In the realm of aspergillosis, a critical concern for immunocompromised patients facing Aspergillus fumigatus, effective management hinges on understanding fungal growth, stress resistance, and ...response to antifungal treatments. Our study investigates the crucial role of fungal plasma membrane proton ATPase (PMA) in nutrient absorption, intertwined with growth and antifungal susceptibility. We employed a high-throughput knockout method to create the PMA gene knockout mutant, ΔAfu-PMA1, in A. fumigatus, alongside a complementation strain. Antifungal susceptibility to triazoles was assessed by micro-dilution method and E-test, revealing decreased sensitivity to voriconazole in ΔAfu-PMA1. Comparative analysis demonstrated significant growth differences, with wild-type strain surpassing ΔAfu-PMA1 by 3.2-fold. Under oxidative stress and heightened osmotic pressure, ΔAfu-PMA1 showed notable growth defects. Loss of PMA led to increased ergosterol and decreased ATP content, alongside pH changes in the culture medium. Transcriptome sequencing unveiled revealed a reduced expression of genes associated with ribosome function, the MAPK pathway, endoplasmic reticulum, and the transport and metabolism of fats, sugars, and proteins in ΔAfu-PMA1, highlighting PMA’s regulatory role in growth and adaptation. These findings emphasise PMA as a potential target for future antifungal drugs, offering hope in combating aspergillosis.
Diabetes-associated cognitive impairment (DACI) can increase the risk of major cardiovascular events and death. Neuronal functionality is highly dependent on mitochondria and emerging evidence has ...shown that mitochondrial transplantation is a potential and effective strategy that can reduce brain injury and associated disorders. Platelets are abundant in blood and can be considered a readily available source of small-size mitochondria. These cells can be easily acquired from the peripheral blood with minimal invasion via simple venipuncture. The present study aimed to investigate whether transplantation of platelet-derived mitochondria (Mito-Plt) could improve DACI. Cognitive behaviors were assessed using the Morris water maze test in db/db mice. The results demonstrated that Mito-Plt was internalized into hippocampal neurons 24 h following intracerebroventricular injection. Importantly, one month following Mito-Plt transplantation, DACI was alleviated in db/db mice and the effect was accompanied with increased mitochondrial number, restored mitochondrial function, attenuated oxidative stress and neuronal apoptosis, as well as decreased accumulation of Aβ and Tau in the hippocampus. Taken together, the data demonstrated that transplantation of Mito-Plt attenuated cognitive impairment and mitochondrial dysfunction in db/db mice. This method may be a potential therapeutic application for the treatment of DACI.
Background and aims: Dietary diversity change is associated with cognitive function, however, whether the effect still exists among the oldest-old (80+) is unclear. Our aim was to examine the effect ...of dietary diversity changes on cognitive impairment for the oldest-old in a large prospective cohort. Methods: Within the Chinese Longitudinal Healthy Longevity Study, 6237 adults older than 80 years were included. The dietary diversity score (DDS) was assessed by a simplified food frequency questionnaire (FFQ). Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score lower than 18 points. Cognitive decline was defined as a reduction of total MMSE score ≥3 points, and cognitive decline of different subdomains was defined as a reduction of ≥15% in the corresponding cognitive domain. The multivariate-adjusted Cox proportional hazard model evaluated the effects of DDS change on cognitive decline. The linear mixed-effect model was used to test subsequent changes in MMSE over the years. Results: During 32,813 person-years of follow-up, 1829 participants developed cognitive impairment. Relative to the high–high DDS change pattern, participants in the low–low and high–low patterns were associated with an increased risk of cognitive impairment with a hazard ratio (95% confidential interval, CI) of 1.43 (1.25, 1.63) and 1.44 (1.24, 1.67), and a faster decline in the MMSE score over the follow-up year. Participants with the low–high pattern had a similar incidence of cognitive impairment with HRs (95% CI) of 1.03 (0.88, 1.20). Compared with the stable DDS status group (−1–1), the risk of cognitive impairment was higher for those with large declines in DDS (≤−5) and the HR was 1.70 (95% CI: 1.44, 2.01). Conclusions: Even for people older than 80, dietary diversity change is a simple method to identify those who had a high risk of cognitive decline. Keeping high dietary diversity is beneficial for cognitive function and its subdomain even in the final phase of life, especially for females and the illiterate oldest-old.
A novel welding method, induction pressure welding (IPW) process was used to join steel and aluminum alloy. The effects of input power, air gap and heating time on welding point width, intermetallic ...compound (IMC) thickness and tensile strength were investigated during the IPW process using response surface method. The results indicate that the heating time has the most marked effect on micro-structure and mechanical performance in all single factors. The air gap and heating time have the greatest interaction effect on tensile strength and welding point width while the input power and heating time have the greatest interaction influence on IMC thickness. The most desirable process parameters with input power 30kW, air gap 4.4mm, and heating time 10s are expected to be able to minimize IMC thickness and maximize tensile strength. The comparison between the predicted and experimental results for tensile strength and IMC thickness indicates that the mathematical model built by response surface method is reliability.
