Genome-wide identification, phylogenetic and expression of MAPKKK gene family in Arabidopsis pumila.

Mitogen-activated protein kinase kinase kinases (MAPKKKs) are important components of the MAPK cascade and play crucial roles in development and stress responses. Arabidopsis pumila is an ephemeral Brassicaceae plant growing in Xinjiang desert regions, which possesses salt tolerance. To explore the evolution and function of the MAPKKK gene family in A. pumila, 143 ApMAPKKK genes were identified from A. pumila genome by genome-wide analysis, which were categorized into three subfamilies: ZIK (20), MEKK (36) and RAF (87). There existed 74 and 72 colinear genes between A. thaliana, A. lyrata and A. pumila, respectively, indicating that this gene family expanded obviously in A. pumila genome. Evolutionary analysis revealed that there were 64 duplicated gene pairs with Ka/Ks less than 1, and purifying selection was dominant. RNA-seq data were used to analyze the expression characteristics of ApMAPKKK genes in response to salt stress and in different tissues. The results showed that most ApMAPKKK genes were up-regulated under 250 mmol/L NaCl stress. For example, ApMAPKKK18-1/2 and ApMAPKKK17-1/2 were substantially up-regulated. Tissue expression profiles showed that ApMAPKKK mainly presented six expression patterns. Some duplicated genes were differentially expressed in response to salt stress and in different tissues. These results lay a foundation for further understanding the complex mechanism of MAPKKK gene family transduction pathway in response to abiotic stresses in A. pumila.

Integrated analysis of DNA methylome and transcriptome reveals epigenetic regulation of CAM photosynthesis in pineapple.

BACKGROUND: Crassulacean acid metabolism (CAM) photosynthesis is an important carbon fixation pathway especially in arid environments because it leads to higher water-use efficiency compared to C3 and C4 plants. However, the role of DNA methylation in regulation CAM photosynthesis is not fully understood. RESULTS: Here, we performed temporal DNA methylome and transcriptome analysis of non-photosynthetic (white base) and photosynthetic (green tip) tissues of pineapple leaf. The DNA methylation patterns and levels in these two tissues were generally similar for the CG and CHG cytosine sequence contexts. However, CHH methylation was reduced in white base leaf tissue compared with green tip tissue across diel time course in both gene and transposon regions. We identified thousands of local differentially methylated regions (DMRs) between green tip and white base at different diel periods. We also showed that thousands of genes that overlapped with DMRs were differentially expressed between white base and green tip leaf tissue across diel time course, including several important CAM pathway-related genes, such as beta-CA, PEPC, PPCK, and MDH. CONCLUSIONS: Together, these detailed DNA methylome and transcriptome maps provide insight into DNA methylation changes and enhance our understanding of the relationships between DNA methylation and CAM photosynthesis.

Comparative Expression Profiling Reveals Genes Involved in Megasporogenesis.

Megasporogenesis is a key step during ovule development in angiosperms, but the small number and inaccessibility of these cells have hampered molecular and genome-wide studies. Thus, many questions remain regarding the molecular basis of cell specification, differentiation, and development in the female gametophyte. Here, taking advantage of the correlation between spikelet length and ovule development in rice (Oryza sativa), we studied the transcriptome dynamics of young ovules at three stages, the archesporial cell, the megaspore mother cell before meiosis, and the functional megaspore after meiosis, using expression profiling based on RNA sequencing. Our analysis showed that 5,274 genes were preferentially expressed in ovules during megasporogenesis as compared to ovules at the mature female gametophyte stage. Out of these, 958 (18.16%) genes were archesporial cell- and/or megaspore mother cell-preferential genes, and represent a significant enrichment of genes involved in hormone signal transduction and plant pathogen interaction pathways, as well as genes encoding transcription factors. The expression patterns of nine genes that were preferentially expressed in ovules of different developmental stages, including the OsERECTA2 (OsER2) receptor-like kinase gene, were confirmed by in situ hybridization. We further characterized the OsER2 loss-of-function mutant, which had an excessive number of female germline cells and an abnormal female gametophyte, suggesting that OsER2 regulates germline cell specification during megasporogenesis in rice. These results expand our understanding of the molecular control of megasporogenesis in rice and contribute to the functional studies of genes involved in megasporogenesis.

