Cyclin B1/CDK1-regulated mitochondrial bioenergetics in cell cycle progression and tumor resistance.

A mammalian cell houses two genomes located separately in the nucleus and mitochondria. During evolution, communications and adaptations between these two genomes occur extensively to achieve and sustain homeostasis for cellular functions and regeneration. Mitochondria provide the major cellular energy and contribute to gene regulation in the nucleus, whereas more than 98% of mitochondrial proteins are encoded by the nuclear genome. Such two-way signaling traffic presents an orchestrated dynamic between energy metabolism and consumption in cells. Recent reports have elucidated the way how mitochondrial bioenergetics synchronizes with the energy consumption for cell cycle progression mediated by cyclin B1/CDK1 as the communicator. This review is to recapitulate cyclin B1/CDK1 mediated mitochondrial activities in cell cycle progression and stress response as well as its potential link to reprogram energy metabolism in tumor adaptive resistance. Cyclin B1/CDK1-mediated mitochondrial bioenergetics is applied as an example to show how mitochondria could timely sense the cellular fuel demand and then coordinate ATP output. Such nucleus-mitochondria oscillation may play key roles in the flexible bioenergetics required for tumor cell survival and compromising the efficacy of anti-cancer therapy. Further deciphering the cyclin B1/CDK1-controlled mitochondrial metabolism may invent effect targets to treat resistant cancers

Comparative pharmacokinetics of polymyxin B in critically ill elderly patients with extensively drug-resistant gram-negative bacteria infections

Introduction: Elderly patients are more prone to develop acute kidney injury during infections and polymyxin B (PMB)-associated nephrotoxicity than young patients. The differential response to PMB between the elderly and young critically ill patients is unknown. We aimed to assess PMB exposure in elderly patients compared with young critically ill patients, and to determine the covariates of PMB pharmacokinetics in critically ill patients.Methods: Seventeen elderly patients (age ≥ 65 years) and six young critically ill patients (age < 65 years) were enrolled. Six to eight blood samples were collected during the 12 h intervals after at least six doses of intravenous PMB in each patient. PMB plasma concentrations were quantified by high-performance liquid chromatography-tandem mass spectrometry. The primary outcome was PMB exposure as assessed by the area under the concentration-time curve over 24 h at steady state (AUCss, 0–24 h).Results and Discussion: The elderly group had lower total body weight (TBW) and higher Charlson comorbidity scores than young group. Neither AUCss, 0–24 h nor normalized AUCss, 0–24 h (adjusting AUC for the daily dose in mg/kg of TBW) was significantly different between the elderly group and young group. The half-life time was longer in the elderly patients than in young patients (11.21 vs 6.56 h respectively, p = 0.003). Age and TBW were the covariates of half-life time (r = 0.415, p = 0.049 and r = −0.489, p = 0.018, respectively). TBW was the covariate of clearance (r = 0.527, p = 0.010) and AUCss, 0–24 h (r = −0.414, p = 0.049). Patients with AUCss, 0–24 h ≥ 100 mg·h/L had higher baseline serum creatinine levels and lower TBW than patients with AUCss, 0–24 h < 50 mg·h/L or patients with AUCss, 0–24 h 50–100 mg·h/L. The PMB exposures were comparable in elderly and young critically ill patients. High baseline serum creatinine levels and low TBW was associated with PMB overdose.Trial registration: ChiCTR2300073896 retrospectively registered on 25 July 2023

Infusing Sodium Bicarbonate Suppresses Hydrogen Peroxide Accumulation and Superoxide Dismutase Activity in Hypoxic-Reoxygenated Newborn Piglets

The effectiveness of sodium bicarbonate (SB) has recently been questioned although it is often used to correct metabolic acidosis of neonates. The aim of the present study was to examine its effect on hemodynamic changes and hydrogen peroxide (H(2)O(2)) generation in the resuscitation of hypoxic newborn animals with severe acidosis.Newborn piglets were block-randomized into a sham-operated control group without hypoxia (n = 6) and two hypoxia-reoxygenation groups (2 h normocapnic alveolar hypoxia followed by 4 h room-air reoxygenation, n = 8/group). At 10 min after reoxygenation, piglets were given either i.v. SB (2 mEq/kg), or saline (hypoxia-reoxygenation controls) in a blinded, randomized fashion. Hemodynamic data and blood gas were collected at specific time points and cerebral cortical H(2)O(2) production was continuously monitored throughout experimental period. Plasma superoxide dismutase and catalase and brain tissue glutathione, superoxide dismutase, catalase, nitrotyrosine and lactate levels were assayed.Two hours of normocapnic alveolar hypoxia caused cardiogenic shock with metabolic acidosis (PH: 6.99 ± 0.07, HCO(3)(-): 8.5 ± 1.6 mmol/L). Upon resuscitation, systemic hemodynamics immediately recovered and then gradually deteriorated with normalization of acid-base imbalance over 4 h of reoxygenation. SB administration significantly enhanced the recovery of both pH and HCO(3-) recovery within the first hour of reoxygenation but did not cause any significant effect in the acid-base at 4 h of reoxygenation and the temporal hemodynamic changes. SB administration significantly suppressed the increase in H(2)O(2) accumulation in the brain with inhibition of superoxide dismutase, but not catalase, activity during hypoxia-reoxygenation as compared to those of saline-treated controls.Despite enhancing the normalization of acid-base imbalance, SB administration during resuscitation did not provide any beneficial effects on hemodynamic recovery in asphyxiated newborn piglets. SB treatment also reduced the H(2)O(2) accumulation in the cerebral cortex without significant effects on oxidative stress markers presumably by suppressing superoxide dismutase but not catalase activity

