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BACKGROUND: The widespread use of quercetin is limited by its instability, low solubility and poor oral bioavailability. Encapsulation of quercetin using a nanoparticle delivery system is an effective way to overcome these drawbacks. RESULTS: The effect of the molecular weight (Mw) of chitosan (CS) (100, 200, 500 and 1000 kDa) on quercetin-loaded chitosan nanoparticles (QCNPs) was investigated. The structure, stability, release properties and antioxidant activities of the nanoparticles (QCNP-10, QCNP-20, QCNP-50 and QCNP-100) were assessed. Particle size of QCNPs decreased and polydispersity index increased with the increasing Mw of CS. The main forces involved in the formation of QCNPs were hydrogen bonding and hydrophobic interaction. X-ray diffraction verified that quercetin was loaded into CS nanoparticles. The photostability and thermal stability of QCNPs increased with increasing Mw of CS. QCNP-100 exhibited the lowest release rate in a mixture of water and anhydrous ethanol. The antioxidant activities of QCNPs were enhanced with increasing Mw of CS, and QCNP-100 possessed the highest antioxidant activities, which might be relevant to its smallest particle size. CONCLUSION: Overall, these results revealed that the Mw of CS affected the properties of QCNPs, and QCNP-100 possessed the smallest particle, best stability, lowest release rate and highest antioxidant activities. © 2024 Society of Chemical Industry.
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BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) typically present with a complex anatomical distribution, often accompanied by insidious symptoms. This combination contributes to its high incidence and poor prognosis. It is now understood that the immune features of cellular components within the tumor ecosystem and their complex interactions are critical factors influencing both tumor progression and the effective immune response. METHODS: We obtained single-cell RNA sequencing data of 26,496 cells from three tumor tissues and five normal tissues and performed subsequent analyses. Immunohistochemical staining on tumor sections was used to validate the presence of malignant cells. Additionally, we included bulk RNA sequencing data from 502 HNSCC patients. Kaplan-Meier analysis and the log-rank test were employed to assess predictors of patient outcomes. RESULTS: We identified three epithelial subclusters exhibiting immune-related features. These subclusters promoted the infiltration of T cells, dendritic cells, and monocytes into the tumor microenvironment. Additionally, cancer-associated fibroblasts displayed tumor-promoting and angiogenesis characteristics, contrasting with the predominant antigen-presenting and inflammatory roles observed in fibroblasts from normal tissues. Furthermore, tumor endothelial subsets exhibited a double-sided effect, promoting tumor progression and enhancing the effectiveness of immune response. Finally, follicular helper T cells and T helper 17 cells were found to be significantly correlated with improved outcomes in HNSCC patients. These CD4+ T cell subpopulations could promote the anti-tumor immune response by recruiting and activating B and T cells. CONCLUSION: Our findings provide deeper insights into the immune features of the tumor ecosystem and reveal the prognostic significance of follicular helper T cells and T helper 17 cells. These findings may pave the way for the development of therapeutic approaches.
Subject(s)
Head and Neck Neoplasms , Lymphocytes, Tumor-Infiltrating , Single-Cell Gene Expression Analysis , Squamous Cell Carcinoma of Head and Neck , Th17 Cells , Tumor Microenvironment , Female , Humans , Male , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Lymphocytes, Tumor-Infiltrating/immunology , Prognosis , RNA-Seq/methods , Single-Cell Gene Expression Analysis/methods , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , T Follicular Helper Cells/immunology , Th17 Cells/immunology , Tumor Microenvironment/immunologyABSTRACT
BACKGROUND: Antarctic krill peptide (AKP) has gained considerable interest because of its multiple biological functions. However, its application may be limited by its poor stability and susceptibility to degradation. Encapsulation of AKP using a nanoparticle delivery system is an effective way to overcome these problems. In the present study, bovine serum albumin (BSA) and chitosan (CS) were used as delivery vehicles to encapsulate AKP. RESULTS: The results revealed that the particle size (83.3 ± 4.4-222.4 ± 32.7 nm) and zeta-potential (35.1 ± 0.7-45.0 ± 2.7 mV) of nanoparticles (NPs) increased with the increasing content of BSA, but the polydispersity index decreased (1.000 ± 0.002 to 0.306 ± 0.011). Hydrogen bonding, hydrophobic and electrostatic interactions were the main forces to form BSA/CS-AKP NPs. X-ray diffraction revealed that AKP was encapsulated by BSA/CS. Scanning electron microscopy images exhibited that the NPs were spherical in shape, uniform in size and tightly bound. BSA/CS-AKP NPs exhibited excellent stability in the pH range (2-5) and after 15 days of storage, and could hinder the release of AKP in simulated gastric environment and promote the release of AKP in simulated intestinal environment. After simulated digestion, the hypoglycemic activity of encapsulated AKP was better than that of unencapsulated AKP. CONCLUSION: Our results revealed that the BSA/CS showed great potential for protecting and delivering AKP. © 2024 Society of Chemical Industry.
