Comparative genomic analyses on assassin bug Rhynocoris fuscipes (Hemiptera: Reduviidae) reveal genetic bases governing the diet-shift.

Genetic basis underlying the biodiversity and phenotypic plasticity are fascinating questions in evolutionary biology. Such molecular diversity can be achieved at multi-omics levels. Here, we sequenced the first chromosome-level genome of assassin bug Rhynocoris fuscipes, a polyphagous generalist predator for biological control of agroecosystems. Compared to non-predatory true bugs Apolygus lucorum and Riptortus pedestris, the R. fuscipes-specific genes were enriched in diet-related genes (e.g., serine proteinase, cytochrome P450) which had higher expression level and more exons than non-diet genes. Extensive A-to-I RNA editing was identified in all three species and showed enrichment in genes associated with diet in R. fuscipes, diversifying the transcriptome. An extended analysis between five predaceous and 27 phytophagous hemipteran species revealed an expansion of diet-related genes in R. fuscipes. Our findings bridge the gap between genotype and phenotype, and also advance our understanding on genetic and epigenetic bases governing the diet shifts in ture bugs.

Explore the Role of Frailty as a Contributor to the Association Between AT(N) Profiles and Cognition in Alzheimer's Disease.

Background: The relationship between Alzheimer's disease (AD)-related pathology and cognition was not exactly consistent. Objective: To explore whether the association between AD pathology and cognition can be moderated by frailty. Methods: We included 1711 participants from the Alzheimer's Disease Neuroimaging Initiative database. Levels of cerebrospinal fluid amyloid-ß, p-tau, and t-tau were identified for AD-related pathology based on the amyloid-ß/tau/neurodegeneration (AT[N]) framework. Frailty was measured using a modified Frailty Index-11 (mFI-11). Regression and interaction models were utilized to assess the relationship among frailty, AT(N) profiles, and cognition. Moderation models analyzed the correlation between AT(N) profiles and cognition across three frailty levels. All analyses were corrected for age, sex, education, and APOEɛ4 status. Results: In this study, frailty (odds ratio [OR] = 1.71, p < 0.001) and AT(N) profiles (OR = 2.00, p < 0.001) were independently associated with cognitive status. The model fit was improved when frailty was added to the model examining the relationship between AT(N) profiles and cognition (p < 0.001). There was a significant interaction between frailty and AT(N) profiles in relation to cognitive status (OR = 1.12, pinteraction = 0.028). Comparable results were obtained when Mini-Mental State Examination scores were utilized as the measure of cognitive performance. The association between AT(N) profiles and cognition was stronger with the levels of frailty. Conclusions: Frailty may diminish patients' resilience to AD pathology and accelerate cognitive decline resulting from abnormal AD-related pathology. In summary, frailty contributes to elucidating the relationship between AD-related pathology and cognitive impairment.

Complex Pulmonary Arteriovenous Fistula Presented With Ventricular Tachycardia and Type 2 Acute Myocardial Infarction.

Pulmonary arteriovenous fistula (PAVF) is a rare congenital vascular malformation primarily manifested as dyspnea, migraine, ischemic stroke, hemoptysis, and nervous system complications. However, in our case, an 18-year-old male patient with PAVF presented with sudden onset of ventricular tachycardia and type 2 acute myocardial infarction as initial symptoms. A diagnosis was achieved through pulmonary artery computer tomography angiography (CTA) and three-dimensional (3D) computed tomography (CT) reconstruction, revealing a complex and giant PAVF. Following multidisciplinary team (MDT) consultation, the patient underwent thoracoscopic surgery and experienced a successful recovery during follow-up.

The determination of 11 sulfonamide antibiotics in water and foods by developing a N-rich magnetic covalent organic framework combined with ultra-high performance liquid chromatography-tandem mass spectrometry.

