The impact of heat stress on the human plasma lipidome.

The year of 2023 displayed the highest average global temperatures since it has been recorded-the duration and severity of extreme heat are projected to increase. Rising global temperatures represent a major public health threat, especially to occupations exposed to hot environments, such as construction and agricultural workers, and first responders. Despite efforts of the scientific community, there is still a need to characterize the pathophysiological processes leading to heat related illness and develop biomarkers that can predict its onset. Here, we performed a plasma lipidomic analysis on male and female subjects who underwent heat tolerance testing (HTT), consisting of a 2-h treadmill walk at 5 km/h with 2% inclination at a controlled temperature of 40°C. We identified 995 lipids from 27 classes, with nearly half of all detected lipids being responsive to HTT. Lipid classes related to substrate utilization were predominantly affected by HTT, with a downregulation of triacylglycerols and upregulation of free fatty acids and acyl-carnitines (CARs). We additionally examined correlations between changes in plasma lipids by using the physiological strain index (PSI). Here, even chain CAR 4:0, 14:0 and 16:1, suggested by-products of incomplete beta oxidation, and diacylglycerols displayed the highest correlation to PSI. PSI did not correlate with plasma lactate levels, suggesting that correlations between even chain CARs and PSI is related to metabolic efficiency versus physical exertion. Overall, our results show that HTT has a strong impact on the plasma lipidome and that metabolic inefficiencies may underlie heat intolerance.

Semiconductor-Metal Phase Transition and Emergent Charge Density Waves in 1T-ZrX2 (X = Se, Te) at the Two-Dimensional Limit.

A charge density wave (CDW) is a collective quantum phenomenon in metals and features a wavelike modulation of the conduction electron density. A microscopic understanding and experimental control of this many-body electronic state in atomically thin materials remain hot topics in materials physics. By means of material engineering, we realized a dimensionality and Zr intercalation induced semiconductor-metal phase transition in 1T-ZrX2 (X = Se, Te) ultrathin films, accompanied by a commensurate 2 × 2 CDW order. Furthermore, we observed a CDW energy gap of up to 22 meV around the Fermi level. Fourier-transformed scanning tunneling microscopy and angle-resolved photoemission spectroscopy reveal that 1T-ZrX2 films exhibit the simplest Fermi surface among the known CDW materials in TMDCs, consisting only of a Zr 4d derived elliptical electron conduction band at the corners of the Brillouin zone.

Management of chronic myeloid leukemia presenting with isolated thrombocytosis and complex Philadelphia chromosome: A case report.

RATIONALE: Chronic myelogenous leukemia (CML) with thrombocytosis and complex chromosomal translocation is extremely rare in clinical setting. Here, we reported the clinical and pathological characteristics of CML patients, which were characterized by thrombocytosis and complex Philadelphia chromosome translocation. Moreover, we also introduced our therapeutic schedule for this patient as well as review relative literature. PATIENT CONCERNS: A 24-year-old female presented with night sweating, fatigue, and intermittent fever for 1 month. DIAGNOSIS: Fluorescence in situ hybridization results revealed that breakpoint cluster region (BCR)-Abelson (ABL) gene fusion in 62% of the cells and karyotyping showed a complex 3-way 46, XY, t(9;22;11) (q34;q11;q13) [19/20] translocation. This patient was diagnosed with CML complicated with thrombocytosis and complex Philadelphia chromosome translocation. INTERVENTIONS: The patients received continuously oral imatinib mesylate tablets (400 mg) once a day. OUTCOMES: After treatment with imatinib for 3 months, the BCR/ABLIS was less than 0.1% and achieved major molecular response. Moreover, the BCR/ABLIS of this patient achieved major molecular response. The BCR/ABLIS values at 6 months and 12 months were less than 0.01% and 0.0032%, respectively. And no BCR/ABL fusion was detected in the next 2 years follow-up period. LESSONS: Imatinib might represent a preferred therapeutic option for CML patients with rare thrombocytosis and complex chromosomal translocation. In addition, BCR/ABL fusion gene examination in patients with thrombocytosis might represent an effective strategy to avoid the misdiagnosis of this specific CML population.

