Prediction of EGFR mutation status in lung adenocarcinoma based on 18F-FDG PET/CT radiomic features.

The earlier identification of EGFR mutation status in lung adenocarcinoma patients is crucial for treatment decision-making. Radiomics, which involves high-throughput extraction of imaging features from medical images for quantitative analysis, can quantify tumor heterogeneity and assess tumor biology non-invasively. This field has gained attention from researchers in recent years. The aim of this study is to establish a model based on 18F-FDG PET/CT radiomic features to predict the epidermal growth factor receptor (EGFR) mutation status of lung adenocarcinoma and evaluate its performance. 155 patients with lung adenocarcinoma who underwent 18F-FDG PET/CT scans and EGFR gene detection before treatment were retrospectively analyzed. The LIFEx packages was used to perform 3D volume of interest (VOI) segmentation manually on DICOM images and extract 128 radiomic features. The Wilcoxon rank sum test and least absolute shrinkage and selection operator (LASSO) regression algorithm were applied to filter the radiomic features and establish models. The performance of the models was evaluated by the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Among the models we have built, the radiomic model based on 18F-FDG PET/CT has the best prediction performance for EGFR gene mutation status, with an AUC of 0.90 (95% CI 0.84~0.96) in the training set and 0.79 (95% CI 0.64~0.94) in the test set. In conclusion, we have established a radiomics model based on 18F-FDG PET/CT, which has good predictive performance in identifying EGFR gene mutation status in lung adenocarcinoma patients.

Mussel-inspired antibacterial polydopamine/chitosan/temperature-responsive hydrogels for rapid hemostasis.

The aim of this study was to develop an effective wound dressing using a temperature-responsive hydroxybutyl chitosan (HBC) based hydrogel. The HBC - chitosan (CS) - dopamine (HCS-DOPA) composite hydrogels were prepared by the dopamine self-polymerization at different concentrations (0, 0.5, 1.0 and 2.0 mg/mL), termed as HCS, HCS-DOPA-0.5, HCS-DOPA-1 and HCS-DOPA-2, respectively. The gelling characteristic of HBC hydrogel was not influenced by composite CS and DOPA. The HCS-DOPA composite hydrogels were non-cytotoxic to mouse fibroblast cells (L929), and induced under 5.0% hemolysis rate. In vitro antibacterial studies, composite HCS-DOPA-2 hydrogels exhibited lasting inhibition to S. aureus >8 h. The whole blood test in vitro demonstrated that blood clotting time treated with HCS-DOPA-2 composite hydrogels was shortened to 95.6 s compared with that of HCS in vitro hemostasis. The results suggested that HCS-DOPA-2 composite hydrogels could be applied as a promising wound dressing for hemostasis in vitro.

The temperature-responsive hydroxybutyl chitosan hydrogels with polydopamine coating for cell sheet transplantation.

The aim of this study was to develop an effective cell sheet translocation method using a cell adhesive and temperature-responsive hydroxybutyl chitosan hydrogel (HBC). The polydopamine (PD)-coated HBC hydrogels were prepared by the dopamine self-polymerization on the surface of HBC hydrogel with different coating time, termed as P30, P60 and P120, respectively. Gelling property of HBC was not affected by PD coating. The PD-coated HBC hydrogels promoted the attachment and proliferation of mouse fibroblast cells (L929) and human umbilical vein endothelial cells (HUVECs), and allowed formation of monolayer cell sheet. In vitro translocation of HUVECs sheet could be obtained successively through phase transition of PD coated HBC hydrogel from gel to sol, and the cells sheet transferred from P30 hydrogel to a round cell coverglass maintained relatively complete monolayer and normal cell morphology. The results showed that P30 hydrogel has the potential to be used for cell transplantation therapy.

Diagnosis performance of 99mTc-MIBI and multimodality imaging for hyperparathyroidism.

