NSUN2/YBX1 promotes the progression of breast cancer by enhancing HGH1 mRNA stability through m5C methylation.

BACKGROUND: RNA m5C methylation has been extensively implicated in the occurrence and development of tumors. As the main methyltransferase, NSUN2 plays a crucial regulatory role across diverse tumor types. However, the precise impact of NSUN2-mediated m5C modification on breast cancer (BC) remains unclear. Our study aims to elucidate the molecular mechanism underlying how NSUN2 regulates the target gene HGH1 (also known as FAM203) through m5C modification, thereby promoting BC progression. Additionally, this study targets at preliminarily clarifying the biological roles of NSUN2 and HGH1 in BC. METHODS: Tumor and adjacent tissues from 5 BC patients were collected, and the m5C modification target HGH1 in BC was screened through RNA sequencing (RNA-seq) and single-base resolution m5C methylation sequencing (RNA-BisSeq). Methylation RNA immunoprecipitation-qPCR (MeRIP-qPCR) and RNA-binding protein immunoprecipitation-qPCR (RIP-qPCR) confirmed that the methylation molecules NSUN2 and YBX1 specifically recognized and bound to HGH1 through m5C modification. In addition, proteomics, co-immunoprecipitation (co-IP), and Ribosome sequencing (Ribo-Seq) were used to explore the biological role of HGH1 in BC. RESULTS: As the main m5C methylation molecule, NSUN2 is abnormally overexpressed in BC and increases the overall level of RNA m5C. Knocking down NSUN2 can inhibit BC progression in vitro or in vivo. Combined RNA-seq and RNA-BisSeq analysis identified HGH1 as a potential target of abnormal m5C modifications. We clarified the mechanism by which NSUN2 regulates HGH1 expression through m5C modification, a process that involves interactions with the YBX1 protein, which collectively impacts mRNA stability and protein synthesis. Furthermore, this study is the first to reveal the binding interaction between HGH1 and the translation elongation factor EEF2, providing a comprehensive understanding of its ability to regulate transcript translation efficiency and protein synthesis in BC cells. CONCLUSIONS: This study preliminarily clarifies the regulatory role of the NSUN2-YBX1-m5C-HGH1 axis from post-transcriptional modification to protein translation, revealing the key role of abnormal RNA m5C modification in BC and suggesting that HGH1 may be a new epigenetic biomarker and potential therapeutic target for BC.

Development of a Novel 99mTc-Labeled Folate Derivative Containing Phenyl Isonitrile to Target Folate Receptor with Reduced Renal Uptake.

The folate receptor has attracted much attention in the field of radiolabeled imaging agents due to the significant difference in its expression levels between tumor cells and most normal cells. However, the development of folate-based imaging agents has been limited by their high uptake in the kidney. In this study, to reduce the high renal uptake of radiolabeled folate-based tracers, a phenyl-isonitrile folate derivative (CNMBFA) was designed and labeled with technetium-99m. The complex obtained via the one-step kit labeling method had a high labeling yield (>95%) and high in vitro stability and hydrophilicity (log D7.4 = -1.72 ± 0.13). The results of the in vitro cell uptake and blocking studies and competitive binding experiments revealed that the [[99mTc]Tc-(CNMBFA)6]+ complex was specific for the folate receptor. Biodistribution and inhibition studies in KB tumor-bearing mice revealed moderate uptake and significant inhibition of the complex in tumors, whereas the renal uptake of [[99mTc]Tc-(CNMBFA)6]+ was significantly lower than that of previously reported tracers. Micro-SPECT/CT images further supported its ability to target the folate receptor for tumor imaging. Taken together, these results indicate that [[99mTc]Tc-(CNMBFA)6]+ is a potential tumor imaging agent that has good tumor-targeting properties with minimal radiation damage to the kidney.

The coevolution of bullying and friendship networks.

