Search

Abstract Recruitment of non-canonical BCOR-PRC1.1 to non-methylated CpG islands via KDM2B plays a fundamental role in transcription control during developmental processes and cancer progression. However, the mechanism is still largely unknown on how this recruitment is regulated. Here, we unveiled the importance of the Poly-D/E regions within the linker of BCOR for its binding to KDM2B. Interestingly, we also demonstrated that these negatively charged Poly-D/E regions on BCOR play autoinhibitory roles in liquid-liquid phase separation (LLPS) of BCORANK-linker-PUFD/PCGF1RAWUL. Through neutralizing negative charges of these Poly-D/E regions, Ca2+ not only weakens the interaction between BCOR/PCGF1 and KDM2B, but also promotes co-condensation of the enzymatic core of BCOR-PRC1.1 with KDM2B into liquid-like droplet. Accordingly, we propose that Ca2+ could modulate the compartmentation and recruitment of the enzymatic core of BCOR-PRC1.1 on KDM2B target loci. Thus, our finding advances the mechanistic understanding on how the tethering of BCOR-PRC1.1 enzymatic core to KDM2B is regulated.

GPCR-G protein signaling from endosomes plays a crucial role in various physiological and pathological processes. However, the mechanism by which endosomal G protein signaling is terminated remains largely unknown. In this study, we aimed to investigate the regulatory mechanisms involved in terminating the signaling of Gα subunits from endosomes. Through structural analysis and cell-based assays, we have discovered that SNX25, a protein that targets endosomes via its PXA or PXC domain, interacts with regulator of G protein signaling (RGS) proteins (including RGS2, RGS4, RGS8, and RGS17) in a redox-regulated manner. The interaction between SNX25 and these RGS proteins enhances their GTPase-accelerating activity towards Gαi/q and their ability to bind GDP-bound (inactive form) Gαi/q. As a result, SNX25 recruits these RGS proteins to endosomes, leading to the termination of endosomal Gαi/q signaling. Furthermore, we have found that the SNX25/RGS complex also exerts a negative regulatory effect on Gαi/q signaling from the plasma membrane. This is achieved by recruiting Gαi/q to endosomes and preventing its activation on the plasma membrane. Our findings shed light on the previously unknown role of redox-modulated SNX25 in inhibiting Gαi/q signaling, thereby uncovering a novel mechanism for terminating Gαi/q signaling from endosomes. Importantly, this study expands our understanding of the regulation of GPCR-Gαi/q signaling beyond the plasma membrane.

ObjectiveThis study investigates the prognostic significance of inflammatory nutritional scores in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) undergoing neoadjuvant chemoimmunotherapy.MethodsA total of 190 LA-ESCC patients were recruited from three medical centers across China. Pre-treatment laboratory tests were utilized to calculate inflammatory nutritional scores. LASSO regression and multivariate logistic regression analyses were conducted to pinpoint predictors of pathological response. Kaplan-Meier and Cox regression analyses were employed to assess disease-free survival (DFS) prognostic factors.ResultsThe cohort comprised 154 males (81.05%) and 36 females (18.95%), with a median age of 61.4 years. Pathological complete response (pCR) was achieved in 17.38% of patients, while 44.78% attained major pathological response (MPR). LASSO and multivariate logistic regression analyses identified that hemoglobin, albumin, lymphocyte, and platelet (HALP) (P=0.02) as an independent predictors of MPR in LA-ESCC patients receiving neoadjuvant chemoimmunotherapy. Kaplan-Meier and log-rank tests indicated that patients with low HALP, MPR, ypT1-2, ypN0 and, ypTNM I stages had prolonged DFS (P < 0.05). Furthermore, univariate and multivariate Cox regression analyses underscored HALP (P = 0.019) and ypT (P = 0.029) as independent predictive factors for DFS in ESCC.ConclusionOur study suggests that LA-ESCC patients with lower pre-treatment HALP scores exhibit improved pathological response and reduced recurrence rate. As a comprehensive index of inflammatory nutritional status, pre-treatment HALP may be a reliable prognostic marker in ESCC patients undergoing neoadjuvant chemoimmunotherapy.

Synechococcus are widely distributed in the global ocean, from the pelagic zone to coastal waters. However, little is known about Synechococcus in coastal seawater due to limitations in isolation and culture conditions. In this study, a combination of metagenomic sequencing technology, flow cytometry sorting, and multiple displacement amplification was used to investigate Synechococcus in the coastal seawater of Xiamen Island. The results revealed 18 clades of Synechococcus and diverse metabolic genes that appear to contribute to their adaptation to the coastal environment. Intriguingly, some metabolic genes related to the metabolism of carbohydrates, energy, nucleotides, and amino acids were found in 89 prophage regions that were detected in 16,258 Synechococcus sequences. The detected metabolic genes can enable prophages to contribute to the adaptation of Synechococcus hosts to the coastal marine environment. The detection of prophages also suggests that the cyanophages have infected Synechococcus. On the other hand, the identification of 773 genes associated with antiviral defense systems indicates that Synechococcus in Xiamen have evolved genetic traits in response to cyanophage infection. Studying the community diversity and functional genes of Synechococcus provides insights into their role in environmental adaptation and marine ecosystems.

