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1.
Int Braz J Urol ; 502024 Aug 12.
Article in English | MEDLINE | ID: mdl-39133792

ABSTRACT

INTRODUCTION: We aim to compare the safety and effectiveness of the KangDuo (KD)-Surgical Robot-01 (KD-SR-01) system and the da Vinci (DV) system for robot-assisted radical nephroureterectomy (RARNU). MATERIALS AND METHODS: This multicenter prospective randomized controlled trial was conducted between March 2022 and September 2023. Group 1 included 29 patients undergoing KD-RARNU. Group 2 included 29 patients undergoing DV-RARNU. Patient demographic and clinical characteristics, perioperative data, and follow-up outcomes were collected prospectively and compared between the two groups. RESULTS: There were no significant differences in patient baseline demographic and preoperative characteristics between the two groups. The success rates in both groups were 100% without conversion to open or laparoscopic surgery or positive surgical margins. No significant difference was observed in docking time [242 (120-951) s vs 253 (62-498) s, P = 0.780], console time [137 (55-290) min vs 105 (62-220) min, P = 0.114], operative time [207 (121-460) min vs 185 (96-305) min, P = 0.091], EBL [50 (10-600) mL vs 50 (10-700) mL, P = 0.507], National Aeronautics and Space Administration Task Load Index scores, and postoperative serum creatinine levels between the two groups. None of the patients showed evidence of distant metastasis, local recurrence, or equipment-related adverse events during the four-week follow-up. One (3.4%) patient in Group 2 experienced postoperative enterovaginal and enterovesical fistulas (Clavien-Dindo grade III). CONCLUSIONS: The KD-SR-01 system is safe and effective for RARNU compared to the DV Si or Xi system. Further randomized controlled studies with larger sample sizes and longer durations are required.

2.
Nat Biotechnol ; 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39090305

ABSTRACT

Therapeutic small interfering RNA (siRNA) requires sugar and backbone modifications to inhibit nuclease degradation. However, metabolic stabilization by phosphorothioate (PS), the only backbone chemistry used clinically, may be insufficient for targeting extrahepatic tissues. To improve oligonucleotide stabilization, we report the discovery, synthesis and characterization of extended nucleic acid (exNA) consisting of a methylene insertion between the 5'-C and 5'-OH of a nucleoside. exNA incorporation is compatible with common oligonucleotide synthetic protocols and the PS backbone, provides stabilization against 3' and 5' exonucleases and is tolerated at multiple oligonucleotide positions. A combined exNA-PS backbone enhances resistance to 3' exonuclease by ~32-fold over the conventional PS backbone and by >1,000-fold over the natural phosphodiester backbone, improving tissue exposure, tissue accumulation and efficacy in mice, both systemically and in the brain. The improved efficacy and durability imparted by exNA may enable therapeutic interventions in extrahepatic tissues, both with siRNA and with other oligonucleotides such as CRISPR guide RNA, antisense oligonucleotides, mRNA and tRNA.

3.
Sci Data ; 11(1): 856, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39122795

ABSTRACT

The Eastern Pamir, distinguished with high altitude, extremely arid and cold climate, limited nutrients and sparse vegetation, is a unique ecological reservoir. Microbial communities play a central role in maintaining Eastern Pamir's ecosystem functioning. Despite the ecological significance, due to the difficulty of sample collection and microbial isolation, the microbial diversity and its functionality at the Pamir Plateau have been rarely documented. To fill this gap, 80 soil samples from 17 sites across different elevations were collected, performed the rDNA amplicon sequencing to present the first large-scale overview of bacterial, archaeal, and fungal communities in the Eastern Pamir. Microbiome analysis revealed that the bacteria Actinobacteria, Alphaproteobacteria and Bacteroidia, alongside such as archaea Nitrososphaeria and Halobacteria, and fungi including Dothideomycetes, Sordariomycetes and Eurotiomycetes were dominant lineages at class level in soil microbial communities. The community structure and biodiversity of soil microorganisms provided by this dataset would be pivotal for future studies aimed at understanding the biogeographical distribution, ecological functions and environmental responses of microbial communities of the Pamir Plateau.


Subject(s)
Archaea , Bacteria , Fungi , Microbiota , Soil Microbiology , China , Archaea/genetics , Archaea/classification , Bacteria/genetics , Bacteria/classification , Fungi/genetics , Fungi/classification , DNA, Ribosomal/genetics , Biodiversity , Soil/chemistry
4.
Chem Sci ; 15(32): 13111, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39148772

ABSTRACT

[This corrects the article DOI: 10.1039/D4SC02201G.].