The coevolution of bullying and friendship networks and the moderating effects of classroom bullying popularity norms were examined in a sample of 965 students (52.1% boys) in 22 fourth- and fifth-grade classes. Longitudinal social network analysis showed that children were more likely to bully their friends' victims (bully influence effect) and to be bullied by their friends' bullies (victim influence effect); two children bullying the same child were likely to be friends (bully selection effect), and two victims bullied by the same child were likely to be friends (victim selection effect). Bullying popularity norms served as moderators, and the bully selection effect was significant weaker in the context of low bullying popularity norms. This study adds understanding of bullying as a group process and provides implications for preventing school bullying.

Synthesis and Evaluation of [18F]SiFA-Conjugated Ligands for Fibroblast Activation Protein Imaging.

In recent years, fibroblast activation protein (FAP) has emerged as an important target for the diagnosis and therapy of various tumors due to its high expression on the cell surface of cancer-associated fibroblasts, which are the major components of the tumor stroma. In this study, we synthesized and evaluated 18F-labeled FAP inhibitors (FAPIs) for FAP imaging. Two silicon fluoride acceptor (SiFA)-conjugated FAPIs were synthesized: one containing a γ-carboxy-l-glutamic acid (Gla) residue (1) and another containing two Gla residues (2). Both ligands exhibited high binding affinities for FAP. 18F/19F exchange reactions on both ligands were performed in the presence of 2% water. This resulted in the formation of radioligands [18F]1 and [18F]2 in high radiochemical yields. Radioligand [18F]2, with a more favorable partition coefficient, was selected for the U87MG cell binding study, and the results showed FAP-specific binding of the radioligand to the cells. An ex vivo biodistribution study in U87MG tumor-bearing mice 60 min after injection demonstrated a 5.8-fold higher tumor accumulation of [18F]2 than that of [18F]1. Furthermore, PET and ex vivo biodistribution studies of [18F]2 in U87MG tumor-bearing mice showed high and persistent tumor uptake over time, which was significantly blocked by the preinjection of FAPI-04. Our results indicate that [18F]SiFA-(Gla)2-conjugated FAPI ([18F]2) has the potential for FAP imaging.

Serum perfluoroalkyl substances and growth and development in US adolescents: a nationally representative cross-sectional study.

Per- and polyfluoroalkyl substances (PFAS), synthetic organic chemicals, have been discovered in the blood of both humans and animals throughout the world. This has raised widespread concerns about its toxicity, especially for growing children and adolescents. Most research on growth and development to date has concentrated on children at birth and during the first two years, while few studies have analyzed weight, height, and Body Mass Index (BMI) changes in children later in life. The present study aims to assess the association between serum PFAS levels and growth and development in adolescents. Through multiple linear regression, we explored the relationship between serum PFAS levels and weight, height, and BMI in adolescents (aged 12 to 19 years) participating in the 2015-2018 National Health and Nutrition Examination Survey (NHANES). After covariate adjustment, serum perfluorooctane sulfonic acid (PFOS) was associated with decreased weight-for-age z-score in females (tertile 2 of PFOS: ß = - 0.22, 95% CI: -0.68, 0.23; tertile 3 of PFOS: ß = - 0.78, 95% CI: -1.20, - 0.36; P for trend = 0.009), while serum perfluorononanoic acid (PFNA) was associated with decreased weight-for-age z-score in males (tertile 2 of PFNA: ß = 0.09, 95% CI: -0.40, 0.58; tertile 3 of PFNA: ß = - 0.44, 95% CI: -0.86, - 0.03; P for trend = 0.018).In addition, serum PFOS was associated with decreased BMI z-score in all participants (tertile 2 of PFOS: ß = - 0.15, 95% CI: -0.46, 0.16; tertile 3 of PFOS: ß = - 0.63, 95% CI: -1.06, - 0.20; P for trend = 0.013). CONCLUSION: Our findings indicate a negative association between serum PFAS levels and weight, and BMI among adolescents, and we observed that the negative association was sex-specific in weight. WHAT IS KNOWN: • Wide exposure to PFAS has led to concerns about its adverse effects, especially for children during their growth and development. • So far, much research has evaluated the effects of prenatal PFAS exposures on children, and the current results are mixed, with some research showing that there are sex differences. WHAT IS NEW: • This study investigated the relationship between serum PFAS levels and height and weight in adolescents and is a good addition to current research. • Our study found that exposure to PFAS negatively affects adolescent growth and development and that this effect is sex-specific.

