Ageing, a leading cause of the decline/deficits in human learning, memory, and cognitive abilities, is a major risk factor for age-associated neurodegenerative disorders such as Alzheimer's disease. ...Emerging evidence suggests that epigenetics, an inheritable but reversible biochemical process, plays a crucial role in the pathogenesis of age-related neurological disorders. DNA methylation, the best-known epigenetic mark, has attracted most attention in this regard. DNA methyltransferases (DNMTs) are key enzymes in mediating the DNA methylation process, by which a methyl group is transferred, faithfully or anew, to genomic DNA sequences. Biologically, DNMTs are important for gene imprinting. Accumulating evidence suggests that DNMTs not only play critical roles, including gene imprinting and transcription regulation, in early development stages of the central nervous system (CNS), but also are indispensable in adult learning, memory, and cognition. Therefore, the impact of DNMTs and DNA methylation on age-associated cognitive functions and neurodegenerative diseases has emerged as a pivotal topic in the field. In this review, the effects of each DNMT on CNS development and healthy and pathological ageing are discussed.
During software evolution, complex structural dependencies between source files pose a great challenge on maintenance activities. Some of these dependencies propagate defects among files, incurring ...frequent bugs or changes, and consuming significant maintenance costs. They can be referred to as flawed structural dependencies. In this paper, we proposed a method to identify these potential problematic dependencies at an early stage during software evolution, by combing structural and semantic dependencies, so that developers can save maintenance costs by fixing these issues in time. Our method works as follows: First, we extract structural dependencies from the source code syntax and semantic dependencies from the source code lexicon. Second, we collect suspect file pairs by calculating the difference between structural and semantic dependencies. Next, we exhaustively examine each source file in the system and locate the interaction of its impacted subordinated files and suspect file pairs (SFP) as suspect dependencies. Finally, we gather all the suspect dependencies as flawed structural dependencies candidates. We evaluate our method using 838 releases of 15 open source projects, including 33353 bug reports and 86690 revision commits. The detection result shows that our identified dependencies use 14% of all the files to capture almost 70% of top 10% bug-prone files or change-prone files with enough high precision: 92%. Moreover, our identified dependencies also incur 957% of bug frequencies and 1050% of change frequencies than average in future versions. In summary, our method can effectively and efficiently detect flawed structural dependencies in time during software evolution.
Aerobic granular sludge (AGS) is promising in wastewater treatment. However, the formation and existence of AGS under low organic loading rate (OLR) is still not fully understood due to a knowledge ...gap in the variations and correlations of N-acyl-homoserine lactones (AHLs), the microbial community, extracellular polymeric substances (EPS) and other physiochemical granule properties. This study comprehensively investigated the AHL-mediated quorum sensing (QS) and microbial community characters in the AGS fed with ammonium-rich wastewater under a low OLR of 0.15 kg COD (m3 d)−1. The results showed that the AGS appeared within 90 days, and the size of mature granules was over 700 μm with strong settleability and ammonium removal performance. More tightly-bound extracellular polysaccharide and tightly-bound extracelluar protein were produced in the larger AGS. C10-HSL and C12-HSL gradually became dominant in sludge, and short-chain AHLs dominated in water. EPS producers and autotrophic nitrifiers were successfully retained in the AGS under low OLR. AHL-mediated QS utilized C10-HSL, C12-HSL and 3OC6-HSL as the critical AHLs to regulate the TB-EPS in aerobic granulation, and autotrophic nitrifiers may perform interspecific communication with C10-HSL. The correlations of bacterial genera with AGS properties and AHLs were complex due to the dynamic fluctuations of microbial composition and other variable factors in the mixed-culture system. These findings confirmed the participation of AHL-mediated QS in the regulation of microbial community characters and AGS properties under low OLR, which may provide guidance for the operation of AGS systems under low OLR from a microbiological viewpoint.