The concentration of antibiotic residues in water and animal-derived foods is low and the matrix is complex, and effective extraction of antibiotic residues in them is a key factor for accurate quantification. It is important to establish a rapid and effective method for the analytical determination of antibiotics in water and foods. In this study, a type of novel magnetic COF (Fe3O4@SiO2@PDE-TAPB-COF) was synthesized and characterized. Moreover, Fe3O4@SiO2@PDE-TAPB-COF combined with ultra-high performance liquid chromatography-tandem mass spectrometry was used to determine the 11 sulfonamide antibiotics (SAs) in water and food. The parameters including pH, adsorption amount, adsorption time, type of elution solvent and elution time were optimized. Under the optimal conditions, the standard curves of 11 SAs showed good linearity (R 2 > 0.999) in their respective concentration ranges and had lower detection and quantification limits. The spiked recoveries of the developed MSPE-UPLC-MS/MS method for the 11 SAs in water and foods were 74.3-107.2% and 75.1-102.5%, respectively. And the relative standard deviations (RSDs) were less than 9.56% (n = 7). The results indicated that the method can be used for the determination of SAs in foods and water with low detection limits and high sensitivity.

Early life malnutrition and risk of T2DM adulthood: evidence from the lower socioeconomic status of northwest Chinese population.

Objective: This study aimed to explore whether famine exposure during early life are associated with a high risk of Type 2 Diabetes Mellitus (T2DM) in adulthood and the role of socioeconomic status (SES) on this effect. Materials and methods: We conducted a secondary data analysis based on data from a cross-sectional survey, collected 3,355 participants born between January 1, 1941 and December 31, 1966. Participants were categorized into four groups based on their date of birth, unexposed (individuals born in 1963-1966), infant exposed (individuals born in 1959-1962), childhood exposed (individuals born in 1949-1958), and adolescent exposed (born in 1941-1948). The association of famine exposure with T2DM risk in adults and conducted separately in plain area and mountain area was assessed using logistics regression model. Result: 22.35% of participants were diagnosed with T2DM, of which 43.47% were from the childhood famine-exposed group, representing the highest proportion among all subgroups (p < 0.001). Participants exposed to famine during childhood and adolescence from the lower SES mountain areas showed a significantly higher prevalence of T2DM in adulthood than those from the plain areas (p < 0.001). The adolescence stage exposed famine will increase the risk of T2DM in the mountain area (OR 2.46, 95% CI 1.61, 3.77). Conclusion: No strong evidence demonstrates that exposure to famine during the early life stage increases the risk of developing T2DM in adulthood. However, populations with lower SES are likely to be exposed to more risk factors for T2DM.

Design of novel broad-spectrum antiviral nucleoside analogues using natural bases ring-opening strategy.

The global prevalence of RNA virus infections has presented significant challenges to public health in recent years, necessitating the expansion of its alternative therapeutic library. Due to its evolutional conservation, RNA-dependent RNA polymerase (RdRp) has emerged as a potential target for broad-spectrum antiviral nucleoside analogues. However, after over half a century of structural modification, exploring unclaimed chemical space using frequently-used structural substitution methods to design new nucleoside analogues is challenging. In this study, we explore the use of the "ring-opening" strategy to design new base mimics, thereby using these base mimics to design new nucleoside analogues with broad-spectrum antiviral activities. A total of 29 compounds were synthesized. Their activity against viral RdRp was initially screened using an influenza A virus RdRp high-throughput screening model. Then, the antiviral activity of 38a was verified against influenza virus strain A/PR/8/34 (H1N1), demonstrating a 50% inhibitory concentration (IC50) value of 9.95 µM, which was superior to that of ribavirin (the positive control, IC50 = 11.43 µM). Moreover, 38a also has inhibitory activity against coronavirus 229E with an IC50 of 30.82 µM. In addition, compounds 42 and 46f exhibit an 82% inhibition rate against vesicular stomatitis virus at a concentration of 20 µM and hardly induce cytotoxicity in host cells. This work demonstrates the feasibility of designing nucleoside analogues with "ring-opening" bases and suggests the "ring-opening" nucleosides may have greater polarity, and designing prodrugs is an important aspect of optimizing their antiviral activity. Future research should focus on enhancing the conformational restriction of open-loop bases to mimic Watson-Crick base pairing better and improve antiviral activity.

Learning from the Codon Table: Convergent Recoding Provides Novel Understanding on the Evolution of A-to-I RNA Editing.

