Emerging role of PES1 in disease: A promising therapeutic target?

Pescadillo ribosomal biogenesis factor 1 (PES1), a nucleolar protein initially identified in zebrafish, plays an important role in embryonic development and ribosomal biogenesis. Notably, PES1 has been found to be overexpressed in a number of cancer types, where it contributes to tumorigenesis and cancer progression by promoting cell proliferation, suppressing cellular senescence, modulating the tumor microenvironment (TME) and promoting drug resistance in cancer cells. Moreover, recent emerging evidence suggests that PES1 expression is significantly elevated in the livers of Type 2 diabetes mellitus (T2DM) and obese patients, indicating its involvement in the pathogenesis of metabolic diseases through lipid metabolism regulation. In this review, we present the structural characteristics and biological functions of PES1, as well as complexes in which PES1 participates. Furthermore, we comprehensively summarize the multifaceted role of PES1 in various diseases and the latest insights into its underlying molecular mechanisms. Finally, we discuss the potential clinical translational perspectives of targeting PES1, highlighting its promising as a therapeutic intervention and treatment target.

Exploration of the impact of different drying methods on the quality of Gastrodia elata: A study based on drying kinetics and multidimensional quality evaluation.

In this study, the drying kinetics and multidimensional quality of Gastrodia elata (GE) obtained through five different drying methods were analyzed. The Page model provided the best fit. Though widely used, hot-air drying (HA-D) showed mediocre performance. Due to strong heat penetration, microwave drying (MV-D) and infrared drying (IR-D) effectively reduced drying time and energy consumption. However, they experienced Maillard and caramelization reactions, resulting in notable cell structure shrinkage, severe browning, pronounced caramel taste, and poor retention of active ingredients. Conversely, freeze-drying (F-D) and vacuum drying (V-D), due to the involvement of low-temperature or vacuum environments, demonstrated optimal performance in preserving microstructure, antioxidant activity, active ingredients, and flavor. However, F-D was time-consuming (1320 min) and had an energy consumption of 2.69 times that of HA-D, limiting its large-scale application. V-D struck the best balance between energy consumption and product quality, making it a highly promising drying method for GE.

Soybean isoflavones protect dopaminergic neurons from atrazine damage by inhibiting VPS13A to increase autophagy.

Atrazine (ATR) is a broad-spectrum herbicide with dopaminergic (DAergic) neurotoxicity that can cause Parkinson's disease (PD)-like syndrome. However, research on preventing ATR neurotoxicity is unclear. Soybean isoflavones (SI) are natural plant compounds with neuroprotective effects. In this study, we found that pre-administration of SI prevented ATR-induced motor dysfunction and substantia nigra pathological damage. RNA-seq datasets revealed that the neuroprotective effect of SI was related to autophagy. Further experiments showed that ATR inhibited autophagy, and SI pre-administration before ATR exposure increased autophagy. In addition, single-cell data analysis combined with experimental verification showed that the gene VPS13A was a key target by which SI protected DAergic neurons from ATR damage, and inhibiting VPS13A-induced autophagy was a key mechanism enabling SI prevention of neuron damage. Together, these findings provide new insights for the development of preventive measures and intervention targets protecting against functional neuronal damage caused by ATR and other herbicides.

A Multiplex PCR Assay for Simultaneous Detection of Giardia duodenalis, Cryptosporidium parvum, Blastocystis spp. and Enterocytozoon bieneusi in Goats.

Giardia duodenalis, Cryptosporidium parvum, Blastocystis spp. and Enterocytozoon bieneusi are four common zoonotic parasites associated with severe diarrhea and enteric diseases. In this study, we developed a multiplex PCR assay for the simultaneous detection of these four zoonotic protozoans in goat stool samples and assessed its detection efficiency. Specific primers were designed from conserved gene sequences retrieved from GenBank, and the PCR conditions were optimized. Genomic DNA from 130 samples was subjected to both single-target PCR and multiplex PCR. The multiplex PCR assay successfully amplified specific gene fragments (G. duodenalis, 1400 bp; C. parvum, 755 bp; Blastocystis spp., 573 bp; E. bieneusi, 314 bp). The assay sensitivity was ≥102 copies of pathogenic DNA clones with high specificity confirmed by negative results for other intestinal parasites. The detection rates were 23.08% (30/130) for G. duodenalis, 24.62% (32/130) for C. parvum, 41.54% (54/130) for Blastocystis spp., and 12.31% (16/130) for E. bieneusi, matching the single-target PCR results. The sensitivity and predictive values were 100.00%. This multiplex PCR provided a rapid, sensitive, specific, and cost-effective approach for detecting these four parasites. It also provided essential technical support for the rapid detection and epidemiological investigation of G. duodenalis, C. parvum, Blastocystis spp., and E. bieneusi infections in goat fecal samples.

