Identification of a novel macrophage-related prognostic signature in colorectal cancer.

Colorectal cancer (CRC) is one of the most prevalent and deadliest illnesses all around the world. Growing proofs demonstrate that tumor-associated macrophages (TAMs) are of critical importance in CRC pathogenesis, but their mechanisms remain yet unknown. The current research was designed to recognize underlying biomarkers associated with TAMs in CRC. We screened macrophage-related gene modules through WGCNA, selected hub genes utilizing the LASSO algorithm and COX regression, and established a model. External validation was performed by expression analysis using datasets GSE14333, GSE74602, and GSE87211. After validating the bioinformatics results using real-time quantitative reverse transcription PCR, we identified SPP1, C5AR1, MMP3, TIMP1, ADAM8 as potential biomarkers associated with macrophages in CRC.

Cell sheet-basedin vitrobone defect model for long term evaluation of bone repair materials.

Development of tissue-engineeredin vitrohuman bone defect models for evaluation of bone repair materials (BRMs) is a promising approach for addressing both translational and ethical concerns regarding animal models. In this study, human bone marrow mesenchymal stem cell sheets were stacked to form a periosteum like tissue. HE staining showed a cell-dense, multilayered structure. BRMs were implanted in the defect area of the three-dimensional (3D) model. The CCK-8 test demonstrated that the 3D model was stronger in resisting the cytotoxicity of three kinds of commercial BRMs than the 2D culture model, which was consistent within vivoresults. After 28 d implantation in the 3D model, western blot and RT-qPCR showed that three materials induced increased expressions of RUNX2, OSX, OCN, OPN, while Materials B and C seemed to have stronger osteoinductivity than A.In vivoexperiments also confirmed the osteoinductivity of the BRMs after 28 and 182 d implantation. Alizarin red staining proved that the mineralized nodules of Materials B and C were more than that of A. The differences of osteogenic properties among three BMRs might be attributed to calcium ion release. This cell sheet-based bone tissue model can resist cytotoxicity of BRMs, demonstrating the priority of long-term evaluation of osteoinductivity of BRMs. Further, the osteoinduction results of the 3D model corresponded to that ofin vivoexperiments, suggesting this model may have a potential to be used as a novel tool for rapid, accurate evaluation of BRMs, and thus shorten their research and development process.

[Application of U-Net network in automatic image segmentation of adenoid and airway of nasopharynx].

Objective:To explore the effect of fully automatic image segmentation of adenoid and nasopharyngeal airway by deep learning model based on U-Net network. Methods:From March 2021 to March 2022, 240 children underwent cone beam computed tomography（CBCT） in the Department of Otolaryngology, Head and Neck Surgery, General Hospital of Shenzhen University. 52 of them were selected for manual labeling of nasopharynx airway and adenoid, and then were trained and verified by the deep learning model. After applying the model to the remaining data, compare the differences between conventional two-dimensional indicators and deep learning three-dimensional indicators in 240 datasets. Results:For the 52 cases of modeling and training data sets, there was no significant difference between the prediction results of deep learning and the manual labeling results of doctors（P>0.05）. The model evaluation index of nasopharyngeal airway volume: Mean Intersection over Union（MIOU） s （86.32±0.54）%; Dice Similarity Coefficient（DSC）: （92.91±0.23）%; Accuracy: （95.92±0.25）%; Precision: （91.93±0.14）%; and the model evaluation index of Adenoid volume: MIOU: （86.28±0.61）%; DSC: （92.88±0.17）%; Accuracy: （95.90±0.29）%; Precision: （92.30±0.23）%. There was a positive correlation between the two-dimensional index A/N and the three-dimensional index AV/（AV+NAV） in 240 children of different age groups（P<0.05）, and the correlation coefficient of 9-13 years old was 0.74. Conclusion:The deep learning model based on U-Net network has a good effect on the automatic image segmentation of adenoid and nasopharynx airway, and has high application value. The model has a certain generalization ability.

[Pediatric oral maxillofacial management and artificial intelligence].

With the enhancement of aesthetic awareness of children's oral maxillofacial development, multi-disciplinary doctors pay attention to children's oral maxillofacial management. Artificial intelligence (AI) technology has been gradually applied to all fields of children's oral maxillofacial management because of its outstanding advantages in medical screening and auxiliary decision-making. This article reviews the application of AI technology in the screening, diagnosis, treatment and follow-up of oral maxillofacial management in children.

