Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important issue. Autophagy, a ...self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal. Therefore, research on the regulation of autophagy to combat MDR is expanding and is becoming increasingly important. We summarize advanced studies of autophagy in MDR tumors, including the variable role of autophagy in MDR cancer cells.
Chlorine disinfection to drinking water plays an important role in preventing and controlling waterborne disease outbreaks globally. Nevertheless, little is known about why it enriches the antibiotic ...resistance genes (ARGs) in bacteria after chlorination. Here, ARGs released from killed antibiotic-resistant bacteria (ARB), and culturable chlorine-injured bacteria produced in the chlorination process as the recipient, were investigated to determine their contribution to the horizontal transfer of ARGs during disinfection treatment. We discovered Escherichia coli, Salmonella aberdeen, Pseudomonas aeruginosa and Enterococcus faecalis showed diverse resistance to sodium hypochlorite, and transferable RP4 could be released from killed sensitive donor consistently. Meanwhile, the survival of chlorine-tolerant injured bacteria with enhanced cell membrane permeabilisation and a strong oxidative stress-response demonstrated that a physiologically competent cell could be transferred by RP4 with an improved transformation frequency of up to 550 times compared with the corresponding untreated bacteria. Furthermore, the water quality factors involving chemical oxygen demand (COD
), ammonium nitrogen and metal ions (Ca
and K
) could significantly promote above transformation frequency of released RP4 into injured E. faecalis. Our findings demonstrated that the chlorination process promoted the horizontal transfer of plasmids by natural transformation, which resulted in the exchange of ARGs across bacterial genera and the emergence of new ARB, as well as the transfer of chlorine-injured opportunistic pathogen from non-ARB to ARB. Considering that the transfer elements were quite resistant to degradation through disinfection, this situation poses a potential risk to public health.
The long noncoding RNA NEAT1 (nuclear enriched abundant transcript 1) nucleates the formation of paraspeckles, which constitute a type of nuclear body with multiple roles in gene expression. Here we ...identify NEAT1 regulators using an endogenous NEAT1 promoter-driven enhanced green fluorescent protein reporter in human cells coupled with genome-wide RNAi screens. The screens unexpectedly yield gene candidates involved in mitochondrial functions as essential regulators of NEAT1 expression and paraspeckle formation. Depletion of mitochondrial proteins and treatment of mitochondrial stressors both lead to aberrant NEAT1 expression via ATF2 as well as altered morphology and numbers of paraspeckles. These changes result in enhanced retention of mRNAs of nuclear-encoded mitochondrial proteins (mito-mRNAs) in paraspeckles. Correspondingly, NEAT1 depletion has profound effects on mitochondrial dynamics and function by altering the sequestration of mito-mRNAs in paraspeckles. Overall, our data provide a rich resource for understanding NEAT1 and paraspeckle regulation, and reveal a cross-regulation between paraspeckles and mitochondria.
Multicopper oxidases (MCOs) are a pervasive family of enzymes that oxidize a wide range of phenolic and nonphenolic aromatic substrates, concomitantly with the reduction of dioxygen to water. MCOs ...are usually divided into two functional classes: metalloxidases and laccases. Given their broad substrate specificity and eco-friendliness (molecular oxygen from air as is used as the final electron acceptor and they only release water as byproduct), laccases are regarded as promising biological green tools for an array of applications. Among these laccases, those of bacterial origin have attracted research attention because of their notable advantages, including broad substrate spectrum, wide pH range, high thermostability, and tolerance to alkaline environments. This review aims to summarize the significant research efforts on the properties, mechanisms and structures, laccase-mediator systems, genetic engineering, immobilization, and biotechnological applications of the bacteria-source laccases and laccase-like enzymes, which principally include
Bacillus
laccases, actinomycetic laccases and some other species of bacterial laccases. In addition, these enzymes may offer tremendous potential for environmental and industrial applications.
Abstract
Background
Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This ...study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19.
Methods
This cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. In total, 466 uninfected spouses of COVID-19 patients were selected as controls. The current cognitive status was assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and the longitudinal cognitive decline was assessed using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge.
Results
Compared with controls, COVID-19 patients had lower TICS-40 scores and higher IQCODE scores TICS-40 median (IQR): 29 (25 to 32) vs. 30 (26 to 33),
p
< 0.001; IQCODE median (IQR): 3.19 (3.00 to 3.63) vs. 3.06 (3.00 to 3.38),
p
< 0.001. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33),
p
< 0.001; IQCODE median (IQR): 3.63 (3.13 to 4.31) vs. 3.13 (3.00 to 3.56),
p
< 0.001 and controls TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33),
p
< 0.001; IQCODE median (IQR) 3.63 (3.13 to 4.31) vs. 3.06 (3.00 to 3.38),
p
< 0.001. Severe COVID-19 patients had a higher proportion of cases with current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients dementia: 25 (10.50 %) vs. 9 (0.69 %),
p
< 0.001; Mild cognitive impairment (MCI): 60 (25.21 %) vs. 63 (4.84 %),
p
< 0.001 and controls dementia: 25 (10.50 %) vs. 0 (0 %),
p
< 0.001; MCI: 60 (25.21 %) vs. 20 (4.29 %),
p
< 0.001). COVID-19 severity, delirium and COPD were risk factors of current cognitive impairment. Low education level, severe COVID-19, delirium, hypertension and COPD were risk factors of longitudinal cognitive decline.