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Phytohormones play a role in regulating microalgae cells tolerance to adversity. This paper examines the effects of different temperatures (20 °C, 25 °C, 30 °C and 35 °C) on the physiological characteristics and endogenous phytohormones of the Isochrysis Zhanjiangensis (IZ) and its mutagenic strain (3005). The results showed that the endogenous phytohormones indole acetic acid (IAA) and jasmonic acid (JA) exhibited significant differences (P<0.05) between the two strains. The addition of 0.5 mg·L-1 exogenous JA inhibitor ibuprofen (IBU) improved cell growth of IZ, and was extremely effective in the accumulation of polysaccharides, which accounted for 33.25 %. Transcriptomic analyses revealed that genes involved in photosynthesis, such as PetC and PsbO, exhibited significantly elevated expression of the strain IZ, while the pathways related to JA synthesis may be the factor affecting microalgae temperature tolerance. This study provides a theoretical foundation for elucidating the underlying mechanisms and potential applications for high temperature tolerance in IZ.
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Native core microbiomes represent a unique opportunity to support food provision and plant-based industries. Yet, these microbiomes are often neglected when developing synthetic communities (SynComs) to support plant health and growth. Here, we study the contribution of native core, native non-core and non-native microorganisms to support plant production. We construct four alternative SynComs based on the excellent growth promoting ability of individual stain and paired non-antagonistic action. One of microbiome based SynCom (SC2) shows a high niche breadth and low average variation degree in-vitro interaction. The promoting-growth effect of SC2 can be transferred to non-sterile environment, attributing to the colonization of native core microorganisms and the improvement of rhizosphere promoting-growth function including nitrogen fixation, IAA production, and dissolved phosphorus. Further, microbial fertilizer based on SC2 and composite carrier (rapeseed cake fertilizer + rice husk carbon) increase the net biomass of plant by 129%. Our results highlight the fundamental importance of native core microorganisms to boost plant production.
Subject(s)
Fertilizers , Microbiota , Plant Development , Rhizosphere , Soil Microbiology , Biomass , Soil/chemistry , Nitrogen Fixation , Phosphorus/metabolism , Plant Roots/microbiology , Plant Roots/growth & development , Indoleacetic Acids/metabolismABSTRACT
Crop pedigrees incorporate information on the kinship and genetic evolutionary history of breeding materials. Complete and accurate pedigree information is vital for effective genetic improvement of crops and maximal exploitation of heterosis in crop production. It is difficult for breeders to accurately extrapolate the selection of germplasm resources with missing genealogical information based on breeding experience. In this study, an algorithm called PidTools was developed, consisting of five sets of algorithms from three core modules, for accurate pedigree identification analysis. The algorithms and associated tools are suitable for all crops, for the reconstruction and visualization of a complete pedigree for breeding materials. The algorithm and tools were validated with the model crop maize. A genotype database was constructed using Maize6H-60K array data from 5791 maize inbred lines. The pedigree of the maize inbred line Jing72464 was identified without prior provision of any parental information. The pedigree information for Zheng58 was fully identified at the genome-wide scale. With regard to group identification, the parents of a doubled-haploid group were identified based on the genotyping data. The pedigree of 21 Dan340 derived lines were visualized using PidTools. The algorithms are incorporated into a user-friendly online analytical platform, PidTools-WS, with an associated customizable toolkit program, PidTools-CLI. These analytical tools and the present results provide useful information for future maize breeding. The PidTools online analysis platform is available at https://PidTools.plantdna.site/.