Influence of bilateral nasal packing on sleep oxygen saturation after general anesthesia: A prospective cohort study.

Objective: This study aims to evaluate the effect of bilateral nasal packing on sleep oxygen saturation and its influencing factors on the first night after general anesthesia. Method: A total of 36 adult patients who underwent bilateral nasal packing with a nonabsorbable expanding sponge after general anesthesia surgery were prospectively studied. All these patients underwent overnight oximetry tests before and the first night after surgery. The following oximetry variables were collected for analysis: the lowest oxygen saturation (LSAT), the average oxygen saturation (ASAT), the oxygen desaturation index of ≥4% (ODI4), and the percentage of time with oxygen saturation below 90% (CT90). Results: Among the 36 patients, the incidences of both sleep hypoxemia and moderate-to-severe sleep hypoxemia increased with bilateral nasal packing after general anesthesia surgery. All the pulse oximetry variables we studied deteriorated significantly after surgery: both LSAT and ASAT decreased significantly (P < 0.05), while both ODI4 and CT90 increased significantly (P < 0.05). In a multiple logistic regression analysis, body mass index (BMI), LSAT, and modified Mallampati grade were found to be independently predictive for a larger decrease in LSAT (≥5%) after surgery (all P's < 0.05). Conclusion: Bilateral nasal packing after general anesthesia could induce or aggravate sleep hypoxemia, especially in patients with obesity, relatively normal sleep oxygen saturation, and high modified Mallampati grades.

Nasopharyngeal tube effects on alleviating sleep hypoxemia during the first night following velopharyngeal surgery in patients with obstructive sleep apnea syndrome.

STUDY OBJECTIVES: To investigate the feasibility and effectiveness of nasopharyngeal tube (NPT) insertion in alleviating sleep hypoxemia during the first night after velopharyngeal surgery in patients with obstructive sleep apnea syndrome (OSAS). METHODS: In this prospective nonblinded, randomized, controlled study, 46 patients with obstructive sleep apnea syndrome (OSAS) who underwent velopharyngeal surgery were enrolled and randomly allocated to the control group (with no NPT insertion) and the NPT insertion group. Both groups underwent overnight pulse oximetry tests during the first postoperative night. RESULTS: One patient in the NPT insertion group was excluded because of involuntary self-removal of NPT during sleep. A total of 45 patients with OSAS were included for analysis, with 23 in the control group and 22 in the NPT insertion group. No significant differences in preoperative baseline information were found between the two groups. Compared with the patients in the control group, those patients in the NPT insertion group showed a significantly higher value of the lowest oxygen saturation of oximetry during the first postoperative night (85.0 ± 4.0% vs 79.3 ± 8.0%) (P = .005). The percentage of patients with lowest oxygen saturation of oximetry < 80% in the NPT insertion group was only 9.1% (2 of 22), which was significantly lower than 39.1% (9 of 23) in the control group (P = .035). No patient reported unbearable discomfort related to NPT insertion. The most common mild discomfort was occasional pharyngeal foreign body sensation (6 of 22, 27.3%). CONCLUSIONS: NPT insertion could lessen the severity of sleep hypoxemia during the first night after velopharyngeal surgery in patients with OSAS and showed excellent compliance. This method could be a potential alternative option for decreasing the risks of complications related to severe sleep hypoxemia during the early postoperative days. CITATION: Zhang J, Guan S, Zhang C, Du X, Li T, Xiao S. Nasopharyngeal tube effects on alleviating sleep hypoxemia during the first night following velopharyngeal surgery in patients with obstructive sleep apnea syndrome. J Clin Sleep Med. 2023;19(2):303-308.

Macromolecular crowding facilitates rapid fabrication of intact, robust cell sheets.