Promoting chondrogenesis by targeted delivery to the degenerating cartilage in early treatment of osteoarthritis.

Osteoarthritis (OA) is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis. The cartilage matrix is mainly composed of collagen, a matrix protein with a hallmark triple-helix structure, which unfolds with collagen degradation on the cartilage surface. A collagen hybridizing peptide (CHP) is a synthetic peptide that binds the denatured collagen triple helix, conferring a potential disease-targeting possibility for early-stage OA. Here, we constructed an albumin nanoparticle (An) conjugated with CHP, loaded with a chondrogenesis-promoting small molecule drug, kartogenin (KGN). The CHP-KGN-An particle exhibited sustained release of KGN in vitro and prolonged in vivo retention selectively within the degenerated cartilage in the knee joints of model mice with early-stage OA. Compared to treatment with KGN alone, CHP-KGN-An robustly attenuated cartilage degradation, synovitis, osteophyte formation, and subchondral bone sclerosis in OA model mice and exhibited a more prominent effect on physical activity improvement and pain alleviation. Our study showcases that targeting the degenerated cartilage by collagen hybridization can remarkably promote the efficacy of small molecule drugs and may provide a novel delivery strategy for early-stage OA therapeutics.

Application of MIDD to accelerate the development of anti-infectives: Current status and future perspectives.

This review examines the role of model-informed drug development (MIDD) in advancing antibacterial and antiviral drug development, with an emphasis on the inclusion of host system dynamics into modeling efforts. Amidst the growing challenges of multidrug resistance and diminishing market returns, innovative methodologies are crucial for continuous drug discovery and development. The MIDD approach, with its robust capacity to integrate diverse data types, offers a promising solution. In particular, the utilization of appropriate modeling and simulation techniques for better characterization and early assessment of drug resistance are discussed. The evolution of MIDD practices across different infectious disease fields is also summarized, and compared to advancements achieved in oncology. Moving forward, the application of MIDD should expand into host system dynamics as these considerations are critical for the development of "live drugs" (e.g. chimeric antigen receptor T cells or bacteriophages) to address issues like antibiotic resistance or latent viral infections.

Relationship of different left bundle branch pacing sites and clinical outcomes in patients with heart failure.

BACKGROUND: Left bundle branch pacing (LBBP) is a novel physiological pacing modality. However, whether it delivers comparable efficacy with different capture sites in patients with heart failure remains unclear. OBJECTIVE: This study aimed to assess the association between different pacing sites and the response of LBBP. METHODS: Forty-three consecutive patients with heart failure, referred for successful LBBP implantation, were prospectively recruited in this study. Patients were assigned to 3 subgroups according to the paced QRS complex morphology (left bundle branch trunk pacing [LBTP], left posterior fascicular pacing, or left anterior fascicular pacing groups). Echocardiograms and electrocardiograms were recorded and analyzed at baseline and 6-month follow-up. RESULTS: The response rate was 95.0%, 88.2%, and 83.3% in LBTP, left posterior fascicular pacing, and left anterior fascicular pacing groups, respectively. All subgroups were efficient in narrowing the QRS complex (QRS complex narrowing: 38.1 ± 10.8 ms, 36.4 ± 12.6 ms, and 40.8 ± 10.8 ms) and improving cardiac function (LVEF improvement： 25.7% ± 8.1%, 15.3% ± 8.1%, and 18.8% ± 4.4%). Compared with left fascicular pacing, LBTP resulted in longer peak left ventricular activation time (76.5 ± 10.2 ms vs 82.3 ± 6.5 ms; P = .037) and shorter duration from intrinsicoid deflection in V1 or V2 to QRS end (128.0 ± 6.0 ms vs 113.3 ± 5.2 ms; P＜.0001), along with better improvement in septal systolic longitudinal strain (P = .007) and lateral-septal myocardial loading inhomogeneity (P = .036). Linear regression analysis further revealed that left bundle branch capture sites were strongly associated with the improvement in peak strain dispersion (model R2 = 0.586; P = .042) and LVEF (model R2 = 0.425; P < .0001). CONCLUSION: Different left bundle branch capture sites led to a subtle difference in mechanical synchrony, which may, in turn, affect LVEF improvement in patients with heart failure.

