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MuB is a non-specific DNA-binding protein and AAA+ ATPase that significantly influences the DNA transposition process of bacteriophage Mu, especially in target DNA selection for transposition. While studies have established the ATP-dependent formation of MuB filament as pivotal to this process, the high-resolution structure of a full-length MuB protomer and the underlying molecular mechanisms governing its oligomerization remain elusive. Here, we use cryo-EM to obtain a 3.4-Å resolution structure of the ATP(+)-DNA(+)-MuB helical filament, which encapsulates the DNA substrate within its axial channel. The structure categorizes MuB within the initiator clade of the AAA+ protein family and precisely locates the ATP and DNA binding sites. Further investigation into the oligomeric states of MuB show the existence of various forms of the filament. These findings lead to a mechanistic model where MuB forms opposite helical filaments along the DNA, exposing potential target sites on the bare DNA and then recruiting MuA, which stimulates MuB's ATPase activity and disrupts the previously formed helical structure. When this happens, MuB generates larger ring structures and dissociates from the DNA. Here, Zhao et al. use cryo-EM to show how MuB forms helical filaments around DNA. These structures play a crucial role in target DNA selection and transposition, shedding light on MuB's functional mechanism. [ABSTRACT FROM AUTHOR]

Addressing environmental pollution, the present study proposes the utilization of natural products as alternatives to chemical additives in soap manufacturing. Specifically, the study explores the potential of the above-ground parts of Paris polyphylla (AGPP), an abundant but underexploited resource, in contrast to its overexploited and endangered underground parts of Paris polyphylla (UGPP). The AGPP was extracted with 75% (V/V) ethanol, yielding a significantly higher content of saponin VII compared to the UGPP extract (41.02 mg/g vs. 10.41 mg/g). Radical scavenging assays demonstrated the extract's effectiveness against DPPH, hydroxyl, and superoxide anion radicals. The extract was subsequently incorporated into a soap base, optimized via D-optimal mixture design to comprise 20.5% coconut oil, 42.5% olive oil, and 37% palm oil. Antibacterial studies indicated that the soap containing AGPP extract exhibited potent activity against Candida albicans and Propionibacterium acnes. These findings suggest the promising role of AGPP extract as a natural antioxidant and antimicrobial agent in the formulation of eco-friendly soap [ABSTRACT FROM AUTHOR]

In this paper, we establish an in situ visualization analysis method to image the spatial distribution of metabolites in different parts (sclerotium, coremium) and different microregions of Cordyceps cicadae (C. cicadae) to achieve the in situ visual characterization of tissues for a variety of metabolites such as nucleosides, amino acids, polysaccharides, organic acids, fatty acids, and so on. The study included LC–MS chemical composition identification, preparation of C. cicadae tissue sections, DEDI-MSI analysis, DESI combined with Q-TOF/MS to obtain high-resolution imaging of mass-to-charge ratio and space, imaging of C. cicadae in positive–negative ion mode with a spatial resolution of 100 μm, and localizing and identifying its chemical compositions based on its precise mass. A total of 62 compounds were identified; nucleosides were mainly distributed in the coremium, L-threonine and DL-isoleucine, and other essential amino acids; peptides were mainly distributed in the sclerotium of C. cicadae; and the rest of the amino acids did not have a clear pattern; sugars and sugar alcohols were mainly distributed in the coremium of C. cicadae; organic acids and fatty acids were distributed in the nucleus of C. cicadae more than in the sclerotium, and the mass spectrometry imaging method is established in the research. The mass spectrometry imaging method established in this study is simple and fast and can visualize and analyse the spatial distribution of metabolites of C. cicadae, which is of great significance in characterizing the metabolic network of C. cicadae, and provides support for the quality evaluation of C. cicadae and the study of the temporal and spatial metabolic network of chemical compounds. [ABSTRACT FROM AUTHOR]

Active fluids display collective phenomena such as active turbulence or odd viscosity, which refer to spontaneous complex and transverse flow. The simultaneous emergence of these seemingly separate phenomena is here reported in experiment for a chiral active fluid composed of a carpet of standing and spinning colloidal rods, and in simulations for synchronously rotating hard discs in a hydrodynamic explicit solvent. Experiments and simulations reveal that multi-scale eddies emerge, a hallmark of active turbulence, with a power-law decay of the kinetic-energy spectrum, a feature of self-similar dynamics. Moreover, the particles are dragged to the centre of the vortices, a telltale sign of odd viscosity. The weak compressibility of the system enables an explicit measurement of the odd viscosity in bulk via the relation between local vorticity and excess density. Our findings are relevant for the understanding of biological systems and for the design of microrobots with collective self-organized behavior. The investigation of a chiral active fluid composed of a carpet of standing and spinning colloidal rods, combined with simulations for synchronously rotating hard discs in a hydrodynamic explicit solvent reveals here the simultaneous occurrence and relation of two seemingly separate phenomena: active turbulence and odd viscosity. [ABSTRACT FROM AUTHOR]