This study aimed to examine the diagnosis performance of 99mTc-methoxyisobutylisonitrisonitrile (99mTc-MIBI) and multimodality imaging [ultrasound, single-photon emission computed tomography/computed tomography (SPECT/CT)] for hyperparathyroidism (HPT). From Nov. 2009 to Dec. 2015, clinical data of a total of 43 HPT patients (16 males and 27 females; 26-70 years old, average age: 51.60±10.66 years old) were retrospectively analyzed. Among them, 19 patients with primary hyperparathyroidism (PHPT) underwent 99mTc-MIBI planar imaging, 24 [15 with PHPT and 9 with secondary hyperparathyroidism (SHPT)] underwent SPECT/CT hybrid imaging, and 41 (33 with PHPT and 8 with SHPT) had neck ultrasound imaging. Final diagnosis was determined by pathological examination after surgery. The positive rate was compared between different imaging modalities, and the correlation analysis was conducted between imaging results and lesion size or serum parathyroid hormone (PTH) level. The results showed that the total positive rates of 99mTc-MIBI imaging, ultrasound, and the two combined imaging in the 43 HPT cases were 90.70% (39/43), 58.54% (24/41), and 100% (41/41), respectively. According to lesion numbers, the positive rates were 79.10% (53/67), 53.23% (33/62), and 88.71% (55/62), respectively. SPECT/CT hybrid images were positive in all the 24 patients who underwent this examination. The mean maximum diameters of the lesions in 99mTc-MIBI positive and negative patients were 1.96±0.95 cm and 1.36±0.67 cm respectively, with statistically significant difference noted (P=0.03). The T/NT of 99mTc-MIBI imaging at the early phase was correlated positively with serum PTH level (r=0.40, P=0.01). The T/NT of 99mTc-MIBI imaging at both the early phase and the delay phase was correlated positively with lesion size (r=0.51, and r=0.45, respectively; P<0.01 for both). It was concluded that 99mTc-MIBI imaging presents significant value for location diagnosis of HPT, especially when combined with SPECT/CT hybrid imaging or ultrasound. The 99mTc-MIBI uptake correlates positively with serum PTH level and lesion size.

Transcriptome profiling analysis reveals metabolic changes across various growth phases in Bacillus pumilus BA06.

BACKGROUND: Bacillus pumilus can secret abundant extracellular enzymes, and may be used as a potential host for the industrial production of enzymes. It is necessary to understand the metabolic processes during cellular growth. Here, an RNA-seq based transcriptome analysis was applied to examine B. pumilus BA06 across various growth stages to reveal metabolic changes under two conditions. RESULTS: Based on the gene expression levels, changes to metabolism pathways that were specific to various growth phases were enriched by KEGG analysis. Upon entry into the transition from the exponential growth phase, striking changes were revealed that included down-regulation of the tricarboxylic acid cycle, oxidative phosphorylation, flagellar assembly, and chemotaxis signaling. In contrast, the expression of stress-responding genes was induced when entering the transition phase, suggesting that the cell may suffer from stress during this growth stage. As expected, up-regulation of sporulation-related genes was continuous during the stationary growth phase, which was consistent with the observed sporulation. However, the expression pattern of the various extracellular proteases was different, suggesting that the regulatory mechanism may be distinct for various proteases. In addition, two protein secretion pathways were enriched with genes responsive to the observed protein secretion in B. pumilus. However, the expression of some genes that encode sporulation-related proteins and extracellular proteases was delayed by the addition of gelatin to the minimal medium. CONCLUSIONS: The transcriptome data depict global alterations in the genome-wide transcriptome across the various growth phases, which will enable an understanding of the physiology and phenotype of B. pumilus through gene expression.

Multilayer micro-dispersing system as oral carriers for co-delivery of doxorubicin hydrochloride and P-gp inhibitor.

The primary constraints for efficient oral delivery of anticancer drugs include the efflux pump function of the multidrug transporter P-glycoprotein (P-gp) for anticancer drugs and the barriers to drug absorption in gastrointestinal (GI) tract. To improve bypassing P-gp drug efflux pumps and oral bioavailability of doxorubicin hydrochloride (DOX), Multilayer micro-dispersing system (MMS) was constructed by co-immobilization of DOX loaded chitosan/carboxymethyl chitosan nanogels (DOX:CS/CMCS-NGs), along with quercetin (Qu) in the core of multilayer sodium alginate beads (DOX:NGs/Qu-M-ALG-Beads). The obtained DOX:NGs/Qu-M-ALG-Beads possessed layer-by-layer structure and porous core with many nanoscale particles. The swelling characteristic and drug release results indicated that DOX:NGs/Qu-M-ALG-Beads exhibited favorable gastric acid tolerance and targeting release of intact DOX:CS/CMCS-NGs and Qu in small intestine. After oral administration of DOX:NGs/Qu-M-ALG-Beads in rats, DOX was effectively delivered into systemic circulation due to P-gp inhibitory properties of Qu. The absolute bioavailability reached 55.75%, about 18.65 folds higher than oral DOX. Tissue distribution results showed that the liver exhibited the highest DOX level, followed by kidney, heart, lung, and spleen. These results implied that DOX:NGs/Qu-M-ALG-Beads had great potential to be applied as dual drug delivery for oral chemotherapy.