Intra-marrow delivery of human interleukin-6-loaded biodegradable microspheres promotes growth of patient-derived multiple myeloma cells in mice.

Not available.

Biological self-protection inspired engineering of nanomaterials to construct a robust bio-nano system for environmental applications.

Nanomaterials can empower microbial-based chemical production or pollutant removal, e.g., nano zero-valent iron (nZVI) as an electron source to enhance microbial reducing pollutants. Constructing bio-nano interfaces is critical for bio-nano system operation, but low interfacial compatibility due to nanotoxicity challenges the system performance. Inspired by microorganisms' resistance to nanotoxicity by secreting extracellular polymeric substances (EPS), which can act as electron shuttling media, we design a highly compatible bio-nano interface by modifying nZVI with EPS, markedly improving the performance of a bio-nano system consisting of nZVI and bacteria. EPS modification reduced membrane damage and oxidative stress induced by nZVI. Moreover, EPS alleviated nZVI agglomeration and probably reduced bacterial rejection of nZVI by wrapping camouflage, contributing to the bio-nano interface formation, thereby facilitating nZVI to provide electrons for bacterial reducing pollutant via membrane-anchoring cytochrome c. This work provides a strategy for designing a highly biocompatible interface to construct robust and efficient bio-nano systems for environmental implication.

Molecular farming expression of recombinant fusion proteins applied to skincare strategies.

This review discusses the current research progress in molecular farming technology in the field of skincare, with an emphasis on molecular farming expression strategies. The strategies of transdermal drug delivery and their advantages are also highlighted. The expression of cosmetically relevant fused proteins has become an important way to enhance the efficacy of the proteins. Therefore, we also discuss the feasibility and strategies for expressing fusion proteins in A. thaliana, specifically the fusion of Epidermal growth factor (EGF) to a cell-penetrating peptide (CPP), in which the production can be greatly enhanced via plant expression systems since these systems offer higher biosecurity, flexibility, and expansibility than prokaryotic, animal and mammalian expression systems. While the fusion of EGF to CCP can enhance its transdermal ability, the effects of the fusion protein on skin repair, melasma, whitening, and anti-aging are poorly explored. Beyond this, fusing proteins with transdermal peptides presents multiple possibilities for the development of tissue repair and regeneration therapeutics, as well as cosmetics and beauty products. As certain plant extracts are known to contain proteins beneficial for skin health, the expression of these proteins in plant systems will better maintain their integrity and biological activities, thereby facilitating the development of more effective skincare products.

Current status and influencing factors of protective motivation for body mass management during pregnancy.

OBJECTIVE: Excessive weight gain, obesity, or insufficient weight gain during pregnancy can adversely affect both the mother and her offspring. This study aims to investigate the relationship between pregnant women's self-perception and beliefs and their body weight management during pregnancy. METHODS: A cross-sectional survey involving 350 pregnant women in Changsha City was conducted from July to September 2023. Instruments included a sociodemographic data sheet, protective motivation questionnaire for pregnancy body quality management, and scales measuring body image, anxiety, self-efficacy, and social support. Univariate analysis and multiple linear regression were employed to identify factors influencing protective motivation for body quality management during pregnancy. RESULTS: The average score of the protective motivation questionnaire was 124 (SD = 13.07), suggesting a need for enhanced weight management. Key factors influencing protective motivation included household income, cooperation with healthcare workers, sources of pregnancy information, midnight snacking habits, prepregnancy exercise, body image, and self-efficacy (P < 0.05). CONCLUSION: The study highlights significant factors influencing pregnant women's motivation for body quality management. These include economic status, healthcare collaboration, information accessibility, lifestyle habits, and psychological factors. The findings underscore the need for healthcare professionals to integrate these factors into pregnancy care programs to improve body quality management.

Exploring the pathogenicity of Mycoplasma pneumoniae: Focus on community-acquired respiratory distress syndrome toxins.

