The GP2a 91/97/98 amino acid substitutions play critical roles in determining PRRSV tropism and infectivity but do not affect immune responses.

Unlabelled: Porcine reproductive and respiratory syndrome virus (PRRSV) isolates share a restricted cellular tropism. Marc-145 cells derived from African green monkey are one of the few cell lines supporting PRRSV propagation and are commonly used for PRRS vaccine development. However, currently prevalent PRRSV isolates display different Marc-145 cell tropism while the exact determinant is not clarified yet.

Orthosteric interactions with PIP activate TMEM16A channels.

TMEM16A channels pass Ca -activated Cl currents that drive a plethora of fundamental physiological processes. TMEM16A channels are activated by a rise in intracellular Ca levels but also require interactions with the signaling phospholipid phosphatidylinositol 4,5-bisphosphate (PIP ) to gate open. Although PIP is essential for the activity of many types of ion channels, its precise binding site and role in channel gating remain poorly understood in most cases, limiting efforts to study channel dynamics and design targeted modulators.

Cryo-EM structure of the MexY multidrug efflux pump.

Unlabelled: , a Gram-negative pathogen, has emerged as one of the most highly antibiotic-resistant bacteria worldwide and subsequently has become a leading cause of healthcare-associated, life-threatening infections. multidrug efflux Y (MexY) is an efflux pump that belongs to the resistance-nodulation-cell division (RND) superfamily. It is a major determinant for resistance to aminoglycosides in this opportunistic pathogen.

Labile Carbon Input Mitigates the Negative Legacy Effects of Nitrogen Addition on Arbuscular Mycorrhizal Symbiosis in a Temperate Grassland.

Nitrogen (N) deposition and carbon (C) addition significantly influence the dynamics of plant-microbe interactions, particularly altering the symbiotic relationship between plants and arbuscular mycorrhizal fungi (AMF). However, the effects and underlying mechanisms of labile C input on the relationship between AMF and various plant species in a nitrogen-enriched environment remain a knowledge gap. A seven-year field experiment was conducted to examine how six levels of N and three levels of labile C addition impact AMF colonization in four key plant species: (Trin.

Immunotherapy targeting a leader sequence cathepsin G-derived peptide.

Myeloid azurophil granules provide a rich source of intracellular leukemia antigens. Cathepsin G (CG) is a serine protease that has higher expression in acute myeloid leukemia (AML) blasts in comparison to normal myeloid progenitors. Based on the unique biology of HLA-A*0201 (HLA-A2), in which presentation of leader sequence (LS)-derived peptides is favored, we focused on the LS-CG-derived peptide CG1 (FLLPTGAEA).

Prognostic significance of programmed cell death 1 expression on CD8+T cells in various cancers: a systematic review and meta-analysis.

Background: Increased PD-1 expression on CD8+ T cells is considered as a hallmark for T-cell exhaustion, and is thought to be related to the prognosis of cancer patients. However, discrepant results have made it difficult to apply PD-1+CD8+T cells and tumor prognosis to clinical practice. Therefore, we conducted a meta-analysis to evaluate its prognostic value in human cancers.

Electrophysiological characterization of human KCNT1 channel modulators and the therapeutic potential of hydroquinine and tipepidine in KCNT1 mutation-associated epilepsy mouse model.

Patients suffering epilepsy caused by the gain-of-function mutants of the hKCNT1 potassium channels are drug refractory. In this study, we cloned a novel human KCNT1B channel isoform using the brain cDNA library and conducted patch-clamp and molecular docking analyses to characterize the pharmacological properties of the hKCNT1B channel using thirteen drugs. Among cinchona alkaloids, we found that hydroquinine exerted the strongest blocking effect on the hKCNT1B channel, especially the F313L mutant.

Isolation and Genomic Characterization of a Novel Porcine Reproductive and Respiratory Syndrome Virus 1 from Severely Diseased Piglets in China in 2024.

Since the first isolation of the porcine reproductive and respiratory syndrome virus 1 (PRRSV-1) BJEU06-1 strain from a Beijing pig farm in 2006, more and more PRRSV-1 isolates have been identified in China. In this study, we performed the routine detection of PRRSV-1 using 1521 clinical samples collected in 12 provinces/cities from February 2022 to May 2024. Only three lung samples from severely diseased piglets collected in January 2024 were detected as PRRSV-1-positive (0.