Reassessing the impact of tumor size on operative approach in adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is often a contraindication to minimally invasive adrenalectomy (MIA). We used an administrative data set to analyze postoperative outcomes. We hypothesized that small tumors would have better short- and long-term outcomes, independent of the operative approach. METHODS: The National Cancer Database (2010-2016) identified patients with ACC who underwent adrenalectomy. Tumors were grouped: <5 cm (n = 125), 5-10 cm (n = 431), and >10 cm (n = 443). The primary and secondary outcomes were margin positivity and overall survival, respectively. RESULTS: Nine hundred and ninety-nine patients were analyzed: 37% MIA and 63% open adrenalectomy (OA). As the size increased, the rate of attempted MIA decreased. Larger tumors were associated with conversion to open. Although tumors with local invasion and those which required conversion to open were associated with an increased likelihood of a positive margin, tumor size was not. Although "complete" MIA (vs. OA) and tumor size were not associated with differences in survival, conversion (HR = 1.83, p = .02), positive margins (HR = 1.54, p = .01), and local invasion (HR = 1.84, p < .001) were associated with poor survival. CONCLUSION: Positive margins are associated with poor survival in ACC. Tumors ≥ 5 cm were associated with an increased conversion rate and subsequent increase in margin positivity. MIA may be considered for select patients with small tumors but adequate oncologic resection is critical.

Novel brain-targeted nanomicelles for anti-glioma therapy mediated by the ApoE-enriched protein corona in vivo.

BACKGROUND: The interactions between nanoparticles (NPs) and plasma proteins form a protein corona around NPs after entering the biological environment, which provides new biological properties to NPs and mediates their interactions with cells and biological barriers. Given the inevitable interactions, we regard nanoparticle‒protein interactions as a tool for designing protein corona-mediated drug delivery systems. Herein, we demonstrate the successful application of protein corona-mediated brain-targeted nanomicelles in the treatment of glioma, loading them with paclitaxel (PTX), and decorating them with amyloid ß-protein (Aß)-CN peptide (PTX/Aß-CN-PMs). Aß-CN peptide, like the Aß1-42 peptide, specifically binds to the lipid-binding domain of apolipoprotein E (ApoE) in vivo to form the ApoE-enriched protein corona surrounding Aß-CN-PMs (ApoE/PTX/Aß-CN-PMs). The receptor-binding domain of the ApoE then combines with low-density lipoprotein receptor (LDLr) and LDLr-related protein 1 receptor (LRP1r) expressed in the blood-brain barrier and glioma, effectively mediating brain-targeted delivery. METHODS: PTX/Aß-CN-PMs were prepared using a film hydration method with sonication, which was simple and feasible. The specific formation of the ApoE-enriched protein corona around nanoparticles was characterized by Western blotting analysis and LC-MS/MS. The in vitro physicochemical properties and in vivo anti-glioma effects of PTX/Aß-CN-PMs were also well studied. RESULTS: The average size and zeta potential of PTX/Aß-CN-PMs and ApoE/PTX/Aß-CN-PMs were 103.1 nm, 172.3 nm, 7.23 mV, and 0.715 mV, respectively. PTX was efficiently loaded into PTX/Aß-CN-PMs, and the PTX release from rhApoE/PTX/Aß-CN-PMs exhibited a sustained-release pattern in vitro. The formation of the ApoE-enriched protein corona significantly improved the cellular uptake of Aß-CN-PMs on C6 cells and human umbilical vein endothelial cells (HUVECs) and enhanced permeability to the blood-brain tumor barrier in vitro. Meanwhile, PTX/Aß-CN-PMs with ApoE-enriched protein corona had a greater ability to inhibit cell proliferation and induce cell apoptosis than taxol. Importantly, PTX/Aß-CN-PMs exhibited better anti-glioma effects and tissue distribution profile with rapid accumulation in glioma tissues in vivo and prolonged median survival of glioma-bearing mice compared to those associated with PMs without the ApoE protein corona. CONCLUSIONS: The designed PTX/Aß-CN-PMs exhibited significantly enhanced anti-glioma efficacy. Importantly, this study provided a strategy for the rational design of a protein corona-based brain-targeted drug delivery system. More crucially, we utilized the unfavorable side of the protein corona and converted it into an advantage to achieve brain-targeted drug delivery.

