Recent advances in the molecular design and applications of viral RNA-targeting antiviral modalities.

Pathogenic viruses are a profound threat to global public health, underscoring the urgent need for the development of efficacious antiviral therapeutics. The advent of RNA-targeting antiviral strategies has marked a significant paradigm shift in the management of viral infections, offering a potent means of control and potential cure. In this review, we delve into the cutting-edge progress in RNA-targeting antiviral agents, encompassing antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), small and bifunctional molecules. We provide an in-depth examination of their strategic molecular design and elucidate the underlying mechanisms of action that confer their antiviral efficacy. By synthesizing recent findings, we shed light on the innovative potential of RNA-targeting approaches and their pivotal role in advancing the frontiers of antiviral drug discovery.

Multi-target Compounds against Trypanosomatid Parasites and Mycobacterium tuberculosis.

Multi-target drug treatment has become popular as a substitute for traditional monotherapy. Monotherapy can lead to resistance and side effects. Multi-target drug discovery is gaining importance as data on bioactivity becomes more abundant. The design of multi-target drugs is expected to be an important development in the pharmaceutical industry in the near future. This review presents multi-target compounds against trypanosomatid parasites (Trypanosoma cruzi, T. brucei, and Leishmania sp.) and tuberculosis (Mycobacterium tuberculosis), which mainly affect populations in socioeconomically unfavorable conditions. The article analyzes the studies, including their chemical structures, viral strains, and molecular docking studies, when available. The objective of this review is to establish a foundation for designing new multi-target inhibitors for these diseases.

Discovery of piperine derivatives as inhibitors of human dihydroorotate dehydrogenase to induce ferroptosis in cancer cells.

Inhibition of human dihydroorotate dehydrogenase (hDHODH) represents a promising strategy for suppressing the proliferation of cancer cells. To identify novel and potent hDHODH inhibitors, a total of 28 piperine derivatives were designed and synthesized. Their cytotoxicities against three human cancer cell lines (NCI-H226, HCT-116, and MDA-MB-231) and hDHODH inhibitory activities were also evaluated. Among them, compound H19, exhibited the strongest inhibitory activities (NCI-H226 IC50 = 0.95 µM, hDHODH IC50 = 0.21 µM). Further pharmacological investigations revealed that H19 exerted anticancer effects by inducing ferroptosis in NCI-H226 cells, with its cytotoxicity being reversed by ferroptosis inhibitors. This was supported by the intracellular growth or decline of ferroptosis markers, including lipid peroxidation, Fe2+, GSH, and 4-HNE. Overall, H19 emerges as a promising hDHODH inhibitor with potential anticancer properties warranting development.

Metagenomic and culture-dependent analysis of Rhinopithecius bieti gut microbiota and characterization of a novel genus of Sphingobacteriaceae.

Culture-dependent and metagenomic binning techniques were employed to gain an insight into the diversification of gut bacteria in Rhinopithecius bieti, a highly endangered primate endemic to China. Our analyses revealed that Bacillota_A and Bacteroidota were the dominant phyla. These two phyla species are rich in carbohydrate active enzymes, which could provide nutrients and energy for their own or hosts' survival under different circumstances. Among the culturable bacteria, one novel bacterium, designated as WQ 2009T, formed a distinct branch that had a low similarity to the known species in the family Sphingobacteriaceae, based on the phylogenetic analysis of its 16S rRNA gene sequence or phylogenomic analysis. The ANI, dDDH and AAI values between WQ 2009T and its most closely related strains S. kitahiroshimense 10CT, S. pakistanense NCCP-246T and S. faecium DSM 11690T were significantly lower than the accepted cut-off values for microbial species delineation. All results demonstrated that WQ 2009T represent a novel genus, for which names Rhinopithecimicrobium gen. nov. and Rhinopithecimicrobium faecis sp. nov. (Type strain WQ 2009T = CCTCC AA 2021153T = KCTC 82941T) are proposed.