The influence of social status on children's merit-based resource allocation: The potential explanation of expectation.

How 3- to 11-year-old children integrate recipients' merit and social status when allocating resources was examined in 2021 and 2022. Study 1 (Han Chinese, n = 309, 150 girls) showed that while children prioritized merit, they developed from favoring high-status recipients to favoring low-status recipients. Study 2 (n = 194, 98 girls) and Study 3 (n = 138, 68 girls) revealed that children held stereotypes about the relation between merit and social status which shifted with age from expecting high-status peers to expecting low-status peers to work harder, these expectations corresponded allocation decisions. These findings suggest children shift from perpetuating to rectifying inequity and changing stereotypes about people of different social status may serve an important function in the process.

Preparation and Bioevaluation of 99mTc-Labeled FAP Inhibitors as Tumor Radiotracers to Target the Fibroblast Activation Protein.

Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts (CAFs) in a majority of human epithelial cancers. With low expression in normal organs, FAP has become a promising molecular target for tumor theranostics. To develop a lower cost and more widely available alternative to positron emission tomography (PET), two isocyanide-containing FAP inhibitors (CN-C5-FAPI and CN-PEG4-FAPI) were synthesized and radiolabeled with 99mTc to obtain [99mTc][Tc-(CN-C5-FAPI)6]+ and [99mTc][Tc-(CN-PEG4-FAPI)6]+ in high yields (>95%). They showed good stability in saline and mouse serum. The partition coefficient (log P) values of [99mTc][Tc-(CN-C5-FAPI)6]+ and [99mTc][Tc-(CN-PEG4-FAPI)6]+ were -0.86 ± 0.03 and -2.38 ± 0.07, respectively, indicating that they were good hydrophilic complexes. The low nanomolar IC50 values of CN-C5-FAPI and CN-PEG4-FAPI indicated that they had specificity to FAP. In vitro cellular uptake and blocking experiments implied a FAP-targeted uptake mechanism. The nanomolar Kd values from the saturation binding assay indicated that they had significantly high target affinity to FAP. The biodistribution and blocking study in BALB/c nude mice bearing U87MG tumors showed that both exhibited specific tumor uptake. [99mTc][Tc-(CN-PEG4-FAPI)6]+ showed a higher tumor uptake and a higher tumor/nontarget ratio than [99mTc][Tc-(CN-C5-FAPI)6]+. The results of micro-single-photon emission computed tomography (SPECT) imaging studies of [99mTc][Tc-(CN-C5-FAPI)6]+ and [99mTc][Tc-(CN-PEG4-FAPI)6]+ were in accordance with the biodistribution results, suggesting that [99mTc][Tc-(CN-PEG4-FAPI)6]+ is a promising tumor imaging agent for targeting FAP.

99mTc-CN7DG: A Highly Expected SPECT Imaging Agent of Cancer with Satisfactory Tumor Uptake and Tumor-to-Nontarget Ratios.