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Receptor-binding peptides are promising candidates for tumor target therapy. However, the inability to occupy "hot spots" on the PPI interface and rapid metabolic instability are significant limitations to their clinical application. We investigated a new strategy in which an FGFR1-binding peptide (Pep1) was site-specifically functionalized with the dinitrophenyl (DNP) hapten at the C-terminus. The resulting Pep1-DNP conjugates retained FGFR1 binding affinity and exhibited a similar potency in inhibiting FGF2-dependent cell proliferation, comparable to that of native Pep1 in vitro. In addition, three conjugates could recruit anti-DNP antibodies onto the surface of cancer cells, thereby mediating the CDC efficacy. In vivo pharmacokinetic studies and antitumor studies demonstrated that optimal conjugate 9 exhibited significantly prolonged half-lives and improved antitumor efficacy without prominent toxicity compared to those of native Pep1. This is a general and cost-effective approach for generating peptidomimetic immunotherapeutics with multiple antitumor mechanisms that may have broad applications in cancer therapy.
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Continuous recombination and variation during replication could lead to rapid evolution and genetic diversity of HIV-1. Some studies had identified that it was easy to develop new recombinant strains of HIV-1 among the populations of men who have sex with men (MSM). Surveillance of genetic variants of HIV-1 in key populations was crucial for comprehending the development of regional HIV-1 epidemics. The finding was reported the identification of two new unique recombinant forms (URF 20110561 and 21110743) from individuals infected with HIV-1 in Tongzhou, Beijing in 2020-2022. Sequences of near full-length genome (NFLG) were amplified, then identification of amplification products used phylogenetic analyses. The result showed that CRF01_AE was the main backbone of 20110561 and 21110743. In the gag region of the virus, 20110561 was inserted two fragments from CRF07_BC, while in the pol and tat regions of the virus, 21110743 was inserted four fragments from CRF07_BC. The CRF01_AE parental origin in the genomes of the two URFs was derived from the CRF01_AE Cluster 4. In the phylogenetic tree, the CRF07_BC parental origin of 20110561 clustered with 07BC_N and the CRF07_BC parental origin of 21110743 clustered with 07BC_O. In summary, the prevalence of novel second-generation URFs of HIV-1 was monitored in Tongzhou, Beijing. The emergence of the novel CRF01_AE/CRF07_BC recombination demonstrated that there was a great significance of continuous monitoring of new URFs in MSM populations to prevent and control the spreading of new HIV-1 URFs.
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Background: Conditional survival analysis can serve as a dynamic prognostic metric, which helps to estimate the real-time survival probability over time. The present study conducted a conditional recurrence-free survival (CRFS) analysis for locally advanced intrahepatic cholangiocarcinoma (ICC) after R0 hepatectomy from an inflammatory-nutritional perspective using the competing risk method. Methods: We extracted the medical data of 164 locally advanced ICC patients after R0 resection from Sun Yat-sen University Cancer Center. The calculation formula of the CRFS rate is CRFS(y/x) = RFS(y + x)/RFS(x). Univariable and multivariable COX regression analysis and competing risk analysis were conducted to identify RFS indicators. Results: Considering death before recurrence as a competing risk factor, the conditional RFS rates every 6 months gradually increased over time. The 24-month RFS rate increased from 29.2 % to 49.9 %, 68.5 %, and 85.1 % given 6, 12, and 18-month already recurrence-free survival, respectively. Both in multivariate COX regression analysis and competing risk analysis, tumor diameter and number, lymph node metastasis, aggregate systemic inflammation index score (AISI), and albumin-bilirubin score (ALBI) all remained significant. For both AISI and ALBI variables, the CRFS rates in the low-value set were higher than those of the high-value set. Conclusions: Conditional RFS rates of locally advanced ICC after R0 hepatectomy dynamically increased over time, which contributed to reducing survivors' psychological distress and facilitating personalized follow-up schedules. In addition, a person's inflammatory and nutritional status significantly impact the recurrence risk. Oncologists should consider the role of inflammation-nutritional status when making decisions for patients with locally advanced ICC.