KLU suppresses megasporocyte cell fate through SWR1-mediated activation of WRKY28 expression in Arabidopsis.

Germ-line specification is essential for sexual reproduction. In the ovules of most flowering plants, only a single hypodermal cell enlarges and differentiates into a megaspore mother cell (MMC), the founder cell of the female germ-line lineage. The molecular mechanisms restricting MMC specification to a single cell remain elusive. We show that the Arabidopsis transcription factor WRKY28 is exclusively expressed in hypodermal somatic cells surrounding the MMC and is required to repress these cells from acquiring MMC-like cell identity. In this process, the SWR1 chromatin remodeling complex mediates the incorporation of the histone variant H2A.Z at the WRKY28 locus. Moreover, the cytochrome P450 gene KLU, expressed in inner integument primordia, non-cell-autonomously promotes WRKY28 expression through H2A.Z deposition at WRKY28. Taken together, our findings show how somatic cells in ovule primordia cooperatively use chromatin remodeling to restrict germ-line cell specification to a single cell.

Studies on genome size estimation, chromosome number, gametophyte development and plant morphology of salt-tolerant halophyte Suaeda salsa.

BACKGROUND: Soil salinization and alkalization are among the major agricultural threats that affect crop productivity worldwide, which are increasing day by day with an alarming rate. In recent years, several halophytes have been investigated for their utilization in soil remediation and to decipher the mechanism of salt-tolerance in these high salt tolerant genetic repositories. Suaeda salsa is an annual halophytic herb in the family Amaranthaceae, displaying high salt and alkali-resistance and having nutritive value. However, the fundamental biological characteristics of this valuable plant remain to be elucidated until today. RESULTS: In this study, we observed the morphology and development of Suaeda salsa, including seed morphology, seed germination, plant morphology, and flower development. Using microscopy, we observed the male and female gametophyte developments of Suaeda salsa. Also, chromosome behaviour during the meiosis of male gametophyte was studied. Eventually, the genome size of Suaeda salsa was estimated through flow cytometry using Arabidopsis as reference. CONCLUSIONS: Our findings suggest that the male and female gametophyte developments of Suaeda salsa are similar to those of the model plant Arabidopsis, and the diploid Suaeda salsa contains nine pairs of chromosomes. The findings also indicate that the haploid genome of Suaeda salsa is approximately 437.5 MB. The observations and results discussed in this study will provide an insight into future research on Suaeda salsa.

MEMS Gyroscope Automatic Real-Time Mode-Matching Method Based on Phase-Shifted 45° Additional Force Demodulation.

In order to solve the problem where existing mode-matching methods in microelectromechanical systems (MEMS) vibrating gyroscopes fail to meet real-time and reliability requirements, this paper presents a novel method to accomplish automatic and real-time mode-matching based on phase-shifted 45° additional force demodulation (45° AFD-RM). The phase-shifted 45° additional force signal has the same frequency as the quadrature force signal, but it is phase-shifted by 45° and applied to the sense mode. In addition, two-way phase-shifted 45° demodulations are used at the sense-mode detection output to obtain a phase metric that is independent of the Coriolis force and can reflect the mode-matching state. Then, this phase metric is used as a control variable to adaptively control the tuning voltage, so as to change the sense-mode frequency through the negative stiffness effect and ultimately achieve real-time mode-matching. Simulation and experimental results show that the proposed 45° AFD-RM method can achieve real-time matching. The mode frequency split is controlled within 0.1 Hz, and the gyroscope scale factor, zero-bias instability, and angle random walk are effectively improved.