5.
Int J Mol Sci ; 25(15)2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39125724

ABSTRACT

Auxin Response Factors (ARFs) make up a plant-specific transcription factor family that mainly couples perception of the phytohormone, auxin, and gene expression programs and plays an important and multi-faceted role during plant growth and development. Lemongrass (Cymbopogon flexuosus) is a representative Cymbopogon species widely used in gardening, beverages, fragrances, traditional medicine, and heavy metal phytoremediation. Biomass yield is an important trait for several agro-economic purposes of lemongrass, such as landscaping, essential oil production, and phytoremediation. Therefore, we performed gene mining of CfARFs and identified 26 and 27 CfARF-encoding genes in each of the haplotype genomes of lemongrass, respectively. Phylogenetic and domain architecture analyses showed that CfARFs can be divided into four groups, among which groups 1, 2, and 3 correspond to activator, repressor, and ETTN-like ARFs, respectively. To identify the CfARFs that may play major roles during the growth of lemongrass plants, RNA-seq was performed on three tissues (leaf, stem, and root) and four developmental stages (3-leaf, 4-leaf, 5-leaf. and mature stages). The expression profiling of CfARFs identified several highly expressed activator and repressor CfARFs and three CfARFs (CfARF3, 18, and 35) with gradually increased levels during leaf growth. Haplotype-resolved transcriptome analysis revealed that biallelic expression dominance is frequent among CfARFs and contributes to their gene expression patterns. In addition, co-expression network analysis identified the modules enriched with CfARFs. By establishing orthologous relationships among CfARFs, sorghum ARFs, and maize ARFs, we showed that CfARFs were mainly expanded by whole-genome duplications, and that the duplicated CfARFs might have been divergent due to differential expression and variations in domains and motifs. Our work provides a detailed catalog of CfARFs in lemongrass, representing a first step toward characterizing CfARF functions, and may be useful in molecular breeding to enhance lemongrass plant growth.


Subject(s)
Cymbopogon , Gene Expression Regulation, Plant , Indoleacetic Acids , Phylogeny , Plant Proteins , Cymbopogon/genetics , Cymbopogon/metabolism , Cymbopogon/growth & development , Indoleacetic Acids/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Plant Development/genetics , Plant Growth Regulators/metabolism , Gene Expression Profiling , Haplotypes
6.
Article in English | MEDLINE | ID: mdl-39143669

ABSTRACT

OBJECTIVES: In recent years, the use of shear-wave elastography (SWE) as a diagnostic tool for detecting malignant breast lesions has shown promising results. This study aims to determine the clinical diagnostic value of SWE in detecting malignant nipple retraction. METHODS: Both US and SWE (Philips EPIQ7 system) were performed for 41 consecutive patients with nipple retraction (56 nipples). The mean, median, and maximum tissue elasticity values (in kilopascals) were determined for each nipple by using SWE. The sensitivity, specificity, and overall accuracy of each measurement was determined by using the surgical pathology results or clinical diagnosis as the gold standard. RESULTS: Of the 56 retracted nipples, 32 were due to benign lesions, and 24 were due to malignant lesions. No significant differences in dimensions or echo features were found between the benign and malignant groups. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the color Doppler flow imaging (CDFI) pattern were 63.89% (23/36), 95% (19/20), 95.83 (23/24), 59.38 (19/32), and 75% (42/56), respectively; the corresponding values for median elasticity on SWE were 88.46% (23/26), 96.67% (29/30), 95.83 (23/24), 90.63 (29/32), and 92.85 (52/56), respectively. CONCLUSIONS: The addition of SWE to conventional US could help differentiate benign from malignant lesions associated with nipple retraction.

