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DNA glycosylase, as one member of DNA repair machineries, plays an essential role in correcting mismatched/damaged DNA nucleotides by cleaving the N-glycosidic bond between the sugar and target nucleobase through the base excision repair (BER) pathways. Efficient corrections of these DNA lesions are critical for maintaining genome integrity and preventing premature aging and cancers. The target-site searching/recognition mechanisms and the subsequent conformational dynamics of DNA glycosylase, however, remain challenging to be characterized using experimental techniques. In this review, we summarize our recent studies of sequential structural changes of thymine DNA glycosylase (TDG) during the DNA repair process, achieved mostly by molecular dynamics (MD) simulations. Computational simulations allow us to reveal atomic-level structural dynamics of TDG as it approaches the target-site, and pinpoint the key structural elements responsible for regulating the translocation of TDG along DNA. Subsequently, upon locating the lesions, TDG adopts a base-flipping mechanism to extrude the mispaired nucleobase into the enzyme active-site. The constructed kinetic network model elucidates six metastable states during the base-extrusion process and suggests an active role of TDG in flipping the intrahelical nucleobase. Finally, the molecular mechanism of product release dynamics after catalysis is also summarized. Taken together, we highlight to what extent the computational simulations advance our knowledge and understanding of the molecular mechanism underlying the conformational dynamics of TDG, as well as the limitations of current theoretical work.

Membrane materials that resist nonspecific or specific adsorption are urgently required in widespread practical applications, such as water purification, food processing, and life sciences. In water purification, inevitable membrane fouling not only limits membrane separation performance, leading to a decline in both permeance and selectivity, but also remarkably increases operation requirements, and augments extra maintenance costs and higher energy consumption. In this work, we report a freestanding interfacial polymerization (IP) fabrication strategy for in situ creation of asymmetric block copolymer (BCP) nanofilms with antifouling properties, greatly outperforming the conventional surface post‐modification approaches. The resultant free‐standing asymmetric BCP nanofilms with highly‐dense, highly‐hydrophilic polyethylene glycol (PEG) brushes on one side, can be readily formed via a typical IP process of a well‐defined double‐hydrophilic BCP composed of a highly‐efficient antifouling PEG block and a membrane‐forming multiamine block. The asymmetric BCP nanofilms have been applied for efficient and sustainable natural water purification, demonstrating extraordinary antifouling capabilities accompanied with superior separation performance far beyond commercial polyamide nanofiltration membranes. The antifouling behaviors of asymmetric BCP nanofilms derived from the combined effect of the hydration layer, electrostatic repulsion and steric hindrance were further elucidated by water flux and fouling resistance in combination with all‐atom molecular dynamics (MD) simulation. This work opens up a new avenue for the large‐scale and low‐cost creation of broad‐spectrum, asymmetric membrane materials with diverse functional "defect‐free" surfaces in real‐world applications. [ABSTRACT FROM AUTHOR]

The combustion process is complex and harsh, and the supersonic combustion flow field is also characterized by short duration and supersonic speed, which makes the real-time diagnostic technology for the transient environment extremely demanding. It is of great significance to realize high time-resolved accurate measurement of temperature, component concentration, and other parametric information of the combustion field to study the transient chemical reaction dynamics of the combustion field. Femtosecond CARS spectroscopy can effectively avoid the collision effect between particles in the measurement process and reduce the influence of the non-resonant background to improve the measurement accuracy and realize the time-resolved measurement on a millisecond scale. This paper introduces the development history of femtosecond CARS spectroscopy, points out its advantages and disadvantages, and looks forward to the future development trend to carry out high time-resolved measurements, establish a database of temperature changes in various complex combustion fields, and provide support for the study of engine mechanisms. [ABSTRACT FROM AUTHOR]

Background: Multiple cell death modalities are implicated in sepsis pathobiology. However, the clinical relevance of NINJ1, a key mediator of plasma membrane rupture during lytic cell death, in sepsis progression and outcomes has remained poorly explored., Methods: Circulating NINJ1 levels were measured in 116 septic ICU patients, 16 non-septic ICU controls, and 16 healthy controls. Comparative analysis of serum NINJ1 across these groups was performed. Correlations between NINJ1 and clinical disease severity scores (SOFA, APACHE II) as well as laboratory parameters were examined in the sepsis cohort. Furthermore, we assessed the prognostic performance of NINJ1 for predicting 28-day mortality in septic patients using receiver operating characteristic (ROC) analyses., Results: Circulating NINJ1 levels were elevated in septic patients and positively correlated with sepsis severity scores. NINJ1 also showed positive correlations with liver injury markers (AST/ALT) and coagulation parameters (D-dimer, APTT, PT, TT) in sepsis. Further analysis using the ISTH overt DIC scoring system revealed an association between NINJ1 and sepsis-induced coagulopathy.ROC analysis demonstrated NINJ1 outperformed traditional inflammatory biomarkers PCT and CRP in predicting 28-day sepsis mortality, although its prognostic accuracy was lower than SOFA and APACHE II scores. Combining NINJ1 with SOFA improved mortality prediction from an AUC of 0.6843 to 0.773., Conclusions: Circulating NINJ1 serves as a novel sepsis biomarker indicative of disease severity, coagulopathy and mortality risk, and its integration with SOFA and APACHE II scores substantially enhances prognostic risk stratification. These findings highlight the prospective clinical utility of NINJ1 for sepsis prognostication and monitoring, warranting further validation studies to facilitate implementation., (Copyright © 2024 by the Shock Society.)

Aβ 16 - 22 is believed to have critical role in early aggregation of full length amyloids that are associated with the Alzheimer's disease and can aggregate to form amyloid fibrils. However, the early aggregation mechanism is still unsolved. Here, multiple long-term molecular dynamics simulations combining with Markov state model were used to probe the early oligomerization mechanism of Aβ 16-22 peptides. The identified dimeric form adopted either globular random-coil or extended β-strand like conformations. The observed dimers of these variants shared many overall conformational characteristics but differed in several aspects at detailed level. In all cases, the most common type of secondary structure was intermolecular antiparallel β-sheets. The inter-state transitions were very frequent ranges from few to hundred nanoseconds. More strikingly, those states which contain fraction of β secondary structure and significant amount of extended coiled structures, therefore exposed to the solvent, were majorly participated in aggregation. The assembly of low-energy dimers, in which the peptides form antiparallel β sheets, occurred by multiple pathways with the formation of an obligatory intermediates. We proposed that these states might facilitate the Aβ 16-22 aggregation through a significant component of the conformational selection mechanism, because they might increase the aggregates population by promoting the inter-chain hydrophobic and the hydrogen bond contacts. The formation of early stage antiparallel β sheet structures is critical for oligomerization, and at the same time provided a flat geometry to seed the ordered β-strand packing of the fibrils. Our findings hint at reorganization of this part of the molecule as a potentially critical step in Aβ aggregation and will insight into early oligomerization for large β amyloids., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Physiological and behavioral rhythms are governed by an endogenous circadian clock. In this paper are reported the studies on soldier's circadian of melatonin concentrations by means of electricity and light pulses presented to the popliteal region (behind the knee). The results showed that the phase of melatonin concentrations can be regulated by both the electricity pulses and the light pulses. A systematic relation was found between the timing of the electro-stimulating and the magnitude and direction of phase shifts, resulting in the generation of a phase response curve. The phase response curve displayed photic model. These findings have implications for the development of more effective treatments for sleep and circadian rhythm disorders.