Response to: The mechanism for GTP-mediated RNA capping by the SARS-CoV-2 NiRAN domain remains unresolved.

The SARS-CoV-2 polymerase NiRAN domain initiates RNA capping. Previous results showed that both GTP and GDP can be utilized by NiRAN to yield GpppA together with RNAylated nsp9 (RNA-nsp9); however, the G-pocket substrate selection and the working mechanism of NiRAN remain unclear. Small et al.

Structural Basis and Rational Design of Nucleotide Analogue Inhibitor Evading the SARS-CoV-2 Proofreading Enzyme.

All coronaviruses (CoVs) encode an exoribonuclease in nonstructural protein nsp14 (nsp14 ExoN), which is required for the excision of mismatched nucleotides or nucleotide analogues (NAs) that are incorporated into nascent RNA. Here, we investigated the mechanism by which NAs evade SARS-CoV-2 nsp14 ExoN cleavage using chemically synthesized RNA with NAs incorporated at the 3' end. Nsp14 ExoN exhibited significantly attenuated activity on RNA with sofosbuvir monophosphate (SMP) compared with natural nucleotides, remdesivir/molnupiravir monophosphate, and, in particular, AT-9010 monophosphate (ATMP), which has the same chemically modified ribose moiety as SMP, incorporated at the 3' end.

Delivery of penetration-enhancing antioxidant polyphenol nanoparticles with Codonopsis pilosula polysaccharide microneedles for synergistic treatment of psoriasis.

Poor drug penetration due to local skin thickening and microenvironmental redox imbalance remain a critical challenge in the treatment of epidermal diseases. Considering that oxidative stress due to the overproduction of Reactive Oxygen Species (ROS) in the skin microenvironment is one of the main mechanisms in the pathogenesis of psoriasis, we developed a ROS-sensitive transdermal drug delivery system to enhance topical treatment of psoriasis. Cross-linked cyclodextrin metal-organic framework (COF) containing curcumin (CUR) was dispersed in two types of dissolving polysaccharide microneedles (CPPAP-MNs-CUR@COF, CPPNP-MNs-CUR@COF) made from Codonopsis pilosula neutral polysaccharides (CPPNP) and acidic polysaccharides (CPPAP) for topical administration.

Warming-Induced Plant Species Shifts Lead to Substantial Losses of Wetland Soil Carbon.

Wetlands are large reservoirs of soil organic carbon (SOC), storing one-third of global SOC within 6% of the land surface. However, the feedback direction and magnitude of wetland SOC storage to climate warming remain unclear. Here we present results from an 8-year (2014-2022) wetland warming experiment in the Yellow River Delta, revealing that wetland SOC storage responds to warming in a phase-dependent manner.

Structural basis for the dual roles of DPW in lipid and UDP-sugar metabolism during rice anther development.

Fatty acids and uridine diphosphate (UDP)-sugars are essential metabolites involved in the biosynthesis of polysaccharides and lipids, both of which are critical for anther development in plants. Our previous study identified Defective Pollen Wall (DPW), a rice fatty acyl carrier protein reductase (FAR), as a key factor in pollen wall formation. In this study, we demonstrate that the structure of DPW in complex with its cofactor NADP exhibits structural similarities to that of UDP-glucose epimerase (UGE).

Association between serum neurofilament light chains and Life's Essential 8: A cross-sectional analysis.

Background And Aim: Serum neurofilament light chain (sNfL), a protein released into the bloodstream post-neuronal axonal damage, has been validated as a robust biomarker for a range of neurological and systemic diseases. Concurrently, Life's Essential 8 (LE8) comprises a holistic suite of health behaviors and metabolic markers that are essential for assessing and enhancing cardiovascular health. Nevertheless, the interrelation between LE8 and sNfL is not yet fully elucidated.

Discovery of a 2'-α-Fluoro-2'-β--(fluoromethyl) Purine Nucleotide Prodrug as a Potential Oral Anti-SARS-CoV-2 Agent.

A novel 2'-α-fluoro-2'-β--(fluoromethyl) purine nucleoside phosphoramidate prodrug has been designed and synthesized to treat SARS-CoV-2 infection. The SARS-CoV-2 central replication transcription complex (C-RTC, nsp12-nsp7-nsp8) catalyzed in vitro RNA synthesis was effectively inhibited by the corresponding bioactive nucleoside triphosphate (). The cryo-electron microscopy structure of the C-RTC: complex was also determined.

Relationship between oxidative balance score and post-stroke depression: insights from the NHANES 2005-2018 cross-sectional study.

Introduction: The Oxidative Balance Score (OBS) represents an integrated measure of oxidative-reductive homeostasis. Despite the established role of oxidative stress in the development of post-stroke depression (PSD), the association between OBS and PSD in the general population remains unclear. This study aims to explore this relationship using data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005-2018.

Artificial trimerization of β-glucosidase for enhanced thermostability and activity via computational redesign.

The improvement of enzyme thermostability is of great significance in the biotechnology industry. Herein, we modified the C-terminus of β-glucosidase via the computer-aided rational design and successfully obtained six variants that exhibit improved optimal temperatures and thermal inactivation half-lives at 65 °C. Among these variants, the thermal inactivation half-life and hydrolytic activity of TrCel1b-H13 at 65 °C were increased by 416 and 3223 folds, respectively, compared to those of the wild type.

The influence of vermicompost on atrazine microbial degradation performance and pathway in black soil, Northeast China.