7.
BMC Cardiovasc Disord ; 24(1): 432, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39152369

ABSTRACT

BACKGROUND: Heart failure (HF), which is caused by cardiac overload and injury, is linked to significant mortality. Writers of RNA modification (WRMs) play a crucial role in the regulation of epigenetic processes involved in immune response and cardiovascular disease. However, the potential roles of these writers in the immunological milieu of HF remain unknown. METHODS: We comprehensively characterized the expressions of 28 WRMs using datasets GSE145154 and GSE141910 to map the cardiac immunological microenvironment in HF patients. Based on the expression of WRMs, the immunological cells in the datasets were scored. RESULTS: Single-cell transcriptomics analysis (GSE145154) revealed immunological dysregulation in HF as well as differential expression of WRMs in immunological cells from HF and non-HF (NHF) samples. WRM-scored immunological cells were positively correlated with the immunological response, and the high WRM score group exhibited elevated immunological cell infiltration. WRMs are involved in the differentiation of T cells and myeloid cells. WRM scores of T cell and myeloid cell subtypes were significantly reduced in the HF group compared to the NHF group. We identified a myogenesis-related resident macrophage population in the heart, Macro-MYL2, that was characterized by an increased expression of cardiomyocyte structural genes (MYL2, TNNI3, TNNC1, TCAP, and TNNT2) and was regulated by TRMT10C. Based on the WRM expression pattern, the transcriptomics data (GSE141910) identified two distinct clusters of HF samples, each with distinct functional enrichments and immunological characteristics. CONCLUSION: Our study demonstrated a significant relationship between the WRMs and immunological microenvironment in HF, as well as a novel resident macrophage population, Macro-MYL2, characterized by myogenesis. These results provide a novel perspective on the underlying mechanisms and therapeutic targets for HF. Further experiments are required to validate the regulation of WRMs and Macro-MYL2 macrophage subtype in the cardiac immunological milieu.


Subject(s)
Gene Expression Profiling , Heart Failure , Macrophages , Single-Cell Analysis , Transcriptome , Humans , Heart Failure/genetics , Heart Failure/immunology , Heart Failure/metabolism , Macrophages/metabolism , Macrophages/immunology , Databases, Genetic , Cellular Microenvironment , RNA Processing, Post-Transcriptional , Animals , Case-Control Studies , Gene Expression Regulation
8.
Cell Host Microbe ; 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39106871

ABSTRACT

Viral suppressor RNA silencing (VSR) is essential for successful infection. Nucleotide-binding and leucine-rich repeat (NLR)-based and autophagy-mediated immune responses have been reported to target VSR as counter-defense strategies. Here, we report a protein arginine methyltransferase 6 (PRMT6)-mediated defense mechanism targeting VSR. The knockout and overexpression of PRMT6 in tomato plants lead to enhanced and reduced disease symptoms, respectively, during tomato bush stunt virus (TBSV) infection. PRMT6 interacts with and inhibits the VSR function of TBSV P19 by methylating its key arginine residues R43 and R115, thereby reducing its dimerization and small RNA-binding activities. Analysis of the natural tomato population reveals that two major alleles associated with high and low levels of PRMT6 expression are significantly associated with high and low levels of viral resistance, respectively. Our study establishes PRMT6-mediated arginine methylation of VSR as a mechanism of plant immunity against viruses.

9.
Comput Biol Med ; 180: 108876, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39089112

ABSTRACT

Pharmacokinetic/Pharmacodynamic (PK/PD) modeling is crucial in the development of new drugs. However, traditional population-based PK/PD models encounter challenges when modeling for individual patients. We aim to explore the potential of constructing a pharmacodynamic model for individual breast cancer pharmacodynamics leveraging only limited data from early clinical trial phases. While previous studies on Neural Ordinary Differential Equations (ODEs) suggest promising results in clinical trial practices, they primarily focused on theoretical applications or independent PK/PD modeling. PD modeling from complex and irregular clinical trial data, especially when interacting with PK parameters, is still unclear. To achieve that, we introduce a Data-driven Neural Ordinary Differential Equation (DN-ODE) modeling for breast cancer tumor dynamics and progression-free survival data. To validate this approach, experiments are conducted with early-phase clinical trial data from the Amcenestrant (an oral treatment for breast cancer) dataset (AMEERA 1-2), aiming to predict pharmacodynamics in the later phase (AMEERA 3). DN-ODE model achieves RMSE scores of 8.78 and 0.21 in tumor size and progression-free survival, respectively, with R2 scores over 0.9 for each task. Compared to PK/PD methodologies, DN-ODE is able to predict robust individual tumor dynamics with only limited cycle data. We also introduce Principal Component Analysis visualizations for encoder results, demonstrating the DN-ODE's capability to discern individual distributions and diverse tumor growth patterns. Therefore, DN-ODE facilitates comprehensive drug efficacy assessments, pinpoints potential responders, and aids in trial design.