OBJECTIVES: To develop a rapid and simple method to fabricate intact, robust cell sheets from common cell culture dishes by combination of a macromolecular crowding (MMC) reagent and vitamin C. RESULTS: It was found that 3T3 fibroblasts or human bone marrow mesenchymal stem cells (hBMSCs) and their secreted cell derived extracellular matrices could be easily detached as intact cell sheets under gently pipetting after treated by MMC and vitamin C for 4 days. This method also allowed fabrication of functional multi-layered hepatic cell sheets by culturing 10 × 104 cells/cm2 HepG2 cells on top of confluent 3T3 fibroblast layers. What's more, MMC induced hBMSC cell sheets demonstrated 1.9 times larger area and 1.6 times greater cell number than that of cell sheets harvested from temperature-responsive cell culture dishes. CONCLUSION: MMC based method make it possible to fabricate various types of cell sheets more conveniently, economically, and thus may facilitate wide application of cell sheet technology.

Design of Cyclic Peptide-Based Nanospheres and the Delivery of siRNA.

In recent years, cyclic peptides have attracted much attention due to their chemical and enzymatic stability, low toxicity, and easy modification. In general, the self-assembled nanostructures of cyclic peptides tend to form nanotubes in a cyclic stacking manner through hydrogen bonding. However, studies exploring other assembly strategies are scarce. In this context, we proposed a new assembly strategy based on cyclic peptides with covalent self-assembly. Here, cyclic peptide-(DPDPDP) was rationally designed and used as a building block to construct new assemblies. With cyclo-(DP)3 as the structural unit and 2,2'-diamino-N-methyldiethylamine as the linker, positively charged nanospheres ((CP)6NS) based on cyclo-(DP)3 were successfully constructed by covalent self-assembly. We assessed their size and morphology by scanning electron microscopy (SEM), TEM, and DLS. (CP)6NS were found to have a strong positive charge, so they could bind to siRNA through electrostatic interactions. Confocal microscopy analysis and cell viability assays showed that (CP)6NS had high cellular internalization efficiency and low cytotoxicity. More importantly, real-time polymerase chain reaction (PCR) and flow cytometry analyses indicated that (CP)6NS-siRNA complexes potently inhibited gene expression and promoted tumor cell apoptosis. These results suggest that (CP)6NS may be a potential siRNA carrier for gene therapy.

Design and anti-tumor activity of self-loaded nanocarriers of siRNA.

Polypeptide carriers have a good cell compatibility, rich functionality, and facile synthesis and modification, make them promising materials as siRNA vectors. Phenylalanine dipeptide (FF) has been previously assessed as an siRNA vector and showed to have two major drawbacks, namely poor water solubility and poor serum stability. Herein, the FF backbone was modified by ligating a PEG-Arg-Ala (PEG-RA) sequence at the N-terminus to increase its hydrophilicity and serum stability. Arg is a typical amino acid in the cell penetrating peptide, which can increase the efficiency of cell internalization. Ala acts as a spacer to avoid steric hindrance. The target sequence PEG-RAFF was synthesized by a solid phase peptide synthesis. The morphology, particle size, and siRNA ratio were assessed by SEM, TEM, DLS, and gel electrophoresis. Further, MCF-7 cells were used as a model and survivin-siRNA as a passenger to assess cell internalization, inhibition of gene expression rate, and apoptosis rate using confocal microscopy, real-time PCR, and flow cytometry. At a concentration of 1 mg/mL, PEG-RAFF took the form of nanovesicles with a diameter of 154.74 ±â€¯14.36 nm. The optimal PEG-RAFF to siRNA ratio was N/P = 100:1. Compared with the control group, the red fluorescence of TAMRA(Carboxytetramethylrhodamine, Red fluorescence)-siRNA transfected into cells was clearly visible in the confocal microscope image. The inhibition rate of survivin was 67.99 ±â€¯10.31%, and the apoptotic rate was 16.07%. Therefore, PEG-RAFF has potential as an siRNA carrier in cancer treatment.

A dendrimer consisting of a pyrene core and a 9-phenylcarbazole periphery as a multi-functional fluorescent probe for iodide, iron(III) and mercury(II).