Direct Observation of Full-Gap Superconductivity and Pseudogap in Two-Dimensional Fullerides.

Alkali-fulleride superconductors with a maximum critical temperature T_{c}∼40 K exhibit a similar electronic phase diagram to that of unconventional high-T_{c} superconductors. Here we employ cryogenic scanning tunneling microscopy to show that trilayer K_{3}C_{60} displays fully gapped strong coupling s-wave superconductivity, accompanied by a pseudogap above T_{c}∼22 K and within vortices. A precise control of the electronic correlations and potassium doping enables us to reveal that superconductivity occurs near a superconductor-Mott-insulator transition and reaches maximum at half-filling. The s-wave symmetry retains over the entire phase diagram, which, in conjunction with an abrupt decline of the superconductivity below half-filling, indicates that alkali fullerides are predominantly phonon-mediated superconductors, although the electronic correlations also come into play.

Gene expression profiling of humans under exertional heat stress: Comparisons between persons with and without exertional heat stroke.

Exertional heat stroke (EHS) is a leading cause of preventable morbidity and mortality among both athletes and warfighters. Therefore, it is important to find blood biomarkers to predict susceptibility to EHS. We compared gene expression profiling from blood cells between two groups of participants - those with and those without a history EHS - by using genome-wide microarray analysis. Subjects with a history of EHS (n = 6) and non-EHS controls without a history of EHS (n = 18) underwent a heat tolerance test and a thermoneutral exercise challenge on separate days. The heat tolerance test comprised of 2-h of walking, at 5 km/h and 2% incline, with ambient conditions set at 40 °C, 40% relative humidity; the thermoneutral test was similar, but had ambient conditions set at 22 °C. Next, we examined gene expression profiles, quantified based on arithmetic differences (post minus pre) during the heat test minus changes during the thermoneutral test. Genes related to interleukins and cellular stress were significantly down-regulated in participants with a history of EHS compared to their non-EHS counterparts. Suppression of these genes may be associated with susceptibility to exertional heat injury. Prospective research is required to determine whether similar gene expression profiling can be potentially used as blood biomarkers to predict susceptibility to EHS.

YM155 inhibits topoisomerase function.

YM155 (sepantronium bromide) has been evaluated in clinical trials as a survivin suppressant, but despite positive signals from early work, later studies were negative. Clarification of the mechanism of action of YM155 is important for its further development. YM155 affects cells in a cell cycle-specific manner. When cells are in G1, YM155 prevented their progression through the S phase, leaving the cells at G1/S when exposed to YM155. Passage through mitosis from G2 is also defective following YM155 exposure. In this study, YM155 did not behave like a typical DNA intercalator in viscosity, circular dichroism, and absorption spectroscopy studies. In addition, molecular modeling experiments ruled out YM155 DNA interaction to produce DNA intercalation. We show that YM155 inhibited topoisomerase 2α decatenation and topoisomerase 1-mediated cleavage of DNA, suggesting that YM155 inhibits the enzyme function. Consistent with these findings, DNA double-strand break repair was also inhibited by YM155.

[Effect of Soluble CD40L on Leukemia K562 Cells and Its Mechanism].

OBJECTIVE: To investigate the effect of sCD40L on biological behavior of leukemia cell line K562 and the possible mechanism. METHODS: The different concentration of sCD40L was used to treat K562 cells, and the optimum concentration of sCD40L was screened by detecting the proliferation inhibition rate of K562 cells. The optimum concentration of sCD40L was used to treat K562 cells, the cell apoptosis rate and expression level of P53 and BCL-2 were detected by flow cytometry and the expression levels of Caspase 8 and Caspase 3 were detected by ELISA. RESULTS: The optimum concentration of sCD40L was 4 µg/ml. After treated with sCD40L, the cell apoptosis rate, the expression of apoptosis-related factor P53 and the expression of Caspase 8 and Caspase 3 were significantly up-regulated in K562 cells,but the expression of BCL-2 was significantly down-regulated. CONCLUSION: 4 µg/ml sCD40L can inhibit the cell proliferation and promote the apoptosis of K562 cells, its mechanism may be related with mitochondrial and P53 pathway.