Blood Coagulation Testing Smartphone Platform Using Quartz Crystal Microbalance Dissipation Method.

Blood coagulation function monitoring is important for people who are receiving anticoagulation treatment and a portable device is needed by these patients for blood coagulation self-testing. In this paper, a novel smartphone based blood coagulation test platform was proposed. It was developed based on parylene-C coated quartz crystal microbalance (QCM) dissipation measuring and analysis. The parylene-C coating constructed a robust and adhesive surface for fibrin capturing. The dissipation factor was obtained by measuring the frequency response of the sensor. All measured data were sent to a smartphone via Bluetooth for dissipation calculation and blood coagulation results computation. Two major coagulation indexes, activated partial thromboplastin time (APTT) and prothrombin time (PT) were measured on this platform compared with results by a commercial hemostasis system in a clinical laboratory. The measurement results showed that the adjusted R-square (R²) value for APTT and PT measurements were 0.985 and 0.961 respectively. The QCM dissipation method for blood coagulation measurement was reliable and effective and the platform together with the QCM dissipation method was a promising solution for point of care blood coagulation testing.

ERECTA signaling controls Arabidopsis inflorescence architecture through chromatin-mediated activation of PRE1 expression.

Flowering plants display a remarkable diversity in inflorescence architecture, and pedicel length is one of the key contributors to this diversity. In Arabidopsis thaliana, the receptor-like kinase ERECTA (ER) mediated signaling pathway plays important roles in regulating inflorescence architecture by promoting cell proliferation. However, the regulating mechanism remains elusive in the pedicel. Genetic interactions between ERECTA signaling and the chromatin remodeling complex SWR1 in the control of inflorescence architecture were studied. Comparative transcriptome analysis was applied to identify downstream components. Chromatin immunoprecipitation and nucleosome occupancy was further investigated. The results indicated that the chromatin remodeler SWR1 coordinates with ERECTA signaling in regulating inflorescence architecture by activating the expression of PRE1 family genes and promoting pedicel elongation. It was found that SWR1 is required for the incorporation of the H2A.Z histone variant into nucleosomes of the whole PRE1 gene family and the ERECTA controlled expression of PRE1 gene family through regulating nucleosome dynamics. We propose that utilization of a chromatin remodeling complex to regulate gene expression is a common theme in developmental control across kingdoms. These findings shed light on the mechanisms through which chromatin remodelers orchestrate complex transcriptional regulation of gene expression in coordination with a developmental cue.

OsAUX1 controls lateral root initiation in rice (Oryza sativa†L.).

Polar auxin transport, mediated by influx and efflux transporters, controls many aspects of plant growth and development. The auxin influx carriers in Arabidopsis have been shown to control lateral root development and gravitropism, but little is known about these proteins in rice. This paper reports on the functional characterization of OsAUX1. Three OsAUX1 T-DNA insertion mutants and RNAi knockdown transgenic plants reduced lateral root initiation compared with wild-type (WT) plants. OsAUX1 overexpression plants exhibited increased lateral root initiation and OsAUX1 was highly expressed in lateral roots and lateral root primordia. Similarly, the auxin reporter, DR5-GUS, was expressed at lower levels in osaux1 than in the WT plants, which indicated that the auxin levels in the mutant roots had decreased. Exogenous 1-naphthylacetic acid (NAA) treatment rescued the defective phenotype in osaux1-1 plants, whereas indole-3-acetic acid (IAA) and 2,4-D could not, which suggested that OsAUX1 was a putative auxin influx carrier. The transcript levels of several auxin signalling genes and cell cycle genes significantly declined in osaux1, hinting that the regulatory role of OsAUX1 may be mediated by auxin signalling and cell cycle genes. Overall, our results indicated that OsAUX1 was involved in polar auxin transport and functioned to control auxin-mediated lateral root initiation in rice.

