Molecular basis of global promoter sensing and nucleosome capture by the SWR1 chromatin remodeler.

The SWR1 chromatin remodeling complex is recruited to +1 nucleosomes downstream of transcription start sites of eukaryotic promoters, where it exchanges histone H2A for the specialized variant H2A.Z. Here, we use cryoelectron microscopy (cryo-EM) to resolve the structural basis of the SWR1 interaction with free DNA, revealing a distinct open conformation of the Swr1 ATPase that enables sliding from accessible DNA to nucleosomes. A complete structural model of the SWR1-nucleosome complex illustrates critical roles for Swc2 and Swc3 subunits in oriented nucleosome engagement by SWR1. Moreover, an extended DNA-binding α helix within the Swc3 subunit enables sensing of nucleosome linker length and is essential for SWR1-promoter-specific recruitment and activity. The previously unresolved N-SWR1 subcomplex forms a flexible extended structure, enabling multivalent recognition of acetylated histone tails by reader domains to further direct SWR1 toward the +1 nucleosome. Altogether, our findings provide a generalizable mechanism for promoter-specific targeting of chromatin and transcription complexes.

Optical super-resolution nanothermometry via stimulated emission depletion imaging of upconverting nanoparticles.

From engineering improved device performance to unraveling the breakdown of classical heat transfer laws, far-field optical temperature mapping with nanoscale spatial resolution would benefit diverse areas. However, these attributes are traditionally in opposition because conventional far-field optical temperature mapping techniques are inherently diffraction limited. Optical super-resolution imaging techniques revolutionized biological imaging, but such approaches have yet to be applied to thermometry. Here, we demonstrate a super-resolution nanothermometry technique based on highly doped upconverting nanoparticles (UCNPs) that enable stimulated emission depletion (STED) super-resolution imaging. We identify a ratiometric thermometry signal and maintain imaging resolution better than ~120 nm for the relevant spectral bands. We also form self-assembled UCNP monolayers and multilayers and implement a detection scheme with scan times >0.25 µm2/min. We further show that STED nanothermometry reveals a temperature gradient across a joule-heated microstructure that is undetectable with diffraction limited thermometry, indicating the potential of this technique to uncover local temperature variation in wide-ranging practical applications.

Psychological impacts of lobectomy and total thyroidectomy in PTC measuring 1 to 4 cm with low to intermediate risk of recurrence.

PURPOSE: To investigate the implications of Lobectomy (LT) or total thyroidectomy (TT) on psychological distress and sleep quality in PTC patients with a low to intermediate risk of recurrence and tumors measuring 1 to 4 cm. METHODS: Patients who were admitted to our hospital between July 2021 and July 2022 were prospectively enrolled in this survey. Psychological distress and sleep quality were assessed at hospitalization, discharge, and 1, 3, and 6 months post-treatment using validated scales. Participants were divided into LT and TT groups, with propensity score matching (PSM) applied for analyses. RESULTS: Among 525 eligible PTC patients, 440 patients completed all the questionnaires throughout the follow-up. After PSM, 166 patients underwent LT, and 166 patients underwent TT were enrolled. The psychological distress and sleep quality of patients in the LT group remained relatively stable during the 6-month follow-up, but patients in the TT group may have faced greater sleep quality concerns in the longitudinal assessment. Additionally, the sleep quality of the TT group was also worse than that of the LT group postoperatively. CONCLUSIONS: The sleep quality rather than other psychological distress of patients with PTC with a low to intermediate risk of recurrence is associated with the extent of surgery.

On-chip photonic convolution by phase-change in-memory computing cells with quasi-continuous tuning.

Matrix multiplication acceleration by on-chip photonic integrated circuits (PICs) is emerging as one of the attractive and promising solutions, offering outstanding benefits in speed and bandwidth as compared to non-photonic approaches. Incorporating nonvolatile phase-change materials into PICs or devices enables optical storage and computing, surpassing their electrical counterparts. In this paper, we propose a design of on-chip photonic convolution for optical in-memory computing by integrating the phase change chalcogenide of Ge2Sb2Se4Te1 (GSST) into an asymmetric directional coupler for constructions of an in-memory computing cell, marrying the advantages of both the large bandwidth of Mach-Zehnder interferometers (MZIs) and the small size of micro-ring resonators (MRRs). Through quasi-continuous electro-thermal tuning of the GSST-integrated in-memory computing cells, numerical calculations about the optical and electro-thermal behaviors during GSST phase transition confirm the tunability of the programmable elements stored in the in-memory computing cells within [-1, 1]. For proof-of-concept verification, we apply the proposed optical convolutional kernel to a typical image edge detection application. As evidenced by the evaluation results, the prototype achieves the same accuracy as the convolution kernel implemented on a common digital computer, demonstrating the feasibility of the proposed scheme for on-chip photonic convolution and optical in-memory computing.