Diagnosis Performance of 99mTc-MIBI and Multimodality Imaging for Hyperparathyroidism / 华中科技大学学报（医学）（英德文版）

This study aimed to examine the diagnosis performance of 99mTc-methoxyisobutylisonitrisonitrile (99mTc-MIBI) and multimodality imaging [ultrasound,single-photon emission computed tomography/computed tomography (SPECT/CT)] for hyperparathyroidism (HPT).From Nov.2009 to Dec.2015,clinical data of a total of 43 HPT patients (16 males and 27 females;26-70 years old,average age:51.60±10.66 years old) were retrospectively analyzed.Among them,19 patients with primary hyperparathyroidism (PHPT) underwent 99mTc-MIBI planar imaging,24 [15 with PHPT and 9 with secondary hyperparathyroidism (SHPT)] underwent SPECT/CT hybrid imaging,and 41 (33 with PHPT and 8 with SHPT) had neck ultrasound imaging.Final diagnosis was determined by pathological examination after surgery.The positive rate was compared between different imaging modalities,and the correlation analysis was conducted between imaging results and lesion size or serum parathyroid hormone (PTH) level.The results showed that the total positive rates of 99mTc-MIBI imaging,ultrasound,and the two combined imaging in the 43 HPT cases were 90.70％ (39/43),58.54％ (24/41),and 100％ (41/41),respectively.According to lesion numbers,the positive rates were 79.10％ (53/67),53.23％ (33/62),and 88.71％ (55/62),respectively.SPECT/CT hybrid images were positive in all the 24 patients who underwent this examination.The mean maximum diameters of the lesions in 99mTc-MIBI positive and negative patients were 1.96±0.95 cm and 1.36±0.67 cm respectively,with statistically significant difference noted (P=0.03).The T/NT of 99mTc-MIBI imaging at the early phase was correlated positively with serum PTH level (r=0.40,P=0.01).The T/NT of 99mTc-MIBI imaging at both the early phase and the delay phase was correlated positively with lesion size (r=0.51,and r=0.45,respectively;P＜0.01 for both).It was concluded that 99mTc-MIBI imaging presents significant value for location diagnosis of HPT,especially when combined with SPECT/CT hybrid imaging or ultrasound.The 99mTc-MIBI uptake correlates positively with serum PTH level and lesion size.

Chitosan-Coated Diatom Silica as Hemostatic Agent for Hemorrhage Control.

Uncontrolled hemorrhage leads to high death risk both in military and civilian trauma. Current hemostatic agents still have various limitations and side effects. In this study, natural diatom silica obtained from diatomite and diatom culture was purified and developed for hemorrhage control. To improve the biocompatibility and hemostatic performance of diatom silica, a series of chitosan-coated diatom (CS-diatom) was developed. The composition of CS-diatom prepared was optimized by in vitro hemocompatibility and blood coagulation evaluation for that prepared with 0.5%, 1%, 3%, and 5% chitosan. The results demonstrated that the CS-diatom prepared with 1% chitosan exhibited favorable biocompatibility (hemolysis ratio < 5%, no cytotoxicity to MEFs), great fluid absorbility (24.39 ± 1.53 times the weight of liquid), and desirable hemostasis effect (351 ± 14.73 s at 5 mg/mL, 248 ± 32.42s at 10 mg/mL). Further blood coagulation mechanism study indicated that CS-diatom could provide an ideal interface to induce erythrocyte absorption and aggregation, along with activating the intrinsic coagulation pathway and thus accelerated blood coagulation. Benefitting from the multiple hemostatic performances, CS-diatom showed the shortest clotting time (98.34 ± 26.54 s) and lowest blood loss (0.31 ± 0.11 g) in rat-tail amputation model compare to diatomite and diatom as well as gauze and commercial QuikClot zeolite. The results evidenced that the CS-diatom was a safe and effective hemostatic agent and provided a new understanding of nonsynthetic mesoporous materials for hemorrhage control.