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Background: Physical activity has been shown to have an effect on Carotid plaque (CP) which is a predictor of Cardiovascular disease (CVD). Studies have shown that physical activity can alter the composition of gut microbiota, whether its influence on CP was mediated by gut microbiota has yet to be proved. Methods: We conducted a case-control study involving 30 CP patients and 31 controls. Logistic regression was used to analyze the association between CP and physical activity. LefSe was used to explore the association between gut microbiota and physical activity as well as CP, and PhyloMed was used to examine the mediating effect of gut microbiota in the association between physical activity and CP. Results: After adjusting for potential confounders, adequate physical activity showed a significant association with a decreased risk of CP (ORadj: 0.25, 95%CI: 0.06, 0.97). CP was associated with enrichment in the order Bacteroidales within the phylum Bacteroidetes and the predominant microbiota in individuals without plaque was the order Clostridiales (LDA scores >3). Individuals with adequate physical activity had a higher abundance of the order Clostridiales, while the order Bacteroidetes was enriched in individuals with inadequate physical activity (LDA scores >3). The PhyloMed revealed a significant mediation effect of gut microbiota in the association between physical activity and CP (p = 0.03). Conclusion: Adequate physical activity was significantly associated with a decreased risk of CP, and this association was mediated by an increase in the abundance of gut microbiota in the order Clostridiales.
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The effect of rehmannioside A (ReA) on systemic lupus erythematosus (SLE) is not clear and needs further study. In this study, SLE-related targets were obtained from the DisGeNet and GeneCards databases, while ReA-related targets were obtained from the SwissTarget and SuperPred databases. A protein-protein interaction network of intersected targets was constructed using the STRING platform. After selecting the intersected targets, GO and KEGG enrichment analyses were performed via the R package "clusterProfiler". The relationships between ReA and various core targets were assessed via molecular docking, and molecular dynamics simulation was conducted for optimal core protein-compound complexes obtained by molecular docking. The top five targets in the ranking of degree value were HSP90AA1, HIF1A, PIK3CA, MTOR, and TLR4. Significant biological processes mainly included response to oxidative stress and response to reactive oxygen species. The potential pathways of ReA in the treatment of SLE mainly focused on the PI3K-Akt signaling pathway, neutrophil extracellular trap formation, and Apoptosis. Molecular docking showed that ReA had the highest binding affinity for mTOR, suggesting that mTOR is a key target of ReA against SLE. Molecular dynamics simulations revealed good binding abilities between ReA and mTOR. In conclusion, ReA exerts its effects on SLE through multiple targets and pathways, with mTOR being a key target of ReA against SLE.
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In the post-harvest phase, fruit is inexorably subjected to extrinsic stressors that expedite energy expenditure and truncate the storage lifespan. The present study endeavors to elucidate the response strategies of litchi to the alterations of energy state caused by 2,4-Dinitrophenol (DNP) treatment through energy metabolism and sugar metabolism. It was observed that the DNP treatment reduced the energy state of the fruit, exacerbated membrane damage and triggered rapid browning in the pericarp after 24 h of storage. Furthermore, the expression of genes germane to energy metabolism (LcAtpB, LcAOX1, LcUCP1, LcAAC1, and, LcSnRK2) reached their peak within the initial 24 h of storage, accompanied by an elevation in the respiratory rate, which effectively suppressed the rise in browning index of litchi pericarp. The study also posits that, to cope with the decrease of energy levels and membrane damage, litchi may augment the concentrations of fructose, glucose, inositol, galactose, and sorbose, thus safeguarding the canonical metabolic functions of the fruit. Collectively, these findings suggest that litchi can modulate energy and sugar metabolism to cope with fruit senescence under conditions of energy deficiency. This study significantly advances the understanding of the physiological responses exhibited by litchi fruit to post-harvest external stressors.