Identification, characterization, and transcription analysis of xylogen-like arabinogalactan proteins in rice (Oryza sativa L.).

BACKGROUND: Xylogen, a chimeric arabinogalactan protein containing a non-specific lipid transfer protein domain, can promote xylem cell differentiation. No comprehensive study has been carried out on the XYLP gene family in rice. As a first step in research on this gene family and as a useful strategy in general, a genome-wide analysis of the OsXYLP gene family is thus needed. RESULTS: In this study, we identified 21 XYLP genes from the rice genome and comprehensively analyzed their protein structures, phylogenetic relationships, chromosomal locations, and gene duplication status. Our results indicate that gene duplication has played major roles in the expansion of the OsXYLP gene family. We used expressed sequence tag, microarray, massively parallel signature sequencing, and quantitative real-time PCR data to analyze OsXYLP gene expression during various developmental stages and under abiotic stress conditions. We found that many OsXYLP genes are abundantly expressed in vascular tissues and seeds, with some genes regulated under hormonal or abiotic stresses. In addition, we identified knockout mutants of OsXYLP7 and OsXYLP16 and discovered that the mutant xylp7 has a defect in stem height. CONCLUSIONS: We analyzed expression profiles of 21 XYLP genes and characterized the structures and evolutionary relationships of their proteins. Our results demonstrate that the rice XYLP gene family may play roles in plant vascular system development and hormone signaling. Among the 21 detected OsXYLPs, 19 are newly identified genes encoding arabinogalactan proteins. Our results provide comprehensive insights that will assist future research on the biological functions of the rice XYLP gene family.

Pediatric thyroid cancer: Socioeconomic disparities and their impact on access to care.

BACKGROUND: Few studies have examined the disparities in access to care for pediatric thyroid cancers. We sought to clarify socioeconomic and patient factors that affect access to care for pediatric differentiated thyroid cancer and aggressive variants of papillary thyroid cancer. METHODS: Using the National Cancer Database, we performed a retrospective study on pediatric differentiated thyroid cancer and aggressive variants of papillary thyroid cancer (2004-2019). Patients were divided into three periods (2004-2008, 2009-2013, 2014-2019) to assess for trends. The χ2 analysis and Kruskal-Wallis test were used to test for independence of groupings for each socioeconomic and disease-related factor. RESULTS: In all, 6,275 patients with pediatric differentiated thyroid cancer and 182 with aggressive variants of papillary thyroid cancer were analyzed. Differentiated thyroid cancer patients with Medicaid (median 18.0 miles) and those from lower-income households (median 21-30 miles) had to travel greater distances for care in recent years (2014-2019). Racial/ethnic disparities were evident; Black and Hispanic patients have higher odds of waiting >30 days for surgery (odds ratio 1.39, 1.49, P < .05, respectively) than White patients. Black patients with differentiated thyroid cancer had a higher risk of mortality compared with White and Hispanic patients (hazard ratio 4.31, 95% confidence interval: 1.95-9.51, P < .05). Nodal positivity was higher in Hispanic patients with differentiated thyroid cancer (60%, P < .05, White patients 51% and Black patients 36%). Socioeconomic factors did not significantly affect survival or nodal positivity in aggressive variants of papillary thyroid cancer. CONCLUSION: This study highlights disparities in access to care and survival outcomes in pediatric differentiated thyroid cancer and aggressive variants of papillary thyroid cancer. Race, income status, and type of insurance all play a role in these disparities. Understanding the complex etiologies and developing interventions to improve access and patient outcomes are crucial.