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•Successful aerobic granulation is achieved at a low OLR of 0.15 kg COD (m3 d)−1.•EPS producers and autotrophic nitrifiers successfully survive under low OLR.•AHL-mediated QS regulates the EPS production with 3OC6-HSL, C10-HSL and C12-HSL.•Autotrophic nitrifiers may perform interspecific communication with C10-HSL.
Skeletal muscle serves as the optimal effective organ to balance glucose homeostasis, but insulin resistance (IR) in skeletal muscle breaks this balance by impeding glucose uptake and causes ...metabolic disorders. IR in skeletal muscle is caused by multiple factors, and it has been reported that systemic low-grade inflammation is related to skeletal muscle IR, though its molecular mechanisms need to be ulteriorly studied. Pyroptosis is a novel inflammatory-mediated type of cell death. It has recently been reported that pyroptosis is associated with a decline in insulin sensitivity in skeletal muscle. The appropriate occurrence of pyroptosis positively eliminates pathogenic factors, whereas its excessive activation may aggravate inflammatory responses and expedite disease progression. The relationship between pyroptosis and IR in skeletal muscle and its underlined mechanism need to be further illustrated. The role of pyroptosis during the process of IR alleviation induced by non-drug interventions, such as exercise, also needs to be clarified. In this paper, we review and describe the molecular mechanisms of pyroptosis and further comb the roles of its relevant key factors in skeletal muscle IR, aiming to propose a novel theoretical basis for the relationship between pyroptosis and muscle IR and provide new research targets for the improvement of IR-related diseases.
The enrichment of radioactive iodine in the waste of nuclear industries threatens human health, and thus the efficient capture of iodine has attracted a great deal of attention in recent years. ...Porous organic polymers (POPs) and metal-organic frameworks (MOFs), new classes of porous materials, act as outstanding candidate adsorbent materials in this field due to their high surface areas, permanent tunable porosities, controllable structures, high thermal/chemical stabilities, versatility in molecular design and potential for post-synthetic modification. Herein, this review focuses on the research progress of these two types of porous materials for highly efficient iodine capture. We analyze and discuss some valid strategies for enhancing their iodine uptake, including increasing their surface area and pore volume, using organic building units with unique configurations and functions, introducing chemical functional groups to provide high-enthalpy binding sites, and further processing of POP and MOF materials. Indeed, there are many special structural and functional features found in porous POP and MOF materials, which make them unique and merit further exploration. Thus, we expect to see their usage grow as this field progresses.
This review focuses on the research progress of the efficient iodine capture in porous POP and MOF materials.
Background
Current guidelines did not provide recommendations on indications of an additional implantable cardioverter‐defibrillator (ICD) to patients receiving cardiac resynchronization therapy ...(CRT), and it still remains controversial due to lack of evidence from randomized controlled trials.
Method
PubMed, Embase, and Cochrane CENTRAL from the inception to May 2020 were systematically screened for studies reporting on the comparison of cardiac resynchronization therapy with defibrillator (CRT‐D) and cardiac resynchronization therapy with pacemaker (CRT‐P), focusing on the adjusted hazard ratio (aHR) of all‐cause mortality. We pooled the effects using a random‐effect model.
Results
Twenty‐one studies encompassing 69,919 patients were included in this meta‐analysis. With no restriction to characteristics of including population, CRT‐D was associated with a lower all‐cause mortality compared with CRT‐P significantly (aHR: 0.80, 95% confidence interval CI: 0.74‐0.87, I2 = 36.8%, p < .001). This mortality benefit was also observed in patients with ischemic cardiomyopathy (aHR: 0.74, 95% CI: 0.64‐0.86, I2 = 0%, p < .001). However, there is no significant difference in patients with nonischemic cardiomyopathy (NICM) (aHR: 0.91, 95% CI: 0.82‐1.01, I2 = 0%, p = .087), older age (age ≥75 years, aHR: 0.96, 95% CI: 0.83‐1.12, I2 = 0%, p = .610). Subgroup analysis was performed and indicated the survival benefit of CRT‐D for primary prevention compared with CRT‐P (aHR: 0.87, 95% CI: 0.79‐0.95, I2 = 0%, p = .003).
