Oxidative stress-mediated activation of extracellular signal-regulated kinase contributes to mild cognitive impairment-related mitochondrial dysfunction

Mild cognitive impairment (MCI) occurs during the pre-dementia stage of Alzheimer’s disease (AD) and is characterized by a decline in cognitive abilities that frequently represents a transition between normal cognition and AD dementia. Its pathogenesis is not well understood. Here, we demonstrate the direct consequences and potential mechanisms of oxidative stress, mitochondrial dynamic and functional defects in MCI-derived mitochondria. Using cytoplasmic hybrid (cybrid) cell model in which mitochondria from MCI or age-matched non-MCI subjects were incorporated into a human neuronal cell line depleted of endogenous mitochondrial DNA, we evaluated the mitochondrial dynamics and functions, as well as the role of oxidative stress in the resultant cybrid lines. We demonstrated increased expression levels of mitofusin 2 (Mfn2) is markedly induced by oxidative stress in MCI-derived mitochondria along with aberrant mitochondrial functions. Inhibition of oxidative stress rescues MCI-impaired mitochondrial fusion/fission balance as shown by the suppression of Mfn2 expression, attenuation of abnormal mitochondrial morphology and distribution, and improvement in mitochondrial function. Furthermore, blockade of MCI related stress-mediated activation of extracellular signal-regulated kinase (ERK) signaling not only attenuates aberrant mitochondrial morphology and function but also restores mitochondrial fission and fusion balance, in particular inhibition of overexpressed Mfn2. Our results provide new insights into the role of the oxidative stress-ERK-Mfn2 signal axis in MCI-related mitochondrial abnormalities, indicating that the MCI phase may be targetable for the development new therapeutic approaches that improve mitochondrial function in age-related neurodegeneration

Characterization of the Nitrogen Removal Potential of Two Newly Isolated <i>Acinetobacter</i> Strains under Low Temperature

Excess nitrogen and phosphorus in the water causes several ecological problems for nutrients. Biological nitrogen removal is an economical and efficient way to prevent excessive nitrogen in the environment. For most areas of China, temperatures are usually lower than 20 °C except during the summertime. It is necessary to discover microbes that can efficiently remove nitrogen at low temperatures. In this study, two Acinetobacter strains were isolated from a sample in a wastewater tank in Taizhou for their capabilities to remove NO3−–N and NO2−–N at 15 °C. Heterotrophic nitrification experiments showed that both strains could efficiently remove nitrogen from the culture medium. The maximum removal rates of NH4+–N were 3.15 mg/L·h and 4.74 mg/L·h for heterotrophic nitrification by the strains F and H, respectively. Strain H grew faster and removed both nitrite and nitrate more efficiently than strain F. Genome sequencing showed that strains F and H could be classified into Acinetobacter johnsonii and Acinetobacter bereziniae, respectively. NO2−–N (100 mg/L) was completely removed in 3 days by strain H. The maximum NO3−–N removal rate was 3.53 mg/L·h for strain F. When strain H was cultured in a broth with 200 mg/L NO3−–N, 97.46% of NH4+–N (200 mg/L) was removed in 5 days, and the maximum NH4+–N removal rate was 4.04 mg/L·h. Genomic sequence analysis showed that both the strains lacked genes involved in the denitrification pathway that transforms NO3− into N2. This implies that nitrate or nitrite is removed through the nitrogen assimilation pathway. Genes responsible for nitrate assimilation are clustered together with molybdopterin cofactor biosynthesis genes. Strain H contains fewer resistance genes and transfer elements. All the above data demonstrate that strain H is a promising candidate for nitrogen removal at lower temperatures. But there is still a lot to be done to systematically evaluate the potential of A. bereziniae strain H in treating wastewater at a pilot scale. These include the long-term performance, environmental tolerance, and nitrogen removal efficiency in wastewater. And the application of these Acinetobacter strains in diverse wastewater treatment settings might require careful optimization and real-time monitoring

Bump feature detection of the road surface based on the Bi-LSTM

The road network is the basic facility for transportation systems in the city. Every day, a large number of vehicles move on the road and exert different pressure on the ground, which leads to various problems for the road surface, such as the bump features of the road surface (BFRS). However, traditional methods, such as detecting BFRS manually or with professional equipment, require a lot of professional management and devices. Based on the mobile sensor and the bidirectional long short-term memory (Bi-LSTM), a detection method for BFRS is proposed. The BFRS detection method proposed in this article solves the problem that other BFRS detection methods cannot detect large area road surface efficiently and provides an algorithm idea for efficient detection of large area road surface BFRS. The mobile phone with multi-sensors is carried on vehicles, and the BFRS information is logged during the movements. The orientation of the mobile is computed according to the gyroscope. The actual posture of the acceleration sensor is adjusted with the reference coordinate system, whose z-axis is vertical to the ground. This article uses the adjusted acceleration data as the training dataset and labels it according to time stamps and videos recorded by the driving recorder. Finally, the Bi-LSTM is constructed and trained, followed by the BFRS detection. The results show that it can detect BFRS in different regions. The detection accuracy of the campus section and the extended experiment was 92.85 and 87.99%, respectively