A novel glucose derivative (CN7DG) possessing an isonitrile as a coordinating group was synthesized, and 99mTc-CN7DG, which was expected to be a powerful tumor imaging agent for SPECT, was prepared in a kit by the reaction of CN7DG with SnCl2·2H2O and 99mTcO4-. 99mTc-CN7DG exhibited good stability and was transported via glucose transporters. Biodistribution results in mice bearing A549 tumor models showed that 99mTc-CN7DG had a higher uptake at the tumor sites and better tumor/blood and tumor/muscle ratios than did [18F]FDG and 99mTc-CN5DG. SPECT/CT imaging studies showed obvious accumulation in tumor sites, suggesting that 99mTc-CN7DG is a promising candidate for tumor imaging. Because 99mTc and 188Re stand for a "theranostic pair", 188Re-CN7DG is expected to be prepared as a promising agent for tumor therapy.

RETRACTED: Loss of microRNA-30e induced by extracellular vesicles from cancer-associated fibroblasts promotes breast cancer progression by binding to CTHRC1.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the authors as "some data in this study are not solid enough and need to be further explored". The authors stated that they "found abnormalities in the re-identification of CAF-EVs, the extracted extracellular vesicles may be polluted and the elliptical structure under electron microscope is not owned by CAF-EVs. The identification of CAF-EVs by Western Blots did not refer to the definition of international society." The authors informed the journal that, after the re-experiment, they found that "there is no vesicle specific protein expression, whether the results of subsequent experiments are generated by CAF-EVs needs to be re-tested".

Radiolabeling and evaluation of a novel [99mTcN]2+ complex with deferoxamine dithiocarbamate as a potential agent for bacterial infection imaging.

In order to find a 99mTc-labeled deferoxamine radiotracer for bacterial infection imaging, deferoxamine dithiocarbamate (DFODTC) was successfully synthesized and it was radiolabeled with [99mTcN]2+ core to prepare the 99mTcN(DFODTC)2 complex. 99mTcN(DFODTC)2 was obtained with high radiochemical purity without further purification. The complex was lipophilic and exhibited good in vitro stability. According to the result of bacterial binding study, the binding of 99mTcN(DFODTC)2 to bacteria was specific. Biodistribution in mice study indicated that 99mTcN(DFODTC)2 had a higher uptake in bacterial infection tissues than in turpentine-induced abscesses at 120 min after injection, which showed that the radiotracer could differentiate between bacterial infection and sterile inflammation. SPECT/CT images showed that there was a clear accumulation in infection sites, suggesting that 99mTcN(DFODTC)2 could be a potential bacterial infection imaging radiotracer.

Material and relational asymmetry: The role of receivers' wealth and power status in children's resource allocation.

Asymmetries in social status, specifically social status related to wealth and relational power, appear to influence the ways in which children allocate resources. However, the impact of wealth and relational power status on children's resource allocation decisions has yet to be examined among children developing within a Chinese cultural context. In addition, how children weight the relative importance of these factors when they exist concurrently is not well understood. In Study 1, we examined the impact of recipients' wealth and relational power status on Chinese children's (3- to 8-year-olds; N = 199) allocation decisions. We found that across both categories of social status, 3- and 4-year-olds gave more to high-status individuals, whereas 7- and 8-year-olds gave more to low-status individuals, despite younger children also showing a strong egalitarian preference when the resources could be allocated equally. In Study 2, we investigated how children (3- to 8-year-olds; N = 219) weigh the relative importance of these two types of social status in situations where the level of recipients' wealth and relational power were either consistent or in conflict. When they needed to allocate the resources unequally, the youngest children were found to place greater emphasis on wealth over relational power and favored the high-status individual, whereas older children tended to favor the low-status individual and placed greater importance on relational power over wealth. Overall, we found a consistent age-related shift from favoring high-status individuals toward compensating low-status individuals, suggesting a developing concern for social equity.

Preparation and Evaluation of Novel Folate Isonitrile 99mTc Complexes as Potential Tumor Imaging Agents to Target Folate Receptors.