Corneal Biomechanical Characteristics and Correlation Analysis in Children With Different Refractive States.

To investigate the correlation between corneal biomechanical characteristics and refractive status in adolescents aged 5-13 years. A cross-sectional study involved 339 children aged 5-13 with a spherical equivalent (SE) range from -6.00 to +2.

The Relative Contribution of Root Morphology and Arbuscular Mycorrhizal Fungal Colonization on Phosphorus Uptake in Rice/Soybean Intercropping Under Dry Cultivation.

Intercropping has the potential to improve phosphorus (P) uptake and crop growth, but the potential benefits and relative contributions of root morphology and arbuscular mycorrhizal fungi (AMF) colonization are largely unknown for the intercropping of rice and soybean under dry cultivation. Both field and pot experiments were conducted with dry-cultivated rice ( L.) and soybean ( L.

The replication efficacy of NADC34-like porcine reproductive and respiratory syndrome virus 2 is not directly associated with the pathogenicity.

NADC34-like porcine reproductive and respiratory syndrome virus 2 (NADC34-like PRRSV-2) is currently a major prevalent strain in Chinese swine industry. Within which, recombination events are frequently detected. Previous studies have shown that the pathogenicity of NADC34-like PRRSV-2 isolates is highly variable.

Dynamic characteristics of high-risk HPV infection in women with low-grade cervical intraepithelial neoplasia, based on a community longitudinal study.

Background: High-risk human papillomavirus (HR-HPV) infection is the primary cause of cervical cancer and precancerous lesions. Approximately 35% of women with low-grade cervical intraepithelial neoplasia (CIN1) may experience persistence or progression to high-grade lesions. Yet, the dynamic characteristics of HR-HPV infection in women with CIN1 remain unclear.

The NCR1 transporter is an antimalarial target that exports cholesterol from the parasite's plasma membrane.

Malaria, a devastating parasitic infection, is the leading cause of death in many developing countries. Unfortunately, the most deadliest causative agent of malaria, , has developed resistance to nearly all currently available antimalarial drugs. The Niemann-Pick type C1-related (PfNCR1) transporter has been identified as a druggable target, but its structure and detailed molecular mechanism are not yet available.

Design of intelligent human-machine collaborative robot-assisted craniotomy system.

Objectives: To develop an intelligent human-machine collaborative control robot-assisted craniotomy system, and test its efficacy by experiments.

Methods: The system integrated a UR5 robotic arm (Universal Robots, Denmark), a host computer, a double six-degree-of-freedom force sensor(Nanjing Yuli Instrument Co., Ltd.

Structure-Induced Energetic Coordination Compounds as Additives for Laser Initiation Primary Explosives.

Laser ignition of primary explosives presents more reliable alternative to traditional electrical initiation methods. However, the commercial initiator lead azide (LA) requires a high-power density laser to detonate, with the minimum laser initiation energy (E) of 2402 mJ. Currently, the laser-ignitable metal complex-based igniters still suffer from weak detonation capabilities and high E values.

Synthesis of novel composite hydrogel based on carboxymethyl cellulose/acrylamide/β-cyclodextrin for drug delivery.

Polysaccharide-based hydrogels have attracted significant attention in fields such as drug delivery, tissue engineering, and wound healing, primarily due to their excellent water-retention capacity, biocompatibility, and biodegradability. This study reports the preparation of a hydrogel through the copolymerization of acrylamide (AM) and carboxymethyl cellulose (CMC) using a simple free-radical polymerization method. β-cyclodextrin (β-CD), capable of encapsulating hydrophobic drugs, was chemically modified with double bonds (Ac-β-CD) and incorporated as a pendant unit in the polymerization reaction, forming a ternary copolymer hydrogel with CMC, AM, and Ac-β-CD.

Positivity Status and Molecular Characterization of Porcine Parvoviruses 1 Through 8 (PPV1-PPV8) from Slaughtered Pigs in China.

Porcine parvoviruses one through eight (PPV1-PPV8) are prevalent in Chinese swine herds. However, the infection status of all these PPVs in slaughtered pigs is still unclarified. In this study, we detected PPV1-PPV8 in 353 tissue samples collected from slaughtered pigs from six regions of China in 2023.

A Comprehensive Methodology for Investigating Cocurrent Spontaneous Imbibition in Coal.