Community-Acquired Respiratory Distress Syndrome Toxin (CARDS TX) is a unique exotoxin produced by Mycoplasma pneumoniae (MP) and has been confirmed to possess ADP-ribosyltransferase (ART) and vacuolating activities. CARDS TX binds to receptors on the surfaces of mammalian cells followed by entry into the cells through clathrin-mediated endocytosis, and exerts cytotoxic effects by undergoing retrograde transport and finally cleavage on endosomes and cellular organelles. In addition, CARDS TX can trigger severe inflammatory reactions resulting in airway dysfunction, producing allergic inflammation and asthma-like conditions. As a newly discovered virulence factor of MP, CARDS TX has been extensively studied in recent years. As resistance to macrolide drugs has increased significantly in recent years and there is no vaccine against MP, the development of a vaccine targeting CARDS TX is considered a potential preventive measure. This review focuses on recent studies and insights into this toxin, providing directions for a better understanding of MP pathogenesis and treatment. IMPORTANCE: A serious hazard to worldwide public health in recent years, Mycoplasma pneumoniae (MP) is a prominent bacterium that causes community-acquired pneumonia (CAP) in hospitalized children. Due to their high prevalence and fatality rates, MP infections often cause both respiratory illnesses and extensive extrapulmonary symptoms. It has recently been shown that MP produces a distinct exotoxin known as Community-Acquired Respiratory Distress Syndrome Toxin (CARDS TX). Mycoplasma pneumoniae pneumonia (MPP)-like tissue injury is caused by this toxin because it has both ADP-ribosyltransferase and vacuolating properties. A better knowledge of MP etiology and therapy is provided by this review, which focuses on latest research and insights into this toxin.

Epidemiology and laboratory detection of non-tuberculous mycobacteria.

The global incidence of non-tuberculous mycobacteria (NTM) infections is on the rise. This study systematically searched several databases, including PubMed, Web of Science, Google Scholar, and two Chinese libraries (Chinese National Knowledge Infrastructure and Wanfang) to identify relevant published between 2013 and 2023 related to the isolation of NTM in clinical specimens from various countries and provinces of China. Furthermore, a comprehensive literature review was conducted in PubMed and Google Scholar to identify randomized clinical trials, meta-analyses, systematic reviews, and observational studies that evaluated the diagnostic accuracy and impact of laboratory detection methods on clinical outcomes. This review presented the most recent epidemiological data and species distributions of NTM isolates in several countries and provinces of China. Moreover, it provided insights into laboratory bacteriological detection, including the identified strains, advantages and disadvantages, recent advancements, and the commercial Mycobacterium identification kits available for clinical use. This review aimed to aid healthcare workers in understanding this aspect, enhance the standards of clinical diagnosis and treatment, and enlighten them on the existing gaps and future research priorities.

KGF-2 ameliorates UVB-triggered skin photodamage in mice by attenuating DNA damage and inflammatory response and mitochondrial dysfunction.

BACKGROUND: Long-term exposure to UVB induces DNA damage, inflammatory response, mitochondrial dysfunction, and apoptosis in skin cells, thus causing skin photodamage. Research has demonstrated the noteworthy antioxidant, anti-inflammatory, DNA repair, and mitochondrial protective properties of keratinocyte growth factor-2 (KGF-2). METHODS: To examine the impact of KGF-2 on UVB-triggered skin photodamage in mice, hair-removed mice were initially exposed under UVB radiation and subsequently treated with KGF-2 hydrogel and repeated for 6 days. On day 7, the assessment of histopathological alterations, inflammation, DNA damage, mitochondrial function, and apoptosis in mouse skin was assessed. RESULTS: It was found that KGF-2 could effectively relieve cutaneous photodamage symptoms and inhibit epidermal proliferation in mice. Meanwhile, KGF-2 was found to significantly reduce DNA damage, attenuate the inflammatory response, and inhibit the mitochondria-mediated intrinsic apoptotic pathway in the UVB-exposed mouse skin photodamage model. CONCLUSION: To summarize, our results indicated that KGF-2 reduces the severity of mouse skin photodamage caused by UVB rays by attenuating DNA damage and the inflammatory response, besides inhibiting the mitochondria-mediated intrinsic apoptosis pathway.

Complete mitochondrial genome of the edible mushroom Singerocybe alboinfundibuliformis (Clitocybaceae, Agaricales).

