Strong and Tough Poly(2-Isopropenyl-2-Oxazoline) Hydrogels with Terpyridine as Dual Orthogonal Covalent and Non-Covalent Crosslinker.

Developing simple and efficient methods to mechanically reinforce single-network hydrogels for practical applications remains an important challenge. This study presents a strategy for preparing poly(2-isopropenyl-2-oxazoline) (PiPOx) hydrogels using a dicarboxylic acid functionalized terpyridine (TPy) dual orthogonal crosslinker that acts as both a permanent covalent crosslinker and a dynamic non-covalent crosslinker upon metal complexation. In this dual orthogonal crosslinking approach, PiPOx is first crosslinked with the dicarboxylic acid functionalized TPy in DMSO to form a stable covalent network, followed by solvent exchange to water, drying and the introduction of reversible coordination bonds through swelling in an aqueous zinc(II) ion solution.

Structural insights into higher-order natural RNA-only multimers.

RNA-only complexes adopt intricate three-dimensional structures to fulfill diverse functions independently of protein partners. Although multimeric RNA-only structures have been engineered in synthetic RNA nanomaterials, naturally occurring RNA-only complexes have primarily been observed as monomers or dimers, leaving higher-order assemblies largely unexplored. ROOL (rumen-originating, ornate, large) and GOLLD (giant, ornate, lake- and Lactobacillales-derived) RNAs are conserved non-coding RNAs with complex secondary structures, but their high-resolution architectures remain unknown.

Regulatory role of transcription factor c-Myc in the pathogenesis of psoriasis.

Psoriasis is a chronic relapsing dermatosis characterized by hyperproliferation and poor differentiation of keratinocytes (KCs). The c-Myc gene is one of the main members of the Myc family and exerts multiple biological functions. C-Myc is highly expressed in psoriatic lesions.

Genome-Wide Characterization of the Heat Shock Transcription Factor Gene Family in Reveals Promising Candidates for Heat Tolerance.

() is a popular ornamental plant widely used in landscapes such as plazas and flower beds, and it is also commonly grown as a potted plant indoors. It is known for its adaptability to high temperatures, drought, and shade. Under heat-tolerant conditions, heat shock transcription factors (HSFs) are key transcriptional regulatory proteins that play crucial roles in cellular processes.

The PAZ pocket and dimerization drive CpAgo's guide-independent and DNA-guided dual catalysis.

Argonaute proteins (Agos) play essential roles in nucleic acid targeting across life domains. While eukaryotic Agos (eAgos) utilize small-interfering RNAs (siRNAs) or microRNAs (miRNAs) for RNA interference, the mechanisms driving prokaryotic Agos (pAgos) in bacterial defense remain underexplored. Here, we characterize the mesophilic pAgo from Clostridium perfringens (CpAgo), which exhibits robust guide-independent and DNA-guided activity at 37 °C.

Endocrine Resistance Score Based on Three Key Genes Predicts Prognosis and Reveals Potential Therapeutic Targets for ER+HER2- Breast Cancer.

Endocrine resistance is a leading cause of mortality in oestrogen receptor-positive and human epidermal growth factor receptor 2-negative (ER+HER2-) breast cancer (BC), highlighting the urgent need to understand its underlying molecular mechanisms and identify potentially resistant patients for effective management. In this study, we constructed endocrine-resistant cell lines through long-term oestrogen deprivation and identified differentially expressed genes (DEGs) via transcriptome analysis. Key endocrine-resistant genes were defined through Cox regression analysis.

Genome-Wide Identification and Functional Analysis of the Gene Family in 'Super Olympia' Reveal Its Potential Role in Regulating Flowering.

The phosphatidylethanolamine-binding protein (PEBP) gene family, known for its pivotal role in controlling floral transition, regulates flowering time, and, thus, shapes the continuous-flowering trait in ornamental plants. In this study, we conducted the first genome-wide identification and bioinformatics analysis of the gene family in 'Super Olympia', a variety that exhibits year-round flowering. Via phylogenetic analysis, a total of 10 genes were identified and categorized into four subfamilies: the FT-like (two members), TFL1-like (three members), PEBP-like (three members), and MFT-like (two members) subfamilies.

Direct visual proof for the micellar solubilization of RNA models during its transesterification.