The atrazine (ATR) is extensively used in dryland crops like corn and sorghum in black soil region of Northeast China, posing ecological risks due to toxic metabolites. Vermicompost are known for soil organic pollution remediation but their role in pesticide degradation in black soil remains understudied. The influence of vermicompost on the microbial degradation pathway of atrazine was assessed in this study.

Drought shortens subtropical understory growing season by advancing leaf senescence.

Subtropical forests, recognized for their intricate vertical canopy stratification, exhibit high resistance to extreme drought. However, the response of leaf phenology to drought in the species-rich understory remains poorly understood. In this study, we constructed a digital camera system, amassing over 360,000 images through a 70% throughfall exclusion experiment, to explore the drought response of understory leaf phenology.

Crystal structure of calreticulin and the structural basis of its complement evasion mechanism involving C1q.

Helminths produce calreticulin (CRT) to immunomodulate the host immune system as a survival strategy. However, the structure of helminth-derived CRT and the structural basis of the immune evasion process remains unclarified. Previous study found that the tissue-dwelling helminth produces calreticulin (TsCRT), which binds C1q to inhibit activation of the complement classical pathway.

Astaxanthin attenuates cigarette smoke-induced small airway remodeling via the AKT1 signaling pathway.

Background: Astaxanthin (AXT) is a keto-carotenoid with a variety of biological functions, including antioxidant and antifibrotic effects. Small airway remodeling is the main pathology of chronic obstructive pulmonary disease (COPD) and is caused by epithelial-to-mesenchymal transition (EMT) and fibroblast differentiation and proliferation. Effective therapies are still lacking.

HDAC6-selective inhibitor CAY10603 ameliorates cigarette smoke-induced small airway remodeling by regulating epithelial barrier dysfunction and reversing.

Background: Small airway remodelling is a vital characteristic of chronic obstructive pulmonary disease (COPD), which is mainly caused by epithelial barrier dysfunction and epithelial-mesenchymal transition (EMT). Recent studies have indicated that histone deacetylase 6 (HDAC6) plays an important role in the dysregulation of epithelial function. In this study, we investigated the therapeutic effects and underlying mechanisms of an inhibitor with high selectivity for HDAC6 in COPD.

Efficacy of high-flow nasal cannula in patients with acute heart failure: a systematic review and meta-analysis.

Background: Acute heart failure (AHF) is often associated with diffuse insufficiency and arterial hypoxemia, requiring respiratory support for rapid and effective correction. We aimed to compare the effects of high-flow nasal cannula(HFNC) with those of conventional oxygen therapy(COT) or non-invasive ventilation(NIV) on the prognosis of patients with AHF.

Methods: We performed the search using PubMed, Embase, Web of Science, MEDLINE, the Cochrane Library, CNKI, Wanfang, and VIP databases from the inception to August 31, 2023 for relevant studies in English and Chinese.

Point-of-care ultrasound-guided submucosal paclitaxel injection in tracheal stenosis model.

Background And Objectives: Transcutaneous point-of-care ultrasound (POCUS) is a good tool to monitor the trachea in many clinical practices. The aim of our study is to verify the feasibility of POCUS-guided submucosal injection as a potential drug delivery method for the treatment of tracheal stenosis.

Materials And Methods: The inner wall of the trachea was monitored a bronchoscope during the POCUS-guided submucosal injection of methylene blue in fresh porcine trachea to evaluate the distribution of methylene blue.

The various effect of cow manure compost on the degradation of imazethapyr in different soil types.

Adding compost to soil is an effective strategy to promote the degradation of organic pollutants and reduce ecological risks. However, the effect of compost on the degradation of imazethapyr (IMET) in different soil types is not clear. To address this issue, a pot experiment was conducted, and high-throughput sequencing and mass spectrometry technology were used to identify the influence of cow manure compost on the degradation efficiency of IMET in black soil and saline-alkali soil and the role of key microorganisms.

Glycyl-l-histidyl-l-lysine-Cu rescues cigarette smoking-induced skeletal muscle dysfunction via a sirtuin 1-dependent pathway.

Background: Skeletal muscle dysfunction is an important co-morbidity in patients with chronic obstructive pulmonary disease (COPD) and is significantly associated with increased mortality. Oxidative stress has been demonstrated an important trigger for COPD-related skeletal muscle dysfunction. Glycine-histidine-lysine (GHK) is an active tripeptide, which is a normal component of human plasma, saliva, and urine; promotes tissue regeneration; and acts as an anti-inflammatory and antioxidant properties.

Spatial and temporal regulation of homogeneous nucleation and crystal growth for high-flux electrochemical water softening.

Electrochemical softening is an effective technology for the treatment of circulating cooling water, but its hardness removal efficiency is limited because that nucleation and growth of scale crystals depended on cathode surface. In this study, a novel method was proposed to break through this limit via spatiotemporal management of nucleation and growth processes. A cube reactor was divided into cathodic chamber and anodic chamber via installing a sandwich structure module composed of mesh cathode, nylon nets, and mesh anode.

Ultrasound Assessment of the Rectus Femoris in Patients with Chronic Obstructive Pulmonary Disease Predicts Sarcopenia.

Purpose: Sarcopenia, an age-related loss of skeletal muscle mass and function, is frequent in patients with chronic obstructive pulmonary disease (COPD) and is linked to a poor prognosis. The diagnosis of sarcopenia requires specific equipment and is inconvenient to introduce into clinical practice. Ultrasound is an innovative method to assess muscle quantity.