Singerocybe alboinfundibuliformis (Seok et al.) Yang, Qin & Takah 2014 is an edible mushroom distributed in several East or Southeast Asian countries. Herein, we report the mitochondrial genome of S. alboinfundibuliformis based on Illumina sequencing data. The overall length of the mitochondrial genome is 64,279 bp, with a GC content of 29.0%. It contains 14 typical protein-coding genes, 27 tRNA genes, two rRNA genes, and 13 intergenic ORFs. Most of these genes (39 out of 56) are transcribed at the forward strand, and few (17 out of 56) are transcribed at the reverse strand. Among these genes, only the rnl gene is invaded by an intron, and all other genes are intron-free. Phylogenetic analysis based on mitochondrial amino acid sequences supports the phylogenetic position of S. alboinfundibuliformis in Clitocybaceae, being close to Lepista sordida (Schumach.) Singer 1951. This study serves as a springboard for future investigation on fungal evolution in Clitocybaceae.

In vitro efficacy of Rosa damascena solid state fermentation liquid and water extract on skin care.

BACKGROUND: As a medicinal and food homologous plant, Rosa damascena is not only highly ornamental, but also rich in a variety of active ingredients such as polyphenols and flavonoids. It is widely used in cosmetics, food and pharmaceutical industries. OBJECTIVE: To study the in vitro efficacy of Rosa damascena solid state fermentation liquid (RDF) and water extract (RDE). METHODS: Firstly, the effect of RDF and RDE on the proliferation rate of B16F10 cells was detected by CCK-8 method, and the melanin content was measured by sodium hydroxide lysis method to evaluate the whitening effect of them. Finally, the antioxidant, anti-wrinkling and soothing effects of RDF and RDE were evaluated by biochemical methods in vitro. RESULTS: RDF and RDE within a certain concentration range (0.05%-0.5%) had no effect on the proliferation of B16F10 cells. Compared with Rosa damascena extract (RDE), RDF showed significant effects on bleaching, antioxidant, anti-wrinkling and soothing, among which 0.5% RDF showed the best effect. CONCLUSION: Both RDF and RDE at a certain concentration have effect on skin care in vitro, but the effect of RDF is more significant than that of RDE.

Theory-driven design of cadmium mineralizing layered double hydroxides for environmental remediation.

The environmental concern posed by toxic heavy metal pollution in soil and water has grown. Ca-based layered double hydroxides (LDHs) have shown exceptional efficacy in eliminating heavy metal cations through the formation of super-stable mineralization structures (SSMS). Nevertheless, it is still unclear how the intricate coordination environment of Ca2+ in Ca-based LDH materials affects the mineralization performance, which hinders the development and application of Ca-based LDH materials as efficient mineralizers. Herein, we discover that, in comparison to a standard LDH, the mineralization efficiency for Cd2+ ions may be significantly enhanced in the pentacoordinated structure of defect-containing Ca-5-LDH utilizing both density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations. Furthermore, the calcination-reconstruction technique can be utilized to successfully produce pentacoordinated Ca-5-LDH. Subsequent investigations verified that Ca-5-LDH exhibited double the mineralization performance (421.5 mg g-1) in comparison to the corresponding pristine seven coordinated Ca-7OH/H2O-LDH (191.2 mg g-1). The coordination-relative mineralization mechanism of Ca-based LDH was confirmed by both theoretical calculations and experimental results. The understanding of LDH materials and their possible use in environmental remediation are advanced by this research.

Coke oven emissions exacerbate allergic asthma by promoting ferroptosis in airway epithelial cells.

Epidemiological studies have shown that coke oven emissions (COEs) affect the deterioration of asthma, but has not been proven by experimental results. In this study, we found for the first time that COEs exacerbate allergen house dust mite (HDM)-induced allergic asthma in the mouse model. The findings reveal that airway inflammation, airway remodeling and allergic reaction were aggravated in the COE + HDM combined exposure group compared with the individual exposure group. Mechanism studies indicated higher levels of iron and MDA in the COE + HDM combined exposure group, along with increased expression of Ptgs2 and reduced GPX4 expression. Iron chelator deferoxamine (DFO) effectively inhibited ferroptosis induced by COE synergistically with HDM in vitro. Further studies highlighted the role of ferritinophagy in the COE + HDM-induced ferroptosis. 3-methyladenine (3-MA) could inhibit ferroptosis in the COE + HDM exposure group. Interestingly, we injected DFO intraperitoneally into mice in the combined exposure group and found DFO could significantly inhibit the COE-exacerbated ferroptosis and allergic asthma. Our findings link ferroptosis with COE-exacerbated allergic asthma, implying that ferroptosis may have important therapeutic potential for asthma in patients with occupational exposure of COE.