Conclusion
After adjusted the differences in clinical characteristics, additional ICD therapy was associated with a reduced all‐cause mortality in patients receiving CRT. However, our work suggested that additional ICD may not be applied to elderly (≥75 years) or patients with NICM.
Mycelial pellet of
Aspergillus niger Y3 was used as a biomass carrier to immobilize the aniline-degrading bacterium,
Acinetobacter calcoaceticus JH-9 and the mix culture of the COD rapid degradation ...bacteria. In order to investigate its removal effect on aniline and COD, the combined mycelial pellets were applied in the SBR. Comparison of the performances was conducted between another SBR inoculated with sole strain JH-9 and the above SBR. The results showed that the stable degradations of aniline and COD were observed in both reactors. In the SBR with combined mycelial pellet, the biological removal efficiency was about 0.9
mg aniline/(L·d). It was much higher than that in the activated sludge reactor. Meanwhile, the performances of the sedimentation velocity, liquid–solid phase separation and the effluent quality were better in the SBR. According to SEM images and PCR–DGGE analysis, the species immobilized on the biomass carrier were more predominant in this system.
Myeloid-derived suppressor cells (MDSCs) possess immunosuppressive activities, which allow cancers to escape immune surveillance and become non-responsive to immune checkpoints blockade. Here we ...report hypoxia as a cause of MDSC accumulation. Using hepatocellular carcinoma (HCC) as a cancer model, we show that hypoxia, through stabilization of hypoxia-inducible factor-1 (HIF-1), induces ectoenzyme, ectonucleoside triphosphate diphosphohydrolase 2 (ENTPD2/CD39L1), in cancer cells, causing its overexpression in HCC clinical specimens. Overexpression of ENTPD2 is found as a poor prognostic indicator for HCC. Mechanistically, we demonstrate that ENTPD2 converts extracellular ATP to 5'-AMP, which prevents the differentiation of MDSCs and therefore promotes the maintenance of MDSCs. We further find that ENTPD2 inhibition is able to mitigate cancer growth and enhance the efficiency and efficacy of immune checkpoint inhibitors. Our data suggest that ENTPD2 may be a good prognostic marker and therapeutic target for cancer patients, especially those receiving immune therapy.Myeloid-derived suppressor cells (MDSCs) promote tumor immune escape. Here, the authors show that in hepatocellular carcinoma, hypoxia induces the expression of ENTPD2 on cancer cells leading to elevated extracellular 5'-AMP, which in turn promote the maintenance of MDSCs by preventing their differentiation.
Alzheimer’s disease (AD) is a disease characterized by insidious and progressive neurodegeneration, with clinical syndromes of memory and visuospatial skills damage. The pathogenic mechanism of AD is ...complex in which neural inflammation and neuron death play important roles. Pyroptosis, an inflammatory programmed cell death, has been reported to be involved in neuron death. Pyroptosis is executed by the protein family of gasdermins which punch pores on plasma membrane when activated by the upstream signals including the activation of NLRP3 and caspases, and subsequently triggers the inflammatory cascades featured by the release of interleukin (IL) -1β and IL-18. Herein, we summarized the current research on the roles of neuron pyroptosis in AD, aiming to provide a comprehensive view of the molecular mechanisms underlying AD pathogenesis and potential therapeutic targets for AD.
This article investigates the adaptive fixed-time fault-tolerant tracking fuzzy control issue for nonlinear switched systems with dynamic uncertainties. Actuator faults considered in this article ...simultaneously contain the loss of effectiveness and time-varying bias fault depending on the switching signal. The generated scheme extends the fixed-time convergence to switched nonlinear systems with unmodeled dynamics. An improved adaptive fixed-time fault-tolerant controller is proposed by employing the backstepping method and fuzzy logic estimator. In particular, the presented framework removes the singularity, and the convergence time is assignable for any initial condition. Finally, a numerical simulation example and a resistor-capacitor-inductor circuit system example are given to prove the system output can converge to a desired trajectory within a fixed time.
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