Purpose: The study aim to construct an effective model for predicting the survival period of COVID-19 patients. Methods: Clinical data of 386 COVID-19 patients were collected from December 2022 to January 2023. The patients were randomly divided into training and validation cohorts in a 7:3 ratio. LASSO regression and multivariate Cox regression analyses were used to identify prognostic factors, and a nomogram was constructed. Nomogram was evaluated using decision curve analysis, receiver operating characteristic curve, consistency index (c-index), and calibration curve. Results: 86 patients (22.3%) died. A new nomogram for predicting the survival was established based on age, resting oxygen saturation, Blood urea nitrogen (BUN), c-reactive protein-to-albumin ratio (CAR), and pneumonia visual score. The decision curve indicated high clinical applicability. The nomogram c-indexes in the training and validation cohorts were 0.846 and 0.81, respectively. The area under the curves (AUCs) for the 15-day and 30-day survival probabilities were 0.906 and 0.869 in the training cohort, and 0.851 and 0.843 in the validation cohort. The calibration curves demonstrated consistency between predicted and actual survival probabilities. Conclusions: Our nomogram has the capacity to assist clinical practitioners in estimating the survival rate of COVID-19 patients, thereby facilitating more optimal management strategies and therapeutic interventions with substantial clinical applicability.

The phase separation behaviour of non-structure protein nsp8 of SARS CoV2 in the primer synthesis mechanism is presented, underpinning the replication of coronavirus.

PurposeThe present study aims to identify factors related to anastomotic leakage before esophagectomy and to construct a prediction model.MethodsA retrospective analysis of 285 patients who underwent minimally invasive esophagectomy (MIE). An absolute shrinkage and selection operator was applied to screen the variables, and predictive models were developed using binary logistic regression.ResultsA total of 28 variables were collected in this study. LASSO regression analysis, combined with previous literature and clinical experience, finally screened out four variables, including aortic calcification, heart disease, BMI, and FEV1. A binary logistic regression was conducted on the four predictors, and a prediction model was established. The prediction model showed good discrimination and calibration, with a C-statistic of 0.67 (95% CI, 0.593–0.743), a calibration curve fitting a 45° slope, and a Brier score of 0.179. The DCA demonstrated that the prediction nomogram was clinically useful. In the internal validation, the C-statistic still reaches 0.66, and the calibration curve has a good effect.ConclusionsWhen patients have aortic calcification, heart disease, obesity, and a low FEV1, the risk of anastomotic leakage is higher, and relevant surgical techniques can be used to prevent it. Therefore, the clinical prediction model is a practical tool to guide surgeons in the primary prevention of anastomotic leakage.

Abstract The quality of high energy flash X‐ray images is crucial to the high‐precision diagnosis of object density. High energy flash X‐ray radiography is susceptible to the system blur, which usually causes the poor quality of static images. In response to this, a novel restoration algorithm using region extrema and kernel optimization (REKO) is presented. Based on the observation that the region extrema distribution of blurred high energy flash X‐ray images deviates from opposite ends of image grey domain, the sparseness‐inducing prior for regularizing image region extrema is applied to construct the restoration model. Considering the sparse characteristics of blur kernels, the sparseness‐inducing regularization is incorporated to constrain blur kernels in the restoration model. The non‐convex and non‐linear objective function is gradually minimized through energy alternating minimization and dually linear approximation. Furthermore, a continuity enforced kernel optimization algorithm is proposed to estimate more accurate blur kernels. The discontinuous kernel elements are suppressed by extracting the main structure of blur kernels and constructing kernel continuity function in cross windows. Experimental results demonstrate that our algorithm can more accurately estimate blur kernels and achieve restoration results with sharper edges on high energy flash X‐ray images.

In this study, solidified films of CaO-Al2O3-BaO-CaF2-Li2O-based mold fluxes with different contents of Al2O3 addition were acquired by immersing an improved water-cooled copper probe in bulk molten slags. This probe can obtain films with representative structures. Different slag temperatures and probe immersion times were employed to investigate the crystallization process. The crystals in the solidified films were identified using X-ray diffraction, the morphologies of the crystals were observed using optical microscopy and scanning electron microscopy, and the kinetic conditions, especially the activation energy of devitrified crystallization in glassy slags, were calculated and discussed based on the differential scanning calorimetry. The results indicated that after adding extra Al2O3, the growing speed and thickness of the solidified films increased, and more time was required for the film thickness to reach a steady state. In addition, fine spinel (MgAl2O4) precipitated in the films at the early stage of solidification after adding 10 wt% of extra Al2O3. Together with LiAlO2, spinel (MgAl2O4) acted as nuclei for the precipitation of BaAl2O4. The apparent activation energy of initial devitrified crystallization decreased from 314.16 KJ/mol (original slag) to 297.32 KJ/mol (5 wt% Al2O3 added) and 269.46 KJ/mol (10 wt% Al2O3 added). The crystallization ratio of the films also increased after adding extra Al2O3.