10.
Nat Commun ; 15(1): 6215, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39043664

ABSTRACT

Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Neoplasm Recurrence, Local , Humans , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Male , Female , Neoplasm Recurrence, Local/genetics , Middle Aged , Aged , Prognosis , Genomics/methods , Adult , Neoplasm Staging , Deep Learning , Disease-Free Survival
11.
Front Microbiol ; 15: 1427806, 2024.
Article in English | MEDLINE | ID: mdl-38962116

ABSTRACT

Altitude and ultraviolet (UV) radiation may affect the community composition and distribution of microorganisms in soil ecosystems. In this study, 49 soil samples from 10 locations were collected from different elevations on the eastern Pamir Plateau and analyzed for soil microbial community structure and function using high-throughput sequencing. The results showed that soil samples from different elevations of the eastern Pamir Plateau contained 6834 OTUs in 26 phyla and 399 genera. The dominant phyla common to different elevations were Actinobacteria, Proteobacteria, Bacteroidota, Acidobacteriota, and Gemmatimonadota. The dominant genera were Rubrobacter, Sphingomonas, Nocardioides, and Solirubrobacter. Species richness increased slightly with elevation, and there were significant differences in community composition between the elevations. Elevation and UV exposure are important factors that drive changes in bacterial communities. The results of the KEGG pathway showed that drug resistance, antineoplastic, aging, replication, and repair were enhanced and then slightly decreased with increasing elevation. Bacterial communities at different elevations were rich in radiation-resistant microorganisms, and the main genera were Rubrobacter, Sphingomonas, Nocardioides, Pontibacter, and Streptomyces. The findings have shown the composition and distribution of bacterial communities at different elevations on the Eastern Pamir Plateau. Potentially radiation tolerant microbial species were also examined. The results are of considerable importance for the succession of bacterial microorganisms in the plateau region, the study of radiation tolerant bacterial germplasm resources, and the application of biofunctionality.

12.
Insect Mol Biol ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956869

ABSTRACT

Uridine diphosphate (UDP)-glycosyltransferases (UGTs) are important metabolizing enzymes functioning by adding a sugar moiety to a small lipophilic substrate molecule and play critical roles in drug/toxin metabolism for all realms of life. In this study, the silkworm Bombyx mori UGT33D1 gene was characterized in detail. UGT33D1 was found localized in the endoplasmic reticulum (ER) compartment just like other animal UGTs and was mainly expressed in the silkworm midgut. We first reported that UGT33D1 was important to BmNPV infection, as silencing UGT33D1 inhibited the BmNPV infection in silkworm BmN cells, while overexpressing the gene promoted viral infection. The molecular pathways regulated by UGT33D1 were analysed via transcriptome sequencing upon UGT33D1 knockdown, highlighting the important role of the gene in maintaining a balanced oxidoreductive state of the organism. In addition, proteins that physically interact with UGT33D1 were identified through immunoprecipitation and mass spectrometry analysis, which includes tubulin, elongation factor, certain ribosomal proteins, histone proteins and zinc finger proteins that had been previously reported for human UGT-interacting proteins. This study provided preliminary but important functional information on UGT33D1 and is hoped to trigger deeper investigations into silkworm UGTs and their functional mechanisms.

13.
ACR Open Rheumatol ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38973625

ABSTRACT

OBJECTIVE: Anti-histidyl-transfer RNA synthetase (Jo-1) antibodies are associated with myositis as well as different extramuscular organ complications comprising the anti-synthetase syndrome. This study aimed to clarify the relationship between anti-Jo-1 epitope recognition patterns and specific clinical features of this syndrome. METHODS: B cell epitope mapping was performed via enzyme-linked immunosorbent assay in 180 patients who were anti-Jo-1 antibody-positive using overlapping peptides/protein fragments spanning the amino-terminal 151 amino acids of Jo-1 as substrate antigens. Statistical associations with clinical features were assessed through rank-sum, correlation, and cluster analyses. RESULTS: The level of reactivity against subfragments spanning amino acids 1-151 of Jo-1 paralleled that of full-length Jo-1, confirming the immunodominance of this amino-terminal region. The corresponding frequencies of reactivity to peptides 1 (amino acids [aa] 1-21), 3 (aa 27-47), 4 (aa 40-60), 10 (aa 118-138), and 11 (aa 131-151) were 6.1%, 42.5%, 6.8%, 6.7%, and 20.3%. While anti-full-length Jo-1 antibodies were significantly associated with Raynaud phenomenon, anti-fragment A2 (aa 1-60) and A3 (aa 1-90) antibodies were associated with proximal muscle weakness, Raynaud phenomenon, arthritis, and sicca syndrome. Anti-fragment A4 (aa 1-120) and A5 (aa 1-151) antibodies were also associated with sicca syndrome. Peptide 1 (aa 1-21) antibodies were associated with Raynaud phenomenon and dysphagia. Whereas anti-peptide 3 (aa 27-47) antibodies were also linked to Raynaud phenomenon, anti-peptide 9 (aa 105-125) antibodies were associated with mechanic's hands. CONCLUSION: Autoantibodies targeting different amino-terminal subfragments and/or peptides of Jo-1 were associated with specific clinical features of the anti-synthetase syndrome, demonstrating the biomarker potential of B cell epitope profiling in this disorder.