A consensus reverse docking approach for identification of a competitive inhibitor of acetyltransferase enhanced intracellular survival protein from Mycobacterium tuberculosis.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), which remains a significant global health challenge. The emergence of multidrug-resistant (MDR) Mtb strains imposes the development of new therapeutic strategies. This study focuses on the identification and evaluation of potential inhibitors against Mtb H37Ra through a comprehensive screening of an in-house chemolibrary. Subsequently, a promising pyrimidine derivative (LQM495) was identified as promising and then further investigated by experimental and in silico approaches. In this context, computational techniques were used to elucidate the potential molecular target underlying the inhibitory action of LQM495. Then, a consensus reverse docking (CRD) protocol was used to investigate the interactions between this compound and several Mtb targets. Out of 98 Mtb targets investigated, the enhanced intracellular survival (Eis) protein emerged as a target for LQM495. To gain insights into the stability of the LQM495-Eis complex, molecular dynamics (MD) simulations were conducted over a 400 ns trajectory. Further insights into its binding modes within the Eis binding site were obtained through a Quantum mechanics (QM) approach, using density functional theory (DFT), with B3LYP/D3 basis set. These calculations shed light on the electronic properties and reactivity of LQM495. Subsequently, inhibition assays and kinetic studies of the Eis activity were used to investigate the activity of LQM495. Then, an IC50 value of 11.0 ± 1.4 µM was found for LQM495 upon Eis protein. Additionally, its Vmax, Km, and Ki parameters indicated that it is a competitive inhibitor. Lastly, this study presents LQM495 as a promising inhibitor of Mtb Eis protein, which could be further explored for developing novel anti-TB drugs in the future.

Hydrophobic tagging of small molecules: an overview of the literature and future outlook.

INTRODUCTION: Hydrophobic tagging (HyT) technology presents a distinct therapeutic strategy diverging from conventional small molecule drugs, providing an innovative approach to drug design. This review aims to provide an overview of the HyT literature and future outlook to offer guidance for drug design. AREAS COVERED: In this review, the authors introduce the composition, mechanisms and advantages of HyT technology, as well as summarize the detailed applications of HyT technology in anti-cancer, neurodegenerative diseases (NDs), autoimmune disorders, cardiovascular diseases (CVDs), and other fields. Furthermore, this review discusses key aspects of the future development of HyT molecules. EXPERT OPINION: HyT emerges as a highly promising targeted protein degradation (TPD) strategy, following the successful development of proteolysis targeting chimeras (PROTAC) and molecular glue. Based on exploring new avenues, modification of the HyT molecule itself potentially enhances the technology. Improved synthetic pathways and emphasis on pharmacokinetic (PK) properties will facilitate the development of HyT. Furthermore, elucidating the biochemical basis by which the compound's hydrophobic moiety recruits the protein homeostasis network will enable the development of more precise assays that can guide the optimization of the linker and hydrophobic moiety.

Therapeutic Inhibition of LincRNA-p21 Protects Against Cardiac Hypertrophy.