A dendrimer (termed G2) containing pyrene as the core and 9-phenylcarbazole (PCZ) on the periphery is shown to be a multi-functional fluorescent probe for iodide, iron(III) and mercury(II). It serves as the fluorometric/colorimetric dual-channel probe for these ions. As a fluorometric probe, the fluorescence of G2 is quenched both by iodide and iron(III). After that, the fluorescence of G2 which has been added iodide will recover when added mercury(II); as a colorimetric probe, the color of G2 solution can turn to yellow only by iodide which will change from yellow to colorless again when adding mercury(II). The color change is sensitive and observed visually at 0.1 mM for iodide. G2 also is an electroactive precursor for preparation of fluorescent films via electropolymerization. The resulting films can be used as the fluorescent films to sense the ions. This is attributed to the presence of a large specific surface, highly cross-linked microstructures and enhanced π conjugation. The electropolymerized film has blue fluorescence with excitation/emission maxima at 365/460 nm. The limits of detection (LOD) of G2 for iodide, iron(III) and mercury(II) were calculated to be 9.3, 37.1 and 22.0 nM in solution and 5.1, 12.0 and 6.1 nM in films, respectively. The linear range is from 2 to 10 µM for G2 electropolymerized films. The detection range is from 2 to 400 µM for iron(III) and mercury(II). The detection range is from 2 to 130 µM for iodide. For a third application, G2 displays compelling sensing performance in environmental systems and in living roundworms. Graphical abstractAs schematic presentation, after adding iodide, the fluorescence of G2 is quenched and the color changes to yellow. When adding Hg2+ to G2-iodide, the fluorescence and color of G2 recover. Iron(III) can also quench G2, but the color does not change.

Construction of a reconfigurable DNA nanocage for encapsulating a TMV disk.

A new reconfigurable DNA nanocage based on a DNA origami method has been constructed to capture a tobacco mosaic virus (TMV) disk. We used a hairpin to control the transformation of the nanocage and a strand of TMV RNA to attract the TMV disk. Our design could inspire new DNA-protein complex designs.

Diselenium-containing ultrathin polymer nanocapsules for highly efficient targeted drug delivery and combined anticancer effect.

The combination of selenium and pillararenes to prepare selenium-containing pillararene-based biomaterials is of great significance for the development of biomedicine. Herein, using a covalent self-assembly strategy, we successfully developed new diselenium-containing ultrathin polymer nanocapsules based on lateral cross-linked pillararenes. The new system exhibited a very potent anticancer effect; additionally, the incorporation of the cleavable redox diselenium bond into the polymer nanocapsules provided a smart nanocarrier for drug delivery. Moreover, the polymer nanocapsules were developed for anticancer drug targeting delivery by loading an anticancer drug and introducing the tumor-penetrating peptide RGD through the host-guest interaction strategy. The targeting DOX-loaded diselenium-containing polymer nanocapsules exhibited enhanced stability, self-anticancer effect, targeted delivery and controlled drug release, resulting in effective combined inhibition of tumor progression.

A Novel Peroxidase Mimics and Ameliorates Alzheimer's Disease-Related Pathology and Cognitive Decline in Mice.

Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly, which is characterized by the accumulation of amyloid ß (Aß) plaques, oxidative stress, and neuronal loss. Therefore, clearing Aß aggregates and reducing oxidative stress could be an effective therapeutic strategy for AD. Deuterohemin-AlaHisThrValGluLys (DhHP-6), a novel deuterohemin-containing peptide mimetic of the natural microperoxidase-11 (MP-11), shows higher antioxidant activity and stability compared to the natural microperoxidases. DhHP-6 possesses the ability of extending lifespan and alleviating paralysis in the Aß1-42 transgenic Caenorhabditis elegans CL4176 model of AD, as shown in our previous study. Therefore, this study was aimed at exploring the neuroprotective effect of DhHP-6 in the APPswe/PSEN1dE9 transgenic mouse model of AD. DhHP-6 reduced the diameter and fiber structure of Aß1-42 aggregation in vitro, as shown by dynamic light scattering and transmission electron microscope. DhHP-6 exerted its neuroprotective effect by inhibiting Aß aggregation and plaque formation, and by reducing Aß1-42 oligomers-induced neurotoxicity on HT22 (mouse hippocampal neuronal) and SH-SY5Y (human neuroblastoma) cells. In the AD mouse model, DhHP-6 significantly ameliorated cognitive decline and improved spatial learning ability in behavioral tests including the Morris water maze, Y-maze, novel object recognition, open field, and nest-building test. Moreover, DhHP-6 reduced the deposition of Aß plaques in the cerebral cortex and hippocampus. More importantly, DhHP-6 restored the morphology of astrocytes and microglia, and significantly reduced the levels of pro-inflammatory cytokines. Our findings provide a basis for considering the non-toxic, peroxidase mimetic DhHP-6 as a new candidate drug against AD.