14.
Commun Biol ; 7(1): 787, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38951550

ABSTRACT

Adipose tissue development begins in the fetal period, and continues to expand after birth. Dysregulation of adipose tissue during weaning may predispose individuals to lifelong metabolic disorders. However, the developmental remodeling of adipose tissue during weaning remains largely unexplored. Here we comprehensively compare the changes in mouse subcutaneous white adipose tissue from 7 days after birth to 7 days after weaning using single-cell RNA sequencing along with other molecular and histologic assays. We characterize the developmental trajectory of preadipocytes and indicate the commitment of preadipocytes with beige potential during weaning. Meanwhile, we find immune cells unique to weaning period, whose expression of extracellular matrix proteins implies potential regulation on preadipocyte. Finally, the strongest cell-cell interaction during weaning determined by the TGFß ligand-receptor pairs is between preadipocytes and endotheliocytes. Our results provide a detailed and unbiased cellular landscape and offer insights into the potential regulation of adipose tissue remodeling during weaning.


Subject(s)
Adipose Tissue, White , Single-Cell Analysis , Subcutaneous Fat , Weaning , Animals , Mice , Adipose Tissue, White/metabolism , Adipose Tissue, White/cytology , Subcutaneous Fat/metabolism , Subcutaneous Fat/cytology , Mice, Inbred C57BL , Adipocytes/metabolism , Adipocytes/cytology , Male , Female
15.
ACS Cent Sci ; 10(6): 1135-1147, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38947200

ABSTRACT

The proximitome is defined as the entire collection of biomolecules spatially in the proximity of a biomolecule of interest. More broadly, the concept of the proximitome can be extended to the totality of cells proximal to a specific cell type. Since the spatial organization of biomolecules and cells is essential for almost all biological processes, proximitomics has recently emerged as an active area of scientific research. One of the growing strategies for proximitomics leverages reactive species-which are generated in situ and spatially confined, to chemically tag and capture proximal biomolecules and cells for systematic analysis. In this Outlook, we summarize different types of reactive species that have been exploited for proximitomics and discuss their pros and cons for specific applications. In addition, we discuss the current challenges and future directions of this exciting field.

16.
Theranostics ; 14(9): 3583-3602, 2024.
Article in English | MEDLINE | ID: mdl-38948067

ABSTRACT

Rationale: Mesenchymal stromal cells (MSCs) are considered a promising resource for cell therapy, exhibiting efficacy in ameliorating diverse bone diseases. However, most MSCs undergo apoptosis shortly after transplantation and produce apoptotic extracellular vesicles (ApoEVs). This study aims to clarify the potential role of ApoEVs from apoptotic MSCs in ameliorating osteoporosis and molecular mechanism. Methods: In this study, Dio-labeled bone marrow mesenchymal stem cells (BMSCs) were injected into mice to track BMSCs apoptosis and ApoEVs production. ApoEVs were isolated from BMSCs after inducing apoptosis, the morphology, size distribution, marker proteins expression of ApoEVs were characterized. Protein mass spectrometry analysis revealed functional differences in proteins between ApoEVs and BMSCs. BMSCs were adopted to test the cellular response to ApoEVs. Ovariectomy mice were used to further compare the ability of ApoEVs in promoting bone formation. SiRNA and lentivirus were used for gain and loss-of-function assay. Results: The results showed that BMSCs underwent apoptosis within 2 days after being injected into mice and produce a substantial quantity of ApoEVs. Proteomic analysis revealed that ApoEVs carried a diverse functional array of proteins, and easily traversed the circulation to reach the bone. After being phagocytized by endogenous BMSCs, ApoEVs efficiently promoted the proliferation, migration, and osteogenic differentiation of BMSCs. In an osteoporosis mouse model, treatment of ApoEVs alleviated bone loss and promoted bone formation. Mechanistically, ApoEVs carried Ras protein and activated the Ras/Raf1/Mek/Erk pathway to promote osteogenesis and bone formation in vitro and in vivo. Conclusion: Given that BMSC-derived ApoEVs are high-yield and easily obtained, our data underscore the substantive role of ApoEVs from dying BMSCs to treat bone loss, presenting broad implications for cell-free therapeutic modalities.


