Abstract Epidemiological studies have raised the possibility of caffeine serving as a neuroprotective agent in Parkinson's disease (PD). This possibility has gained support from findings that ...dopaminergic neuron toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or other neurotoxins is attenuated by co-administration of caffeine in mice. Here we examined the time window of caffeine's neuroprotection as well as the effects of caffeine's metabolites (theophylline and paraxanthine) in the MPTP mouse model of PD. In the first experiment, caffeine pre-treatment (30 mg/kg ip) significantly attenuated MPTP-induced striatal dopamine depletion when it was given 10 min, 30 min, 1 h, or 2 h but not 6 h before MPTP (40 mg/kg ip) treatment. Meanwhile, caffeine post-treatment also significantly attenuated striatal dopamine loss when it was given 10 min, 30 min, 1 h or 2 h but not 4 h, 8 h or 24 h after MPTP injection. In the second experiment, both theophylline (10 or 20 mg/kg) and paraxanthine (10 or 30 mg/kg) administration (10 min before MPTP) significantly attenuated MPTP-induced dopamine depletion in mice, as did caffeine (10 mg/kg) treatment. Thus the metabolites of caffeine also provide neuroprotective effects in this mouse model of PD. The data suggest that if caffeine protects against putative toxin-induced dopaminergic neuron injury in humans, then precise temporal pairing between caffeine and toxin exposures may not be critical because the duration of neuroprotection by caffeine may be extended by protective effects of its major metabolites.
The intrinsic magnetic topological insulatorMnBi2Te4exhibits rich topological effects such as quantum anomalous Hall effect and axion electrodynamics. Here, by combining the use of synchrotron and ...laser light sources, we carry out comprehensive and high-resolution angle-resolved photoemission spectroscopy studies onMnBi2Te4and clearly identify its topological electronic structure. In contrast to theoretical predictions and previous studies, we observe topological surface states with diminished gap forming a characteristic Dirac cone. We argue that the topological surface states are mediated by multidomains of different magnetization orientations. In addition, the temperature evolution of the energy bands clearly reveals their interplay with the magnetic phase transition by showing interesting differences between the bulk and surface states, respectively. The investigation of the detailed electronic structure ofMnBi2Te4and its temperature evolution provides important insight into not only the exotic properties ofMnBi2Te4, but also the generic understanding of the interplay between magnetism and topological electronic structure in magnetic topological quantum materials.
Background and purpose
Neutrophils, a pivotal immune responder to ischaemic brain insult, have been involved in neuroplasticity and increase after stroke. Recombinant tissue plasminogen activator ...(r‐tPA), a promising treatment improving neuroplasticity, promotes neutrophil degranulation. However, the dynamic profile of neutrophils after r‐tPA treatment and their effect on neurological recovery after stroke are not well studied.
Methods
Cell counts of neutrophils, lymphocytes and their ratio (NLR) were measured on admission and 24 h after r‐tPA infusion in 372 consecutively recruited acute ischaemic stroke patients (mean age 64 years). Death or major disability at 3 months after stroke was diagnosed based on the modified Rankin Scale (mRS ≥ 3) obtained by neurologists who were blinded to any hospital records. The longitudinal associations of percentage increase in neutrophils, lymphocytes and the NLR with death or major disability were examined by logistic regression adjusting for covariates including neurological deficits at baseline.
Results
Neutrophils exhibited a steeper increase after r‐tPA infusion in patients with death or major disability than in those without (P < 0.001). A 10% increase in neutrophils after r‐tPA infusion was associated with an 83% increased risk for death or major disability within 3 months after stroke onset odds ratio (OR) 1.99, P = 0.009. Increased neutrophils at 24 h after r‐tPA (OR 6.30, P < 0.001 after log transformation) but not on admission significantly predicted increased risks for death or major disability within 3 months after stroke onset. A similar phenomenon was also observed for the NLR.
Conclusions
A dynamic increase in neutrophils after stroke significantly predicts 3‐month death or major disability in acute ischaemic stroke patients receiving r‐tPA treatment.
Our previous study revealed that microRNA-125a-5p plays a crucial role in regulating hepatic glycolipid metabolism by targeting STAT3 in type 2 diabetes mellitus (T2DM). Dioscin, a major active ...ingredient in Dioscoreae nipponicae rhizomes, displays various pharmacological activities, but its role in T2DM has not been reported.
The aim of this study was to investigate the effect of dioscin on T2DM and elucidate its potential mechanism.
The effect of dioscin on glycolipid metabolic disorder in insulin-induced HepG2 cells, palmitic acid-induced AML12 cells, high-fat diet- and streptozotocin- induced T2DM rats, and spontaneous T2DM KK-Ay mice were evaluated. Then, the possible mechanisms of dioscin were comprehensively evaluated.