Transcriptome analysis confers a complex disease resistance network in wild rice Oryza meyeriana against Xanthomonas oryzae pv. oryzae.

Rice bacterial blight (BB), caused by Xanthomonas oryzae pv. oryzae (Xoo), is one of the devastating diseases of rice. It is well established that the wild rice Oryza meyeriana is immune to BB. In this study, the transcriptomic analysis was carried out by RNA sequencing of O. meyeriana leaves, inoculated with Xoo to understand the transcriptional responses and interaction between the host and pathogen. Totally, 57,313 unitranscripts were de novo assembled from 58.7 Gb clean reads and 14,143 unitranscripts were identified after Xoo inoculation. The significant metabolic pathways related to the disease resistance enriched by KEGG, were revealed to plant-pathogen interaction, phytohormone signaling, ubiquitin mediated proteolysis, and phenylpropanoid biosynthesis. Further, many disease resistance genes were also identified to be differentially expressed in response to Xoo infection. Conclusively, the present study indicated that the induced innate immunity comprise the basal defence frontier of O. meyeriana against Xoo infection. And then, the resistance genes are activated. Simultaneously, the other signaling transduction pathways like phytohormones and ubiquitin mediated proteolysis may contribute to the disease defence through modulation of the disease-related genes or pathways. This could be an useful information for further investigating the molecular mechanism associated with disease resistance in O. meyeriana.

Nano-polyplex based on oleoyl-carboxymethy-chitosan (OCMCS) and hyaluronic acid for oral gene vaccine delivery.

Here we described nano-polyplexes (NPs) made of oleoyl-carboxymethy-chitosan (OCMCS)/hyaluronic acid (HA) as novel potential carriers for oral gene vaccines delivery. Aerolysin gene (aerA) of Aeromonas hydrophila as microbial antigen was efficiently loaded to form OCMCS-HA/aerA (OHA) NPs. OHA NPs performed the optimal parameters, i.e. smallest (154.5±9.4nm), positive charged (+7.9±0.5mV) and monodispersed system with the N/P ratio of 5 and OCMCS/HA weight ratio of 4. Upon the introduction of HA, OHA NPs was beneficial for the DNA release in intestinal environments in comparison to OA NPs. The mean fluorescence intensity detected in Caco-2 cells incubated with OHA NPs was about 2.5-fold higher than that of OA NPs; however, it decreased significantly in the presence of excess free HA. The OHA NPs and OA NPs decreased the transepithelial electric resistance (TEER) of Caco-2 monolayers obviously and induced increasing the apparent permeability coefficient (Papp) of DNA by 5.45-6.09 folds compared with free DNA. Significantly higher (P<0.05) antigen-specific antibodies were detected in serum after orally immunized with OHA NPs than that immunized with OA NPs and DNA alone in carps. These results enable the OHA NPs might resolve challenges arising from gastrointestinal damage to gene antigens, and offer an approach applicable for oral vaccination.

Isolation and characterization of cDNAs and genomic DNAs encoding ADP-glucose pyrophosphorylase large and small subunits from sweet potato.

Sweet potato [Ipomoea batatas (L.) Lam.], the world's seventh most important food crop, is also a major industrial raw material for starch and ethanol production. In the plant starch biosynthesis pathway, ADP-glucose pyrophosphorylase (AGPase) catalyzes the first, rate-limiting step and plays a pivotal role in regulating this process. In spite of the importance of sweet potato as a starch source, only a few studies have focused on the molecular aspects of starch biosynthesis in sweet potato and almost no intensive research has been carried out on the AGPase gene family in this species. In this study, cDNAs encoding two small subunits (SSs) and four large subunits (LSs) of AGPase isoforms were cloned from sweet potato and the genomic organizations of the corresponding AGPase genes were elucidated. Expression pattern analysis revealed that the two SSs were constitutively expressed, whereas the four LSs displayed differential expression patterns in various tissues and at different developmental stages. Co-expression of SSs with different LSs in Escherichia coli yielded eight heterotetramers showing different catalytic activities. Interactions between different SSs and LSs were confirmed by a yeast two-hybrid experiment. Our findings provide comprehensive information about AGPase gene sequences, structures, expression profiles, and subunit interactions in sweet potato. The results can serve as a foundation for elucidation of molecular mechanisms of starch synthesis in tuberous roots, and should contribute to future regulation of starch biosynthesis to improve sweet potato starch yield.