Subject(s)
Apoptosis , Extracellular Vesicles , Mesenchymal Stem Cells , Osteogenesis , Osteoporosis , Animals , Extracellular Vesicles/metabolism , Extracellular Vesicles/transplantation , Mesenchymal Stem Cells/metabolism , Osteoporosis/therapy , Osteoporosis/metabolism , Mice , Female , Osteogenesis/physiology , Cell Differentiation , Mesenchymal Stem Cell Transplantation/methods , Cell Proliferation , Mice, Inbred C57BL , Disease Models, Animal , Ovariectomy , Proteomics , Signal Transduction
17.
mLife ; 3(2): 251-268, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38948143

ABSTRACT

Broad-spectrum antibacterial drugs often lack specificity, leading to indiscriminate bactericidal activity, which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration. In this study, we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure-function relationship through one-factor modification. SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S. aureus. Moreover, SFK2 showed excellent biocompatibility in mice and piglet, and demonstrated significant therapeutic efficacy against S. aureus infection. In conclusion, our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S. aureus, providing a theoretical basis for developing targeted antimicrobial peptides.

18.
World J Oncol ; 15(4): 527-542, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38993251

ABSTRACT

Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype, which is also characterized by the aggressive phenotype, high recurrence rate, and poor prognosis. Antibody-drug conjugate (ADC) is a monoclonal antibody with a cytotoxic payload connected by a linker. ADC is gaining more and more attention as a targeted anti-cancer agent. Clinical studies of emerging ADC drugs such as sacituzumab govitecan and trastuzumab deruxtecan in patients with metastatic breast cancer (including TNBC) are progressing rapidly. In view of its excellent clinical efficacy and good tolerability, Sacituzumab govitecan gained accelerated approval by the FDA for the treatment of advanced metastatic TNBC in 2020. This review discusses the treatment status and challenges in TNBC, with an emphasis on the current status of ADC development and clinical trials in TNBC and metastatic breast cancer. We also summarize the clinical experience and future exploration directions of ADC development for TNBC patients.

20.
Int J Mol Sci ; 25(14)2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39062882

ABSTRACT

SINA (Seven in absentia) E3 ubiquitin ligases are a family of RING (really interesting new gene) E3 ubiquitin ligases, and they play a crucial role in regulating plant growth and development, hormone response, and abiotic and biotic stress. However, there is little research on the SINA gene family in U. rhynchophylla. In this study, a total of 10 UrSINA genes were identified from the U. rhynchophylla genome. The results of multiple sequence alignments and chromosomal locations show that 10 UrSINA genes were unevenly located on 22 chromosomes, and each UrSINA protein contained a SINA domain at the N-terminal and RING domains at the C-terminal. Synteny analysis showed that there are no tandem duplication gene pairs and there are four segmental gene pairs in U. rhynchophylla, contributing to the expansion of the gene family. Furthermore, almost all UrSINA genes contained the same gene structure, with three exons and two introns, and there were many cis-acting elements relating to plant hormones, light responses, and biotic and abiotic stress. The results of qRT-PCR show that most UrSINA genes were expressed in stems, with the least expression in roots; meanwhile, most UrSINA genes and key enzyme genes were responsive to ABA and MeJA hormones with overlapping but different expression patterns. Co-expression analysis showed that UrSINA1 might participate in the TIA pathway under ABA treatment, and UrSINA5 and UrSINA6 might participate in the TIA pathway under MeJA treatment. The mining of UrSINA genes in the U. rhynchophylla provided novel information for understanding the SINA gene and its function in plant secondary metabolites, growth, and development.


Subject(s)
Gene Expression Regulation, Plant , Multigene Family , Phylogeny , Plant Growth Regulators , Ubiquitin-Protein Ligases , Plant Growth Regulators/pharmacology , Plant Growth Regulators/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Genome, Plant , Stress, Physiological/genetics , Gene Expression Profiling , Synteny , Chromosomes, Plant/genetics
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