Reductive-Responsive, Single-Molecular-Layer Polymer Nanocapsules Prepared by Lateral-Functionalized Pillar[5]arenes for Targeting Anticancer Drug Delivery.

Herein, a new reductive-responsive pillar[5]arene-based, single-molecule-layer polymer nanocapsule is constructed for drug delivery. The functionalized system shows good biocompatibility, efficient internalization into targeted cells and obvious triggered release of entrapped drugs in a reducing environment such as cytoplasm. Besides, this smart vehicle loaded with anticancer drug shows excellent inhibition for tumor cell proliferation and exhibits low side effect on normal cells. This work not only demonstrates the development of a new reductive-responsive single molecular layer polymer nanocapsule for anticancer drug targeting delivery but also extends the design of smart materials for biomedical applications.

Endothelial progenitor cells and a stromal cell-derived factor-1α analogue synergistically improve survival in sepsis.

RATIONALE: Endothelial progenitor cells (EPCs) have been associated with human sepsis but their role is incompletely understood. Stromal cell-derived factor (SDF)-1α facilitates EPC recruitment and is elevated in murine sepsis models. Previous studies have demonstrated that the SDF-1α analog CTCE-0214 (CTCE) is beneficial in polymicrobial sepsis induced by cecal ligation and puncture (CLP) in mice. OBJECTIVES: We hypothesized that exogenously administered EPCs are also beneficial in CLP sepsis and that CTCE provides synergistic benefit. METHODS: Mice were subjected to CLP and administered EPCs at varying doses, CTCE, or a combination of the two. Mouse survival, plasma miRNA expression, IL-10 production, and lung vascular leakage were determined. The in vitro effect of CTCE on miRNA expression and EPC function were determined. MEASUREMENTS AND MAIN RESULTS: Survival was improved with EPC therapy at a threshold of 10(6) cells. In coculture studies, EPCs augmented LPS-induced macrophage IL-10 production. In vivo EPC administration in sepsis increased plasma IL-10, suppressed lung vascular leakage, attenuated liver and kidney injury, and augmented miR-126 and -125b expression, which regulate endothelial cell function and/or inflammation. When subthreshold numbers of EPCs were coadministered with CTCE in CLP mice they synergistically improved survival. We demonstrated that CTCE recruits endogenous EPCs in septic mice. In in vitro analysis, CTCE enhanced EPC proliferation, angiogenesis, and prosurvival signaling while inhibiting EPC senescence. These cellular effects were, in part, explained by the effect of CTCE on miR-126, -125b, -34a, and -155 expression in EPCs. CONCLUSIONS: EPCs and CTCE represent important potential therapeutic strategies in sepsis.

Sulfated modification of the water-soluble polysaccharides from Polyporus albicans mycelia and its potential biological activities.

In this study, three chemically sulfated polysaccharides (SPAPs) were derived from one water-soluble polysaccharide (PAP) of Polyporus albicans mycelia by chlorosulfonic acid-pyridine method. The effects of polysaccharides on the immune function were examined after the mice were intragastrical administrated with polysaccharides at three doses of 100, 200, and 300 mg/kg body weight for 7 days. The results showed that both the lymphocytes proliferation and macrophage function were significantly enhanced by SPAP in all groups along with the increase of the substitution degree and dose (P<0.01). It indicated that SPAP could be a potential immunostimulants used in the food and pharmaceutical industry.

A novel polypeptide from Cervus nippon Temminck proliferation of epidermal cells and NIH3T3 cell line.

A novel polypeptide, velvet antler polypeptide (VAPPs), having a stimulary effect on proliferation of some cell was isolated from the velvet antler of sika deer (Cervus nippon Temminck). This polypeptide consists of a single chain of 32 amino-acid residues VLSAT DKTNV LAAWG KVGGN APAFG AEALE RM. VAPPs showed marked stimulary effect on rat epidermal cells and NIH3T3 cell line (dose range from 10-40 mg x L(-1) and 5-80 mg x L(-1), respectively).