Dioscin markedly alleviated the dysregulation of glycolipid metabolism in T2DM by reducing hyperglycemia and hyperlipidemia, improving insulin resistance, increasing hepatic glycogen content, and attenuating lipid accumulation. When the mechanism was investigated, dioscin was found to markedly elevate miR-125a-5p level and decrease STAT3 expression. Consequently, dioscin increased phosphorylation levels of STAT3, PI3K, AKT, GSK-3β, and FoxO1 and decreased gene levels of PEPCK, G6Pase, SREBP-1c, FAS, ACC, and SCD1, leading to an increase in glycogen synthesis and a decrease in gluconeogenesis and lipogenesis. The effects of dioscin on regulating miR-125a-5p/STAT3 pathway were verified by miR-125a-5p overexpression and STAT3 overexpression.
Dioscin showed potent anti-T2DM activity by improving the inhibitory effect of miR-125a-5p on STAT3 signaling to alleviate glycolipid metabolic disorder of T2DM.
High-grade serous ovarian cancer is an aggressive form of epithelial ovarian cancer (EOC), and accounts for the majority of deaths due to EOC. The critical cellular processes and underlying molecular ...mechanisms that define this malignancy remain poorly understood. Using a syngeneic murine model, we investigated the changes that accompanied the progression to increased aggressiveness induced by in vivo passage of mouse EOC cells. We found that enhanced anoikis resistance was a key cellular process associated with greater aggressiveness and tumorigenicity in vivo. Biochemical studies revealed that the enhanced anoikis resistance was associated with the activation of the Src/Akt/Erk signaling pathway. A higher rate of metabolism and autophagy were also associated with increased anoikis resistance. Blocking these pathways with specific inhibitors and/or genetic modifications significantly increased anoikis in vitro and inhibited tumor development in vivo. In addition, we demonstrated that similar signaling pathways were also involved in a human EOC cell line model. Collectively, our data suggest that anoikis resistance represents a critical and a distinguishing feature underlying the aggressiveness of ovarian cancer cells.
Rivers not only function as a conduit for the delivery of terrestrial constituents to oceans, but they also serve as an essential medium for biogeochemical processing of the constituents. While ...extensive research has been conducted on carbon transport in many rivers, little is known about carbon transformation in engineered rivers reconnected with their floodplain network. Being the largest distributary of the levee-confined Mississippi River (MR), the Atchafalaya River (AR) carries 25 % of the MR water, flowing through North America's largest freshwater swamp basin and emptying into the Gulf of Mexico. Previous studies reported that this 200-km long, 5–30-km wide river basin can remove a substantial amount of riverine nutrients and organic carbon. This study aimed to test the hypothesis that the AR emits significantly higher CO2 into the atmosphere as it flows through its extensive floodplain network than the levee-confined MR does. From January 2019 to December 2021, we conducted biweekly – monthly in-situ measurements in the lower AR at Morgan City and in the lower Mississippi River at Baton Rouge. Field measurements included partial pressure of dissolved CO2 (pCO2), water temperature, chlorophyll a, colored dissolved organic matter, dissolved oxygen, pH, and turbidity. During each field sampling, water samples were collected and analyzed for concentrations of dissolved organic and inorganic carbon (DOC and DIC). Mass transport of DOC and DIC and outgassing of CO2 were quantified for the two rivers. We found that pCO2 levels were significantly higher in the AR (mean: 3563 μatm; min-max: 1130–8650 μatm) than those in the MR (1931 μatm, 836–3501 μatm), resulting in a doubled CO2 outgassing rate in the AR (486 mmol m2 d−1) than in the MR (241 mmol m2 d−1). The AR had higher DOC (8.5 mg L−1) but lower chlorophyll a (153.9 AFU) when compared with the MR (7.5 mg L−1 and 164.0 AFU). Water temperature was constantly higher in the AR than in the MR, especially during the wintertime. Since the Mississippi-Atchafalaya River system is among the world's largest and most engineered river systems, our assessment offers a field case study to inform on the potential implications of reconnecting rivers with their floodplains networks.
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•River-floodplain connectivity affects dissolved carbon transport and transformation•Floodplains and river corridor wetlands enhance riverine DIC, DOC, and pCO2 levels•Flow and temperature have greater impacts on carbon dynamics in floodplain-linked rivers•Atchafalaya River ranks 2nd in CO2 areal emission rate among world's large rivers•Levee-confinement of rivers likely reduces riverine CO2 outgassing
► We conducted the case study on the hydrologic response to urbanization using SWAT model. ► Hydrological responses were different in different seasons and hydrological years. ► Urbanization and its ...impacts were more sensitive in the suburban basin close to city. ► Urbanization had a more remarkable impact on surface runoff than on total streamflow. ► Urbanization tended to increase peak discharge and flood volume.