Scutellarein alleviates osteoarthritis progression through the PI3K/Akt/NF-kappaB signaling pathway: In vitro and in vivo studies.

Osteoarthritis (OA), a joint disease that is associated with inflammatory processes is involved in joint destruction. Scutellarein (Scu), a component of the medicinal herbs Scutellaria barbata D. Don and Erigeron breviscapus (vant) Hand Mass, has anti-inflammatory effects. We explored the role of Scu in the development of OA and the underlying mechanisms. CCK-8 assays, Calcein-AM/PI and EdU staining were used to determine chondrocyte viability after Scu exposure. Western blot, qPCR, as well as ELISA were utilized to measure extracellular matrix (ECM) degradation and inflammation. Immunofluorescence (IF), western blot and luciferase assays were used to examine the NF-kappaB (NF-κB) pathway. Scu interacting proteins were predicted using network pharmacology analysis and molecular docking. X-ray, H&E, Safranin O-Fast Green(S-O), toluidine blue, and immunohistochemistry analysis were used to examine the therapeutic effects of Scu in OA using destabilization of medial meniscus (DMM) models. Scu demonstrated inhibitory effects on ECM degradation and pro-inflammatory factor levels in chondrocytes treated with IL-1ß. Mechanistically, Scu inhibited the IL-1ß-induced activation of the PI3K/Akt/ NF-κB signaling pathway cascades. Furthermore, Scu has been shown to have significant binding capacities to PI3K. Additionally, Scu ameliorated the OA progression in DMM models. Our findings suggest that Scu may contribute to the amelioration of OA progression by targeting the PI3K/Akt/NF-κB signaling pathway, implying Scu possesses promising therapeutic potential for the treatment of OA.

A fast and efficient liquid chromatography-tandem mass spectrometry method for measuring l- and d-amino acids in the urine of patients with immunoglobulin A nephropathy.

Immunoglobulin nephropathy (IgAN) stands as the most prevalent primary glomerular nephropathy globally, typically diagnosed through an invasive renal biopsy. Emerging research suggests the significant involvement of chiral amino acids in kidney disease progression. This study introduces a nonderivative LC-tandem mass spectrometry approach, offering efficient separation outcomes within 15 min for identifying chiral amino acids in human urine samples. Subsequently, using this method, the analysis of l- and d-amino acids in the urine of both patients with IgAN and healthy individuals was conducted. Fourteen d-amino acids and 20 l-amino acids were identified in the urine samples obtained from 17 patients with IgAN and 21 healthy individuals. The results indicated notable variances in the concentrations of both l- and d-amino acids between the IgAN and healthy control groups. In contrast to the healthy group, the IgAN group exhibited higher mean urine concentrations of most l-amino acids and lower concentrations of d-amino acids. Furthermore, correlations between amino acids and clinical markers were investigated. These results propose a novel method for monitoring trace amino acids in urine samples and introduce a new concept for potential markers of IgAN.

Generating robust aptamers for food analysis by sequence-based configuration optimization.

Advanced analytical techniques are emerging in the food industry. Aptamer-based biosensors achieve rapid and highly selective analysis, thus drawing particular attention. Aptamers are oligonucleotide probes screened via in vitro Systematic Evolution of Ligands by EXponential Enrichment (SELEX), which can bind with their specific targets by folding into three-dimensional configurations and accept various modifications to be incorporated into biosensors, showing great potential in food analysis. Unfortunately, aptamers obtained by SELEX may not possess satisfactory affinity. Post-SELEX strategies were proposed to optimize aptamers' configuration and enhance the binding affinity, with specificity confirmed. Sequence-based optimization strategies exhibit great advantages in simple operation, good generalization, low cost, etc. This review summarizes the latest study (2015-2023) on generating robust aptamers for food targets by sequence-based configuration optimization, as well as the generated aptamers and aptasensors, with an expectation to provide inspirations for developing aptamer and aptasensors with high performance for food analysis and to safeguard food quality and safety.