In order to seek novel technetium-99m folate receptor-targeting agents, two folate derivatives (CN5FA and CNPFA) were synthesized and radiolabeled to obtain [99mTc]Tc-CN5FA and [99mTc]Tc-CNPFA complexes, which exhibited high radiochemical purity (>95%) without purification, hydrophilicity, and good stability in vitro. The KB cell competitive binding experiments indicated that [99mTc]Tc-CN5FA and [99mTc]Tc-CNPFA had specificity to folate receptor. Biodistribution studies in KB tumor-bearing mice illustrated that [99mTc]Tc-CN5FA and [99mTc]Tc-CNPFA had specific tumor uptake. Compared with [99mTc]Tc-CN5FA, the tumor/muscle ratios of [99mTc]Tc-CNPFA were higher, resulting in a better SPECT/CT imaging background. According to the results, the two 99mTc complexes have potential as tumor imaging agents to target folate receptors.

Synthesis and evaluation of [99mTcN]2+ core and [99mTcO]3+ core labeled complexes with 4-nitroimidazole xanthate derivative for tumor hypoxia imaging.

A 4-nitroimidazole xanthate ligand (NMXT) was synthesized and radiolabeled with [99mTcN]2+ core and [99mTcO]3+ core to obtain 99mTcN-NMXT and 99mTcO-NMXT, respectively. The two 99mTc-complexes were prepared with high radiochemical purity and had good stability. The partition coefficient results indicated both of them were hydrophilic, and cellular uptake studies showed they exhibited good hypoxic selectivity. From the biodistribution study results, 99mTcO-NMXT showed more favourable tumor uptake (1.73 ± 0.14 ID%/g) and higher tumor/muscle ratio (7.01 ± 0.16) than 99mTcN-NMXT at 4 h post-injection. Single photon emission computed tomography (SPECT) imaging study of 99mTcO-NMXT showed there was a visible accumulation in tumor site, suggesting it would be a promising candidate as a tumor hypoxia imaging agent.

Preparation and Biological Evaluation of [99mTc]Tc-CNGU as a PSMA-Targeted Radiotracer for the Imaging of Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is a well-established biological target that is overexpressed on the surface of prostate cancer lesions. Radionuclide-labeled small-molecule PSMA inhibitors have been shown to be promising PSMA-specific agents for the diagnosis and therapy of prostate cancer. In this study, a glutamate-urea-based PSMA-targeted ligand containing an isonitrile (CNGU) was synthesized and labeled with 99mTc to prepare [99mTc]Tc-CNGU with a high radiochemical purity (RCP). The CNGU ligand showed a high affinity toward PSMA (Ki value is 8.79 nM) in LNCaP cells. The [99mTc]Tc-CNGU exhibited a good stability in vitro and hydrophilicity (log P = -1.97 ± 0.03). In biodistribution studies, BALB/c nude mice bearing LNCaP xenografts showed that the complex had a high tumor uptake with 4.86 ± 1.19% ID/g, which decreased to 1.74 ± 0.90% ID/g after a pre-injection of the selective PSMA inhibitor ZJ-43, suggesting that it was a PSMA-specific agent. Micro-SPECT imaging demonstrated that the [99mTc]Tc-CNGU had a tumor uptake and that the uptake was reduced in the image after blocking with ZJ-43, further confirming its PSMA specificity. All of the results in this work indicated that [99mTc]Tc-CNGU is a promising PSMA-specific tracer for the imaging of prostate cancer.

Synthesis and Biological Evaluation of Novel 99mTc-Labeled Palbociclib Derivatives Targeting Cyclin-Dependent Kinase 4/6 (CDK4/6) as Potential Cancer Imaging Agents.