BACKGROUND: Cardiac hypertrophy is an adaptive response to pressure overload aimed at maintaining cardiac function. However, prolonged hypertrophy significantly increases the risk of maladaptive cardiac remodeling and heart failure. Recent studies have implicated long noncoding RNAs in cardiac hypertrophy and cardiomyopathy, but their significance and mechanism(s) of action are not well understood. METHODS: We measured lincRNA-p21 RNA and H3K27ac levels in the hearts of dilated cardiomyopathy patients. We assessed the functional role of lincRNA-p21 in basal and surgical pressure-overload conditions using loss-of-function mice. Genome-wide transcriptome analysis revealed dysregulated genes and pathways. We labeled proteins in proximity to full-length lincRNA-p21 using a novel BioID2-based system. We immunoprecipitated lincRNA-p21-interacting proteins and performed cell fractionation, ChIP-seq (chromatin immunoprecipitation followed by sequencing), and co-immunoprecipitation to investigate molecular interactions and underlying mechanisms. We used GapmeR antisense oligonucleotides to evaluate the therapeutic potential of lincRNA-p21 inhibition in cardiac hypertrophy and associated heart failure. RESULTS: lincRNA-p21 was induced in mice and humans with cardiomyopathy. Global and cardiac-specific lincRNA-p21 knockout significantly suppressed pressure overload-induced ventricular wall thickening, stress marker elevation, and deterioration of cardiac function. Genome-wide transcriptome analysis and transcriptional network analysis revealed that lincRNA-p21 acts in trans to stimulate the NFAT/MEF2 pathway. Mechanistically, lincRNA-p21 is bound to the scaffold protein KAP1. lincRNA-p21 cardiac-specific knockout suppressed stress-induced nuclear accumulation of KAP1, and KAP1 knockdown attenuated cardiac hypertrophy and NFAT activation. KAP1 positively regulates pathological hypertrophy by physically interacting with NFATC4 to promote the overactive status of NFAT/MEF2 signaling. GapmeR antisense oligonucleotide depletion of lincRNA-p21 similarly inhibited cardiac hypertrophy and adverse remodeling, highlighting the therapeutic potential of inhibiting lincRNA-p21. CONCLUSIONS: These findings advance our understanding of the functional significance of stress-induced long noncoding RNA in cardiac hypertrophy and demonstrate the potential of lincRNA-p21 as a novel therapeutic target for cardiac hypertrophy and subsequent heart failure.

Dynamic changes in key factors of the blood-brain barrier in early diabetic mice.

Chronic hyperglycemia can result in damage to the hippocampus and dysfunction of the blood-brain barrier (BBB), potentially leading to neurological disorders. This study examined the histological structure of the hippocampus and the expression of critical genes associated with the BBB at 2 early stage time points in a streptozotocin-induced diabetes mellitus (DM) mouse model. Routine histology revealed vascular congestion and dilation of Virchow-Robin spaces in the hippocampal CA1 region of the DM group. Neuronal alterations included rounding and swelling and reduction in Nissl bodies and increased apoptosis. Compared to the control group, TJP1 mRNA expression in the DM group was significantly lower (P < .05 or P < .01), while mRNA levels of JAM3, TJP3, CLDN5, CLDN3, and OCLN initially increased and then decreased. At 7, 14, and 21 days, mRNA levels of the receptor for advanced glycation end products (AGER) were greater in the DM group than in the control group (P < .05 or P < .01). These findings indicate that early-stage diabetes may cause structural and functional impairments in hippocampal CA1 in mice. These abnormalities may parallel alterations in the expression of key BBB tight junction molecules and elevated AGER expression in early DM patients.

Spatiotemporal Expansion of Algal Blooms in Coastal China Seas.

The coastal seas of China are increasingly threatened by algal blooms, yet their comprehensive spatiotemporal mapping and understanding of underlying drivers remain challenging due to high turbidity and heterogeneous water conditions. We developed a singular value decomposition-based algorithm to map these blooms using two decades of MODIS-Aqua satellite data, spanning from 2003 to 2022. Our findings indicate significant algal activity along the Chinese coastline, impacting an average annual area of approximately 1.8 × 105 km2. The blooms exhibit peak intensity in August, while the maximum affected area occurs in September, featuring multifrequency outbreaks in spring, and pronounced large-scale events in summer and autumn. Notably, our analysis demonstrates a robust 67% increase in bloom occurrences over the study period. This expansion is primarily attributed to increased nutrient inflow from terrestrial sources linked to human activity and precipitation, compounded by rising global sea surface temperatures. These spatiotemporal insights are critical for devising effective management strategies and policies to mitigate the impacts of algal blooms.

Discovery of GluN2A subtype-selective N-methyl-d-aspartate (NMDA) receptor ligands.

The N-methyl-d-aspartate (NMDA) receptors, which belong to the ionotropic Glutamate receptors, constitute a family of ligand-gated ion channels. Within the various subtypes of NMDA receptors, the GluN1/2A subtype plays a significant role in central nervous system (CNS) disorders. The present article aims to provide a comprehensive review of ligands targeting GluN2A-containing NMDA receptors, encompassing negative allosteric modulators (NAMs), positive allosteric modulators (PAMs) and competitive antagonists. Moreover, the ligands' structure-activity relationships (SARs) and the binding models of representative ligands are also discussed, providing valuable insights for the clinical rational design of effective drugs targeting CNS diseases.