Average intensity of a partially coherent anomalous hollow beam propagating in underwater oceanic turbulence

Based on the extended Huygens–Fresnel principle, the cross-spectral density function of a partially coherent anomalous hollow beam (AHB) propagating in underwater oceanic turbulence has been derived. The average intensity of partially coherent AHB propagating in underwater oceanic turbulence has been calculated. The influences of coherence length and the strength of underwater oceanic turbulence on the spreading properties of partially coherent AHB are illustrated and analyzed using numerical examples. It is found that the partially coherent AHB with smaller coherence length and the partially coherent AHB propagating in stronger underwater oceanic turbulence will lose the initial beam profile and evolve into the Gaussian beam faster. The results are useful in applications for underwater wireless optical communication

Deciphering the Effect of Lysine Acetylation on the Misfolding and Aggregation of Human Tau Fragment 171IPAKTPPAPK180 Using Molecular Dynamic Simulation and the Markov State Model

The formation of neurofibrillary tangles (NFT) with &beta;-sheet-rich structure caused by abnormal aggregation of misfolded microtubule-associated protein Tau is a hallmark of tauopathies, including Alzheimer&rsquo;s Disease. It has been reported that acetylation, especially K174 located in the proline-rich region, can largely promote Tau aggregation. So far, the mechanism of the abnormal acetylation of Tau that affects its misfolding and aggregation is still unclear. Therefore, revealing the effect of acetylation on Tau aggregation could help elucidate the pathogenic mechanism of tauopathies. In this study, molecular dynamics simulation combined with multiple computational analytical methods were performed to reveal the effect of K174 acetylation on the spontaneous aggregation of Tau peptide 171IPAKTPPAPK180, and the dimerization mechanism as an early stage of the spontaneous aggregation was further specifically analyzed by Markov state model (MSM) analysis. The results showed that both the actual acetylation and the mutation mimicking the acetylated state at K174 induced the aggregation of the studied Tau fragment; however, the effect of actual acetylation on the aggregation was more pronounced. In addition, acetylated K174 plays a major contributing role in forming and stabilizing the antiparallel &beta;-sheet dimer by forming several hydrogen bonds and side chain van der Waals interactions with residues I171, P172, A173 and T175 of the corresponding chain. In brief, this study uncovered the underlying mechanism of Tau peptide aggregation in response to the lysine K174 acetylation, which can deepen our understanding on the pathogenesis of tauopathies

Analysis of risk factors of fungal superinfections in viral pneumonia patients: A systematic review and meta‐analysis

Abstract Background Infections with fungi, such as Aspergillus species, have been found as common complications of viral pneumonia. This study aims to determine the risk factors of fungal superinfections in viral pneumonia patients using meta‐analysis. Objective This study aims to determine the risk factors of fungal infection s in viral pneumonia patients using meta‐analysis. Methods We reviewed primary literature about fungal infection in viral pneumonia patients published between January 1, 2010 and September 30, 2020, in the Chinese Biomedical Literature, Chinese National Knowledge Infrastructure, Wanfang (China), Cochrane Central Library, Embase, PubMed, and Web of Science databases. These studies were subjected to an array of statistical analyses, including risk of bias and sensitivity analyses. Results In this study, we found a statistically significant difference in the incidence of fungal infections in viral pneumonia patients that received corticosteroid treatment as compared to those without corticosteroid treatment (p < .00001). Additionally, regarding the severity of fungal infections, we observed significant higher incidence of invasive pulmonary aspergillosis (IPA) in patients with high Acute Physiology and Chronic Health Evaluation (APACHE) II scores (p < .001), tumors (p = .005), or immunocompromised patients (p < .0001). Conclusions Our research shows that corticosteroid treatment was an important risk factor for the development of fungal infection in patients with viral pneumonia. High APACHE II scores, tumors, and immunocompromised condition are also important risk factors of developing IPA. The diagnosis of fungal infection in viral pneumonia patients can be facilitated by early serum galactomannan (GM) testing, bronchoalveolar lavage fluid Aspergillus antigen testing, culture, and biopsy