Cancer results from cell proliferation that exceeds normal growth control. There are various specific proteins that control and regulate the cell cycle, such as cyclin-dependent kinases (CDKs), cyclins, and retinoblastoma protein (pRb). The aberration of the cyclin D-CDK4/6-INK4-pRb pathway occurs frequently in cancers; thus, CDK4/6 is an attractive target for the development of radiopharmaceuticals for tumor imaging. In this study, we chose palbociclib, which was approved by the FDA for treating ER+/HER2- advanced breast cancer as the target vector and the isonitrile group, which can coordinate strongly with the [99mTc(CO)3]+ core as the bifunctional chelator, to develop four novel 99mTc-labeled radiotracers for tumor imaging. The ligands (L2, L3, L4, and L5) were synthesized by reacting palbociclib with isocyanide-containing active esters and then radiolabeling with a [99mTc(CO)3]+ core to produce radiotracers (99mTc-L2, 99mTc-L3, 99mTc-L4, and 99mTc-L5) with high radiochemical purity (>95%) and good stability in vitro. The structures of the 99mTc complexes were identified by preparation and characterization of the corresponding stable rhenium complexes. Partition coefficient results indicated that these complexes were lipophilic. A kinase inhibition assay demonstrated the high affinity of the stable Re complexes for CDK4. A cell study showed that all four complexes had substantial uptake by MCF-7 cells and could be significantly inhibited by palbociclib and nonradiolabeled ligand, indicating a CDK4/6-specific uptake mechanism. Biodistribution studies in nude mice bearing MCF-7 tumors showed that the complexes had obvious accumulation in tumors at 2 h postinjection. 99mTc-L2 exhibited the highest tumor uptake and tumor/blood ratio, whereas 99mTc-L4 showed the highest tumor/muscle ratio. The micro-SPECT/CT study showed that complex 99mTc-L4 had visible uptake at the tumor site, and the accumulation was clearly reduced in the image after pretreatment with palbociclib, further indicating CDK4/6 specificity. All the results showed that the 99mTc-labeled complexes in this work have the potential for tumor imaging.

Novel 99mTc-Labeled Glucose Derivative for Single Photon Emission Computed Tomography: A Promising Tumor Imaging Agent.

In this study, a d-glucosamine derivative with an isonitrile group (CN5DG) was synthesized and it was chosen to coordinate with 99mTc for preparing 99mTc-CN5DG. 99mTc-CN5DG could be readily obtained with high radiochemical purity (>95%) and had great in vitro stability and metabolic stability in urine. The radiotracer demonstrated a positive response to the administration of glucose and insulin in S180 and A549 tumor cells in vitro, suggesting the mechanism of 99mTc-CN5DG into tumor cells was related to glucose transporters. Biodistribution studies in mice bearing A549 xenografts showed 99mTc-CN5DG had a high tumor uptake and high tumor-to-background ratios. SPECT/CT images further supported its ability for tumor imaging. As a cheap, conveniently made and widely available probe, 99mTc-CN5DG would become a potential "working horse" and be a breakthrough in 99mTc-labeled radiopharmaceuticals for tumor detection.

Allele-specific methylation contributed by CpG-SNP is associated with regulation of ALOX5AP gene expression in ischemic stroke.

Previous studies have shown that CpG-SNPs might have influence on gene function via allele-specific DNA methylation (ASM). However, association study between DNA methylation and the promoter CpG-SNPs in ALOX5AP gene with IS has not been reported. The present study aims to explore the relationship among CpG-SNPs, methylation levels, and messenger RNA (mRNA) expression levels of ALOX5AP gene. Firstly, we made a two-stage association study to identify a potential associated CpG-SNP (rs4073259) by SNaPshot genotyping approach (P = 0.015, OR = 0.672, 95% CI 0.487-0.927; P = 0.035, OR = 0.809, 95% CI 0.664-0.985, respectively). In addition, the methylation levels of 17 CpG sites located in the promoter of ALOX5AP were tested by MethylTarget sequencing. The methylation level of GG genotype carriers is significantly higher than those with the AG and AA genotypes (P < 0.05). And the GG genotype carriers with higher DNA methylation levels have a decreased mRNA expression levels of ALOX5AP (P < 0.05). Finally, we found that the G allele with higher methylation level has got a lower transcription activity than the A allele by luciferase assay (P = 0.000).The study provided evidence that IS-associated CpG-SNP rs4073259 may affect the expression level of ALOX5AP through allele-specific methylation and consequently the phenotype of the disease.