Dry reforming of methane has received considerable interest as one of the most efficient thermocatalysis routes to co-convert two greenhouse gases (CO2 and CH4) into syngas (CO and H2), requiring a ...robust catalyst for extensive application. CeO2 with a honeycomb-lantern-like structure is fabricated by a facile template-free solvothermal process, followed by calcination, and the nickel-active component is confined on the surface of the honeycomb-lantern-like CeO2 support (namely, Ni/CeO2-H) and employed in dry reforming of methane. The catalytic performance of the prepared sample is evaluated in a fixed-bed tubular reactor, and the CH4 and CO2 conversions could reach 83.94 and 82.81% at 800 °C, respectively. Meanwhile, the Ni/CeO2-H catalysts are thoroughly characterized using X-ray diffraction, N2 adsorption–desorption, scanning electron microscopy, H2 temperature-programmed reduction, CO2 temperature-programmed desorption, X-ray photoelectron spectroscopy, thermogravimetric analysis, and CO2 temperature-programmed oxidation (CO2-TPO), and the results demonstrate the enhancing effect of spatial confinement for the honeycomb-lantern-like structure. Moreover, the kinetics studies reveal that Ni/CeO2-H has the lowest activation energy (97.61 kJ/mol) among these Ni/CeO2 catalyst samples, which can facilitate its excellent catalytic performance effectively. Based on the semiempirical power rate equation, the reaction orders of CH4 and CO2 for Ni/CeO2-H are 0.60 and 0.17, respectively. Furthermore, the activation energy of coke gasification for the spent Ni/CeO2-H catalyst is investigated and determined by the CO2-TPO technique on the basis of extrapolating the Wigner–Polanyi equation.
Although photodynamic-based tumor therapy has attracted considerable attention, the antitumor effect is limited due to the low reactive oxygen species (ROS) generation of photosensitizers. Therefore, ...it is an urgent need for improving ROS production and promoting therapeutic outcome of tumor. We developed a nanoplatform of indocyanine green (ICG)-equipped upconversion nanoparticles (UCNPs)/CeO2 modified with NH2-PEG1000-cRGDfK (UICCIP). This nanoplatform has two pathways of ROS production for mutually enhanced dual photodynamic therapy (PDT) of tumors. The ultraviolet (UV) emission of UCNPs could trigger CeO2 to produce ROS for PDT under 808 nm laser irradiation, and ICG can also produce singlet oxygen (1O2) at the meantime. Importantly, ICG can enhance the luminescence of UCNPs through energy transfer, thus promoting the PDT effect of CeO2. For another, CeO2 could catalyze endogenous H2O2 to provide O2 then overcome the hypoxic environment of tumor to enhance the PDT effect. By highlighting the full use of the various components of the nanoplatform and establishing interrelationships, ROS production can be increased significantly, resulting in efficient PDT of tumor. It is believed that UICCIP will become a potential ROS producer, which will broaden the thought of exploring new antitumor nanoplatforms.
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•ICG-equipped upconversion nanoparticles (UCNPs)/CeO2 has been constructed for dual photodynamic therapy of tumor.•Under NIR light excitation, both CeO2 and ICG could independently generate ROS to induce the apoptosis of tumor cells.•ICG can enhance the luminescence of UCNPs through energy transfer, thus promoting the PDT effect of CeO2.•CeO2 could catalyze endogenous H2O2 to provide O2 to further enhance the PDT effect.•UICCIP could emit NIR emission to determine the optimal treatment window period through NIR fluorescence imaging.
Ozone (O3) pollution is becoming the primary air pollution issue with the large decrease in fine particulate concentrations in eastern China. The development of widely recognized policies for ...controlling O3 pollution episodes is urgent. This study aims to provide actionable and comprehensive suggestions for O3 control policy development, with an emphasis on the precursor emission reductions.
Here, we compared the impacts of different spatial scale reductions on a widespread O3 pollution episode in eastern China by a state-of-the-art regional air quality model. We find that region-scale joint control (in >30 cities) is much more effective than city-scale sporadic reduction in reducing O3 concentration. Sporadic controls only reduce the maximum daily 8-h average (MDA8) O3 by ∼1 μg/m3 in the controlled city, whereas regional controls lead to a MDA8 O3 decrease of ∼8 μg/m3 in the controlled region. In addition, the emission reduction effectiveness increased by 2.6 times from <5 cities to >30 cities. Continuous reductions have a cumulative effect on the decrease of MDA8 O3, showing the strongest effects within 24 h and diminishing after 48 h, which underscores the importance of reducing emissions 24 h prior to an episode. Moreover, the effect of control measures on MDA8 O3 varies spatially depending on the ratio of volatile organic compounds (VOCs) to nitrogen oxides (NOx) (VOCs/NOx). Both the reductions of VOC and NOx emissions have a positive effect on the decrease of MDA8 O3 in summer, but the effects of VOC reductions are 1.2 to 1.7 times higher than those of NOx reductions. The residential sector, due to its high VOCs/NOx emission ratio, exhibits the highest efficiency in the reduction of O3 concentrations. Our results highlight the importance of regional joint control and synergistic reduction of VOCs and NOx in eastern China.