Adenosine-to-inosine (A-to-I) RNA editing recodes the genetic information. Apart from diversifying the proteome, another tempting advantage of RNA recoding is to correct deleterious DNA mutation and restore ancestral allele. Solid evidences for beneficial restorative editing are very rare in animals. By searching for "convergent recoding" under a phylogenetic context, we proposed this term for judging the potential restorative functions of particular editing site. For the well-known mammalian Gln>Arg (Q>R) recoding site, its ancestral state in vertebrate genomes was the pre-editing Gln, and all 470 available mammalian genomes strictly avoid other three equivalent ways to achieve Arg in protein. The absence of convergent recoding from His>Arg, or synonymous mutations on Gln codons, could be attributed to the strong maintenance on editing motif and structure, but the absence of direct A-to-G mutation is extremely unexpected. With similar ideas, we found cases of convergent recoding in Drosophila genus, reducing the possibility of their restorative function. In summary, we defined an interesting scenario of convergent recoding, the occurrence of which could be used as preliminary judgements for whether a recoding site has a sole restorative role. Our work provides novel insights to the natural selection and evolution of RNA editing.

Outcomes of endoscopic modified cartilage-perichondrium tympanoplasty on different sized perforations.

OBJECTIVES: To evaluate the anatomic and functional outcomes of type1 tympanoplasty with endoscopic modified butterfly cartilage-perichondrium technique. METHODS: In our modification, perichondrium was elevated circumferentially till the attached part of the composite graft was approximately same size and shape of the perforation, cartilage was trimmed based on the perforation but 0.5 mm larger. Cartilage portion of the graft was placed medial to the edge of the perforation, then perichondrium was rolled out and draped on the circumferential raw surface of remaining tympanic membrane around. RESULTS: At 4 months postop, the anatomic integrity rate of the tympanic membrane perforation for small & medium sized perforation and large sized perforation group were 100 % and 94 % (p > 0.05). For the small & medium perforation group, the mean pre and 4 months postop ACs were 30 ± 8 dB and 18 ± 6.4 dB (p < 0.01). The mean pre and 4 months postop ABGs were 19 ± 11 dB and 9 ± 3 dB (p < 0.01). For the large perforation group, the mean pre and 4 months postop ACs were 43 ± 12.5 dB and 21.5 ± 7 dB (p < 0.01). The mean pre and 4 months postop ABGs were 34 ± 8.5 dB and 12.5 ± 6 dB (p < 0.01). The differences of mean 4 months postop ACs and mean 4 months postop ABGs between the two groups were not significant (p > 0.05). CONCLUSIONS: Compared to the conventional inlay butterfly cartilage tympanoplasty technique, large or marginal perforations can be sealed more securely by this modification.

Association Between Body Mass Index or Serum Albumin and Different Dementia Populations.

INTRODUCTION: There is limited understanding of Body Mass Index (BMI) and serum albumin levels in patients with dementia. This study aims to investigate the association between BMI, serum albumin levels, and dementia in patients with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Parkinson's disease with dementia (PDD). METHODS: A total of 336 patients with dementia (173 with AD, 112 with DLB, 51 with PDD) and 220 healthy controls were recruited. Pearson and Spearman correlation analyses were performed to examine the relationships between BMI or serum albumin and MMSE scores, as well as neuropathological markers. Logistic regression models were used to analyze the data, adjusting for confounding variables. RESULTS: Using the highest BMI quartile (≥ 26.04 kg/m²) and serum albumin quartile (≥ 41.21 g/L) as reference groups, the lowest BMI quartile (< 21.91 kg/m²) was significantly associated with AD (p < 0.001) and DLB (p = 0.003). The lowest serum albumin quartile (≤ 37.60 g/L) was independently associated with DLB (p < 0.001) and AD (p = 0.006). In AD patients, BMI was associated with Aß1-42 and p-Tau181 in cerebrospinal fluid after controlling for confounders, while serum albumin was correlated with T-Tau and T-tau/Aß1-42 (p < 0.05). CONCLUSION: Decreased serum albumin and BMI levels are associated with DLB and AD in dementia patients. Although no correlation was found between BMI or serum albumin and MMSE scores, there was a significant association with AD cerebrospinal fluid pathologic markers.

A Solid Electrolyte RHE for Electrode Diagnosis of Proton Exchange Membrane Water Electrolyzers.