Asymmetric Facet Joint Osteoarthritis and Its Relationships to Facet Orientation, Facet Tropism, and Ligamentum Flavum Thickening.

STUDY DESIGN: The degrees of osteoarthritis of the left and right facet joints were evaluated by using computerized tomography among elderly patients with low back or leg pain. OBJECTIVE: To reveal the phenomenon of asymmetry regarding facet joint osteoarthritis (FJOA) in old patients and establish its relationships to spinal level, facet orientation, facet tropism and ligamentum flavum (LF) thickening. SUMMARY OF BACKGROUND DATA: There were few reports regarding left-right asymmetry among severity of FJOA and its relationships to spinal level, facet orientation, facet tropism, and LF thickening remained unclear. METHODS: The grade of bilateral FJOA was evaluated using 4-grade scale on computerized tomography images at the L3-4, L4-5, and L5-S1 levels of patients with age ranging from 60 to 80 years. All subjects were divided into 2 groups: symmetric FJOA group (FJOA I-II on both sides or FJOA III-IV on both sides) and asymmetric FJOA group (FJOA I-II on one side and FJOA III-IV on the other side). The relationships of FJOA to spinal level, facet orientation, facet tropism, and LF hypertrophy were evaluated. RESULTS: No association between asymmetric FJOA and spinal level was noted (P>0.05). In asymmetric FJOA group, significant difference in facet orientation between 2 sides was observed at the L4-5 (P=0.018) and L5-S1 levels (P=0.033). Compared with symmetric FJOA, asymmetric FJOA showed significant difference in prevalence of facet tropism at the L5-S1 level (P<0.001). The LF showed significantly thicker on the side of FJOA III-IV than the side of FJOA I-II at each level in asymmetric FJOA group (P<0.05). However, no difference was found in thickness between 2 sides in symmetric FJOA group (P>0.05). CONCLUSIONS: Asymmetric FJOA is associated with facet orientation and tropism, but not with spinal level. There is a close relationship between severity of FJOA and LF thickness.

A novel shell-like supramolecular assembly of 4,4'-bipyridyl derivatives and a twisted cucurbit[14]uril molecule.

This work showed that the 4,4'-bipyridyl group and alkyl chains of 4,4'-bipyridyl derivatives are completely located in the shell-like cavity of the twisted cucurbit[14]uril molecule and formed novel shell-like 1 : 1 inclusion complexes. As it is enthalpy-driven the complexation benefits from ion-dipole interactions.

Surface charge effect on mucoadhesion of chitosan based nanogels for local anti-colorectal cancer drug delivery.

To develop more effective anticancer mucoadhesive drug delivery system for the treatment of colorectal cancer, chitosan based nanogels (NGs) were prepared by electrostatic interaction between chitosan (CS) and carboxymethyl-chitosan (CMCS). By respectively using tripolyphosphate (TPP) and CaCl2 as ionic crosslinker, two well-characterized doxorubicin hydrochloride (DOX) loaded NGs with opposite zeta potential (DOX:CS/CMCS/TPP NGs, -32.6±1.1 mV and DOX:CS/CMCS/Ca2+ NGs, +31.8±0.9 mV) were obtained. Compared with DOX:CS/CMCS/TPP NGs, DOX:CS/CMCS/Ca2+ NGs were taken up to a greater extent by colorectal cancer cells, resulting in greater reduction in percentage of cell viability. Owing to high binding capability to mucin and inhibited paracellular transport by colon, DOX:CS/CMCS/Ca2+ NGs exhibited improved mucoadhesion and limited permeability. This is beneficial to prolong the contact time of formulation onto intestinal mucosa and improved local drug concentration. The results provided evidence DOX:CS/CMCS/Ca2+ NGs to be exciting and promising for the treatment of colorectal cancer.

In vitro and in vivo evaluation of chitosan microspheres with different deacetylation degree as potential embolic agent.