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Tissue-resident memory T cells (TRMs) play a critical role in cancer immunity by offering quick and effective immune responses. However, the cellular heterogeneity of TRMs and their significance in cervical cancer (CC) remain unknown. In this study, we generated and analyzed single-cell RNA sequencing data from 12,945 TRMs (ITGAE+ CD3D+) and 25,627 non-TRMs (ITGAE- CD3D+), derived from 11 CC tissues and 5 normal cervical tissues. We found that TRMs were more immunoreactive than non-TRMs, and TRMs in CC tissues were more activated than those in normal cervical tissues. Six CD8+ TRM subclusters and one CD4+ TRM subcluster were identified. Among them, CXCL13+ CD8+ TRMs were more abundant in CC tissues than in normal cervical tissues, had both cytotoxic and inhibitory features, and were enriched in pathways related to defense responses to the virus. Meanwhile, PLAC8+ CD8+ TRMs were less abundant in CC tissues than in normal cervical tissues but had highly cytotoxic features. The signature gene set scores of both cell subclusters were positively correlated with the overall survival and progression-free survival of patients with CC following radiotherapy. Of note, the association between HLA-E and NKG2A, either alone or in a complex with CD94, was enriched in CXCL13+ CD8+ TRMs interacting with epithelial cells at CC tissues. The in-depth characterization of TRMs heterogeneity in the microenvironment of CC could have important implications for advancing treatment and improving the prognosis of patients with CC.
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Selenium (Se) is an essential trace element for humans. Low concentrations of Se can promote plant growth and development. Enhancing grain yield and crop Se content is significant, as major food crops generally have low Se content. Studies have shown that Se biofortification can significantly increase Se content in plant tissues. In this study, the genetic transformation of wheat was conducted to evaluate the agronomic traits of non-transgenic control and transgenic wheat before and after Se application. Se content, speciation, and transfer coefficients in wheat grains were detected. Molecular docking simulations and transcriptome data were utilized to explore the effects of selenium-binding protein-A TaSBP-A on wheat growth and grain Se accumulation and transport. The results showed that TaSBP-A gene overexpression significantly increased plant height (by 18.50%), number of spikelets (by 11.74%), and number of grains in a spike (by 35.66%) in wheat. Under normal growth conditions, Se content in transgenic wheat grains did not change significantly, but after applying sodium selenite, Se content in transgenic wheat grains significantly increased. Analysis of Se speciation revealed that organic forms of selenomethionine (SeMet) and selenocysteine (SeCys) predominated in both W48 and transgenic wheat grains. Moreover, TaSBP-A significantly increased the transfer coefficients of Se from solution to roots and from flag leaves to grains. Additionally, it was found that with the increase in TaSBP-A gene overexpression levels in transgenic wheat, the transfer coefficient of Se from flag leaves to grains also increased.
Subject(s)
Gene Expression Regulation, Plant , Plant Proteins , Plants, Genetically Modified , Selenium-Binding Proteins , Selenium , Sodium Selenite , Triticum , Triticum/genetics , Triticum/metabolism , Triticum/growth & development , Selenium-Binding Proteins/metabolism , Selenium-Binding Proteins/genetics , Selenium/metabolism , Plants, Genetically Modified/growth & development , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Sodium Selenite/metabolism , Edible Grain/metabolism , Edible Grain/genetics , Edible Grain/growth & development , Molecular Docking Simulation , Seeds/growth & development , Seeds/metabolism , Seeds/genetics , Seeds/drug effectsABSTRACT
Elymus species, belonging to Triticeae tribe, is a tertiary gene pool for improvement of major cereal crops. Elymus sibiricus, a tetraploid with StH genome, is a typical species in the genus Elymus, which is widely utilized as a high-quality perennial forage grass in template regions. In this study, we report the construction of a chromosome-scale reference assembly of E. sibiricus line Gaomu No. 1 based on PacBio HiFi reads and chromosome conformation capture. Subgenome St and H were well phased by assisting with kmer and subgenome-specific repetitive sequence. The total assembly size was 6.929 Gb with a contig N50 of 49.518 Mb. In total, 89,800 protein-coding genes were predicted. The repetitive sequences accounted for 82.49% of the genome in E. sibiricus. Comparative genome analysis confirmed a major species-specific 4H/6H reciprocal translocation in E. sibiricus. The E. sibiricus assembly will be much helpful to exploit genetic resource of StH species in genus Elymus, and provides an important tool for E. sibiricus domestication.