Boosting the Electrochemical Storage Properties of Co3O4 Nanowires by the Mn Doping Strategy with Appropriate Mn Doping Concentrations.

High specific capacitance, high energy density, and high power density have always been important directions for the improvement of electrode materials for supercapacitors. In this paper, Co3O4 nanowire arrays with various Mn doping concentrations (Mn:Co molar ratio = 1:11, 1:5, 1:2) directly grown on nickel foam (NF) were prepared by a simple hydrothermal method and annealing process. The influence of Mn doping on the morphology, structure, and electrochemical behaviors of Co3O4 was investigated. The results show that partial substitution of Co ions with Mn ions in the spinel structure does not change the nanowire morphology of pure Co3O4 but increases the lattice parameter and decreases the crystallinity of cobalt oxide. Electrochemical measurements showed that Mn doping in Co3O4 could effectively enhance the redox activity, especially Co3O4 with a Mn doping ratio of 1:5, which exhibits the most excellent electrochemical performance, with the maximum specific capacitance of 1210.8 F·g-1 at 1 A·g-1 and a rate capability of 33.0% at 30 A·g-1. The asymmetric supercapacitor (ASC) device assembled with the optimal Mn-Co3O4 (1:5) and activated carbon (AC) electrode performs a high specific capacitance of 105.8 F·g-1, a high energy density of 33 Wh·kg-1 at a power density of 748.1 W·kg-1, and a capacitance retention of 60.2% after 5000 cycles. This work indicates that an appropriate Mn doping concentration in the Co3O4 lattice structure will have great potential in rationalizing the design of spinel oxides for efficient electrochemical performance.

The ldp1 Mutation Affects the Expression of Auxin-Related Genes and Enhances SAM Size in Rice.

Panicle type is one of the important factors affecting rice (Oryza sativa L.) yield, and the identification of regulatory genes in panicle development can provide significant insights into the molecular network involved. This study identified a large and dense panicle 1 (ldp1) mutant produced from the Wuyunjing 7 (WYJ7) genotype, which displayed significant relative increases in panicle length, number of primary and secondary branches, number of grains per panicle, grain width, and grain yield per plant. Scanning electron microscopy results showed that the shoot apical meristem (SAM) of ldp1 was relatively larger at the bract stage (BM), with a significantly increased number of primary (PBM) and secondary branch (SBM) meristematic centers, indicating that the ldp1 mutation affects early stages in SAM development Comparative RNA-Seq analysis of meristem tissues from WYJ7 and ldp1 at the BM, PBM, and SBM developmental stages indicated that the number of differentially expressed genes (DEGs) were highest (1407) during the BM stage. Weighted gene coexpression network analysis (WGCNA) revealed that genes in one module (turquoise) are associated with the ldp1 phenotype and highly expressed during the BM stage, suggesting their roles in the identity transition and branch differentiation stages of rice inflorescences. Hub genes involved in auxin synthesis and transport pathways, such as OsAUX1, OsAUX4, and OsSAUR25, were identified. Moreover, GO and KEGG analysis of the DEGs in the turquoise module and the 1407 DEGs in the BM stage revealed that a majority of genes involved in tryptophan metabolism and auxin signaling pathway were differentially expressed between WYJ and ldp1. The genetic analysis indicated that the ldp1 phenotype is controlled by a recessive monogene (LDP1), which was mapped to a region between 16.9 and 18.1 Mb on chromosome seven. This study suggests that the ldp1 mutation may affect the expression of key genes in auxin synthesis and signal transduction, enhance the size of SAM, and thus affect panicle development. This study provides insights into the molecular regulatory network underlying rice panicle morphogenesis and lays an important foundation for further understanding the function and molecular mechanism of LDP1 during panicle development.

Expression profiling of ALOG family genes during inflorescence development and abiotic stress responses in rice (Oryza sativa L.).