Conclusions
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of long-term cognitive decline in elderly population. COVID-19 patients, especially severe patients, should be intensively monitored for post-infection cognitive decline.
Purpose
To generate diagnostic
18
F-FDG PET images of pediatric cancer patients from ultra-low-dose
18
F-FDG PET input images, using a novel artificial intelligence (AI) algorithm.
Methods
We used ...whole-body
18
F-FDG-PET/MRI scans of 33 children and young adults with lymphoma (3–30 years) to develop a convolutional neural network (CNN), which combines inputs from simulated 6.25% ultra-low-dose
18
F-FDG PET scans and simultaneously acquired MRI scans to produce a standard-dose
18
F-FDG PET scan. The image quality of ultra-low-dose PET scans, AI-augmented PET scans, and clinical standard PET scans was evaluated by traditional metrics in computer vision and by expert radiologists and nuclear medicine physicians, using Wilcoxon signed-rank tests and weighted kappa statistics.
Results
The peak signal-to-noise ratio and structural similarity index were significantly higher, and the normalized root-mean-square error was significantly lower on the AI-reconstructed PET images compared to simulated 6.25% dose images (
p
< 0.001). Compared to the ground-truth standard-dose PET, SUV
max
values of tumors and reference tissues were significantly higher on the simulated 6.25% ultra-low-dose PET scans as a result of image noise. After the CNN augmentation, the SUV
max
values were recovered to values similar to the standard-dose PET. Quantitative measures of the readers’ diagnostic confidence demonstrated significantly higher agreement between standard clinical scans and AI-reconstructed PET scans (kappa = 0.942) than 6.25% dose scans (kappa = 0.650).
Conclusions
Our CNN model could generate simulated clinical standard
18
F-FDG PET images from ultra-low-dose inputs, while maintaining clinically relevant information in terms of diagnostic accuracy and quantitative SUV measurements.
Evaluation of actual zero energy buildings (ZEBs) performance and identification of its regional characteristics are of great significance for similar future projects. Based on more than 400 cases in ...cold regions, this study compared the post-evaluation and drivers of ZEBs from China, the US and the European Union (EU). Results found that ZEB definition, energy drivers, standard, regional policies, technology adoption and their adoption ratio determine the energy performance of cases. Not all EU and China cases reach the net-zero energy target; however, most ZEBs in the US do. ZEBs in cold regions adopted multiple technologies to achieve high energy-efficiency. The adoption ratio of passive technologies is higher than that of active technologies, especially in China. The active technologies in cold regions are mainly seen in the application of advanced HVAC systems. Such application of renewable technologies exhibits strong regional characteristics; for example, the EU’s carbon emission reduction policies promoted the use of biomass-based technologies. The analysis also found that energy policies greatly enhance the development of ZEBs. Overall, achieving zero energy is a process, not an endpoint and many projects need further refinement after occupancy.
•The post-evaluation of zero energy buildings in cold regions is carried out.•The actual operation data of more than 400 cases were collected.•The energy performance, cost, design feature, technology selection are studied.•The regional difference in China, the United States, and the EU is compared.•Experience and recommendations for zero energy building in cold regions is provided.
Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary dysfunctional disease, characterized by progressive vascular remodeling. Inflammation is an increasingly recognized feature of PAH, ...which is important for the initiation and maintenance of vascular remodeling. High levels of various inflammatory mediators have been documented in both PAH patients and experimental models of PAH. Similarly, multiple immune cells were found to accumulate in and around the wall of remodeled pulmonary vessels and in the vicinity of plexiform lesions, respectively. On the other hand, inflammation is also a bridge from autoimmune diseases to PAH. Autoimmune diseases always lead to chronic inflammation, characterized by the low-level persistent infiltration of immune cells, and elevated levels of several pro-inflammatory cytokines and chemokines. In addition, circulating autoantibodies are found in the peripheral blood of patients, indicating a possible role of autoimmunity in the pathogenesis of PAH. Thus, anti-inflammatory and immunotherapy might be new strategies to prevent or even reverse the process of PAH. Many anti-inflammatory agents and immunotherapies have been confirmed in animal models while some clinical trials employing immunotherapies are completed or currently underway. Here, we review pathological mechanisms associated with inflammation and immunity in the development of PAH, and discuss potential interventions for the treatment of PAH.
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It is well known that unmanned aerial vehicles (UAVs) can help terrestrial base stations (BSs) offload data traffic from crowded areas to improve coverage and boost throughput. However, the limited ...backhaul capacity cannot cope with the ever-increasing data demands, for which caching is introduced to relieve the backhaul bottleneck. In this paper, we focus on a multi-UAV assisted wireless network, and target to fully utilize the benefits of wireless caching and UAV mobility for multiuser content delivery. By taking into account the limited storage, our goal is to maximize the minimum throughput among UAV-served users by jointly optimizing cache placement, UAV trajectory, and transmission power in a finite period. The resultant problem is a mixed-integer non-convex optimization problem. To facilitate solving this problem, an alternating iterative algorithm is proposed by adopting the block alternating descent and successive convex approximation methods. Specifically, this problem is split into three subproblems, namely cache placement optimization, trajectory optimization, and power allocation optimization. Then these subproblems are solved alternately in an iterative manner. We show that the proposed algorithm can converge to the set of stationary solutions of this problem. Besides, we further analyze the computational complexity of this algorithm. Numerical results show that great throughput enhancement is achieved by applying our proposed joint design in comparison with other benchmarks without trajectory design and power control.
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