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•The synergistic effect of regional joint control increases with the expansion of emission reduction areas.•The emission control 24 h in advance has a strong cumulative effect on the reduction of O3 concentrations.•The response of MDA8 O3 changes to the emission reduction depends on the ratios of VOCs/NOx.•Reduction in residential sector is effective for O3 mitigation, while the industrial sector makes the largest contribution.
Vascular calcification (VC) is a major risk factor for increasing cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS), a representative uremic ...toxin, is closely associated with VC in CKD patients. Matrix Gla protein (MGP) plays pivotal role in VC as a calcification inhibitor. The aim of this work was to explore whether MGP was involved in IS-induced VC. Here, we demonstrated the role of MGP in the IS-induced osteogenic differentiation of human aortic smooth muscle cells (HASMCs). The methods included Von Kossa staining, immunohistochemistry, Alizarin Red staining, quantitative real-time PCR and western blotting. MGP was decreased in calcified arteries both in CKD patients and rats. In vitro, IS suppressed MGP expression in HASMCs by activating ROS/NF-κB signaling in parallel with osteogenic differentiation, which was mitigated by inhibiting ROS and NF-κB with diphenyleneiodonium and Bay11-7082. Further investigation showed that IS induced NF-κB-responsive microRNA (miR)-155-5p mediating MGP downregulation. Overexpression of miR-155-5p with mimics aggravated IS-induced MGP reduction and osteogenic differentiation. In contrast, these conditions were diminished by silencing miR-155-5p. We demonstrate that IS promotes the HASMCs phenotype switch by suppressing MGP expression via ROS/NF-κB/miR-155-5p signaling and provide a new insight for the pathogenesis of IS-induced VC.
•MGP expression is decreased in medial calcified vessels of CKD patients and rats.•Downregulation of MGP occurs in IS-induced osteogenic differentiation of HASMCs.•IS suppressed MGP expression by activating ROS/NF-κB/miR-155-5p signaling pathway.
Kidney aging accelerates the progression of various acute and chronic kidney diseases and can also induce pathological changes in other organs throughout the body. Circular RNAs (circRNAs), have been ...demonstrated to play a vital role in aging and age-related diseases. However, biological functions and the underlying molecular mechanism of circRNAs in kidney aging remain largely unclear. Uncovering the functions of circRNAs in kidney aging and their underlying regulatory mechanisms may shed new light on the development of novel diagnostic and therapeutic strategies for human aging. Here we report the important role of circVmn2r1 in the progression of kidney aging. We found that circVmn2r1 was one of the top expressed circRNAs in mouse kidney by RNA sequencing and was significantly upregulated in 24-month-old mouse kidney compared to 3-month-old. More importantly, we demonstrated that overexpression of circVmn2r1 promoted kidney aging in senescence-accelerated mouse prone 8 (SAMP8) mice. Cellular assays with mouse kidney tubular epithelium (TCMK-1) cells under both gain-of-function and loss-of-function conditions demonstrated that circVmn2r1 inhibited proliferation and promoted senescence, whereas miR-223-3p counteracted these effects. Mechanistic analysis demonstrated that circVmn2r1 acted as a miR-223-3p sponge to relieve the repressive effect of miR-223-3p on its target NLRP3, which we proved could inhibit proliferation and promote senescence of TCMK-1 cells. Our results indicate that circVmn2r1 promotes kidney aging through acting as a miR-223-3p sponge, consequently upregulating NLRP3 expression, and can be a valuable diagnostic marker and an important therapeutic target for kidney aging.
In this paper, a novel recursive filtering scheme combined with collaborative prediction (CP) method is proposed for a class of linear time-varying systems under duty cycle communication scheduling. ...The communication between the sensor nodes and the remote filter is implemented through wireless networks. In order to save energy even further, the working states of sensor nodes alternate between activation and dormancy depending on the preset duty cycle. The aim of this paper is to design a usable recursive filtering scheme for linear time-varying system subject to the duty cycle scheduling (DCS) in the case of limited energy. The DCS is modeled according to the corresponding scheduling rule. The unsent measurement outputs due to sensors being dormancy state are predicted by CP algorithm, based on which a recursive filtering scheme is developed. Also, the filter gain is calculated by minimizing the trace of error covariance. Subsequently, the boundedness of the designed filtering algorithm is analyzed. Finally, a numerical simulation example is presented to illustrate the effectiveness of the proposed recursive filtering approach based on CP algorithm subject to the DCS.
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