Reference electrode is the foundation of electrochemical study; thus, most electrode materials are tested in a three-electrode mode to acquire potential-dependent kinetics. However, it is difficult to directly use conventional reference electrodes to detect potential information in solid electrolyte devices due to their compact assembly structure. Therefore, the kinetic study of an electrochemical device faces challenges in precise identification of specific problems originating from the anode or cathode. Here, focusing on proton exchange membrane water electrolysis, we design a solid electrolyte reversible hydrogen electrode (SE-RHE), which can be used for electrode diagnosis under various operating conditions. Compared to the reference electrodes reported in the literature, which are mainly based on liquid electrolyte, the SE-RHE is highly sensitive and compatible, as well as easy to assemble. The potential deviation is less than ±0.5 mV, and the cell voltage derived from the electrode potential well reproduces the value that was directly measured with a deviation less than 0.2%. The reference electrode developed in this work enables the kinetic study of a specific electrode rather than the entire cell. For instance, an interesting observation is that the cathode shows distinct stability under stable and fluctuating operations. Differing from the high stability under stable operation, the cathode degrades significantly under fluctuating operations.

Laparoscopy is non-inferior to open surgery for rectal cancer: A systematic review and meta-analysis.

BACKGROUND: Laparoscopic surgery has been endorsed by clinical guidelines for colon cancer, but not for rectal cancer on account of unapproved oncologic equivalence with open surgery. AIMS: We started this largest-to-date meta-analysis to comprehensively evaluate the safety and efficacy of laparoscopy in the treatment of rectal cancer compared with open surgery. MATERIALS & METHODS: Both randomized and nonrandomized controlled trials comparing laparoscopic proctectomy and open surgery between January 1990 and March 2020 were searched in PubMed, Cochrane Library and Embase Databases (PROSPERO registration number CRD42020211718). The data of intraoperative, pathological, postoperative and survival outcomes were compared between two groups. RESULTS: Twenty RCTs and 93 NRCTs including 216,615 patients fulfilled the inclusion criteria, with 48,888 patients received laparoscopic surgery and 167,727 patients underwent open surgery. Compared with open surgery, laparoscopic surgery group showed faster recovery, less complications and decreased mortality within 30 days. The positive rate of circumferential margin (RR = 0.79, 95% CI: 0.72 to 0.85, p < 0.0001) and distal margin (RR = 0.75, 95% CI: 0.66 to 0.85 p < 0.0001) was significantly reduced in the laparoscopic surgery group, but the completeness of total mesorectal excision showed no significant difference. The 3-year and 5-year local recurrence, disease-free survival and overall survival were all improved in the laparoscopic surgery group, while the distal recurrence did not differ significantly between the two approaches. CONCLUSION: Laparoscopy is non-inferior to open surgery for rectal cancer with respect to oncological outcomes and long-term survival. Moreover, laparoscopic surgery provides short-term advantages, including faster recovery and less complications.

The potential roles of PKM2 in cerebrovascular diseases.

Pyruvate kinase M2 (PKM2), a key enzyme involved in glycolysis,plays an important role in regulating cell metabolism and growth under different physiological conditions. PKM2 has been intensively investigated in multiple cancer diseases. Recent years, many studies have found its pivotal role in cerebrovascular diseases (CeVDs), the disturbances in intracranial blood circulation. CeVDs has been confirmed to be closely associated with oxidative stress (OS), mitochondrial dynamics, systemic inflammation, and local neuroinflammation in the brain. It has further been revealed that PKM2 exerts various biological functions in the regulation of energy supply, OS, inflammatory responses, and mitochondrial dysfunction. The roles of PKM2 are closely related to its different isoforms, expression levels in subcellular localization, and post-translational modifications. Therefore, summarizing the roles of PKM2 in CeVDs will help further understanding the molecular mechanisms of CeVDs. In this review, we illustrate the characteristics of PKM2, the regulated PKM2 expression, and the biological roles of PKM2 in CeVDs.

TFAP2A is involved in neuropathic pain by regulating Grin1 expression in glial cells of the dorsal root ganglion.