Development of a novel 99m Tc-labeled small molecular antagonist for CXCR4 positive tumor imaging.

The chemokine receptor 4 (CXCR4) has been an attractive molecular target for tumor imaging, because it is overexpressed in many tumor types and involved in tumor progression and metastasis. The purpose of this study is to examine the CXCR4 targeting properties of 99m Tc-labeled AMD3465, a small molecule antagonist of CXCR4. 99m Tc-AMD3465 was prepared in high yield (>95%) and stable in mice serum at least for 4 hours. In vitro cell binding experiments were performed with Chinese hamster ovary (CHO), MCF-7 (breast cancer), and CHO-CXCR4 (CHO stably transfected to express CXCR4) cell lines. Small animal single photon emission computed tomography/computed tomography imaging studies in nude mice bearing MCF-7 and CHO xenografts showed that the uptakes of the radiotracer in MCF-7 tumors were significantly higher than those in the CXCR4-negative CHO tumors (P < 0.05), and the MCF-7 tumors uptake could be blocked with an excess of unlabeled AMD3465 (P < 0.05). These results suggested that 99m Tc-AMD3465 could be a potential single photon emission computed tomography radiotracer for CXCR4 imaging.

Ab Initio Studies on the Clathrate Hydrates of Some Nitrogen- and Sulfur-Containing Gases.

Ab initio calculations are performed to investigate the host-guest interactions and multiple occupancies of some sulfur- (H2S, CS2) and nitrogen-containing (N2, NO, and NH3) molecules in dodecahedral, tetrakaidecahedral, and hexakaidecahedral water cages in this work. Five functionals in the framework of density functional theory are compared, and the M06-2X method appears to be the best to predict the binding energies as well as the geometries. Results show that N2 and NO molecules are more stable in the 51264 cage, while NH3 and H2S prefer to stabilize in the 51262 cage. This suggests that the sI hydrates of NH3 and H2S exhibit higher stability than the sII structures and that sII NO hydrate is more stable than sI NO hydrate. N2 is found to be more stable in type II structure with single occupancy and to form type I hydrate with multiple occupancy, which is consistent with the experimental observations. As to the guest molecule CS2, it may undergo severe structural deformation in the 512 and 51262 cage. For multiple occupancies, the 512, 51262, and 51264 water cages can trap up to two N2 molecules, and the 51264 water cage can accommodate two H2S molecules. This work is expected to provide new insight into the formation mechanism of clathrate hydrates for atmospherically important molecules.

Synthesis and biological evaluation of (68) Ga-labeled Pteroyl-Lys conjugates for folate receptor-targeted tumor imaging.

In order to develop novel (68) Ga-labeled PET tracers for folate receptor imaging, two DOTA-conjugated Pteroyl-Lys derivatives, Pteroyl-Lys-DOTA and Pteroyl-Lys-DAV-DOTA, were designed, synthesized and radiolabeled with (68) Ga. Biological evaluations of the two radiotracers were performed with FR-positive KB cell line and athymic nude mice bearing KB tumors. Both (68) Ga-DOTA-Lys-Pteroyl and (68) Ga-DOTA-DAV-Lys-Pteroyl exhibited receptor specific binding in KB cells in vitro. The tumor uptake values of (68) Ga-DOTA-Lys-Pteroyl and (68) Ga-DOTA-DAV-Lys-Pteroy were 10.06 ± 0.59%ID/g and 11.05 ± 0.60%ID/g at 2 h post-injection, respectively. Flank KB tumor was clearly visualized with (68) Ga-DOTA-DAV-Lys-Pteroyl by Micro-PET imaging at 2 h post-injection, suggesting the feasibility of using (68) Ga-labeled Pteroyl-Lys conjugates as a novel class of FR targeted probes.