Dissolved organic matter (DOM) changes in quantity and quality over time and space, especially in highly dynamic coastal estuaries. Bacterioplankton usually display seasonal and spatial variations in abundance and composition in the coastal regions, and influence the DOM pool via assimilation, transformation and release of organic molecules. The change in DOM can also affect the composition of bacterial community. However, little is known on the correspondence between DOM molecules and bacterial composition, particularly through a systematic field survey. In this study, the spatiotemporal signatures of microbial communities and DOM composition in the subtropical coastal estuary of Xiamen are investigated over one and half years. The co-occurrence analysis between bacteria and DOM suggested microorganisms likely transformed the DOM from a relatively high (>400 Da) to a low (

In order to achieve the dual needs of single-phase vibration reduction and lightweight, a square honeycomb acoustic metamaterials with local resonant Archimedean spirals (SHAMLRAS) is proposed. The independent geometry parameters of SHAMLRAS structures are acquired by changing the spiral control equation. The mechanism of low-frequency bandgap generation and the directional attenuation mechanism of in-plane elastic waves are both explored through mode shapes, dispersion surfaces, and group velocities. Meanwhile, the effect of the spiral arrangement and the adjustment of the equation parameters on the width and position of the low-frequency bandgap are discussed separately. In addition, a rational period design of the SHAMLRAS plate structure is used to analyze the filtering performance with transmission loss experiments and numerical simulations. The results show that the design of acoustic metamaterials with multiple Archimedean spirals has good local resonance properties, and forms multiple low-frequency bandgaps below 500 Hz by reasonable parameter control. The spectrograms calculated from the excitation and response data of acceleration sensors are found to be in good agreement with the band structure. The work provides effective design ideas and a low-cost solution for low-frequency noise and vibration control in the aeronautic and astronautic industries.

To better monitor the state of isolating switches, an efficient binocular vision-based state measurement system is proposed in this article. Two optimal cameras are selected as the vision of our inspection system. Firstly, stereo calibration and distortion rectification are performed on acquired image pair. Secondly, to recover the three-dimensional information of switch, we propose a semi-global stereo matching method by using data- and structure-driven cost volume fusion and then optimizing raw disparity map with weighted- and edge discriminated-smoothness prior. Gradient content is enforced on the weight for suppressing small-weight-accumulation problem in weak-textured regions. Besides, Hough transform with feature constraints is implemented for removing the chaotic lines and extracting center line of the switch arm. Finally, based on the center line and corresponding disparity map of the switch arm, triangulation principle is used for calculating the true angle between the switch arm and insulator such that whether or not the isolating switch is fully closed can be detected. The experimental results demonstrate that the proposed stereo matching method can achieve good performance in Middlebury v.3 data set and switch images, and the system can precisely measure the state of switches.

Thermostability and substrate specificity are important characteristics of enzymes for industrial application, which can be improved by protein engineering. SMG1 lipase from Malassezia globosa is a mono- and diacylglycerol lipase (MDL) that shows activity toward mono- and diacylglycerols, but no activity toward triacylglycerols. SMG1 lipase is considered a potential biocatalyst applied in oil/fat modification and its crystal structure revealed that an interesting residue-Asn277 may contribute to stabilize loop 273–278 and the 3104 helix which are important to enzyme characterization. In this study, to explore its role in affecting the stability and catalytic activity, mutagenesis of N277 with Asp (D), Val (V), Leu (L) and Phe (F) was conducted. Circular dichroism (CD) spectral analysis and half-life measurement showed that the N277D mutant has better thermostability. The melting temperature and half-life of the N277D mutant were 56.6 °C and 187 min, respectively, while that was 54.6 °C and 121 min for SMG1 wild type (WT). Biochemical characterization of SMG1 mutants were carried out to test whether catalytic properties were affected by mutagenesis. N277D had similar enzymatic properties as SMG1 WT, but N277F showed a different substrate selectivity profile as compared to other SMG1 mutants. Analysis of the SMG1 3D model suggested that N277D formed a salt bridge via its negative charged carboxyl group with a positively charged guanidino group of R227, which might contribute to confer N277D higher temperature stability. These findings not only provide some clues to understand the molecular basis of the lipase structure/function relationship but also lay the framework for engineering suitable MDL lipases for industrial applications.

Clay-aggregate mixtures are frequently used in engineering practice. To improve the understanding of the effects of coarse particles on the dynamic behavior of clay-aggregate mixtures, series of stress controlled cyclic triaxial tests were performed on clay specimens with various glass bead contents. The results show that the initial shear modulus of clay-aggregate mixtures increased with the increase of the coarse aggregate content and the confining stress. At the confining stress of 100, 200, and 400 kPa, the addition of 32% coarse particles caused an increase in the initial shear modulus of 117%, 110%, and 67%, respectively. Moreover, the normalized shear modulus decreased and damping ratio increased with the coarse aggregate content, and the influence of the confining stress on the strain-dependent dynamic properties was negligible. The specimen with a higher coarse aggregate content was observed to have larger cyclic shear strength and smaller excess pore water pressure, but the effects of the coarse aggregate content became less pronounced under large cyclic stresses.