Breastfeeding in infancy and cardiovascular disease in middle-aged and older adulthood: a prospective study of 0.36 million UK Biobank participants.

BACKGROUND: Cardiovascular disease originates in early life. We aimed to investigate the association between breastfeeding in infancy and cardiovascular disease in adult life. METHODS: We followed 364,240 participants from UK Biobank aged 40-73 years from 2006 - 2010 to 2021. Information on breastfeeding in infancy was self-reported by questionnaire. Cox proportional hazard regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the association between breastfeeding and cardiovascular disease in middle-aged and older adulthood. The multivariable Cox models were used by adjusting for the age (used as the time scale), sex, ethnicity, assessment centre, birth weight, multiple birth status, maternal smoking during pregnancy, Townsend deprivation index, smoking status, alcohol drinker status, physical activity, and menopausal status for women. Binary and multinomial multivariable logistic regression models were used to explore the associations of breastfeeding in infancy with cardiovascular disease risk factors including obesity, body composition, metabolic and inflammatory disorders. RESULTS: During a median of 12.6 years of follow-up, we documented 29,796 new cases of cardiovascular disease, including 24,797 coronary heart disease and 6229 stroke. The multivariable adjusted HRs for breastfed versus non-breastfed were 0.94 (95% CI: 0.91, 0.96) for cardiovascular disease, 0.94 (95% CI: 0.91, 0.96) for coronary heart disease, and 0.95 (95% CI: 0.89, 1.01) for stroke. Furthermore, the strength of observed association between breastfeeding and cardiovascular disease seems to decrease with age (P for interaction <0.001), and increase with polygenic risk for cardiovascular disease (P for interaction <0.001). Consistently, breastfeeding in infancy was associated with cardiovascular disease risk factors including lower body mass index 0.92 (95% CI: 0.89, 0.95), body fat percentage 0.85 (95% CI: 0.83, 0.87), android to gynoid fat ratio 0.89 (95% CI: 0.83, 0.96), visceral adipose tissue 0.92 (95% CI: 0.84, 1.01), as well as lower C-reactive protein level 0.95 (95% CI: 0.94, 0.97) and a lower risk of metabolic syndrome 0.89 (95% CI: 0.85, 0.92). CONCLUSIONS: Breastfeeding in infancy was associated with a lower risk of cardiovascular disease in middle-aged and older adulthood. Promoting breastfeeding is vital not only for promoting child health, but also for halting the increasing trend of cardiovascular disease in adults.

Inhibition of SARS-CoV-2 Replication by Self-Assembled siRNA Nanoparticles Targeting Multiple Highly Conserved Viral Sequences.

Coronavirus infectious disease 2019 (COVID-19), caused by severe acute respiratory virus type 2 (SARS-CoV-2), has caused a global public health crisis. As an RNA virus, the high gene mutability of SARS-CoV-2 poses significant challenges to the development of broad-spectrum vaccines and antiviral therapeutics. There remains a lack of specific therapeutics directly targeting SARS-CoV-2. With the ability to efficiently inhibit the expression of target genes in a sequence-specific way, small interfering RNA (siRNA) therapy has exhibited significant potential in antiviral and other disease treatments. In this work, we presented a highly effective self-assembled siRNA nanoparticle targeting multiple highly conserved regions of SARS-CoV-2. The siRNA sequences targeting viral conserved regions were first screened and evaluated by their thermodynamic features, off-target effects, and secondary structure toxicities. RNA motifs including siRNA sequences were then designed and self-assembled into siRNA nanoparticles. These siRNA nanoparticles demonstrated remarkable uniformity and stability and efficiently entered cells directly through cellular endocytic pathways. Moreover, these nanoparticles effectively inhibited the replication of SARS-CoV-2, exhibiting a superior inhibitory effect compared to free siRNA. These results demonstrated that these self-assembled siRNA nanoparticles targeting highly conserved regions of SARS-CoV-2 represent highly effective antiviral candidates for the treatment of infections, and are promisingly effective against current and future viral variants.