In this study, the micellar effects on the transesterification of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) - a classic RNA model-were evaluated in the presence of three dinuclear copper(II) complexes (CuLCl, CuLCl, CuLCl) with new bidentate 'NNO' ligands. In both nonmicellar and micellar systems, bromine-bearing CuLCl displayed the best activity in contrast to the other analogues due to the positive electron-withdrawing ability of bromine. The introduction of cationic micelles resulted in a significant rate enhancement of the HPNP transesterification, achieving improvements of one order of magnitude (upping to 45 times) in contrast with nonmicellar system.

Acupoint Injection Combined with BCG-PSN and Thymosin Enteric-Coated Tablets Improve China Han Psoriasis Vulgaris by Regulating T Cell Subsets.

Purpose: Psoriasis is a common chronic inflammatory skin disease. Acupoint injection is reported to be used for the treatment of psoriasis, however its mechanism is not yet clear. The study aimed to investigate the efficiency of combined treatment including acupoint injection in the treatment of psoriasis.

Identification of circulating tumor cells marker genes as prognostic signature in triple-negative breast cancer.

Background: Breast cancer represents a significant contributor to cancer-related mortality among women worldwide, with triple-negative breast cancer (TNBC) often exhibiting more aggressive clinical features and a heightened lethality rate. The emergence of malignant progression, along with issues of drug resistance, poses substantial challenges in the clinical management of this disease.

Methods: The analysis of gene expression profiles at the single-cell level was conducted on circulating tumor cells (CTCs) obtained from TNBC patients, with the objective of identifying specific marker genes associated with CTCs.

Reactivating cGAS-STING Signaling by Targeting SOS1 Enhances Antitumor Immunity in NRAS-Mutant Tumors.

Unlabelled: NRAS is commonly mutated in several different types of human cancer. NRAS-mutant tumors are aggressive and associated with poor outcomes. Although the development of targeted therapies as well as immune checkpoint inhibitors has led to a substantial improvement in the overall survival of patients with NRAS wild-type (WT) tumors, current therapies for NRAS-mutant cancers are limited.

Profiling triple-negative breast cancer-specific super-enhancers identifies high-risk mesenchymal development subtype and BETi-Targetable vulnerabilities.

Background: Super-enhancers (SEs) are critical regulators of tumorigenesis and represent promising targets for bromodomain and extra-terminal domain inhibitors (BETi). However, clinical studies across various solid tumors, including triple-negative breast cancer (TNBC), have demonstrated limited BETi efficacy. This study aims to investigate SE heterogeneity in TNBC and its influence on BETi effectiveness, with the goal of advancing BETi precision treatment strategies and enhancing therapeutic efficacy.

X-ray-Induced Photodegradation of Hydrogels by the Incorporation of X-ray-Activated Long Persistent Luminescent Nanoparticles.

The development of on-demand degradable hydrogels remains an important challenge. Even though photodegradable hydrogels offer spatiotemporal control over degradation, it is difficult to use ultraviolet, visible, or near-infrared light as a tool for noninvasive triggering in vivo due to the poor tissue-penetration capacity. In contrast, X-ray irradiation can penetrate deep tissue and has virtually no penetration limitations for biological soft tissues.

Crotonylation deficiency of S100A7 K49 promotes psoriatic keratinocyte proliferation through enhanced interaction with RAGE.

Psoriasis is a chronic inflammatory dermatosis characterized by the hyperproliferative of keratinocytes. S100A7 plays a pivotal role in the pathogenesis of psoriasis. Lysine crotonylation of proteins is a newly identified modification that impacts diverse biological processes and its dysregulation has been implicated in autoimmune diseases.

Targeting site-specific N-glycosylated B7H3 induces potent antitumor immunity.

B7H3, an immune checkpoint molecule, is a highly N-glycosylated membrane protein. However, the key glycosylated asparagine residues that mediate the function of the B7H3 protein are still unclear. Here we identify that N-glycans attached to asparagine residues N91/309 and N104/322 are required for proper B7H3 localization on the cell surface membrane.

The Role of Complement Component 3 (C3) in Psoriasis.

Psoriasis is a chronic inflammatory disease driven by immune dysfunction, with its pathogenesis still not fully understood. This article explores the crucial roles of complement molecules in psoriasis, emphasizing complement C3's pathogenic mechanisms and its potential as a therapeutic target. The complement system's structure and function highlight its significance in immune response and inflammation regulation.