Tailored Triggering of High-Quality Multi-Dimensional Coupled Topological States in Valley Photonic Crystals.

The combination of higher-order topological insulators and valley photonic crystals has recently aroused extensive attentions due to the great potential in flexible and efficient optical field manipulations. Here, we computationally propose a photonic device for the 1550 nm communication band, in which the topologically protected electromagnetic modes with high quality can be selectively triggered and modulated on demand. Through introducing two valley photonic crystal units without any structural alteration, we successfully achieve multi-dimensional coupled topological states thanks to the diverse electromagnetic characteristics of two valley edge states. According to the simulations, the constructed topological photonic devices can realize Fano lines on the spectrum and show high-quality localized modes by tuning the coupling strength between the zero-dimensional valley corner states and the one-dimensional valley edge states. Furthermore, we extend the valley-locked properties of edge states to higher-order valley topological insulators, where the selected corner states can be directionally excited by chiral source. More interestingly, we find that the modulation of multi-dimensional coupled photonic topological states with pseudospin dependence become more efficient compared with those uncoupled modes. This work presents a valuable approach for multi-dimensional optical field manipulation, which may support potential applications in on-chip integrated nanophotonic devices.

Simple and scalable preparation of lignin based porous carbon coated nano-clay composites and their efficient removal for the diversified iodine.

Here, lignin and nano-clay were used to prepare novel composite adsorbents by one-step carbonization without adding activators for radioactive iodine capture. Specially, 1D nano-clay such as halloysite (Hal), palygorskite (Pal) and sepiolite (Sep) were selected as skeleton components, respectively, enzymatic hydrolysis lignin (EHL) as carbon source, lignin based porous carbon/nano-clay composites (ELC-X) were prepared through ultrasonic impregnation, freeze drying, and carbonization. Characterization results indicated lignin based porous carbon (ELC) well coated on the surface of nano-clay, and made its surface areas increase to 252 m2/g. These composites appeared the micro-mesoporous hierarchical structure, considerable N doping and good chemical stability. Results of adsorption experiments showed that the introduction of ELC could well promote iodine vapor uptake of nano-clay, and up to 435.0 mg/g. Meanwhile, the synergistic effect between lignin based carbon and nano-clay was very significant for the adsorption of iodine/n-hexane and iodine ions, their capacity were far exceed those of a single material, respectively. The relevant adsorption kinetic and thermodynamics, and mechanism of ELC-X composites were clarified. This work provided a class of low-cost and environmentally friendly adsorbents for radioactive iodine capture, and opened up ideas for the comprehensive utilization of waste lignin and natural clay minerals.

Efficient Electrosynthesis of Urea over Single-Atom Alloy with Electronic Metal Support Interaction.

Urea electrosynthesis from carbon dioxide (CO2) and nitrate (NO3 -) is an alternative approach to traditional energy-intensive urea synthesis technology. Herein, we report a CuAu single-atom alloy (SAA) with electronic metal support interaction (EMSI), achieving a high urea yield rate of 813.6 µg h-1 mgcat -1 at -0.94 V versus reversible hydrogen electrode (vs. RHE) and a Faradaic efficiency (FE) of 45.2 % at -0.74 V vs. RHE. In situ experiments and theoretical calculations demonstrated that single-atom Cu sites modulate the adsorption behavior of intermediate species. Bimetallic sites synergistically accelerate C-N bond formation through spontaneous coupling of *CO and *NO to form *ONCO as key intermediates. More importantly, electronic metal support interaction between CuAu SAA and CeO2 carrier further modulates electron structure and interfacial microenvironment, endowing electrocatalysts with superior activity and durability. This work constructs SAA electrocatalysts with EMSI effect to tailor C-N coupling at the atomic level, which can provide guidance for the development of C-N coupling systems.

The long noncoding RNA CARDINAL attenuates cardiac hypertrophy by modulating protein translation.