To evaluate the potential of N-acetylated chitosan microspheres used as a chemoembolic agent in vivo and in vitro. Calibrated spherical chitosan microspheres (CMs) were prepared via Water-in-Oil emulsification method and CMs were acetylated (ACMs). The swelling rate of CMs was greatly affected by pH than that of ACMs and both of them affected by temperature. Microspheres with excellent thermal stability demonstrated controllable degradation in lysozyme solution. Doxorubicin was released from microspheres in vitro and exhibited excellent control release profile. ACMs caused hemolysis less than CMs (<5% of the time). Co-culture with mouse embryo fibroblasts revealed that microspheres have non-cytotoxic nature. Microspheres planted in a rat gluteal muscle demonstrated that it were biodegradable and biocompatible. ACMs were performed in rabbit ear embolization model and ischemic necrosis on ear was visible due to the vascular occlusion after 15 days. Acetylated chitosan microspheres could be used as potential biocompatible and biodegradable embolic agents.

[CdCl4]2- anion-induced coordination of alkaline earth metal ions to cucurbit[7]uril, corresponding supramolecular self-assemblies and potential application.

In the present work, we describe three cucurbit[7]uril-based coordination supermolecular self-assemblies in the presence of [M(trans)Cl4](2-). It can affect the construction of Q[7]/metal ions-based coordination polymers, at the same time it can result in the formation of Q[7]-based supramolecular assemblies when introducing the [M(trans)Cl4](2-) into the Q[7]/metal ions system.

Tetrachloridometallate dianion-induced cucurbit[8]uril supramolecular assemblies with large channels and their potential applications for extraction coating on solid-phase microextraction fibers.

Q[8]-based porous materials were synthesized in the presence of [Md-blockCl4](2-) anions as structure inducers. The driving forces of the structure-directing effect of the [Md-blockCl4](2-) anions may be due to the ion-dipole interaction and hydrogen bonding between the [Md-blockCl4](2-) anions and ≡CH or ═CH2 groups on the backs of Q[8] molecules. Moreover, the tests of potential applications show that these porous materials can not only capture organic molecules through the cavity of Q[8] moieties but also adsorb larger organic molecules with different selectivities.

Cucurbit[n]uril-based coordination chemistry: from simple coordination complexes to novel poly-dimensional coordination polymers.

Cucurbit[n]urils are a family of molecular container hosts bearing a rigid hydrophobic cavity and two identical carbonyl fringed portals. They have attracted much attention in supramolecular chemistry because of their superior molecular recognition properties in aqueous media. This review highlights the recent advances and challenges in the field of cucurbit[n]uril-based coordination chemistry. It not only presents progress in the knowledge of such macrocyclic compounds, which range from simple to complicated architectures, but also presents new routes of synthesis and their advantages in hybrid porous solids. The concept of structure "inducer" for their structural design to achieve predictable structures and controlled pores is described. The large pore sizes and hydrophobic cavities of these compounds that lead to unprecedented properties and potential applications are also discussed.

[Normal pneumatization time of paranasal sinuses in 799 children: evaluation with magnetic resonance imaging].

OBJECTIVE: To evaluate the onset of initial pneumatization of paranasal sinuses with magnetic resonance imaging (MRI) and provides references in the diagnosis and treatment of pediatric paranasal sinuses disease. METHODS: The MRI images of paranasal sinuses were retrospectively reviewed for 799 children of 0 month to 15 years old and the first pneumatization time of paranasal sinuses were analyzed. RESULTS: The ethmoidal sinuses was the first pneumatized in 100% (46/46) of newborn children. And 45.7% (21/46) of maxillary sinuses showed pneumatization during the first month of life and 97.8% (45/46) were pneumatized at 7 - 12 months. The pneumatized sphenoid sinuses was first identified as early as 4 months. And 86% (43/50) were pneumatized from 1 to 2 years old. Frontal sinuses was the last pneumatized paranasal sinuses. And 8% (4/50) of frontal sinuses were pneumatized at 1 - 2 years old and 97.8% (42/43) showed pneumatization at 14 - 15 years old. CONCLUSION: MRI may be used to observe the pneumatization of paranasal sinuses. The initial pneumatization time of paranasal sinuses is earlier than previously described.