Subject(s)
Chromosomes, Plant , Elymus , Genome, Plant , Elymus/genetics , Chromosomes, Plant/genetics , Edible Grain/genetics , Repetitive Sequences, Nucleic AcidABSTRACT
Pulmonary hypertension (PH) is a malignant pulmonary vascular disease with a poor prognosis. Although the development of targeted drugs for this disease has made some breakthroughs in recent decades, PH remains incurable. Therefore, innovative clinical treatment methods and drugs for PH are still urgently needed. DYZY01 is a new drug whose main ingredient is high-purity cannabidiol, a non-psychoactive constituent of cannabinoids that was demonstrated to have anti-inflammatory and anti-pyroptosis properties. Several recent studies have found cannabidiol could improve experimental PH, whereas the mechanistic effect of it warrants further investigation. Thus, this study aimed to investigate whether DYZY01 can treat PH by inhibiting inflammation and pyroptosis and to reveal its underlying mechanism. We established hypoxia and monocrotaline (MCT)-induced PH rat models in vivo and treated them with either DYZY01 (10,50 mg/kg/d) or Riociguat (10 mg/kg/d) by oral administration. The mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVHI), and extent of vascular remodeling were measured. Meanwhile, the effect of DYZY01 on human pulmonary arterial endothelial cells (HPAECs) was assessed in vitro. The results indicated that DYZY01 significantly reduced mPAP and RVHI in PH rats and reversed the extent of pulmonary vascular remodeling. This improvement may have been achieved by reducing endothelial cell pyroptosis via inhibiting the NF-κB/NLRP3/Caspase-1 pathway. Furthermore, DYZY01 could improve endothelial vascular function, possibly by regulating the secretion of vasodilator factors and inhibiting the proliferation and migration of pulmonary endothelial cells.
Subject(s)
Endothelial Cells , Hypertension, Pulmonary , Pyroptosis , Rats, Sprague-Dawley , Animals , Pyroptosis/drug effects , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/pathology , Rats , Male , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Humans , NF-kappa B/metabolism , Vascular Remodeling/drug effects , Cannabidiol/pharmacology , Cannabidiol/therapeutic use , Disease Models, Animal , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Pulmonary Artery/drug effects , Pulmonary Artery/pathology , Signal Transduction/drug effectsABSTRACT
This study describes the design and synthesis of five TF-based cancer vaccine candidates using a lipid A mimetic as the carrier and a built-in adjuvant. All synthesized conjugates elicited robust and consistent TF-specific immune responses in mice without external adjuvants. Immunological studies subsequently conducted in wild-type and TLR4 knockout C57BL/6 mice demonstrated that the activation of TLR4 was the main reason that the synthesized lipid A mimetics increased the TF-specific immune responses. All antisera induced by these conjugates can specifically recognize, bind to, and induce the lysis of TF-positive cancer cells. Moreover, representative conjugates 2 and 3 could effectively reduce the growth of tumors and prolong the survival time of mice in vivo, and the efficacies were better than glycoprotein TF-CRM197 with alum adjuvant. Lipid A mimetics could therefore be a promising platform for the development of new carbohydrate-based vaccine carriers with self-adjuvanting properties for the treatment of cancer.
Subject(s)
Adjuvants, Immunologic , Cancer Vaccines , Drug Design , Lipid A , Mice, Inbred C57BL , Animals , Lipid A/analogs & derivatives , Lipid A/chemistry , Lipid A/pharmacology , Cancer Vaccines/immunology , Cancer Vaccines/pharmacology , Cancer Vaccines/chemical synthesis , Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/chemical synthesis , Adjuvants, Immunologic/chemistry , Mice , Mice, Knockout , Humans , Female , Toll-Like Receptor 4/metabolism , Cell Line, TumorABSTRACT
Insertion sequences (ISs) exist widely in bacterial genomes, but their roles in the evolution of bacterial antiphage defense remain to be clarified. Here, we report that, under the pressure of phage infection, the IS1096 transposition of Mycobacterium smegmatis into the lsr2 gene can occur at high frequencies, which endows the mutant mycobacterium with a broad-spectrum antiphage ability. Lsr2 functions as a negative regulator and directly silences expression of a gene island composed of 11 lipid metabolism-related genes. The complete or partial loss of the gene island leads to a significant decrease of bacteriophage adsorption to the mycobacterium, thus defending against phage infection. Strikingly, a phage that has evolved mutations in two tail-filament genes can re-escape from the lsr2 inactivation-triggered host defense. This study uncovered a new signaling pathway for activating antimycobacteriophage immunity by IS transposition and provided insight into the natural evolution of bacterial antiphage defense.