Quercetin, a typical flavonoid derived from a common natural plant, has multiple biological activities. Previous research in animal models has demonstrated the effectiveness of quercetin in treating rheumatoid arthritis (RA). The pharmacological effects and probable mechanisms of quercetin were evaluated in this study. Three databases, PubMed, Web of Science, and Embase, were searched for relevant studies from the creation of the databases to November 2022. Methodological quality was assessed using the SYRCLE risk of bias tool. STATA 15.1 was used to perform the statistical analysis. This research included 17 studies involving 251 animals. The results indicated that quercetin was able to reduce arthritis scores, paw swelling, histopathological scores, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), C-reactive protein (CRP), malondialdehyde (MDA), reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), nuclear factor kappa B (NF-kB) and increase interleukin-10 (IL-10), catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), glutathione (GSH), and heme oxygenase-1 (HO-1). These may be related to quercetin's potential anti-inflammatory, anti-oxidative stress, and osteoprotective properties. However, more high-quality animal studies are needed to assess the effect of quercetin on RA. Additionally, the safety of quercetin requires further confirmation. Given the importance of the active ingredient, dose selection and the improvement of quercetin's bioavailability remain to be explored. [ABSTRACT FROM AUTHOR]

The transient receptor potential channel subfamily A member 1 (TRPA1) ion channel is an evolutionary conserved polymodal sensor responding to noxious temperature or chemical stimuli. Notably, the thermosensitivity of TRPA1 varies among different species or even different isoforms in the same species. However, the underlying molecular basis of its thermo-gating remains largely unknown. Here, we determine the structures of a heat-sensitive isoform of TRPA1 in Drosophila melanogaster in two distinct conformations with cryo-samples prepared at 8 °C. Large conformational changes are observed in the ankyrin repeat domain (ARD) and the coiled-coil domain between the two states. Remarkably, all 17 ankyrin repeats are mapped in the newly resolved conformation, forming a propeller-like architecture. Two intersubunit interfaces are identified in the amino (N)-terminal domain, and play vital roles during both heat and chemical activation as shown by electrophysiological analysis. With cryo-samples prepared at 35 °C, only one conformation is resolved, suggesting possible state transitions during heat responses. These findings provide a basis for further understanding how the ARD regulates channel functions, and insights into the gating mechanism of TRPA1. [ABSTRACT FROM AUTHOR]

Stomata play a critical role in the regulation of gas exchange and photosynthesis in plants. Stomatal closure participates in multiple stress responses, and is regulated by a complex network including abscisic acid (ABA) signaling and ion-flux-induced turgor changes. The slow-type anion channel SLAC1 has been identified to be a central controller of stomatal closure and phosphoactivated by several kinases. Here, we report the structure of SLAC1 in Arabidopsis thaliana (AtSLAC1) in an inactivated, closed state. The cytosolic amino (N)-terminus and carboxyl (C)-terminus of AtSLAC1 are partially resolved and form a plug-like structure which packs against the transmembrane domain (TMD). Breaking the interactions between the cytosolic plug and transmembrane domain triggers channel activation. An inhibition-release model is proposed for SLAC1 activation by phosphorylation that the cytosolic plug dissociates from the transmembrane domain upon phosphorylation, and induces conformational changes to open the pore. These findings facilitate our understanding of the regulation of SLAC1 activity and stomatal aperture in plants. The anion channel SLAC1 controls stomatal closure upon phosphoactivation. Here via structural analysis and electrophysiology, the authors propose an inhibition-release model where phosphorylation causes dissociation of a cytosolic plug from the SLAC1 transmembrane domains to induce conformational change in the pore-forming helices. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the changes of Helper T cells 17 (Th17 cells), Regulatory T cells (Treg cells), Treg/Th17, Interleukin-17 (IL-17) and Interleukin-10 (IL-10) in patients with type 2 diabetes mellitus (T2DM). Methods: Four electronic resource databases were searched from their inception to 1 August 2021. Case-control studies about changes of Th17 cells, Treg cells, Treg/Th17, IL-17 and IL-10 in patients with T2DM were retrieved. We performed this meta-analysis via RevMan V.5.3 and Stata14. Results: 20 studies with 1242 individuals were included in the meta-analysis. Compared with the controls, the patients with T2DM had significantly increased levels of percentage of Th17 cells (SMD, 1.74; 95% CI, 0.47–3.01; p < 0.001), IL-17 (SMD, 2.17; 95% CI, 0.06–4.28; p < 0.001), IL-10 (SMD, 1.20; 95% CI, 0.81–1.59; p = 0.003), but decreased levels of percentage of Treg cells (SMD, −1.17; 95% CI, −2.22 to −0.13; p < 0.001) and Treg/Th17 ratio (SMD, −4.43; 95% CI, −7.07 to −1.78; p < 0.001). Subgroup analysis showed that percentage of CD4+CD25+FOXP3+ Tregs (SMD, −2.36; 95% CI, −3.19 to −1.52; p = 0.003) in patients was notably lower than controls. While not significant changes were found in the percentage of CD4+CD25+Tregs (SMD, 0.03; 95% CI, −0.34–0.40; p = 0.63) between patients and controls. For plasma or serum IL-10, a higher plasma IL-10 level (SMD,1.37; 95% CI, 0.92–1.82; p = 0.01) was observed in T2DM. While serum IL-10 (SMD, 0.73; 95% CI, 0.35–1.12; p = 0.79) had no obvious difference between patients and controls. For ELISA or flow cytometry, IL-10 (SMD, 1.2; 95% CI, 0.71–1.70; p = 0.001) was higher in T2DM patients by using detection method of ELISA. Yet IL-10 using flow cytometry and subgroup analysis of IL-17 had no significant differences. Conclusions: Adaptive immune system indeed plays an essential role in the process of T2DM. Imbalance between Th17 and Treg triggers pro-inflammatory environment in patients with T2DM. [ABSTRACT FROM AUTHOR]