Surface Treatment on Nickel Oxide to Enhance the Efficiency of Inverted Perovskite Solar Cells

The organic-inorganic hybrid perovskites such as CH3NH3PbI3 have been considered as one of the most promising candidates for the next-generation photovoltaic materials due to its high absorption coefficient, low exciton binding energy, and long diffusion length. Herein, we have chosen NiOx as the hole transport material because metal oxides exhibit robust properties in air. We synthesized the NiOx film by a common sol-gel method. It is found that high-temperature annealing (500 degrees C) is required to ensure the perovskite solar cell (PSC) with an efficiency over 15%. Low-temperature annealing (100 degrees C) cannot convert the precursor materials to fully covered NiOx film, while the PSC based on mediate-temperature annealing (300 degrees C) NiOx has larger resistance and thus lower efficiency. Fortunately, we have found that UV-ozone treatment on the NiOx film can reduce the resistance of the device based on 300 degrees C annealed NiOx. The champion device can reach 16% efficiency with UV-ozone-treated 300 degrees C annealed NiOx. This work has made it possible to reduce the annealing temperature of the sol-gel NiOx for high-efficiency PSCs, and it is believed that this simple surface treatment can be further employed in other metal oxide-based optoelectronic devices

Optimal Investment Timing and Size of a Logistics Park: A Real Options Perspective

This paper uses a real options approach to address optimal timing and size of a logistics park investment with logistics demand volatility. Two important problems are examined: when should an investment be introduced, and what size should it be? A real option model is proposed to explicitly incorporate the effect of government subsidies on logistics park investment. Logistic demand that triggers the threshold for investment in a logistics park project is explored analytically. Comparative static analyses of logistics park investment are also carried out. Our analytical results show that (1) investors will select smaller sized logistics parks and prepone the investment if government subsidies are considered; (2) the real option will postpone the optimal investment timing of logistics parks compared with net present value approach; and (3) logistic demands can significantly affect the optimal investment size and timing of logistics park investment

Tagging single nucleotide polymorphisms in the IRF1 and IRF8 genes and tuberculosis susceptibility.

Genes encoding IRF1 and IRF8 protein have been proposed as candidate tuberculosis susceptibility genes. In order to elucidate whether the IRF1 and IRF8 variants were associated with tuberculosis susceptibility, we conducted a case-control study consisting of 495 controls and 452 ethnically matched cases with tuberculosis in a Chinese population. Seven haplotype tagging single-nucleotide polymorphisms (tagSNPs) (rs2057656; rs2706381; rs2070724; rs2070721; rs2549008; rs2549007; rs2706386) from HapMap database were analyzed, which provided an almost complete coverage of the genetic variations in the IRF1 gene. Fifteen tagSNPs (rs12924316; rs182511; rs305080; rs2292980; rs925994; rs424971; rs16939967; rs11117415; rs4843860; rs9926411; rs8064189; rs12929551; rs10514611; rs1044873; rs6638) were observed in the IRF8 gene. All these tagSNPs were genotyped by SNPstream genotyping and SNaPshot typing. None of the seven tagSNPs was individually associated with tuberculosis in the IRF1 gene. In the IRF8 gene, interestingly, we found that three tagSNPs (rs925994 and rs11117415 located in the intron region; rs10514611 located in the 3'UTR) were associated with risk of tuberculosis after Bonferroni correction. Per allele OR was 1.75 (95% CI 1.35 ~ 2.27, P = 0.002), 4.75 (95% CI 2.16 ~ 10.43, P = 0.002) and 3.39 (95% CI 1.60 ~ 7.20, P = 0.015) respectively. Luciferase reporter gene assay showed that the construct that contained the non-risk allele C of rs10514611 showed significantly higher luciferase activity than did the risk T allele (P<0.01), which implied rs10514611 was a potential functional SNP site. Our results indicated that the IRF8 gene might participate in genetic susceptibility to tuberculosis in a Chinese population

Thermal Hazard of Ionic Liquids: Modeling Thermal Decomposition Temperatures of Imidazolium Ionic Liquids via QSPR Method

Thermal hazard, which is closely related to the potential fire risk under high temperature, has become one of the most important characteristics of various ionic liquids (ILs). This study proposed a quantitative structure–property relationship (QSPR) model to predict the thermal decomposition temperature (<i>T</i>_d) of imidazolium ILs from their molecular structures. Not only the descriptors for single cation and anion but also those for describing their interactions were considered to numerically represent the structure characteristics of ILs. Genetic algorithm-based multiple linear regression was used to select the most statistically effective descriptors on the <i>T</i>_d of imidazolium ILs. The resulted model is a multilinear equation with seven variables, including two descriptors for cations, four descriptors for anions, and one interaction descriptor. The developed model was rigorously validated using multiple strategies and further extensively compared to other previously published models. The results demonstrated the robustness, validity, and satisfactory predictivity of the proposed model. The predominant structure characteristics responsible for <i>T</i>_d were also identified through model interpretation. The proposed model could be reasonably expected to reliably predict the thermal hazard of novel imidazolium ILs and provide guidance for prioritizing design and manufacture of safer ILs with desired properties