The ALOG (Arabidopsis LSH1 and Oryza G1) family proteins, namely, DUF640 domain-containing proteins, have been reported to function as transcription factors in various plants. However, the understanding of the response and function of ALOG family genes during reproductive development and under abiotic stress is still largely limited. In this study, we comprehensively analyzed the structural characteristics of ALOG family proteins and their expression profiles during inflorescence development and under abiotic stress in rice. The results showed that OsG1/OsG1L1/2/3/4/5/6/7/8/9 all had four conserved helical structures and an inserted Zinc-Ribbon (ZnR), the other four proteins OsG1L10/11/12/13 lacked complete Helix-1 and Helix-2. In the ALOG gene promoters, there were abundant cis-acting elements, including ABA, MeJA, and drought-responsive elements. Most ALOG genes show a decrease in expression levels within 24 h under ABA and drought treatments, while OsG1L2 expression levels show an upregulated trend under ABA and drought treatments. The expression analysis at different stages of inflorescence development indicated that OsG1L1/2/3/8/11 were mainly expressed in the P1 stage; in the P4 stage, OsG1/OsG1L4/5/9/12 had a higher expression level. These results lay a good foundation for further studying the expression of rice ALOG family genes under abiotic stresses, and provide important experimental support for their functional research.

Corrigendum: Expression profiling of ALOG family genes during inflorescence development and abiotic stress responses in rice (Oryza sativa L.).

[This corrects the article DOI: 10.3389/fgene.2024.1381690.].

Varying impact of patient age on the rising rate of pediatric thyroid cancer: Analysis of NCDB database (2004-2017).

Pediatric thyroid carcinoma is on the rise. We sought to better characterize patient factors associated with this and evaluate for trends based on age groups. Additionally, we examined surgical management over time, and whether it aligns with recommendations made by the American Thyroid Association. Using the National Cancer Database (NCDB), we examined cases of thyroid cancer from 2004 to 2017, ages 1-18 years. We subdivided this cohort by age group: those <10y, 10-15y, and >15y. NCDB query yielded 5,814 cases. The annual proportion of total cases ranged from 3% to 8% for <10y, 31%-40% for 10-15y, and 52%-66% for >15y. 80-90% of cases in all age groups did indeed receive total thyroidectomy which is consistent with ATA guidelines. Our results verify an overall increase in pediatric thyroid cancer cases, occurring mostly in the 10-18 years old age range with the largest year-to-year increases in the >15y group.

Development of Novel Paclitaxel-Loaded ZIF-8 Metal-Organic Framework Nanoparticles Modified with Peptide Dimers and an Evaluation of Its Inhibitory Effect against Prostate Cancer Cells.

Prostate cancer (PC) is one of the common malignant tumors of the male genitourinary system. Here, we constructed PTX@ZIF-8, which is a metal-organic-framework-encapsulated drug delivery nanoparticle with paclitaxel (PTX) as a model drug, and further modified the synthesized peptide dimer (Di-PEG2000-COOH) onto the surface of PTX@ZIF-8 to prepare a nanotargeted drug delivery system (Di-PEG@PTX@ZIF-8) for the treatment of prostate cancer. This study investigated the morphology, particle size distribution, zeta potential, drug loading, encapsulation rate, stability, in vitro release behavior, and cytotoxicity of this targeted drug delivery system, and explored the uptake of Di-PEG@PTX@ZIF-8 by human prostate cancer Lncap cells at the in vitro cellular level, as well as the proliferation inhibition and promotion of apoptosis of Lncap cells by the composite nanoparticles. The results suggest that Di-PEG@PTX@ZIF-8, as a zeolitic imidazolate frameworks-8-loaded paclitaxel nanoparticle, has promising potential for the treatment of prostate cancer, which may provide a novel strategy for the delivery system targeting prostate cancer.

Research advances in peptide‒drug conjugates.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, linkers and drugs used to construct PDCs, and summarize the clinical applications and challenges of PDC drugs.