The interaction of platelet GPIbα with von Willebrand factor (VWF) is essential to initiate platelet adhesion and thrombosis, particularly under high shear stress conditions. However, no drug targeting GPIbα has been developed for clinical practice. Here we characterized anfibatide, a GPIbα antagonist purified from snake (Deinagkistrodon acutus) venom, and evaluated its interaction with GPIbα by surface plasmon resonance and in silico modeling. We demonstrated that anfibatide interferds with both VWF and thrombin binding, inhibited ristocetin/botrocetin- and low-dose thrombin-induced human platelet aggregation, and decreased thrombus volume and stability in blood flowing over collagen. In a single-center, randomized, and open-label phase I clinical trial, anfibatide was administered intravenously to 94 healthy volunteers either as a single dose bolus, or a bolus followed by a constant rate infusion of anfibatide for 24 h. Anfibatide inhibited VWF-mediated platelet aggregation without significantly altering bleeding time or coagulation. The inhibitory effects disappeared within 8 h after drug withdrawal. No thrombocytopenia or anti-anfibatide antibodies were detected, and no serious adverse events or allergic reactions were observed during the studies. Therefore, anfibatide was well-tolerated among healthy subjects. Interestingly, anfibatide exhibited pharmacologic effects in vivo at concentrations thousand-fold lower than in vitro, a phenomenon which deserves further investigation. Trial registration: Clinicaltrials.gov NCT01588132. [ABSTRACT FROM AUTHOR]

Electrocardiography is a useful diagnostic tool for various cardiovascular diseases, such as myocardial infarction (MI). An electrocardiograph (ECG) records the electrical activity of the heart, which can reflect any abnormal activity. MI recognition by visual examination of an ECG requires an expert's interpretation and is difficult because of the short duration and small amplitude of the changes in ECG signals associated with MI. Therefore, we propose a new method for the automatic detection of MI using ECG signals. In this study, we used maximal overlap discrete wavelet transform to decompose the data, extracted the variance, inter-quartile range, Pearson correlation coefficient, Hoeffding's D correlation coefficient and Shannon entropy of the wavelet coefficients and used the k-nearest neighbor model to detect MI. The accuracy, sensitivity and specificity of the model were 99.57%, 99.82% and 98.79%, respectively. Therefore, the system can be used in clinics to help diagnose MI. [ABSTRACT FROM AUTHOR]

The deep-lake facies of the Yanchang Formation represents a large outflowing lake basin in the Ordos area. Its deposition can be divided into four stages: lake genetic and expanding stage, peak stage, inversion stage and dying stage. All the stages are obviously consistent with the evolution of depositional environment and the paleoclimate in the region. The study indicates that the lake basin has evolution fluctuations from highstand to lowstand for four times in its evolution history, and the deposition center of the lake has not obviously moved, staying along the Huachi-Yijun belt. The deep lake sedimentary system mainly consists of deep water deltas and turbidite fans during the entire evolution course of the lake basin in the Late Triassic. The former mainly developed on the slope of steep shore of the delta in the early period of the deep-water expansion and gradually experienced a big shift from deep-water deltas to shallow-water platform delta. And the latter appeared almost in all the above stages and had two types of turbidite fans, slope-moving turbidite fans and slump turbidite fans. The slope-moving turbidite fans have relatively complete facies belts overlapping one another vertically and consist of the slope channel of inter fans, the turbidite channel, inter turbidite channel and turbidite channel front of middle fans and outer fans (or lakebottom plain). However, the slide-moving turbidity fans are formed in the deep lake with their microfacies difficult to be distinguished, and only the center microfacies and edge microfacies can be determined. The two types of the turbidity fans are similarly distributing in the near-root-slope and far-root-slope regions. The deep-lake deposition governs the distribution of the hydrocarbon and reservoir, while the slope-moving turbidite fans are excellent reservoirs for oil-gas exploration due to their great thickness, widespread distribution and accumulation properties. [ABSTRACT FROM AUTHOR]