One of the features of pathological cardiac hypertrophy is enhanced translation and protein synthesis. Translational inhibition has been shown to be an effective means of treating cardiac hypertrophy, although system-wide side effects are common. Regulators of translation, such as cardiac-specific long noncoding RNAs (lncRNAs), could provide new, more targeted therapeutic approaches to inhibit cardiac hypertrophy. Therefore, we generated mice lacking a previously identified lncRNA named CARDINAL to examine its cardiac function. We demonstrate that CARDINAL is a cardiac-specific, ribosome-associated lncRNA and show that its expression was induced in the heart upon pathological cardiac hypertrophy and that its deletion in mice exacerbated stress-induced cardiac hypertrophy and augmented protein translation. In contrast, overexpression of CARDINAL attenuated cardiac hypertrophy in vivo and in vitro and suppressed hypertrophy-induced protein translation. Mechanistically, CARDINAL interacted with developmentally regulated GTP-binding protein 1 (DRG1) and blocked its interaction with DRG family regulatory protein 1 (DFRP1); as a result, DRG1 was downregulated, thereby modulating the rate of protein translation in the heart in response to stress. This study provides evidence for the therapeutic potential of targeting cardiac-specific lncRNAs to suppress disease-induced translational changes and to treat cardiac hypertrophy and heart failure.

Osthole exhibits the remedial potential for polycystic ovary syndrome mice through Nrf2-Foxo1-GSH-NF-κB pathway.

Polycystic ovary syndrome (PCOS) is the primary cause of female infertility with a lack of universal therapeutic regimen. Although osthole exhibits numerous pharmacological activities in treating various diseases, its therapeutic effect on PCOS is undiscovered. The present study found that application of osthole improved the symptoms of PCOS mice through preventing ovarian granulosa cells (GCs) production of more estrogen and alleviating the liberation of pro-inflammatory cytokine interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha. Meanwhile, osthole enhanced ovarian antioxidant capacity and alleviated intracellular reactive oxygen species (ROS) accumulation with a concurrent attenuation for oxidative stress, while intervention of antioxidant enzymic activity and glutathione (GSH) synthesis neutralized the salvation of osthole on GCs secretory disorder and chronic inflammation. Further analysis revealed that osthole restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and forkhead box O 1 (Foxo1) whose repression antagonized the amelioration of osthole on the insufficiency of antioxidant capacity and accumulation of ROS. Moreover, Nrf2 served as an intermedium to mediate the regulation of osthole on Foxo1. Additionally, osthole restricted the phosphorylation of IκBα and nuclear factor kappa B (NF-κB) subunit p65 by DHEA and weakened the transcriptional activity of NF-κB, but this effectiveness was abrogated by the obstruction of Nrf2 and Foxo1, whereas adjunction of GSH renewed the redemptive effect of osthole on NF-κB whose activation caused an invalidation of osthole in rescuing the aberration of GCs secretory function and inflammation response. Collectively, osthole might relieve the symptoms of PCOS mice via Nrf2-Foxo1-GSH-NF-κB pathway.

Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Designing a Magnesium/Sodium Hybrid Battery Using Hierarchical Iron Selenide Architecture as Cathode Material and Modified Dual-Ion Salts in Ether as Electrolyte.

We developed a magnesium/sodium (Mg/Na) hybrid battery using a hierarchical disk-whisker FeSe2 architecture (HD-FeSe2) as the cathode material and a modified dual-ion electrolyte. The polarizable Se2- anion reduced the Mg2+ migration barrier, and the 3D configuration possessed a large surface area, which facilitated both Mg2+/Na+ cation diffusion and electron transport. The dual-ion salts with NaTFSI in ether reduced the Mg plating/stripping overvoltage in a symmetric cell. The hybrid battery exhibited an energy density of 260.9 Wh kg-1 and a power density of 600.8 W kg-1 at 0.2 A g-1. It showed a capacity retention of 154 mAh g-1 and a Coulombic efficiency of over 99.5% under 1.0 A g-1 after 800 long cycles. The battery also displayed outstanding temperature tolerance. The findings of 3D architecture as cathode material and hybrid electrolyte provide a pathway to design a highly reliable Mg/Na hybrid battery.