Complex water networks visualized by cryogenic electron microscopy of RNA.

The stability and function of biomolecules are directly influenced by their myriad interactions with water. Here we investigated water through cryogenic electron microscopy (cryo-EM) on a highly solvated molecule: the Tetrahymena ribozyme. By using segmentation-guided water and ion modelling (SWIM), an approach combining resolvability and chemical parameters, we automatically modelled and cross-validated water molecules and Mg ions in the ribozyme core, revealing the extensive involvement of water in mediating RNA non-canonical interactions.

A nomogram for predicting mortality risk in geriatric patients with hip fractures complicated by pneumonia: A multicenter study.

Objectives: Pneumonia is a common perioperative complication in geriatric patients with hip fractures. This study aimed to analyze demographic characteristics, mortality rates, postoperative outcomes, and perioperative comorbidities, identify risk factors for mortality, and develop a nomogram for predicting the prognosis of these patients.

Methods: Data on patients hospitalized for arthroplasty for hip fractures from 2020 to 2023 at three hospitals were retrospectively analyzed.

Structural insights into dynamics of the BMV TLS aminoacylation.

Brome Mosaic Virus (BMV) utilizes a tRNA-like structure (TLS) within its 3' untranslated region to mimic host tRNA functions, aiding aminoacylation and viral replication. This study explores the structural dynamics of BMV TLS interacting with tyrosyl-tRNA synthetase (TyrRS) during aminoacylation. Using cryo-EM, we capture multiple states of the TLS-TyrRS complex, including unbound TLS, pre-1a, post-1a, and catalysis states, with resolutions of 4.

Complex Water Networks Visualized through 2.2-2.3 Å Cryogenic Electron Microscopy of RNA.

The stability and function of biomolecules are directly influenced by their myriad interactions with water. In this study, we investigated water through cryogenic electron microscopy (cryo-EM) on a highly solvated molecule, the ribozyme, determined at 2.2 and 2.

Normal dermal mesenchymal stem cells improve the functions of psoriatic keratinocytes by inducing autophagy.

Objective: Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation and abnormal differentiation of keratinocytes. Although stem cell-based therapies have shown promise in treating psoriasis, the underlying mechanisms remain unclear. This study aimed to established a psoriatic cell model to investigate the effect of normal dermal mesenchymal stem cell (DMSCs) on keratinocyte proliferation, inflammation responses and the associated mechanism.

Angiopoietins/Tie2 signaling axis and its role in angiogenesis of psoriasis.

Hyperplasia of microvessels in the superficial dermis is the main pathological feature of psoriasis, and is linked to the pathogenesis of psoriasis. Thus, anti-angiogenic therapy may be effective for psoriasis. Angiopoietins (Angs) are crucial angiogenic factors.

An adenosine analog shows high antiviral potency against coronavirus and arenavirus mainly through an unusual base pairing mode.

By targeting the essential viral RNA-dependent RNA polymerase (RdRP), nucleoside analogs (NAs) have exhibited great potential in antiviral therapy for RNA virus-related diseases. However, most ribose-modified NAs do not present broad-spectrum features, likely due to differences in ribose-RdRP interactions across virus families. Here, we show that HNC-1664, an adenosine analog with modifications both in ribose and base, has broad-spectrum antiviral activity against positive-strand coronaviruses and negative-strand arenaviruses.

Regulation of epidermal barrier function and pathogenesis of psoriasis by serine protease inhibitors.

Serine protease inhibitors (Serpins) are a protein superfamily of protease inhibitors that are thought to play a role in the regulation of inflammation, immunity, tumorigenesis, coagulation, blood pressure and cancer metastasis. Serpins is enriched in the skin and play a vital role in modulating the epidermal barrier and maintaining skin homeostasis. Psoriasis is a chronic inflammatory immune-mediated skin disease.

Crotonylation modification and its role in diseases.

Protein lysine crotonylation is a novel acylation modification discovered in 2011, which plays a key role in the regulation of various biological processes. Thousands of crotonylation sites have been identified in histone and non-histone proteins over the past decades. Crotonylation is conserved and is regulated by a series of enzymes including "writer", "eraser", and "reader".