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PURPOSE: To investigate the feasibility, safety and efficacy of high intensity focused ultrasound ablation (HIFU) as a preoperative treatment for challenging hysteroscopic myomectomies. MATERIALS AND METHODS: A total of 75 patients diagnosed with types 0-III of uterine fibroids were enrolled. Based on the Size, Topography, Extension of the base, Penetration and lateral Wall position (STEPW) classification scoring system, 25 cases with a score ≥ 5 points were treated with HIFU followed by hysteroscopic myomectomy (HIFU + HM group), whereas 50 cases with a score < 5 points were treated with hysteroscopic myomectomy (HM group). RESULTS: The median preoperative STEPW score was 7 in the HIFU + HM group and 2 in the HM group. The average non-perfused volume (NPV) ratio achieved in fibroids after HIFU was 86.87%. Patients in the HIFU + HM group underwent hysteroscopic myomectomy one to four days after HIFU, and downgrading was observed in 81.81% of fibroids. The operation time for patients in the HIFU + HM group was 73 min and the success rate of myomectomy in a single attempt was 60%. The volume of distention medium used during the operation was greater in the HIFU + HM group than in the HM group (15,500 ml vs. 7500 ml). No significant difference was observed between the two groups in terms of intraoperative blood loss, the incidence of intraoperative and postoperative complications, menstrual volume score, or uterine fibroid quality of life score. CONCLUSION: HIFU can be utilized as a preoperative treatment for large submucosal fibroids prior to hysteroscopic myomectomy. HIFU offers a novel approach in the management of this subset of patients.
Subject(s)
High-Intensity Focused Ultrasound Ablation , Hysteroscopy , Leiomyoma , Uterine Myomectomy , Humans , Female , High-Intensity Focused Ultrasound Ablation/methods , Adult , Uterine Myomectomy/methods , Hysteroscopy/methods , Middle Aged , Leiomyoma/surgery , Leiomyoma/therapy , Feasibility Studies , Treatment Outcome , Uterine Neoplasms/surgeryABSTRACT
BACKGROUND: In China, economic, urbanization, and policy differences between the eastern and western regions lead to uneven healthcare resources. This disparity is more pronounced in the west due to fewer healthcare personnel per thousand individuals and imbalanced doctor-to-nurse ratios, which exacerbates healthcare challenges. This study examines the spatial distribution of human resources in maternal and child healthcare from 2016 to 2021, highlighting regional disparities and offering insights for future policy development. METHODS: The data were sourced from the "China Health and Family Planning Statistical Yearbook" (2017) and the "China Health and Health Statistics Yearbook" (2018-2022). This study utilized GeoDa 1.8.6 software to conduct both global and local spatial autocorrelation analyses, using China's administrative map as the base dataset. RESULTS: From 2016 to 2021, there was an upward trend in the number of health personnel and various types of health technical personnel in Chinese maternal and child healthcare institutions. The spatial distribution of these personnel from 2016 to 2021 revealed clusters characterized as high-high, low-low, high-low and low-high. Specifically, high-high clusters were identified in Guangxi, Hunan, Jiangxi, and Guangdong provinces; low-low in Xinjiang Uygur Autonomous Region and Inner Mongolia Autonomous Region; high-low in Sichuan province; and low-high in Fujian and Anhui provinces. CONCLUSIONS: From 2016 to 2021, there was evident spatial clustering of health personnel and various health technical personnel in Chinese maternal and child healthcare institutions, indicating regional imbalances.