotecan, and the inhibitory activities of these prodrugs against acetylcholinesterase (AchE) were significantly reduced, with IC50 values more than 6.8 times greater than that of irinotecan. In addition, compound 5e exhibited the same level of tumor growth inhibitory activity as irinotecan (CPT-11) in a human colon xenograft model in vivo