Visualizing and quantifying fluid distribution during spontaneous imbibition at the nanomicro scale is vital for understanding microfluid flow and dynamic wettability in coalbed methane (CBM) reservoirs, which could serve as a fundamental basis for optimizing the parameters of the hydraulic fracturing process. In this study, fluid distribution and flow behavior can be acquired by combining nuclear magnetic resonance (NMR) and in situ X-ray microcomputed tomography (μ-CT) technologies. Meanwhile, spontaneous imbibition stages were studied to analyze gas-water exchange efficiency.

Effect of supplementation with lutein, zeaxanthin, and omega-3 fatty acids on macular pigment and visual function in young adults with long-term use of digital devices: study protocol for a randomized double-blind placebo-controlled study.

Background: Growing evidence emphasizes the importance of xanthophyll carotenoids and omega-3 fatty acids in eye health. However, the beneficial effects of such supplementation have not been thoroughly discussed among adults with high screen exposure. Current trial evidence on lutein bioavailability is contradictory, and the interactions of dietary intervention with host-related factors remain elusive.

Molecular mechanism of GIRK2 channel gating modulated by cholesteryl hemisuccinate.

Cholesterol, an essential lipid of cell membranes, regulates G protein-gated inwardly rectifying potassium (GIRK) channel activity. Previous studies have shown that cholesterol activates GIRK2 homotetrameric channels, which are expressed in dopaminergic neurons of the brain. Deletion of GIRK2 channels affects both GIRK2 homo- and heterotetrames and can lead to abnormal neuronal excitability, including conditions such as epilepsy and addiction.

Dexmedetomidine Combined With Patient-Controlled Analgesia for Palliative Sedation in Terminal-Stage Cancer Patients With Refractory Pain: A Retrospective Analysis of Nine Cases.

Cancer-related pain is a pervasive symptom affecting the quality of life in patients with malignant tumors. For those with refractory pain, palliative sedation combined with pain management is recommended. Dexmedetomidine (DEX), known for its unique "awake sedation" effect, remains relatively unexplored when used in conjunction with patient-controlled analgesia (PCA) for terminal-stage cancer patients.

Recent Advances in Lipid Nanoparticles and Their Safety Concerns for mRNA Delivery.

The advent of lipid nanoparticles (LNPs) as a delivery platform for mRNA therapeutics has revolutionized the biomedical field, particularly in treating infectious diseases, cancer, genetic disorders, and metabolic diseases. Recent Advances in Therapeutic LNPs: LNPs, composed of ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, facilitate efficient cellular uptake and cytosolic release of mRNA while mitigating degradation by nucleases. However, as synthetic entities, LNPs face challenges that alter their therapeutic efficacy and safety concerns.

Molecular Dynamics (MD) Simulations Provide Insights into the Activation Mechanisms of 5-HT Receptors.

Recent breakthroughs in the determination of atomic resolution 3-D cryo-electron microscopy structures of membrane proteins present an unprecedented opportunity for drug discovery. Structure-based drug discovery utilizing in silico methods enables the study of dynamic connectivity of stable conformations induced by the drug in achieving its effect. With the ever-expanding computational power, simulations of this type reveal protein dynamics in the nano-, micro-, and even millisecond time scales.

Structures of the mycobacterial MmpL4 and MmpL5 transporters provide insights into their role in siderophore export and iron acquisition.

The Mycobacterium tuberculosis (Mtb) pathogen, the causative agent of the airborne infection tuberculosis (TB), harbors a number of mycobacterial membrane protein large (MmpL) transporters. These membrane proteins can be separated into 2 distinct subclasses, where they perform important functional roles, and thus, are considered potential drug targets to combat TB. Previously, we reported both X-ray and cryo-EM structures of the MmpL3 transporter, providing high-resolution structural information for this subclass of the MmpL proteins.

Influence of spectral and molecular composition of dissolved organic matter on labile Cd mobility in riparian soils in the Three Gorges Reservoir, China.

The periodic anti-seasonal inundation of the Three Gorges Reservoir (TGR) leads to changes in the molecular composition of dissolved organic matter (DOM) in riparian soils, further impacting the geochemical processes and ecological risk of heavy metals. However, the intrinsic driving mechanisms of DOM influencing the cadmium (Cd), a major pollutant in riparian soils in TGR, at the molecular level remain unclear. In this study, the DOM molecular composition, labile Cd in riparian soils and the key driving mechanism before and after flooding were explored using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), the diffusive gradients in thin films (DGT) and partial least squares path modeling (PLS-PM).