The Main objective of the study is to understand and quantify the hydrological responses of land use and land cover changes. The Yangtze River Delta is one of the most developed regions in China with the rapid development of urbanization which serves as an excellent case study site for understanding the hydrological response to urbanization and land use change. The Xitiaoxi River basin, one of the main upstream rivers to the Taihu Lake in the Yangtze River Delta, was selected to perform the study. The urban area in the basin increased from 37.8km2 in 1985 to 105km2 in 2008. SWAT model, which makes direct use of land cover and land use data in simulating streamflow, provides as a useful tool for performing such studies and is therefore used in this study. The results showed that (1) the expansion of urban areas had a slight influence on the simulated annual streamflow and evapotranspiration (ET) as far as the whole catchment is concerned; (2) surface runoff and baseflow were found more sensitive to urbanization, which had increased by 11.3% and declined by 11.2%, respectively; (3) changes in streamflow, evapotranspiration and surface runoff were more pronounced during the wet season (from May to August), while baseflow and lateral flow had a slight seasonal variation; (4) the model simulated peak discharge increased 1.6–4.3% and flood volume increased 0.7–2.3% for the selected storm rainfall events at the entire basin level, and the change rate was larger for smaller flood events than for larger events; (5) spatially, changes of hydrological fluxes were more remarkable in the suburban basin which had a relative larger increase in urbanization than in rural sub-basins; and (6) analysis of future scenarios showed the impacts of urbanization on hydrological fluxes would be more obvious with growth in impervious areas from 15% to 30%. In conclusion, the urbanization would have a slight impact on annual water yield, but a remarkable impact was found on surface runoff, peak discharge and flood volume especially in suburban basins in the study area. The study suggested that more attention must be paid for flood mitigation and water resources management in planning future urban development in the region.
Universal quantum computation1 is striking for its unprecedented capability in processing information, but its scalability is challenging in practice because of the inevitable environment noise. ...Although quantum error correction (QEC) techniques2–8 have been developed to protect stored quantum information from leading orders of error, the noise-resilient processing of the QEC-protected quantum information is highly demanded but remains elusive9. Here, we demonstrate phase gate operations on a logical qubit encoded in a bosonic oscillator in an error-transparent (ET) manner. Inspired by refs. 10,11, the ET gates are extended to the bosonic code and are able to tolerate errors on the logical qubit during gate operations, regardless of the random occurrence time of the error. With precisely designed gate Hamiltonians through photon-number-resolved a.c. Stark shifts, the ET condition is fulfilled experimentally. We verify that the ET gates outperform the non-ET gates with a substantial improvement of gate fidelity after an occurrence of the single-photon-loss error. Our ET gates in superconducting quantum circuits can be readily extended to multiple encoded qubits and a universal gate set is within reach, holding the potential for reliable quantum information processing.Error-transparent quantum gates that can tolerate certain error during the execution of quantum operations have been demonstrated. Substantial improvement of the gate fidelity sheds lights on large-scale universal quantum computation.
Searching topological states in artificial systems has recently become a rapidly growing field of research. Meanwhile, significant experimental progress on observing topological phenomena has been ...made in superconducting circuits. However, topological insulator states have not yet been reported in this system. Here, for the first time, we experimentally realize a tunable dimerized spin chain model and observe the topological magnon insulator states in a superconducting qubit chain. Via parametric modulations of the qubit frequencies, we show that the qubit chain can be flexibly tuned into topologically trivial or nontrivial magnon insulator states. Based on monitoring the quantum dynamics of a single-qubit excitation in the chain, we not only measure the topological winding numbers, but also observe the topological magnon edge and defect states. Our experiment exhibits the great potential of tunable superconducting qubit chain as a versatile platform for exploring noninteracting and interacting symmetry-protected topological states.
Rivers and lakes have been traditionally studied as separate entities for carbon transport. However, there is a gap in our knowledge of the connectivity of dissolved carbon in a river-lake continuum. ...In this study, we analyzed dissolved carbon along the Little River-Catahoula Lake in subtropical Louisiana, United States to assess carbon biogeochemistry in such a river-lake continuum. Monthly in-situ measurements and water sample collections were made at four locations during April 2015 to February 2016 to determine riverine carbon transport into and out of the lake. Results show that much of the dissolved inorganic carbon (DIC) in the river-lake continuum originated from 13C depleted sources with an average δ13CDIC of −18.5‰. Significant decreases in DIC were found after the river passed through the lake (from 482 to 399 μmol L−1), which was most prevalent when the lake was not affected by backwater flow from the downstream river. CO2 outgassing could be mainly responsible for the sink behavior of the lake for DIC. Dissolved organic carbon (DOC) in the studied watershed were mostly terrigenous with low δ13CDOC averaged at −29.2‰. Significant, consistent decreases in DOC concentrations were found from the river to the lake inflow and then to the lake outflow. During the majority of the year, the lake reduced DOC concentrations from the river inflow water, but switched to functioning as a source of DOC during warmer, dryer conditions in September and October due to increased water residence time. Therefore, the lake functioned both as a sink and as a source for DOC.
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•In 9 out of 11 months the lake was a sink for DOC sustained by terrigenous sources.•The lake changed to a DOC source during months with extended water residence time.•DIC in the river-lake continuum originated mainly from 13C depleted sources.•CO2 outgassing made the lake a sink for the down-network DIC transport.•Backwater containing high-level DIC could offset the sink function of the lake.
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