Neuropathic pain is a highly prevalent and refractory condition, yet its mechanism remains poorly understood. While NR1, the essential subunit of NMDA receptors, has long been recognized for its pivotal role in nociceptive transmission, its involvement in presynaptic stimulation is incompletely elucidated. Transcription factors can regulate the expression of both pro-nociceptive and analgesic factors. Our study shows that transcription factor TFAP2A was up-regulated in the dorsal root ganglion (DRG) neurons, satellite glial cells (SGCs), and Schwann cells following spinal nerve ligation (SNL). Intrathecal injection of siRNA targeting Tfap2a immediately or 7 days after SNL effectively alleviated SNL-induced pain hypersensitivity and reduced Tfap2a expression levels. Bioinformatics analysis revealed that TFAP2A may regulate the expression of the Grin1 gene, which encodes NR1. Dual-luciferase reporter assays confirmed TFAP2A's positive regulation of Grin1 expression. Notably, both Tfap2a and Grin1 were expressed in the primary SGCs and upregulated by lipopolysaccharides. The expression of Grin1 was also down-regulated in the DRG following Tfap2a knockdown. Furthermore, intrathecal injection of siRNA targeting Grin1 immediately or 7 days post-SNL effectively alleviated SNL-induced mechanical allodynia and thermal hyperalgesia. Finally, intrathecal Tfap2a siRNA alleviated SNL-induced neuronal hypersensitivity, and incubation of primary SGCs with Tfap2a siRNA decreased NMDA-induced upregulation of proinflammatory cytokines. Collectively, our study reveals the role of TFAP2A-Grin1 in regulating neuropathic pain in peripheral glia, offering a new strategy for the development of novel analgesics.

Detection and margin assessment of thyroid carcinoma with microscopic hyperspectral imaging using transformer networks.

Significance: Hyperspectral imaging (HSI) is an emerging imaging modality for oncological applications and can improve cancer detection with digital pathology. Aim: The study aims to highlight the increased accuracy and sensitivity of detecting the margin of thyroid carcinoma in hematoxylin and eosin (H&E)-stained histological slides using HSI and data augmentation methods. Approach: Using an automated microscopic imaging system, we captured 2599 hyperspectral images from 65 H&E-stained human thyroid slides. Images were then preprocessed into 153,906 image patches of dimension 250 × 250 × 84 pixels . We modified the TimeSformer network architecture, which used alternating spectral attention and spatial attention layers. We implemented several data augmentation methods for HSI based on the RandAugment algorithm. We compared the performances of TimeSformer on HSI against the performances of pretrained ConvNext and pretrained vision transformers (ViT) networks on red, green, and blue (RGB) images. Finally, we applied attention unrolling techniques on the trained TimeSformer network to identify the biological features to which the network paid attention. Results: In the testing dataset, TimeSformer achieved an accuracy of 90.87%, a weighted F 1 score of 89.79%, a sensitivity of 91.50%, and an area under the receiving operator characteristic curve (AU-ROC) score of 97.04%. Additionally, TimeSformer produced thyroid carcinoma tumor margins with an average Jaccard score of 0.76 mm. Without data augmentation, TimeSformer achieved an accuracy of 88.23%, a weighted F 1 score of 86.46%, a sensitivity of 85.53%, and an AU-ROC score of 94.94%. In comparison, the ViT network achieved an 89.98% accuracy, an 88.14% weighted F 1 score, an 84.77% sensitivity, and a 96.17% AU-ROC. Our visualization results showed that the network paid attention to biological features. Conclusions: The TimeSformer model trained with hyperspectral histological data consistently outperformed conventional RGB-based models, highlighting the superiority of HSI in this context. Our proposed augmentation methods improved the accuracy, the F 1 score, and the sensitivity score.

The relationship between depression and lipid accumulation product: a population-based study.

Background: Lipid Accumulation Product (LAP) is a new type of obesity index. The relationship between LAP and depression is unclear, and this cross-sectional study was conducted to explore the relationship between LAP and depression using the National Health and Nutrition Examination Survey (NHANES) database from 2005-2018. Methods: In our study, logistic regression analysis was used to calculate the odds ratio between depression and LAP, and subgroup analysis and sensitivity analysis were also performed to verify the robustness of the results. Results: The analysis included 13,240 participants aged 20 years or older. After adjusting for multiple variables, LAP was positively associated with depression, OR 1. 50 (95% CI, 1. 05-2. 12). In subgroup analysis, LAP was significantly positively, associated with depression among male (2. 52, OR; 95% CI, 1. 39,4. 57), non-Hispanic Black (2. 55, OR; 95% CI, 1. 49,4. 36), those without diabetes (1. 67, OR; 95% CI, (1. 06,2. 61) or in the overweight (2. 09, OR; 95% CI, (1. 23,3. 54) subgroups. After inverse probability of treatment weighting (IPTW), the OR for the highest versus lowest quartile was 1. 55 (95% CI: 1. 24 - 1. 95). Conclusion: There are positive results between LAP and depression after adjusting for multiple potential variables, and prospective studies are needed to verify the results.