Disordered C-terminal domain drives spatiotemporal confinement of RNAPII to enhance search for chromatin targets.

Efficient gene expression requires RNA polymerase II (RNAPII) to find chromatin targets precisely in space and time. How RNAPII manages this complex diffusive search in three-dimensional nuclear space remains largely unknown. The disordered carboxy-terminal domain (CTD) of RNAPII, which is essential for recruiting transcription-associated proteins, forms phase-separated droplets in vitro, hinting at a potential role in modulating RNAPII dynamics. In the present study, we use single-molecule tracking and spatiotemporal mapping in living yeast to show that the CTD is required for confining RNAPII diffusion within a subnuclear region enriched for active genes, but without apparent phase separation into condensates. Both Mediator and global chromatin organization are required for sustaining RNAPII confinement. Remarkably, truncating the CTD disrupts RNAPII spatial confinement, prolongs target search, diminishes chromatin binding, impairs pre-initiation complex formation and reduces transcription bursting. The present study illuminates the pivotal role of the CTD in driving spatiotemporal confinement of RNAPII for efficient gene expression.

Clinical Outcomes and Implications of Radioactive Iodine Therapy on Cancer-specific Survival in WHO Classification of FTC.

BACKGROUND: The clinical outcomes and implications of radioactive iodine therapy (RAIT) on cancer-specific survival (CSS) in World Health Organization classification of follicular thyroid carcinoma (FTC) are not well established. MATERIAL AND METHODS: The data of eligible patients with minimally invasive FTC (mi-FTC), encapsulated angioinvasive FTC (ea-FTC), or widely invasive FTC (wi-FTC) between 2000 and 2020 were extracted from the Surveillance, Epidemiology, and End Results database. CSS, the primary outcome, was compared among the 3 subtypes of patients with FTC before and after adjusting for differences using propensity score matching (PSM). The patients with FTC in different subtypes were then divided into 2 groups: the RAIT group and the no-RAIT group. Cox proportional hazards regression analyses were applied to discover the relationships of factors associated with CSS in the each PSM cohort. RESULTS: A total of 2433 patients with mi-FTC, 216 patients with ea-FTC, and 554 patients with wi-FTC were enrolled in the original cohorts, respectively. Patients with mi-FTC or ea-FTC had similar CSS (P = .805), which was better than that of patients with wi-FTC (P < .001; P = .021). Cox proportional hazards regression analysis revealed that RAIT was not associated with improved CSS in either the mi-FTC PSM cohort (hazard ratio [HR], 1.21; 95% CI, .46-3.18; P = .705) or the wi-FTC PSM cohort (HR, 0.56; 95% CI, .35-1.08; P = .086). However, subgroup analysis demonstrated that patients with wi-FTC and N1 stage (HR, 0.44; 95% CI, .20-.99; P = .018) or M1 stage (HR, 0.25; 95% CI, .11-.53; P < .001) could gain CSS advantage from RAIT. CONCLUSION: The RAIT can provide a CSS advantage for patients with wi-FTC who with N1-stage or M1-stage disease.

Luminescence Thermometry Beyond the Biological Realm.

As the field of luminescence thermometry has matured, practical applications of luminescence thermometry techniques have grown in both frequency and scope. Due to the biocompatibility of most luminescent thermometers, many of these applications fall within the realm of biology. However, luminescence thermometry is increasingly employed beyond the biological realm, with expanding applications in areas such as thermal characterization of microelectronics, catalysis, and plasmonics. Here, we review the motivations, methodologies, and advances linked to nonbiological applications of luminescence thermometry. We begin with a brief overview of luminescence thermometry probes and techniques, focusing on those most commonly used for nonbiological applications. We then address measurement capabilities that are particularly relevant for these applications and provide a detailed survey of results across various application categories. Throughout the review, we highlight measurement challenges and requirements that are distinct from those of biological applications. Finally, we discuss emerging areas and future directions that present opportunities for continued research.