Discovery of Novel Aryl Triazolone Dihydropyridines (ATDPs) Targeting Highly Conserved Residue W229 as Promising HIV-1 NNRTIs.

NNRTI is an important component of the highly active antiretroviral therapy (HAART), but the rapid emergence of drug resistance and poor pharmacokinetics limited their clinical application. Herein, a series of novel aryl triazolone dihydropyridines (ATDPs) were designed by structure-guided design with the aim of improving drug resistance profiles and pharmacokinetic profiles. Compound 10n (EC50 = 0.009-17.7 µM) exhibited the most active potency, being superior to or comparable to that of doravirine (DOR) against the whole tested viral panel. Molecular docking was performed to clarify the reason for its higher resistance profiles. Moreover, 10n demonstrated excellent pharmacokinetic profile (T1/2 = 5.09 h, F = 108.96%) compared that of DOR (T1/2 = 4.4 h, F = 57%). Additionally, 10n was also verified to have no in vivo acute or subacute toxicity (LD50 > 2000 mg/kg), suggesting that 10n is worth further investigation as a novel oral NNRTIs for HIV-1 therapy.

Uridine diphosphate glucosyltransferase is vital for fenpropathrin resistance in Bombyx mori (Lepidoptera).

The silkworm (Bombyx mori) is an important model lepidopteran insect and can be used to identify pesticide resistance-related genes of great significance for biological control of pests. Uridine diphosphate glucosyltransferases (UGTs), found in all organisms, are the main secondary enzymes involved in the metabolism of heterologous substances. However, it remains uncertain if silkworm resistance to fenpropathrin involves UGT. This study observes significant variations in BmUGT expression among B. mori strains with variable fenpropathrin resistance post-feeding, indicating BmUGT's role in fenpropathrin detoxification. Knockdown of BmUGT with RNA interference and overexpression of BmUGT significantly decreased and increased BmN cell activity, respectively, indicating that BmUGT plays an important role in the resistance of silkworms to fenpropathrin. In addition, fenpropathrin residues were significantly reduced after incubation for 12 h with different concentrations of a recombinant BmUGT fusion protein. Finally, we verified the conservation of UGT to detoxify fenpropathrin in Spodoptera exigua: Its resistance to fenpropathrin decreased significantly after knocking down SeUGT. In a word, UGT plays an important role in silkworm resistance to fenpropathrin by directly degrading the compound, a function seen across other insects. The results of this study are of great significance for breeding silkworm varieties with high resistance and for biological control of pests.

Exploring the Risk Factors for Deep Vein Thrombosis after Percutaneous Nephrolithotomy.

BACKGROUND: Deep vein thrombosis (DVT), a frequent complication following percutaneous nephrolithotomy (PCNL), may lead to severe conditions like pulmonary embolism. Current knowledge on postoperative DVT risk factors is, however, limited. The aim of our study was to investigate the risk of DVT after PCNL. METHODS: A retrospective study was conducted on patients who underwent PCNL from March 2020 to March 2023 at our institution. Patient demographics and clinical data, including, DVT-specific information, preoperative labs, and surgical details, was evaluated. RESULTS: One hundred patients were included. Thirty-two (20 males, 12 females, mean age 52.5 ± 7.4 years) developed lower limb DVT post-surgery, while the remaining 68 (48 males, 20 females, mean age 51.1 ± 5.5 years) had no DVT symptoms. Analysis revealed significant correlations between hyperlipidemia, operating time, postoperative bed rest duration, D-dimer level on the first day after surgery, Caprini risk assessment model (RAM) score, and DVT risk. D-dimer on the first day after percutaneous nephrolithotomy, postoperative bed rest time and Caprini RAM scores were independent risk factors for DVT after PCNL. Sex, age, hypertension status, diabetes status and smoking and drinking habits were not significantly associated with DVT risk. CONCLUSIONS: D-dimer on the first day after PCNL, postoperative bed rest time and Caprini RAM scores were independent risk factors for DVT after PCNL.