Preparation of magnetic cationic Schiff base polymeric material for highly selective enrichment of avermectins from surface water and milk samples.

Herein, a magnetic cationic Schiff base polymeric material (Fe3O4@SiO2-Schiff-TAPB-DA) was fabricated simply and rapidly, which was explored as a magnetic adsorbent for magnetic solid-phase extraction (MSPE) for enriching seven avermectins insecticides in surface water and milk matrices combined with ultra-high performance liquid chromatography mass spectrometry (UPLC-MS/MS). Under the optimized pretreatment and instrumental parameters, the analytes showed good linearity in the range of 0.5-200.0 ng·mL-1 with a correlation coefficient (R2) greater than 0.9990 and high precision. The limits of detection for the analytes were 0.004-0.047 µg·L-1 for surface water sample and 0.008-0.250 µg·kg-1 for milk samples. Satisfactory recoveries of spiked target compounds were in the range of 82.25- 100.87 % for surface water sample and 72.73- 119.62 % for milk samples. The results indicated powerfully Fe3O4@SiO2-Schiff-TAPB-DA was of significant potential as an MSPE adsorbent for the detection of avermectin insecticides in surface water and milk, which provides a quick and efficient idea for enriching avermectins insecticides in complicated matrices.

The effect of centromere protein Fta2 phosphorylation during meiosis.

During meiosis, defects in cohesin localization within the centromere region can result in various diseases. Accurate cohesin localization depends on the Mis4-Ssl3 loading complex. Although it is known that cohesin completes the loading process with the help of the loading complex, the mechanisms underlying its localization in the centromere region remain unclear. Previous studies suggest cohesin localization in the centromere is mediated by phosphorylation of centromeric proteins. In this study, we focused on the Fta2 protein, a component of the Sim4 centromere protein complex. Using bioinformatics methods, potential phosphorylation sites were identified, and fta2-9A and fta2-9D mutants were constructed in Schizosaccharomyces pombe. The phenotypes of these mutants were characterized through testing thiabendazole (TBZ) sensitivity and fluorescent microscopy localization. Results indicated that Fta2 phosphorylation did not impact mitosis but affected chromosome segregation during meiosis. This study suggests that Fta2 phosphorylation is vital for meiosis and may be related to the specific localization of cohesin during this process.

Genome-wide meta-analysis identifies ancestry-specific loci for Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is a devastating neurological disease with complex genetic etiology. Yet most known loci have only identified from the late-onset type AD in populations of European ancestry. METHODS: We performed a two-stage genome-wide association study (GWAS) of AD totaling 6878 Chinese and 63,926 European individuals. RESULTS: In addition to the apolipoprotein E (APOE) locus, our GWAS of two independent Chinese samples uncovered three novel AD susceptibility loci (KIAA2013, SLC52A3, and TCN2) and a novel ancestry-specific variant within EGFR (rs1815157). More replicated variants were observed in the Chinese (31%) than in the European samples (15%). In combining genome-wide associations and functional annotations, EGFR and TCN2 were prioritized as two of the most biologically significant genes. Phenome-wide Mendelian randomization suggests that high mean corpuscular hemoglobin concentration might protect against AD. DISCUSSION: The current study reveals novel AD susceptibility loci, emphasizes the importance of diverse populations in AD genetic research, and advances our understanding of disease etiology. HIGHLIGHTS: Loci KIAA2013, SLC52A3, and TCN2 were associated with Alzheimer's disease (AD) in Chinese populations. rs1815157 within the EGFR locus was associated with AD in Chinese populations. The genetic architecture of AD varied between Chinese and European populations. EGFR and TCN2 were prioritized as two of the most biologically significant genes. High mean corpuscular hemoglobin concentrations might have protective effects against AD.

Construction of ROS-Responsive Hyaluronic Acid Modified Paclitaxel and Diosgenin Liposomes and Study on Synergistic Enhancement of Anti-Ovarian Cancer Efficacy.

Purpose: Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG2000-HA and DSPE-PEG2000-TK-PEG5000, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration. Methods and Results: PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects. Conclusion: The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.